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Clinical Trial Results:
A Phase IIb Randomized, Controlled, Partially Blinded Clinical Trial to Investigate Safety, Efficacy and Dose-response of BMS-986001 in Treatment-naive HIV-1-infected Subjects, Followed by an Open-label Period on the Recommended Dose.

Summary
EudraCT number	2011-003329-89
Trial protocol	HU ES DE PL
Global end of trial date	11 Jul 2014

Results information
Results version number	v1(current)
This version publication date	24 Nov 2016
First version publication date	24 Nov 2016
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

AI467-003

ISRCTN number

US NCT number

NCT01489046

WHO universal trial number (UTN)

Sponsor organisation name

Bristol-Myers Squibb

Sponsor organisation address

Chausée de la Hulpe 185,, Brussels, Belgium, 1170

Public contact

Bristol-Myers Squibb Study Director, Bristol-Myers Squibb International Corporation, clinical.trials@bms.com

Scientific contact

Bristol-Myers Squibb Study Director, Bristol-Myers Squibb International Corporation, clinical.trials@bms.com

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

11 Jul 2014

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

11 Jul 2014

Was the trial ended prematurely?

Yes

Main objective of the trial

The main objectives of this trial were to assess the efficacy of three doses of BMS-986001 by determining the proportion of subjects with plasma HIV-1 RNA < 50 c/mL as measured by PCR analyses at Week 24 and to assess the safety of three doses of BMS-986001 in treatment-naive HIV-1 infected subjects as measured by numbers of subjects with SAEs and numbers of subjects with AEs leading to discontinuations through Week 24.

Protection of trial subjects

The study was in compliance with the ethical principles derived from the Declaration of Helsinki and in compliance with all International Conference on Harmonization Good Clinical Practice Guidelines. All the local regulatory requirements pertinent to safety of trial subjects were followed.

Background therapy

Subjects in all 4 treatment groups received once daily (QD) efavirenz (EFV) 600 mg and lamivudine (3TC) 300 mg in addition to their assigned blinded study therapy. EFV and 3TC were open label throughout the study. All doses were taken daily on an empty stomach at bedtime.

Evidence for comparator

Per current HIV guidelines an early start of antiretroviral (ARV) therapy is recommended while subjects have higher CD4+ T-cell counts. Tenofovir disoproxil fumarate (TDF), a nucleoside/nucleotide reverse transcriptase inhibitor (NRTI), is a widely used first-line regimen, but there are concerns about potential long-term toxicities.

Actual start date of recruitment

21 Mar 2012

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Spain: 17

Country: Number of subjects enrolled

France: 1

Country: Number of subjects enrolled

Hungary: 1

Country: Number of subjects enrolled

Australia: 10

Country: Number of subjects enrolled

Canada: 5

Country: Number of subjects enrolled

Chile: 22

Country: Number of subjects enrolled

Colombia: 16

Country: Number of subjects enrolled

Mexico: 9

Country: Number of subjects enrolled

Peru: 83

Country: Number of subjects enrolled

South Africa: 385

Country: Number of subjects enrolled

Thailand: 124

Country: Number of subjects enrolled

United States: 84

Worldwide total number of subjects

757

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

756

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

The study was conducted at 41 sites in 12 countries.

Screening details

757 subjects enrolled, 301 subjects were randomized. Reasons not randomized: 14 withdrew consent, 4 lost to follow-up, 1 administrative reason by sponsor, 414 no longer met study criteria, 1 poor/non-compliance, 22 other. 297 subjects treated. Reasons not treated: 2 no longer met study criteria, 2 withdrew consent.

Period 1 title

Treatment Stage 1 (up to Week 96)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Carer, Assessor

Blinding implementation details

Blinding was conducted up to the Week 48 analysis. After Week 48, the study was un-blinded for the rest of the trial.

Are arms mutually exclusive

Yes

BMS-986001 100 mg QD + EFV 600 mg QD + 3TC 300 mg QD

Arm description

In Stage 1, subjects were administered a QD dose of 100 mg BMS-986001, 600 mg EFV, and 300 mg 3TC under fasted conditions at bedtime. While blinded, subjects took 4 capsules, 1 from each of 4 bottles that were a blinded combination of 100 mg active dose of BMS-986001 and matched-placebo. Dosing was open-label for EFV and 3TC. After the Week 48 analysis, the study became un-blinded and subjects switched to an optimal QD dose of 400 mg BMS-986001, 600 mg EFV, and 300 mg 3TC under fasted conditions at bedtime through the rest of stage 1.

Arm type

Experimental

Investigational medicinal product name

BMS-986001

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule, hard

Routes of administration

Oral use

Dosage and administration details

Up to the Week 48 analysis, subjects were administered a QD dose of 100 mg BMS-986001 under fasted conditions at bedtime. After the Week 48 analysis, subjects were switched to the optimal QD dose of 400 mg BMS-986001 under fasted conditions at bedtime. The therapy was administered as a two piece, gray, opaque, size #0, hard gelatin capsule filled with white to off-white powder.

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule, hard

Routes of administration

Oral use

Dosage and administration details

Subjects were administered a QD dose of placebo matching to BMS-986001 under fasted conditions at bedtime. The therapy was administered as a two piece, gray, opaque, size #0, hard gelatin capsule filled with white to off-white powder.

Investigational medicinal product name

EFV

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Subjects were administered a QD dose of 600 mg EFV under fasted conditions at bedtime. The therapy was administered as a yellow capsular shaped film-coated tablet. Upon sponsor request EFV could also be administered as three 200mg tablets.

Investigational medicinal product name

3TC

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Subjects were administered a QD dose of 300 mg 3TC under fasted conditions at bedtime. The therapy was administered as a grey diamond-shaped film-coated tablet.

BMS-986001 200 mg QD + EFV 600 mg QD + 3TC 300 mg QD

Arm description

Arm type

Experimental

Investigational medicinal product name

BMS-986001

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule, hard

Routes of administration

Oral use

Dosage and administration details

Up to the Week 48 analysis, subjects were administered a QD dose of 200 mg BMS-986001 under fasted conditions at bedtime. After the Week 48 analysis, subjects were switched to the optimal QD dose of 400 mg BMS-986001 under fasted conditions at bedtime. The therapy was administered as a two piece, gray, opaque, size #0, hard gelatin capsule filled with white to off-white powder.

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule, hard

Routes of administration

Oral use

Dosage and administration details

Investigational medicinal product name

EFV

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Investigational medicinal product name

3TC

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Subjects were administered a QD dose of 300 mg 3TC under fasted conditions at bedtime. The therapy was administered as a grey diamond-shaped film-coated tablet.

BMS-986001 400 mg QD + EFV 600 mg QD + 3TC 300 mg QD

Arm description

In Stage 1, subjects were administered a QD dose of 400 mg BMS-986001, 600 mg EFV, and 300 mg 3TC under fasted conditions at bedtime. While blinded, subjects took 4 capsules, 1 from each of 4 bottles that were a blinded combination of 400 mg active dose of BMS-986001. Dosing was open-label for EFV and 3TC. After the Week 48 analysis, the study became un-blinded and subjects continued the optimal QD dose of 400 mg BMS-986001, 600 mg EFV, and 300 mg 3TC under fasted conditions at bedtime through the rest of stage 1.

Arm type

Experimental

Investigational medicinal product name

BMS-986001

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule, hard

Routes of administration

Oral use

Dosage and administration details

Up to the Week 48 analysis, subjects were administered a QD dose of 400 mg BMS-986001 under fasted conditions at bedtime. After the Week 48 analysis, subjects continued at the optimal QD dose of 400 mg BMS-986001 under fasted conditions at bedtime. The therapy was administered as a two piece, gray, opaque, size #0, hard gelatin capsule filled with white to off-white powder.

Investigational medicinal product name

EFV

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Investigational medicinal product name

3TC

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Subjects were administered a QD dose of 300 mg 3TC under fasted conditions at bedtime. The therapy was administered as a grey diamond-shaped film-coated tablet.

TDF 300 mg QD + EFV 600 mg QD + 3TC 300 mg QD

Arm description

In Stage 1, subjects were administered a QD dose of 300 mg TDF, 600 mg EFV, and 300 mg 3TC under fasted conditions at bedtime. Dosing was open-label for TDF, EFV and 3TC.

Arm type

Active comparator

Investigational medicinal product name

TDF

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Subjects were administered a QD dose of 300 mg TDF under fasted conditions at bedtime. The therapy was administered as an almond-shaped light blue film-coated tablet.

Investigational medicinal product name

EFV

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Investigational medicinal product name

3TC

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Subjects were administered a QD dose of 300 mg 3TC under fasted conditions at bedtime. The therapy was administered as a grey diamond-shaped film-coated tablet.

Number of subjects in period 1 ^[1]	BMS-986001 100 mg QD + EFV 600 mg QD + 3TC 300 mg QD	BMS-986001 200 mg QD + EFV 600 mg QD + 3TC 300 mg QD	BMS-986001 400 mg QD + EFV 600 mg QD + 3TC 300 mg QD	TDF 300 mg QD + EFV 600 mg QD + 3TC 300 mg QD
Started	65	67	66	99
Completed	34	38	40	44
Not completed	31	29	26	55
Consent withdrawn by subject	1	2	-	4
Poor/Non-Compliance	1	-	1	2
Adverse event, non-fatal	1	5	3	4
Other	-	-	-	1
Subject No Longer Met Study Criteria	7	6	2	-
Pregnancy	1	-	-	2
Subject Request to Discontinue Study Treatment	-	-	1	2
Lost to follow-up	6	3	3	10
Administrative Reason by Sponsor	12	13	15	29
Lack of efficacy	2	-	1	1

Notes
[1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
Justification: The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial as out of 757 subjects who were enrolled, 297 subjects were treated in the study.

Period 2 title

Treatment Stage 2 (post Week 96)

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

BMS-986001 100 mg QD + EFV 600 mg QD + 3TC 300 mg QD

Arm description

In Stage 2, subjects continued the un-blinded, post-Week 48 treatment regimen from Stage 1 which consisted of an optimal QD dose of 400 mg BMS-986001, 600 mg EFV, and 300 mg 3TC under fasted conditions at bedtime. During Stage 1 (prior to Week 48), the subjects in this group were originally administered a blinded QD dose of 100 mg BMS-986001, 600 mg EFV, and 300 mg 3TC under fasted conditions at bedtime.

Arm type

Experimental

Investigational medicinal product name

BMS-986001

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule, hard

Routes of administration

Oral use

Dosage and administration details

In Stage 2, subjects continued the post-Week 48 regimen where they were administered the optimal QD dose of 400 mg BMS-986001 under fasted conditions at bedtime. Prior to Week 48, subjects were originally administered a QD dose of 100 mg BMS-986001 under fasted conditions at bedtime. The therapy was administered as a two piece, gray, opaque, size #0, hard gelatin capsule filled with white to off-white powder.

Investigational medicinal product name

EFV

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Investigational medicinal product name

3TC

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Subjects were administered a QD dose of 300 mg 3TC under fasted conditions at bedtime. The therapy was administered as a grey diamond-shaped film-coated tablet.

BMS-986001 200 mg QD + EFV 600 mg QD + 3TC 300 mg QD

Arm description

In Stage 2, subjects continued the un-blinded, post-Week 48 treatment regimen from Stage 1 which consisted of an optimal QD dose of 400 mg BMS-986001, 600 mg EFV, and 300 mg 3TC under fasted conditions at bedtime. During Stage 1 (prior to Week 48), the subjects in this group were originally administered a blinded QD dose of 200 mg BMS-986001, 600 mg EFV, and 300 mg 3TC under fasted conditions at bedtime.

Arm type

Experimental

Investigational medicinal product name

BMS-986001

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule, hard

Routes of administration

Oral use

Dosage and administration details

In Stage 2, subjects continued the post-Week 48 regimen where they were administered the optimal QD dose of 400 mg BMS-986001 under fasted conditions at bedtime. Prior to Week 48, subjects were originally administered a QD dose of 200 mg BMS-986001 under fasted conditions at bedtime. The therapy was administered as a two piece, gray, opaque, size #0, hard gelatin capsule filled with white to off-white powder.

Investigational medicinal product name

EFV

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Investigational medicinal product name

3TC

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Subjects were administered a QD dose of 300 mg 3TC under fasted conditions at bedtime. The therapy was administered as a grey diamond-shaped film-coated tablet.

BMS-986001 400 mg QD + EFV 600 mg QD + 3TC 300 mg QD

Arm description

In Stage 2, subjects continued the un-blinded, post-Week 48 treatment regimen from Stage 1 which consisted of an optimal QD dose of 400 mg BMS-986001, 600 mg EFV, and 300 mg 3TC under fasted conditions at bedtime. During Stage 1 (prior to Week 48), the subjects in this group were originally administered a blinded QD dose of 400 mg BMS-986001, 600 mg EFV, and 300 mg 3TC under fasted conditions at bedtime.

