Trial of Maraviroc (UK-427,857) in Combination With Optimized Background Therapy Versus Optimized Background Therapy Alone for the Treatment of HIV-1 Infected Subjects (MOTIVATE 2)

This study has been completed.
Sponsor:
Collaborator:
Pfizer
Information provided by (Responsible Party):
ViiV Healthcare
ClinicalTrials.gov Identifier:
NCT00098722
First received: December 7, 2004
Last updated: April 16, 2012
Last verified: April 2012
Results First Received: April 16, 2012  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition: HIV Infections
Interventions: Drug: Maraviroc (UK-427,857)
Drug: optimized background therapy

  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, Double Blind Maraviroc 150 or 300 milligrams (mg) tablet orally once daily (QD) in the evening, dose adjusted according to the other prescribed drugs taken by participants as part of optimized background therapy (OBT) selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations). Placebo matched to maraviroc tablet orally in the morning.
Maraviroc BID, Double Blind Maraviroc 150 or 300 mg tablet orally twice daily (BID) in the morning and evening, dose adjusted according to the other prescribed drugs taken by participants as part of OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations).
Placebo, Double Blind Placebo matched to maraviroc tablet orally BID in the morning and evening, in combination with OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations).
Maraviroc BID, Open Label Participants from maraviroc QD, maraviroc BID and Placebo (double blind phase) who received maraviroc 150 or 300 mg BID in the morning and evening, dose adjusted according to the other prescribed drugs taken by participants as part of OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations) during open label phase.
In Study-off Drug (ISOD), Open Label Participants from maraviroc QD, maraviroc BID and Placebo (double blind phase) who received no study treatment along with OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations) during open label phase.
Maraviroc BID, Observation Phase Participants continuing from open label phase, who received maraviroc 150 or 300 mg BID in the morning and evening, dose adjusted according to the other prescribed drugs taken by participants as part of OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations) during observational phase.
In Study-off Drug (ISOD), Observation Phase Participants continuing from open label phase, who received no study treatment along with OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations) during observational phase.

Participant Flow for 3 periods

Period 1:   Double Blind Phase
    Maraviroc QD, Double Blind     Maraviroc BID, Double Blind     Placebo, Double Blind     Maraviroc BID, Open Label     In Study-off Drug (ISOD), Open Label     Maraviroc BID, Observation Phase     In Study-off Drug (ISOD), Observation Phase  
STARTED     186     194     94     0     0     0     0  
Treated     182     191     91     0     0     0     0  
COMPLETED     0     0     0     0     0     0     0  
NOT COMPLETED     186     194     94     0     0     0     0  
Adverse Event                 7                 7                 3                 0                 0                 0                 0  
Death                 2                 5                 0                 0                 0                 0                 0  
Lack of Efficacy                 21                 23                 15                 0                 0                 0                 0  
Participant defaulted                 16                 11                 9                 0                 0                 0                 0  
Pregnancy                 1                 0                 0                 0                 0                 0                 0  
Randomized, not treated                 4                 3                 3                 0                 0                 0                 0  
Ongoing at cut-off date                 128                 137                 57                 0                 0                 0                 0  
Unspecified                 7                 8                 7                 0                 0                 0                 0  

Period 2:   Open Label Phase
    Maraviroc QD, Double Blind     Maraviroc BID, Double Blind     Placebo, Double Blind     Maraviroc BID, Open Label     In Study-off Drug (ISOD), Open Label     Maraviroc BID, Observation Phase     In Study-off Drug (ISOD), Observation Phase  
STARTED     0     0     0     272     50     0     0  
COMPLETED     0     0     0     0     0     0     0  
NOT COMPLETED     0     0     0     272     50     0     0  
Adverse Event                 0                 0                 0                 5                 0                 0                 0  
Death                 0                 0                 0                 2                 0                 0                 0  
Lack of Efficacy                 0                 0                 0                 8                 0                 0                 0  
Pregnancy                 0                 0                 0                 1                 0                 0                 0  
Participant defaulted                 0                 0                 0                 18                 0                 0                 0  
Ongoing at cut-off date                 0                 0                 0                 220                 50                 0                 0  
Unspecified                 0                 0                 0                 18                 0                 0                 0  

