A Study Evaluating the Pharmacokinetics of Doravirine (MK-1439) in Participants With Severe Renal Impairment (MK-1439-051)

Phase 1

Completed

• Conditions: Renal Impairment
• Interventions: Drug: Doravirine

• Registration Number: NCT02641067
• Lead Sponsor: Merck Sharp & Dohme LLC

Brief Summary

This study will evaluate the effect of severe renal impairment on the pharmacokinetics of doravirine.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2015-12-23
• Study First Submitted QC: 2015-12-23
• Study First Posted: 2015-12-29
• Study Start: 2016-01-26
• Primary Completion: 2016-05-14
• Study Completion: 2016-05-25
• Status Verified: 2018-09
• Results First Submitted: 2018-09-26
• Results First Submitted QC: 2018-09-26
• Last Update Submitted: 2018-09-26
• Results First Posted: 2019-02-08
• Last Update Posted: 2019-02-08

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 16

Inclusion Criteria

• is a non-smoker or moderate smoker
• has a body mass index (BMI) ≥ 18.5 and ≤ 40.0 kg/m^2
• other than renal impairment, participant is judged to be in good health based on medical history, physical examination, vital signs, and laboratory safety tests
• female informed of the risks of pregnancy, agree not to become pregnant while participating in this study. Female of childbearing potential must either be sexually inactive for 14 days prior to dosing and throughout the study, or uses one acceptable birth control method
• female of non-childbearing potential must have undergone sterilization procedures at least 6 months prior to dosing.
• Participants with severe renal impairment only: has baseline estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73m^2

Exclusion Criteria

• is mentally or legally incapacitated or has significant emotional problems
• has a history or presence of clinically significant medical or psychiatric condition or disease
• has history or presence of alcoholism or drug abuse within the past 2 years
• has history or presence of hypersensitivity or idiosyncratic reaction to the study drug, any inactive ingredients, or related compounds
• has history or presence of renal artery stenosis
• has had a renal transplant or nephrectomy
• has rapidly fluctuating renal function as determined by historical measurements
• female is pregnant or lactating
• has positive results for the urine or saliva drug and urine or breath alcohol screen at screening or check-in
• has positive results at screening for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV)
• is unable to refrain from or anticipates the use of any drug, including prescription and non-prescription medications, herbal remedies, or vitamin supplements beginning 14 days prior to dosing and throughout the study. Certain medications including those to treat kidney disease will be permitted. Other medications may be permitted following consultation with the Sponsor Clinical Monitor.
• is unable to refrain from or anticipates the use of inducers of cytochrome P450 3A (CYP3A) or permeability glycoprotein (P-gp) transporters for at least 28 days prior to dosing and throughout the study.
• has been on a diet incompatible with the on-study diet, within 28 days prior to dosing, and throughout the study
• has donated blood or had significant blood loss within 56 days prior to dosing
• has donated plasma within 7 days prior to dosing
• has participated in another clinical trial within 28 days prior to dosing

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Severe Renal Impairment	Doravirine	Participants with severe renal impairment receive a single oral dose of 100 mg doravirine
Healthy Matched Control	Doravirine	Healthy participants matched for age and weight receive a single oral dose of 100 mg doravirine

Primary Outcome Measures

Name	Time	Method
Area Under the Plasma Concentration Versus Time Curve From 0 Hours to Infinity (AUC0-∞) of Doravirine	Pre-dose, 0.5, 1, 2, 3, 4, 6, 12, 24, 48, 72 hours post-dose for all participants; and 96 hours post-dose for participants with severe renal impairment	Blood was collected for the determination of plasma doravirine using a liquid chromatographic tandem mass spectrometric method.
Plasma Concentration of Doravirine at 24 Hours Postdose (C24)	24 hours postdose	Blood was collected for the determination of plasma doravirine using a liquid chromatographic tandem mass spectrometric method.
Maximum Observed Plasma Concentration (Cmax) of Doravirine	Pre-dose, 0.5, 1, 2, 3, 4, 6, 12, 24, 48, 72 hours post-dose for all participants; and 96 hours post-dose for participants with severe renal impairment	Blood was collected for the determination of plasma doravirine using a liquid chromatographic tandem mass spectrometric method.
Area Under the Plasma Concentration Versus Time Curve From 0 Hours to the Time of Last Quantifiable Sample of Doravirine (AUC 0-last)	Pre-dose, 0.5, 1, 2, 3, 4, 6, 12, 24, 48, 72 hours post-dose for all participants; and 96 hours post-dose for participants with severe renal impairment	Blood was collected for the determination of plasma doravirine using a liquid chromatographic tandem mass spectrometric method.
Time to Maximum Observed Plasma Concentration (Tmax) of Doravirine	Pre-dose, 0.5, 1, 2, 3, 4, 6, 12, 24, 48, 72 hours post-dose for all participants; and 96 hours post-dose for participants with severe renal impairment	Blood was collected for the determination of plasma doravirine using a liquid chromatographic tandem mass spectrometric method.
Apparent Terminal Half-life (t1/2) of Plasma Doravirine	Pre-dose, 0.5, 1, 2, 3, 4, 6, 12, 24, 48, 72 hours post-dose for all participants; and 96 hours post-dose for participants with severe renal impairment	Blood was collected for the determination of plasma doravirine using a liquid chromatographic tandem mass spectrometric method.
Apparent Clearance of Plasma Doravirine After Extravascular Administration (CL/F)	Pre-dose, 0.5, 1, 2, 3, 4, 6, 12, 24, 48, 72 hours post-dose for all participants; and 96 hours post-dose for participants with severe renal impairment	Blood was collected for the determination of plasma doravirine using a liquid chromatographic tandem mass spectrometric method.
Apparent Volume of Distribution of Plasma Doravirine During the Terminal Phase (Vz/F)	Pre-dose, 0.5, 1, 2, 3, 4, 6, 12, 24, 48, 72 hours post-dose for all participants; and 96 hours post-dose for participants with severe renal impairment	Blood was collected for the determination of plasma doravirine using a liquid chromatographic tandem mass spectrometric method.