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MK-8510 Monotherapy for the Treatment of Anti-retroviral naïve Human Immunodeficiency Virus Type 1 (HIV-1) Infected Participants (MK-8510-002)

Primary Purpose

HIV-1, Human Immunodeficiency Virus 1, Immunodeficiency Virus Type 1, Human

Status
Withdrawn
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
MK-8510
Sponsored by
Merck Sharp & Dohme LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for HIV-1

Eligibility Criteria

18 Years - 60 Years (Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Has HIV-1 infection, and is in good health based on medical history, physical examination, vital signs (VS) measurements, and laboratory safety tests. Has documented HIV-1 positive, as determined by a positive enzyme-linked immunosorbent assay (ELISA) or real-time quantitative polymerase chain reaction (QT-PCR) with confirmation (eg, Western Blot). Is anti-retroviral therapy (ART)-naïve, which is defined as: Having never received any anti-retroviral agent; or ART-experienced but has not received any ART for HIV-1 infection within 60 days; or Has received pre-exposure prophylaxis (PrEP) treatment prior to diagnosis of HIV-infection but has not received any PrEP within 30 days. Is willing to receive no other ART prior to Day 11 post-dose of the study. Has a body mass index (BMI) ≤35 kg/m2. Exclusion Criteria: Has acute (primary) HIV-1 infection. Has a history of clinically significant endocrine, gastrointestinal (GI), cardiovascular, hematological, hepatic, immunological, renal, respiratory, genitourinary, or major neurological (including stroke and chronic seizures) abnormalities or diseases. Has remote history of uncomplicated medical events (eg, uncomplicated kidney stones, as defined as spontaneous passage and no recurrence in the last 5 years, or childhood asthma). Is mentally or legally incapacitated or has significant emotional problems. Has history of cancer (malignancy). Has a history of significant multiple and/or severe allergies (eg, food, drug, latex allergy), or has had an anaphylactic reaction or significant intolerability (i.e, systemic allergic reaction) to prescription or nonprescription drugs or food. Has positive hepatitis B surface antigen (HBsAg). Has a history of chronic hepatitis C unless there has been documented cure and/or participant with a positive serologic test for hepatitis C virus (HCV) has a negative HCV viral load (VL). Had a major surgery and/or donated or lost 1 unit of blood (approximately 500 mL) within 4 weeks prior to the prestudy (screening) visit. Has participated in another investigational study within 4 weeks. Has a clinically significant abnormality on the electrocardiogram (ECG) performed at the pre-study visit. Has been committed to an institution by way of official or judicial order. Is under the age of legal consent or not capable of giving consent. Does not agree to follow the smoking restrictions as defined by the clinical research unit (CRU). Consumes greater than 3 servings of alcoholic beverages (1 serving is approximately equivalent to: beer [354 mL/12 ounces], wine [118 mL/4 ounces], or distilled spirits [29.5 mL/1 ounce]) per day. Consumes excessive amounts, defined as greater than 6 servings (1 serving is approximately equivalent to 120 mg of caffeine) of coffee, tea, cola, energy drinks, or other caffeinated beverages per day. Is a regular user of any illicit drugs (not including cannabis) or has an history of drug (including alcohol) abuse within approximately 12 months.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm 3

    Arm 4

    Arm Type

    Experimental

    Experimental

    Experimental

    Experimental

    Arm Label

    Panel A: MK-8510 at dose level 1

    Panel B: MK-8510 at dose level 2

    Panel C: MK-8510 at dose level 3

    Panel D: MK-8510 at dose level 4

    Arm Description

    Single oral dose of MK-8510 administered at dose level 1 (≤1800 mg) following a 10-hour fast. Dose level 1 shall not exceed 1800 mg.

    Single oral dose of MK-8510 administered at dose level 2 (≤2200 mg) following a 10-hour fast. Dose level 2 shall not exceed 2200 mg.

    Single oral dose of MK-8510 administered at dose level 3 (≤2200 mg) following a 10-hour fast. Dose level 3 shall not exceed 2200 mg.

    Single oral dose of MK-8510 administered at dose level 4 (≤2200 mg) following a 10-hour fast. Dose level 4 shall not exceed 2200 mg.

    Outcomes

    Primary Outcome Measures

    Change from Baseline in Plasma HIV-1 Ribonucleic Acid (RNA)
    The plasma HIV-RNA will be measured based on a longitudinal data analysis model containing fixed effects for dose level, and dose level by time interaction, and a random effect of MK-8510 (prodrug). The change from baseline for each dose level at 168-hours post baseline will be estimated from this model.
    Percentage of Participants Who Experience an Adverse Event (AE)
    An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment.
    Percentage of Participants Who Discontinued from Study Due to an Adverse Event (AE)
    The percentage of participants who discontinue study due to an AE will be presented.

    Secondary Outcome Measures

    Area Under the Concentration-Time Curve of MK-8558 From Time 0 to 168 Hours (AUC0-168 hr)
    The AUC0-168 of MK-8558 (active drug) after administration of MK-8510 (prodrug) in plasma will be calculated pre-dose, and 0.25, 0.5, 1, 2, 3, 4, 5, 6, 12, 24, 48, 72, 120, 168 hours post-dose.
    Area Under the Concentration-Time Curve of MK-8558 From Time 0 to last (AUC0-last)
    AUC0-last of MK-8558 (active drug) after administration of MK-8510 (prodrug) in plasma will be calculated pre-dose, and 0.25, 0.5, 1, 2, 3, 4, 5, 6, 12, 24, 48, 72, 120, 168, 240, 336, 504 hours post-dose.
    Concentration at 168 Hours Post-dose (C168) of MK-8558
    C168hr of MK-8558 (active drug) after administration of MK-8510 (prodrug) in plasma will be calculated.
    Maximum Concentration (Cmax) of MK-8558
    Cmax of MK-8558 (active drug) after administration of MK-8510 (prodrug) in plasma will be calculated pre-dose, and 0.25, 0.5, 1, 2, 3, 4, 5, 6, 12, 24, 48, 72, 120, 168, 240, 336, 504 hours post-dose.
    Time to Maximum Plasma Concentration (Tmax) of MK-8558
    Tmax of MK-8558 (active drug) after administration of MK-8510 (prodrug) in plasma will be calculated pre-dose, and 0.25, 0.5, 1, 2, 3, 4, 5, 6, 12, 24, 48, 72, 120, 168, 240, 336, 504 hours post-dose.
    Half Life (t1/2) of MK-8558
    t1/2 of MK-8558 (active drug) after administration of MK-8510 (prodrug) in plasma will be calculated pre-dose, and 0.25, 0.5, 1, 2, 3, 4, 5, 6, 12, 24, 48, 72, 120, 168, 240, 336, 504 hours post-dose.
    Apparent Plasma Clearance of Drug After Extravascular Administration (CL/F) of MK-8558
    CL/F of MK-8558 (active drug) after administration of MK-8510 (prodrug) in plasma will be calculated pre-dose, and 0.25, 0.5, 1, 2, 3, 4, 5, 6, 12, 24, 48, 72, 120, 168, 240, 336, 504 hours post-dose.
    Apparent Volume of Distribution in the Terminal State After Extravascular Administration (Vz/F) of MK-8558
    Vz/F of MK-8558 (active drug) after administration of MK-8510 (prodrug) in plasma will be calculated pre-dose, and 0.25, 0.5, 1, 2, 3, 4, 5, 6, 12, 24, 48, 72, 120, 168, 240, 336, 504 hours post-dose.
    Terminal t1/2 of MK-8558
    Terminal t1/2 of MK-8558 (active drug) after administration of MK-8510 (prodrug) in plasma will be calculated pre-dose, and 0.25, 0.5, 1, 2, 3, 4, 5, 6, 12, 24, 48, 72, 120, 168, 240, 336, 504 hours post-dose.

    Full Information

    First Posted
    January 17, 2023
    Last Updated
    March 23, 2023
    Sponsor
    Merck Sharp & Dohme LLC
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    1. Study Identification

    Unique Protocol Identification Number
    NCT05700734
    Brief Title
    MK-8510 Monotherapy for the Treatment of Anti-retroviral naïve Human Immunodeficiency Virus Type 1 (HIV-1) Infected Participants (MK-8510-002)
    Official Title
    A Single-dose Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Anti-retroviral Activity of MK-8510 Monotherapy in Anti-retroviral-naïve HIV-1 Infected Participants
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    March 2023
    Overall Recruitment Status
    Withdrawn
    Why Stopped
    Business Reasons
    Study Start Date
    April 17, 2023 (Anticipated)
    Primary Completion Date
    February 14, 2024 (Anticipated)
    Study Completion Date
    February 14, 2024 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Merck Sharp & Dohme LLC

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    Yes
    Studies a U.S. FDA-regulated Device Product
    No
    Product Manufactured in and Exported from the U.S.
    Yes
    Data Monitoring Committee
    No

    5. Study Description

    Brief Summary
    The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics and anti-retroviral activity of MK-8510 monotherapy in anti-retroviral-naïve HIV-1 infected participants.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    HIV-1, Human Immunodeficiency Virus 1, Immunodeficiency Virus Type 1, Human, Human Immunodeficiency Virus Type 1

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 1
    Interventional Study Model
    Sequential Assignment
    Masking
    None (Open Label)
    Allocation
    Randomized
    Enrollment
    0 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Panel A: MK-8510 at dose level 1
    Arm Type
    Experimental
    Arm Description
    Single oral dose of MK-8510 administered at dose level 1 (≤1800 mg) following a 10-hour fast. Dose level 1 shall not exceed 1800 mg.
    Arm Title
    Panel B: MK-8510 at dose level 2
    Arm Type
    Experimental
    Arm Description
    Single oral dose of MK-8510 administered at dose level 2 (≤2200 mg) following a 10-hour fast. Dose level 2 shall not exceed 2200 mg.
    Arm Title
    Panel C: MK-8510 at dose level 3
    Arm Type
    Experimental
    Arm Description
    Single oral dose of MK-8510 administered at dose level 3 (≤2200 mg) following a 10-hour fast. Dose level 3 shall not exceed 2200 mg.
    Arm Title
    Panel D: MK-8510 at dose level 4
    Arm Type
    Experimental
    Arm Description
    Single oral dose of MK-8510 administered at dose level 4 (≤2200 mg) following a 10-hour fast. Dose level 4 shall not exceed 2200 mg.
    Intervention Type
    Drug
    Intervention Name(s)
    MK-8510
    Intervention Description
    Single dose of MK-8510 administered as a tablet at a dose up to 2200 mg.
    Primary Outcome Measure Information:
    Title
    Change from Baseline in Plasma HIV-1 Ribonucleic Acid (RNA)
    Description
    The plasma HIV-RNA will be measured based on a longitudinal data analysis model containing fixed effects for dose level, and dose level by time interaction, and a random effect of MK-8510 (prodrug). The change from baseline for each dose level at 168-hours post baseline will be estimated from this model.
    Time Frame
    Baseline and 168 hours post-dose
    Title
    Percentage of Participants Who Experience an Adverse Event (AE)
    Description
    An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment.
    Time Frame
    Up to 36 days
    Title
    Percentage of Participants Who Discontinued from Study Due to an Adverse Event (AE)
    Description
    The percentage of participants who discontinue study due to an AE will be presented.
    Time Frame
    Up to 36 days
    Secondary Outcome Measure Information:
    Title
    Area Under the Concentration-Time Curve of MK-8558 From Time 0 to 168 Hours (AUC0-168 hr)
    Description
    The AUC0-168 of MK-8558 (active drug) after administration of MK-8510 (prodrug) in plasma will be calculated pre-dose, and 0.25, 0.5, 1, 2, 3, 4, 5, 6, 12, 24, 48, 72, 120, 168 hours post-dose.
    Time Frame
    At protocol specific timepoints up to 168 hours post-dose
    Title
    Area Under the Concentration-Time Curve of MK-8558 From Time 0 to last (AUC0-last)
    Description
    AUC0-last of MK-8558 (active drug) after administration of MK-8510 (prodrug) in plasma will be calculated pre-dose, and 0.25, 0.5, 1, 2, 3, 4, 5, 6, 12, 24, 48, 72, 120, 168, 240, 336, 504 hours post-dose.
    Time Frame
    At protocol specific time points up to 504 hours post-dose
    Title
    Concentration at 168 Hours Post-dose (C168) of MK-8558
    Description
    C168hr of MK-8558 (active drug) after administration of MK-8510 (prodrug) in plasma will be calculated.
    Time Frame
    168 hours post-dose
    Title
    Maximum Concentration (Cmax) of MK-8558
    Description
    Cmax of MK-8558 (active drug) after administration of MK-8510 (prodrug) in plasma will be calculated pre-dose, and 0.25, 0.5, 1, 2, 3, 4, 5, 6, 12, 24, 48, 72, 120, 168, 240, 336, 504 hours post-dose.
    Time Frame
    At protocol specific time points up to 504 hours post-dose
    Title
    Time to Maximum Plasma Concentration (Tmax) of MK-8558
    Description
    Tmax of MK-8558 (active drug) after administration of MK-8510 (prodrug) in plasma will be calculated pre-dose, and 0.25, 0.5, 1, 2, 3, 4, 5, 6, 12, 24, 48, 72, 120, 168, 240, 336, 504 hours post-dose.
    Time Frame
    At protocol specific time points up to 504 hours post-dose
    Title
    Half Life (t1/2) of MK-8558
    Description
    t1/2 of MK-8558 (active drug) after administration of MK-8510 (prodrug) in plasma will be calculated pre-dose, and 0.25, 0.5, 1, 2, 3, 4, 5, 6, 12, 24, 48, 72, 120, 168, 240, 336, 504 hours post-dose.
    Time Frame
    At protocol specific time points up to 504 hours post-dose
    Title
    Apparent Plasma Clearance of Drug After Extravascular Administration (CL/F) of MK-8558
    Description
    CL/F of MK-8558 (active drug) after administration of MK-8510 (prodrug) in plasma will be calculated pre-dose, and 0.25, 0.5, 1, 2, 3, 4, 5, 6, 12, 24, 48, 72, 120, 168, 240, 336, 504 hours post-dose.
    Time Frame
    At protocol specific time points up to 504 hours post-dose
    Title
    Apparent Volume of Distribution in the Terminal State After Extravascular Administration (Vz/F) of MK-8558
    Description
    Vz/F of MK-8558 (active drug) after administration of MK-8510 (prodrug) in plasma will be calculated pre-dose, and 0.25, 0.5, 1, 2, 3, 4, 5, 6, 12, 24, 48, 72, 120, 168, 240, 336, 504 hours post-dose.
    Time Frame
    At protocol specific time points up to 504 hours post-dose
    Title
    Terminal t1/2 of MK-8558
    Description
    Terminal t1/2 of MK-8558 (active drug) after administration of MK-8510 (prodrug) in plasma will be calculated pre-dose, and 0.25, 0.5, 1, 2, 3, 4, 5, 6, 12, 24, 48, 72, 120, 168, 240, 336, 504 hours post-dose.
    Time Frame
    At protocol specific time points up to 504 hours post-dose