Period 3:   Observation Phase
    Maraviroc QD, Double Blind     Maraviroc BID, Double Blind     Placebo, Double Blind     Maraviroc BID, Open Label     In Study-off Drug (ISOD), Open Label     Maraviroc BID, Observation Phase     In Study-off Drug (ISOD), Observation Phase  
STARTED     0     0     0     0     0     205     65  
COMPLETED     0     0     0     0     0     160     48  
NOT COMPLETED     0     0     0     0     0     45     17  
Death                 0                 0                 0                 0                 0                 5                 3  
Lack of Efficacy                 0                 0                 0                 0                 0                 2                 0  
Participant defaulted                 0                 0                 0                 0                 0                 17                 4  
Unspecified                 0                 0                 0                 0                 0                 21                 10  



  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 or 300 milligrams (mg) tablet orally once daily (QD) in the evening, dose adjusted according to the other prescribed drugs taken by participants as part of optimized background therapy (OBT) selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations). Placebo matched to maraviroc tablet orally in the morning.
Maraviroc BID Maraviroc 150 or 300 mg tablet orally twice daily (BID) in the morning and evening, dose adjusted according to the other prescribed drugs taken by participants as part of OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations).
Placebo Placebo matched to maraviroc tablet orally BID in the morning and evening, in combination with OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations).
Total Total of all reporting groups

Baseline Measures
    Maraviroc QD     Maraviroc BID     Placebo     Total  
Number of Participants  
[units: participants]
  182     191     91     464  
Age, Customized [1]
[units: participants]
       
Less than 18 years     1     0     0     1  
18 to 24 years     1     1     0     2  
25 to 34 years     8     9     6     23  
35 to 44 years     85     71     40     196  
45 to 54 years     63     70     32     165  
55 to 64 years     19     37     11     67  
Greater than or equal to 65 years     5     3     2     10  
Gender [2]
[units: participants]
       
Female     29     21     12     62  
Male     153     170     79     402  
[1] Out of a total of 474 participants, data for baseline measure (age) was available for 464 participants who were treated.
[2] Out of a total of 474 participants, data for baseline measure (gender) was available for 464 participants who were treated.



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Log 10-transformed Human Immunodeficiency Virus Ribonucleic Acid (HIV-1 RNA) Levels at Baseline   [ Time Frame: Baseline ]

2.  Primary:   Change From Baseline in Log 10-transformed HIV-1 RNA Levels at Week 24   [ Time Frame: Baseline and Week 24 ]

3.  Primary:   Change From Baseline in Log 10-transformed HIV-1 RNA Levels at Week 48   [ Time Frame: Baseline and Week 48 ]

4.  Secondary:   Percentage of Participants With HIV-1 RNA Levels Less Than 400 Copies/mL   [ Time Frame: Week 24 and 48 ]

5.  Secondary:   Percentage of Participants With HIV-1 RNA Levels Less Than 400 Copies/ml or With at Least 0.5 log10 Decrease From Baseline   [ Time Frame: Week 24 and 48 ]

6.  Secondary:   Percentage of Participants With HIV-1 RNA Levels Less Than 400 Copies/ml or With at Least 1.0 log10 Decrease From Baseline   [ Time Frame: Week 24 and 48 ]

7.  Secondary:   Percentage of Participants With HIV-1 RNA Levels Less Than 50 Copies/mL   [ Time Frame: Week 24 and 48 ]

8.  Secondary:   Cluster of Differentiation 4 (CD4) and Cluster of Differentiation 8 (CD8) Cell Count at Baseline   [ Time Frame: Baseline ]

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

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

11.  Secondary:   Time to Virological Failure   [ Time Frame: Week 48 ]

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

13.  Secondary:   Number of Participants With Genotypic Susceptibility Score (GSS) and Phenotypic Susceptibility Score (PSS) at Screening   [ Time Frame: Screening ]

14.  Secondary:   Number of Participants With Change in GSS and PSS From Screening at the Time of Treatment Failure Through Week 24   [ Time Frame: Screening and time of failure through Week 24 ]

15.  Secondary:   Number of Participants With Change in GSS and PSS From Screening at the Time of Treatment Failure Through Week 48   [ Time Frame: Screening and time of failure through Week 48 ]
  Hide Outcome Measure 15

Measure Type Secondary
Measure Title Number of Participants With Change in GSS and PSS From Screening at the Time of Treatment Failure Through Week 48
Measure Description Number of participants with GSS and PSS were used as surrogates for genotype and phenotype. Genotypic and phenotypic resistance to PIs, NRTIs, NNRTIs were evaluated at screening and time of treatment failure analyzed through Week 48 visit, by Monogram Biosciences PhenoSense GT assay. Score was determined for each drug in OBT, giving 1:drug ‘sensitive'/'susceptible' and 0:'resistant'. GSS and PSS score range:0 to >3. Genotypic enfuvirtide value was used for PSS, no phenotypic enfuvirtide was recorded.
Time Frame Screening and time of failure through Week 48  
Safety Issue No  

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.
FAS; 'N' (number of participants analyzed) is signifying those participants who experienced treatment failure defined as discontinuation due to insufficient response. 'n' is number of participants who were evaluable for the given change in GSS and PSS score for each arm group respectively.

Reporting Groups
  Description
Maraviroc QD Maraviroc 150 or 300 milligrams (mg) tablet orally once daily (QD) in the evening, dose adjusted according to the other prescribed drugs taken by participants as part of optimized background therapy (OBT) selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations). Placebo matched to maraviroc tablet orally in the morning.
Maraviroc BID Maraviroc 150 or 300 mg tablet orally twice daily (BID) in the morning and evening, dose adjusted according to the other prescribed drugs taken by participants as part of OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations).
Placebo Placebo matched to maraviroc tablet orally BID in the morning and evening, in combination with OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations).

Measured Values
    Maraviroc QD     Maraviroc BID     Placebo  
Number of Participants Analyzed  
[units: participants]
  41     38     49  
Number of Participants With Change in GSS and PSS From Screening at the Time of Treatment Failure Through Week 48  
[units: participants]
     
Change in GSS by less than -3 (n= 35, 33, 46)     0     1     0  
Change in GSS by -3 (n= 35, 33, 46)     0     0     0  
Change in GSS by -2 (n= 35, 33, 46)     0     0     2  
Change in GSS by -1 (n= 35, 33, 46)     12     6     17  
Change in GSS by 0 (n= 35, 33, 46)     23     22     24  
Change in GSS by 1 (n= 35, 33, 46)     0     4     2  
Change in GSS by 2 (n= 35, 33, 46)     0     0     1  
Change in GSS by 3 (n= 35, 33, 46)     0     0     0  
Change in GSS by greater than 3 (n= 35, 33, 46)     0     0     0  
Change in PSS by less than -3 (n= 35, 32, 46)     0     0     0  
Change in PSS by -3 (n= 35, 32, 46)     1     0     3  
Change in PSS by -2 (n= 35, 32, 46)     3     3     4  
Change in PSS by -1 (n= 35, 32, 46)     13     9     18  
Change in PSS by 0 (n= 35, 32, 46)     16     19     19  
Change in PSS by 1 (n= 35, 32, 46)     2     0     2  
Change in PSS by 2 (n= 35, 32, 46)     0     1     0  
Change in PSS by 3 (n= 35, 32, 46)     0     0     0  
Change in PSS by greater than 3 (n= 35, 32, 46)     0     0     0  

No statistical analysis provided for Number of Participants With Change in GSS and PSS From Screening at the Time of Treatment Failure Through Week 48



16.  Secondary:   Number of Participants Per Tropism Status at Baseline and at the Time of Treatment Failure Through Week 24   [ Time Frame: Baseline and time of failure through Week 24 ]

17.  Secondary:   Number of Participants Per Tropism Status at Baseline and at the Time of Treatment Failure Through Week 48   [ Time Frame: Baseline and time of failure through Week 48 ]

18.  Secondary:   Change From Baseline in Viral Load at Week 24 and Week 48 by Overall Susceptibility Score (OSS) at Screening   [ Time Frame: Baseline, Week 24 and Week 48 ]


  Serious Adverse Events


  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
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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.


Results Point of Contact:  
Name/Title: Pfizer ClinicalTrials.gov Call Center
Organization: Pfizer, Inc.
phone: 1-800-718-1021
e-mail: ClinicalTrials.gov_Inquiries@pfizer.com


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Publications automatically indexed to this study:

Responsible Party: ViiV Healthcare
ClinicalTrials.gov Identifier: NCT00098722     History of Changes
Other Study ID Numbers: A4001028
Study First Received: December 7, 2004
Results First Received: April 16, 2012
Last Updated: April 16, 2012
Health Authority: United States: Food and Drug Administration