A Single-Ascending-Dose Study of MK-4318 in Healthy Participants

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Merck Sharp & Dohme LLC

Participant type

Healthy volunteers

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

2 May 2023 → 4 Jan 2024

Decision date (initial)

2023-04-26

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Merck Sharp & Dohme LLC

External identifiers

EU CT number

2023-503360-16-00

WHO UTN

U1111-1287-1173

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Others, Pharmacokinetic, Safety, Pharmacogenomic, Pharmacogenetic

1. Parts 1 and 2: To assess the safety and tolerability of single rising doses of MK-4318 in healthy adult participants.
2. Parts 1 and 2: To assess the plasma PK of MK-4318 following single doses of MK-4318 administered as fit for purpose (FFP) capsules to healthy adult participants.

Secondary objectives 1

1. Part 1: To assess the effects of a high-fat meal on plasma PK of a single dose of MK-4318 administered as fit for purpose capsules relative to plasma PK in the fasted state in healthy adult male participants.

Conditions and MedDRA coding

Acute and chronic pain

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 3

1. For Part 1, has a body mass index (BMI) between 18 to ≤30 kg/m2, inclusive, and for Part 2, has a BMI between 18 to 32 kg/m2, inclusive.
2. Is assigned male sex at birth, from 18 years to 45 years of age inclusive, at the time of providing the informed consent (Part 1 only).
3. Is assigned female sex at birth, from 18 years to 60 years of age inclusive at the time of providing the informed consent (Part 2 only).

Exclusion criteria 10

1. Has a history of clinically significant endocrine, gastrointestinal (GI), cardiovascular, hematological, hepatic, immunological, renal, respiratory, genitourinary, or major neurological (including stroke and chronic seizures) abnormalities or diseases.
2. Is mentally or legally incapacitated, has significant emotional problems at the time of prestudy (screening) visit or expected during the conduct of the study or has a history of clinically significant psychiatric disorder of the last 5 years.
3. Has a history of cancer (malignancy).
4. Is positive for hepatitis B surface antigen (HBsAg), hepatitis C antibodies or human immunodeficiency virus (HIV).
5. Had a major surgery and/or donated or lost 1 unit of blood (approximately 500 mL) within 4 weeks prior to the prestudy (screening) visit.
6. Has a history of cardiac arrythmia or recurrent unexplained syncopal events.
7. Has a first degree relative with multiple unexplained syncopal events, unexplained cardiac arrest or sudden cardiac death, or has a known family history of an inherited arrythmia syndrome (including Brugada syndrome).
8. Has participated in another investigational study within 4 weeks (or 5 half-lives, whichever is greater) prior to the prestudy (screening) visit.
9. Meets any of the following cardiac parameters: Fridericia's Correction Formula (QTcF) interval >450 msec for males or >470 msec for females, a history of risk factors for Torsades de Pointes (eg, heart failure/cardiomyopathy or family history of long QT syndrome), uncorrected hypokalemia or hypomagnesemia, or is taking concomitant medications that prolong the QT/QTcF interval.
10. Is a smoker and/or has used nicotine or nicotine-containing products (eg, nicotine patch and electronic cigarette) within 3 months of screening.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 11

1. Number of participants who experienced adverse events (AEs)
2. Number of participants who discontinued study intervention due to AEs
3. Area under the plasma concentration-time curve from 0 to infinity (AUC0-inf)) of MK-4318
4. Area under the plasma concentration-time curve from 0 to 24 hours (AUC0-24) of MK-4318
5. Time to maximum plasma concentration (Tmax) of MK-4318
6. Maximum plasma concentration (Cmax) of MK-4318
7. Plasma Concentration at 24 hours (C24) of MK-4318
8. Apparent oral clearance (CL/F) of MK-4318
9. Apparent Volume of Distribution During Terminal Phase (Vz/F) of MK-4318
10. Apparent terminal half-life (t½) of plasma concentration of MK-4318
11. Plasma Concentration at 12 hours (C12) of MK-4318

Secondary endpoints 4

1. AUC-inf of MK-4318 with food effect
2. Cmax of MK-4318 with food effect
3. C24 of MK-4318 with food effect
4. C12 of MK-4318 with food effect

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Placebo 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Merck Sharp & Dohme LLC

Sponsor organisation

Merck Sharp & Dohme LLC

Address

126 East Lincoln Avenue

City

Rahway

Postcode

07065-4607

Country

United States

Scientific contact point

Organisation

Merck Sharp & Dohme LLC

Contact name

Jonathan Kurz

Public contact point

Organisation

Merck Sharp & Dohme LLC

Contact name

Jonathan Kurz

Third parties 6

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 5 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications