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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:
ClinicalTrials.gov Identifier:
NCT00098748
First Posted: December 8, 2004
Last Update Posted: December 7, 2010
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborator:
Pfizer
Information provided by:
ViiV Healthcare
Results First Submitted: March 25, 2010  
Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, 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
No text entered.

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 
Other                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.
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.
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


  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   5%  

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.

Other Adverse Events
    Maraviroc QD   Maraviroc BID   Placebo
Total, Other (not including serious) Adverse Events       
# participants affected / at risk   46/63 (73.02%)   51/62 (82.26%)   42/61 (68.85%) 
Blood and lymphatic system disorders       
Anaemia † 1       
# participants affected / at risk   4/63 (6.35%)   0/62 (0.00%)   1/61 (1.64%) 
Gastrointestinal disorders       
Constipation † 1       
# participants affected / at risk   6/63 (9.52%)   5/62 (8.06%)   1/61 (1.64%) 
Diarrhoea † 1       
# participants affected / at risk   18/63 (28.57%)   12/62 (19.35%)   13/61 (21.31%) 
Nausea † 1       
# participants affected / at risk   9/63 (14.29%)   8/62 (12.90%)   12/61 (19.67%) 
Vomiting † 1       
# participants affected / at risk   8/63 (12.70%)   3/62 (4.84%)   8/61 (13.11%) 
General disorders       
Asthenia † 1       
# participants affected / at risk   0/63 (0.00%)   2/62 (3.23%)   7/61 (11.48%) 
Fatigue † 1       
# participants affected / at risk   8/63 (12.70%)   10/62 (16.13%)   11/61 (18.03%) 
Injection site reaction † 1       
# participants affected / at risk   7/63 (11.11%)   13/62 (20.97%)   9/61 (14.75%) 
Pyrexia † 1       
# participants affected / at risk   5/63 (7.94%)   6/62 (9.68%)   4/61 (6.56%) 
Infections and infestations       
Bronchitis † 1       
# participants affected / at risk   4/63 (6.35%)   6/62 (9.68%)   2/61 (3.28%) 
Herpes simplex † 1       
# participants affected / at risk   4/63 (6.35%)   4/62 (6.45%)   2/61 (3.28%) 
Influenza † 1       
# participants affected / at risk   1/63 (1.59%)   4/62 (6.45%)   1/61 (1.64%) 
Nasopharyngitis † 1       
# participants affected / at risk   5/63 (7.94%)   3/62 (4.84%)   3/61 (4.92%) 
Oral candidiasis † 1       
# participants affected / at risk   1/63 (1.59%)   5/62 (8.06%)   0/61 (0.00%) 
Pharyngitis † 1       
# participants affected / at risk   1/63 (1.59%)   5/62 (8.06%)   0/61 (0.00%) 
Sinusitis † 1       
# participants affected / at risk   3/63 (4.76%)   6/62 (9.68%)   4/61 (6.56%) 
Upper respiratory tract infection † 1       
# participants affected / at risk   5/63 (7.94%)   10/62 (16.13%)   5/61 (8.20%) 
Investigations       
Weight increased † 1       
# participants affected / at risk   4/63 (6.35%)   0/62 (0.00%)   0/61 (0.00%) 
Musculoskeletal and connective tissue disorders       
Arthralgia † 1       
# participants affected / at risk   3/63 (4.76%)   4/62 (6.45%)   1/61 (1.64%) 
Back pain † 1       
# participants affected / at risk   5/63 (7.94%)   8/62 (12.90%)   2/61 (3.28%) 
Pain in extremity † 1       
# participants affected / at risk   0/63 (0.00%)   6/62 (9.68%)   2/61 (3.28%) 
Nervous system disorders       
Dizziness † 1       
# participants affected / at risk   6/63 (9.52%)   6/62 (9.68%)   3/61 (4.92%) 
Headache † 1       
# participants affected / at risk   13/63 (20.63%)   11/62 (17.74%)   5/61 (8.20%) 
Psychiatric disorders       
Insomnia † 1       
# participants affected / at risk   5/63 (7.94%)   5/62 (8.06%)   3/61 (4.92%) 
Respiratory, thoracic and mediastinal disorders       
Cough † 1       
# participants affected / at risk   7/63 (11.11%)   6/62 (9.68%)   4/61 (6.56%) 
Oropharyngeal pain † 1       
# participants affected / at risk   3/63 (4.76%)   4/62 (6.45%)   1/61 (1.64%) 
Rhinorrhoea † 1       
# participants affected / at risk   0/63 (0.00%)   4/62 (6.45%)   0/61 (0.00%) 
Skin and subcutaneous tissue disorders       
Night sweats † 1       
# participants affected / at risk   4/63 (6.35%)   3/62 (4.84%)   1/61 (1.64%) 
Pruritus † 1       
# participants affected / at risk   2/63 (3.17%)   3/62 (4.84%)   5/61 (8.20%) 
Rash † 1       
# participants affected / at risk   7/63 (11.11%)   6/62 (9.68%)   7/61 (11.48%) 
Events were collected by systematic assessment
1 Term from vocabulary, MedDRA (12.0)



  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