Safety and Efficacy of an Investigational Drug in Human Immunodeficiency Virus (HIV)-Infected Patients Failing Current Antiretroviral Therapies (0518-005)(COMPLETED)

• ClinicalTrials.gov Identifier: NCT00105157
• Recruitment Status: Completed
• First Posted: March 9, 2005
• Results First Posted: April 12, 2010
• Last Update Posted: December 4, 2015
• Sponsor: Merck Sharp & Dohme Corp.
• Information provided by (Responsible Party): Merck Sharp & Dohme Corp.

Study Description

Brief Summary:

This study will investigate the safety and efficacy of different doses of an investigational drug (MK0518) as a therapy for HIV-infected patients failing current antiretroviral therapies.

Condition or disease	Intervention/treatment	Phase
HIV Infections; Acquired Immunodeficiency Syndrome	Drug: Comparator: MK0518; Drug: MK0518; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 179 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Multicenter Study to Evaluate the Safety and Efficacy of MK0518 in Combination With An Optimized Background Therapy (OBT), Versus OBT Alone, in HIV-Infected Patients With Documented Resistance
• Study Start Date: March 2005
• Actual Primary Completion Date: October 2006
• Actual Study Completion Date: July 2009

Arms and Interventions

Arm	Intervention/treatment
Experimental: 1; MK0518 200 mg	Drug: Comparator: MK0518; MK0518 oral tablets 200 mg b.i.d, for 24 weeks; Other Name: MK0518
Experimental: 2; MK0518 400 mg	Drug: MK0518; MK0518 oral tablets 400 mg b.i.d, for 24 weeks
Experimental: 3; MK0518 600 mg	Drug: MK0518; MK0518 oral tablets 600 mg b.i.d, for 24 weeks
Placebo Comparator: 4; Placebo	Drug: Placebo; Placebo to MK0518, oral tablet b.i.d, for 24 weeks

Outcome Measures

Primary Outcome Measures :

1. Change From Baseline in Plasma HIV RNA (log10 Copies/mL) at Week 24 [ Time Frame: Baseline and Week 24 ]
   Mean change from baseline at Week 24 in HIV RNA (log10 copies/mL) in all patients

Secondary Outcome Measures :

1. Number of Patients With Virologic Responses at Week 24 [ Time Frame: 24 weeks ]
   Number of patients who achieve HIV RNA <400 copies/mL; HIV RNA level <50 copies/mL at Week 24; or reduction from baseline in HIV RNA (log10 copies/mL) exceeding 1.0 log10 copies/mL at Week 24; at Week 24
2. Change From Baseline in CD4 Cell Count at Week 24 [ Time Frame: Baseline and Week 24 ]
   Mean change from baseline at Week 24 in CD4 Cell Count (cells/mm3)
3. Number of Patients With Clinical Adverse Experiences (CAEs) at 48 Weeks [ Time Frame: 48 weeks ]
   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
4. Number of Patients With Serious CAEs at 48 Weeks [ Time Frame: 48 weeks ]
   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
5. Number of Patients With Drug-related CAEs at 48 Weeks [ Time Frame: 48 weeks ]
   Patients with drug-related (as assessed by an investigator who is a qualified physician according to his/her best clinical judgment) CAEs
6. Number of Patients With Serious Drug-related CAEs at 48 Weeks [ Time Frame: 48 weeks ]
   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.
7. Number of Patients That Died by 48 Weeks [ Time Frame: 48 weeks ]
8. Number of Patients That Discontinued With CAEs at 48 Weeks [ Time Frame: 48 weeks ]
9. Number of Patients That Discontinued With Drug-related CAEs at 48 Weeks [ Time Frame: 48 weeks ]
10. Number of Patients That Discontinued With Serious CAEs at 48 Weeks [ Time Frame: 48 weeks ]
11. Number of Patients That Discontinued With Serious Drug-related CAEs at 48 Weeks [ Time Frame: 48 weeks ]
12. Number of Patients With Laboratory Adverse Experiences (LAEs) at 48 Weeks [ Time Frame: 48 weeks ]
    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
13. Number of Patients With Drug-related LAEs at 48 Weeks [ Time Frame: 48 weeks ]
    Patients with drug-related (as assessed by an investigator who is a qualified physician according to his/her best clinical judgment) LAEs
14. Number of Patients Discontinued With Laboratory Adverse Experiences (LAEs) at 48 Weeks [ Time Frame: 48 weeks ]
15. Number of Patients Discontinued With Drug-related LAEs at 48 Weeks [ Time Frame: 48 weeks ]
16. Number of Patients With Clinical Adverse Experiences (CAEs) at 96 Weeks [ Time Frame: 96 weeks ]
    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
17. Number of Patients With Serious CAEs at 96 Weeks [ Time Frame: 96 weeks ]
    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
18. Number of Patients With Drug-related CAEs at 96 Weeks [ Time Frame: 96 weeks ]
    Patients with drug-related (as assessed by an investigator who is a qualified physician according to his/her best clinical judgment) CAEs
19. Number of Patients With Serious Drug-related CAEs at 96 Weeks [ Time Frame: 96 weeks ]
    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.
20. Number of Patients That Died by 96 Weeks [ Time Frame: 96 weeks ]
21. Number of Patients That Discontinued With CAEs at 96 Weeks [ Time Frame: 96 weeks ]
22. Number of Patients That Discontinued With Drug-related CAEs at 96 Weeks [ Time Frame: 96 weeks ]
23. Number of Patients That Discontinued With Serious CAEs at 96 Weeks [ Time Frame: 96 weeks ]
24. Number of Patients That Discontinued With Serious Drug-related CAEs at 96 Weeks [ Time Frame: 96 weeks ]
25. Number of Patients With Laboratory Adverse Experiences (LAEs) at 96 Weeks [ Time Frame: 96 weeks ]
    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
26. Number of Patients With Drug-related LAEs at 96 Weeks [ Time Frame: 96 weeks ]
    Patients with drug-related (as assessed by an investigator who is a qualified physician according to his/her best clinical judgment) LAEs
27. Number of Patients Discontinued With Laboratory Adverse Experiences (LAEs) at 96 Weeks [ Time Frame: 96 weeks ]
28. Number of Patients Discontinued With Drug-related LAEs at 96 Weeks [ Time Frame: 96 weeks ]
29. Number of Patients With Clinical Adverse Experiences (CAEs) at 168 Weeks [ Time Frame: 168 weeks ]
    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
30. Number of Patients With Serious CAEs at 168 Weeks [ Time Frame: 168 weeks ]
    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
31. Number of Patients With Drug-related CAEs at 168 Weeks [ Time Frame: 168 weeks ]
    Patients with drug-related (as assessed by an investigator who is a qualified physician according to his/her best clinical judgment) CAEs
32. Number of Patients With Serious Drug-related CAEs at 168 Weeks [ Time Frame: 168 weeks ]
    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.
33. Number of Patients That Died by 168 Weeks [ Time Frame: 168 weeks ]
34. Number of Patients That Discontinued With CAEs at 168 Weeks [ Time Frame: 168 weeks ]
35. Number of Patients That Discontinued With Drug-related CAEs at 168 Weeks [ Time Frame: 168 weeks ]
36. Number of Patients That Discontinued With Serious CAEs at 168 Weeks [ Time Frame: 168 weeks ]
37. Number of Patients That Discontinued With Serious Drug-related CAEs at 168 Weeks [ Time Frame: 168 weeks ]
38. Number of Patients With Laboratory Adverse Experiences (LAEs) at 168 Weeks [ Time Frame: 168 weeks ]
    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
39. Number of Patients With Serious LAEs at 168 Weeks [ Time Frame: 168 weeks ]
    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
40. Number of Patients Discontinued With Drug-related LAEs at 168 Weeks [ Time Frame: 168 weeks ]
41. Number of Patients With Drug-related LAEs at 168 Weeks [ Time Frame: 168 weeks ]
    Patients with drug-related (as assessed by an investigator who is a qualified physician according to his/her best clinical judgment) LAEs
42. Number of Patients With Serious Drug-related LAEs at 168 Weeks [ Time Frame: 168 weeks ]
    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
43. Number of Patients Discontinued With LAEs at 168 Weeks [ Time Frame: 168 weeks ]

