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Trial of Maraviroc (UK-427,857) in Combination With Optimized Background Therapy Versus Optimized Background Therapy Alone for the Treatment of Antiretroviral-Experienced NonCCR5-Tropic HIV-1 Infected Subjects

This study has been completed.
Sponsor:
Collaborator:
Pfizer
Information provided by:
ViiV Healthcare
ClinicalTrials.gov Identifier:
NCT00098748
First received: December 7, 2004
Last updated: November 19, 2010
Last verified: November 2010
Results First Received: March 25, 2010  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Investigator);   Primary Purpose: Treatment
Condition: HIV Infections
Interventions: Drug: Optimized Background Therapy (OBT)
Drug: maraviroc (UK-427,857)

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
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Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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Reporting Groups
  Description
Maraviroc QD Maraviroc 150 mg by mouth (PO) once daily (QD) in combination with optimized background therapy (OBT) (3 to 6 drugs based on treatment history and resistance testing). The 150 mg QD arm = placebo drug in the morning and active drug in the evening.
Maraviroc BID Maraviroc 150 mg PO twice a day (BID) in combination with OBT (3 to 6 drugs based on treatment history and resistance testing). The 150 mg BID arm = active drug in the morning and evening.
Placebo Placebo BID in combination with OBT (3 to 6 drugs based on treatment history and resistance testing). The placebo arm = placebo drug in the morning and evening.

Participant Flow for 3 periods

Period 1:   Assigned to Study Treatment
    Maraviroc QD   Maraviroc BID   Placebo
STARTED   63   63   64 
COMPLETED   63   61   62 
NOT COMPLETED   0   2   2 
Randomized, but not treated                0                2                2 

Period 2:   Received Study Treatment
    Maraviroc QD   Maraviroc BID   Placebo
STARTED   63   61 [1]   62 [2] 
Dual-tropic Subjects by Phenotype Assay   57 [3]   52   58 
COMPLETED   15   25   18 
NOT COMPLETED   48   36   44 
Death                2                1                2 
Adverse Event                1                2                5 
Lack of Efficacy                40                27                27 
Unspecified                2                2                6 
Subject defaulted                3                4                4 
[1] Due to 1 placebo subject switched to maraviroc BID, BID = 62 subjects in Adverse event tables.
[2] Due to 1 placebo subject switched to maraviroc BID, Placebo = 61 subjects in Adverse event tables.
[3] Dual-tropic: Virus capable of using both CCR5 and CXCR4 coreceptors for cell entry.

Period 3:   Continued on Open-Label Treatment
    Maraviroc QD   Maraviroc BID   Placebo
STARTED   15   25   0 [1] 
COMPLETED   7   10   0 
NOT COMPLETED   8   15   0 
Adverse Event                0                1                0 
Lack of Efficacy                1                2                0 
Other reason includes protocol violation                6                7                0 
Lost to Follow-up                1                1                0 
Withdrawal by Subject                0                4                0 
[1] Placebo group not offered open-label maraviroc due to study not reaching primary endpoint at Week 24



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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Reporting Groups
  Description
Maraviroc QD Maraviroc 150 mg by mouth (PO) once daily (QD) in combination with optimized background therapy (OBT) (3 to 6 drugs based on treatment history and resistance testing). The 150 mg QD arm = placebo drug in the morning and active drug in the evening.
Maraviroc BID Maraviroc 150 mg PO twice a day (BID) in combination with OBT (3 to 6 drugs based on treatment history and resistance testing). The 150 mg BID arm = active drug in the morning and evening.
Placebo Placebo BID in combination with OBT (3 to 6 drugs based on treatment history and resistance testing). The placebo arm = placebo drug in the morning and evening.
Total Total of all reporting groups

Baseline Measures
   Maraviroc QD   Maraviroc BID   Placebo   Total 
Overall Participants Analyzed 
[Units: Participants]
 63   61   62   186 
Age, Customized 
[Units: Participants]
       
<18 years   2   2   0   4 
Between 18 and 24 years   1   1   1   3 
Between 25 and 34 years   2   3   2   7 
Between 35 and 44 years   30   31   31   92 
Between 45 and 54 years   25   21   20   66 
Between 55 and 64 years   3   3   7   13 
≥65 years   0   0   1   1 
Age 
[Units: Years]
Mean (Full Range)
 42.7 
 (16 to 59) 
 42.5 
 (16 to 62) 
 44.6 
 (23 to 65) 
 43.3 
 (16 to 65) 
Gender 
[Units: Participants]
       
Female   10   6   9   25 
Male   53   55   53   161 


  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Change From Baseline in Human Immunodeficiency Virus (HIV-1) Viral Load (Ribonucleic Acid [RNA])   [ Time Frame: Baseline to Week 24 and Week 48 ]

2.  Secondary:   Number of Subjects With HIV-1 RNA Levels < 400 Copies/mL   [ Time Frame: Week 24, Week 48 ]

3.  Secondary:   Number of Subjects With HIV-1 RNA Levels < 400 Copies/mL or at Least 0.5 Log 10-transformed Decrease From Baseline in HIV-1 RNA Levels   [ Time Frame: Baseline, Week 24, Week 48 ]

4.  Secondary:   Number of Subjects With HIV-1 RNA Levels < 400 Copies/mL or at Least 1.0 Log 10-transformed Decrease From Baseline in HIV-1 RNA Levels   [ Time Frame: Baseline, Week 24, Week 48 ]

5.  Secondary:   Number of Subjects With HIV-1 RNA Levels < 50 Copies/mL   [ Time Frame: Baseline, Week 24, Week 48 ]

6.  Secondary:   Change From Baseline in CD4 Cell Count   [ Time Frame: Baseline to Week 24 and Week 48 ]

7.  Secondary:   Change From Baseline in CD8 Cell Count   [ Time Frame: Baseline to Week 24 and Week 48 ]

8.  Secondary:   Time (50% Quartile Point Estimate) to Virologic Failure   [ Time Frame: Day 1 through Week 24 and through Week 48 ]

9.  Secondary:   Change From Baseline in Time Averaged Difference (TAD) in log10 HIV-1 RNA   [ Time Frame: Baseline to Week 24 and Week 48 ]

10.  Secondary:   Number of Subjects Per Genotype and Phenotype at Baseline and at Time of Failure   [ Time Frame: Baseline through Week 48 ]

11.  Secondary:   Number of Subjects Per Tropism Status at Screening and at the Time of Treatment Failure (Analysis at Week 24)   [ Time Frame: Screening through Week 24 ]

12.  Secondary:   Number of Subjects Per Tropism Status at Screening and Time of Treatment Failure (Analysis at Week 48)   [ Time Frame: Screening through Week 48 ]

13.  Secondary:   Number of Subjects With Treatment Failure at Week 24 by Overall Susceptibility Score (OSS) at Screening   [ Time Frame: Screening, Week 24 ]

14.  Secondary:   Number of Subjects With Treatment Failure at Week 48 by Overall Susceptibility Score (OSS) at Screening   [ Time Frame: Screening, Week48 ]

15.  Secondary:   Number of Subjects With Acquired Immunodeficiency Syndrome (AIDS)-Defining Opportunistic Illnesses (Analysis at Week 24)   [ Time Frame: Baseline through Week 24 ]

16.  Secondary:   Number of Subjects With Acquired Immunodeficiency Syndrome (AIDS)-Defining Opportunistic Illnesses (Analysis at Week 48)   [ Time Frame: Baseline through Week 48 ]


  Serious Adverse Events
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Reporting Groups
  Description
Maraviroc QD Maraviroc 150 mg by mouth (PO) once daily (QD) in combination with optimized background therapy (OBT) (3 to 6 drugs based on treatment history and resistance testing). The 150 mg QD arm = placebo drug in the morning and active drug in the evening.
Maraviroc BID Maraviroc 150 mg PO twice a day (BID) in combination with OBT (3 to 6 drugs based on treatment history and resistance testing). The 150 mg BID arm = active drug in the morning and evening.
Placebo Placebo BID in combination with OBT (3 to 6 drugs based on treatment history and resistance testing). The placebo arm = placebo drug in the morning and evening.

