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

An Open-Label, Single-Dose Study to Evaluate the Pharmacokinetics of MK-1439 (Doravirine) in Subjects With Severe Renal Impairment

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

Study Overview

• Status: Completed
• Conditions: Renal Impairment
• Intervention / Treatment: Drug: Doravirine

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Severe Renal Impairment; Participants with severe renal impairment receive a single oral dose of 100 mg doravirine	Drug: Doravirine; Following an overnight fast, a single coated tablet of 100 mg doravirine will be administered orally; Other Names: MK-1439, PIFELTRO
Experimental: Healthy Matched Control; Healthy participants matched for age and weight receive a single oral dose of 100 mg doravirine	Drug: Doravirine; Following an overnight fast, a single coated tablet of 100 mg doravirine will be administered orally; Other Names: MK-1439, PIFELTRO

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Plasma Concentration Versus Time Curve From 0 Hours to Infinity (AUC0-∞) of Doravirine	Blood was collected for the determination of plasma doravirine using a liquid chromatographic tandem mass spectrometric method.	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
Plasma Concentration of Doravirine at 24 Hours Postdose (C24)	Blood was collected for the determination of plasma doravirine using a liquid chromatographic tandem mass spectrometric method.	24 hours postdose
Maximum Observed Plasma Concentration (Cmax) of Doravirine	Blood was collected for the determination of plasma doravirine using a liquid chromatographic tandem mass spectrometric method.	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
Area Under the Plasma Concentration Versus Time Curve From 0 Hours to the Time of Last Quantifiable Sample of Doravirine (AUC 0-last)	Blood was collected for the determination of plasma doravirine using a liquid chromatographic tandem mass spectrometric method.	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
Time to Maximum Observed Plasma Concentration (Tmax) of Doravirine	Blood was collected for the determination of plasma doravirine using a liquid chromatographic tandem mass spectrometric method.	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
Apparent Terminal Half-life (t1/2) of Plasma Doravirine	Blood was collected for the determination of plasma doravirine using a liquid chromatographic tandem mass spectrometric method.	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
Apparent Clearance of Plasma Doravirine After Extravascular Administration (CL/F)	Blood was collected for the determination of plasma doravirine using a liquid chromatographic tandem mass spectrometric method.	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
Apparent Volume of Distribution of Plasma Doravirine During the Terminal Phase (Vz/F)	Blood was collected for the determination of plasma doravirine using a liquid chromatographic tandem mass spectrometric method.	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

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Publications and helpful links

General Publications

• Ankrom W, Yee KL, Sanchez RI, Adedoyin A, Fan L, Marbury T, Preston RA, Iwamoto M, Khalilieh SG. Severe Renal Impairment Has Minimal Impact on Doravirine Pharmacokinetics. Antimicrob Agents Chemother. 2018 Jul 27;62(8):e00326-18. doi: 10.1128/AAC.00326-18. Print 2018 Aug.

Study record dates

Study Major Dates

• Study Start (Actual): January 26, 2016
• Primary Completion (Actual): May 14, 2016
• Study Completion (Actual): May 25, 2016

Study Registration Dates

• First Submitted: December 23, 2015
• First Submitted That Met QC Criteria: December 23, 2015
• First Posted (Estimate): December 29, 2015

Study Record Updates

• Last Update Posted (Actual): February 8, 2019
• Last Update Submitted That Met QC Criteria: September 26, 2018
• Last Verified: September 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Renal Insufficiency
• Other Study ID Numbers: 1439-051; MK-1439-051 (Other Identifier: Merck Protocol Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf