Clinical trial NCT01466985: A Study of Doravirine (MK-1439) in Human Immunodeficiency Virus Type 1 (HIV-1)-Infected Participants (MK-1439-005)
Official title: A Multiple Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Antiretroviral Activity of MK-1439 in HIV-1 Infected Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: HIV-1 Infection
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2011-11-08
Enrollment: 18
Sex: MALE
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Percentage Change From Baseline in HIV-1 Ribonucleic Acid (RNA) Viral Load
timeFrame: Baseline and Day 7
Secondary outcomes:
measure: Area Under the Plasma Concentration Time Curve From Dosing to 24 Hours Postdose (AUC0-24hr) of Doravirine on Day 7
timeFrame: Predose and 1, 2, 4, 6, 8, 10, 12 and 24 hours postdose on Day 7
measure: Maximum Plasma Concentration (Cmax) of Doravirine on Day 7
timeFrame: Predose and 1, 2, 4, 6, 8, 10, 12 and 24 hours postdose on Day 7
measure: Plasma Concentration 24 Hours Postdose (C24hr) of Doravirine on Day 7
timeFrame: 24 hours postdose on Day 7 (Day 8)
measure: Time to Maximum Plasma Concentration (Tmax) of Doravirine on Day 7
timeFrame: Predose and 1, 2, 4, 6, 8, 10, 12 and 24 hours postdose on Day 7
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: 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.