A Study of Doravirine (MK-1439) in Human Immunodeficiency Virus Type 1 (HIV-1)-Infected Participants (MK-1439-005)

NCT01466985 | Completed Phase 1 Results

• 3 other identifiers: 1439-0052011-003508-19MK-1439-005
• Study Type: interventional
• Target: 18
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a study to evaluate the safety, tolerability, pharmacokinetics, and antiretroviral activity of doravirine (MK-1439) as monotherapy in antiretroviral therapy (ART)-naïve, HIV-1-infected participants.

Conditions

HIV-1 Infection

Outcome Measures

Primary Outcomes (1)

• Percentage Change From Baseline in HIV-1 Ribonucleic Acid (RNA) Viral Load

  The change from baseline to Day 7 in plasma HIV RNA viral load was determined for each arm. Results are expressed as change in HIV RNA log10 copies/mL after 7 daily doses of doravirine or placebo. It was hypothesized that at least 1 dose of doravirine would be superior to placebo as documented by the upper bound of the 90% confidence interval \<-1. Plasma HIV RNA levels were determined using the Abbott RealTime HIV assay which has a linear range from 40 to 10 million copies/mL.

  Baseline and Day 7

Secondary Outcomes (4)

• Area Under the Plasma Concentration Time Curve From Dosing to 24 Hours Postdose (AUC0-24hr) of Doravirine on Day 7

  Predose and 1, 2, 4, 6, 8, 10, 12 and 24 hours postdose on Day 7

• Maximum Plasma Concentration (Cmax) of Doravirine on Day 7

  Predose and 1, 2, 4, 6, 8, 10, 12 and 24 hours postdose on Day 7

• Plasma Concentration 24 Hours Postdose (C24hr) of Doravirine on Day 7

  24 hours postdose on Day 7 (Day 8)

• Time to Maximum Plasma Concentration (Tmax) of Doravirine on Day 7

  Predose and 1, 2, 4, 6, 8, 10, 12 and 24 hours postdose on Day 7

Study Arms (3)

Panel A: Doravirine 25 mg or Placebo

EXPERIMENTAL

Participants will receive oral doses of doravirine 25 mg or placebo once daily for 7 days.

Drug: Doravirine; Drug: Placebo

Panel B: Doravirine 200 mg or Placebo

EXPERIMENTAL

Panel B (doravirine 200 mg or placebo once daily for 7 days) will initiate upon satisfactory review of safety and tolerability from Panel A, and all safety, tolerability and pharmacokinetic data from the study MK-1439-001.

Drug: Doravirine; Drug: Placebo

Panel C: Doravirine or Placebo

EXPERIMENTAL

Panel C is optional. If conducted, the dose will be confirmed after review of data from prior panels.

Drug: Doravirine; Drug: Placebo

Interventions

Doravirine DRUG

Doravirine tablets, orally, once daily for 7 days at a dose of 25 mg in Panel A and 200 mg in Panel B; dose in Panel C to be determined (≤200 mg).

Also known as: MK-1439

Panel A: Doravirine 25 mg or Placebo; Panel B: Doravirine 200 mg or Placebo; Panel C: Doravirine or Placebo

Placebo DRUG

Placebo tablets once daily for 7 days.

Panel A: Doravirine 25 mg or Placebo; Panel B: Doravirine 200 mg or Placebo; Panel C: Doravirine or Placebo

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Diagnosis of HIV-1-infection ≥3 months prior to screening
• Participants with female partner(s) of child-bearing potential must agree to use a medically acceptable method of contraception during the study and for 90 days after the last dose of study drug
• Body Mass Index (BMI) ≤35 kg/m\^2
• Other than HIV infection, participant's baseline health is judged to be stable
• No clinically significant abnormality on electrocardiogram (ECG)
• Participant is ART-naïve (defined as having never received any antiretroviral agent or ≤30 consecutive days of an investigational antiretroviral agent (excluding an Non-Nucleoside Reverse Transcriptase Inhibitor \[NNRTI\]) or ≤60 consecutive days of combination ART not including an NNRTI)
• Participant is willing to receive no other ART for the duration of the treatment phase of this study.

You may not qualify if:

• History of stroke, chronic seizures, or major neurological disorder
• History of clinically significant endocrine, gastrointestinal, cardiovascular, hematological, hepatic, immunological (outside of HIV-1 infection), renal, respiratory, or genitourinary abnormalities or diseases
• History of clinically significant neoplastic disease
• Participant has used any immune therapy agents or immunosuppressive therapy within 1 month prior to treatment in this study
• Participant has one or more pre-existing risk factors for Torsades de Pointes (New York Heart Association Functional Classification II through IV heart failure, familial long-QT-syndrome, uncorrected hypokalemia, QTcF \>470 msec)
• Participant requires or is anticipated to require chronic daily prescription medications
• Current (active) diagnosis of acute hepatitis due to any cause
• History of chronic Hepatitis C virus (HCV) unless there has been documented cure and/or patient with a positive serologic test for HCV has a negative HCV viral load.
• Positive Hepatitis B surface antigen
• Participant is unable to refrain from or anticipates the use of any medication, including prescription and non-prescription drugs or herbal remedies (such as St. John's Wort \[Hypericum perforatum\]) beginning approximately 2 weeks (or 5 half-lives) prior to administration of the initial dose of study drug, throughout the study, until the post-study visit
• Participant consumes excessive amounts of alcohol, defined as greater than 3 glasses of alcoholic beverages (1 glass is approximately equivalent to: beer \[284 mL/10 ounces\], wine \[125 mL/4 ounces\], or distilled spirits \[25 mL/1 ounce\]) per day
• Participant consumes excessive amounts, defined as greater than 6 servings (1 serving is approximately equivalent to 120 mg of caffeine) of coffee, tea, cola, or other caffeinated beverages per day
• Participant is an excessive smoker (i.e., more than 10 cigarettes/day) and is unwilling to restrict smoking to ≤10 cigarettes per day
• Major surgery, donated or lost 1 unit of blood (approximately 500 mL) within 4 weeks prior to the prestudy (screening) visit
• Participation in another investigational study within 4 weeks prior to the prestudy (screening) visit

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Publications (1)

• Schurmann D, Sobotha C, Gilmartin J, Robberechts M, De Lepeleire I, Yee KL, Guo Y, Liu R, Wagner F, Wagner JA, Butterton JR, Anderson MS. A randomized, double-blind, placebo-controlled, short-term monotherapy study of doravirine in treatment-naive HIV-infected individuals. AIDS. 2016 Jan 2;30(1):57-63. doi: 10.1097/QAD.0000000000000876.

  PMID: 26372481 BACKGROUND

MeSH Terms

Interventions

doravirine

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: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 4, 2011
• First Posted: November 8, 2011
• Study Start: October 21, 2011
• Primary Completion: April 10, 2012
• Study Completion: April 10, 2012
• Last Updated: February 15, 2019
• Results First Posted: February 15, 2019

Record last verified: 2018-09

Data Sharing

• IPD Sharing: Will share