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

NCT ID: NCT01466985

Last Updated: 2019-02-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 18 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-10-21
• Study Completion Date: 2012-04-10

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Panel A: Doravirine 25 mg or Placebo

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

Group Type: EXPERIMENTAL

Doravirine

Intervention Type: 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).

Placebo

Intervention Type: DRUG

Placebo tablets once daily for 7 days.

Panel B: Doravirine 200 mg or 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.

Group Type: EXPERIMENTAL

Doravirine

Intervention Type: 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).

Placebo

Intervention Type: DRUG

Placebo tablets once daily for 7 days.

Panel C: Doravirine or Placebo

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

Group Type: EXPERIMENTAL

Doravirine

Intervention Type: 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).

Placebo

Intervention Type: DRUG

Placebo tablets once daily for 7 days.

Interventions

Doravirine

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).

Intervention Type: DRUG

Placebo

Placebo tablets once daily for 7 days.

Intervention Type: DRUG

Other Intervention Names

MK-1439

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

References

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.

Reference Type: BACKGROUND

PMID: 26372481 (View on PubMed)

Other Identifiers

2011-003508-19

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

MK-1439-005

Identifier Type: OTHER

Identifier Source: secondary_id

1439-005

Identifier Type: -

Identifier Source: org_study_id