Diabetes MellitusPhase 1NCT01982630
Study of the Safety and Efficacy of MK-8521 Compared to Placebo and a Diabetes Drug in Participants With Type 2 Diabetes Mellitus (MK-8521-003)
A Phase 1 study testing MK-8521 and Liraglutide in people with Diabetes Mellitus, run by Merck Sharp & Dohme LLC.
Trial summary
This study will evaluate the safety, efficacy, and pharmacokinetics of MK-8521 given once daily compared to placebo and another diabetes drug in participants with Type 2 diabetes mellitus (T2DM). Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Diabetes Mellitus
- What is being tested?
- MK-8521 and Liraglutide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 87 participants
- Where
- No sites listed yet
- Study dates
- 7 Nov 2013to 3 Oct 2014
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Male, or female of non-childbearing potential with Type 2 diabetes mellitus (Parts 1 and 2) or non-diabetic (Part 2)
- Body mass index (BMI) between: ≥27 and ≤40 kg/m^2
- A1C (average blood sugar for the past 2 to 3 months) value ≥7.0 and ≤11.0 % (Part 1) or ≥ 6.5 and ≤11.0 % (Part 2) at the time of screening (T2DM participants)
- A1C value <5.7 at the time of screening (non-diabetic subjects in Part 2 only)
- On a stable dose of metformin (≥1000 mg total daily dose) for at least 12 weeks at the time of screening (T2DM participants)
Who cannot join
- Mentally or legally incapacitated
- History of clinically significant psychiatric disorder of the last 5 years. Participants with situational depression may be enrolled in the trial at the discretion of the Investigator
- History of Type 1 diabetes mellitus or a history of ketoacidosis
- History of clinically significant gastrointestinal, hematological, hepatic, immunological, renal, respiratory, genitourinary or major neurological abnormalities or diseases
- History of cardiovascular disease or cardiac conduction disorder
- History of cancer (malignancy). Exceptions may include adequately treated non-melanomatous skin carcinoma or carcinoma in situ of the cervix or other malignancies which have been successfully treated ≥10 years prior to the pre-screening visit
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- History of proliferative diabetic retinopathy or maculopathy
- Clinically significant diabetic autonomic neuropathy
- QTc interval ≥470 msec (for males) or ≥480 msec (for females)
- Clinical significant electrocardiogram (ECG) abnormality
- Positive for hepatitis B surface antigen, hepatitis C antibodies, or human immunodeficiency virus (HIV)
- On a weight loss program and is not weight-stable (weight stable is defined history of <5% change in body weight in the last 3 months
- On a weight loss medication or has undergone bariatric surgery
- Major surgery, donated or lost 1 unit of blood (approximately 500 mL) within 4 weeks prior to the pretrial (screening) visit
- Participated in another investigational trial within 4 weeks prior to the pretrial (screening) visit
- History of acute or chronic pancreatitis of any etiology
- Mean value for triplicate semi-recumbent systolic blood pressure >160 mm Hg and/or diastolic blood pressure >90 mm Hg (after at least a 10-minute seated rest) and blood pressure is considered unlikely to be below these limits by Day-1 (Randomization) with initiation or adjustment of antihypertensive medication
- Event of severe hypoglycemia with seizure or loss of consciousness in the past 12 months
- Treated with anti-hyperglycemic agents other than metformin within the last 12 weeks
- Previous exposure to any glucagon-like peptide-1 (GLP-1) receptor agonist (e.g. Byetta™, Victoza™ or investigational agents)
About this study
Official title: A Phase Ib, Multicenter, Placebo and Active- Comparator-Controlled, Randomized, Double-Blind, Clinical Trial to Evaluate the Safety and Efficacy of MK-8521 Compared to Placebo and a Diabetes Drug in Subjects With Type 2 Diabetes Mellitus
This study will evaluate the safety, efficacy, and pharmacokinetics of MK-8521 given once daily compared to placebo and another diabetes drug in participants with Type 2 diabetes mellitus (T2DM).
This study was modified by a protocol amendment to a 2-part trial to further test the safety and tolerability of MK-8521 at higher doses and to compare MK-8521 pharmacokinetics between participants with T2DM and healthy participants. An additional cohort of T2DM participants and a cohort of non-diabetic obese participants has been added.
- Conditions
- Diabetes Mellitus
- Being tested
- MK-8521, Liraglutide, Placebo
- Medical subject headings
- Diabetes Mellitus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MK-8521Drug
LiraglutideDrug
PlaceboDrug
| Study group | Role | What they receive |
|---|---|---|
| Part 1: MK-8521 64/120 μg/day | Experimental | Type 2 diabetes mellitus (T2DM) participants received once daily subcutaneous MK-8521 starting at 64 μg on Days 1 to 7 and escalated to 120 μg on Days 8 to 14. Receives: Drug: MK-8521 |
| Part 1: MK-8521 34/72 μg/day | Experimental | T2DM participants received once daily subcutaneous MK-8521 starting at 34 μg on Days 1 to 7 and escalated to 72 μg on Days 8 to 14. Receives: Drug: MK-8521 |
| Part 1: Liraglutide 0.6/1.2/1.8 mg/day | Active comparator | T2DM participants received once daily subcutaneous liraglutide starting at 0.6 mg on Day 1 and 2, escalated to 1.2 mg on Days 3 to 7, and escalated to 1.8 mg on Days 8 to 14. Receives: Drug: Liraglutide |
| Part 1: Placebo for MK-8521 | Placebo comparator | T2DM participants received once daily subcutaneous placebo for MK-8521 for 14 days. Receives: Drug: Placebo |
| Part 2: MK-8521 64/120/180/240/300 µg/day-T2DM | Experimental | T2DM participants received once daily subcutaneous MK-8521 titrated to 300 µg starting at 64 µg and increasing to 120 µg on Day 8, 180 µg on Day 15, 240 µg on Day 20, and 300 µg on Day 25. The total number of dosing days was 29. Receives: Drug: MK-8521 |
| Part 2: Liraglutide 0.6/1.2/1.8 mg/day-T2DM | Active comparator | T2DM participants received once daily subcutaneous liraglutide titrated to 1.8 mg starting at 0.6 mg and increasing to 1.2 mg on Day 8, and 1.8 mg on Day 15. The total number of dosing days was 29. Receives: Drug: Liraglutide |
| Part 2: Placebo for MK-8521-T2DM | Placebo comparator | T2DM participants received once daily subcutaneous placebo for MK-8521 for 29 days. Receives: Drug: Placebo |
| Part 2: MK-8521 64/120 µg/day-Non-Diabetic Overweight/Obese | Experimental | Non-diabetic overweight/obese participants received once daily subcutaneous MK-8521 titrated to 120 µg starting at 64 µg and increasing to 120 µg on Day 8. The total number of dosing days was 14. Receives: Drug: MK-8521 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants Experiencing Adverse Events (AEs) in Part 1
An AE is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE. AEs are presented by individual dose received by participants during titration in an assigned study treatment sequence.
Measured: Up to approximately 42 days
Number of Participants Experiencing Adverse Events (AEs) in Part 2
An AE is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE. AEs are presented by individual dose received by participants during titration in an assigned study treatment sequence.
Measured: Up to approximately 57 days
Number of Participants Discontinuing Study Drug Due to Adverse Events (AEs) in Part 1
An AE is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE. Discontinuations are presented by individual dose received by participants during titration in an assigned study treatment sequence.
Measured: Up to approximately 14 days
Number of Participants Discontinuing Study Drug Due to Adverse Events (AEs) in Part 2
An AE is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE. Discontinuations are presented by individual dose received by participants during titration in an assigned study treatment sequence.
Measured: Up to approximately 29 days
Change From Baseline in Time-weighted Average From 0 to 24 Hours (TWA0-24hr) of Heart Rate (HR) After 7 Days of Treatment in Type 2 Diabetes Mellitus (T2DM) Participants in Part 1
Semi-recumbent heart rate was assessed at baseline on Day 1; Day 7 at predose, 2, 4, 6, 8, 12, 13, 14, 15, 16, 22 hours postdose; and prior to dosing on Day 8. Heart rate was measured in triplicate with at least a 1-2-minute interval between measurements. The repeated measurements were averaged before conducting the statistical analysis. TWA0-24hr was calculated as the area under the measurement-time curve (AUC) divided by the time period of over which the measurements were made (i.e. 24 hrs.). Change from baseline TWA0-24hr HR was calculated as the TWA0-24hr HR at Day 7 minus baseline where baseline was defined as predose on Day 1.
