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Strategy-confirming Study of BMS-955176 to Treat HIV-1 Infected Treatment-experienced Adults

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ClinicalTrials.gov Identifier: NCT02386098
Recruitment Status : Terminated (GI Intolerability)
First Posted : March 11, 2015
Results First Posted : August 20, 2018
Last Update Posted : August 20, 2018
Sponsor:
Collaborator:
GlaxoSmithKline
Information provided by (Responsible Party):
ViiV Healthcare

Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition: HIV Infections
Interventions: Drug: BMS-955176
Drug: Atazanavir (ATV)
Drug: Ritonavir (RTV)
Drug: Dolutegravir (DTG)
Drug: Tenofovir (TDF)

  Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
This study was planned to be conducted in two Stages (96 weeks each); but was terminated early during Stage 1 due to high rates of gastrointestinal (GI) intolerability and early end of the concurrent, 205891 (NCT02415595) formal dose-finding study. Hence, data was collected only in Stage 1 and no participants were enrolled in Stage 2.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
A total of 288 participants were screened, of which 86 were randomized in a ratio of 1:1 to one of the two treatment arms in Stage 1.

Reporting Groups
  Description
Stage 1: BMS-955176 120 mg QD+ATV/r 300/100 mg QD+DTG 50 mg QD Participants were administered a once daily (QD) oral dose of 120 milligram (mg) BMS-955176 in combination with atazanavir boosted with ritonavir (ATV/r) 300/100 mg QD and dolutegravir (DTG) 50 mg QD for a duration of 96 weeks. The doses were administered in the morning with a meal.
Stage 1: TDF 300 mg QD+ATV/r 300/100 mg QD+DTG 50 mg QD Participants were administered a QD oral dose of 300 mg tenofovir (TDF) in combination with ATV/r 300/100 mg QD and DTG 50 mg QD for a duration of 96 weeks. The doses were administered in the morning with a meal.
Stage 2: BMS-955176 120 mg QD+ATV 400 mg QD+DTG 50 mg QD Participants were planned to be administered a QD oral dose of 120 mg BMS-955176 in combination with atazanavir without ritonavir (ATV) 400 mg QD and DTG 50 mg QD for a duration of 96 weeks.
Stage 2: BMS-955176 180 mg QD+ATV 400 mg QD+DTG 50 mg QD Participants were planned to be administered a QD oral dose of 180 mg BMS-955176 in combination with ATV 400 mg QD and DTG 50 mg QD for a duration of 96 weeks.
Stage 2: TDF 300 mg QD+ATV/r 300/100 mg QD+DTG 50 mg QD Participants were planned to be administered a QD oral dose of 300 mg TDF in combination with ATV/r 300/100 mg QD and DTG 50 mg QD for a duration of 96 weeks.

Participant Flow for 2 periods

Period 1:   Stage 1 (96 Weeks)
    Stage 1: BMS-955176 120 mg QD+ATV/r 300/100 mg QD+DTG 50 mg QD   Stage 1: TDF 300 mg QD+ATV/r 300/100 mg QD+DTG 50 mg QD   Stage 2: BMS-955176 120 mg QD+ATV 400 mg QD+DTG 50 mg QD   Stage 2: BMS-955176 180 mg QD+ATV 400 mg QD+DTG 50 mg QD   Stage 2: TDF 300 mg QD+ATV/r 300/100 mg QD+DTG 50 mg QD
STARTED   43   43   0   0   0 
COMPLETED   0   0   0   0   0 
NOT COMPLETED   43   43   0   0   0 
Other: Administrative reason by sponsor                30                29                0                0                0 
Adverse Event                2                1                0                0                0 
Lost to Follow-up                2                2                0                0                0 
Other:Protocol defined stopping criteria                0                2                0                0                0 
Withdrawal by Subject                3                1                0                0                0 
Other                1                0                0                0                0 
Other: Breach of good clinical practice                5                8                0                0                0 

Period 2:   Stage 2 (96 Weeks)
    Stage 1: BMS-955176 120 mg QD+ATV/r 300/100 mg QD+DTG 50 mg QD   Stage 1: TDF 300 mg QD+ATV/r 300/100 mg QD+DTG 50 mg QD   Stage 2: BMS-955176 120 mg QD+ATV 400 mg QD+DTG 50 mg QD   Stage 2: BMS-955176 180 mg QD+ATV 400 mg QD+DTG 50 mg QD   Stage 2: TDF 300 mg QD+ATV/r 300/100 mg QD+DTG 50 mg QD
STARTED   0   0   0   0   0 
COMPLETED   0   0   0   0   0 
NOT COMPLETED   0   0   0   0   0 



  Baseline Characteristics

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.
Modified intent to treat (mITT) Population comprised of randomized participants who received at least one dose of BMS-955176 or TDF. Data from 13 participants randomized at a single site were excluded due to a breach of good clinical practice (GCP) that indicated participants may not have been properly consented to participate in the study.

Reporting Groups
  Description
Stage 1: BMS-955176 120 mg QD+ATV/r 300/100 mg QD+DTG 50 mg QD Participants were administered a once daily (QD) oral dose of 120 milligram (mg) BMS-955176 in combination with atazanavir boosted with ritonavir (ATV/r) 300/100 mg QD and dolutegravir (DTG) 50 mg QD for a duration of 96 weeks. The doses were administered in the morning with a meal.
Stage 1: TDF 300 mg QD+ATV/r 300/100 mg QD+DTG 50 mg QD Participants were administered a QD oral dose of 300 mg tenofovir (TDF) in combination with ATV/r 300/100 mg QD and DTG 50 mg QD for a duration of 96 weeks. The doses were administered in the morning with a meal.
Stage 2: BMS-955176 120 mg QD+ATV 400 mg QD+DTG 50 mg QD Participants were planned to be administered a QD oral dose of 120 mg BMS-955176 in combination with atazanavir without ritonavir (ATV) 400 mg QD and DTG 50 mg QD for a duration of 96 weeks.
Stage 2: BMS-955176 180 mg QD+ATV 400 mg QD+DTG 50 mg QD Participants were planned to be administered a QD oral dose of 180 mg BMS-955176 in combination with ATV 400 mg QD and DTG 50 mg QD for a duration of 96 weeks.
Stage 2: TDF 300 mg QD+ATV/r 300/100 mg QD+DTG 50 mg QD Participants were planned to be administered a QD oral dose of 300 mg TDF in combination with ATV/r 300/100 mg QD and DTG 50 mg QD for a duration of 96 weeks.
Total Total of all reporting groups

Baseline Measures
   Stage 1: BMS-955176 120 mg QD+ATV/r 300/100 mg QD+DTG 50 mg QD   Stage 1: TDF 300 mg QD+ATV/r 300/100 mg QD+DTG 50 mg QD   Stage 2: BMS-955176 120 mg QD+ATV 400 mg QD+DTG 50 mg QD   Stage 2: BMS-955176 180 mg QD+ATV 400 mg QD+DTG 50 mg QD   Stage 2: TDF 300 mg QD+ATV/r 300/100 mg QD+DTG 50 mg QD   Total 
Overall Participants Analyzed 
[Units: Participants]
 38   35   0   0   0   73 
Age 
[Units: Years]
Mean (Standard Deviation)
 39.8  (11.45)   41.7  (12.06)            40.7  (11.70) 
Sex: Female, Male 
[Units: Participants]
Count of Participants
           
Female      7  18.4%      8  22.9%               15  20.5% 
Male      31  81.6%      27  77.1%               58  79.5% 
Race/Ethnicity, Customized 
[Units: Participants]
Count of Participants
           
White      14  36.8%      17  48.6%               31  42.5% 
Black/African American      6  15.8%      2   5.7%               8  11.0% 
Asian      4  10.5%      4  11.4%               8  11.0% 
Unknown      14  36.8%      12  34.3%               26  35.6% 


  Outcome Measures

1.  Primary:   Percentage of Participants With Plasma Human Immunodeficiency Virus-1 (HIV-1) Ribonucleic Acid (RNA) <40 Copies Per Milliliter (c/mL) at Week 24-Stage 1   [ Time Frame: Week 24 ]

2.  Primary:   Percentage of Participants With Plasma HIV-1 RNA <40 c/mL at Week 24-Stage 2   [ Time Frame: Week 24 ]

3.  Secondary:   Percentage of Participants With Plasma HIV-1 RNA <40 c/mL at Weeks 48 and 96-Stage 1   [ Time Frame: Weeks 48 and 96 ]

4.  Secondary:   Percentage of Participants With Plasma HIV-1 RNA <40 c/mL at Weeks 48 and 96-Stage 2   [ Time Frame: Weeks 48 and 96 ]

5.  Secondary:   Percentage of Participants With HIV-1 RNA <200 c/mL at Weeks 24, 48 and 96-Stage 1   [ Time Frame: Weeks 24, 48 and 96 ]

6.  Secondary:   Percentage of Participants With HIV-1 RNA <200 c/mL at Weeks 24, 48 and 96-Stage 2   [ Time Frame: Weeks 24, 48 and 96 ]

7.  Secondary:   Change From Baseline in Logarithm to the Base 10 (log10) HIV-1 RNA Over Time-Stage 1   [ Time Frame: Baseline and up to Week 72 ]

8.  Secondary:   Change From Baseline in log10 HIV-1 RNA Over Time-Stage 2   [ Time Frame: Baseline and up to Week 96 ]

9.  Secondary:   Change From Baseline in Cluster of Differentiation 4+ (CD4+) Cell Count Over Time-Stage 1   [ Time Frame: Baseline and up to Week 72 ]

