Pharmacokinetics of Islatravir in Participants With Severe Renal Impairment (MK-8591-026)

NCT04303156 | Completed Phase 1 Results FDA Drug

• 3 other identifiers: 8591-0262020-000153-27MK-8591-026
• Study Type: interventional
• Target: 12
• Locations: 2 countries
• Sites: 2

Brief Summary

This study will evaluate the general tolerability and pharmacokinetics (PK) of a single 60 mg dose of MK-8591 (Islatravir) in participants with severe renal insufficiency, compared to participants in good health.

Conditions

Human Immunodeficiency Virus (HIV) Infection

Outcome Measures

Primary Outcomes (7)

• Area Under the Curve From Time 0 to Infinity (AUC0-inf) of Plasma Islatravir (ISL)

  Participants were treated with islatravir (ISL), and blood samples were collected from pre-dose up to 168 hours post-dose to determine the concentration of plasma ISL. The 95% confidence interval was derived from a fixed effects model performed on natural log-transformed values.

  Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 168 hours post-dose

• Area Under the Curve From Time 0 to Last Sampling Time (AUC0-last) of Plasma ISL

  Participants were treated with ISL, and blood samples were collected from pre-dose up to 168 hours post-dose to determine the concentration of plasma ISL. The 95% confidence interval was derived from a fixed effects model performed on natural log-transformed values.

  Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 168 hours post-dose

• Maximum Concentration (Cmax) of Plasma ISL

  Participants were treated with ISL, and blood samples were collected from pre-dose up to 168 hours post-dose to determine the concentration of plasma ISL. The 95% confidence interval was derived from a fixed effects model performed on natural log-transformed values.

  Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 168 hours post-dose

• Time of Maximum Concentration (Tmax) of Plasma ISL

  Participants were treated with ISL, and blood samples were collected from pre-dose up to 168 hours post-dose to determine the concentration of plasma ISL. The Tmax of plasma ISL was expressed as a median.

  Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 168 hours post-dose

• Apparent Terminal Half-life (t1/2) of Plasma ISL

  Participants were treated with ISL, and blood samples were collected from pre-dose up to 168 hours post-dose to determine the concentration of plasma ISL. The Geometric Coefficient of Variation was expressed as a percent (%CV), and is calculated from the square root of corresponding estimated variance obtained for each population in fixed effect model multiplied by 100.

  Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 168 hours post-dose

• Apparent Clearance (CL/F) of Plasma ISL

  Participants were treated with ISL, and blood samples were collected from pre-dose up to 168 hours post-dose to determine the concentration of plasma ISL. The 95% confidence interval was derived from a fixed effects model performed on natural log-transformed values.

  Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 168 hours post-dose

• Apparent Volume of Distribution (Vz/F) of Plasma ISL

  Participants were treated with ISL, and blood samples were collected from pre-dose up to 168 hours post-dose to determine the concentration of plasma ISL. The 95% confidence interval was derived from a fixed effects model performed on natural log-transformed values.

  Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 168 hours post-dose

Secondary Outcomes (10)

• AUC0-inf of ISL Triphosphate (ISL-TP) in Peripheral Blood Mononuclear Cells (PBMC)

  Pre-dose, 4, 24, 48, 96, 168 hours post-dose

• AUC0-last of ISL-TP in PBMC

  Pre-dose, 4, 24, 48, 96, 168 hours post-dose

• Cmax of ISL-TP in PBMC

  Pre-dose, 4, 24, 48, 96, 168 hours post-dose

• Tmax of ISL-TP in PBMC

  Pre-dose, 4, 24, 48, 96, 168 hours post-dose

• Concentration at 24 Hours Post Dose (C24) of ISL-TP in PBMC

  24 hours post-dose

Study Arms (2)

Severe Renal Impairment

EXPERIMENTAL

Participants with severe renal impairment received a single oral dose of 60 mg MK-8591 (Islatravir) administered in capsule form.

Drug: Islatravir

Healthy

EXPERIMENTAL

Healthy participants received a single oral dose of 60 mg Islatravir administered in capsule form.

Drug: Islatravir

Interventions

Islatravir DRUG

Single oral dose of 60 mg Islatravir administered in capsule form

Also known as: MK-8591

Healthy; Severe Renal Impairment

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Healthy participants must have the following:
• Is in good health
• Has a body mass index (BMI) ≥18.5 and ≤40 kg/m2.
• Female is not pregnant or breastfeeding, and is not one of the following: a woman of childbearing potential (WOCBP); if a WOCBP, is using an acceptable contraceptive method, or is abstinent from heterosexual intercourse as their preferred and usual lifestyle; a WOCBP must have a negative highly sensitive pregnancy test within 24 hours before the first dose of study intervention
• Renally impaired participants must have the following:
• With the exception of renal impairment, is in generally good health
• Has a BMI ≥ 18.5 and ≤ 40 kg/m2
• Female is not pregnant or breastfeeding, and is not one of the following: a woman of childbearing potential (WOCBP); if a WOCBP, is using an acceptable contraceptive method, or is abstinent from heterosexual intercourse as their preferred and usual lifestyle; a WOCBP must have a negative highly sensitive pregnancy test within 24 hours before the first dose of study intervention

You may not qualify if:

• Healthy participants must have the following:
• Has a history of clinically significant endocrine, gastrointestinal, cardiovascular, hematological, hepatic, immunological, renal, respiratory, genitourinary, or major neurological (including stroke and chronic seizures) abnormalities or diseases.
• Is mentally or legally incapacitated, has significant emotional problems
• Has known hypersensitivity to the active substance or any of the excipients of the study drug
• 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, hepatitis C antibodies or HIV.
• Had major surgery, donated or lost 1 unit of blood (approximately 500 mL) within prior 4 weeks
• Is taking medications to treat chronic medical conditions and/or conditions associated with renal disease
• Has participated in another investigational study within prior 4 weeks
• Does not agree to follow the smoking restrictions
• Consumes greater than 1 glass for women, or 2 glasses for men of alcoholic beverages per day
• Consumes excessive amounts,of caffeinated beverages per day.
• Is a regular user of cannabis, any illicit drugs or has a history of drug (including alcohol) abuse within approximately prior 3 months.
• Renally impaired participants must have the following:
• Has a history or presence of renal artery stenosis.

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (2)

Clinical Pharmacology of Miami ( Site 0001)

Miami, Florida, 33014, United States

Location

Charite Research Organisation GmbH ( Site 0003)

Berlin, 10117, Germany

Location

Related Publications (1)

• Matthews RP, Cao Y, Patel M, Weissler VL, Bhattacharyya A, De Lepeleire I, Last S, Rondon JC, Vargo R, Stoch SA, Iwamoto M. Safety and Pharmacokinetics of Islatravir in Individuals with Severe Renal Insufficiency. Antimicrob Agents Chemother. 2022 Dec 20;66(12):e0093122. doi: 10.1128/aac.00931-22. Epub 2022 Nov 8.

  PMID: 36346229 DERIVED

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome

Interventions

islatravir

Condition Hierarchy (Ancestors)

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

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: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 9, 2020
• First Posted: March 10, 2020
• Study Start: June 18, 2020
• Primary Completion: October 19, 2020
• Study Completion: October 19, 2020
• Last Updated: October 28, 2021
• Results First Posted: October 28, 2021

Record last verified: 2021-09

Data Sharing

• IPD Sharing: Will share

Locations

US (1); DE (1)