Arm type

Experimental

Investigational medicinal product name

BMS-986001

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule, hard

Routes of administration

Oral use

Dosage and administration details

Up to the Week 48 analysis, subjects were administered a QD dose of 400 mg BMS-986001 under fasted conditions at bedtime. After the Week 48 analysis, subjects continued the optimal QD dose of 400 mg BMS-986001 under fasted conditions at bedtime. The therapy was administered as a two piece, gray, opaque, size #0, hard gelatin capsule filled with white to off-white powder.

Investigational medicinal product name

EFV

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Investigational medicinal product name

3TC

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Subjects were administered a QD dose of 300 mg 3TC under fasted conditions at bedtime. The therapy was administered as a grey diamond-shaped film-coated tablet.

TDF 300 mg QD + EFV 600 mg QD + 3TC 300 mg QD

Arm description

In Stage 2, subjects continued the treatment regimen from Stage 1 which consisted of a QD dose of 300 mg TDF, 600 mg EFV, and 300 mg 3TC under fasted conditions at bedtime. Dosing was open-label for TDF, EFV and 3TC.

Arm type

Active comparator

Investigational medicinal product name

TDF

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Subjects were administered a QD dose of 300 mg TDF under fasted conditions at bedtime. The therapy was administered as an almond-shaped light blue film-coated tablet.

Investigational medicinal product name

EFV

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Investigational medicinal product name

3TC

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Subjects were administered a QD dose of 300 mg 3TC under fasted conditions at bedtime. The therapy was administered as a grey diamond-shaped film-coated tablet.

Number of subjects in period 2 ^[2]	BMS-986001 100 mg QD + EFV 600 mg QD + 3TC 300 mg QD	BMS-986001 200 mg QD + EFV 600 mg QD + 3TC 300 mg QD	BMS-986001 400 mg QD + EFV 600 mg QD + 3TC 300 mg QD	TDF 300 mg QD + EFV 600 mg QD + 3TC 300 mg QD
Started	20	25	23	22
Completed	0	0	0	0
Not completed	20	25	23	22
Lost to follow-up	1	-	-	-
Administrative Reason by Sponsor	19	25	23	22

Notes
[2] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
Justification: The number of subjects reported to start the period is not consistent with the number completing the preceding period as out of 156 subjects who completed the previous period (Stage 1), only 92 subjects opted to continue to to this period (Stage 2) in the study.

Baseline characteristics

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Reporting group title

BMS-986001 100 mg QD + EFV 600 mg QD + 3TC 300 mg QD

Reporting group description

Reporting group title

BMS-986001 200 mg QD + EFV 600 mg QD + 3TC 300 mg QD

Reporting group description

Reporting group title

BMS-986001 400 mg QD + EFV 600 mg QD + 3TC 300 mg QD

Reporting group description

Reporting group title

TDF 300 mg QD + EFV 600 mg QD + 3TC 300 mg QD

Reporting group description

In Stage 1, subjects were administered a QD dose of 300 mg TDF, 600 mg EFV, and 300 mg 3TC under fasted conditions at bedtime. Dosing was open-label for TDF, EFV and 3TC.

Reporting group values	BMS-986001 100 mg QD + EFV 600 mg QD + 3TC 300 mg QD	BMS-986001 200 mg QD + EFV 600 mg QD + 3TC 300 mg QD	BMS-986001 400 mg QD + EFV 600 mg QD + 3TC 300 mg QD	TDF 300 mg QD + EFV 600 mg QD + 3TC 300 mg QD	Total
Number of subjects	65	67	66	99	297
Age categorical
Units: Subjects
Adults (18 to 64 years)	65	67	66	99	297
Age continuous
Units: years
arithmetic mean (full range (min-max))	32.1 (18 to 64)	32.7 (18 to 53)	34.5 (19 to 57)	31.8 (18 to 61)	-
Gender categorical
Units: Subjects
Female	22	25	25	29	101
Male	43	42	41	70	196
Race
“Other” included Cape colored, South American, multiracial, and mixed
Units: Subjects
White	11	10	7	15	43
Black/African American	31	32	35	40	138
Asian	15	15	14	27	71
Other	8	10	10	17	45
HIV-1 RNA Categories
Units: Subjects
< 30,000 c/mL	37	37	34	61	169
30,000 c/mL to < 100,000 c/mL	17	18	20	21	76
100,000 c/mL to < 500,000 c/mL	10	10	11	17	48
≥ 500,000 c/mL	1	2	1	0	4
CD4+ T-cell Categories
Units: Subjects
100 to < 200 cells/uL	6	3	4	12	25
200 to < 350 cells/uL	40	39	36	59	174
350 to < 500 cells/uL	12	17	20	19	68
≥ 500 cells/uL	7	8	6	9	30
HIV-1 Subtype
Units: Subjects
Type AE	14	13	8	25	60
Type B	28	22	24	36	110
Type BF	0	0	1	1	2
Type C	22	30	29	33	114
Complex	1	2	4	4	11
Plasma HIV-1 RNA
Units: (log 10 c/mL
median (standard deviation)	4.34 ( 0.683 )	4.43 ( 0.6398 )	4.455 ( 0.6361 )	4.38 ( 0.61 )	-
CD4+ T-Cell Counts
Units: cells/UL
median (standard deviation)	290 ( 130.55 )	325 ( 125.36 )	330 ( 138.08 )	301 ( 141.79 )	-

End points

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Reporting group title

BMS-986001 100 mg QD + EFV 600 mg QD + 3TC 300 mg QD

Reporting group description

Reporting group title

BMS-986001 200 mg QD + EFV 600 mg QD + 3TC 300 mg QD

Reporting group description

Reporting group title

BMS-986001 400 mg QD + EFV 600 mg QD + 3TC 300 mg QD

Reporting group description

Reporting group title

TDF 300 mg QD + EFV 600 mg QD + 3TC 300 mg QD

Reporting group description

In Stage 1, subjects were administered a QD dose of 300 mg TDF, 600 mg EFV, and 300 mg 3TC under fasted conditions at bedtime. Dosing was open-label for TDF, EFV and 3TC.

Reporting group title

BMS-986001 100 mg QD + EFV 600 mg QD + 3TC 300 mg QD

Reporting group description

Reporting group title

BMS-986001 200 mg QD + EFV 600 mg QD + 3TC 300 mg QD

Reporting group description

In Stage 2, subjects continued the un-blinded, post-Week 48 treatment regimen from Stage 1 which consisted of an optimal QD dose of 400 mg BMS-986001, 600 mg EFV, and 300 mg 3TC under fasted conditions at bedtime. During Stage 1 (prior to Week 48), the subjects in this group were originally administered a blinded QD dose of 200 mg BMS-986001, 600 mg EFV, and 300 mg 3TC under fasted conditions at bedtime.

Reporting group title

BMS-986001 400 mg QD + EFV 600 mg QD + 3TC 300 mg QD

Reporting group description

In Stage 2, subjects continued the un-blinded, post-Week 48 treatment regimen from Stage 1 which consisted of an optimal QD dose of 400 mg BMS-986001, 600 mg EFV, and 300 mg 3TC under fasted conditions at bedtime. During Stage 1 (prior to Week 48), the subjects in this group were originally administered a blinded QD dose of 400 mg BMS-986001, 600 mg EFV, and 300 mg 3TC under fasted conditions at bedtime.

Reporting group title

TDF 300 mg QD + EFV 600 mg QD + 3TC 300 mg QD

Reporting group description

Primary: Proportion of subjects with HIV-1 RNA < 50 c/mL at Week 24

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End point title

Proportion of subjects with HIV-1 RNA < 50 c/mL at Week 24 ^[1]

End point description

The proportion of subjects with plasma human immunodeficiency virus 1 (HIV-1) ribonucleic acid (RNA) levels less than 50 copies per milliliter (c/ml) consisted of the modified intent to treat (mITT) population and was defined as a percentage where the number of subjects with plasma HIV-1 RNA < 50 c/ml at Week 24 was divided by the total number of treated subjects. Treated subjects were randomized subjects who received at least 1 dose of study therapy. Response was assessed with the snapshot algorithm, which used the last plasma HIV-1 RNA value in the predefined visit window to classify a subject's response status.

End point type

Primary

End point timeframe

Week 24

Notes
[1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive summary statistics were planned for this outcome measure.

End point values	BMS-986001 100 mg QD + EFV 600 mg QD + 3TC 300 mg QD	BMS-986001 200 mg QD + EFV 600 mg QD + 3TC 300 mg QD	BMS-986001 400 mg QD + EFV 600 mg QD + 3TC 300 mg QD	TDF 300 mg QD + EFV 600 mg QD + 3TC 300 mg QD
Number of subjects analysed	65	67	66	99
Units: proportion of subjects
number (confidence interval 95%)	87.7 (77.2 to 94.5)	80.6 (69.1 to 89.2)	93.9 (85.2 to 98.3)	87.9 (79.8 to 93.6)

No statistical analyses for this end point

Primary: Number of Subjects with SAEs, AEs leading to discontinuation, Death through Week 24

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End point title

Number of Subjects with SAEs, AEs leading to discontinuation, Death through Week 24 ^[2]

End point description

An adverse event (AE) was defined as any new untoward medical occurrence or worsening of a pre-existing medical condition in a clinical investigation subject administered an investigational (medicinal) product and that does not necessarily have a causal relationship with this treatment. A serious adverse event (SAE) was defined as a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Death was a fatal event leading to permanent cessations of all vital functions of the body. The analysis was performed in the safety set, defined as all treated subjects. Treated subjects were randomized subjects who received at least 1 dose of study therapy.

End point type

Primary

End point timeframe

Day 1 to Week 24

Notes
[2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive summary statistics were planned for this outcome measure.

End point values	BMS-986001 100 mg QD + EFV 600 mg QD + 3TC 300 mg QD	BMS-986001 200 mg QD + EFV 600 mg QD + 3TC 300 mg QD	BMS-986001 400 mg QD + EFV 600 mg QD + 3TC 300 mg QD	TDF 300 mg QD + EFV 600 mg QD + 3TC 300 mg QD
Number of subjects analysed	65	67	66	99
Units: subjects
SAEs	4	4	4	9
AEs Leading to Discontinuation	0	5	0	3
Death	0	1	0	0

No statistical analyses for this end point

Secondary: Proportion of subjects with HIV-1 RNA < 50 c/mL through Weeks 48 and 96

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End point title

Proportion of subjects with HIV-1 RNA < 50 c/mL through Weeks 48 and 96

End point description

The proportion of subjects with plasma HIV-1 RNA levels less than 50 c/ml consisted of the mITT population and was defined as a percentage where the number of subjects with plasma HIV-1 RNA < 50 c/ml at Week 48 or 96 was divided by the total number of treated subjects. Treated subjects were randomized subjects who received at least 1 dose of study therapy. Response was assessed with the snapshot algorithm, which used the last plasma HIV-1 RNA value in the predefined visit window to classify a subject's response status.

End point type

Secondary

End point timeframe

Day 1 to Week 96

End point values	BMS-986001 100 mg QD + EFV 600 mg QD + 3TC 300 mg QD	BMS-986001 200 mg QD + EFV 600 mg QD + 3TC 300 mg QD	BMS-986001 400 mg QD + EFV 600 mg QD + 3TC 300 mg QD	TDF 300 mg QD + EFV 600 mg QD + 3TC 300 mg QD
Number of subjects analysed	65	67	66	99
Units: proportion of subjects
number (confidence interval 95%)
Week 48	75.4 (63.1 to 85.2)	80.6 (69.1 to 89.2)	89.4 (79.4 to 95.6)	81.8 (72.8 to 88.9)
Week 96	46.2 (33.7 to 59)	52.2 (39.7 to 64.6)	59.1 (46.3 to 71)	42.4 (32.5 to 52.8)

No statistical analyses for this end point

Secondary: Number of Subjects with SAEs, AEs leading to discontinuation, Death through Week 96

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End point title

Number of Subjects with SAEs, AEs leading to discontinuation, Death through Week 96

End point description

AE was defined as any new untoward medical occurrence or worsening of a pre-existing medical condition in a clinical investigation subject administered an investigational (medicinal) product and that does not necessarily have a causal relationship with this treatment. A SAE was defined as a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Death was a fatal event leading to permanent cessations of all vital functions of the body. The analysis was performed in the safety set, defined as all treated subjects. Treated subjects were randomized subjects who received at least 1 dose of study therapy.