10.  Secondary:   Change From Baseline in CD4+ Cell Count Over Time-Stage 2   [ Time Frame: Baseline and up to Week 96 ]

11.  Secondary:   Change From Baseline in Percentage of CD4+ Cells Over Time-Stage 1   [ Time Frame: Baseline and up to Week 72 ]

12.  Secondary:   Change From Baseline in Percentage of CD4+ Cells Over Time-Stage 2   [ Time Frame: Baseline and up to Week 96 ]

13.  Secondary:   Number of Participants With Serious Adverse Events (SAEs) and Adverse Events (AEs) Leading to Discontinuation (AELD)-Stage 1   [ Time Frame: Up to Week 96 ]

14.  Secondary:   Number of Participants With SAEs and AELDs-Stage 2   [ Time Frame: Up to Week 96 ]

15.  Secondary:   Number of Participants With Occurrence of New Acquired Immunodeficiency Syndrome (AIDS) Defining Events-Stage 1   [ Time Frame: Up to Week 96 ]

16.  Secondary:   Number of Participants With Occurrence of New AIDS Defining Events-Stage 2   [ Time Frame: Up to Week 96 ]

17.  Secondary:   Maximum Observed Concentration (Cmax) for BMS-955176-Stage 1   [ Time Frame: Week 2 (pre-dose, 1, 2, 2.5, 3, 4, 4.5, 5, 6, 8, 12 hours post-dose and 24 hours [morning pre-dose]) ]

18.  Secondary:   Cmax for BMS-955176-Stage 2   [ Time Frame: Week 2 (pre-dose, 1, 2, 2.5, 3, 4, 4.5, 5, 6, 8, 12 hours post-dose and 24 hours [morning pre-dose]) ]

19.  Secondary:   Time of Maximum Observed Plasma Concentration (Tmax) for BMS-955176-Stage 1   [ Time Frame: Week 2 (pre-dose, 1, 2, 2.5, 3, 4, 4.5, 5, 6, 8, 12 hours post-dose and 24 hours [morning pre-dose]) ]

20.  Secondary:   Tmax for BMS-955176-Stage 2   [ Time Frame: Week 2 (pre-dose, 1, 2, 2.5, 3, 4, 4.5, 5, 6, 8, 12 hours post-dose and 24 hours [morning pre-dose]) ]

21.  Secondary:   Observed Plasma Concentration at the End of a Dosing Interval (Ctau) for BMS-955176-Stage 1   [ Time Frame: Week 2 (pre-dose, 1, 2, 2.5, 3, 4, 4.5, 5, 6, 8, 12 hours post-dose and 24 hours [morning pre-dose]) ]

22.  Secondary:   Ctau for BMS-955176-Stage 2   [ Time Frame: Week 2 (pre-dose, 1, 2, 2.5, 3, 4, 4.5, 5, 6, 8, 12 hours post-dose and 24 hours [morning pre-dose]) ]

23.  Secondary:   Observed Pre-dose Plasma Concentration (C0) for BMS-955176-Stage 1   [ Time Frame: Week 2 (pre-dose, 1, 2, 2.5, 3, 4, 4.5, 5, 6, 8, 12 hours post-dose and 24 hours [morning pre-dose]) ]

24.  Secondary:   C0 for BMS-955176-Stage 2   [ Time Frame: Week 2 (pre-dose, 1, 2, 2.5, 3, 4, 4.5, 5, 6, 8, 12 hours post-dose and 24 hours [morning pre-dose]) ]

25.  Secondary:   Area Under the Concentration-time Curve in One Dosing Interval (AUC[Tau]) for BMS-955176-Stage 1   [ Time Frame: Week 2 (pre-dose, 1, 2, 2.5, 3, 4, 4.5, 5, 6, 8, 12 hours post-dose and 24 hours [morning pre-dose]) ]

26.  Secondary:   AUC(Tau) for BMS-955176-Stage 2   [ Time Frame: Week 2 (pre-dose, 1, 2, 2.5, 3, 4, 4.5, 5, 6, 8, 12 hours post-dose and 24 hours [morning pre-dose]) ]

27.  Secondary:   Number of Participants With Emergence of HIV Drug Resistance-Stage 1   [ Time Frame: Up to Week 96 ]

28.  Secondary:   Number of Participants With Emergence of HIV Drug Resistance-Stage 2   [ Time Frame: Up to Week 96 ]


  Serious Adverse Events


  Other Adverse Events


  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.


  More Information

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: GSK Response Center
Organization: GlaxoSmithKline
phone: 866-435-7343
e-mail: GSKClinicalSupportHD@gsk.com



Responsible Party: ViiV Healthcare
ClinicalTrials.gov Identifier: NCT02386098     History of Changes
Other Study ID Numbers: 205892
AI468-048 ( Other Identifier: Bristol-Myers Squibb )
First Submitted: March 6, 2015
First Posted: March 11, 2015
Results First Submitted: June 4, 2018
Results First Posted: August 20, 2018
Last Update Posted: August 20, 2018