search
Back to results

A Study to Evaluate the Safety and Efficacy of an Investigational Drug in HIV Infected Patients (0518-004)(COMPLETED)

Primary Purpose

HIV Infections, Acquired Immunodeficiency Syndrome

Status
Completed
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Comparator: MK0518 monotherapy
Comparator: MK0518 combination therapy
Comparator: efavirenz
Comparator: tenofovir
Comparator: lamivudine
Placebo monotherapy
Sponsored by
Merck Sharp & Dohme LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for HIV Infections

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Patient must be HIV positive who must have received less than 7 days total of any antiretroviral therapy (HIV related therapy) Extension Studies: First extension: Patient completed the 48-week base study Second extension: Patient completed the first 144-week extension study Exclusion Criteria: Less than 18 years of age Individuals who currently do not test positive for HIV

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm 3

    Arm 4

    Arm 5

    Arm 6

    Arm 7

    Arm 8

    Arm 9

    Arm 10

    Arm Type

    Experimental

    Experimental

    Experimental

    Experimental

    Placebo Comparator

    Experimental

    Experimental

    Experimental

    Experimental

    Active Comparator

    Arm Label

    600 mg monotherapy

    400 mg monotherapy

    200 mg monotherapy

    100 mg monotherapy

    placebo monotherapy

    600 mg combo therapy

    400 mg combo therapy

    200 mg combo therapy

    100 mg combo therapy

    EFV combo therapy

    Arm Description

    MK0518 600 mg twice daily

    MK0518 400 mg twice daily

    MK0518 200 mg twice daily

    MK0518 100 mg twice daily

    Placebo to MK0518 twice daily

    MK0518 600 mg + tenofovir + lamivudine

    MK0518 400 mg + tenofovir + lamivudine

    MK0518 200 mg + tenofovir + lamivudine

    MK0518 100 mg + tenofovir + lamivudine

    efavirenz + tenofovir + lamivudine

    Outcomes

    Primary Outcome Measures

    Change From Baseline in Plasma Human Immunodeficiency Virus (HIV) Ribonucleic Acid (RNA) on Day 10 (Cohort I)
    Mean change from baseline on Day 10 in plasma Human Immunodeficiency Virus (HIV) Ribonucleic acid (RNA) (copies/mL)
    Number of Patients With Clinical Adverse Experiences (CAEs) and Number of Patients With Serious CAEs at Day 10 (Cohort I)
    An adverse experience (AE) is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the SPONSOR'S product, whether or not considered related to the use of the product. Serious CAEs are any AEs occurring at any dose that; Results in death; or Is life threatening; or Results in a persistent or significant disability/incapacity; or Results in or prolongs an existing inpatient hospitalization; or Is a congenital anomaly/birth defect; or Is a cancer; or Is an overdose.
    Number of Participants With HIV RNA Levels Below 400 Copies/mL at Week 24 (Cohort II)
    Number of Patients With Clinical Adverse Experiences (CAEs)
    An adverse experience (AE) is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the SPONSOR'S product, whether or not considered related to the use of the product.
    Number of Patients With Serious CAEs (Cohort I and II Combined)
    Serious CAEs are any AEs occurring at any dose that; Results in death; or Is life threatening; or Results in a persistent or significant disability/incapacity; or Results in or prolongs an existing inpatient hospitalization; or Is a congenital anomaly/birth defect; or Is a cancer; or Is an overdose
    Number of Patients With Serious CAEs and Non-serious CAEs at Week 144
    An adverse experience (AE) is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the SPONSOR'S product, whether or not considered related to the use of the product An adverse experience (AE) is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the SPONSOR'S product, whether or not considered related to the use of the product
    Number of Participants With Clinical Adverse Experiences (AEs)and Serious Adverse Experiences (SAEs)
    An AE was defined as any unfavorable & unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study drug, whether or not considered related to its use. Any worsening of a preexisting condition which was temporally associated with the use of the study drug, was also an AE. A SAE was any AE that resulted in death, was life threatening, resulted in a persistent or significant disability/incapacity, resulted in or prolonged an existing inpatient hospitalization, was a congenital anomaly/birth defect, was cancer, or was an overdose.
    Number of Participants With HIV RNA (Human Immunodeficiency Virus Ribonucleic Acid) Levels Below 50 Copies/mL at Week 240
    HIV RNA levels were determined by AMPLICOR HIV-1 Monitor™ UltraSensitive Assay.

