Safety, Tolerability and Pharmacokinetics Study of MK-7252 in Healthy Adult Participants (MK-7252-001)

NCT03326986 | Completed Phase 1 Results

• 3 other identifiers: 7252-0012017-003407-22MK-7252-001
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Pharmacokinetics; Cancer

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  Up to approximately 19 weeks

Secondary Outcomes (15)

• MK-7252 Area Under the Concentration-Time Curve From Zero to Infinity (AUC0-∞)

  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)

  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)

  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)

  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)

  Predose (Day 1), 0.25, 0.5, 1, 2, 4, 8, 10, 12, 24, 48, and 72 hours postdose

Study Arms (3)

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

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

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

Drug: MK-7252; Drug: Placebo

Interventions

MK-7252 DRUG

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

Panel A; Panel B; Panel C

Placebo DRUG

Placebo powder for oral suspension administered with a water volume that brings the total ingested volume to approximately 240 mL

Panel A; Panel B; Panel C

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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).
• 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.

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (1)

Universitair Ziekenhuis Gent ( Site 0001)

Ghent, 9000, Belgium

Location

MeSH Terms

Conditions

Neoplasms

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 27, 2017
• First Posted: October 31, 2017
• Study Start: November 10, 2017
• Primary Completion: December 17, 2018
• Study Completion: December 17, 2018
• Last Updated: January 9, 2020
• Results First Posted: January 9, 2020

Record last verified: 2019-12

Data Sharing

• IPD Sharing: Will share

Locations

BE (1)