PharmacokineticsPhase 1NCT03326986
Safety, Tolerability and Pharmacokinetics Study of MK-7252 in Healthy Adult Participants (MK-7252-001)
A Phase 1 study testing MK-7252 in people with Pharmacokinetics and Cancer, run by Merck Sharp & Dohme LLC at 1 site in Belgium.
Trial summary
The purpose of this study is to assess the safety, tolerability and pharmacokinetics (PK) of MK-7252 in healthy adults. Participants receive ascending doses of MK-7252 over five treatment periods. Each treatment period is separated by a 7-day washout period. Read more about this study
- Who is it for?
- Ages 18 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Pharmacokinetics, Cancer
- What is being tested?
- MK-7252
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 24 participants
- Where
- 1 siteBelgium
- Study dates
- 10 Nov 2017to 17 Dec 2018
- 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 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Male or female participants of non-childbearing potential (Note: If postmenopausal female: participant is without menses for at least 1 year and has a documented follicle stimulating hormone [FSH] level in the postmenopausal range at pre-trial [screening] - OR - If surgically sterile female: participant is status post hysterectomy, oophorectomy or tubal ligation.)
- Body Mass Index (BMI) between 18.5 and 32 kg/m^2, inclusive. BMI = weight (kg)/height (m)^2.
- While in semi-recumbent position, has a systolic blood pressure ≤140 mmHg and diastolic blood pressure ≤90 mm Hg and a respiratory rate ≤20 breaths/min at the pre-study (screening) visit and prior to randomization.
- Judged to be in good health based on medical history, physical examination, vital sign measurements and electrocardiogram (ECG) performed prior to randomization.
- Non-smoker and/or has not used nicotine or nicotine-containing products (e.g., nicotine patch) for at least approximately 3 months.
Who cannot join
- Mentally or legally incapacitated, has significant emotional problems at the time of pretrial (screening) visit or expected during the conduct of the study or has a history of clinically significant psychiatric disorder of the last 5 years.
- History of clinically significant endocrine, gastrointestinal, cardiovascular, hematological, hepatic, immunological, renal, respiratory, genitourinary or major neurological (including stroke and chronic seizures) abnormalities or diseases.
- History of liver disease (chronic hepatitis, cirrhosis, etc.).
- History of cancer (malignancy). Exceptions include adequately treated non-melanomatous skin carcinoma or carcinoma in situ of the cervix and other malignancies which have been successfully treated ≥10 years prior to the pre-study (screening) visit.
- History of significant multiple and/or severe allergies (e.g. food, drug, latex allergy), or has had an anaphylactic reaction or significant intolerability (i.e. systemic allergic reaction) to prescription or non-prescription drugs or food.
- Tests positive for hepatitis B surface antigen, hepatitis C antibodies or human immunodeficiency virus (HIV).
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- Had major surgery, donated or lost 1 unit of blood (approximately 500 mL) within 4 weeks prior to the pre-study (screening) visit.
- Participated in another investigational study within 4 weeks (or 5 half-lives), whichever is greater, prior to the pre-study (screening) visit.
- QTc interval ≥470 msec (for males) and ≥480 msec (for females).
- Taken a Proton Pump Inhibitor (PPI) during the 5 days prior to start of study treatment.
- Unable to refrain from or anticipates the use of any medication, including prescription and non-prescription drugs or herbal remedies beginning approximately 2 weeks (or 5 half-lives) prior to administration of the initial dose of study drug, throughout the study (including washout intervals between treatment periods), until the post-study visit.
- Consumes >3 glasses of alcoholic beverages (1 glass is approximately equivalent to: beer [354 mL/12 ounces], wine [118 mL/4 ounces], or distilled spirits [29.5 mL/1 ounce]) per day.
- Consumes excessive amounts, defined as >6 servings (1 serving is approximately equivalent to 120 mg of caffeine) of coffee, tea, cola, energy-drinks, or other caffeinated beverages per day.