Other Outcome Measures:

1. Change From Baseline in Plasma HIV RNA (log10 Copies/mL) at Week 168 in Combined Substudies [ Time Frame: Baseline and Week 168 ]
   Mean change from baseline at Week 168 in HIV RNA (log10 copies/mL) in patients from combined substudies in the double-blind plus open-label phases.
2. Change From Baseline in CD4 Cell Count at Week 168 in Combined Substudies [ Time Frame: Baseline and Week 168 ]
   Mean change from baseline at Week 168 in CD4 Cell Count (cells/mm3) in patients from combined substudies in the double-blind plus open-label phases.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Patient must be HIV positive with Human Immunodeficiency Virus (HIV) Ribonucleic Acid (RNA) values that are within ranges required by the study
• Patient must be currently on antiretroviral therapy (ART)

Exclusion Criteria:

• Patient less than 18 years of age
• Additional exclusion criteria will be discussed and identified by the study doctor

Contacts and Locations

Sponsors and Collaborators

Merck Sharp & Dohme Corp.

Investigators

• Study Director: Medical Monitor; Merck Sharp & Dohme Corp.

More Information

Publications:

Grinsztejn B, Nguyen BY, Katlama C, Gatell JM, Lazzarin A, Vittecoq D, Gonzalez CJ, Chen J, Harvey CM, Isaacs RD; Protocol 005 Team. Safety and efficacy of the HIV-1 integrase inhibitor raltegravir (MK-0518) in treatment-experienced patients with multidrug-resistant virus: a phase II randomised controlled trial. Lancet. 2007 Apr 14;369(9569):1261-1269. doi: 10.1016/S0140-6736(07)60597-2.

• Responsible Party: Merck Sharp & Dohme Corp.
• ClinicalTrials.gov Identifier: NCT00105157
• Other Study ID Numbers: 0518-005; MK0518-005; 2005_007
• First Posted: March 9, 2005
• Results First Posted: April 12, 2010
• Last Update Posted: December 4, 2015
• Last Verified: December 2015

Additional relevant MeSH terms:

HIV Infections; Acquired Immunodeficiency Syndrome; Immunologic Deficiency Syndromes; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Immune System Diseases; Slow Virus Diseases; Raltegravir Potassium; Anti-HIV Agents; Anti-Retroviral Agents; Antiviral Agents; Anti-Infective Agents; HIV Integrase Inhibitors; Integrase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action