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

NCT02641067 | Completed Phase 1 Results

• 2 other identifiers: 1439-051MK-1439-051
• Study Type: interventional
• Target: 16
• Locations: 0 countries
• Sites: N/A

Brief Summary

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

Conditions

Renal Impairment

Outcome Measures

Primary Outcomes (8)

• 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

Study Arms (2)

Severe Renal Impairment

EXPERIMENTAL

Participants with severe renal impairment receive a single oral dose of 100 mg doravirine

Drug: Doravirine

Healthy Matched Control

EXPERIMENTAL

Healthy participants matched for age and weight receive a single oral dose of 100 mg doravirine

Drug: Doravirine

Interventions

Doravirine DRUG

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

Also known as: MK-1439, PIFELTRO

Healthy Matched Control; Severe Renal Impairment

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Publications (1)

• 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.

  PMID: 29891610 DERIVED

MeSH Terms

Conditions

Renal Insufficiency

Interventions

doravirine

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 23, 2015
• First Posted: December 29, 2015
• Study Start: January 26, 2016
• Primary Completion: May 14, 2016
• Study Completion: May 25, 2016
• Last Updated: February 8, 2019
• Results First Posted: February 8, 2019

Record last verified: 2018-09

Data Sharing

• IPD Sharing: Will share