- Regular user of cannabis, any illicit drugs or has a history of drug (including alcohol) abuse within approximately 1 year. Participants must have a negative result for urine drug screen test prior to randomization.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Single Ascending Dose Clinical Trial to Study the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of MK-7252 in Healthy Subjects
The purpose of this study is to assess the safety, tolerability and pharmacokinetics (PK) of MK-7252 in healthy adults. Participants receive ascending doses of MK-7252 over five treatment periods. Each treatment period is separated by a 7-day washout period.
Upon review of the interim safety and preliminary PK data of human exposure to date, Protocol Amendment 3 includes a third panel of participants, Panel C, to assess the PK of higher doses of MK-7252 and to assess the food effect of MK-7252.
Read the detailed description
Three panels (Panels A, B, and C) of 8 healthy participants (n=6 MK-7252, n=2 placebo) are enrolled. In Panels A and B, participants will alternately receive single rising doses of MK-7252 or placebo for 5 treatment periods. In Panel C, participants will receive single rising doses of MK-7252 or placebo for up to 5 treatment periods. All doses in Panels A and B will be administered in the fasted state during the 5 treatment periods. Doses in Panel C will be administered in a fasted state in treatment periods 1 through 4 and the treatment period 1 dose will be repeated in a fed state during treatment period 5. Panel A will begin first. At least 3 days will elapse before participants in Panel B will receive the next higher dose. For all panels, there will be at least 7 days washout between treatment periods for any given participant. Participants may only be enrolled in one panel of the study. The planned dose levels may be adjusted downward or replaced based on evaluation of safety, tolerability, pharmacokinetic and/or pharmacodynamic data observed after previous treatment periods. All participants in the treatment periods of all panels (with exception of 120 mg fasted/fed periods in Panel C) will be randomly assigned to either study drug or placebo; that is a participant could be assigned to receive study drug in one period and placebo in another. As per the protocol allocation plan, the same participants in Panel C will receive 120 mg MK-7252 in a fasted and fed state. In addition, during any of the treatment periods if a participant demonstrates change in any one of the protocol-defined parameters lasting ≥2 hours, dose escalation in that participant will be halted and the participant may be withdrawn from the study or re-challenged at same dose or at a lower or divided dose. Participants that meet criteria listed will be followed up until parameters no longer meet stopping rule criteria.
During the study, participants in Panel A were planned to receive placebo, 1 mg, 6 mg, 24 mg, 72 mg and 108 mg, all in a fasted state in 5 periods. Participants in Panel B were planned to receive placebo, 3 mg, 12 mg, 48 mg, 72 mg and 162 mg, all in a fasted state in 5 periods. All periods in Panels A and B were conducted. Participants in Panel C were planned to receive placebo fasted, placebo fed, 120 mg fasted, 240 mg fasted, 360 mg fasted, 540 mg fasted, and 120 mg fed in 5 periods. Periods 4 and 5 were not conducted and, as a result, the 240 mg fasted, 360 mg fasted, 540 mg fasted, 120 mg fed, and placebo fed doses were not administered. A 180 mg fasted dose was added during Period 3.
