Type 2 Diabetes MellitusPhase 1NCT01971554

Safety, Tolerability, Pharmacodynamics, and Pharmacokinetics of MK-8666 in Participants With Type 2 Diabetes Mellitus (MK-8666-003)

A Phase 1 study testing MK-8666 in people with Type 2 Diabetes Mellitus, run by Merck Sharp & Dohme LLC.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial summary

Who is it for?: Ages 18 to 65 years
Conditions the study is for: Type 2 Diabetes Mellitus
What is being tested?: MK-8666
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 63 participants
Where: No sites listed yet
Study dates: 14 Oct 2013to 26 Apr 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
No healthy volunteers
Adult, Older adult

Who may be able to join

If female, must be either postmenopausal or surgically sterile
A Body Mass Index (BMI) ≥18 kg/m^2 to ≤40 kg/m^2, inclusive.
A diagnosis of T2DM
Drug naïve or is being treated with no more than 2 oral antihyperglycemic agents (thiazolidenediones are excluded)
Judged to be in good health except for T2DM
Willing to follow a standard weight maintaining diet throughout the study
A nonsmoker or has not used nicotine or nicotine-containing products for at least 3 months

Who cannot join

A history of clinically significant endocrine (except T2DM), gastrointestinal, cardiovascular, hematological, hepatic, immunological, renal, respiratory, or genitourinary abnormalities or diseases
A history of myositis or complaints including diffuse myalgias, muscle tenderness, or weakness.
A history of cancer (malignancy) excepting adequately treated non-melanomatous skin carcinoma or carcinoma in situ of the cervix
Has clinically unstable diabetic retinopathy, neuropathy, and/or clinical evidence of gastroparesis (frequent nausea, bloating or vomiting, severe gastroesophageal reflux, early satiety)
A history of type 1 diabetes mellitus and/or history of ketoacidosis
Taking a medication for a co-morbid condition that is not permitted during the study

Show all 12Show fewer

A history of significant multiple and/or severe allergies
Positive for hepatitis B surface antigen, hepatitis C antibodies or human immunodeficiency virus
Had major surgery, donated or lost 1 unit of blood within 4 weeks prior to study participation
Participated in another investigational trial within 4 weeks prior to study participation
Consumes excessive amounts of alcoholic or caffeine-containing beverages
A regular user of illicit drugs or a history of drug or alcohol abuse within the past year

About this study

Official title: A Multiple Dose Clinical Trial to Study the Safety, Tolerability, Pharmacodynamics, and Pharmacokinetics of MK-8666 in Type 2 Diabetes Mellitus Patients

This is a study of the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of MK-8666 in participants with type 2 diabetes mellitus (T2DM). Participants enrolled in this trial would be either treatment-naive or have washed off of oral anti-hyperglycemic agents. MK-8666 is planned to be administered orally for up to 2 weeks. The primary hypothesis for this study is that after 14 days of once daily treatment with MK-8666, at a dose that is safe and well tolerated, the placebo-corrected fasting plasma glucose reduction from baseline is ≥34 mg/dL.

Conditions: Type 2 Diabetes Mellitus
Being tested: MK-8666, Placebo
Medical subject headings: Diabetes Mellitus, Type 2

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

MK-8666Drug
MK-8666, capsules, oral, QD, Days 1 to 14
PlaceboDrug
Placebo, capsules, oral, QD, Days 1 to 14

Study groups in NCT01971554
Study group	Role	What they receive
MK-8666 50 mg	Experimental	MK-8666, 50 mg, oral, once a day (QD) for Days 1 to 14. Receives: Drug: MK-8666; Drug: Placebo
MK-8666 150 mg	Experimental	MK-8666, 150 mg, oral, QD, for Days 1 to 14 Receives: Drug: MK-8666; Drug: Placebo
MK-8666 500 mg	Experimental	MK-8666, 500 mg, oral, QD for Days 1 to 14 Receives: Drug: MK-8666; Drug: Placebo
Placebo	Placebo comparator	Placebo, oral, QD for Days 1 to 14 Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

Change From Baseline in Fasting Plasma Glucose (FPG) at Day 15
Blood glucose was measured on a fasting basis (collected after an 8-hour fast). Blood was collected on Day -1 (pre-planned dose), predose on Days 1, 3, 7, and 14, and 24h postdose Day 14 (Day 15). The baseline measurement was computed as the average of the Day -1 and predose Day 1 measurements. FPG is expressed as mg/dL. This change from baseline reflects values for Day 15 FPG minus Day 0 FPG values.
Measured: Predose (Baseline) and 24 h postdose Day 14 (Day 15)
Number of Participants Who Experienced at Least Once Adverse Event
An adverse event (AE) is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.
Measured: Up to 28 days
Number of Participants Who Discontinued Study Drug Due to an AE
An adverse event (AE) is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.
Measured: Up to 14 days