    Secondary Outcome Measures

    Number of Participants With HIV RNA Levels Below 50 Copies/mL at Week 24 (Cohort II)
    Change From Baseline in Plasma HIV RNA at Week 24 (Cohort II)
    Mean change from baseline at Week 24 in plasma HIV RNA (copies/mL)
    Change From Baseline in Cluster of Differentiation 4 (CD4) Cell Count at Week 24 (Cohort II)
    Mean change from baseline at Week 24 in CD4 Cell Count (cells/mm3)
    Number of Patients With HIV RNA Level Below 50 Copies/mL and HIV RNA Level Below 400 Copies/mL at Week 96
    Change From Baseline in Plasma HIV RNA at Week 96
    Change From Baseline in CD4 Cell Count at Week 96
    Number of Participants With HIV RNA Levels Below 400 Copies/mL at Week 240
    HIV RNA levels were determined by AMPLICOR HIV-1 Monitor™ Standard Assay.
    Change From Baseline in Plasma HIV RNA at Week 240
    HIV RNA levels were determined by AMPLICOR HIV-1 Monitor™ Standard Assay.
    Change From Baseline in CD4 (T-helper) Cell Count at Week 240
    Change in number of CD4 cells/mm^3 from baseline to Week 240.

    Full Information

    First Posted
    December 22, 2004
    Last Updated
    September 4, 2015
    Sponsor
    Merck Sharp & Dohme LLC
    search

    1. Study Identification

    Unique Protocol Identification Number
    NCT00100048
    Brief Title
    A Study to Evaluate the Safety and Efficacy of an Investigational Drug in HIV Infected Patients (0518-004)(COMPLETED)
    Official Title
    Multicenter, Double-Blind, Randomized, Dose Ranging Study to Compare the Safety and Activity of MK0518 Plus Tenofovir and Lamivudine (3TC) Versus Efavirenz Plus Tenofovir and Lamivudine (3TC) in ART-Naive, HIV-Infected Patients
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    September 2015
    Overall Recruitment Status
    Completed
    Study Start Date
    January 2005 (undefined)
    Primary Completion Date
    October 2006 (Actual)
    Study Completion Date
    July 2010 (Actual)

    3. Sponsor/Collaborators

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

    4. Oversight

    Data Monitoring Committee
    No

    5. Study Description

    Brief Summary
    This is a study that will investigate the safety and efficacy of an investigational drug in Human immunodeficiency virus (HIV) infected patients.
    Detailed Description
    Participants who completed 48 weeks of the original 48-week double-blind study were invited to continue in two extensions: MK0518-004-10 (NCT00100048), which extended the study to 144 weeks, and MK0518-004-20 (NCT00100048), which extended the study to 240 weeks. Participants who had been randomized to MK0518 in the base study continued at 400 mg MK0518 twice daily. Participants randomized to efavirenz in the base study continued to receive efavirenz at the dosage given in the base study. The doses of open label tenofovir and lamivudine continued unchanged.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    HIV Infections, Acquired Immunodeficiency Syndrome

