Phase 1
Completed N=12
Activity of MK-8504 in Anti-retroviral-naïve, Human Immunodeficiency Virus 1 (HIV-1) Infected Participants (MK-8504-002)
Source: ClinicalTrials.gov NCT03188523 ↗Enrolled (actual)
12
Serious AEs
0.0%
Results posted
Jul 2019
Primary outcomePrimary: Change From Baseline in Plasma HIV-1 Ribonucleic Acid (RNA) at 168 Hours Post-Dose — -1.06; -0.95 log10 (copies/mL)
Summary
This study aims to evaluate the safety, tolerability, pharmacokinetics (PK), and anti-retroviral therapy (ART) activity of monotherapy with MK-8504 (a tenofovir pro-drug), in ART-naïve Human Immunodeficiency Virus (HIV)-1 infected participants. The primary hypothesis is that MK-8504, at a dose that is sufficiently safe and well tolerated, has superior antiretroviral activity compared to placebo, as measured by change from baseline in plasma HIV-1 ribonucleic acid (RNA) at 168 hours post-dose.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Change From Baseline in Plasma HIV-1 Ribonucleic Acid (RNA) at 168 Hours Post-Dose |
-1.06; -0.95 | — |
| PRIMARY Number of Participants Who Experienced At Least One Adverse Event (AE) |
5; 6 | — |
| PRIMARY Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE) |
0; 0 | — |
| SECONDARY Area Under the Concentration-Time Curve of MK-8504 in Plasma From Time 0 to Last Measurable Concentration (AUC0-last) |
2.58; 6.20 | — |
| SECONDARY Area Under the Concentration-Time Curve of MK-8504 in Plasma From Time 0 to Infinity (AUC0-inf) |
2.59; 6.25 | — |
| SECONDARY Area Under the Concentration-Time Curve of MK-8504 in Plasma From Time 0 to 168 Hours (AUC0-168hr) |
2.61; 6.26 | — |
| SECONDARY Time to Maximum Concentration of MK-8504 in Plasma (Tmax) |
1.00; 0.75 | — |
| SECONDARY Maximum Concentration of MK-8504 in Plasma (Cmax) |
2.72; 5.32 | — |
| SECONDARY Apparent Terminal Half Life of MK-8504 in Plasma (t½) |
3.02; 6.27 | — |
| SECONDARY Apparent Total Clearance of MK-8504 in Plasma (CL/F) |
67.7; 67.4 | — |
| SECONDARY Apparent Volume of Distribution During Terminal Phase (Vz/F) of MK-8504 in Plasma |
295; 609 | — |
| SECONDARY Intracellular Area Under the Concentration-Time Curve of Tenofovir-Diphosphate (TFV-DP) From Time 0 to 168 Hours (Intracellular AUC0-168hr) In Peripheral Blood Mononuclear Cells (PBMCs) |
346; 885 | — |
| SECONDARY Intracellular Area Under the Concentration-Time Curve of Tenofovir-Diphosphate (TFV-DP) From Time 0 to Infinity (Intracellular AUC0-inf) In Peripheral Blood Mononuclear Cells (PBMCs) |
433; 1020 | — |
| SECONDARY Intracellular Time to Maximum Concentration (Intracellular Tmax) of Tenofovir-Diphosphate (TFV-DP) In Peripheral Blood Mononuclear Cells (PBMCs) |
4.00; 12.00 | — |
| SECONDARY Intracellular Maximum Concentration (Intracellular Cmax) of Tenofovir-Diphosphate (TFV-DP) In Peripheral Blood Mononuclear Cells (PBMCs) |
5.89; 15.1 | — |
| SECONDARY Intracellular Apparent Terminal Half Life (Intracellular t½) of Tenofovir-Diphosphate (TFV-DP) In Peripheral Blood Mononuclear Cells (PBMCs) |
72.4; 67.5 | — |
| SECONDARY Intracellular Concentration of Tenofovir-Diphosphate (TFV-DP) at 168 Hours (Intracellular C168hr) In Peripheral Blood Mononuclear Cells (PBMCs) |
0.910; 1.35 | — |
| SECONDARY Area Under the Concentration-Time Curve of Tenofovir in Plasma From Time 0 to Last Measurable Concentration (AUC0-last) |
1.71; 4.47 | — |
| SECONDARY Area Under the Concentration-Time Curve of Tenofovir in Plasma From Time 0 to Infinity (AUC0-inf) |
2.19; 6.00 | — |
| SECONDARY Area Under the Concentration-Time Curve of Tenofovir in Plasma From Time 0 to 168 Hours (AUC0-168hr) |
2.13; 5.72 | — |
| SECONDARY Time to Maximum Concentration of Tenofovir in Plasma (Tmax) |
2.00; 2.00 | — |
| SECONDARY Maximum Concentration of Tenofovir in Plasma (Cmax) |
0.0727; 0.156 | — |
| SECONDARY Apparent Terminal Half Life of Tenofovir in Plasma (t½) |
32.3; 35.3 | — |
Eligibility Criteria
Inclusion Criteria
- Male or non-pregnant and non-breast feeding female
- Have a Body Mass Index (BMI) ≤35 kg/m^2
- Other than HIV infection, have stable baseline health based on medical history, physical examination, vital sign measurements, and laboratory safety test
- Is documented HIV-1 positive
- Is diagnosed with HIV-1 infection 3 months prior to screening
- Is ART-naïve
- Has not received an investigational agent or marketed ART within 30 days of study drug administration and is willing to receive no other ART for the duration of this study
- Agree to follow smoking and other trial restrictions
Exclusion Criteria
- Is mentally or legally institutionalized / incapacitated, has significant emotional problems at the time of pretrial (screening) visit or expected during the conduct of the trial or has a history of clinically significant psychiatric disorder of the last 5 years
- Has a history of clinically significant endocrine, gastrointestinal, cardiovascular, hematological, hepatic, immunological (outside of HIV-1 infection), renal, respiratory, genitourinary or major neurological (including stroke and chronic seizures) abnormalities or diseases
- Has a history of cancer (malignancy)
- Has a history of significant multiple and/or severe allergies (e.g. food, drug, latex allergy), or has had an anaphylactic reaction or significant intolerability (i.e. systemic allergic reaction) to prescription or non-prescription drugs or food
- Is positive for hepatitis B surface antigen
- Has a history of chronic Hepatitis C
- Has had major surgery, donated or lost 1 unit of blood (approximately 500 mL) within 4 weeks prior to the pretrial (screening) visit.
- Has participated in another investigational trial within 4 weeks or 5 half-lives, whichever is greater, prior to the Day 1 Dosing visit
- Is unable to refrain from or anticipates the use of any medication, including prescription and non-prescription drugs or herbal remedies beginning approximately 2 weeks (or 5 half-lives) prior to administration of the initial dose of trial drug, throughout the trial, until the post-trial visit
- Consumes greater than 3 glasses of alcoholic beverages or distilled spirits per day
- Consumes excessive amounts, defined as greater than 6 servings of coffee, tea, cola, energy-drinks, or other caffeinated beverages per day
- Is an excessive smoker (i.e., more than 10 cigarettes/day) and is unwilling to restrict smoking to ≤10 cigarettes per day
- Have clinically significant abnormality on the electrocardiogram (ECG) performed at the prestudy (screening) visit and/or prior to administration of the initial dose of study drug
- Has a positive urine drug screen (except for cannabis) at screening and/or predose, rechecks are allowed
Data sourced from ClinicalTrials.gov (NCT03188523). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.