Secondary outcomes (4)

Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC0-24h)
AUC0-last is a measure of the total amount of drug in the plasma from the dose to 24 hours after the dose of study drug. Pharmacokinetic parameter analysis was not performed on the Placebo group. Method of dispersion for AUC0-24h was geometric mean coefficient of variation percentage.
Measured: Day 1: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, and 24 hours postdose; Day 14 : Predose, 0.5, 1, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 48, 72 hours postdose
Maximum Plasma Drug Concentration After Dosing (Cmax)
Cmax is a measure of the maximum amount of drug in the plasma after the dose of study drug. Pharmacokinetic parameter analysis was not performed on the Placebo group. Method of dispersion for Cmax was geometric mean coefficient of variation percentage.
Measured: Day 1: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, and 24 hours postdose; Day 14 : Predose, 0.5, 1, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 48, 72 hours postdose
Time to Reach Cmax (Tmax)
Tmax is a measure of the time to reach the maximum concentration in the plasma after the dose of study drug. Pharmacokinetic parameter analysis was not performed on the Placebo group.
Measured: Day 1: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, and 24 hours postdose; Day 14 : Predose, 0.5, 1, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 48, 72 hours postdose
Change From Baseline in 24-Hour Weighted Mean Glucose (24h-WMG) at Day 15
The 24h-WMG was considered to provide an integrated assessment of the glycemic exposure over the 24-hour period, and was derived from 18 blood samples collected immediately prior to, and after each meal, and overnight and fasting one hour pre-dose. A "weighted" rather than a "simple" mean is used to avoid overrepresentation of post-meal glucose values. On each day (Day -1 and Day 14), the WMG was computed as a time-weighted average of the 18 individual measurements.
Measured: Baseline and Day 15

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

14 Oct 201326 Apr 2014

First posted29 Oct 2013 (estimated)
Study start14 Oct 2013
Primary completion26 Apr 2014
Study completion26 Apr 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.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Type 2 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: 63 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01971554
Sponsor's protocol ID: 8666-003
Status last verified: Aug 2018
First submitted: 14 Oct 2013
Last updated: 10 Sep 2018
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
Individual data sharing: Yes: https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf

Publications

Krug AW, Vaddady P, Railkar RA, Musser BJ, Cote J, Ederveen A, Krefetz DG, DeNoia E, Free AL, Morrow L, Chakravarthy MV, Kauh E, Tatosian DA, Kothare PA. Leveraging a Clinical Phase Ib Proof-of-Concept Study for the GPR40 Agonist MK-8666 in Patients With Type 2 Diabetes for Model-Informed Phase II Dose Selection. Clin Transl Sci. 2017 Sep;10(5):404-411. doi: 10.1111/cts.12479. Epub 2017 Jul 20.
PubMed 28727908

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

Official record

Not yet recruitingPhase 3
Efficacy and Safety of Once-Weekly SHR-3167 Compared With Once-Daily Insulin Glargine in Adults With Insulin-Naive Type 2 Diabetes
Type 2 Diabetes
Active, not recruiting
Digital Reinforcement of Motivational Interviewing Micro-Skills Among Primary Care Healthcare Professionals
Hypertension (Without Type 2 Diabetes Mellitus)
Recruiting
Investigating Vascular Properties of HEMI and SPG Signals in Individuals With or at Risk for Chronic Kidney Disease
Chronic Kidney Disease, Hypertension (HTN)
Not yet recruitingPhase 3
A Study to Evaluate the Effectiveness and Safety of the Drug AZD6234 for Managing Weight in Adults Who Are Obese or Overweight. These Participants May or May Not Also Have Type 2 Diabetes
Obesity, Overweight
Not yet recruiting
Impact of Endoscopic Sleeve Gastroplasty (ESG) in Obese Adults With Type 2 Diabetes (T2D)
Type 2 Diabetes Mellitus (T2D), Obesity (BMI>30)