End point type

Secondary

End point timeframe

Day 1 to Week 96

End point values	BMS-986001 100 mg QD + EFV 600 mg QD + 3TC 300 mg QD	BMS-986001 200 mg QD + EFV 600 mg QD + 3TC 300 mg QD	BMS-986001 400 mg QD + EFV 600 mg QD + 3TC 300 mg QD	TDF 300 mg QD + EFV 600 mg QD + 3TC 300 mg QD
Number of subjects analysed	65	65	65	99
Units: subjects
SAE, Week 96	7	7	9	11
AEs leading to discontinuation, Week 96	1	5	3	4
Death, Week 96	0	1	0	0

No statistical analyses for this end point

Secondary: Mean Change from Baseline in Cluster of Differentiation 4 Positive (CD4+) T-cell count through Weeks 24, 48, and 96

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End point title

Mean Change from Baseline in Cluster of Differentiation 4 Positive (CD4+) T-cell count through Weeks 24, 48, and 96

End point description

Changes from baseline in CD4+ T-cell counts were determined as cells per microliter (cells/ul). The analysis was performed in the observed set of the treated population, defined as subjects with CD4 < 50 c/mL at each measured week divided by the total number of treated subjects with CD4 at each measured week. Treated subjects were randomized subjects who received at least 1 dose of study therapy. Here n = number of subjects analysed and signifies evaluable subjects for this end point.

End point type

Secondary

End point timeframe

Day 1 to Week 96

End point values	BMS-986001 100 mg QD + EFV 600 mg QD + 3TC 300 mg QD	BMS-986001 200 mg QD + EFV 600 mg QD + 3TC 300 mg QD	BMS-986001 400 mg QD + EFV 600 mg QD + 3TC 300 mg QD	TDF 300 mg QD + EFV 600 mg QD + 3TC 300 mg QD
Number of subjects analysed	59	54	63	89
Units: cells/ul
arithmetic mean (standard error)
Week 24 (n=59, 54, 63, 89)	171.4 ( 16.379 )	139.6 ( 16.9 )	122.7 ( 14.243 )	133.1 ( 12.149 )
Week 48 (n=51, 52, 57, 82)	189.2 ( 20.072 )	155.3 ( 17.591 )	155.4 ( 15.772 )	179.8 ( 19.377 )
Week 96 (n=37, 43, 45, 56)	264.1 ( 27.36 )	255.6 ( 27.765 )	199.2 ( 19.598 )	215.7 ( 24.671 )

No statistical analyses for this end point

Secondary: Number of subjects with virologic failure who exhibited genotypic substitutions in viral RNA through Weeks 24, 48, and 96

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End point title

Number of subjects with virologic failure who exhibited genotypic substitutions in viral RNA through Weeks 24, 48, and 96

End point description

Virologic failure was defined as confirmed HIV-1 RNA >= 400 copies/mL after achieving viral suppression (HIV-1 RNA < 50 copies/mL) or discontinuation from study prior to achieving viral suppression after Week 8 with the last plasma HIV-1 RNA >= 400 copies/mL. The analysis was performed on all treated subjects with resistance profiles up to the specified week analysis. Here n = number of subjects analysed and signifies evaluable subjects for this end point.

End point type

Secondary

End point timeframe

Day 1 to Week 96

End point values	BMS-986001 100 mg QD + EFV 600 mg QD + 3TC 300 mg QD	BMS-986001 200 mg QD + EFV 600 mg QD + 3TC 300 mg QD	BMS-986001 400 mg QD + EFV 600 mg QD + 3TC 300 mg QD	TDF 300 mg QD + EFV 600 mg QD + 3TC 300 mg QD
Number of subjects analysed	12	7	3	6
Units: subjects
Week 24 (n=6, 5, 1, 2)	4	2	1	0
Week 48 (n=10, 6, 2, 4)	5	2	1	0
Week 96 (n=12, 7, 3, 6)	5	3	2	1

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

From Day 1 up to 30 days after the last dose of the study drug (approximately 28 months)

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

17.0

Reporting group title

BMS-986001 100 mg QD + EFV 600 mg QD + 3TC 300 mg QD

Reporting group description

Reporting group title

BMS-986001 200 mg QD + EFV 600 mg QD + 3TC 300 mg QD

Reporting group description

In Stage 1, subjects were administered a QD dose of 200 mg BMS-986001, 600 mg EFV, and 300 mg 3TC under fasted conditions at bedtime. While blinded, subjects took 4 capsules, 1 from each of 4 bottles that were a blinded combination of 200 mg active dose of BMS-986001 and matched-placebo. Dosing was open-label for EFV and 3TC. After the Week 48 analysis, the study became un-blinded and subjects switched to an optimal QD dose of 400 mg BMS-986001, 600 mg EFV, and 300 mg 3TC under fasted conditions at bedtime through the rest of stage 1. After the Week 48 analysis, the study became un-blinded and subjects switched to an optimal QD dose of 400 mg BMS-986001, 600 mg EFV, and 300 mg 3TC under fasted conditions at bedtime through the rest of stage 1 and the completion of stage 2.

Reporting group title

BMS-986001 400 mg QD + EFV 600 mg QD + 3TC 300 mg QD

Reporting group description

Reporting group title

TDF 300 mg QD + EFV 600 mg QD + 3TC 300 mg QD

Reporting group description

In Stage 1, subjects were administered a QD dose of 300 mg TDF, 600 mg EFV, and 300 mg 3TC under fasted conditions at bedtime. Dosing was open-label for TDF, EFV and 3TC. In Stage 2, subjects continued the treatment regimen from stage 1.

Serious adverse events	BMS-986001 100 mg QD + EFV 600 mg QD + 3TC 300 mg QD	BMS-986001 200 mg QD + EFV 600 mg QD + 3TC 300 mg QD	BMS-986001 400 mg QD + EFV 600 mg QD + 3TC 300 mg QD	TDF 300 mg QD + EFV 600 mg QD + 3TC 300 mg QD
Total subjects affected by serious adverse events
subjects affected / exposed	7 / 65 (10.77%)	7 / 67 (10.45%)	9 / 66 (13.64%)	11 / 99 (11.11%)
number of deaths (all causes)	0	1	0	0
number of deaths resulting from adverse events	0	0	0	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Hodgkin's disease
subjects affected / exposed	0 / 65 (0.00%)	0 / 67 (0.00%)	1 / 66 (1.52%)	0 / 99 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Uterine leiomyoma
subjects affected / exposed	0 / 65 (0.00%)	0 / 67 (0.00%)	1 / 66 (1.52%)	0 / 99 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Vascular disorders
Deep vein thrombosis
subjects affected / exposed	0 / 65 (0.00%)	0 / 67 (0.00%)	1 / 66 (1.52%)	1 / 99 (1.01%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
Chest pain
subjects affected / exposed	0 / 65 (0.00%)	0 / 67 (0.00%)	0 / 66 (0.00%)	1 / 99 (1.01%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Immune system disorders
Amyloidosis
subjects affected / exposed	0 / 65 (0.00%)	0 / 67 (0.00%)	0 / 66 (0.00%)	1 / 99 (1.01%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Reproductive system and breast disorders
Cervical dysplasia
subjects affected / exposed	0 / 65 (0.00%)	0 / 67 (0.00%)	0 / 66 (0.00%)	1 / 99 (1.01%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Dysfunctional uterine bleeding
subjects affected / exposed	0 / 65 (0.00%)	0 / 67 (0.00%)	0 / 66 (0.00%)	1 / 99 (1.01%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Genital ulceration
subjects affected / exposed	0 / 65 (0.00%)	1 / 67 (1.49%)	0 / 66 (0.00%)	0 / 99 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Menorrhagia
subjects affected / exposed	1 / 65 (1.54%)	0 / 67 (0.00%)	1 / 66 (1.52%)	0 / 99 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Pneumothorax
subjects affected / exposed	0 / 65 (0.00%)	0 / 67 (0.00%)	0 / 66 (0.00%)	1 / 99 (1.01%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Psychiatric disorders
Depression
subjects affected / exposed	0 / 65 (0.00%)	0 / 67 (0.00%)	0 / 66 (0.00%)	1 / 99 (1.01%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Major depression
subjects affected / exposed	1 / 65 (1.54%)	0 / 67 (0.00%)	1 / 66 (1.52%)	0 / 99 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Suicide attempt
subjects affected / exposed	0 / 65 (0.00%)	0 / 67 (0.00%)	0 / 66 (0.00%)	1 / 99 (1.01%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
Contusion
subjects affected / exposed	1 / 65 (1.54%)	0 / 67 (0.00%)	0 / 66 (0.00%)	0 / 99 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Overdose
subjects affected / exposed	0 / 65 (0.00%)	0 / 67 (0.00%)	0 / 66 (0.00%)	1 / 99 (1.01%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Road traffic accident
subjects affected / exposed	1 / 65 (1.54%)	0 / 67 (0.00%)	0 / 66 (0.00%)	0 / 99 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac disorders
Pericarditis
subjects affected / exposed	0 / 65 (0.00%)	0 / 67 (0.00%)	1 / 66 (1.52%)	0 / 99 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Nervous system disorders
Dizziness
subjects affected / exposed	0 / 65 (0.00%)	0 / 67 (0.00%)	1 / 66 (1.52%)	0 / 99 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Syncope
subjects affected / exposed	0 / 65 (0.00%)	0 / 67 (0.00%)	1 / 66 (1.52%)	0 / 99 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	1 / 65 (1.54%)	0 / 67 (0.00%)	0 / 66 (0.00%)	0 / 99 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Thrombocytopenia
subjects affected / exposed	0 / 65 (0.00%)	0 / 67 (0.00%)	1 / 66 (1.52%)	0 / 99 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Abdominal pain
subjects affected / exposed	0 / 65 (0.00%)	0 / 67 (0.00%)	1 / 66 (1.52%)	0 / 99 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hiatus hernia
subjects affected / exposed	1 / 65 (1.54%)	0 / 67 (0.00%)	0 / 66 (0.00%)	0 / 99 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Ileal perforation
subjects affected / exposed	0 / 65 (0.00%)	0 / 67 (0.00%)	1 / 66 (1.52%)	0 / 99 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Intestinal ischaemia
subjects affected / exposed	1 / 65 (1.54%)	0 / 67 (0.00%)	0 / 66 (0.00%)	0 / 99 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Intestinal obstruction
subjects affected / exposed	0 / 65 (0.00%)	0 / 67 (0.00%)	1 / 66 (1.52%)	0 / 99 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Mouth ulceration
subjects affected / exposed	0 / 65 (0.00%)	1 / 67 (1.49%)	0 / 66 (0.00%)	0 / 99 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Oesophagitis
subjects affected / exposed	1 / 65 (1.54%)	0 / 67 (0.00%)	0 / 66 (0.00%)	0 / 99 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Upper gastrointestinal haemorrhage
subjects affected / exposed	0 / 65 (0.00%)	0 / 67 (0.00%)	0 / 66 (0.00%)	1 / 99 (1.01%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hepatobiliary disorders
Drug-Induced liver injury
subjects affected / exposed	0 / 65 (0.00%)	0 / 67 (0.00%)	0 / 66 (0.00%)	1 / 99 (1.01%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hepatic pain
subjects affected / exposed	1 / 65 (1.54%)	0 / 67 (0.00%)	0 / 66 (0.00%)	0 / 99 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Skin and subcutaneous tissue disorders
Drug eruption
subjects affected / exposed	0 / 65 (0.00%)	1 / 67 (1.49%)	0 / 66 (0.00%)	0 / 99 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Erythema nodosum
subjects affected / exposed	0 / 65 (0.00%)	1 / 67 (1.49%)	0 / 66 (0.00%)	0 / 99 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Lipodystrophy acquired
subjects affected / exposed	0 / 65 (0.00%)	0 / 67 (0.00%)	0 / 66 (0.00%)	1 / 99 (1.01%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Renal and urinary disorders
Calculus bladder
subjects affected / exposed	0 / 65 (0.00%)	1 / 67 (1.49%)	0 / 66 (0.00%)	0 / 99 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
subjects affected / exposed	1 / 65 (1.54%)	0 / 67 (0.00%)	0 / 66 (0.00%)	0 / 99 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Appendicitis
subjects affected / exposed	0 / 65 (0.00%)	1 / 67 (1.49%)	0 / 66 (0.00%)	0 / 99 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cystitis
subjects affected / exposed	0 / 65 (0.00%)	0 / 67 (0.00%)	1 / 66 (1.52%)	0 / 99 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Dengue fever
subjects affected / exposed	0 / 65 (0.00%)	1 / 67 (1.49%)	0 / 66 (0.00%)	0 / 99 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Disseminated tuberculosis
subjects affected / exposed	0 / 65 (0.00%)	0 / 67 (0.00%)	0 / 66 (0.00%)	1 / 99 (1.01%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastroenteritis
subjects affected / exposed	0 / 65 (0.00%)	1 / 67 (1.49%)	1 / 66 (1.52%)	0 / 99 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Lobar pneumonia
