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

NCT00100048 | Completed Phase 2 Results

• 2 other identifiers: 0518-0042004_096
• Study Type: interventional
• Target: 206
• Locations: 0 countries
• Sites: N/A

Brief Summary

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

Conditions

HIV Infections; Acquired Immunodeficiency Syndrome

Outcome Measures

Primary Outcomes (8)

• 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 Outcomes (9)

• 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)

  Baseline and Week 24

• Change From Baseline in Cluster of Differentiation 4 (CD4) Cell Count at Week 24 (Cohort II)

  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

Other Outcomes (9)

• Number of Participants With HIV RNA Levels Below 400 Copies/mL at Week 48

  48 weeks

• Number of Patients With Drug-related CAEs

  48 weeks

• Number of Patients With Serious Drug-related CAEs

  48 Weeks

Study Arms (10)

600 mg monotherapy

EXPERIMENTAL

MK0518 600 mg twice daily

Drug: Comparator: MK0518 monotherapy

400 mg monotherapy

EXPERIMENTAL

MK0518 400 mg twice daily

Drug: Comparator: MK0518 monotherapy

200 mg monotherapy

EXPERIMENTAL

MK0518 200 mg twice daily

Drug: Comparator: MK0518 monotherapy

100 mg monotherapy

EXPERIMENTAL

MK0518 100 mg twice daily

Drug: Comparator: MK0518 monotherapy

placebo monotherapy

PLACEBO COMPARATOR

Placebo to MK0518 twice daily

Drug: Placebo monotherapy

600 mg combo therapy

EXPERIMENTAL

MK0518 600 mg + tenofovir + lamivudine

Drug: Comparator: MK0518 combination therapy; Drug: Comparator: tenofovir; Drug: Comparator: lamivudine

400 mg combo therapy

EXPERIMENTAL

MK0518 400 mg + tenofovir + lamivudine

Drug: Comparator: MK0518 combination therapy; Drug: Comparator: tenofovir; Drug: Comparator: lamivudine

200 mg combo therapy

EXPERIMENTAL

MK0518 200 mg + tenofovir + lamivudine

Drug: Comparator: MK0518 combination therapy; Drug: Comparator: tenofovir; Drug: Comparator: lamivudine

100 mg combo therapy

EXPERIMENTAL

MK0518 100 mg + tenofovir + lamivudine

Drug: Comparator: MK0518 combination therapy; Drug: Comparator: tenofovir; Drug: Comparator: lamivudine

EFV combo therapy

ACTIVE COMPARATOR

efavirenz + tenofovir + lamivudine

Drug: Comparator: efavirenz; Drug: Comparator: tenofovir; Drug: Comparator: lamivudine

Interventions

Comparator: MK0518 monotherapy DRUG

MK0518 twice daily for 10 days

100 mg monotherapy; 200 mg monotherapy; 400 mg monotherapy; 600 mg monotherapy

Comparator: MK0518 combination therapy DRUG

MK0518 twice daily for 48 weeks

100 mg combo therapy; 200 mg combo therapy; 400 mg combo therapy; 600 mg combo therapy

Comparator: efavirenz DRUG

efavirenz 600 mg every night at bedtime for 48 weeks

EFV combo therapy

Comparator: tenofovir DRUG

tenofovir 300 mg daily for 48 weeks

100 mg combo therapy; 200 mg combo therapy; 400 mg combo therapy; 600 mg combo therapy; EFV combo therapy

Comparator: lamivudine DRUG

lamivudine 300 mg daily for 48 weeks

100 mg combo therapy; 200 mg combo therapy; 400 mg combo therapy; 600 mg combo therapy; EFV combo therapy

Placebo monotherapy DRUG

Placebo to MK0518 twice daily

placebo monotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• Less than 18 years of age
• Individuals who currently do not test positive for HIV

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related 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. doi: 10.1097/QAI.0b013e31802b4956.

  PMID: 17133211 BACKGROUND

• 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.

  PMID: 18090280 BACKGROUND

• 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.

  PMID: 17721395 BACKGROUND

• 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.

  PMID: 19648823 BACKGROUND

MeSH Terms

Conditions

HIV Infections; Acquired Immunodeficiency Syndrome

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Slow Virus Diseases

Results Point of Contact

• Title: Vice President, Late Stage Development Group Leader
• Organization: Merck Sharp & Dohme Corp

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Monitor

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 22, 2004
• First Posted: December 23, 2004
• Study Start: January 1, 2005
• Primary Completion: October 1, 2006
• Study Completion: July 1, 2010
• Last Updated: September 9, 2015
• Results First Posted: March 29, 2010

Record last verified: 2015-09