All Type 2 Diabetes Mellitus trials

Study at a glance

From the registry record, last updated by the sponsor on 10 Sep 2018. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Multiple Dose Clinical Trial to Study the Safety, Tolerability, Pharmacodynamics, and Pharmacokinetics of MK-8666 in Type 2 Diabetes Mellitus Patients
ClinicalTrials.gov ID: NCT01971554
Acronym / sponsor ID: 8666-003
Conditions: Type 2 Diabetes Mellitus
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 63 participants (actual)
Lead sponsor: Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
Study start: 14 Oct 2013 (actual)
Primary completion: 26 Apr 2014 (actual)
Study completion: 26 Apr 2014 (actual)
First posted: 29 Oct 2013 (estimated)
Results: Posted 8 Dec 2016

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind (participant, investigator)
Number of arms: 4

Arm	Type	Receives
MK-8666 50 mg	Experimental	Drug: MK-8666, Drug: PlaceboMK-8666, 50 mg, oral, once a day (QD) for Days 1 to 14.
MK-8666 150 mg	Experimental	Drug: MK-8666, Drug: PlaceboMK-8666, 150 mg, oral, QD, for Days 1 to 14
MK-8666 500 mg	Experimental	Drug: MK-8666, Drug: PlaceboMK-8666, 500 mg, oral, QD for Days 1 to 14
Placebo	Placebo comparator	Drug: PlaceboPlacebo, oral, QD for Days 1 to 14

Who may qualify

Ages: 18 to 65 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (7 listed)

If female, must be either postmenopausal or surgically sterile
A Body Mass Index (BMI) ≥18 kg/m^2 to ≤40 kg/m^2, inclusive.
A diagnosis of T2DM
Drug naïve or is being treated with no more than 2 oral antihyperglycemic agents (thiazolidenediones are excluded)
Judged to be in good health except for T2DM

Key exclusion criteria (12 listed)

A history of clinically significant endocrine (except T2DM), gastrointestinal, cardiovascular, hematological, hepatic, immunological, renal, respiratory, or genitourinary abnormalities or diseases
A history of myositis or complaints including diffuse myalgias, muscle tenderness, or weakness.
A history of cancer (malignancy) excepting adequately treated non-melanomatous skin carcinoma or carcinoma in situ of the cervix
Has clinically unstable diabetic retinopathy, neuropathy, and/or clinical evidence of gastroparesis (frequent nausea, bloating or vomiting, severe gastroesophageal reflux, early satiety)
A history of type 1 diabetes mellitus and/or history of ketoacidosis

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-8666MK-8666, capsules, oral, QD, Days 1 to 14	Drug	MK-8666 150 mg, MK-8666 50 mg, MK-8666 500 mg
PlaceboPlacebo, capsules, oral, QD, Days 1 to 14	Drug	MK-8666 150 mg, MK-8666 50 mg, MK-8666 500 mg, Placebo

Primary outcome

Change From Baseline in Fasting Plasma Glucose (FPG) at Day 15
Time frame: Predose (Baseline) and 24 h postdose Day 14 (Day 15)
Blood glucose was measured on a fasting basis (collected after an 8-hour fast). Blood was collected on Day -1 (pre-planned dose), predose on Days 1, 3, 7, and 14, and 24h postdose Day 14 (Day 15). The baseline measurement was computed as the average of the Day -1 and predose Day 1 measurements. FPG is expressed as mg/dL. This change from baseline reflects values for Day 15 FPG minus Day 0 FPG values.
Number of Participants Who Experienced at Least Once Adverse Event
Time frame: Up to 28 days
An adverse event (AE) is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.
Number of Participants Who Discontinued Study Drug Due to an AE
Time frame: Up to 14 days
An adverse event (AE) is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.

4 secondary outcomes

Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC0-24h)
Time frame: Day 1: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, and 24 hours postdose; Day 14 : Predose, 0.5, 1, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 48, 72 hours postdose
Maximum Plasma Drug Concentration After Dosing (Cmax)
Time frame: Day 1: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, and 24 hours postdose; Day 14 : Predose, 0.5, 1, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 48, 72 hours postdose
Time to Reach Cmax (Tmax)
Time frame: Day 1: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, and 24 hours postdose; Day 14 : Predose, 0.5, 1, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 48, 72 hours postdose
Change From Baseline in 24-Hour Weighted Mean Glucose (24h-WMG) at Day 15
Time frame: Baseline and Day 15

Results and safety

Results posted to the registry on 8 Dec 2016, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
MK-8666 50 mg	9	8
MK-8666 150 mg	18	18
MK-8666 500 mg	18	18
Placebo	18	18