Measured: Baseline (predose Day 1) and up to 24 hours post Day 7 dose
Change From Baseline in Time-weighted Average From 0 to 24 Hours (TWA0-24hr) of Heart Rate (HR) After 7 Days of Treatment in Type 2 Diabetes Mellitus (T2DM) Participants in Part 2
Semi-recumbent HR was measured in triplicate with at least a 1-2-minute interval between measurements at the following time points: baseline on Day 1; Day 7: predose, 2, 4, 6, 8, 12, and 16 hours postdose; and prior to dosing on Day 8. The repeated measurements were averaged before conducting the analysis. TWA0-24hr was calculated as the AUC divided by the time period of over which the measurements were made (i.e. 24 hrs.). Change from baseline TWA0-24hr HR was calculated as the TWA0-24hr HR at Day 7 minus baseline where baseline was defined as predose on Day 1.
Measured: Baseline (predose Day 1) and up to 24 hours post Day 7 dose
Change From Baseline in Time-weighted Average From 0 to 24 Hours (TWA0-24hr) of Heart Rate (HR) After 14 Days of Treatment in Type 2 Diabetes Mellitus (T2DM) Participants in Part 1
Semi-recumbent HR was measured in triplicate with at least a 1-2-minute interval between measurements at the following time points: baseline on Day 1; Day 14: predose, 2, 4, 6, 8, 12, 13, 14, 15, 16, 22 hours postdose and prior to dosing on Day 15. The repeated measurements were averaged before conducting the analysis. TWA0-24hr was calculated as the AUC divided by the time period of over which the measurements were made (i.e. 24 hrs.). Change from baseline TWA0-24hr HR was calculated as the TWA0-24hr HR at Day 14 minus baseline where baseline was defined as predose on Day 1.
Measured: Baseline (predose Day 1) and up to 24 hours post Day 14 dose
Change From Baseline in Time-weighted Average From 0 to 24 Hours (TWA0-24hr) of Heart Rate (HR) After 14 Days of Treatment in Type 2 Diabetes Mellitus (T2DM) Participants in Part 2
Semi-recumbent HR was measured in triplicate with at least a 1-2-minute interval between measurements at the following time points: baseline on Day 1; Day 14: predose, 2, 4, 6, 8, 12, 16, hours postdose; and prior to dosing on Day 15. The repeated measurements were averaged before conducting the analysis. TWA0-24hr was calculated as the AUC divided by the time period of over which the measurements were made (i.e. 24 hrs.). Change from baseline TWA0-24hr HR was calculated as the TWA0-24hr HR at Day 14 minus baseline where baseline was defined as predose on Day 1.
Measured: Baseline (predose Day 1) and up to 24 hours post Day 14 dose
Change From Baseline in Time-weighted Average From 0 to 24 Hours (TWA0-24hr) of Heart Rate (HR) After 19 Days of Treatment in Type 2 Diabetes Mellitus (T2DM) Participants in Part 2
Semi-recumbent HR was measured in triplicate with at least a 1-2-minute interval between measurements at the following time points: baseline on Day 1; Day 19: predose, 2, 4, 6, 8, 12, 16, hours post dose; and prior to dosing on Day 20. The repeated measurements were averaged before conducting the analysis. TWA0-24hr was calculated as the AUC divided by the time period of over which the measurements were made (i.e. 24 hrs.). Change from baseline TWA0-24hr HR was calculated as the TWA0-24hr HR at Day 19 minus baseline where baseline was defined as predose on Day 1.
Measured: Baseline (predose Day 1) and up to 24 hours post Day 19 dose
Change From Baseline in Time-weighted Average From 0 to 24 Hours (TWA0-24hr) of Heart Rate (HR) After 24 Days of Treatment in Type 2 Diabetes Mellitus (T2DM) Participants in Part 2
Semi-recumbent HR was measured in triplicate with at least a 1-2-minute interval between measurements at the following time points: baseline on Day 1; Day 24: predose, 2, 4, 6, 8, 12, 16, hours postdose; and prior to dosing on Day 25. The repeated measurements were averaged before conducting the analysis. TWA0-24hr was calculated as the AUC divided by the time period of over which the measurements were made (i.e. 24 hrs.). Change from baseline TWA0-24hr HR was calculated as the TWA0-24hr HR at Day 24 minus baseline where baseline was defined as predose on Day 1.
Measured: Baseline (predose Day 1) and up to 24 hours post Day 24 dose
Change From Baseline in Time-weighted Average From 0 to 24 Hours (TWA0-24hr) of Heart Rate (HR) After 29 Days of Treatment in Type 2 Diabetes Mellitus (T2DM) Participants in Part 2
Semi-recumbent HR was measured in triplicate with at least a 1-2-minute interval between measurements at the following time points: baseline on Day 1; and Day 29: predose, 2, 4, 6, 8, 12, 16 and 24 hours postdose. The repeated measurements were averaged before conducting the analysis. TWA0-24hr was calculated as the AUC divided by the time period of over which the measurements were made (i.e. 24 hrs.). Change from baseline TWA0-24hr HR was calculated as the TWA0-24hr HR at Day 29 minus baseline where baseline was defined as predose on Day 1.
Measured: Baseline (predose Day 1) and up to 24 hours post Day 29 dose
Change From Baseline in Peak Heart Rate (PHR) at Day 7 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2
PHR was defined as the maximum time matched baseline adjusted heart rate over 24 hours. Semi-recumbent PHR was measured in triplicate with at least a 1-2-minute interval between measurements at the following time points: baseline on Day 1; Day 7: predose, 2, 4, 6, 8, 12, and 16 hours postdose; and prior to dosing on Day 8. The repeated measurements were averaged before conducting the analysis. Change from baseline PHR was calculated as the peak heart rate at Day 7 minus baseline where baseline was defined as predose on Day 1.
Measured: Baseline (predose Day 1) and up to 24 hours post Day 7 dose
Change From Baseline in Peak Heart Rate (PHR) at Day 14 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2
PHR was defined as the maximum time matched baseline adjusted heart rate over 24 hours. Semi-recumbent PHR was measured in triplicate with at least a 1-2-minute interval between measurements at the following time points: baseline on Day 1; Day 14: predose, 2, 4, 6, 8, 12, and 16 hours postdose; and prior to dosing on Day 15. The repeated measurements were averaged before conducting the analysis. Change from baseline PHR was calculated as the peak heart rate at Day 14 minus baseline where baseline was defined as predose on Day 1.
Measured: Baseline (predose Day 1) and up to 24 hours post Day 14 dose
Change From Baseline in Peak Heart Rate (PHR) at Day 19 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2
PHR was defined as the maximum time matched baseline adjusted heart rate over 24 hours. Semi-recumbent PHR was measured in triplicate with at least a 1-2-minute interval between measurements at the following time points: baseline on Day 1; Day 19: predose, 2, 4, 6, 8, 12, and 16 hours postdose; and prior to dosing on Day 20. The repeated measurements were averaged before conducting the analysis. Change from baseline PHR was calculated as the peak heart rate at Day 19 minus baseline where baseline was defined as predose on Day 1.
Measured: Baseline (predose Day 1) and up to 24 hours post Day 19 dose
Change From Baseline in Peak Heart Rate (PHR) at Day 24 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2
PHR was defined as the maximum time matched baseline adjusted heart rate over 24 hours. Semi-recumbent PHR was measured in triplicate with at least a 1-2-minute interval between measurements at the following time points: baseline on Day 1; Day 24: predose, 2, 4, 6, 8, 12, and 16 hours postdose; and prior to dosing on Day 25. The repeated measurements were averaged before conducting the analysis. Change from baseline PHR was calculated as the peak heart rate at Day 24 minus baseline where baseline was defined as predose on Day 1.
Measured: Baseline (predose Day 1) and up to 24 hours post Day 24 dose
Change From Baseline in Peak Heart Rate (PHR) at Day 29 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2
PHR was defined as the maximum time matched baseline adjusted heart rate over 24 hours. Semi-recumbent PHR was measured in triplicate with at least a 1-2-minute interval between measurements at the following time points: baseline on Day 1; and Day 29: predose 2, 4, 6, 8, 12, 16, and 24 hours post dose. The repeated measurements were averaged before conducting the analysis. Change from baseline PHR was calculated as the peak heart rate at Day 29 minus baseline where baseline was defined as predose on Day 1.
Measured: Baseline (predose Day 1) and up to 24 hours post Day 29 dose
Change From Baseline in Resting Morning Heart Rate (RMHR) After the Day 7 Dose for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2
Semi-recumbent RMHR was measured in triplicate with at least a 1-2-minute interval between measurements. The repeated measurements were averaged for each time point. Change from baseline RMHR was calculated as the RMHR 24 hours after the Day 7 dose (predose Day 8) minus baseline. Baseline was an average of 2 readings prior to dosing on Day 1.
Measured: Baseline (predose Day 1) and Day 8 (24 hours after Day 7)
Change From Baseline in Resting Morning Heart Rate (RMHR) After the Day 14 Dose for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2
Semi-recumbent RMHR was measured in triplicate with at least a 1-2-minute interval between measurements. The repeated measurements were averaged for each time point. Change from baseline RMHR was calculated as the RMHR 24 hours after the Day 14 dose (predose Day 15) minus baseline. Baseline was an average of 2 readings prior to dosing on Day 1.
Measured: Baseline (predose Day 1) and Day 15 (24 hours after Day 14)
Change From Baseline in Resting Morning Heart Rate (RMHR) After the Day 19 Dose for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2
Semi-recumbent RMHR was measured in triplicate with at least a 1-2-minute interval between measurements. The repeated measurements were averaged for each time point. Change from baseline RMHR was calculated as the RMHR 24 hours after the Day 19 dose (predose Day 20) minus baseline. Baseline was an average of 2 readings prior to dosing on Day 1.
Measured: Baseline (predose Day 1) and Day 20 (24 hours after Day 19)
Change From Baseline in Resting Morning Heart Rate (RMHR) After the Day 24 Dose for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2
Semi-recumbent RMHR was measured in triplicate with at least a 1-2-minute interval between measurements. The repeated measurements were averaged for each time point. Change from baseline RMHR was calculated as the RMHR 24 hours after the Day 24 dose (predose Day 25) minus baseline. Baseline was an average of 2 readings prior to dosing on Day 1.
Measured: Baseline (predose Day 1) and Day 25 (24 hours after Day 24)
Change From Baseline in Resting Morning Heart Rate (RMHR) After the Day 29 Dose for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2
Semi-recumbent RMHR was measured in triplicate with at least a 1-2-minute interval between measurements. The repeated measurements were averaged for each time point. Change from baseline RMHR was calculated as the RMHR 24 hours after the Day 29 dose minus baseline. Baseline was an average of 2 readings prior to dosing on Day 1.
Measured: Baseline (predose Day 1) and Day 30 (24 hours after Day 29)
Area Under the Concentration-time Curve From 0 to 24 Hours (AUC0-24hr) of MK-8521 on Days 1, 7, and 14 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 1
AUC0-24hr was the area under the concentration-time curve of MK-8521 from time zero to 24 hours after administration. Plasma samples were collected from predose to 24 hours postdose for determination of AUC0-24hr. Individual values were natural log-transformed and evaluated with a linear-mixed effects model containing fixed effects for treatment, day, and treatment by day interaction, and a random effect for participant. Kenward and Roger's method was used to calculate the degree of freedom for the fixed effects. AUC0-24hr is presented as geometric mean and percent coefficient of variation of geometric mean.
Measured: Predose and 1, 2, 4, 6, 8, 10, 12, 16, and 24 hours post-dose on Days 1, 7, and 14
Maximum Concentration (Cmax) of MK-8521 on Days 1 and 7 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 1
Cmax was the maximum observed concentration of MK-8521 in plasma after administration. Plasma samples were collected from predose to 24 hours postdose for determination of Cmax. Individual values were natural log-transformed and evaluated with a linear-mixed effects model containing fixed effects for treatment, day, and treatment by day interaction, and a random effect for participant. Kenward and Roger's method was used to calculate the degree of freedom for the fixed effects. Cmax is presented as geometric mean and percent coefficient of variation of geometric mean.
Measured: Predose and 1, 2, 4, 6, 8, 10, 12, 16, and 24 hours post-dose on Days 1 and 7
Maximum Concentration (Cmax) of MK-8521 on Day 14 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 1
Cmax was the maximum observed concentration of MK-8521 in plasma after administration on Day 14. Plasma samples were collected from predose to 120 hours postdose for determination of Cmax. Individual values were natural log-transformed and evaluated with a linear-mixed effects model containing fixed effects for treatment, day, and treatment by day interaction, and a random effect for participant. Kenward and Roger's method was used to calculate the degree of freedom for the fixed effects. Cmax is presented as geometric mean and percent coefficient of variation of geometric mean.
Measured: Predose and 1, 2, 4, 6, 8, 10, 12, 16, 24, 72, 96, and 120 hours post-dose on Day 14
Trough Concentration (Ctrough) of MK-8521 on Days 1, 7, and 14 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 1
Ctrough was the lowest observed concentration of MK-8521 in plasma. Plasma samples were collected predose on Day 2 (sampled after the Day 1 dose and prior to Day 2 dose), 7, and 14 for determination of Ctrough. Individual values were natural log-transformed and evaluated with a linear-mixed effects model containing fixed effects for treatment, day, and treatment by day interaction, and a random effect for participant. Kenward and Roger's method was used to calculate the degree of freedom for the fixed effects. Ctrough is presented as geometric mean and percent coefficient of variation of geometric mean.
Measured: Predose on Days 2, 7, and 14
Time to Maximum Concentration (Tmax) of MK-8521 on Days 1 and 7 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 1
Tmax was the time required to reach the maximum concentration of MK-8521 in plasma. Plasma samples were collected from predose to 24 hours postdose for determination of Tmax. Tmax is presented as median with a full range.
Measured: Predose and 1, 2, 4, 6, 8, 10, 12, 16, and 24 hours post-dose on Days 1 and 7
Time to Maximum Concentration (Tmax) of MK-8521 on Day 14 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 1
Tmax was the time required to reach the maximum concentration of MK-8521 in plasma. Plasma samples were collected from predose to 120 hours postdose for determination of Tmax. Tmax is presented as median with a full range.
Measured: Predose and 1, 2, 4, 6, 8, 10, 12, 16, 24, 72, 96, and 120 hours post-dose on Day 14
Apparent Terminal Half Life (t1/2) of MK-8521 on Days 1 and 7 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 1
t1/2 was the time required to divide the MK-8521 concentration by half after reaching pseudo-equilibrium. Plasma samples were collected from predose to 24 hours postdose for determination of t1/2. t1/2 is presented as geometric mean and percent coefficient of variation of geometric mean.
Measured: Predose and 1, 2, 4, 6, 8, 10, 12, 16, and 24 hours post-dose on Days 1 and 7
Apparent Terminal Half Life (t1/2) of MK-8521 on Day 14 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 1
t1/2 was the time required to divide the MK-8521 concentration by half after reaching pseudo-equilibrium. Plasma samples were collected from predose to 120 hours postdose for determination of t1/2. t1/2 was measured on Day 14 which is the longest time point for sampling for T2DM participants in Part 1. t1/2 is presented as geometric mean and percent coefficient of variation of geometric mean.
Measured: Predose and 1, 2, 4, 6, 8, 10, 12, 16, 24, 72, 96, and 120 hours post-dose on Day 14
Accumulation Ratio of the Area Under the Concentration-time Curve From 0 to 24 Hours (AUC0-24hr) of MK-8521 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 1
Plasma samples were collected from predose to 24 hours postdose for determination of the accumulation ratio of AUC0-24hr. The geometric mean accumulation ratio was calculated as Day 7 AUC0-24hr/Day 1 AUC0-24hr and presented as geometric mean ratio with a full range.
Measured: Predose and 1, 2, 4, 6, 8, 10, 12, 16, and 24 hours post-dose on Days 1 and 7
Accumulation Ratio of the Maximum Concentration (Cmax) of MK-8521 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 1
Plasma samples were collected from predose to 24 hours postdose for determination of the accumulation ratio of Cmax. The geometric mean accumulation ratio was calculated as Day 7 Cmax/Day 1 Cmax and presented as geometric mean ratio with a full range.
Measured: Predose and 1, 2, 4, 6, 8, 10, 12, 16, and 24 hours post-dose on Days 1 and 7
Accumulation Ratio of the Trough Concentration (Ctrough) of MK-8521 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 1
Plasma samples were collected predose on Days 2 (sampled after the Day 1 dose and prior to Day 2 dose) and 7 for determination of the accumulation ratio of Ctrough. The geometric mean accumulation ratio was calculated as Day 7 Ctrough/Day 1 Ctrough (sampled after the Day 1 dose and prior to Day 2 dose) and presented as geometric mean ratio with a full range.
Measured: Predose on Days 2 and 7
Area Under the Concentration-time Curve From 0 to 24 Hours (AUC0-24hr) of MK-8521 on Days 1, 7, and 14 for Type 2 Diabetes Mellitus (T2DM) and Non-Diabetic Overweight/Obese Participants in Part 2
AUC0-24hr was the area under the concentration-time curve of MK-8521 from time zero to 24 hours after administration. Plasma samples were collected from predose to 24 hours postdose for determination of AUC0-24hr. Individual values were natural log-transformed and evaluated with a linear-mixed effects model containing fixed effects for treatment, day, and treatment by day interaction, and a random effect for participant. Kenward and Roger's method was used to calculate the degree of freedom for the fixed effects. AUC0-24hr is presented as geometric mean and percent coefficient of variation of geometric mean.
Measured: Predose and 1, 2, 6, 10, 16, and 24 hours postdose on Days 1, 7, and 14
Accumulation Ratio of the Area Under the Concentration-time Curve From 0 to 24 Hours (AUC0-24hr) of MK-8521 for Type 2 Diabetes Mellitus (T2DM) and Non-Diabetic Overweight/Obese Participants in Part 2
Plasma samples were collected from predose to 24 hours postdose for determination of the accumulation ratio of AUC0-24hr. The geometric mean accumulation ratio was calculated as Day 7 AUC0-24hr/Day 1 AUC0-24hr and presented as geometric mean ratio and percent geometric coefficient of variation.
