Clinical trial NCT00100048: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: HIV Infections
Acquired Immunodeficiency Syndrome
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2004-12-23
Enrollment: 206
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: 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.

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

Primary outcomes:
measure: Change From Baseline in Plasma Human Immunodeficiency Virus (HIV) Ribonucleic Acid (RNA) on Day 10 (Cohort I)
timeFrame: Baseline and Day 10
measure: Number of Patients With Clinical Adverse Experiences (CAEs) and Number of Patients With Serious CAEs at Day 10 (Cohort I)
timeFrame: 10 days
measure: Number of Participants With HIV RNA Levels Below 400 Copies/mL at Week 24 (Cohort II)
timeFrame: Week 24
measure: Number of Patients With Clinical Adverse Experiences (CAEs)
timeFrame: 48 weeks
measure: Number of Patients With Serious CAEs (Cohort I and II Combined)
timeFrame: 48 weeks
measure: Number of Patients With Serious CAEs and Non-serious CAEs at Week 144
timeFrame: 144 Weeks
measure: Number of Participants With Clinical Adverse Experiences (AEs)and Serious Adverse Experiences (SAEs)
timeFrame: Week 240
measure: Number of Participants With HIV RNA (Human Immunodeficiency Virus Ribonucleic Acid) Levels Below 50 Copies/mL at Week 240
timeFrame: Week 240
Secondary outcomes:
measure: Number of Participants With HIV RNA Levels Below 50 Copies/mL at Week 24 (Cohort II)
timeFrame: Week 24
measure: Change From Baseline in Plasma HIV RNA at Week 24 (Cohort II)
timeFrame: Baseline and Week 24
measure: Change From Baseline in Cluster of Differentiation 4 (CD4) Cell Count at Week 24 (Cohort II)
timeFrame: Baseline and Week 24
measure: Number of Patients With HIV RNA Level Below 50 Copies/mL and HIV RNA Level Below 400 Copies/mL at Week 96
timeFrame: 96 Weeks
measure: Change From Baseline in Plasma HIV RNA at Week 96
timeFrame: Baseline and Week 96
measure: Change From Baseline in CD4 Cell Count at Week 96
timeFrame: Baseline and Week 96
measure: Number of Participants With HIV RNA Levels Below 400 Copies/mL at Week 240
timeFrame: Week 240
measure: Change From Baseline in Plasma HIV RNA at Week 240
timeFrame: Baseline and Week 240
measure: Change From Baseline in CD4 (T-helper) Cell Count at Week 240
timeFrame: Baseline and Week 240
Other outcomes:
measure: Number of Participants With HIV RNA Levels Below 400 Copies/mL at Week 48
timeFrame: 48 weeks
measure: Number of Patients With Drug-related CAEs
timeFrame: 48 weeks
measure: Number of Patients With Serious Drug-related CAEs
timeFrame: 48 Weeks
measure: Number of Patients That Discontinued With CAEs
timeFrame: 48 Weeks
measure: Number of Patients With Laboratory Adverse Experiences (LAEs)
timeFrame: 48 Weeks
measure: Number of Patients With Serious LAEs
timeFrame: 48 Weeks
measure: Number of Patients With Drug-related LAEs
timeFrame: 48 Weeks
measure: Number of Patients With Serious Drug-related LAEs
timeFrame: 48 Weeks
measure: Number of Patients That Discontinued With LAEs
timeFrame: 48 Weeks
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Monitor
role: STUDY_DIRECTOR
References:
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.
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.
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.
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.