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

Phase 1

Completed

• Conditions: HIV-1 Infection
• Interventions: Drug: Doravirine; Drug: Placebo

• Registration Number: NCT01466985
• Lead Sponsor: Merck Sharp & Dohme LLC

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2011-10-21
• Study First Submitted: 2011-11-04
• Study First Submitted QC: 2011-11-04
• Study First Posted: 2011-11-08
• Primary Completion: 2012-04-10
• Study Completion: 2012-04-10
• Status Verified: 2018-09
• Results First Submitted: 2018-09-24
• Results First Submitted QC: 2018-09-24
• Last Update Submitted: 2018-09-24
• Results First Posted: 2019-02-15
• Last Update Posted: 2019-02-15

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 18

Inclusion Criteria

• 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.

Exclusion Criteria

• 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
• History of significant multiple and/or severe allergies (including latex allergy), or has had an anaphylactic reaction or significant intolerability to prescription or non-prescription drugs or food
• Current regular user (including use of any illicit drugs) or has a history of drug (including alcohol) abuse within approximately 1 year

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Panel C: Doravirine or Placebo	Placebo	Panel C is optional. If conducted, the dose will be confirmed after review of data from prior panels.
Panel A: Doravirine 25 mg or Placebo	Placebo	Participants will receive oral doses of doravirine 25 mg or placebo once daily for 7 days.
Panel B: Doravirine 200 mg or Placebo	Placebo	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.
Panel A: Doravirine 25 mg or Placebo	Doravirine	Participants will receive oral doses of doravirine 25 mg or placebo once daily for 7 days.
Panel C: Doravirine or Placebo	Doravirine	Panel C is optional. If conducted, the dose will be confirmed after review of data from prior panels.
Panel B: Doravirine 200 mg or Placebo	Doravirine	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.

Primary Outcome Measures

Name	Time	Method
Percentage Change From Baseline in HIV-1 Ribonucleic Acid (RNA) Viral Load	Baseline and Day 7	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.

Secondary Outcome Measures

Name	Time	Method
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	The AUC0-24hr of doravirine on Day 7 was determined in the doravirine treatment arms.
Plasma Concentration 24 Hours Postdose (C24hr) of Doravirine on Day 7	24 hours postdose on Day 7 (Day 8)	The C24hr of doravirine on Day 7 was determined in the doravirine treatment arms.
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	The Tmax of doravirine on Day 7 was determined in the doravirine treatment arms.
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	The Cmax of doravirine on Day 7 was determined in the doravirine treatment arms.