Measured: Predose and 1, 2, 6, 10, 16, and 24 hours post-dose on Days 1 and 7
Secondary outcomes (17)
Change From Baseline in Fasting Plasma Glucose (FPG) at Day 7 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 1
FPG was measured predose on Days 1 and 7. The change from baseline of FPG was calculated as the difference between the predose measurement on Day 1 (baseline) and the measurement obtained predose on Day 7. FPG is presented as mean change from baseline with a standard error.
Measured: Predose on Days 1 (baseline) and 7
Change From Baseline in Fasting Plasma Glucose (FPG) at Day 14 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 1
FPG was measured predose on Days 1 and 14. The change from baseline of FPG was calculated as the difference between the predose measurement on Day 1 (baseline) and the measurement obtained predose on Day 14. FPG is presented as mean change from baseline with a standard error.
Measured: Predose on Days 1 (baseline) and 14
Change From Baseline in 24-hour Weighted Mean Glucose (WMG) at Day 7 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 1
The 24-hour WMG was calculated as the area under the 24-hour glucose curve (AUC0-24hr) divided by 24 hours. Blood samples for glucose were collected immediately prior to, and after each meal. The change from baseline value for 24-hour WMG was calculated where baseline was the WMG before food and prior to treatment on Day 1. Blood for plasma glucose concentrations was obtained at predose Day 1 at pre meal (breakfast), 0.5, 1, 2, 3, 4 (pre lunch), 4.5, 5, 6, 7, 10 (pre dinner), 10.5, 11, 12, 13, 15 and 23 hours post breakfast meal; and on Day 7 at 1 (pre breakfast), 1.5, 2, 3, 4, 5 (pre lunch), 5.5, 6, 7, 8, 11 (pre dinner), 11.5, 12, 13, 14, 16, 24 hours post dose. Individual change from baseline 24-hour WMG was analyzed in a linear mixed effects model with fixed effects for treatment, day and treatment by day interaction, a random effect for participant, and baseline 24-hour WMG as a covariate. WMG is presented as least squares mean with a 95% confidence interval.
Measured: Baseline (predose and before food on Day 1) and up to 24 hours post Day 7 dose
Change From Baseline in 24-hour Weighted Mean Glucose (WMG) at Day 14 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 1
The 24-hour WMG was calculated as the area under the 24-hour glucose curve (AUC0-24hr) divided by 24 hours. Blood samples for glucose were collected immediately prior to and after each meal. The change from baseline value for 24-hour WMG was calculated where baseline was the WMG before food and prior to treatment on Day 1. Blood for plasma glucose concentrations was obtained on Day -1 at pre meal (breakfast), 0.5, 1, 2, 3, 4 (pre lunch), 4.5, 5, 6, 7, 10 (pre dinner), 10.5, 11, 12, 13, 15 and 23 hours post breakfast meal; and on Day 14 at 1 (pre breakfast), 1.5, 2, 3, 4, 5 (pre lunch), 5.5, 6, 7, 8, 11(pre dinner), 11.5, 12, 13, 14, 16, 24 hours post dose. Individual change from baseline 24-hour WMG was analyzed in a linear mixed effects model with fixed effects for treatment, day and treatment by day interaction, a random effect for participant, and baseline 24-hour WMG as a covariate. WMG is presented as least squares mean with a 95% confidence interval.
Measured: Baseline (predose and before food on Day 1) and up to 24 hours post Day 14 dose
Change From Baseline in Fasting Plasma Glucose (FPG) at Day 14 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2
FPG was measured predose on Days 1 and 14. The change from baseline of FPG was calculated as the difference between the predose measurement on Day 1 (baseline) and the measurement obtained predose on Day 14. FPG is presented as least squares mean change from baseline with a 95% confidence interval.
Measured: Predose on Days 1 (baseline) and 14
Change From Baseline in Fasting Plasma Glucose (FPG) at Day 19 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2
FPG was measured predose on Days 1 and 19. The change from baseline of FPG was calculated as the difference between the predose measurement on Day 1 (baseline) and the measurement obtained predose on Day 19. FPG is presented as least squares mean change from baseline with a 95% confidence interval.
Measured: Predose on Days 1 (baseline) and 19
Change From Baseline in Fasting Plasma Glucose (FPG) at Day 24 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2
FPG was measured predose on Days 1 and 24. The change from baseline of FPG was calculated as the difference between the predose measurement on Day 1 (baseline) and the measurement obtained predose on Day 24. FPG is presented as least squares mean change from baseline with a 95% confidence interval.
Measured: Predose on Days 1 (baseline) and 24
Change From Baseline in Fasting Plasma Glucose (FPG) at Day 29 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2
FPG was measured predose on Days 1 and 29. The change from baseline of FPG was calculated as the difference between the predose measurement on Day 1 (baseline) and the measurement obtained predose on Day 29. FPG is presented as least squares mean change from baseline with a 95% confidence interval.
Measured: Predose on Days 1 (baseline) and 29
Change From Baseline in 24-hour Weighted Mean Glucose (WMG) at Day 14 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2
The 24-hour WMG was calculated as the area under the 24-hour glucose curve (AUC0-24hr) divided by 24 hours. Plasma glucose concentrations were obtained on Day -1 at pre meal (breakfast), 1, 3, 4 (pre lunch), 5, 7, 10 (pre dinner), 11, 13, 15 and 23 hours post breakfast meal and Day 14 at 1 (pre breakfast), 2, 4, 5 (pre lunch), 6, 8, 11 (pre dinner), 12, 14, 16, 24 hours post dose. The timing of samples on Day -1 are relative to the breakfast meal. Day 14 samples are relative to dosing. The change from baseline value for 24-hour WMG was calculated where baseline was the WMG before food and prior to treatment on Day 1. Individual change from baseline 24-hour WMG was analyzed in a linear mixed effects model with group, day and group by day interaction as fixed effects, baseline 24-hour WMG as a covariate, and participant as a random effect. WMG is presented as least squares mean with a 95% confidence interval.
Measured: Baseline (predose and before food on Day 1) and up to 24 hours post Day 14 dose
Change From Baseline in 24-hour Weighted Mean Glucose (WMG) at Day 19 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2
The 24-hour WMG was calculated as the area under the 24-hour glucose curve (AUC0-24hr) divided by 24 hours. Plasma glucose concentrations were obtained on Day -1 at pre meal (breakfast), 1, 3, 4 (pre lunch), 5, 7, 10 (pre dinner), 11, 13, 15 and 23 hours post breakfast meal and Day 19 at 1 (pre breakfast), 2, 4, 5 (pre lunch), 6, 8, 11 (pre dinner), 12, 14, 16, 24 hours post dose. The timing of samples on Day -1 are relative to the breakfast meal. Day 19 samples are relative to dosing. The change from baseline value for 24-hour WMG was calculated where baseline was the WMG before food and prior to treatment on Day 1. Individual change from baseline 24-hour WMG was analyzed in a linear mixed effects model with group, day and group by day interaction as fixed effects, baseline 24-hour WMG as a covariate, and participant as a random effect. WMG is presented as least squares mean with a 95% confidence interval.
Measured: Baseline (predose and before food on Day 1) and up to 24 hours post Day 19 dose
Change From Baseline in 24-hour Weighted Mean Glucose (WMG) at Day 24 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2
The 24-hour WMG was calculated as the area under the 24-hour glucose curve (AUC0-24hr) divided by 24 hours. Plasma glucose concentrations were obtained on Day -1 at pre meal (breakfast), 1, 3, 4 (pre lunch), 5, 7, 10 (pre dinner), 11, 13, 15 and 23 hours post breakfast meal and Day 24 at 1 (pre breakfast), 2, 4, 5 (pre lunch), 6, 8, 11 (pre dinner), 12, 14, 16, 24 hours post dose. The timing of samples on Day -1 are relative to the breakfast meal. Day 24 samples are relative to dosing. The change from baseline value for 24-hour WMG was calculated where baseline was the WMG before food and prior to treatment on Day 1. Individual change from baseline 24-hour WMG was analyzed in a linear mixed effects model with group, day and group by day interaction as fixed effects, baseline 24-hour WMG as a covariate, and participant as a random effect. WMG is presented as least squares mean with a 95% confidence interval.