subjects affected / exposed	0 / 65 (0.00%)	1 / 67 (1.49%)	0 / 66 (0.00%)	0 / 99 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Lymph node tuberculosis
subjects affected / exposed	0 / 65 (0.00%)	0 / 67 (0.00%)	0 / 66 (0.00%)	1 / 99 (1.01%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pelvic inflammatory disease
subjects affected / exposed	0 / 65 (0.00%)	0 / 67 (0.00%)	1 / 66 (1.52%)	0 / 99 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Peritonitis
subjects affected / exposed	0 / 65 (0.00%)	0 / 67 (0.00%)	1 / 66 (1.52%)	0 / 99 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia
subjects affected / exposed	0 / 65 (0.00%)	1 / 67 (1.49%)	0 / 66 (0.00%)	0 / 99 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
Pulmonary tuberculosis
subjects affected / exposed	0 / 65 (0.00%)	1 / 67 (1.49%)	0 / 66 (0.00%)	0 / 99 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pyelonephritis
subjects affected / exposed	0 / 65 (0.00%)	0 / 67 (0.00%)	0 / 66 (0.00%)	1 / 99 (1.01%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Syphilis
subjects affected / exposed	1 / 65 (1.54%)	0 / 67 (0.00%)	0 / 66 (0.00%)	0 / 99 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	BMS-986001 100 mg QD + EFV 600 mg QD + 3TC 300 mg QD	BMS-986001 200 mg QD + EFV 600 mg QD + 3TC 300 mg QD	BMS-986001 400 mg QD + EFV 600 mg QD + 3TC 300 mg QD	TDF 300 mg QD + EFV 600 mg QD + 3TC 300 mg QD
Total subjects affected by non serious adverse events
subjects affected / exposed	59 / 65 (90.77%)	61 / 67 (91.04%)	60 / 66 (90.91%)	88 / 99 (88.89%)
Nervous system disorders
Dizziness
subjects affected / exposed	30 / 65 (46.15%)	32 / 67 (47.76%)	29 / 66 (43.94%)	38 / 99 (38.38%)
occurrences all number	34	35	35	40
Headache
subjects affected / exposed	14 / 65 (21.54%)	16 / 67 (23.88%)	10 / 66 (15.15%)	23 / 99 (23.23%)
occurrences all number	18	21	13	27
Somnolence
subjects affected / exposed	4 / 65 (6.15%)	1 / 67 (1.49%)	1 / 66 (1.52%)	3 / 99 (3.03%)
occurrences all number	6	1	1	3
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	1 / 65 (1.54%)	1 / 67 (1.49%)	4 / 66 (6.06%)	3 / 99 (3.03%)
occurrences all number	1	3	4	4
General disorders and administration site conditions
Fatigue
subjects affected / exposed	2 / 65 (3.08%)	5 / 67 (7.46%)	6 / 66 (9.09%)	8 / 99 (8.08%)
occurrences all number	2	5	6	8
Pyrexia
subjects affected / exposed	2 / 65 (3.08%)	3 / 67 (4.48%)	1 / 66 (1.52%)	7 / 99 (7.07%)
occurrences all number	2	3	1	7
Ear and labyrinth disorders
Vertigo
subjects affected / exposed	1 / 65 (1.54%)	0 / 67 (0.00%)	1 / 66 (1.52%)	5 / 99 (5.05%)
occurrences all number	1	0	1	5
Gastrointestinal disorders
Abdominal pain
subjects affected / exposed	6 / 65 (9.23%)	2 / 67 (2.99%)	5 / 66 (7.58%)	3 / 99 (3.03%)
occurrences all number	6	2	5	3
Constipation
subjects affected / exposed	2 / 65 (3.08%)	1 / 67 (1.49%)	4 / 66 (6.06%)	0 / 99 (0.00%)
occurrences all number	2	1	4	0
Diarrhoea
subjects affected / exposed	12 / 65 (18.46%)	15 / 67 (22.39%)	8 / 66 (12.12%)	14 / 99 (14.14%)
occurrences all number	17	18	8	15
Dyspepsia
subjects affected / exposed	4 / 65 (6.15%)	3 / 67 (4.48%)	4 / 66 (6.06%)	3 / 99 (3.03%)
occurrences all number	5	3	4	3
Haemorrhoids
subjects affected / exposed	1 / 65 (1.54%)	4 / 67 (5.97%)	3 / 66 (4.55%)	1 / 99 (1.01%)
occurrences all number	1	4	3	1
Nausea
subjects affected / exposed	7 / 65 (10.77%)	6 / 67 (8.96%)	4 / 66 (6.06%)	7 / 99 (7.07%)
occurrences all number	7	6	4	11
Vomiting
subjects affected / exposed	2 / 65 (3.08%)	1 / 67 (1.49%)	4 / 66 (6.06%)	4 / 99 (4.04%)
occurrences all number	2	1	4	4
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed	4 / 65 (6.15%)	4 / 67 (5.97%)	3 / 66 (4.55%)	10 / 99 (10.10%)
occurrences all number	4	4	4	10
Skin and subcutaneous tissue disorders
Dermatitis
subjects affected / exposed	5 / 65 (7.69%)	4 / 67 (5.97%)	1 / 66 (1.52%)	1 / 99 (1.01%)
occurrences all number	5	7	1	1
Rash
subjects affected / exposed	14 / 65 (21.54%)	10 / 67 (14.93%)	12 / 66 (18.18%)	12 / 99 (12.12%)
occurrences all number	19	12	12	12
Psychiatric disorders
Abnormal dreams
subjects affected / exposed	6 / 65 (9.23%)	2 / 67 (2.99%)	1 / 66 (1.52%)	7 / 99 (7.07%)
occurrences all number	6	2	1	7
Insomnia
subjects affected / exposed	2 / 65 (3.08%)	2 / 67 (2.99%)	4 / 66 (6.06%)	7 / 99 (7.07%)
occurrences all number	2	3	4	9
Nightmare
subjects affected / exposed	3 / 65 (4.62%)	4 / 67 (5.97%)	1 / 66 (1.52%)	3 / 99 (3.03%)
occurrences all number	3	4	1	3
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	2 / 65 (3.08%)	3 / 67 (4.48%)	7 / 66 (10.61%)	1 / 99 (1.01%)
occurrences all number	2	3	9	1
Back pain
subjects affected / exposed	5 / 65 (7.69%)	5 / 67 (7.46%)	8 / 66 (12.12%)	6 / 99 (6.06%)
occurrences all number	5	5	10	6
Osteopenia
subjects affected / exposed	2 / 65 (3.08%)	2 / 67 (2.99%)	1 / 66 (1.52%)	9 / 99 (9.09%)
occurrences all number	2	2	1	9
Infections and infestations
Bronchitis
subjects affected / exposed	4 / 65 (6.15%)	1 / 67 (1.49%)	3 / 66 (4.55%)	3 / 99 (3.03%)
occurrences all number	4	1	3	3
Conjunctivitis
subjects affected / exposed	5 / 65 (7.69%)	3 / 67 (4.48%)	3 / 66 (4.55%)	3 / 99 (3.03%)
occurrences all number	7	3	4	3
Folliculitis
subjects affected / exposed	1 / 65 (1.54%)	1 / 67 (1.49%)	1 / 66 (1.52%)	5 / 99 (5.05%)
occurrences all number	1	2	1	7
Furuncle
subjects affected / exposed	4 / 65 (6.15%)	0 / 67 (0.00%)	1 / 66 (1.52%)	1 / 99 (1.01%)
occurrences all number	4	0	1	1
Gastroenteritis
subjects affected / exposed	2 / 65 (3.08%)	4 / 67 (5.97%)	3 / 66 (4.55%)	8 / 99 (8.08%)
occurrences all number	2	5	3	8
Herpes zoster
subjects affected / exposed	3 / 65 (4.62%)	0 / 67 (0.00%)	6 / 66 (9.09%)	3 / 99 (3.03%)
occurrences all number	3	0	6	3
Influenza
subjects affected / exposed	9 / 65 (13.85%)	14 / 67 (20.90%)	13 / 66 (19.70%)	8 / 99 (8.08%)
occurrences all number	10	27	18	15
Lower respiratory tract infection
subjects affected / exposed	1 / 65 (1.54%)	1 / 67 (1.49%)	3 / 66 (4.55%)	5 / 99 (5.05%)
occurrences all number	1	1	3	6
Nasopharyngitis
subjects affected / exposed	4 / 65 (6.15%)	2 / 67 (2.99%)	3 / 66 (4.55%)	6 / 99 (6.06%)
occurrences all number	6	4	5	13
Otitis media
subjects affected / exposed	4 / 65 (6.15%)	3 / 67 (4.48%)	0 / 66 (0.00%)	1 / 99 (1.01%)
occurrences all number	4	3	0	2
Tonsillitis
subjects affected / exposed	6 / 65 (9.23%)	0 / 67 (0.00%)	1 / 66 (1.52%)	0 / 99 (0.00%)
occurrences all number	7	0	1	0
Upper respiratory tract infection
subjects affected / exposed	17 / 65 (26.15%)	12 / 67 (17.91%)	16 / 66 (24.24%)	12 / 99 (12.12%)
occurrences all number	31	15	24	15
Urinary tract infection
subjects affected / exposed	4 / 65 (6.15%)	10 / 67 (14.93%)	4 / 66 (6.06%)	3 / 99 (3.03%)
occurrences all number	6	13	5	3
Metabolism and nutrition disorders
Decreased appetite
subjects affected / exposed	2 / 65 (3.08%)	2 / 67 (2.99%)	4 / 66 (6.06%)	7 / 99 (7.07%)
occurrences all number	2	2	6	8
Hypercholesterolaemia
subjects affected / exposed	5 / 65 (7.69%)	4 / 67 (5.97%)	5 / 66 (7.58%)	2 / 99 (2.02%)
occurrences all number	6	6	9	2

