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)

HIV Infection Clinical Trial

— onceMRK  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02131233
• Other study ID #: 0518-292
• Secondary ID: 2013-001939-47
• Status: Completed
• Phase: Phase 3
• Start date: May 23, 2014
• Est. completion date: December 19, 2016

Study information

• Verified date: January 2019
• Source: Merck Sharp & Dohme Corp.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 802
• Est. completion date: December 19, 2016
• Est. primary completion date: December 21, 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acquired Immunodeficiency Syndrome
• HIV Infection
• HIV Infections

Intervention

Drug:
• Reformulated Raltegravir
Reformulated raltegravir 1200 mg (2x 600 mg tablets) orally once daily
• Raltegravir
Raltegravir 400 mg tablet orally twice daily
• TRUVADA™
Emtricitabine / tenofovir disoproxil fumarate 200 / 300 mg tablet administered once-daily with food (open-label)
• Placebo to Reformulated Raltegravir
Placebo to reformulated raltegravir 2 tablets orally once daily
• Placebo to Raltegravir
Placebo to raltegravir 1 tablet orally twice daily

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme Corp.

References & Publications (2)

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, Tepple — View 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 Tenofov — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants Achieving <40 Copies/mL Human Immunodeficiency Virus-1 (HIV-1) Ribonucleic Acid (RNA) at Week 48	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.	Week 48
Secondary	Percentage of Participants Achieving <40 Copies/mL Human Immunodeficiency Virus-1 (HIV-1) Ribonucleic Acid (RNA) at Week 96	From blood samples collected at week 96, 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.	Week 96
Secondary	Change From Baseline in Cluster of Differentiation 4 (CD4) Cell Count at Week 48	CD4 cells were counted from blood collected at baseline and week 48, and the change from baseline determined from week 48 minus baseline values.	Baseline and Week 48
Secondary	Change From Baseline in CD4 Cell Count at Week 96	CD4 cells were counted from blood collected at baseline and week 96, and the change from baseline determined from week 96 minus baseline values.	Baseline and Week 96
Secondary	Percentage of Participants With an Adverse Event (AE) at Week 48	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.	Up to Week 48
Secondary	Percentage of Participants With an AE After 96 Weeks of Treatment	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.	Up to Week 98 (96 weeks of treatment + 2 weeks of follow up)
Secondary	Percentage of Participants With a Drug-Related AE at Week 48	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.	Up to Week 48
Secondary	Percentage of Participants With a Drug-Related AE After 96 Weeks of Treatment	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.	Up to Week 98 (96 weeks of treatment + 2 weeks of follow up)
Secondary	Percentage of Participants With a Serious Adverse Event (SAE) at Week 48	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.	Up to Week 48
Secondary	Percentage of Participants With a SAE After 96 Weeks of Treatment	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.	Up to Week 98 (96 weeks of treatment + 2 weeks of follow up)
Secondary	Percentage of Participants With a Serious and Drug-Related AE at Week 48	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.	Up to Week 48
Secondary	Percentage of Participants With a Serious and Drug-Related AE After 96 Weeks of Treatment	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.	Up to Week 98 (96 weeks of treatment + 2 weeks of follow up)
Secondary	Percentage of Participants Who Discontinued From Drug Therapy Due to an AE at Week 48	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	Up to Week 48
Secondary	Percentage of Participants Who Discontinued From Drug Therapy Due to an AE up to Week 96	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	Up to Week 96