Serious Adverse Events
    Maraviroc QD   Maraviroc BID   Placebo
Total, serious adverse events       
# participants affected / at risk   13/63 (20.63%)   14/62 (22.58%)   13/61 (21.31%) 
Blood and lymphatic system disorders       
Anaemia † 1       
# participants affected / at risk   1/63 (1.59%)   0/62 (0.00%)   0/61 (0.00%) 
Lymphadenitis † 1       
# participants affected / at risk   0/63 (0.00%)   1/62 (1.61%)   0/61 (0.00%) 
Neutropenia † 1       
# participants affected / at risk   1/63 (1.59%)   0/62 (0.00%)   1/61 (1.64%) 
Cardiac disorders       
Myocardial infarction † 1       
# participants affected / at risk   0/63 (0.00%)   1/62 (1.61%)   0/61 (0.00%) 
Gastrointestinal disorders       
Ascites † 1       
# participants affected / at risk   0/63 (0.00%)   0/62 (0.00%)   1/61 (1.64%) 
Diarrhoea † 1       
# participants affected / at risk   0/63 (0.00%)   1/62 (1.61%)   1/61 (1.64%) 
Pancreatitis acute † 1       
# participants affected / at risk   1/63 (1.59%)   0/62 (0.00%)   0/61 (0.00%) 
General disorders       
Asthenia † 1       
# participants affected / at risk   0/63 (0.00%)   1/62 (1.61%)   1/61 (1.64%) 
Condition aggravated † 1       
# participants affected / at risk   0/63 (0.00%)   0/62 (0.00%)   1/61 (1.64%) 
Disease progression † 1       
# participants affected / at risk   0/63 (0.00%)   1/62 (1.61%)   0/61 (0.00%) 
Fatigue † 1       
# participants affected / at risk   0/63 (0.00%)   0/62 (0.00%)   1/61 (1.64%) 
Pyrexia † 1       
# participants affected / at risk   3/63 (4.76%)   1/62 (1.61%)   0/61 (0.00%) 
Hepatobiliary disorders       
Hepatitis † 1       
# participants affected / at risk   1/63 (1.59%)   0/62 (0.00%)   0/61 (0.00%) 
Immune system disorders       
Hypersensitivity † 1       
# participants affected / at risk   0/63 (0.00%)   1/62 (1.61%)   1/61 (1.64%) 
Infections and infestations       
Abscess † 1       
# participants affected / at risk   0/63 (0.00%)   0/62 (0.00%)   1/61 (1.64%) 
Bronchitis bacterial † 1       
# participants affected / at risk   0/63 (0.00%)   0/62 (0.00%)   1/61 (1.64%) 
Candidiasis † 1       
# participants affected / at risk   0/63 (0.00%)   0/62 (0.00%)   1/61 (1.64%) 
Clostridial infection † 1       
# participants affected / at risk   0/63 (0.00%)   2/62 (3.23%)   0/61 (0.00%) 
Ear infection † 1       
# participants affected / at risk   0/63 (0.00%)   1/62 (1.61%)   0/61 (0.00%) 
Gastroenteritis viral † 1       
# participants affected / at risk   0/63 (0.00%)   1/62 (1.61%)   0/61 (0.00%) 
Histoplasmosis † 1       
# participants affected / at risk   1/63 (1.59%)   0/62 (0.00%)   0/61 (0.00%) 
Lobar pneumonia † 1       
# participants affected / at risk   0/63 (0.00%)   0/62 (0.00%)   1/61 (1.64%) 
Meningitis aseptic † 1       
# participants affected / at risk   1/63 (1.59%)   0/62 (0.00%)   0/61 (0.00%) 
Oesophageal candidiasis † 1       
# participants affected / at risk   0/63 (0.00%)   2/62 (3.23%)   0/61 (0.00%) 
Pneumococcal sepsis † 1       
# participants affected / at risk   0/63 (0.00%)   1/62 (1.61%)   0/61 (0.00%) 
Pneumocystis jiroveci pneumonia † 1       
# participants affected / at risk   3/63 (4.76%)   0/62 (0.00%)   0/61 (0.00%) 
Pneumonia † 1       
# participants affected / at risk   3/63 (4.76%)   2/62 (3.23%)   1/61 (1.64%) 
Pneumonia bacterial † 1       
# participants affected / at risk   1/63 (1.59%)   0/62 (0.00%)   0/61 (0.00%) 
Staphylococcal abscess † 1       
# participants affected / at risk   0/63 (0.00%)   1/62 (1.61%)   0/61 (0.00%) 
Staphylococcal bacteraemia † 1       
# participants affected / at risk   1/63 (1.59%)   0/62 (0.00%)   0/61 (0.00%) 
Staphylococcal infection † 1       
# participants affected / at risk   0/63 (0.00%)   1/62 (1.61%)   1/61 (1.64%) 
Subcutaneous abscess † 1       
# participants affected / at risk   0/63 (0.00%)   0/62 (0.00%)   1/61 (1.64%) 
Urinary tract infection † 1       
# participants affected / at risk   0/63 (0.00%)   1/62 (1.61%)   0/61 (0.00%) 
Injury, poisoning and procedural complications       
Humerus fracture † 1       
# participants affected / at risk   0/63 (0.00%)   0/62 (0.00%)   1/61 (1.64%) 
Metabolism and nutrition disorders       
Anorexia † 1       
# participants affected / at risk   0/63 (0.00%)   0/62 (0.00%)   1/61 (1.64%) 
Dehydration † 1       
# participants affected / at risk   0/63 (0.00%)   1/62 (1.61%)   1/61 (1.64%) 
Diabetes mellitus † 1       
# participants affected / at risk   1/63 (1.59%)   0/62 (0.00%)   0/61 (0.00%) 
Hypoglycaemia † 1       
# participants affected / at risk   1/63 (1.59%)   0/62 (0.00%)   0/61 (0.00%) 
Musculoskeletal and connective tissue disorders       
Pain in extremity † 1       
# participants affected / at risk   1/63 (1.59%)   0/62 (0.00%)   0/61 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
B-cell lymphoma † 1       
# participants affected / at risk   0/63 (0.00%)   1/62 (1.61%)   0/61 (0.00%) 
Burkitt’s lymphoma † 1       
# participants affected / at risk   1/63 (1.59%)   0/62 (0.00%)   0/61 (0.00%) 
Lung adenocarcinoma † 1       
# participants affected / at risk   1/63 (1.59%)   0/62 (0.00%)   0/61 (0.00%) 
Nervous system disorders       
Central nervous system lesion † 1       
# participants affected / at risk   0/63 (0.00%)   0/62 (0.00%)   1/61 (1.64%) 
Encephalitis † 1       
# participants affected / at risk   0/63 (0.00%)   0/62 (0.00%)   1/61 (1.64%) 
Movement disorder † 1       
# participants affected / at risk   1/63 (1.59%)   0/62 (0.00%)   0/61 (0.00%) 
Pregnancy, puerperium and perinatal conditions       
Abortion spontaneous † 1       
# participants affected / at risk   0/63 (0.00%)   0/62 (0.00%)   1/61 (1.64%) 
Pregnancy † 1       
# participants affected / at risk   0/63 (0.00%)   0/62 (0.00%)   1/61 (1.64%) 
Psychiatric disorders       
Depression † 1       
# participants affected / at risk   0/63 (0.00%)   0/62 (0.00%)   2/61 (3.28%) 
Suicidal ideation † 1       
# participants affected / at risk   0/63 (0.00%)   0/62 (0.00%)   1/61 (1.64%) 
Renal and urinary disorders       
Nephrolithiasis † 1       
# participants affected / at risk   1/63 (1.59%)   0/62 (0.00%)   0/61 (0.00%) 
Respiratory, thoracic and mediastinal disorders       
Cough † 1       
# participants affected / at risk   1/63 (1.59%)   0/62 (0.00%)   0/61 (0.00%) 
Dyspnoea † 1       
# participants affected / at risk   1/63 (1.59%)   0/62 (0.00%)   0/61 (0.00%) 
Haemothorax † 1       
# participants affected / at risk   0/63 (0.00%)   0/62 (0.00%)   1/61 (1.64%) 
Pleural effusion † 1       
# participants affected / at risk   0/63 (0.00%)   0/62 (0.00%)   1/61 (1.64%) 
Skin and subcutaneous tissue disorders       
Rash † 1       
# participants affected / at risk   0/63 (0.00%)   1/62 (1.61%)   0/61 (0.00%) 
Events were collected by systematic assessment
1 Term from vocabulary, MedDRA (12.0)




  Other Adverse Events


  Limitations and Caveats
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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
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  More Information