A Study to Evaluate the Safety and Efficacy of Raltegravir (MK0518) in HIV-Infected Patients Failing Current Antiretroviral Therapies - Study Results

Study Type:	Interventional
Study Design:	Randomized, Double Blind (Subject, Investigator), Placebo Control, Parallel Assignment
Condition:	HIV Infections
Interventions:	Drug: raltegravir potassium Drug: Comparator: Placebo

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Phase III; First Patient In: 22-Mar-2006; Last Patient Last Visit for Week 48: 03-Aug-2007 63 sites (Australia, Belgium, Denmark, France, Germany, Italy, Peru, Portugal, Spain, Switzerland, Taiwan, and Thailand), 61 of which randomized patients.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Patients failed prior antiretroviral therapy (HIV RNA >1000 copies/mL), and had documented resistance to at least one drug in each class of licensed oral antiretroviral therapy (Nucleoside Reverse Transcriptase inhibitors, Non-Nucleoside Reverse Transcriptase inhibitors and Protease Inhibitors). All patients must have met laboratory criteria.

Reporting Groups

	Description
Raltegravir 400 mg b.i.d. Plus OBT	No text entered.
Placebo Plus OBT	No text entered.

Participant Flow: Overall Study

	Raltegravir 400 mg b.i.d. Plus OBT	Placebo Plus OBT
STARTED	234	118
Treated	232	118
Continuing in Double-Blind	193	50
COMPLETED	193^[1]	50
NOT COMPLETED	41	68
Never Treated	2	0
Adverse Event	1	1
Death	3	3
Lack of Efficacy	0	2
Lost to Follow-up	1	1
Withdrawal by Subject	1	1
Entered Virological Failure Phase	33	60

[1]	Does not include patients whom entered the open-label post virological

Baseline Characteristics

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Reporting Groups

	Description
Raltegravir 400 mg b.i.d. Plus OBT	No text entered.
Placebo Plus OBT	No text entered.

Baseline Measures

	Raltegravir 400 mg b.i.d. Plus OBT	Placebo Plus OBT	Total
Number of Participants [units: participants]	232	118	350
Age [units: Years] Mean ( Full Range )	46.1 ( 16 to 74 )	43.7 ( 19 to 64 )	45.3 ( 16 to 74 )
Gender [units: participants]
Female	37	15	52
Male	195	103	298
Race/Ethnicity, Customized [units: participants]
White	174	96	270
Black	18	5	23
Asian	14	5	19
Hispanic	6	1	7
Other	20	11	31
Cluster of Differentiation 4 (CD4) Cell Count [units: cells/mm^3] Mean ( Full Range )	156 ( 1 to 792 )	153 ( 3 to 759 )	155 ( 1 to 792 )
Plasma Human Immunodeficiency Virus (HIV) Ribonucleic Acid (RNA) [units: copies/mL] Geometric Mean ( Full Range )	40519 ( 441 to 750000 )	31828 ( 200 to 750000 )	37352 ( 200 to 750000 )

Outcome Measures

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1. Primary:

Proportion of Patients Achieving HIV RNA <400 Copies/mL at Week 16 [ 16 Weeks ]

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2. Secondary:

Change From Baseline in HIV RNA at Week 16 [ Baseline and Week 16 ]

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3. Secondary:

Change From Baseline in HIV RNA at Week 48 [ Baseline and Week 48 ]

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4. Secondary:

Change From Baseline in CD4 Cell Count at Week 16 [ Baseline and Week 16 ]

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5. Secondary:

Change From Baseline in CD4 Cell Count at Week 48 [ Baseline and Week 48 ]

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6. Other Pre-specified:

Proportion of Patients Achieving HIV RNA <50 Copies/mL at Week 48 [ 48 weeks ]

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Serious Adverse Events

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Other Adverse Events

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Time Frame	No text entered.
Additional Description	No text entered.

Frequency Threshold

Threshold above which other adverse events are reported	2%

Reporting Groups

	Description
Raltegravir 400 mg b.i.d. Plus OBT	No text entered.
Placebo Plus OBT	No text entered.

