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

HIV Infections Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00100048
• Other study ID #: 0518-004
• Secondary ID: 2004_096
• Status: Completed
• Phase: Phase 2
• First received: December 22, 2004
• Last updated: September 4, 2015
• Start date: January 2005
• Est. completion date: July 2010

Study information

• Verified date: September 2015
• Source: Merck Sharp & Dohme Corp.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 206
• Est. completion date: July 2010
• Est. primary completion date: October 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acquired Immunodeficiency Syndrome
• HIV Infections
• Immunologic Deficiency Syndromes

Intervention

Drug:
• Comparator: MK0518 monotherapy
MK0518 twice daily for 10 days
• Comparator: MK0518 combination therapy
MK0518 twice daily for 48 weeks
• Comparator: efavirenz
efavirenz 600 mg every night at bedtime for 48 weeks
• Comparator: tenofovir
tenofovir 300 mg daily for 48 weeks
• Comparator: lamivudine
lamivudine 300 mg daily for 48 weeks
• Placebo monotherapy
Placebo to MK0518 twice daily

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme Corp.

References & Publications (4)

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. Erratum in: J Acquir Immune Defic Syndr. 2007 Apr 1;44(4):492. — View 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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Number of Participants With HIV RNA Levels Below 400 Copies/mL at Week 48		48 weeks	No
Other	Number of Patients With Drug-related CAEs	Patients with drug-related (as assessed by an investigator who is a qualified physician according to his/her best clinical judgment) CAEs	48 weeks	Yes
Other	Number of Patients With Serious Drug-related CAEs	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. Drug-related are as assessed by an investigator who is a qualified physician according to his/her best clinical judgment.	48 Weeks	Yes
Other	Number of Patients That Discontinued With CAEs		48 Weeks	Yes
Other	Number of Patients With Laboratory Adverse Experiences (LAEs)	A laboratory adverse experience (LAE) is defined as any unfavorable and unintended change in the 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	Yes
Other	Number of Patients With Serious LAEs	Serious LAEs are any LAEs 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	Yes
Other	Number of Patients With Drug-related LAEs	Patients with drug-related (as assessed by an investigator who is a qualified physician according to his/her best clinical judgment) LAEs	48 Weeks	Yes
Other	Number of Patients With Serious Drug-related LAEs	Serious LAEs are any LAEs 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	Yes
Other	Number of Patients That Discontinued With LAEs		48 Weeks	Yes
Primary	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	No
Primary	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	Yes
Primary	Number of Participants With HIV RNA Levels Below 400 Copies/mL at Week 24 (Cohort II)		Week 24	No
Primary	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	Yes
Primary	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	Yes
Primary	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	Yes
Primary	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	Yes
Primary	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	No
Secondary	Number of Participants With HIV RNA Levels Below 50 Copies/mL at Week 24 (Cohort II)		Week 24	No
Secondary	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	No
Secondary	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	No
Secondary	Number of Patients With HIV RNA Level Below 50 Copies/mL and HIV RNA Level Below 400 Copies/mL at Week 96		96 Weeks	No
Secondary	Change From Baseline in Plasma HIV RNA at Week 96		Baseline and Week 96	No
Secondary	Change From Baseline in CD4 Cell Count at Week 96		Baseline and Week 96	No
Secondary	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	No
Secondary	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	No
Secondary	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	No