- Conditions
- Pharmacokinetics, Cancer
- Being tested
- MK-7252, Placebo
- Medical subject headings
- Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MK-7252Drug
1 mg/mL or 20 mg/mL of powder for oral suspension administered with a water volume that brings the total ingested volume to approximately 240 mL
PlaceboDrug
Placebo powder for oral suspension administered with a water volume that brings the total ingested volume to approximately 240 mL
| Study group | Role | What they receive |
|---|---|---|
| Panel A | Experimental | Participants receive either a single dose of MK-7252 or Placebo in a fasted state in each of five alternating treatment dosing periods as indicated. The planned dose levels include: Placebo for MK-7252, 1 mg of MK-7252, 6 mg of MK-7252, 24 mg of MK-7252, 72 mg of MK-7252, and 108 mg of MK-7252. There is a minimum of a 7-day washout period between each treatment period or dose administration. The planned dose levels may be adjusted downward or replaced based on evaluation of safety, tolerability, pharmacokinetic and/or pharmacodynamic data observed after previous treatment periods Receives: Drug: MK-7252; Drug: Placebo |
| Panel B | Experimental | Participants receive either a single dose of MK-7252 or Placebo in a fasted state in each of five alternating treatment dosing periods as indicated. The planned dose levels include: Placebo for MK-7252, 3 mg of MK-7252, 12 mg of MK-7252, 48 mg of MK-7252, 72 mg of MK-7252, and 162 mg of MK-7252. There is a minimum of a 7-day washout period between each treatment period or dose administration. The planned dose levels may be adjusted downward or replaced based on evaluation of safety, tolerability, pharmacokinetic and/or pharmacodynamic data observed after previous treatment periods Receives: Drug: MK-7252; Drug: Placebo |
| Panel C | Experimental | Participants receive either a single dose of MK-7252 or Placebo in up to 5 treatment dosing periods as indicated: Placebo for MK-7252, 120 mg of MK-7252 in a fasted state, 240 mg of MK-7252, 360 mg of MK-7252, 540 mg of MK-7252, and 120 mg of MK-7252 in a fed state. There is a minimum of a 7-day washout period between each treatment period or dose administration. The planned dose levels may be adjusted downward or replaced based on evaluation of safety, tolerability, pharmacokinetic and/or pharmacodynamic data observed after previous treatment periods Receives: Drug: MK-7252; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants Who Experienced at Least One Adverse Event (AE)
An AE was defined as any untoward medical occurrence in a participant administered study treatment and which did not necessarily have to have had a causal relationship with this treatment. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that was temporally associated with the use of study treatment, was also an AE. Adverse events are reported by dose taken at time of event and not by panel or period. The adverse events for placebo are pooled over periods across panels. The number of participants who experienced at least one AE is presented.
Measured: Up to approximately 21 weeks
Number of Participants Who Discontinued Study Treatment Due to an AE
An AE was defined as any untoward medical occurrence in a participant administered study treatment and which did not necessarily have to have had a causal relationship with this treatment. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that was temporally associated with the use of study treatment, was also an AE. Discontinuations are reported by dose taken at time of event. The discontinuations for placebo are pooled over periods across panels. The number of participants who discontinued study treatment due to an AE is presented.
Measured: Up to approximately 19 weeks
Secondary outcomes (15)
MK-7252 Area Under the Concentration-Time Curve From Zero to Infinity (AUC0-∞)
Blood samples were obtained predose (Day 1) and at designated times postdose to calculate the plasma MK-7252 AUC0-∞ reported as back-transformed least squares mean and confidence interval calculated using a linear mixed effects model performed on natural log-transformed values. Pharmacokinetic (PK) results were reported by dose taken in Panels A and B. For Panel C, PK results were reported by dose taken and by individual period. Periods in a panel were not conducted if it became evident that exposures at the escalated dosing would not adequately reach the projected PK target. Although the plasma AUC0-∞ following a high-fat breakfast (fed state) was planned to be compared to the plasma AUC0-∞ in the fasted stated in Panel C, the fed state dose was not administered.
Measured: Predose (Day 1) and 0.25, 0.5, 1, 2, 4, 8, 10, 12, 24, 48, and 72 hours postdose
MK-7252 Area Under the Concentration-Time Curve From Zero to 24 Hours Postdose (AUC0-24hr)
Blood samples were obtained predose (Day 1) and at designated times postdose to calculate the plasma MK-7252 AUC0-24hr reported as back-transformed least squares mean and confidence interval calculated using a linear mixed effects model performed on natural log-transformed values. PK results were reported by dose taken in Panels A and B. For Panel C, PK results were reported by dose taken and by individual period. Periods in a panel were not conducted if it became evident that exposures at the escalated dosing would not adequately reach the projected PK target. Although the plasma AUC0-24hr following a high-fat breakfast (fed state) was planned to be compared to the plasma AUC0-24hr in the fasted stated in Panel C, the fed state dose was not administered.
