Clinical trial NCT02131233: 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)
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: HIV Infection
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2014-05-06
Enrollment: 802
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility 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

Primary outcomes:
measure: Percentage of Participants Achieving <40 Copies/mL Human Immunodeficiency Virus-1 (HIV-1) Ribonucleic Acid (RNA) at Week 48
timeFrame: Week 48
Secondary outcomes:
measure: Percentage of Participants Achieving <40 Copies/mL Human Immunodeficiency Virus-1 (HIV-1) Ribonucleic Acid (RNA) at Week 96
timeFrame: Week 96
measure: Change From Baseline in Cluster of Differentiation 4 (CD4) Cell Count at Week 48
timeFrame: Baseline and Week 48
measure: Change From Baseline in CD4 Cell Count at Week 96
timeFrame: Baseline and Week 96
measure: Percentage of Participants With an Adverse Event (AE) at Week 48
timeFrame: Up to Week 48
measure: Percentage of Participants With an AE After 96 Weeks of Treatment
timeFrame: Up to Week 98 (96 weeks of treatment + 2 weeks of follow up)
measure: Percentage of Participants With a Drug-Related AE at Week 48
timeFrame: Up to Week 48
measure: Percentage of Participants With a Drug-Related AE After 96 Weeks of Treatment
timeFrame: Up to Week 98 (96 weeks of treatment + 2 weeks of follow up)
measure: Percentage of Participants With a Serious Adverse Event (SAE) at Week 48
timeFrame: Up to Week 48
measure: Percentage of Participants With a SAE After 96 Weeks of Treatment
timeFrame: Up to Week 98 (96 weeks of treatment + 2 weeks of follow up)
measure: Percentage of Participants With a Serious and Drug-Related AE at Week 48
timeFrame: Up to Week 48
measure: Percentage of Participants With a Serious and Drug-Related AE After 96 Weeks of Treatment
timeFrame: Up to Week 98 (96 weeks of treatment + 2 weeks of follow up)
measure: Percentage of Participants Who Discontinued From Drug Therapy Due to an AE at Week 48
timeFrame: Up to Week 48
measure: Percentage of Participants Who Discontinued From Drug Therapy Due to an AE up to Week 96
timeFrame: Up to Week 96
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: Cahn P, Kaplan R, Sax PE, Squires K, Molina JM, Avihingsanon A, Ratanasuwan W, Rojas E, Rassool M, Bloch M, Vandekerckhove L, Ruane P, Yazdanpanah Y, Katlama C, Xu X, Rodgers A, East L, Wenning L, Rawlins S, Homony B, Sklar P, Nguyen BY, Leavitt R, Teppler H; ONCEMRK Study Group. Raltegravir 1200 mg once daily versus raltegravir 400 mg twice daily, with tenofovir disoproxil fumarate and emtricitabine, for previously untreated HIV-1 infection: a randomised, double-blind, parallel-group, phase 3, non-inferiority trial. Lancet HIV. 2017 Nov;4(11):e486-e494. doi: 10.1016/S2352-3018(17)30128-5. Epub 2017 Sep 11.
citation: Cahn P, Sax PE, Squires K, Molina JM, Ratanasuwan W, Rassool M, Bloch M, Xu X, Zhou Y, Homony B, Hepler D, Teppler H, Hanna GJ, Nguyen BY, Greaves W; ONCEMRK Study Group. Raltegravir 1200 mg Once Daily vs 400 mg Twice Daily, With Emtricitabine and Tenofovir Disoproxil Fumarate, for Previously Untreated HIV-1 Infection: Week 96 Results From ONCEMRK, a Randomized, Double-Blind, Noninferiority Trial. J Acquir Immune Defic Syndr. 2018 Aug 15;78(5):589-598. doi: 10.1097/QAI.0000000000001723.