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 2
    Interventional Study Model
    Parallel Assignment
    Masking
    ParticipantInvestigator
    Allocation
    Randomized
    Enrollment
    206 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    600 mg monotherapy
    Arm Type
    Experimental
    Arm Description
    MK0518 600 mg twice daily
    Arm Title
    400 mg monotherapy
    Arm Type
    Experimental
    Arm Description
    MK0518 400 mg twice daily
    Arm Title
    200 mg monotherapy
    Arm Type
    Experimental
    Arm Description
    MK0518 200 mg twice daily
    Arm Title
    100 mg monotherapy
    Arm Type
    Experimental
    Arm Description
    MK0518 100 mg twice daily
    Arm Title
    placebo monotherapy
    Arm Type
    Placebo Comparator
    Arm Description
    Placebo to MK0518 twice daily
    Arm Title
    600 mg combo therapy
    Arm Type
    Experimental
    Arm Description
    MK0518 600 mg + tenofovir + lamivudine
    Arm Title
    400 mg combo therapy
    Arm Type
    Experimental
    Arm Description
    MK0518 400 mg + tenofovir + lamivudine
    Arm Title
    200 mg combo therapy
    Arm Type
    Experimental
    Arm Description
    MK0518 200 mg + tenofovir + lamivudine
    Arm Title
    100 mg combo therapy
    Arm Type
    Experimental
    Arm Description
    MK0518 100 mg + tenofovir + lamivudine
    Arm Title
    EFV combo therapy
    Arm Type
    Active Comparator
    Arm Description
    efavirenz + tenofovir + lamivudine
    Intervention Type
    Drug
    Intervention Name(s)
    Comparator: MK0518 monotherapy
    Intervention Description
    MK0518 twice daily for 10 days
    Intervention Type
    Drug
    Intervention Name(s)
    Comparator: MK0518 combination therapy
    Intervention Description
    MK0518 twice daily for 48 weeks
    Intervention Type
    Drug
    Intervention Name(s)
    Comparator: efavirenz
    Intervention Description
    efavirenz 600 mg every night at bedtime for 48 weeks
    Intervention Type
    Drug
    Intervention Name(s)
    Comparator: tenofovir
    Intervention Description
    tenofovir 300 mg daily for 48 weeks
    Intervention Type
    Drug
    Intervention Name(s)
    Comparator: lamivudine
    Intervention Description
    lamivudine 300 mg daily for 48 weeks
    Intervention Type
    Drug
    Intervention Name(s)
    Placebo monotherapy
    Intervention Description
    Placebo to MK0518 twice daily
    Primary Outcome Measure Information:
    Title
    Change From Baseline in Plasma Human Immunodeficiency Virus (HIV) Ribonucleic Acid (RNA) on Day 10 (Cohort I)
    Description
    Mean change from baseline on Day 10 in plasma Human Immunodeficiency Virus (HIV) Ribonucleic acid (RNA) (copies/mL)
    Time Frame
    Baseline and Day 10
    Title
    Number of Patients With Clinical Adverse Experiences (CAEs) and Number of Patients With Serious CAEs at Day 10 (Cohort I)
    Description
    An adverse experience (AE) is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the SPONSOR'S product, whether or not considered related to the use of the product. Serious CAEs are any AEs occurring at any dose that; Results in death; or Is life threatening; or Results in a persistent or significant disability/incapacity; or Results in or prolongs an existing inpatient hospitalization; or Is a congenital anomaly/birth defect; or Is a cancer; or Is an overdose.
    Time Frame
    10 days
    Title
    Number of Participants With HIV RNA Levels Below 400 Copies/mL at Week 24 (Cohort II)
    Time Frame
    Week 24
    Title
    Number of Patients With Clinical Adverse Experiences (CAEs)
    Description
    An adverse experience (AE) is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the SPONSOR'S product, whether or not considered related to the use of the product.
    Time Frame
    48 weeks
    Title
    Number of Patients With Serious CAEs (Cohort I and II Combined)
    Description
    Serious CAEs are any AEs occurring at any dose that; Results in death; or Is life threatening; or Results in a persistent or significant disability/incapacity; or Results in or prolongs an existing inpatient hospitalization; or Is a congenital anomaly/birth defect; or Is a cancer; or Is an overdose
    Time Frame
    48 weeks
    Title
    Number of Patients With Serious CAEs and Non-serious CAEs at Week 144
    Description
    An adverse experience (AE) is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the SPONSOR'S product, whether or not considered related to the use of the product An adverse experience (AE) is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the SPONSOR'S product, whether or not considered related to the use of the product
    Time Frame
    144 Weeks
    Title
    Number of Participants With Clinical Adverse Experiences (AEs)and Serious Adverse Experiences (SAEs)
    Description
