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

Study Overview
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Brief Summary
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This study will evaluate the effect of severe renal impairment on the pharmacokinetics of doravirine.

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

Conditions
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Renal Impairment

Intervention / Treatment
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* Drug: Doravirine


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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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 |