Clinical trial NCT03552536: MK-8583 Single Dose Study in Human Immunodeficiency Virus Type 1 (HIV-1) Infected Participants (MK-8583-002)
Official title: A Single-Dose Clinical Trial to Study the Safety, Tolerability, Pharmacokinetics, and Anti- Retroviral Activity of MK-8583 Monotherapy in Anti-Retroviral Therapy (ART)-Naïve, 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: 2018-06-12
Enrollment: 5
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: This study aims to evaluate the safety, tolerability, pharmacokinetics (PK), and anti-retroviral therapy (ART) activity of the tenofovir prodrug, MK-8583 monotherapy in ART-naïve, HIV-1 infected participants. The primary hypothesis is that at a dose that is sufficiently safe and generally well tolerated, MK-8583 has superior anti-retroviral activity compared to historical placebo, as measured by change from baseline in plasma HIV-1 ribonucleic acid (RNA) (log10 copies/mL) at 168 hours post-dose.


Eligibility criteria: Inclusion Criteria:

* Male with female partner(s) of child-bearing potential use required methods of birth control.
* Female of reproductive potential must demonstrate a nongravid state at the pretrial (screening) visit and agree to use acceptable methods of birth control beginning at the pretrial (screening) visit, throughout the trial and until 30 days following cessation of treatment.
* Postmenopausal female, defined as without menses for at least 1 year and have a documented follicle stimulating hormone (FSH) level in the postmenopausal range at pretrial (screening).
* Surgically sterile female's status is post hysterectomy or oophorectomy.
* Is documented HIV-1 positive
* Is diagnosed with HIV-1 infection ≥ 3 months prior to screening.
* Is ART-naïve, defined as having never received any anti-retroviral agent; or ≤ 30 consecutive days of an investigational anti-retroviral agent, excluding a nucleoside reverse transcriptase inhibitor (NRTI), or ≤ 60 consecutive days of combination ART not including a NRTI.

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 over 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 unless there has been documented cure.
* 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 pre-trial (screening) visit.
* Uses or anticipates using 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, wine or distilled spirits per day.
* Consumes excessive amounts of 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.
* Has a positive urine drug screen (except for cannabis) at screening and/or pre-dose.
* Has received any investigational agent or any anti-retroviral agent within 60 days of study drug administration; or intends to receive any ART during this study.

Primary outcomes:
measure: Number of Participants With at Least One Adverse Event (AE)
timeFrame: Up to Day 29
measure: Number of Participants Who Discontinued Study Due to an AE
timeFrame: Day 1
measure: Change From Baseline in Plasma Human Immunodeficiency Virus Type 1 (HIV-1) Ribonucleic Acid (RNA) at 168 Hours Post-dose.
timeFrame: Baseline (pre-dose) and 168 hours post-dose.
Secondary outcomes:
measure: Area Under the Concentration Time Curve From Time 0-168 Hours Postdose (AUC0-168hr) of Tenofovir Diphosphate (TFV-DP)
timeFrame: Pre-dose, 4, 12, 24, 48, 72, 96, and 168 hours postdose
measure: Time to Achieve Maximum Concentration (Tmax) of TFV-DP
timeFrame: Pre-dose, 4, 12, 24, 48, 72, 96, 168, 240, 312 and 672 hours postdose
measure: Maximum Concentration (Cmax) of TFV-DP
timeFrame: Pre-dose, 4, 12, 24, 48, 72, 96, 168, 240, 312 and 672 hours postdose
measure: Concentration at 168 Hours Postdose (C168hr) of TFV-DP
timeFrame: 168 hr postdose
measure: Apparent Terminal Half-life (t1/2) of TFV-DP
timeFrame: Pre-dose, 4, 12, 24, 48, 72, 96, 168, 240, 312 and 672 hours postdose
measure: Area Under the Concentration Time Curve From Time 0-last Measurement (AUC0-last) of MK-8583
timeFrame: Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, and 72 hours postdose
measure: Area Under the Concentration Time Curve From Time 0-infinity (AUC0-inf) of MK-8583
timeFrame: Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, and 72 hours postdose
measure: Tmax of Plasma MK-8583.
timeFrame: Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, and 72 hours postdose
measure: Cmax of MK-8583
timeFrame: Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, and 72 hours postdose
measure: t1/2 of MK-8583
timeFrame: Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, and 72 hours postdose
measure: Apparent Total Clearance (CL/F) of MK-8583
timeFrame: Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, and 72 hours postdose
measure: Apparent Volume of Distribution (Vz/F) of MK-8583
timeFrame: Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, and 72 hours postdose
measure: AUC0-last of Tenofovir (TFV)
timeFrame: Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, and 72 hours postdose
measure: AUC0-inf of TFV
timeFrame: Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, and 72 hours postdose
measure: Tmax of TFV
timeFrame: Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, and 72 hours postdose
measure: Cmax of TFV
timeFrame: Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, and 72 hours postdose
measure: t1/2 of TFV
timeFrame: Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, and 72 hours postdose
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: Charite Research Organisation GmbH ( Site 0001)
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: