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Evaluation of the Safety and Efficacy of Reformulated Raltegravir (MK-0518) 1200 mg Once Daily in Combination With TRUVADA™ in Human Immunodeficiency Virus (HIV)-1 Infected, Treatment-Naive Participants (MK-0518-292) (onceMRK)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT02131233
First received: May 2, 2014
Last updated: September 7, 2016
Last verified: August 2016
  Purpose
To evaluate the safety and efficacy of reformulated raltegravir (MK-0518) 1200 mg once daily in combination with TRUVADA™ versus raltegravir 400 mg twice daily in combination with TRUVADA™ in HIV-1 infected, treatment-naive participants. The primary hypothesis being tested is that reformulated raltegravir 1200 mg once-daily is non-inferior to raltegravir 400 mg twice-daily, each in combination therapy with TRUVADA™, as assessed by the proportion of participants achieving HIV-1 ribonucleic acid (RNA) <40 copies/mL at Week 48.

Condition Intervention Phase
HIV Infection
Drug: Reformulated Raltegravir
Drug: Raltegravir
Drug: TRUVADA™
Drug: Placebo to Reformulated Raltegravir
Drug: Placebo to Raltegravir
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase III Multicenter, Double-Blind, Randomized, Active Comparator-Controlled Clinical Trial to Evaluate the Safety and Efficacy of Reformulated Raltegravir 1200 mg Once Daily Versus Raltegravir 400 mg Twice Daily, Each in Combination With TRUVADA™, in Treatment-Naïve HIV-1 Infected Subjects

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • Percentage of Participants Achieving <40 Copies/mL Human Immunodeficiency Virus-1 (HIV-1) Ribonucleic Acid (RNA) at Week 48 [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
    From blood samples collected at week 48, HIV-1 RNA levels were determined by the Abbott RealTime HIV-1 Assay, which has a limit of reliable quantification (LoQ) of 40 copies/mL. The NC=F approach as defined by FDA "snapshot" approach was used as the primary approach to analysis where all missing data were treated as failures regardless of the reason.


Secondary Outcome Measures:
  • Change From Baseline in Cluster of Differentiation 4 (CD4) Cell Count at Week 48 [ Time Frame: Baseline and Week 48 ] [ Designated as safety issue: No ]
    CD4 cells were counted from blood collected at baseline and week 48, and the change from baseline determined from week 48 minus baseline values.

  • Percentage of Participants Achieving <40 Copies/mL HIV-1 RNA at Week 96 [ Time Frame: Week 96 ] [ Designated as safety issue: No ]
    From blood samples collected at week 96, HIV-1 RNA levels will be determined by the Abbott RealTime HIV-1 Assay, which has a limit of reliable quantification (LoQ) of 40 copies/mL.

  • Change From Baseline in CD4 Cell Count at Week 96 [ Time Frame: Baseline and Week 96 ] [ Designated as safety issue: No ]
    CD4 cells will be counted from blood collected at baseline and week 96, and the change from baseline determined from week 96 minus baseline values.

  • Percentage of Participants With an Adverse Event (AE) at Week 48 [ Time Frame: Up to Week 48 ] [ Designated as safety issue: Yes ]
    An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE.

  • Percentage of Participants With a Drug-Related AE at Week 48 [ Time Frame: Up to Week 48 ] [ Designated as safety issue: Yes ]
    An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE. An investigator who is a qualified physician evaluated whether or not an AE was drug-related.

  • Percentage of Participants With a Serious Adverse Event (SAE) at Week 48 [ Time Frame: Up to Week 48 ] [ Designated as safety issue: Yes ]
    A serious adverse event (SAE) is any AE occurring at any dose or during any use of Sponsor's product that does the following: results in death; is life threatening; results in persistent or significant disability/incapacity; results in or prolongs an existing inpatient hospitalization; is a congenital anomaly/birth defect; is a cancer; is associated with an overdose; is another important medical event.

  • Percentage of Participants With a Serious and Drug-Related AE at Week 48 [ Time Frame: Up to Week 48 ] [ Designated as safety issue: Yes ]
    A SAE is any AE occurring at any dose or during any use of Sponsor's product that does the following: results in death; is life threatening; results in persistent or significant disability/incapacity; results in or prolongs an existing inpatient hospitalization; is a congenital anomaly/birth defect; is a cancer; is associated with an overdose; is another important medical event. An investigator who is a qualified physician evaluated whether or not a SAE is drug-related.

  • Percentage of Participants Who Discontinued From Drug Therapy Due to an AE at Week 48 [ Time Frame: Up to Week 48 ] [ Designated as safety issue: Yes ]
    An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE

  • Percentage of Participants With an AE at Week 96 [ Time Frame: Up to Week 96 ] [ Designated as safety issue: Yes ]
    An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE.

