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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 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
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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 
Overall Participants Analyzed 
[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 
[1] Out of a total of 474 participants, data for baseline measure (age) was available for 464 participants who were treated.
Gender [1] 
[Units: Participants]
       
Female   29   21   12   62 
Male   153   170   79   402 
[1] Out of a total of 474 participants, data for baseline measure (gender) was available for 464 participants who were treated.


  Outcome Measures
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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 ]

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 ]
  Hide Outcome Measure 16

Measure Type Secondary
Measure Title Number of Participants Per Tropism Status at Baseline and at the Time of Treatment Failure Through Week 24
Measure Description Number of participants per tropism status (C-X-C chemokine receptor 5 {CCR5} [R5], C-X-C chemokine receptor type 4 {CXCR4} [X4], Dual/Mixed [DM], or Non-reportable/Non-phenotypable [NR/NP]) at baseline and time of treatment failure analyzed through week 24 visit. Treatment failure defined as discontinuation due to insufficient clinical response. HIV-1 RNA viral load <500 copies/ml categorized as below lower limit of quantification (BLQ). The assessment for time of treatment failure was defined as the last on treatment assessment.
Time Frame Baseline and time of failure through Week 24  
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 and had tropism assessment at baseline.

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 
Participants Analyzed 
[Units: Participants]
 26   31   44 
Number of Participants Per Tropism Status at Baseline and at the Time of Treatment Failure Through Week 24 
[Units: Participants]
     
Baseline: R5; Treatment failure: R5   8   7   36 
Baseline: R5; Treatment failure: X4   2   2   0 
Baseline: R5; Treatment failure: DM   5   6   3 
Baseline: R5; Treatment failure: NR/NP   6   5   2 
Baseline: DM; Treatment failure: R5   1   0   2 
Baseline: DM; Treatment failure: X4   0   2   0 
Baseline: DM; Treatment failure: DM   3   7   0 
Baseline: DM; Treatment failure: NR/NP   0   1   0 

No statistical analysis provided for Number of Participants Per Tropism Status at Baseline and at the Time of Treatment 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