Activity of MK-8504 in Anti-retroviral-naïve, Human Immunodeficiency Virus 1 (HIV-1) Infected Participants (MK-8504-002)

NCT03188523 | Completed Phase 1 Results

• 3 other identifiers: 8504-0022017-000998-37MK-8504-002
• Study Type: interventional
• Target: 12
• Locations: 2 countries
• Sites: 2

Brief Summary

This study aims to evaluate the safety, tolerability, pharmacokinetics (PK), and anti-retroviral therapy (ART) activity of monotherapy with MK-8504 (a tenofovir pro-drug), in ART-naïve Human Immunodeficiency Virus (HIV)-1 infected participants. The primary hypothesis is that MK-8504, at a dose that is sufficiently safe and well tolerated, has superior antiretroviral activity compared to placebo, as measured by change from baseline in plasma HIV-1 ribonucleic acid (RNA) at 168 hours post-dose.

Conditions

HIV-1 Infection

Outcome Measures

Primary Outcomes (3)

• Change From Baseline in Plasma HIV-1 Ribonucleic Acid (RNA) at 168 Hours Post-Dose

  Plasma samples were collected from participants after a single dose of MK-8504 to assess viral load. The log10 plasma HIV-RNA (copies/mL) measurements from participants in each panel were pooled and analyzed based on a longitudinal data analysis model. Change from baseline to 168 hours post-dose was determined for each treatment group. Results are expressed as change in HIV RNA log10 (copies/mL).

  Baseline, 168 hours post-dose

• Number of Participants Who Experienced At Least One Adverse Event (AE)

  An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavourable and unintended sign, 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 pre-existing condition that is temporally associated with the use of the Sponsor's product, was also an AE. The number of participants experiencing at least one AE was reported for each arm.

  From Day 1 through Post-Trial Visit (up to 25 days)

• Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE)

  An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavourable and unintended sign, 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 pre-existing condition that is temporally associated with the use of the Sponsor's product, was also an AE. The number of participants that discontinued study treatment due to an AE was reported for each arm.

  Day 1

Secondary Outcomes (20)

• Area Under the Concentration-Time Curve of MK-8504 in Plasma From Time 0 to Last Measurable Concentration (AUC0-last)

  Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, and 72 hours post-dose

• Area Under the Concentration-Time Curve of MK-8504 in Plasma From Time 0 to Infinity (AUC0-inf)

  Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, and 72 hours post-dose

• Area Under the Concentration-Time Curve of MK-8504 in Plasma From Time 0 to 168 Hours (AUC0-168hr)

  Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, and 72 hours post-dose

• Time to Maximum Concentration of MK-8504 in Plasma (Tmax)

  Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, and 72 hours post-dose

• Maximum Concentration of MK-8504 in Plasma (Cmax)

  Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, and 72 hours post-dose

Study Arms (4)

MK-8504 100 mg (Panel A)

EXPERIMENTAL

Participants receive a single oral dose of MK-8504 100 mg.

Drug: MK-8504

MK-8504 240 mg (Panel B)

EXPERIMENTAL

Participants receive a single oral dose of MK-8504 240 mg.

Drug: MK-8504

MK-8504 ≤240 mg (Panel C)

EXPERIMENTAL

Participants receive a single oral dose of MK-8504 ≤240 mg.

Drug: MK-8504

MK-8504 ≤240 mg (Panel D)

EXPERIMENTAL

Participants receive a single oral dose of MK-8504 ≤240 mg.

Drug: MK-8504

Interventions

MK-8504 DRUG

After at least an 8-hour fast, a single oral dose of MK-8504 will be administered in capsule form.

MK-8504 100 mg (Panel A); MK-8504 240 mg (Panel B); MK-8504 ≤240 mg (Panel C); MK-8504 ≤240 mg (Panel D)

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Male or non-pregnant and non-breast feeding female
• Have a Body Mass Index (BMI) ≤35 kg/m\^2
• Other than HIV infection, have stable baseline health based on medical history, physical examination, vital sign measurements, and laboratory safety test
• Is documented HIV-1 positive
• Is diagnosed with HIV-1 infection 3 months prior to screening
• Is ART-naïve
• Has not received an investigational agent or marketed ART within 30 days of study drug administration and is willing to receive no other ART for the duration of this study
• Agree to follow smoking and other trial restrictions

You may not qualify if:

• Is mentally or legally institutionalized / incapacitated, has significant emotional problems at the time of pretrial (screening) visit or expected during the conduct of the trial or has a history of clinically significant psychiatric disorder of the last 5 years
• Has a history of clinically significant endocrine, gastrointestinal, cardiovascular, hematological, hepatic, immunological (outside of HIV-1 infection), renal, respiratory, genitourinary or major neurological (including stroke and chronic seizures) abnormalities or diseases
• Has a history of cancer (malignancy)
• Has a 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
• Is positive for hepatitis B surface antigen
• Has a history of chronic Hepatitis C
• Has had major surgery, donated or lost 1 unit of blood (approximately 500 mL) within 4 weeks prior to the pretrial (screening) visit.
• Has participated in another investigational trial within 4 weeks or 5 half-lives, whichever is greater, prior to the Day 1 Dosing visit
• Is 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 trial drug, throughout the trial, until the post-trial visit
• Consumes greater than 3 glasses of alcoholic beverages or distilled spirits per day
• Consumes excessive amounts, defined as greater than 6 servings of coffee, tea, cola, energy-drinks, or other caffeinated beverages per day
• Is an excessive smoker (i.e., more than 10 cigarettes/day) and is unwilling to restrict smoking to ≤10 cigarettes per day
• Have clinically significant abnormality on the electrocardiogram (ECG) performed at the prestudy (screening) visit and/or prior to administration of the initial dose of study drug
• Has a positive urine drug screen (except for cannabis) at screening and/or predose, rechecks are allowed

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (2)

Charite Research Organisation GmbH. ( Site 0002)

Berlin, Germany

Location

St Stephen's Clinical Research ( Site 0001)

London, United Kingdom

Location

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: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 14, 2017
• First Posted: June 15, 2017
• Study Start: September 8, 2017
• Primary Completion: May 21, 2018
• Study Completion: June 4, 2018
• Last Updated: July 15, 2019
• Results First Posted: July 15, 2019

Record last verified: 2019-05

Data Sharing

• IPD Sharing: Will share

Locations

DE (1); GB (1)