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MK-8583 Single Dose Study in Human Immunodeficiency Virus Type 1 (HIV-1) Infected Participants (MK-8583-002)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03552536
Recruitment Status : Completed
First Posted : June 12, 2018
Last Update Posted : March 25, 2019
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Tracking Information
First Submitted Date  ICMJE May 29, 2018
First Posted Date  ICMJE June 12, 2018
Last Update Posted Date March 25, 2019
Actual Study Start Date  ICMJE October 7, 2018
Actual Primary Completion Date March 11, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 29, 2018)
  • Adverse Events [ Time Frame: Up to Day 29 ]
    Number of participants with at least one adverse event (AE)
  • Discontinuations [ Time Frame: Day 1 ]
    Number of participants who discontinued study due to an AE
  • HIV-1 RNA [ Time Frame: Baseline (pre-dose) and 168 hours post-dose. ]
    Change from baseline in plasma HIV-1 RNA at 168 hours post-dose.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 29, 2018)
  • AUC0-168hr of TFV-DP [ Time Frame: Pre-dose, 4, 12, 24, 48, 72, 96, and 168 hours postdose ]
    Area under the concentration time curve from time 0-168 hours postdose (AUC0-168hr) of intracellular tenofovir diphosphate (TFV-DP) in peripheral blood mononuclear cells (PBMCs)
  • Tmax of TFV-DP [ Time Frame: Pre-dose, 4, 12, 24, 48, 72, 96, 168, 240, 312 and 672 hours postdose ]
    Time to achieve maximum concentration (Tmax) of intracellular TFV-DP in PBMCs
  • Cmax of TFV-DP [ Time Frame: Pre-dose, 4, 12, 24, 48, 72, 96, 168, 240, 312 and 672 hours postdose ]
    Maximum concentration (Cmax) of intracellular TFV-DP in PBMCs
  • C168hr of TFV-DP [ Time Frame: 168 hr postdose ]
    Concentration at 168 hours postdose (C168hr) of TFV-DP in PBMCs
  • t1/2 of TFV-DP [ Time Frame: Pre-dose, 4, 12, 24, 48, 72, 96, 168, 240, 312 and 672 hours postdose ]
    Apparent terminal half-life (t1/2) of intracellular TFV-DP in PBMCs
  • AUC0-last of MK-8583 [ Time Frame: Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, and 72 hours postdose ]
    Area under the concentration time curve from time 0-last measurement (AUC0-last) of plasma MK-8583
  • AUC0-inf of MK-8583 [ Time Frame: Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, and 72 hours postdose ]
    Area under the concentration time curve from time 0-infinity (AUC0-inf) of plasma MK-8583
  • AUC0-168hr of MK-8583 [ Time Frame: Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, and 72 hours postdose ]
    Area under the concentration time curve from time 0-168 hours postdose (AUC0-168hr) of plasma MK-8583
  • Tmax of MK-8583 [ Time Frame: Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, and 72 hours postdose ]
    Time to achieve maximum concentration (Tmax) of plasma MK-8583
  • Cmax of MK-8583 [ Time Frame: Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, and 72 hours postdose ]
    Maximum concentration (Cmax) of plasma MK-8583
  • t1/2 of MK-8583 [ Time Frame: Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, and 72 hours postdose ]
    Apparent terminal half-life (t1/2) of plasma MK-8583
  • CL/F of MK-8583 [ Time Frame: Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, and 72 hours postdose ]
    Apparent total clearance (CL/F) of plasma MK-8583
  • Vz/F of MK-8583 [ Time Frame: Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, and 72 hours postdose ]
    Apparent volume of distribution (Vz/F) of plasma MK-8583
  • AUC0-last of TFV [ Time Frame: Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, and 72 hours postdose ]
    Area under the concentration time curve from time 0-last measurement (AUC0-last) of plasma tenofovir (TFV)
  • AUC0-inf of TFV [ Time Frame: Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, and 72 hours postdose ]
    Area under the concentration time curve from time 0-infinity (AUC0-inf) of plasma TFV
  • Tmax of TFV [ Time Frame: Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, and 72 hours postdose ]
    Time to achieve maximum concentration (Tmax) of plasma TFV
  • Cmax of TFV [ Time Frame: Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, and 72 hours postdose ]
    Maximum concentration (Cmax) of plasma TFV
  • t1/2 of TFV [ Time Frame: Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, and 72 hours postdose ]
    Apparent terminal half-life (t1/2) of plasma TFV
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE MK-8583 Single Dose Study in Human Immunodeficiency Virus Type 1 (HIV-1) Infected Participants (MK-8583-002)
Official Title  ICMJE 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
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE HIV-1 Infection
Intervention  ICMJE Drug: MK-8583
A single oral dose of MK-8583 in capsule form
Study Arms  ICMJE
  • Experimental: A: MK-8583 100mg
    After fasting, a single oral dose of 100 mg MK-8583 in capsule form.
    Intervention: Drug: MK-8583
  • Experimental: B: MK-8583 ≤ 150 mg
    After fasting, a single oral dose of ≤ 150 mg MK-8583 in capsule form, with the dose based on the results from earlier treatments
    Intervention: Drug: MK-8583
  • Experimental: C: MK-8583 ≤ 150 mg
    After fasting, a single oral dose of ≤ 150 mg MK-8583 in capsule form, with the dose based on the results from earlier treatments
    Intervention: Drug: MK-8583
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: March 21, 2019)
5
Original Estimated Enrollment  ICMJE
 (submitted: May 29, 2018)
18
Actual Study Completion Date  ICMJE March 11, 2019
Actual Primary Completion Date March 11, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 60 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Germany
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03552536
Other Study ID Numbers  ICMJE 8583-002
2017-004017-92 ( EudraCT Number )
MK-8583-002 ( Other Identifier: Merck Protocol Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
URL: http://engagezone.msd.com/ds_documentation.php
Responsible Party Merck Sharp & Dohme Corp.
Study Sponsor  ICMJE Merck Sharp & Dohme Corp.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Medical Director Merck Sharp & Dohme Corp.
PRS Account Merck Sharp & Dohme Corp.
Verification Date March 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP