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

Renal Impairment Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02641067
• Other study ID #: 1439-051
• Secondary ID: MK-1439-051
• Status: Completed
• Phase: Phase 1
• Start date: January 26, 2016
• Est. completion date: May 25, 2016

Study information

• Verified date: September 2018
• Source: Merck Sharp & Dohme Corp.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 16
• Est. completion date: May 25, 2016
• Est. primary completion date: May 14, 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Renal Impairment
• Renal Insufficiency

Intervention

Drug:
• Doravirine
Following an overnight fast, a single coated tablet of 100 mg doravirine will be administered orally

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme Corp.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Area Under the Plasma Concentration Versus Time Curve From 0 Hours to Infinity (AUC0-8) 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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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