Other Adverse Events

	Raltegravir 400 mg b.i.d. Plus OBT	Placebo Plus OBT
Total, other (not including serious) adverse events
# participants affected	208	99
Blood and lymphatic system disorders
Anaemia * ^A # participants affected / at risk	5/232 (2.16%)	4/118 (3.39%)
Lymphadenopathy * ^A # participants affected / at risk	7/232 (3.02%)	4/118 (3.39%)
Neutropenia * ^A # participants affected / at risk	5/232 (2.16%)	0/118 (0.00%)
Gastrointestinal disorders
Abdominal Distension * ^A # participants affected / at risk	2/232 (0.86%)	5/118 (4.24%)
Abdominal Pain * ^A # participants affected / at risk	9/232 (3.88%)	5/118 (4.24%)
Abdominal Pain Upper * ^A # participants affected / at risk	5/232 (2.16%)	4/118 (3.39%)
Constipation * ^A # participants affected / at risk	5/232 (2.16%)	1/118 (0.85%)
Diarrhoea ^†^A # participants affected / at risk	40/232 (17.24%)	28/118 (23.73%)
Dyspepsia * ^A # participants affected / at risk	2/232 (0.86%)	3/118 (2.54%)
Flatulence * ^A # participants affected / at risk	2/232 (0.86%)	4/118 (3.39%)
Nausea * ^A # participants affected / at risk	19/232 (8.19%)	13/118 (11.02%)
Vomiting * ^A # participants affected / at risk	15/232 (6.47%)	12/118 (10.17%)
General disorders
Asthenia * ^A # participants affected / at risk	8/232 (3.45%)	6/118 (5.08%)
Fatigue * ^A # participants affected / at risk	10/232 (4.31%)	1/118 (0.85%)
Injection Site Nodule * ^A # participants affected / at risk	1/232 (0.43%)	3/118 (2.54%)
Injection Site Pain * ^A # participants affected / at risk	7/232 (3.02%)	2/118 (1.69%)
Injection Site Reaction * ^A # participants affected / at risk	17/232 (7.33%)	14/118 (11.86%)
Pyrexia * ^A # participants affected / at risk	13/232 (5.60%)	11/118 (9.32%)
Infections and infestations
Bronchitis * ^A # participants affected / at risk	22/232 (9.48%)	4/118 (3.39%)
Folliculitis * ^A # participants affected / at risk	5/232 (2.16%)	1/118 (0.85%)
Gastroenteritis * ^A # participants affected / at risk	9/232 (3.88%)	2/118 (1.69%)
Genital Herpes * ^A # participants affected / at risk	4/232 (1.72%)	4/118 (3.39%)
Herpes Simplex * ^A # participants affected / at risk	6/232 (2.59%)	2/118 (1.69%)
Herpes Zoster * ^A # participants affected / at risk	15/232 (6.47%)	2/118 (1.69%)
Influenza * ^A # participants affected / at risk	15/232 (6.47%)	3/118 (2.54%)
Nasopharyngitis * ^A # participants affected / at risk	22/232 (9.48%)	8/118 (6.78%)
Onychomycosis * ^A # participants affected / at risk	1/232 (0.43%)	3/118 (2.54%)
Oral Candidiasis * ^A # participants affected / at risk	4/232 (1.72%)	9/118 (7.63%)
Respiratory Tract Infection * ^A # participants affected / at risk	10/232 (4.31%)	1/118 (0.85%)
Sinusitis * ^A # participants affected / at risk	4/232 (1.72%)	3/118 (2.54%)
Tooth Infection * ^A # participants affected / at risk	1/232 (0.43%)	3/118 (2.54%)
Upper Respiratory Tract Infection * ^A # participants affected / at risk	7/232 (3.02%)	2/118 (1.69%)
Urinary Tract Infection * ^A # participants affected / at risk	5/232 (2.16%)	3/118 (2.54%)
Investigations
Alanine aminotransferase increased * ^A # participants affected / at risk	15/232 (6.47%)	5/118 (4.24%)
Aspartate aminotransferase increased * ^A # participants affected / at risk	14/232 (6.03%)	5/118 (4.24%)
Blood cholesterol increased * ^A # participants affected / at risk	19/232 (8.19%)	3/118 (2.54%)
Blood triglycerides increased * ^A # participants affected / at risk	14/232 (6.03%)	3/118 (2.54%)
Creatine phosphokinase increased * ^A # participants affected / at risk	5/232 (2.16%)	3/118 (2.54%)
Platelet count decreased * ^A # participants affected / at risk	5/232 (2.16%)	1/118 (0.85%)
Weight Decreased * ^A # participants affected / at risk	3/232 (1.29%)	5/118 (4.24%)
Metabolism and nutrition disorders
Anorexia * ^A # participants affected / at risk	7/232 (3.02%)	3/118 (2.54%)
Musculoskeletal and connective tissue disorders
Arthralgia ^†^A # participants affected / at risk	9/232 (3.88%)	1/118 (0.85%)
Back Pain * ^A # participants affected / at risk	9/232 (3.88%)	3/118 (2.54%)
Muscle Spasms * ^A # participants affected / at risk	4/232 (1.72%)	3/118 (2.54%)
Pain In Extremity * ^A # participants affected / at risk	8/232 (3.45%)	3/118 (2.54%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Skin Papilloma * ^A # participants affected / at risk	8/232 (3.45%)	4/118 (3.39%)
Nervous system disorders
Dizziness * ^A # participants affected / at risk	6/232 (2.59%)	1/118 (0.85%)
Headache * ^A # participants affected / at risk	17/232 (7.33%)	19/118 (16.10%)
Psychiatric disorders
Anxiety ^†^A # participants affected / at risk	6/232 (2.59%)	3/118 (2.54%)
Depression * ^A # participants affected / at risk	3/232 (1.29%)	3/118 (2.54%)
Insomnia * ^A # participants affected / at risk	11/232 (4.74%)	8/118 (6.78%)
Respiratory, thoracic and mediastinal disorders
Cough * ^A # participants affected / at risk	11/232 (4.74%)	3/118 (2.54%)
Pharyngolaryngeal Pain * ^A # participants affected / at risk	2/232 (0.86%)	3/118 (2.54%)
Skin and subcutaneous tissue disorders
Eczema * ^A # participants affected / at risk	2/232 (0.86%)	3/118 (2.54%)
Erythema * ^A # participants affected / at risk	6/232 (2.59%)	1/118 (0.85%)
Hyperhidrosis * ^A # participants affected / at risk	5/232 (2.16%)	1/118 (0.85%)
Lipodystrophy Acquired * ^A # participants affected / at risk	4/232 (1.72%)	4/118 (3.39%)
Pruritus * ^A # participants affected / at risk	10/232 (4.31%)	2/118 (1.69%)
Rash * ^A # participants affected / at risk	13/232 (5.60%)	3/118 (2.54%)
Subcutaneous Nodule * ^A # participants affected / at risk	5/232 (2.16%)	3/118 (2.54%)
Vascular disorders
Hypertension * ^A # participants affected / at risk	9/232 (3.88%)	3/118 (2.54%)