Measured: Baseline (predose and before food on Day 1) and up to 24 hours post Day 24 dose
Change From Baseline in 24-hour Weighted Mean Glucose (WMG) at Day 29 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2
The 24-hour WMG was calculated as the area under the 24-hour glucose curve (AUC0-24hr) divided by 24 hours. Plasma glucose concentrations were obtained on Day -1 at pre meal (breakfast), 1, 3, 4 (pre lunch), 5, 7, 10 (pre dinner), 11, 13, 15 and 23 hours post breakfast meal and Day 29 at 1 (pre breakfast), 2, 4, 5 (pre lunch), 6, 8, 11 (pre dinner), 12, 14, 16, 24 hours post dose. The timing of samples on Day -1 are relative to the breakfast meal. Day 29 samples are relative to dosing. The change from baseline value for 24-hour WMG was calculated where baseline was the WMG before food and prior to treatment on Day 1. Individual change from baseline 24-hour WMG was analyzed in a linear mixed effects model with group, day and group by day interaction as fixed effects, baseline 24-hour WMG as a covariate, and participant as a random effect. WMG is presented as least squares mean with a 95% confidence interval.
Measured: Baseline (predose and before food on Day 1) and up to 24 hours post Day 29 dose
Maximum Concentration (Cmax) of MK-8521 for Type 2 Diabetes Mellitus (T2DM) and Non-Diabetic Overweight/Obese Participants in Part 2
Cmax was the maximum observed concentration of MK-8521 in plasma after administration. Plasma samples were collected from predose to 120 hours postdose for determination of Cmax. Per protocol, Cmax in the non-diabetic overweight/obese participants was not measured on Days 19, 24, and 29 because they only received 14 days of treatment. Individual values were natural log-transformed and evaluated with a linear-mixed effects model containing fixed effects for treatment, day, and treatment by day interaction, and a random effect for participant. Kenward and Roger's method was used to calculate the degree of freedom for the fixed effects. Cmax is presented as geometric mean and percent coefficient of variation of geometric mean.
Measured: Predose and 1, 2, 6, 10, 16, 24 hours post dose on Days 1, 7, 14, 19, 24 (T2DM) and Days 1 and 7 (Non-Diabetic Overweight/Obese); predose and 1, 2, 6, 10, 16, 24, 72, 96. and 120 hours post dose on Day 14 (Non-Diabetic Overweight/Obese) and Day 29 (T2DM).
Trough Concentration (Ctrough) of MK-8521 for Type 2 Diabetes Mellitus (T2DM) and Non-Diabetic Overweight/Obese Participants in Part 2
Ctrough was the lowest observed concentration of MK-8521 in plasma. Plasma samples were collected predose on Day 2 (sampled after the Day 1 dose and prior to Day 2 dose), 7, 14, 19, 24, and 29 for determination of Ctrough. Per protocol, Ctrough in the non-diabetic overweight/obese participants was not measured on Days 19, 24, and 29 because they only received 14 days of treatment. Individual values were natural log-transformed and evaluated with a linear-mixed effects model containing fixed effects for treatment, day, and treatment by day interaction, and a random effect for participant. Kenward and Roger's method was used to calculate the degree of freedom for the fixed effects. Ctrough is presented as geometric mean and percent coefficient of variation of geometric mean.
Measured: Predose on Days 2 (sampled 24 hours after Day 1 dose) and 7, 14, 19, 24, and 29
Time to Maximum Concentration (Tmax) of MK-8521 for Type 2 Diabetes Mellitus (T2DM) and Non-Diabetic Overweight/Obese Participants in Part 2
Tmax was the time required to reach the maximum concentration of MK-8521 in plasma. Plasma samples were collected from predose to 120 hours postdose for determination of Tmax. Per protocol, Tmax in the non-diabetic overweight/obese participants was not measured on Days 19, 24, and 29 because they only received 14 days of treatment. Tmax is presented as median with a full range.
Measured: Predose and 1, 2, 6, 10, 16, 24 hours post dose on Days 1, 7, 14, 19, 24 (T2DM) and Days 1 and 7 (Non-Diabetic Overweight/Obese); predose and 1, 2, 6, 10, 16, 24, 72, 96. and 120 hours post dose on Day 14 (Non-Diabetic Overweight/Obese) and Day 29 (T2DM).
Apparent Terminal Half Life (t1/2) of MK-8521 on Day 29 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2
t1/2 was the time required to divide the MK-8521 concentration by half after reaching pseudo-equilibrium. Plasma samples were collected from predose to 120 hours postdose for determination of t1/2. Per protocol, t1/2 was measured on Day 29 which is the longest time point for sampling for T2DM participants 1/2 is presented as geometric mean and percent coefficient of variation of geometric mean.
Measured: Predose and 1, 2, 6, 10, 16, 24, 72, 96 and 120 hours post dose on Day 29
Apparent Terminal Half Life (t1/2) of MK-8521 on Day 14 for Non-Diabetic Overweight/Obese Participants in Part 2
t1/2 was the time required to divide the MK-8521 concentration by half after reaching pseudo-equilibrium. Plasma samples were collected from predose to 24 hours postdose for determination of t1/2. Per protocol, t1/2 was measured on Day 14 which is the longest time point for sampling for non-diabetic overweight/obese participants 1/2 is presented as geometric mean and percent coefficient of variation of geometric mean.
Measured: Predose and 1, 2, 6, 10, 16, and 24 hours post dose on Day 14
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Nov 2013 (estimated)
- Study start7 Nov 2013
- Primary completion3 Oct 2014
- Study completion3 Oct 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Diabetes MellitusStudies of the same condition, open and under way.
- More trials run by Merck Sharp & Dohme LLCThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 87 participants (actual)
Sponsor and investigators
- Lead sponsor
- Merck Sharp & Dohme LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Merck Sharp & Dohme LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01982630
- Sponsor's protocol ID
- 8521-003
- Status last verified
- Dec 2021
- First submitted
- 6 Nov 2013
- Last updated
- 8 Mar 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- Yes: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
Study at a glance
From the registry record, last updated by the sponsor on 8 Mar 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase Ib, Multicenter, Placebo and Active- Comparator-Controlled, Randomized, Double-Blind, Clinical Trial to Evaluate the Safety and Efficacy of MK-8521 Compared to Placebo and a Diabetes Drug in Subjects With Type 2 Diabetes Mellitus
- ClinicalTrials.gov ID
- NCT01982630
- Acronym / sponsor ID
- 8521-003
- Conditions
- Diabetes Mellitus
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 87 participants (actual)
- Lead sponsor
- Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
- Study start
- 7 Nov 2013 (actual)
- Primary completion
- 3 Oct 2014 (actual)
- Study completion
- 3 Oct 2014 (actual)
- First posted
- 13 Nov 2013 (estimated)
- Results
- Posted 8 Mar 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will evaluate the safety, efficacy, and pharmacokinetics of MK-8521 given once daily compared to placebo and another diabetes drug in participants with Type 2 diabetes mellitus (T2DM).
This study was modified by a protocol amendment to a 2-part trial to further test the safety and tolerability of MK-8521 at higher doses and to compare MK-8521 pharmacokinetics between participants with T2DM and healthy participants. An additional cohort of T2DM participants and a cohort of non-diabetic obese participants has been added.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 8
| Arm | Type | Receives |
|---|---|---|
| Part 1: MK-8521 64/120 μg/day | Experimental | Drug: MK-8521Type 2 diabetes mellitus (T2DM) participants received once daily subcutaneous MK-8521 starting at 64 μg on Days 1 to 7 and escalated to 120 μg on Days 8 to 14. |
| Part 1: MK-8521 34/72 μg/day | Experimental | Drug: MK-8521T2DM participants received once daily subcutaneous MK-8521 starting at 34 μg on Days 1 to 7 and escalated to 72 μg on Days 8 to 14. |
| Part 1: Liraglutide 0.6/1.2/1.8 mg/day | Active comparator | Drug: LiraglutideT2DM participants received once daily subcutaneous liraglutide starting at 0.6 mg on Day 1 and 2, escalated to 1.2 mg on Days 3 to 7, and escalated to 1.8 mg on Days 8 to 14. |
| Part 1: Placebo for MK-8521 | Placebo comparator | Drug: PlaceboT2DM participants received once daily subcutaneous placebo for MK-8521 for 14 days. |
| Part 2: MK-8521 64/120/180/240/300 µg/day-T2DM | Experimental | Drug: MK-8521T2DM participants received once daily subcutaneous MK-8521 titrated to 300 µg starting at 64 µg and increasing to 120 µg on Day 8, 180 µg on Day 15, 240 µg on Day 20, and 300 µg on Day 25. The total number of dosing days was 29. |
| Part 2: Liraglutide 0.6/1.2/1.8 mg/day-T2DM | Active comparator | Drug: LiraglutideT2DM participants received once daily subcutaneous liraglutide titrated to 1.8 mg starting at 0.6 mg and increasing to 1.2 mg on Day 8, and 1.8 mg on Day 15. The total number of dosing days was 29. |
| Part 2: Placebo for MK-8521-T2DM | Placebo comparator | Drug: PlaceboT2DM participants received once daily subcutaneous placebo for MK-8521 for 29 days. |
| Part 2: MK-8521 64/120 µg/day-Non-Diabetic Overweight/Obese | Experimental | Drug: MK-8521Non-diabetic overweight/obese participants received once daily subcutaneous MK-8521 titrated to 120 µg starting at 64 µg and increasing to 120 µg on Day 8. The total number of dosing days was 14. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Male, or female of non-childbearing potential with Type 2 diabetes mellitus (Parts 1 and 2) or non-diabetic (Part 2)
- Body mass index (BMI) between: ≥27 and ≤40 kg/m^2
- A1C (average blood sugar for the past 2 to 3 months) value ≥7.0 and ≤11.0 % (Part 1) or ≥ 6.5 and ≤11.0 % (Part 2) at the time of screening (T2DM participants)
- A1C value <5.7 at the time of screening (non-diabetic subjects in Part 2 only)
- On a stable dose of metformin (≥1000 mg total daily dose) for at least 12 weeks at the time of screening (T2DM participants)
Key exclusion criteria (20 listed)
- Mentally or legally incapacitated
- History of clinically significant psychiatric disorder of the last 5 years. Participants with situational depression may be enrolled in the trial at the discretion of the Investigator
- History of Type 1 diabetes mellitus or a history of ketoacidosis
- History of clinically significant gastrointestinal, hematological, hepatic, immunological, renal, respiratory, genitourinary or major neurological abnormalities or diseases
- History of cardiovascular disease or cardiac conduction disorder
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MK-8521 | Drug | Part 1: MK-8521 34/72 μg/day, Part 1: MK-8521 64/120 μg/day, Part 2: MK-8521 64/120 µg/day-Non-Diabetic Overweight/Obese, Part 2: MK-8521 64/120/180/240/300 µg/day-T2DM |
| Liraglutide | Drug | Part 1: Liraglutide 0.6/1.2/1.8 mg/day, Part 2: Liraglutide 0.6/1.2/1.8 mg/day-T2DM |
| Placebo | Drug | Part 1: Placebo for MK-8521, Part 2: Placebo for MK-8521-T2DM |
Primary outcome
Number of Participants Experiencing Adverse Events (AEs) in Part 1
Time frame: Up to approximately 42 days
An AE is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE. AEs are presented by individual dose received by participants during titration in an assigned study treatment sequence.
