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

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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.

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.

Condition or disease Intervention/treatment Phase
HIV-1 Infection Drug: MK-8583 Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 5 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : October 7, 2018
Actual Primary Completion Date : March 11, 2019
Actual Study Completion Date : March 11, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

Arm Intervention/treatment
Experimental: A: MK-8583 100mg
After fasting, a single oral dose of 100 mg MK-8583 in capsule form.
Drug: MK-8583
A single oral dose of MK-8583 in capsule form

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
Drug: MK-8583
A single oral dose of MK-8583 in capsule form

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
Drug: MK-8583
A single oral dose of MK-8583 in capsule form




Primary Outcome Measures :
  1. Adverse Events [ Time Frame: Up to Day 29 ]
    Number of participants with at least one adverse event (AE)

  2. Discontinuations [ Time Frame: Day 1 ]
    Number of participants who discontinued study due to an AE

  3. 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.


Secondary Outcome Measures :
  1. 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)

  2. 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

  3. 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

  4. C168hr of TFV-DP [ Time Frame: 168 hr postdose ]
    Concentration at 168 hours postdose (C168hr) of TFV-DP in PBMCs

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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

  11. 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

  12. 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

  13. 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

  14. 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)

  15. 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

  16. 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

  17. 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

  18. 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



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03552536


Locations
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Germany
Charite Research Organisation GmbH ( Site 0001)
Berlin, Germany, 10117
Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
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Study Director: Medical Director Merck Sharp & Dohme Corp.

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Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT03552536     History of Changes
Other Study ID Numbers: 8583-002
2017-004017-92 ( EudraCT Number )
MK-8583-002 ( Other Identifier: Merck Protocol Number )
First Posted: June 12, 2018    Key Record Dates
Last Update Posted: March 25, 2019
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
URL: http://engagezone.msd.com/ds_documentation.php

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No