Measured: Predose (Day 1), 0.25, 0.5, 1, 2, 4, 8, 10, 12, and 24 hours postdose
MK-7252 Area Under the Concentration-Time Curve From Zero to 12 Hours Postdose (AUC0-12hr)
Blood samples were obtained predose (Day 1) and at designated times postdose to calculate the plasma MK-7252 AUC0-12hr reported as back-transformed least squares mean and confidence interval calculated using a linear mixed effects model performed on natural log-transformed values. PK results were reported by dose taken in Panels A and B. For Panel C, PK results were reported by dose taken and by individual period. Periods in a panel were not conducted if it became evident that exposures at the escalated dosing would not adequately reach the projected PK target. Although the plasma AUC0-12hr following a high-fat breakfast (fed state) was planned to be compared to the plasma AUC0-12hr in the fasted stated in Panel C, the fed state dose was not administered.
Measured: Predose (Day 1), 0.25, 0.5, 1, 2, 4, 8, 10, and 12 hours postdose
MK-7252 Area Under the Concentration-Time Curve From Zero to Last Measurable Concentration (AUClast)
Blood samples were obtained predose (Day 1) and at designated times postdose to calculate the plasma MK-7252 AUClast reported as back-transformed least squares mean and confidence interval calculated using a linear mixed effects model performed on natural log-transformed values. PK results were reported by dose taken in Panels A and B. For Panel C, PK results were reported by dose taken and by individual period. Periods in a panel were not conducted if it became evident that exposures at the escalated dosing would not adequately reach the projected PK target. Although the plasma AUClast following a high-fat breakfast (fed state) was planned to be compared to the plasma AUClast in the fasted stated in Panel C, the fed state dose was not administered.
Measured: Predose (Day 1), 0.25, 0.5, 1, 2, 4, 8, 10, 12, 24, 48, and 72 hours postdose
MK-7252 Maximal Plasma Concentration (Cmax)
Blood samples were obtained predose (Day 1) and at designated times postdose to calculate the plasma MK-7252 Cmax reported as back-transformed least squares mean and confidence interval calculated using a linear mixed effects model performed on natural log-transformed values. PK results were reported by dose taken in Panels A and B. For Panel C, PK results were reported by dose taken and by individual period. Periods in a panel were not conducted if it became evident that exposures at the escalated dosing would not adequately reach the projected PK target. Although the plasma Cmax following a high-fat breakfast (fed state) was planned to be compared to the plasma Cmax in the fasted stated in Panel C, the fed state dose was not administered.
Measured: Predose (Day 1), 0.25, 0.5, 1, 2, 4, 8, 10, 12, 24, 48, and 72 hours postdose
MK-7252 Plasma Concentration at 12 Hours Postdose (C12hr)
Blood samples were obtained 12 hours postdose to calculate the plasma MK-7252 C12hr reported as back-transformed least squares mean and confidence interval calculated using a linear mixed effects model performed on natural log-transformed values. For participants in a given dose that had C12hr values less than the lower limit of quantification (LLOQ), the C12hr value was imputed as half x LLOQ. The LLOQ was 2.74 nmol/L. PK results were reported by dose taken in Panels A and B. For Panel C, PK results were reported by dose taken and by individual period. Periods in a panel were not conducted if it became evident that exposures at the escalated dosing would not adequately reach the projected PK target. Although the plasma C12hr following a high-fat breakfast (fed state) was planned to be compared to the plasma C12hr in the fasted stated in Panel C, the fed state dose was not administered.
Measured: 12 hours postdose
MK-7252 Plasma Concentration at 24 Hours Postdose (C24hr)
Blood samples were obtained 24 hours postdose to calculate the plasma MK-7252 C24hr reported as back-transformed least squares mean and confidence interval calculated using a linear mixed effects model performed on natural log-transformed values. For participants in a given dose that had C24hr values less than the lower limit of quantification (LLOQ), the C24hr value was imputed as half x LLOQ. The LLOQ was 2.74 nmol/L. PK results were reported by dose taken in Panels A and B. For Panel C, PK results were reported by dose taken and by individual period. Periods in a panel were not conducted if it became evident that exposures at the escalated dosing would not adequately reach the projected PK target. Although the plasma C24hr following a high-fat breakfast (fed state) was planned to be compared to the plasma C24hr in the fasted stated in Panel C, the fed state dose was not administered.
