MK-8583 Single Dose Study in Human Immunodeficiency Virus Type 1 (HIV-1) Infected Participants (MK-8583-002)

NCT03552536 | Completed Phase 1 Results FDA Drug

• 3 other identifiers: 8583-0022017-004017-92MK-8583-002
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

This study aims to evaluate the safety, tolerability, pharmacokinetics (PK), and anti-retroviral therapy (ART) activity of the tenofovir prodrug, MK-8583 monotherapy in ART-naïve, HIV-1 infected participants. The primary hypothesis is that at a dose that is sufficiently safe and generally well tolerated, MK-8583 has superior anti-retroviral activity compared to historical placebo, as measured by change from baseline in plasma HIV-1 ribonucleic acid (RNA) (log10 copies/mL) at 168 hours post-dose.

Conditions

HIV-1 Infection

Outcome Measures

Primary Outcomes (3)

• Number of Participants With at Least One Adverse Event (AE)

  An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), 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 preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE.

  Up to Day 29

• Number of Participants Who Discontinued Study Due to an AE

  An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), 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 preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE.

  Day 1

• Change From Baseline in Plasma Human Immunodeficiency Virus Type 1 (HIV-1) Ribonucleic Acid (RNA) at 168 Hours Post-dose.

  Plasma HIV-1 RNA was measured at baseline and 168 hours after dosing. Change from baseline for MK-8583 at 168 hours post-baseline was estimated from longitudinal data analysis (LDA) model containing fixed effects for time (predose, 168 hours postdose) and a random effect for participant. The change from baseline in plasma HIV-1 RNA in participants administered MK-8583 was compared with historical placebo data.

  Baseline (pre-dose) and 168 hours post-dose.

Secondary Outcomes (17)

• Area Under the Concentration Time Curve From Time 0-168 Hours Postdose (AUC0-168hr) of Tenofovir Diphosphate (TFV-DP)

  Pre-dose, 4, 12, 24, 48, 72, 96, and 168 hours postdose

• Time to Achieve Maximum Concentration (Tmax) of TFV-DP

  Pre-dose, 4, 12, 24, 48, 72, 96, 168, 240, 312 and 672 hours postdose

• Maximum Concentration (Cmax) of TFV-DP

  Pre-dose, 4, 12, 24, 48, 72, 96, 168, 240, 312 and 672 hours postdose

• Concentration at 168 Hours Postdose (C168hr) of TFV-DP

  168 hr postdose

• Apparent Terminal Half-life (t1/2) of TFV-DP

  Pre-dose, 4, 12, 24, 48, 72, 96, 168, 240, 312 and 672 hours postdose

Study Arms (3)

A: MK-8583 100mg

EXPERIMENTAL

After fasting, a single oral dose of 100 mg MK-8583 in capsule form.

Drug: MK-8583

B: MK-8583 ≤ 150 mg

EXPERIMENTAL

After fasting, a single oral dose of ≤ 150 mg MK-8583 in capsule form, with the dose based on the results from earlier treatments

Drug: MK-8583

C: MK-8583 ≤ 150 mg

EXPERIMENTAL

After fasting, a single oral dose of ≤ 150 mg MK-8583 in capsule form, with the dose based on the results from earlier treatments

Drug: MK-8583

Interventions

MK-8583 DRUG

A single oral dose of MK-8583 in capsule form

A: MK-8583 100mg; B: MK-8583 ≤ 150 mg; C: MK-8583 ≤ 150 mg

Eligibility Criteria

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

You may qualify if:

• Male with female partner(s) of child-bearing potential use required methods of birth control.
• Female of reproductive potential must demonstrate a nongravid state at the pretrial (screening) visit and agree to use acceptable methods of birth control beginning at the pretrial (screening) visit, throughout the trial and until 30 days following cessation of treatment.
• Postmenopausal female, defined as without menses for at least 1 year and have a documented follicle stimulating hormone (FSH) level in the postmenopausal range at pretrial (screening).
• Surgically sterile female's status is post hysterectomy or oophorectomy.
• Is documented HIV-1 positive
• Is diagnosed with HIV-1 infection ≥ 3 months prior to screening.
• Is ART-naïve, defined as having never received any anti-retroviral agent; or ≤ 30 consecutive days of an investigational anti-retroviral agent, excluding a nucleoside reverse transcriptase inhibitor (NRTI), or ≤ 60 consecutive days of combination ART not including a NRTI.

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 over 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 unless there has been documented cure.
• 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 pre-trial (screening) visit.
• Uses or anticipates using 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, wine or distilled spirits per day.
• Consumes excessive amounts of 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.
• Has a positive urine drug screen (except for cannabis) at screening and/or pre-dose.
• Has received any investigational agent or any anti-retroviral agent within 60 days of study drug administration; or intends to receive any ART during this study.

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (1)

Charite Research Organisation GmbH ( Site 0001)

Berlin, 10117, Germany

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: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 29, 2018
• First Posted: June 12, 2018
• Study Start: October 7, 2018
• Primary Completion: March 11, 2019
• Study Completion: March 11, 2019
• Last Updated: March 4, 2020
• Results First Posted: March 4, 2020

Record last verified: 2020-02

Data Sharing

• IPD Sharing: Will share

Locations

DE (1)