Reformulated raltegravir (1200 mg) once a day versus raltegravir (400 mg) twice a day in treatment-naïve patients

• Register: EUCTR
• Last refreshed on: 8 January 2018
• Main ID: EUCTR2013-001939-47-PT
• Date of registration: 24/03/2014
• Prospective Registration: Yes
• Primary sponsor: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
• Public title: Reformulated raltegravir (1200 mg) once a day versus raltegravir (400 mg) twice a day in treatment-naïve patients
• Scientific 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 - Reformulated raltegravir q.d. (1200 mg) versus raltegravir b.i.d. (400 mg) in ART-naïve pts
• Date of first enrolment: 04/07/2014
• Target sample size: 750
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-001939-47
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Australia, Belgium, Brazil, Canada, Chile, Colombia, France, Germany, Guatemala, Israel, Italy, Korea, Republic of, Malaysia, Mexico, Philippines, Portugal, Russian Federation, South Africa, Spain, Switzerland, Taiwan, Thailand, United Kingdom, United States

Contacts

• Name: Global Clinical Trials Operations
• Affiliation: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.

• Name: Global Clinical Trials Operations
• Affiliation: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.

Key inclusion & exclusion criteria

Inclusion criteria:
1. Male or female at least 18 years of age
2. Understand the study procedures, be able to compile with the study procedures, and voluntarily agree to participate by giving written informed consent for the trial and for Future Biomedical Research (not required to participate).
3. HIV-1 positive as determined by a positive result by enzyme-immunoassay and have screening plasma HIV-1 RNA (determined by the central laboratory) =1000 copies/mL within 60 days prior to the treatment phase of this study.
4. Naïve to ART including investigational ART agents.
5. The following screening laboratory values: Serum creatinine =2.0 x ULN; Alkaline phosphatase =3.0 x ULN; AST (SGOT) and ALT (SGPT) =5.0 x ULN; calculated creatinine clearance = 30 mL/min.
6. Clinically stable with no signs or symptoms of active infection.
7. Agree to one of the following if of reproductive potential: 1) True abstinence or 2) Use of an acceptable method of birth control throughout the study (either by subject or subject’s partner). Acceptable methods of birth control are: oral contraceptives, intrauterine device (IUD), diaphragm with spermicide, contraceptive sponge, condom, vasectomy (All forms of hormonal contraception are acceptable).

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 745
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 5

Exclusion criteria:
1. A history or current evidence of any condition, therapy, laboratory abnormality or other circumstance (ex. recreational or illicit drug use or alcohol abuse or dependence) that might confound the results of the study, or interfere with the subject’s participation for the full duration of the study, such that it is not in the best interest of the subject to participate.
2. 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.
3. Documented or known resistance to raltegravir, emtricitabine, and/or tenofovir prior to the treatment phase of the study.
4. Participated in a study with an investigational compound/device within 30 days of signing informed consent or anticipates participating in such a study involving an investigational compound/device during the course of this study.
5. Use of systemic immunosuppressive therapy or immune modulators within 30 days prior to treatment in this study or is anticipated to need them during the course of the study.
6. Requires or is anticipated to require prohibited medications while in the study.
7. Has significant hypersensitivity or other contraindication to any of the components of the study drugs.
8. Current (active) diagnosis of acute hepatitis due to any cause.
9. Is pregnant, breastfeeding, or expecting to conceive at any time during the study.
10. A female expecting to donate eggs at any time during the study or is a male expecting to donate sperm at any time during the study.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

human immunodeficiency virus infection
MedDRA version: 18.1 Level: PT Classification code 10020161 Term: HIV infection System Organ Class: 10021881 - Infections and infestations

Therapeutic area: Diseases [C] - Immune System Diseases [C20]

Intervention(s)

Product Name: MK-0518 (reformulated raltegravir)
Product Code: MK-0518
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: RALTEGRAVIR
CAS Number: 518048-05-0
Current Sponsor code: MK-0518
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 600-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Trade Name: ISENTRESS ®
Product Name: MK-0518 (raltegravir)
Product Code: MK-0518
Pharmaceutical Form: Film-coated tablet
CAS Number: 871038-72-1
Current Sponsor code: MK-0518
Other descriptive name: RALTEGRAVIR POTASSIUM
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 400-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Trade Name: Truvada
Product Name: Truvada (emtricitabine and tenofovir disoproxil fumarate)
Product Code: Truvada (emtricitabine and tenofovir disoproxil fu
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: EMTRICITABINE
CAS Number: 143491-57-0
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 200-
INN or Proposed INN: TENOFOVIR DISOPROXIL FUMARATE
CAS Number: 202138-50-9
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 300-

Primary Outcome(s)

Primary end point(s): Proportion of Subjects Achieving HIV-1 RNA < 40 copies/mL

Timepoint(s) of evaluation of this end point: Week 48 and Week 96

Main Objective: Evaluate the efficacy of reformulated raltegravir 1200 mg q.d. plus TRUVADA, compared to raltegravir 400 mg b.i.d. plus TRUVADA, measured by the proportion of subjects with HIV-1 RNA <40 cp/mL at Week 48.

Secondary Objective: Evaluate the efficacy of reformulated raltegravir 1200 mg q.d. plus TRUVADA, compared to raltegravir 400 mg b.i.d. plus TRUVADA, measured by proportion of subjects with HIV-1 RNA <40 cp/mL at Week 96, and change from baseline in CD4 cell count at Week 48 and Week 96. Evaluate the safety and tolerability of reformulated raltegravir 1200 mg q.d. plus TRUVADA, compared to raltegravir 400 mg b.i.d. plus TRUVADA, by review of the accumulated safety data at Week 48 and Week 96.

Secondary Outcome(s)

Secondary end point(s): Efficacy: Change from Baseline in CD4 Cell Count
Safety: Adverse Experiences and Predefined Limits of Change (PDLOC)

Timepoint(s) of evaluation of this end point: Week 48 and Week 96

Secondary ID(s)

2013-001939-47-IT

MK-0518-292

Source(s) of Monetary Support

Merck Sharp Dohme Corp.