Measured: 24 hours postdose
MK-7252 Time to Reach Maximal Concentration (Tmax)
Blood samples were obtained predose (Day 1) and at designated times postdose to calculate the plasma MK-7252 Tmax. PK results were reported by dose taken in Panels A and B. For Panel C, PK results were reported by dose taken and by individual period. Periods in a panel were not conducted if it became evident that exposures at the escalated dosing would not adequately reach the projected PK target. Although the plasma Tmax following a high-fat breakfast (fed state) was planned to be compared to the plasma Tmax in the fasted stated in Panel C, the fed state dose was not administered.
Measured: Predose (Day 1), 0.25, 0.5, 1, 2, 4, 8, 10, 12, 24, 48, and 72 hours postdose
MK-7252 Apparent Terminal Half-life (t½)
Blood samples were obtained predose (Day 1) and at designated times postdose to calculate the plasma MK-7252 t½ reported as Geometric Mean with Percent Geometric Coefficient of Variation. PK results were reported by dose taken in Panels A and B. For Panel C, PK results were reported by dose taken and by individual period. Periods in a panel were not conducted if it became evident that exposures at the escalated dosing would not adequately reach the projected PK target. Although the plasma t½ following a high-fat breakfast (fed state) was planned to be compared to the plasma t½ in the fasted stated in Panel C, the fed state dose was not administered.
Measured: Predose (Day 1), 0.25, 0.5, 1, 2, 4, 8, 10, 12, 24, 48, and 72 hours postdose
Change From Baseline in Systolic Blood Pressure (SBP) at 4 Hours
Assessment of the change from baseline in SBP was obtained using a validated, semi-automated oscillometric device. Baseline was defined as the average of predose measurements. A measurement set was considered 2 SBP measurements: baseline and 4 hours postdose. SBP results are reported by dose taken. Placebo measurements are pooled over periods across panels. A positive number indicates an increase in SBP and a negative number indicates a decrease in SBP.
Measured: Baseline (Predose Day 1) and 4 hours postdose
Change From Baseline in Systolic Blood Pressure (SBP) at 24 Hours
Assessment of the change from baseline in SBP was obtained using a validated, semi-automated oscillometric device. Baseline was defined as the average of predose measurements. A measurement set was considered 2 SBP measurements: baseline and 24 hours postdose. SBP results are reported by dose taken. Placebo measurements are pooled over periods across panels. A positive number indicates an increase in SBP and a negative number indicates a decrease in SBP.
Measured: Baseline (Predose Day 1) and 24 hours postdose
Change From Baseline in Diastolic Blood Pressure (DBP) at 4 Hours
Assessment of the change from baseline in DBP was obtained using a validated, semi-automated oscillometric device. Baseline was defined as the average of predose measurements. A measurement set was considered 2 DBP measurements: baseline and 4 hours postdose. DBP results are reported by dose taken. Placebo measurements are pooled over periods across panels. A positive number indicates an increase in DBP and a negative number indicates a decrease in DBP.
Measured: Baseline (Predose Day 1) and 4 hours postdose
Change From Baseline in Diastolic Blood Pressure (DBP) at 24 Hours
Assessment of the change from baseline in DBP was obtained using a validated, semi-automated oscillometric device. Baseline was defined as the average of predose measurements. A measurement set was considered 2 DBP measurements: baseline and 24 hours postdose. DBP results are reported by dose taken. Placebo measurements are pooled over periods across panels. A positive number indicates an increase in DBP and a negative number indicates a decrease in DBP.
Measured: Baseline (Predose Day 1) and 24 hours postdose
Change From Baseline in Heart Rate (HR) at 4 Hours
Assessment of the change from baseline in HR was obtained using a validated, semi-automated oscillometric device. Baseline was defined as the average of predose measurements. A measurement set was considered 2 HR measurements: baseline and 4 hours postdose. HR results are reported by dose taken. Placebo measurements are pooled over periods across panels. A positive number indicates an increase in HR and a negative number indicates a decrease in HR.