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    60 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Has HIV-1 infection, and is in good health based on medical history, physical examination, vital signs (VS) measurements, and laboratory safety tests. Has documented HIV-1 positive, as determined by a positive enzyme-linked immunosorbent assay (ELISA) or real-time quantitative polymerase chain reaction (QT-PCR) with confirmation (eg, Western Blot). Is anti-retroviral therapy (ART)-naïve, which is defined as: Having never received any anti-retroviral agent; or ART-experienced but has not received any ART for HIV-1 infection within 60 days; or Has received pre-exposure prophylaxis (PrEP) treatment prior to diagnosis of HIV-infection but has not received any PrEP within 30 days. Is willing to receive no other ART prior to Day 11 post-dose of the study. Has a body mass index (BMI) ≤35 kg/m2. Exclusion Criteria: Has acute (primary) HIV-1 infection. Has a history of clinically significant endocrine, gastrointestinal (GI), cardiovascular, hematological, hepatic, immunological, renal, respiratory, genitourinary, or major neurological (including stroke and chronic seizures) abnormalities or diseases. Has remote history of uncomplicated medical events (eg, uncomplicated kidney stones, as defined as spontaneous passage and no recurrence in the last 5 years, or childhood asthma). Is mentally or legally incapacitated or has significant emotional problems. Has history of cancer (malignancy). Has a history of significant multiple and/or severe allergies (eg, food, drug, latex allergy), or has had an anaphylactic reaction or significant intolerability (i.e, systemic allergic reaction) to prescription or nonprescription drugs or food. Has positive hepatitis B surface antigen (HBsAg). Has a history of chronic hepatitis C unless there has been documented cure and/or participant with a positive serologic test for hepatitis C virus (HCV) has a negative HCV viral load (VL). Had a major surgery and/or donated or lost 1 unit of blood (approximately 500 mL) within 4 weeks prior to the prestudy (screening) visit. Has participated in another investigational study within 4 weeks. Has a clinically significant abnormality on the electrocardiogram (ECG) performed at the pre-study visit. Has been committed to an institution by way of official or judicial order. Is under the age of legal consent or not capable of giving consent. Does not agree to follow the smoking restrictions as defined by the clinical research unit (CRU). Consumes greater than 3 servings of alcoholic beverages (1 serving is approximately equivalent to: beer [354 mL/12 ounces], wine [118 mL/4 ounces], or distilled spirits [29.5 mL/1 ounce]) per day. Consumes excessive amounts, defined as greater than 6 servings (1 serving is approximately equivalent to 120 mg of caffeine) of coffee, tea, cola, energy drinks, or other caffeinated beverages per day. Is a regular user of any illicit drugs (not including cannabis) or has an history of drug (including alcohol) abuse within approximately 12 months.
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Medical Director
    Organizational Affiliation
    Merck Sharp & Dohme LLC
    Official's Role
    Study Director

    12. IPD Sharing Statement

    Plan to Share IPD
    Yes
    IPD Sharing Plan Description
    http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
    IPD Sharing URL
    http://engagezone.msd.com/ds_documentation.php

    Learn more about this trial

    MK-8510 Monotherapy for the Treatment of Anti-retroviral naïve Human Immunodeficiency Virus Type 1 (HIV-1) Infected Participants (MK-8510-002)

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