    An AE was defined as any unfavorable & unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study drug, whether or not considered related to its use. Any worsening of a preexisting condition which was temporally associated with the use of the study drug, was also an AE. A SAE was any AE that resulted in death, was life threatening, resulted in a persistent or significant disability/incapacity, resulted in or prolonged an existing inpatient hospitalization, was a congenital anomaly/birth defect, was cancer, or was an overdose.
    Time Frame
    Week 240
    Title
    Number of Participants With HIV RNA (Human Immunodeficiency Virus Ribonucleic Acid) Levels Below 50 Copies/mL at Week 240
    Description
    HIV RNA levels were determined by AMPLICOR HIV-1 Monitor™ UltraSensitive Assay.
    Time Frame
    Week 240
    Secondary Outcome Measure Information:
    Title
    Number of Participants With HIV RNA Levels Below 50 Copies/mL at Week 24 (Cohort II)
    Time Frame
    Week 24
    Title
    Change From Baseline in Plasma HIV RNA at Week 24 (Cohort II)
    Description
    Mean change from baseline at Week 24 in plasma HIV RNA (copies/mL)
    Time Frame
    Baseline and Week 24
    Title
    Change From Baseline in Cluster of Differentiation 4 (CD4) Cell Count at Week 24 (Cohort II)
    Description
    Mean change from baseline at Week 24 in CD4 Cell Count (cells/mm3)
    Time Frame
    Baseline and Week 24
    Title
    Number of Patients With HIV RNA Level Below 50 Copies/mL and HIV RNA Level Below 400 Copies/mL at Week 96
    Time Frame
    96 Weeks
    Title
    Change From Baseline in Plasma HIV RNA at Week 96
    Time Frame
    Baseline and Week 96
    Title
    Change From Baseline in CD4 Cell Count at Week 96
    Time Frame
    Baseline and Week 96
    Title
    Number of Participants With HIV RNA Levels Below 400 Copies/mL at Week 240
    Description
    HIV RNA levels were determined by AMPLICOR HIV-1 Monitor™ Standard Assay.
    Time Frame
    Week 240
    Title
    Change From Baseline in Plasma HIV RNA at Week 240
    Description
    HIV RNA levels were determined by AMPLICOR HIV-1 Monitor™ Standard Assay.
    Time Frame
    Baseline and Week 240
    Title
    Change From Baseline in CD4 (T-helper) Cell Count at Week 240
    Description
    Change in number of CD4 cells/mm^3 from baseline to Week 240.
    Time Frame
    Baseline and Week 240
    Other Pre-specified Outcome Measures:
    Title
    Number of Participants With HIV RNA Levels Below 400 Copies/mL at Week 48
    Time Frame
    48 weeks
    Title
    Number of Patients With Drug-related CAEs
    Description
    Patients with drug-related (as assessed by an investigator who is a qualified physician according to his/her best clinical judgment) CAEs
    Time Frame
    48 weeks
    Title
    Number of Patients With Serious Drug-related CAEs
    Description
    Serious CAEs are any AEs occurring at any dose that; Results in death; or Is life threatening; or Results in a persistent or significant disability/incapacity; or Results in or prolongs an existing inpatient hospitalization; or Is a congenital anomaly/birth defect; or Is a cancer; or Is an overdose. Drug-related are as assessed by an investigator who is a qualified physician according to his/her best clinical judgment.
    Time Frame
    48 Weeks
    Title
    Number of Patients That Discontinued With CAEs
    Time Frame
    48 Weeks
    Title
    Number of Patients With Laboratory Adverse Experiences (LAEs)
    Description
    A laboratory adverse experience (LAE) is defined as any unfavorable and unintended change in the chemistry of the body temporally associated with the use of the SPONSOR'S product, whether or not considered related to the use of the product
    Time Frame
    48 Weeks
    Title
    Number of Patients With Serious LAEs
    Description
    Serious LAEs are any LAEs occurring at any dose that; Results in death; or Is life threatening; or Results in a persistent or significant disability/incapacity; or Results in or prolongs an existing inpatient hospitalization; or Is a congenital anomaly/birth defect; or Is a cancer; or Is an overdose
    Time Frame
    48 Weeks
    Title
    Number of Patients With Drug-related LAEs
    Description
    Patients with drug-related (as assessed by an investigator who is a qualified physician according to his/her best clinical judgment) LAEs
    Time Frame
    48 Weeks
    Title
    Number of Patients With Serious Drug-related LAEs
    Description
    Serious LAEs are any LAEs occurring at any dose that; Results in death; or Is life threatening; or Results in a persistent or significant disability/incapacity; or Results in or prolongs an existing inpatient hospitalization; or Is a congenital anomaly/birth defect; or Is a cancer; or Is an overdose
    Time Frame
    48 Weeks
    Title
    Number of Patients That Discontinued With LAEs
    Time Frame
    48 Weeks