Measured: Baseline (Predose Day 1) and 4 hours postdose
Change From Baseline in Heart Rate (HR) at 24 Hours
Assessment of the change from baseline in HR was obtained using a validated, semi-automated oscillometric device. Baseline was defined as the average of predose measurements. A measurement set was considered 2 HR measurements: baseline and 24 hours postdose. HR results are reported by dose taken. Placebo measurements are pooled over periods across panels. A positive number indicates an increase in HR and a negative number indicates a decrease in HR.
Measured: Baseline (Predose Day 1) and 24 hours postdose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Oct 2017
- Study start10 Nov 2017
- Primary completion17 Dec 2018
- Study completion17 Dec 2018
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 PharmacokineticsStudies 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
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 24 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
- NCT03326986
- Sponsor's protocol ID
- 7252-001
- Other IDs
- 2017-003407-22, MK-7252-001, 2017
- Status last verified
- Dec 2019
- First submitted
- 27 Oct 2017
- Last updated
- 9 Jan 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- 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 9 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Single Ascending Dose Clinical Trial to Study the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of MK-7252 in Healthy Subjects
- ClinicalTrials.gov ID
- NCT03326986
- Acronym / sponsor ID
- 7252-001
- Conditions
- Pharmacokinetics, Cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
- Study start
- 10 Nov 2017 (actual)
- Primary completion
- 17 Dec 2018 (actual)
- Study completion
- 17 Dec 2018 (actual)
- First posted
- 31 Oct 2017 (actual)
- Results
- Posted 9 Jan 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to assess the safety, tolerability and pharmacokinetics (PK) of MK-7252 in healthy adults. Participants receive ascending doses of MK-7252 over five treatment periods. Each treatment period is separated by a 7-day washout period.
Upon review of the interim safety and preliminary PK data of human exposure to date, Protocol Amendment 3 includes a third panel of participants, Panel C, to assess the PK of higher doses of MK-7252 and to assess the food effect of MK-7252.
Detailed description
Three panels (Panels A, B, and C) of 8 healthy participants (n=6 MK-7252, n=2 placebo) are enrolled. In Panels A and B, participants will alternately receive single rising doses of MK-7252 or placebo for 5 treatment periods. In Panel C, participants will receive single rising doses of MK-7252 or placebo for up to 5 treatment periods. All doses in Panels A and B will be administered in the fasted state during the 5 treatment periods. Doses in Panel C will be administered in a fasted state in treatment periods 1 through 4 and the treatment period 1 dose will be repeated in a fed state during treatment period 5. Panel A will begin first. At least 3 days will elapse before participants in Panel B will receive the next higher dose. For all panels, there will be at least 7 days washout between treatment periods for any given participant. Participants may only be enrolled in one panel of the study. The planned dose levels may be adjusted downward or replaced based on evaluation of safety, tolerability, pharmacokinetic and/or pharmacodynamic data observed after previous treatment periods. All participants in the treatment periods of all panels (with exception of 120 mg fasted/fed periods in Panel C) will be randomly assigned to either study drug or placebo; that is a participant could be assigned to receive study drug in one period and placebo in another. As per the protocol allocation plan, the same participants in Panel C will receive 120 mg MK-7252 in a fasted and fed state. In addition, during any of the treatment periods if a participant demonstrates change in any one of the protocol-defined parameters lasting ≥2 hours, dose escalation in that participant will be halted and the participant may be withdrawn from the study or re-challenged at same dose or at a lower or divided dose. Participants that meet criteria listed will be followed up until parameters no longer meet stopping rule criteria.
