Evaluation of Safety, Tolerability, Pharmacokinetics, and Antiretroviral Activity of MK-8507 in Human Immunodeficiency Virus (HIV-1)-Infected Participants (MK-8507-003)
Study Details
Study Description
Brief Summary
The study will evaluate the safety, tolerability, pharmacokinetics, and antiretroviral activity of a single dose of MK-8507 in antiretroviral therapy (ART)-naive, HIV-1 infected participants. The hypothesis tested in the study is that at a safe and well-tolerated dose, MK-8507 has superior antiretroviral activity to a historical placebo control, as measured by change from baseline in plasma HIV-1 ribonucleic acid (RNA) at 168 hours postdose.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Panel A: MK-8507 600 mg Single oral dose of MK-8507 600 mg (supplied as 10 mg and 100 mg tablets) administered after an overnight fast |
Drug: MK-8507
MK-8507 administered as a single oral dose
|
| Experimental: Panel B: MK-8507 150 mg Single oral dose of MK-8507 150 mg (supplied as 10 mg and 100 mg tablets) administered after an overnight fast |
Drug: MK-8507
MK-8507 administered as a single oral dose
|
| Experimental: Panel C: MK-8507 <=600 mg Single oral dose of MK-8507 <=600 mg mg (supplied as 10 mg and 100 mg tablets) administered after an overnight fast. Inclusion of Panel C in the study, and the dose selected, will be decided pending evaluation of results for Panels A and B. |
Drug: MK-8507
MK-8507 administered as a single oral dose
|
Outcome Measures
Primary Outcome Measures
- Change from Baseline in Plasma HIV-1 RNA [168 hours (7 days) postdose]
- Number of Participants with One or More Adverse Experiences [Up to 21 days postdose]
Secondary Outcome Measures
- Area Under the Plasma Concentration-Time Curve of MK-8507 (AUC0-168hr) [Up to 168 hours postdose]
- Maximum Plasma Concentration of MK-8507 (Cmax) [Up to 336 hours postdose]
- Time of Maximum Plasma Concentration of MK-8507 (Tmax) [Up to 336 hours postdose]
- Plasma Concentration of MK-8507 at 168 Hours Postdose (C168hr) [168 hours postdose]
- Plasma Concentration of MK-8507 at 336 Hours Postdose (C336hr) [336 hours postdose]
- Apparent Terminal Half-Life (T1/2) of Plasma MK-8507 [Up to 336 hours postdose]
Eligibility Criteria
Criteria
Inclusion Criteria:
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Male, or non-pregnant and non-breastfeeding female, or postmenopausal or surgically sterile female (confirmed with medical records, examination, or laboratory test). Male participants with female partner of childbearing potential agrees to use a medically acceptable method of contraception during the study and 90 days after receiving study drug.
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Body mass index <=35 kg/m^2
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Other than HIV infection, baseline health judged to be stable at screening and/or prior to administration of study drug
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No clinically-significant electrocardiogram abnormality
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Documented to be HIV-1 positive as determined by a positive enzyme-linked immunosorbent assay (ELISA) or quantitative polymerase chain reaction (PCR) result with confirmation
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Has a screening plasma Cluster of Differentiation (CD4) T-cell count of >200 /mm^3
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Has a plasma HIV-1 RNA >= 10,000 copies/mL within 30 days before administration of study drug
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ART-naive, defined as never having received any ART agent, or have received <=30 consecutive days of an investigational ART agent, excluding non-nucleoside reverse transcriptase inhibitors (NNRTIs), or have received <=60 consecutive days of combination ART, excluding NNRTIs
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Has not received an investigational agent or licensed ART within 30 days of study drug administration
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Diagnosed with HIV-1 infection >=3 months before screening
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Willing to receive no other ART for the duration of the study
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Has no evidence of mutations conferring resistance to NNRTIs at screening
Exclusion Criteria:
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Mentally or legally institutionalized or incapacitated, has significant emotional problems, or has a history of clinically significant psychiatric disorder
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History of clinically significant and not stably controlled abnormalities or diseases
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History of cancer, with the exceptions of 1) adequately-treated non-melanomatous skin carcinoma or carcinoma in situ of the cervix, 2) other malignancies which have been successfully treated >=10 years before screening, or 3) participants who are highly unlikely to sustain a recurrence for the duration of the study
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History of significant multiple and/or severe allergies, or has had an anaphylactic reaction or significant intolerability to drugs or food
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Positive for hepatitis B surface antigen
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History of chronic hepatitis C virus (HCV) unless there has been a documented cure or a negative HCV viral load
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Had major surgery, or donated or lost >=1 unit (~500 mL) of blood within 4 weeks before screening
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Participated in another investigational trial within 4 weeks before administration of study drug
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Unable to refrain from or anticipates the use of any medication beginning 4 weeks before administration of study drug and throughout the trial. Certain medications are permitted.
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Consumes >3 glasses of alcoholic beverages per day (1 glass is equivalent to 12 ounces of beer, 4 ounces of wine, or 1 ounce of distilled spirits). Participants who consume 4 glasses of alcoholic beverages per day may be enrolled at the discretion of the investigator.
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Consumes >10 cigarettes per day and is unwilling to restrict smoking to <=10 cigarettes per day
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Regular user of any illicit drugs or has a history of drug abuse (including alcohol) within 2 years
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Has an immediate family member who is investigational site or sponsor staff directly involved with the trial
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Merck Sharp & Dohme LLC
Investigators
- Study Director: Medical Director, Merck Sharp & Dohme LLC
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 8507-003
- 2014-000660-18