^†	Indicates events were collected by systematic assessment.
*	Indicates events were collected by non-systematic assessment.
^A	Term from vocabulary, MedDRA 10.0

More Information

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Certain Agreements:

All Principal Investigators ARE employed by the organization sponsoring the study.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.

Results Point of Contact:

Name/Title: Executive Vice President, Clinical and Quantitative Sciences
Organization: Merck & Co., Inc.
phone: 1-800-672-6372

Publications:

Steigbigel RT, Cooper DA, Kumar PN, Eron JE, Schechter M, Markowitz M, Loutfy MR, Lennox JL, Gatell JM, Rockstroh JK, Katlama C, Yeni P, Lazzarin A, Clotet B, Zhao J, Chen J, Ryan DM, Rhodes RR, Killar JA, Gilde LR, Strohmaier KM, Meibohm AR, Miller MD, Hazuda DJ, Nessly ML, DiNubile MJ, Isaacs RD, Nguyen BY, Teppler H; BENCHMRK Study Teams. Raltegravir with optimized background therapy for resistant HIV-1 infection. N Engl J Med. 2008 Jul 24;359(4):339-54.

Cooper DA, Steigbigel RT, Gatell JM, Rockstroh JK, Katlama C, Yeni P, Lazzarin A, Clotet B, Kumar PN, Eron JE, Schechter M, Markowitz M, Loutfy MR, Lennox JL, Zhao J, Chen J, Ryan DM, Rhodes RR, Killar JA, Gilde LR, Strohmaier KM, Meibohm AR, Miller MD, Hazuda DJ, Nessly ML, DiNubile MJ, Isaacs RD, Teppler H, Nguyen BY; BENCHMRK Study Teams. Subgroup and resistance analyses of raltegravir for resistant HIV-1 infection. N Engl J Med. 2008 Jul 24;359(4):355-65.

Responsible Party:	Merck & Co., Inc. ( Executive Vice President, Clinical and Quantitative Sciences )
Study ID Numbers:	2005_096, MK0518-018
Study First Received:	February 14, 2006
Results First Received:	August 18, 2009
Last Updated:	November 12, 2009
ClinicalTrials.gov Identifier:	NCT00293267 History of Changes
Health Authority:	France: Ministry of Health