During the study, participants in Panel A were planned to receive placebo, 1 mg, 6 mg, 24 mg, 72 mg and 108 mg, all in a fasted state in 5 periods. Participants in Panel B were planned to receive placebo, 3 mg, 12 mg, 48 mg, 72 mg and 162 mg, all in a fasted state in 5 periods. All periods in Panels A and B were conducted. Participants in Panel C were planned to receive placebo fasted, placebo fed, 120 mg fasted, 240 mg fasted, 360 mg fasted, 540 mg fasted, and 120 mg fed in 5 periods. Periods 4 and 5 were not conducted and, as a result, the 240 mg fasted, 360 mg fasted, 540 mg fasted, 120 mg fed, and placebo fed doses were not administered. A 180 mg fasted dose was added during Period 3.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Panel A | Experimental | Drug: MK-7252, Drug: PlaceboParticipants receive either a single dose of MK-7252 or Placebo in a fasted state in each of five alternating treatment dosing periods as indicated. The planned dose levels include: Placebo for MK-7252, 1 mg of MK-7252, 6 mg of MK-7252, 24 mg of MK-7252, 72 mg of MK-7252, and 108 mg of MK-7252. There is a minimum of a 7-day washout period between each treatment period or dose administration. The planned dose levels may be adjusted downward or replaced based on evaluation of safety, tolerability, pharmacokinetic and/or pharmacodynamic data observed after previous treatment periods |
| Panel B | Experimental | Drug: MK-7252, Drug: PlaceboParticipants receive either a single dose of MK-7252 or Placebo in a fasted state in each of five alternating treatment dosing periods as indicated. The planned dose levels include: Placebo for MK-7252, 3 mg of MK-7252, 12 mg of MK-7252, 48 mg of MK-7252, 72 mg of MK-7252, and 162 mg of MK-7252. There is a minimum of a 7-day washout period between each treatment period or dose administration. The planned dose levels may be adjusted downward or replaced based on evaluation of safety, tolerability, pharmacokinetic and/or pharmacodynamic data observed after previous treatment periods |
| Panel C | Experimental | Drug: MK-7252, Drug: PlaceboParticipants receive either a single dose of MK-7252 or Placebo in up to 5 treatment dosing periods as indicated: Placebo for MK-7252, 120 mg of MK-7252 in a fasted state, 240 mg of MK-7252, 360 mg of MK-7252, 540 mg of MK-7252, and 120 mg of MK-7252 in a fed state. There is a minimum of a 7-day washout period between each treatment period or dose administration. The planned dose levels may be adjusted downward or replaced based on evaluation of safety, tolerability, pharmacokinetic and/or pharmacodynamic data observed after previous treatment periods |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- Male or female participants of non-childbearing potential (Note: If postmenopausal female: participant is without menses for at least 1 year and has a documented follicle stimulating hormone [FSH] level in the postmenopausal range at pre-trial [screening] - OR - If surgically sterile female: participant is status post hysterectomy, oophorectomy or tubal ligation.)
- Body Mass Index (BMI) between 18.5 and 32 kg/m^2, inclusive. BMI = weight (kg)/height (m)^2.
- While in semi-recumbent position, has a systolic blood pressure ≤140 mmHg and diastolic blood pressure ≤90 mm Hg and a respiratory rate ≤20 breaths/min at the pre-study (screening) visit and prior to randomization.
- Judged to be in good health based on medical history, physical examination, vital sign measurements and electrocardiogram (ECG) performed prior to randomization.
- Non-smoker and/or has not used nicotine or nicotine-containing products (e.g., nicotine patch) for at least approximately 3 months.
Key exclusion criteria (14 listed)
- Mentally or legally incapacitated, has significant emotional problems at the time of pretrial (screening) visit or expected during the conduct of the study or has a history of clinically significant psychiatric disorder of the last 5 years.
- History of clinically significant endocrine, gastrointestinal, cardiovascular, hematological, hepatic, immunological, renal, respiratory, genitourinary or major neurological (including stroke and chronic seizures) abnormalities or diseases.
- History of liver disease (chronic hepatitis, cirrhosis, etc.).
- History of cancer (malignancy). Exceptions include adequately treated non-melanomatous skin carcinoma or carcinoma in situ of the cervix and other malignancies which have been successfully treated ≥10 years prior to the pre-study (screening) visit.
- History of significant multiple and/or severe allergies (e.g. food, drug, latex allergy), or has had an anaphylactic reaction or significant intolerability (i.e. systemic allergic reaction) to prescription or non-prescription drugs or food.