Primary outcome: Change From Baseline in Fasting Plasma Glucose (FPG) at Day 15

Time frame: Predose (Baseline) and 24 h postdose Day 14 (Day 15). Least squares mean (Standard Error). Unit: mg/dL

Measure	MK-8666 50 mg n = 9	MK-8666 150 mg n = 18	MK-8666 500 mg n = 18	Placebo n = 18
Value	32.8 (9.7)	37.9 (7.0)	56.0 (7.0)	2.0 (7.0)

MK-8666 50 mg vs Placebo: Difference in the least squares means: 30.8 (90% CI 11.3 to 50.3)
MK-8666 150 mg vs Placebo: Difference in the least squares means: 36.0 (90% CI 20.0 to 51.9)
MK-8666 500 mg vs Placebo: Difference in the least squares means: 54.1 (90% CI 38.1 to 70.0)

Population analysed: The Per-Protocol population is the subset of participants who complied with the protocol sufficiently to ensure that these data are likely to exhibit the effects of treatment, according to the underlying scientific model.

Primary outcome: Number of Participants Who Experienced at Least Once Adverse Event

Time frame: Up to 28 days. Number. Unit: Participants

Measure	MK-8666 50 mg n = 9	MK-8666 150 mg n = 18	MK-8666 500 mg n = 18	Placebo n = 18
Value	3	9	10	5

Population analysed: The Safety population consisted of all participants who received at least one dose of study medication.

Primary outcome: Number of Participants Who Discontinued Study Drug Due to an AE

Time frame: Up to 14 days. Number. Unit: Participants

Measure	MK-8666 50 mg n = 9	MK-8666 150 mg n = 18	MK-8666 500 mg n = 18	Placebo n = 18
Value	0	0	0	0

Population analysed: The Safety population consisted of all participants who received at least one dose of study medication.

4 secondary outcomes are reported in the full results.

Adverse events

Time frame: Up to 28 days. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
MK-8666 50 mg	0 of 9 (0%)	3 of 9 (33.3%)	Not reported
MK-8666 150 mg	0 of 18 (0%)	9 of 18 (50%)	Not reported
MK-8666 500 mg	0 of 18 (0%)	10 of 18 (55.6%)	Not reported
Placebo	0 of 18 (0%)	5 of 18 (27.8%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 10 Sep 2018.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 28727908Krug AW, Vaddady P, Railkar RA, Musser BJ, Cote J, Ederveen A, Krefetz DG, DeNoia E, Free AL, Morrow L, Chakravarthy MV, Kauh E, Tatosian DA, Kothare PA. Leveraging a Clinical Phase Ib Proof-of-Concept Study for the GPR40 Agonist MK-8666 in Patients With Type 2 Diabetes for Model-Informed Phase II Dose Selection. Clin Transl Sci. 2017 Sep;10(5):404-411. doi: 10.1111/cts.12479. Epub 2017 Jul 20.
Individual participant dataSharing planned: Yes. https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf

Related trials for Type 2 Diabetes Mellitus

Not yet recruitingPhase 3
Efficacy and Safety of Once-Weekly SHR-3167 Compared With Once-Daily Insulin Glargine in Adults With Insulin-Naive Type 2 Diabetes
Type 2 Diabetes
Active, not recruiting
Digital Reinforcement of Motivational Interviewing Micro-Skills Among Primary Care Healthcare Professionals
Hypertension (Without Type 2 Diabetes Mellitus)
Recruiting
Investigating Vascular Properties of HEMI and SPG Signals in Individuals With or at Risk for Chronic Kidney Disease
Chronic Kidney Disease, Hypertension (HTN)
Not yet recruitingPhase 3
A Study to Evaluate the Effectiveness and Safety of the Drug AZD6234 for Managing Weight in Adults Who Are Obese or Overweight. These Participants May or May Not Also Have Type 2 Diabetes
Obesity, Overweight
Not yet recruiting
Impact of Endoscopic Sleeve Gastroplasty (ESG) in Obese Adults With Type 2 Diabetes (T2D)
Type 2 Diabetes Mellitus (T2D), Obesity (BMI>30)

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-8666 in people with Type 2 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 7 inclusion and 12 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 10 Sep 2018. 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 Dec 2016). 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?

Change From Baseline in Fasting Plasma Glucose (FPG) at Day 15 (time frame: Predose (Baseline) and 24 h postdose Day 14 (Day 15)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01971554, which also lists 1 linked publication.

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 10 Sep 2018.