A Study to Evaluate the Safety and Efficacy of an Investigational Drug in HIV Infected Patients (0518-004)(COMPLETED)

Study Overview
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Brief Summary
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This is a study that will investigate the safety and efficacy of an investigational drug in Human immunodeficiency virus (HIV) infected patients.

Detailed Description
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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.

Official Title
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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

Conditions
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HIV Infections, Acquired Immunodeficiency Syndrome

Intervention / Treatment
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* Drug: Comparator: MK0518 monotherapy
* Drug: Comparator: MK0518 combination therapy
* Drug: Comparator: efavirenz
* Drug: Comparator: tenofovir
* Drug: Comparator: lamivudine
* Drug: Placebo monotherapy


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 600 mg monotherapy<br>MK0518 600 mg twice daily | Drug: Comparator: MK0518 monotherapy<br>* MK0518 twice daily for 10 days<br>|
| Experimental: 400 mg monotherapy<br>MK0518 400 mg twice daily | Drug: Comparator: MK0518 monotherapy<br>* MK0518 twice daily for 10 days<br>|
| Experimental: 200 mg monotherapy<br>MK0518 200 mg twice daily | Drug: Comparator: MK0518 monotherapy<br>* MK0518 twice daily for 10 days<br>|
| Experimental: 100 mg monotherapy<br>MK0518 100 mg twice daily | Drug: Comparator: MK0518 monotherapy<br>* MK0518 twice daily for 10 days<br>|
| Placebo Comparator: placebo monotherapy<br>Placebo to MK0518 twice daily | Drug: Placebo monotherapy<br>* Placebo to MK0518 twice daily<br>|
| Experimental: 600 mg combo therapy<br>MK0518 600 mg + tenofovir + lamivudine | Drug: Comparator: MK0518 combination therapy<br>* MK0518 twice daily for 48 weeks<br>Drug: Comparator: tenofovir<br>* tenofovir 300 mg daily for 48 weeks<br>Drug: Comparator: lamivudine<br>* lamivudine 300 mg daily for 48 weeks<br>|
| Experimental: 400 mg combo therapy<br>MK0518 400 mg + tenofovir + lamivudine | Drug: Comparator: MK0518 combination therapy<br>* MK0518 twice daily for 48 weeks<br>Drug: Comparator: tenofovir<br>* tenofovir 300 mg daily for 48 weeks<br>Drug: Comparator: lamivudine<br>* lamivudine 300 mg daily for 48 weeks<br>|
| Experimental: 200 mg combo therapy<br>MK0518 200 mg + tenofovir + lamivudine | Drug: Comparator: MK0518 combination therapy<br>* MK0518 twice daily for 48 weeks<br>Drug: Comparator: tenofovir<br>* tenofovir 300 mg daily for 48 weeks<br>Drug: Comparator: lamivudine<br>* lamivudine 300 mg daily for 48 weeks<br>|
| Experimental: 100 mg combo therapy<br>MK0518 100 mg + tenofovir + lamivudine | Drug: Comparator: MK0518 combination therapy<br>* MK0518 twice daily for 48 weeks<br>Drug: Comparator: tenofovir<br>* tenofovir 300 mg daily for 48 weeks<br>Drug: Comparator: lamivudine<br>* lamivudine 300 mg daily for 48 weeks<br>|
| Active Comparator: EFV combo therapy<br>efavirenz + tenofovir + lamivudine | Drug: Comparator: efavirenz<br>* efavirenz 600 mg every night at bedtime for 48 weeks<br>Drug: Comparator: tenofovir<br>* tenofovir 300 mg daily for 48 weeks<br>Drug: Comparator: lamivudine<br>* lamivudine 300 mg daily for 48 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Plasma Human Immunodeficiency Virus (HIV) Ribonucleic Acid (RNA) on Day 10 (Cohort I) | Mean change from baseline on Day 10 in plasma Human Immunodeficiency Virus (HIV) Ribonucleic acid (RNA) (copies/mL) | Baseline and Day 10 | 
| Number of Patients With Clinical Adverse Experiences (CAEs) and Number of Patients With Serious CAEs at Day 10 (Cohort I) | An adverse experience (AE) is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the SPONSOR'S product, whether or not considered related to the use of the product. Serious CAEs are any AEs occurring at any dose that; Results in death; or Is life threatening; or Results in a persistent or significant disability/incapacity; or Results in or prolongs an existing inpatient hospitalization; or Is a congenital anomaly/birth defect; or Is a cancer; or Is an overdose. | 10 days | 
| Number of Participants With HIV RNA Levels Below 400 Copies/mL at Week 24 (Cohort II) |  | Week 24 | 
| Number of Patients With Clinical Adverse Experiences (CAEs) | An adverse experience (AE) is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the SPONSOR'S product, whether or not considered related to the use of the product. | 48 weeks | 
| Number of Patients With Serious CAEs (Cohort I and II Combined) | Serious CAEs are any AEs occurring at any dose that; Results in death; or Is life threatening; or Results in a persistent or significant disability/incapacity; or Results in or prolongs an existing inpatient hospitalization; or Is a congenital anomaly/birth defect; or Is a cancer; or Is an overdose | 48 weeks | 
| Number of Patients With Serious CAEs and Non-serious CAEs at Week 144 | An adverse experience (AE) is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the SPONSOR'S product, whether or not considered related to the use of the product An adverse experience (AE) is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the SPONSOR'S product, whether or not considered related to the use of the product | 144 Weeks | 
| Number of Participants With Clinical Adverse Experiences (AEs)and Serious Adverse Experiences (SAEs) | An AE was defined as any unfavorable & unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study drug, whether or not considered related to its use. Any worsening of a preexisting condition which was temporally associated with the use of the study drug, was also an AE. A SAE was any AE that resulted in death, was life threatening, resulted in a persistent or significant disability/incapacity, resulted in or prolonged an existing inpatient hospitalization, was a congenital anomaly/birth defect, was cancer, or was an overdose. | Week 240 | 
| Number of Participants With HIV RNA (Human Immunodeficiency Virus Ribonucleic Acid) Levels Below 50 Copies/mL at Week 240 | HIV RNA levels were determined by AMPLICOR HIV-1 Monitor™ UltraSensitive Assay. | Week 240 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With HIV RNA Levels Below 50 Copies/mL at Week 24 (Cohort II) |  | Week 24 | 
| Change From Baseline in Plasma HIV RNA at Week 24 (Cohort II) | Mean change from baseline at Week 24 in plasma HIV RNA (copies/mL) | Baseline and Week 24 | 
| Change From Baseline in Cluster of Differentiation 4 (CD4) Cell Count at Week 24 (Cohort II) | Mean change from baseline at Week 24 in CD4 Cell Count (cells/mm3) | Baseline and Week 24 | 
| Number of Patients With HIV RNA Level Below 50 Copies/mL and HIV RNA Level Below 400 Copies/mL at Week 96 |  | 96 Weeks | 
| Change From Baseline in Plasma HIV RNA at Week 96 |  | Baseline and Week 96 | 
| Change From Baseline in CD4 Cell Count at Week 96 |  | Baseline and Week 96 | 
| Number of Participants With HIV RNA Levels Below 400 Copies/mL at Week 240 | HIV RNA levels were determined by AMPLICOR HIV-1 Monitor™ Standard Assay. | Week 240 | 
| Change From Baseline in Plasma HIV RNA at Week 240 | HIV RNA levels were determined by AMPLICOR HIV-1 Monitor™ Standard Assay. | Baseline and Week 240 | 
| Change From Baseline in CD4 (T-helper) Cell Count at Week 240 | Change in number of CD4 cells/mm^3 from baseline to Week 240. | Baseline and Week 240 |