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-72521 mg/mL or 20 mg/mL of powder for oral suspension administered with a water volume that brings the total ingested volume to approximately 240 mL | Drug | Panel A, Panel B, Panel C |
| PlaceboPlacebo powder for oral suspension administered with a water volume that brings the total ingested volume to approximately 240 mL | Drug | Panel A, Panel B, Panel C |
Primary outcome
Number of Participants Who Experienced at Least One Adverse Event (AE)
Time frame: Up to approximately 21 weeks
An AE was defined as any untoward medical occurrence in a participant administered study treatment and which did not necessarily have to have had a causal relationship with this treatment. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that was temporally associated with the use of study treatment, was also an AE. Adverse events are reported by dose taken at time of event and not by panel or period. The adverse events for placebo are pooled over periods across panels. The number of participants who experienced at least one AE is presented.
Number of Participants Who Discontinued Study Treatment Due to an AE
Time frame: Up to approximately 19 weeks
An AE was defined as any untoward medical occurrence in a participant administered study treatment and which did not necessarily have to have had a causal relationship with this treatment. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that was temporally associated with the use of study treatment, was also an AE. Discontinuations are reported by dose taken at time of event. The discontinuations for placebo are pooled over periods across panels. The number of participants who discontinued study treatment due to an AE is presented.
15 secondary outcomes
MK-7252 Area Under the Concentration-Time Curve From Zero to Infinity (AUC0-∞)
Time frame: Predose (Day 1) and 0.25, 0.5, 1, 2, 4, 8, 10, 12, 24, 48, and 72 hours postdose
MK-7252 Area Under the Concentration-Time Curve From Zero to 24 Hours Postdose (AUC0-24hr)
Time frame: Predose (Day 1), 0.25, 0.5, 1, 2, 4, 8, 10, 12, and 24 hours postdose
MK-7252 Area Under the Concentration-Time Curve From Zero to 12 Hours Postdose (AUC0-12hr)
Time frame: Predose (Day 1), 0.25, 0.5, 1, 2, 4, 8, 10, and 12 hours postdose
MK-7252 Area Under the Concentration-Time Curve From Zero to Last Measurable Concentration (AUClast)
Time frame: Predose (Day 1), 0.25, 0.5, 1, 2, 4, 8, 10, 12, 24, 48, and 72 hours postdose
MK-7252 Maximal Plasma Concentration (Cmax)
Time frame: Predose (Day 1), 0.25, 0.5, 1, 2, 4, 8, 10, 12, 24, 48, and 72 hours postdose
MK-7252 Plasma Concentration at 12 Hours Postdose (C12hr)
Time frame: 12 hours postdose
MK-7252 Plasma Concentration at 24 Hours Postdose (C24hr)
Time frame: 24 hours postdose
MK-7252 Time to Reach Maximal Concentration (Tmax)
Time frame: Predose (Day 1), 0.25, 0.5, 1, 2, 4, 8, 10, 12, 24, 48, and 72 hours postdose
MK-7252 Apparent Terminal Half-life (t½)
Time frame: Predose (Day 1), 0.25, 0.5, 1, 2, 4, 8, 10, 12, 24, 48, and 72 hours postdose
Change From Baseline in Systolic Blood Pressure (SBP) at 4 Hours
Time frame: Baseline (Predose Day 1) and 4 hours postdose
Change From Baseline in Systolic Blood Pressure (SBP) at 24 Hours
Time frame: Baseline (Predose Day 1) and 24 hours postdose
Change From Baseline in Diastolic Blood Pressure (DBP) at 4 Hours
Time frame: Baseline (Predose Day 1) and 4 hours postdose
Change From Baseline in Diastolic Blood Pressure (DBP) at 24 Hours
Time frame: Baseline (Predose Day 1) and 24 hours postdose
Change From Baseline in Heart Rate (HR) at 4 Hours
Time frame: Baseline (Predose Day 1) and 4 hours postdose
Change From Baseline in Heart Rate (HR) at 24 Hours
Time frame: Baseline (Predose Day 1) and 24 hours postdose
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jan 2020.
- 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
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing MK-7252 in people with Pharmacokinetics and Cancer, run by Merck Sharp & Dohme LLC at 1 site in Belgium.
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 14 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 9 Jan 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. 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 9 Jan 2020). 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 Who Experienced at Least One Adverse Event (AE) (time frame: Up to approximately 21 weeks). The study lists 2 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 9 Jan 2020.