Number of Participants Experiencing Adverse Events (AEs) in Part 2
Time frame: Up to approximately 57 days
An AE is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE. AEs are presented by individual dose received by participants during titration in an assigned study treatment sequence.
Number of Participants Discontinuing Study Drug Due to Adverse Events (AEs) in Part 1
Time frame: Up to approximately 14 days
An AE is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE. Discontinuations are presented by individual dose received by participants during titration in an assigned study treatment sequence.
Number of Participants Discontinuing Study Drug Due to Adverse Events (AEs) in Part 2
Time frame: Up to approximately 29 days
An AE is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE. Discontinuations are presented by individual dose received by participants during titration in an assigned study treatment sequence.
Change From Baseline in Time-weighted Average From 0 to 24 Hours (TWA0-24hr) of Heart Rate (HR) After 7 Days of Treatment in Type 2 Diabetes Mellitus (T2DM) Participants in Part 1
Time frame: Baseline (predose Day 1) and up to 24 hours post Day 7 dose
Semi-recumbent heart rate was assessed at baseline on Day 1; Day 7 at predose, 2, 4, 6, 8, 12, 13, 14, 15, 16, 22 hours postdose; and prior to dosing on Day 8. Heart rate was measured in triplicate with at least a 1-2-minute interval between measurements. The repeated measurements were averaged before conducting the statistical analysis. TWA0-24hr was calculated as the area under the measurement-time curve (AUC) divided by the time period of over which the measurements were made (i.e. 24 hrs.). Change from baseline TWA0-24hr HR was calculated as the TWA0-24hr HR at Day 7 minus baseline where baseline was defined as predose on Day 1.
Change From Baseline in Time-weighted Average From 0 to 24 Hours (TWA0-24hr) of Heart Rate (HR) After 7 Days of Treatment in Type 2 Diabetes Mellitus (T2DM) Participants in Part 2
Time frame: Baseline (predose Day 1) and up to 24 hours post Day 7 dose
Semi-recumbent HR was measured in triplicate with at least a 1-2-minute interval between measurements at the following time points: baseline on Day 1; Day 7: predose, 2, 4, 6, 8, 12, and 16 hours postdose; and prior to dosing on Day 8. The repeated measurements were averaged before conducting the analysis. TWA0-24hr was calculated as the AUC divided by the time period of over which the measurements were made (i.e. 24 hrs.). Change from baseline TWA0-24hr HR was calculated as the TWA0-24hr HR at Day 7 minus baseline where baseline was defined as predose on Day 1.
Change From Baseline in Time-weighted Average From 0 to 24 Hours (TWA0-24hr) of Heart Rate (HR) After 14 Days of Treatment in Type 2 Diabetes Mellitus (T2DM) Participants in Part 1
Time frame: Baseline (predose Day 1) and up to 24 hours post Day 14 dose
Semi-recumbent HR was measured in triplicate with at least a 1-2-minute interval between measurements at the following time points: baseline on Day 1; Day 14: predose, 2, 4, 6, 8, 12, 13, 14, 15, 16, 22 hours postdose and prior to dosing on Day 15. The repeated measurements were averaged before conducting the analysis. TWA0-24hr was calculated as the AUC divided by the time period of over which the measurements were made (i.e. 24 hrs.). Change from baseline TWA0-24hr HR was calculated as the TWA0-24hr HR at Day 14 minus baseline where baseline was defined as predose on Day 1.
Change From Baseline in Time-weighted Average From 0 to 24 Hours (TWA0-24hr) of Heart Rate (HR) After 14 Days of Treatment in Type 2 Diabetes Mellitus (T2DM) Participants in Part 2
Time frame: Baseline (predose Day 1) and up to 24 hours post Day 14 dose
Semi-recumbent HR was measured in triplicate with at least a 1-2-minute interval between measurements at the following time points: baseline on Day 1; Day 14: predose, 2, 4, 6, 8, 12, 16, hours postdose; and prior to dosing on Day 15. The repeated measurements were averaged before conducting the analysis. TWA0-24hr was calculated as the AUC divided by the time period of over which the measurements were made (i.e. 24 hrs.). Change from baseline TWA0-24hr HR was calculated as the TWA0-24hr HR at Day 14 minus baseline where baseline was defined as predose on Day 1.
Change From Baseline in Time-weighted Average From 0 to 24 Hours (TWA0-24hr) of Heart Rate (HR) After 19 Days of Treatment in Type 2 Diabetes Mellitus (T2DM) Participants in Part 2
Time frame: Baseline (predose Day 1) and up to 24 hours post Day 19 dose
Semi-recumbent HR was measured in triplicate with at least a 1-2-minute interval between measurements at the following time points: baseline on Day 1; Day 19: predose, 2, 4, 6, 8, 12, 16, hours post dose; and prior to dosing on Day 20. The repeated measurements were averaged before conducting the analysis. TWA0-24hr was calculated as the AUC divided by the time period of over which the measurements were made (i.e. 24 hrs.). Change from baseline TWA0-24hr HR was calculated as the TWA0-24hr HR at Day 19 minus baseline where baseline was defined as predose on Day 1.
Change From Baseline in Time-weighted Average From 0 to 24 Hours (TWA0-24hr) of Heart Rate (HR) After 24 Days of Treatment in Type 2 Diabetes Mellitus (T2DM) Participants in Part 2
Time frame: Baseline (predose Day 1) and up to 24 hours post Day 24 dose
Semi-recumbent HR was measured in triplicate with at least a 1-2-minute interval between measurements at the following time points: baseline on Day 1; Day 24: predose, 2, 4, 6, 8, 12, 16, hours postdose; and prior to dosing on Day 25. The repeated measurements were averaged before conducting the analysis. TWA0-24hr was calculated as the AUC divided by the time period of over which the measurements were made (i.e. 24 hrs.). Change from baseline TWA0-24hr HR was calculated as the TWA0-24hr HR at Day 24 minus baseline where baseline was defined as predose on Day 1.
Change From Baseline in Time-weighted Average From 0 to 24 Hours (TWA0-24hr) of Heart Rate (HR) After 29 Days of Treatment in Type 2 Diabetes Mellitus (T2DM) Participants in Part 2
Time frame: Baseline (predose Day 1) and up to 24 hours post Day 29 dose
Semi-recumbent HR was measured in triplicate with at least a 1-2-minute interval between measurements at the following time points: baseline on Day 1; and Day 29: predose, 2, 4, 6, 8, 12, 16 and 24 hours postdose. The repeated measurements were averaged before conducting the analysis. TWA0-24hr was calculated as the AUC divided by the time period of over which the measurements were made (i.e. 24 hrs.). Change from baseline TWA0-24hr HR was calculated as the TWA0-24hr HR at Day 29 minus baseline where baseline was defined as predose on Day 1.