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Patient must be HIV positive who must have received less than 7 days total of any antiretroviral therapy (HIV related therapy) Extension Studies: First extension: Patient completed the 48-week base study Second extension: Patient completed the first 144-week extension study Exclusion Criteria: Less than 18 years of age Individuals who currently do not test positive for HIV
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Medical Monitor
    Organizational Affiliation
    Merck Sharp & Dohme LLC
    Official's Role
    Study Director

    12. IPD Sharing Statement

    Citations:
    PubMed Identifier
    17133211
    Citation
    Markowitz M, Morales-Ramirez JO, Nguyen BY, Kovacs CM, Steigbigel RT, Cooper DA, Liporace R, Schwartz R, Isaacs R, Gilde LR, Wenning L, Zhao J, Teppler H. Antiretroviral activity, pharmacokinetics, and tolerability of MK-0518, a novel inhibitor of HIV-1 integrase, dosed as monotherapy for 10 days in treatment-naive HIV-1-infected individuals. J Acquir Immune Defic Syndr. 2006 Dec 15;43(5):509-15. doi: 10.1097/QAI.0b013e31802b4956. Erratum In: J Acquir Immune Defic Syndr. 2007 Apr 1;44(4):492.
    Results Reference
    background
    PubMed Identifier
    18090280
    Citation
    Murray JM, Emery S, Kelleher AD, Law M, Chen J, Hazuda DJ, Nguyen BY, Teppler H, Cooper DA. Antiretroviral therapy with the integrase inhibitor raltegravir alters decay kinetics of HIV, significantly reducing the second phase. AIDS. 2007 Nov 12;21(17):2315-21. doi: 10.1097/QAD.0b013e3282f12377.
    Results Reference
    background
    PubMed Identifier
    17721395
    Citation
    Markowitz M, Nguyen BY, Gotuzzo E, Mendo F, Ratanasuwan W, Kovacs C, Prada G, Morales-Ramirez JO, Crumpacker CS, Isaacs RD, Gilde LR, Wan H, Miller MD, Wenning LA, Teppler H; Protocol 004 Part II Study Team. Rapid and durable antiretroviral effect of the HIV-1 Integrase inhibitor raltegravir as part of combination therapy in treatment-naive patients with HIV-1 infection: results of a 48-week controlled study. J Acquir Immune Defic Syndr. 2007 Oct 1;46(2):125-33. doi: 10.1097/QAI.0b013e318157131c.
    Results Reference
    background
    PubMed Identifier
    19648823
    Citation
    Markowitz M, Nguyen BY, Gotuzzo E, Mendo F, Ratanasuwan W, Kovacs C, Prada G, Morales-Ramirez JO, Crumpacker CS, Isaacs RD, Campbell H, Strohmaier KM, Wan H, Danovich RM, Teppler H; Protocol 004 Part II Study Team. Sustained antiretroviral effect of raltegravir after 96 weeks of combination therapy in treatment-naive patients with HIV-1 infection. J Acquir Immune Defic Syndr. 2009 Nov 1;52(3):350-6. doi: 10.1097/QAI.0b013e3181b064b0.
    Results Reference
    background

    Learn more about this trial

    A Study to Evaluate the Safety and Efficacy of an Investigational Drug in HIV Infected Patients (0518-004)(COMPLETED)

    We'll reach out to this number within 24 hrs