  • Percentage of Participants With a Drug-Related AE at Week 96 [ Time Frame: Up to Week 96 ] [ Designated as safety issue: Yes ]
    An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE. An investigator who is a qualified physician evaluated whether or not an AE was drug-related.

  • Percentage of Participants With a SAE at Week 96 [ Time Frame: Up to Week 96 ] [ Designated as safety issue: Yes ]
    A SAE is any AE occurring at any dose or during any use of Sponsor's product that does the following: results in death; is life threatening; results in persistent or significant disability/incapacity; results in or prolongs an existing inpatient hospitalization; is a congenital anomaly/birth defect; is a cancer; is associated with an overdose; is another important medical event.

  • Percentage of Participants With a Serious and Drug-Related AE at Week 96 [ Time Frame: Up to Week 96 ] [ Designated as safety issue: Yes ]
    A SAE is any AE occurring at any dose or during any use of Sponsor's product that does the following: results in death; is life threatening; results in persistent or significant disability/incapacity; results in or prolongs an existing inpatient hospitalization; is a congenital anomaly/birth defect; is a cancer; is associated with an overdose; is another important medical event. An investigator who is a qualified physician will evaluate whether or not a SAE is drug-related.

  • Percentage of Participants Who Discontinued From Drug Therapy Due to an AE at Week 96 [ Time Frame: Up to Week 96 ] [ Designated as safety issue: Yes ]
    An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE.


Enrollment: 802
Study Start Date: May 2014
Estimated Study Completion Date: December 2016
Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Reformulated Raltegravir
Reformulated raltegravir 1200 mg (2x 600 mg tablets) orally once daily plus placebo to raltegravir 1 tablet orally twice daily plus TRUVADA™ orally once daily for 96 weeks
Drug: Reformulated Raltegravir
Reformulated raltegravir 1200 mg (2x 600 mg tablets) orally once daily
Drug: TRUVADA™
Emtricitabine / tenofovir disoproxil fumarate 200 / 300 mg tablet administered once-daily with food (open-label)
Drug: Placebo to Raltegravir
Placebo to raltegravir 1 tablet orally twice daily
Active Comparator: Raltegravir
Raltegravir 400 mg tablet orally twice daily plus placebo to reformulated raltegravir 2 tablets orally once daily plus TRUVADA™ orally once daily for 96 weeks
Drug: Raltegravir
Raltegravir 400 mg tablet orally twice daily
Drug: TRUVADA™
Emtricitabine / tenofovir disoproxil fumarate 200 / 300 mg tablet administered once-daily with food (open-label)
Drug: Placebo to Reformulated Raltegravir
Placebo to reformulated raltegravir 2 tablets orally once daily

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • HIV-1 positive
  • Naïve to antiretroviral therapy including investigational antiretroviral agents
  • Not of reproductive potential or, if of reproductive potential agrees to 1) true abstinence, or 2) use of an acceptable method of birth control during the study

Exclusion Criteria:

  • Use of recreational or illicit drugs or has recent history of drug or alcohol abuse or dependence
  • Has been treated for a viral infection other than HIV-1 (such as hepatitis B) with an agent that is active against HIV-1 including but not limited to adefovir, tenofovir, entecavir, emtricitabine, or lamivudine
  • Has documented or known resistance to raltegravir, emtricitabine, and/or tenofovir before the first dose of study drug
  • Has participated in a study with an investigational compound or device within 30 days or anticipates participating in such a study during this study
  • Has used systemic immunosuppressive therapy or immune modulators within 30 days or is anticipated to need them during the study (short courses of corticosteroids are allowed)
  • Requires or is anticipated to require any of the following prohibited medications while in the study: phenobarbital, phenytoin, rifampin, rifabutin, or calcium, magnesium and aluminum containing antacids, such as TUMS™, Maalox™ and Milk of Magnesia™
  • Has significant hypersensitivity or other contraindication to any of the components of the study drugs
  • Has current, active diagnosis of acute hepatitis due to any cause
  • Is pregnant, breastfeeding, or expecting to conceive during the study
  • Female participant expecting to donate eggs or male participant expecting to donate sperm during the study
  • Is or has a family member (spouse or children) who is investigational staff or sponsor staff directly involved in this trial
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02131233

Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
Study Director: Medical Director Merck Sharp & Dohme Corp.
  More Information

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT02131233     History of Changes
Other Study ID Numbers: 0518-292  2013-001939-47 
Study First Received: May 2, 2014
Results First Received: September 7, 2016
Last Updated: September 7, 2016
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Raltegravir Potassium
Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
HIV Integrase Inhibitors
Integrase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on December 02, 2016