Change From Baseline in Peak Heart Rate (PHR) at Day 7 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2
Time frame: Baseline (predose Day 1) and up to 24 hours post Day 7 dose
PHR was defined as the maximum time matched baseline adjusted heart rate over 24 hours. Semi-recumbent PHR was measured in triplicate with at least a 1-2-minute interval between measurements at the following time points: baseline on Day 1; Day 7: predose, 2, 4, 6, 8, 12, and 16 hours postdose; and prior to dosing on Day 8. The repeated measurements were averaged before conducting the analysis. Change from baseline PHR was calculated as the peak heart rate at Day 7 minus baseline where baseline was defined as predose on Day 1.
Change From Baseline in Peak Heart Rate (PHR) at Day 14 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2
Time frame: Baseline (predose Day 1) and up to 24 hours post Day 14 dose
PHR was defined as the maximum time matched baseline adjusted heart rate over 24 hours. Semi-recumbent PHR was measured in triplicate with at least a 1-2-minute interval between measurements at the following time points: baseline on Day 1; Day 14: predose, 2, 4, 6, 8, 12, and 16 hours postdose; and prior to dosing on Day 15. The repeated measurements were averaged before conducting the analysis. Change from baseline PHR was calculated as the peak heart rate at Day 14 minus baseline where baseline was defined as predose on Day 1.
Change From Baseline in Peak Heart Rate (PHR) at Day 19 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2
Time frame: Baseline (predose Day 1) and up to 24 hours post Day 19 dose
PHR was defined as the maximum time matched baseline adjusted heart rate over 24 hours. Semi-recumbent PHR was measured in triplicate with at least a 1-2-minute interval between measurements at the following time points: baseline on Day 1; Day 19: predose, 2, 4, 6, 8, 12, and 16 hours postdose; and prior to dosing on Day 20. The repeated measurements were averaged before conducting the analysis. Change from baseline PHR was calculated as the peak heart rate at Day 19 minus baseline where baseline was defined as predose on Day 1.
Change From Baseline in Peak Heart Rate (PHR) at Day 24 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2
Time frame: Baseline (predose Day 1) and up to 24 hours post Day 24 dose
PHR was defined as the maximum time matched baseline adjusted heart rate over 24 hours. Semi-recumbent PHR was measured in triplicate with at least a 1-2-minute interval between measurements at the following time points: baseline on Day 1; Day 24: predose, 2, 4, 6, 8, 12, and 16 hours postdose; and prior to dosing on Day 25. The repeated measurements were averaged before conducting the analysis. Change from baseline PHR was calculated as the peak heart rate at Day 24 minus baseline where baseline was defined as predose on Day 1.
Change From Baseline in Peak Heart Rate (PHR) at Day 29 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2
Time frame: Baseline (predose Day 1) and up to 24 hours post Day 29 dose
PHR was defined as the maximum time matched baseline adjusted heart rate over 24 hours. Semi-recumbent PHR was measured in triplicate with at least a 1-2-minute interval between measurements at the following time points: baseline on Day 1; and Day 29: predose 2, 4, 6, 8, 12, 16, and 24 hours post dose. The repeated measurements were averaged before conducting the analysis. Change from baseline PHR was calculated as the peak heart rate at Day 29 minus baseline where baseline was defined as predose on Day 1.
Change From Baseline in Resting Morning Heart Rate (RMHR) After the Day 7 Dose for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2
Time frame: Baseline (predose Day 1) and Day 8 (24 hours after Day 7)
Semi-recumbent RMHR was measured in triplicate with at least a 1-2-minute interval between measurements. The repeated measurements were averaged for each time point. Change from baseline RMHR was calculated as the RMHR 24 hours after the Day 7 dose (predose Day 8) minus baseline. Baseline was an average of 2 readings prior to dosing on Day 1.
Change From Baseline in Resting Morning Heart Rate (RMHR) After the Day 14 Dose for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2
Time frame: Baseline (predose Day 1) and Day 15 (24 hours after Day 14)
Semi-recumbent RMHR was measured in triplicate with at least a 1-2-minute interval between measurements. The repeated measurements were averaged for each time point. Change from baseline RMHR was calculated as the RMHR 24 hours after the Day 14 dose (predose Day 15) minus baseline. Baseline was an average of 2 readings prior to dosing on Day 1.
Change From Baseline in Resting Morning Heart Rate (RMHR) After the Day 19 Dose for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2
Time frame: Baseline (predose Day 1) and Day 20 (24 hours after Day 19)
Semi-recumbent RMHR was measured in triplicate with at least a 1-2-minute interval between measurements. The repeated measurements were averaged for each time point. Change from baseline RMHR was calculated as the RMHR 24 hours after the Day 19 dose (predose Day 20) minus baseline. Baseline was an average of 2 readings prior to dosing on Day 1.
Change From Baseline in Resting Morning Heart Rate (RMHR) After the Day 24 Dose for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2
Time frame: Baseline (predose Day 1) and Day 25 (24 hours after Day 24)
Semi-recumbent RMHR was measured in triplicate with at least a 1-2-minute interval between measurements. The repeated measurements were averaged for each time point. Change from baseline RMHR was calculated as the RMHR 24 hours after the Day 24 dose (predose Day 25) minus baseline. Baseline was an average of 2 readings prior to dosing on Day 1.
Change From Baseline in Resting Morning Heart Rate (RMHR) After the Day 29 Dose for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2
Time frame: Baseline (predose Day 1) and Day 30 (24 hours after Day 29)
Semi-recumbent RMHR was measured in triplicate with at least a 1-2-minute interval between measurements. The repeated measurements were averaged for each time point. Change from baseline RMHR was calculated as the RMHR 24 hours after the Day 29 dose minus baseline. Baseline was an average of 2 readings prior to dosing on Day 1.
Area Under the Concentration-time Curve From 0 to 24 Hours (AUC0-24hr) of MK-8521 on Days 1, 7, and 14 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 1
Time frame: Predose and 1, 2, 4, 6, 8, 10, 12, 16, and 24 hours post-dose on Days 1, 7, and 14
AUC0-24hr was the area under the concentration-time curve of MK-8521 from time zero to 24 hours after administration. Plasma samples were collected from predose to 24 hours postdose for determination of AUC0-24hr. Individual values were natural log-transformed and evaluated with a linear-mixed effects model containing fixed effects for treatment, day, and treatment by day interaction, and a random effect for participant. Kenward and Roger's method was used to calculate the degree of freedom for the fixed effects. AUC0-24hr is presented as geometric mean and percent coefficient of variation of geometric mean.
Maximum Concentration (Cmax) of MK-8521 on Days 1 and 7 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 1
Time frame: Predose and 1, 2, 4, 6, 8, 10, 12, 16, and 24 hours post-dose on Days 1 and 7
Cmax was the maximum observed concentration of MK-8521 in plasma after administration. Plasma samples were collected from predose to 24 hours postdose for determination of Cmax. Individual values were natural log-transformed and evaluated with a linear-mixed effects model containing fixed effects for treatment, day, and treatment by day interaction, and a random effect for participant. Kenward and Roger's method was used to calculate the degree of freedom for the fixed effects. Cmax is presented as geometric mean and percent coefficient of variation of geometric mean.
Maximum Concentration (Cmax) of MK-8521 on Day 14 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 1
Time frame: Predose and 1, 2, 4, 6, 8, 10, 12, 16, 24, 72, 96, and 120 hours post-dose on Day 14
Cmax was the maximum observed concentration of MK-8521 in plasma after administration on Day 14. Plasma samples were collected from predose to 120 hours postdose for determination of Cmax. Individual values were natural log-transformed and evaluated with a linear-mixed effects model containing fixed effects for treatment, day, and treatment by day interaction, and a random effect for participant. Kenward and Roger's method was used to calculate the degree of freedom for the fixed effects. Cmax is presented as geometric mean and percent coefficient of variation of geometric mean.
Trough Concentration (Ctrough) of MK-8521 on Days 1, 7, and 14 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 1
Time frame: Predose on Days 2, 7, and 14
Ctrough was the lowest observed concentration of MK-8521 in plasma. Plasma samples were collected predose on Day 2 (sampled after the Day 1 dose and prior to Day 2 dose), 7, and 14 for determination of Ctrough. Individual values were natural log-transformed and evaluated with a linear-mixed effects model containing fixed effects for treatment, day, and treatment by day interaction, and a random effect for participant. Kenward and Roger's method was used to calculate the degree of freedom for the fixed effects. Ctrough is presented as geometric mean and percent coefficient of variation of geometric mean.
Time to Maximum Concentration (Tmax) of MK-8521 on Days 1 and 7 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 1
Time frame: Predose and 1, 2, 4, 6, 8, 10, 12, 16, and 24 hours post-dose on Days 1 and 7
Tmax was the time required to reach the maximum concentration of MK-8521 in plasma. Plasma samples were collected from predose to 24 hours postdose for determination of Tmax. Tmax is presented as median with a full range.
