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

HIV-1 Infection Clinical Trial

Official title:

A Multiple Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Antiretroviral Activity of MK-1439 in HIV-1 Infected Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01466985
• Other study ID #: 1439-005
• Secondary ID: 2011-003508-19MK
• Status: Completed
• Phase: Phase 1
• Start date: October 21, 2011
• Est. completion date: April 10, 2012

Study information

• Verified date: September 2018
• Source: Merck Sharp & Dohme Corp.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 18
• Est. completion date: April 10, 2012
• Est. primary completion date: April 10, 2012
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years to 55 Years

Eligibility

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

Related Conditions & MeSH terms

• HIV-1 Infection

Intervention

Drug:
• 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).
• Placebo
Placebo tablets once daily for 7 days.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme Corp.

References & Publications (1)

Schürmann 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Area Under the Plasma Concentration Time Curve From Dosing to 24 Hours Postdose (AUC0-24hr) of Doravirine on Day 7	The AUC0-24hr of doravirine on Day 7 was determined in the doravirine treatment arms.	Predose and 1, 2, 4, 6, 8, 10, 12 and 24 hours postdose on Day 7
Secondary	Maximum Plasma Concentration (Cmax) of Doravirine on Day 7	The Cmax of doravirine on Day 7 was determined in the doravirine treatment arms.	Predose and 1, 2, 4, 6, 8, 10, 12 and 24 hours postdose on Day 7
Secondary	Plasma Concentration 24 Hours Postdose (C24hr) of Doravirine on Day 7	The C24hr of doravirine on Day 7 was determined in the doravirine treatment arms.	24 hours postdose on Day 7 (Day 8)
Secondary	Time to Maximum Plasma Concentration (Tmax) of Doravirine on Day 7	The Tmax of doravirine on Day 7 was determined in the doravirine treatment arms.	Predose and 1, 2, 4, 6, 8, 10, 12 and 24 hours postdose on Day 7