Clinical trial NCT02641067: A Study Evaluating the Pharmacokinetics of Doravirine (MK-1439) in Participants With Severe Renal Impairment (MK-1439-051)
Official title: An Open-Label, Single-Dose Study to Evaluate the Pharmacokinetics of MK-1439 (Doravirine) in Subjects With Severe Renal Impairment
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Renal Impairment
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2015-12-29
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


Eligibility criteria: 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

Primary outcomes:
measure: Area Under the Plasma Concentration Versus Time Curve From 0 Hours to Infinity (AUC0-∞) of Doravirine
timeFrame: 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
measure: Plasma Concentration of Doravirine at 24 Hours Postdose (C24)
timeFrame: 24 hours postdose
measure: Maximum Observed Plasma Concentration (Cmax) of Doravirine
timeFrame: 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
measure: Area Under the Plasma Concentration Versus Time Curve From 0 Hours to the Time of Last Quantifiable Sample of Doravirine (AUC 0-last)
timeFrame: 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
measure: Time to Maximum Observed Plasma Concentration (Tmax) of Doravirine
timeFrame: 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
measure: Apparent Terminal Half-life (t1/2) of Plasma Doravirine
timeFrame: 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
measure: Apparent Clearance of Plasma Doravirine After Extravascular Administration (CL/F)
timeFrame: 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
measure: Apparent Volume of Distribution of Plasma Doravirine During the Terminal Phase (Vz/F)
timeFrame: 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
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: 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.