Time to Maximum Concentration (Tmax) of MK-8521 on Day 14 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 1
Time frame: Predose and 1, 2, 4, 6, 8, 10, 12, 16, 24, 72, 96, and 120 hours post-dose on Day 14
Tmax was the time required to reach the maximum concentration of MK-8521 in plasma. Plasma samples were collected from predose to 120 hours postdose for determination of Tmax. Tmax is presented as median with a full range.
Apparent Terminal Half Life (t1/2) of MK-8521 on Days 1 and 7 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 1
Time frame: Predose and 1, 2, 4, 6, 8, 10, 12, 16, and 24 hours post-dose on Days 1 and 7
t1/2 was the time required to divide the MK-8521 concentration by half after reaching pseudo-equilibrium. Plasma samples were collected from predose to 24 hours postdose for determination of t1/2. t1/2 is presented as geometric mean and percent coefficient of variation of geometric mean.
Apparent Terminal Half Life (t1/2) of MK-8521 on Day 14 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 1
Time frame: Predose and 1, 2, 4, 6, 8, 10, 12, 16, 24, 72, 96, and 120 hours post-dose on Day 14
t1/2 was the time required to divide the MK-8521 concentration by half after reaching pseudo-equilibrium. Plasma samples were collected from predose to 120 hours postdose for determination of t1/2. t1/2 was measured on Day 14 which is the longest time point for sampling for T2DM participants in Part 1. t1/2 is presented as geometric mean and percent coefficient of variation of geometric mean.
Accumulation Ratio of the Area Under the Concentration-time Curve From 0 to 24 Hours (AUC0-24hr) of MK-8521 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 1
Time frame: Predose and 1, 2, 4, 6, 8, 10, 12, 16, and 24 hours post-dose on Days 1 and 7
Plasma samples were collected from predose to 24 hours postdose for determination of the accumulation ratio of AUC0-24hr. The geometric mean accumulation ratio was calculated as Day 7 AUC0-24hr/Day 1 AUC0-24hr and presented as geometric mean ratio with a full range.
Accumulation Ratio of the Maximum Concentration (Cmax) of MK-8521 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 1
Time frame: Predose and 1, 2, 4, 6, 8, 10, 12, 16, and 24 hours post-dose on Days 1 and 7
Plasma samples were collected from predose to 24 hours postdose for determination of the accumulation ratio of Cmax. The geometric mean accumulation ratio was calculated as Day 7 Cmax/Day 1 Cmax and presented as geometric mean ratio with a full range.
Accumulation Ratio of the Trough Concentration (Ctrough) of MK-8521 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 1
Time frame: Predose on Days 2 and 7
Plasma samples were collected predose on Days 2 (sampled after the Day 1 dose and prior to Day 2 dose) and 7 for determination of the accumulation ratio of Ctrough. The geometric mean accumulation ratio was calculated as Day 7 Ctrough/Day 1 Ctrough (sampled after the Day 1 dose and prior to Day 2 dose) and presented as geometric mean ratio with a full range.
Area Under the Concentration-time Curve From 0 to 24 Hours (AUC0-24hr) of MK-8521 on Days 1, 7, and 14 for Type 2 Diabetes Mellitus (T2DM) and Non-Diabetic Overweight/Obese Participants in Part 2
Time frame: Predose and 1, 2, 6, 10, 16, and 24 hours postdose on Days 1, 7, and 14
AUC0-24hr was the area under the concentration-time curve of MK-8521 from time zero to 24 hours after administration. Plasma samples were collected from predose to 24 hours postdose for determination of AUC0-24hr. Individual values were natural log-transformed and evaluated with a linear-mixed effects model containing fixed effects for treatment, day, and treatment by day interaction, and a random effect for participant. Kenward and Roger's method was used to calculate the degree of freedom for the fixed effects. AUC0-24hr is presented as geometric mean and percent coefficient of variation of geometric mean.
Accumulation Ratio of the Area Under the Concentration-time Curve From 0 to 24 Hours (AUC0-24hr) of MK-8521 for Type 2 Diabetes Mellitus (T2DM) and Non-Diabetic Overweight/Obese Participants in Part 2
Time frame: Predose and 1, 2, 6, 10, 16, and 24 hours post-dose on Days 1 and 7
Plasma samples were collected from predose to 24 hours postdose for determination of the accumulation ratio of AUC0-24hr. The geometric mean accumulation ratio was calculated as Day 7 AUC0-24hr/Day 1 AUC0-24hr and presented as geometric mean ratio and percent geometric coefficient of variation.
17 secondary outcomes
Change From Baseline in Fasting Plasma Glucose (FPG) at Day 7 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 1
Time frame: Predose on Days 1 (baseline) and 7
Change From Baseline in Fasting Plasma Glucose (FPG) at Day 14 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 1
Time frame: Predose on Days 1 (baseline) and 14
Change From Baseline in 24-hour Weighted Mean Glucose (WMG) at Day 7 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 1
Time frame: Baseline (predose and before food on Day 1) and up to 24 hours post Day 7 dose
Change From Baseline in 24-hour Weighted Mean Glucose (WMG) at Day 14 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 1
Time frame: Baseline (predose and before food on Day 1) and up to 24 hours post Day 14 dose
Change From Baseline in Fasting Plasma Glucose (FPG) at Day 14 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2
Time frame: Predose on Days 1 (baseline) and 14
Change From Baseline in Fasting Plasma Glucose (FPG) at Day 19 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2
Time frame: Predose on Days 1 (baseline) and 19
Change From Baseline in Fasting Plasma Glucose (FPG) at Day 24 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2
Time frame: Predose on Days 1 (baseline) and 24
Change From Baseline in Fasting Plasma Glucose (FPG) at Day 29 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2
Time frame: Predose on Days 1 (baseline) and 29
Change From Baseline in 24-hour Weighted Mean Glucose (WMG) at Day 14 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2
Time frame: Baseline (predose and before food on Day 1) and up to 24 hours post Day 14 dose
Change From Baseline in 24-hour Weighted Mean Glucose (WMG) at Day 19 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2
Time frame: Baseline (predose and before food on Day 1) and up to 24 hours post Day 19 dose
Change From Baseline in 24-hour Weighted Mean Glucose (WMG) at Day 24 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2
Time frame: Baseline (predose and before food on Day 1) and up to 24 hours post Day 24 dose
Change From Baseline in 24-hour Weighted Mean Glucose (WMG) at Day 29 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2
Time frame: Baseline (predose and before food on Day 1) and up to 24 hours post Day 29 dose
Maximum Concentration (Cmax) of MK-8521 for Type 2 Diabetes Mellitus (T2DM) and Non-Diabetic Overweight/Obese Participants in Part 2
Time frame: Predose and 1, 2, 6, 10, 16, 24 hours post dose on Days 1, 7, 14, 19, 24 (T2DM) and Days 1 and 7 (Non-Diabetic Overweight/Obese); predose and 1, 2, 6, 10, 16, 24, 72, 96. and 120 hours post dose on Day 14 (Non-Diabetic Overweight/Obese) and Day 29 (T2DM).
Trough Concentration (Ctrough) of MK-8521 for Type 2 Diabetes Mellitus (T2DM) and Non-Diabetic Overweight/Obese Participants in Part 2
Time frame: Predose on Days 2 (sampled 24 hours after Day 1 dose) and 7, 14, 19, 24, and 29
Time to Maximum Concentration (Tmax) of MK-8521 for Type 2 Diabetes Mellitus (T2DM) and Non-Diabetic Overweight/Obese Participants in Part 2
Time frame: Predose and 1, 2, 6, 10, 16, 24 hours post dose on Days 1, 7, 14, 19, 24 (T2DM) and Days 1 and 7 (Non-Diabetic Overweight/Obese); predose and 1, 2, 6, 10, 16, 24, 72, 96. and 120 hours post dose on Day 14 (Non-Diabetic Overweight/Obese) and Day 29 (T2DM).
Apparent Terminal Half Life (t1/2) of MK-8521 on Day 29 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2
Time frame: Predose and 1, 2, 6, 10, 16, 24, 72, 96 and 120 hours post dose on Day 29
Apparent Terminal Half Life (t1/2) of MK-8521 on Day 14 for Non-Diabetic Overweight/Obese Participants in Part 2
Time frame: Predose and 1, 2, 6, 10, 16, and 24 hours post dose on Day 14
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Mar 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Director study director
Merck Sharp & Dohme LLC
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing MK-8521 and Liraglutide in people with Diabetes Mellitus, run by Merck Sharp & Dohme LLC.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Mar 2022. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 8 Mar 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants Experiencing Adverse Events (AEs) in Part 1 (time frame: Up to approximately 42 days). The study lists 34 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Mar 2022.