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

NCT ID: NCT04303156

Last Updated: 2021-10-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-06-18
• Study Completion Date: 2020-10-19

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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Severe Renal Impairment

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

Group Type: EXPERIMENTAL

Islatravir

Intervention Type: DRUG

Single oral dose of 60 mg Islatravir administered in capsule form

Healthy

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

Group Type: EXPERIMENTAL

Islatravir

Intervention Type: DRUG

Single oral dose of 60 mg Islatravir administered in capsule form

Interventions

Islatravir

Single oral dose of 60 mg Islatravir administered in capsule form

Intervention Type: DRUG

Other Intervention Names

MK-8591

Eligibility Criteria

Inclusion Criteria

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

Exclusion Criteria

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

Other exclusions for healthy participants:

• 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.
• Has had a renal transplant or nephrectomy.
• Has rapidly fluctuating renal function as determined by historical measurements.
• Has known hypersensitivity to the active substance or any of the excipients of the study drug.
• 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, 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 prestudy (screening) visit.
• Is taking medications to treat chronic medical conditions and/or conditions associated with renal disease and has not been on a stable regimen for at least 1 month and/or is unable to withhold the use of the medication(s) within 4 hours prior to and 8 hours after administration of the study drug.
• Has participated in another investigational study within 4 weeks (or 5 half-lives, whichever is greater) prior to the prestudy (screening) visit.

Other exclusions for renally impaired participants

• 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 3 months.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

Locations

Clinical Pharmacology of Miami ( Site 0001)

Miami, Florida, United States

Charite Research Organisation GmbH ( Site 0003)

Berlin, , Germany

Countries

United States; Germany

References

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.

Reference Type: DERIVED

PMID: 36346229 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

2020-000153-27

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

MK-8591-026

Identifier Type: OTHER

Identifier Source: secondary_id

8591-026

Identifier Type: -

Identifier Source: org_study_id