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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
History of Changes
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
No text entered.

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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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  
Number of Participants  
[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
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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 ]
  Show Outcome Measure 1

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

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 ]
  Show Outcome Measure 3

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 ]
  Show Outcome Measure 4

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

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

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

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

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

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

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 ]
  Show Outcome Measure 11

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 ]
  Show Outcome Measure 12

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

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

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

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


  Serious Adverse Events
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Time Frame No text entered.
Additional Description No text entered.

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
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  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


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: Pfizer ClinicalTrials.gov Call Center
Organization: Pfizer, Inc.
phone: 1-800-718-1021
e-mail: ClinicalTrials.govCallCenter@pfizer.com


No publications provided by ViiV Healthcare

Publications automatically indexed to this study:


Responsible Party: Director, Clinical Trial Disclosure Group, Pfizer, Inc.
ClinicalTrials.gov Identifier: NCT00098748     History of Changes
Other Study ID Numbers: A4001029
Study First Received: December 7, 2004
Results First Received: March 25, 2010
Last Updated: November 19, 2010
Health Authority: United States: Food and Drug Administration