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Were there any global substantial amendments to the protocol? Yes

11 Oct 2011

This amendment made the following changes: - Defined in the Synopsis that BMS-986001 is an NRTI - Further clarified throughout the protocol that TDF, EFV and 3TC are all open label, regardless of treatment group in which they were used - Additionally excluded subjects with resistance to HIV protease inhibitors and included a list of exclusionary PI mutations - Clarified among the secondary endpoints that “genotypic substitutions” referred to “drug resistance genotypic substitutions” - Clarified that safety and tolerability were assessed through AE collection, laboratory tests, and toxicity biomarkers - Inserted guidelines for the management of subjects in the event that a BMS-986001 treatment group was determined to be suboptimal prior to the selection of the optimal dose, as well as for subjects who had HIV RNA ≥ 200 c/mL after Week 48. Included additional exclusionary resistance mutations for EFV, TDF, and 3TC - Corrected the identification of CD4+ and CD8+ T-cell lab assessments and location for skin biopsies - Clarified the Stopping Guidelines intended to be Stopping Rules - Addressed administrative and/or typographical changes/errors

04 Jun 2012

This amendment addressed 3 primary changes to the protocol: monitoring study subjects for the development of thrombocytopenia based on preclinical findings in 3 monkeys, allowing treatment with rifampin for subjects who developed TB while on study, and excluding anemic subjects from participation in the optional Week 2 Intensive PK visit.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

Based on data through Week 48, BMS determined BMS-986001 did not meet the desired drug attributes and target profile established by BMS to warrant continued development. BMS elected to terminate the study after all subjects had completed Week 48.

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Clinical trials

Clinical Trial Results:
A Phase IIb Randomized, Controlled, Partially Blinded Clinical Trial to Investigate Safety, Efficacy and Dose-response of BMS-986001 in Treatment-naive HIV-1-infected Subjects, Followed by an Open-label Period on the Recommended Dose.

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Proportion of subjects with HIV-1 RNA < 50 c/mL at Week 24

Primary: Proportion of subjects with HIV-1 RNA < 50 c/mL at Week 24

Primary: Number of Subjects with SAEs, AEs leading to discontinuation, Death through Week 24

Primary: Number of Subjects with SAEs, AEs leading to discontinuation, Death through Week 24

Secondary: Proportion of subjects with HIV-1 RNA < 50 c/mL through Weeks 48 and 96

Secondary: Proportion of subjects with HIV-1 RNA < 50 c/mL through Weeks 48 and 96

Secondary: Number of Subjects with SAEs, AEs leading to discontinuation, Death through Week 96

Secondary: Number of Subjects with SAEs, AEs leading to discontinuation, Death through Week 96

Secondary: Mean Change from Baseline in Cluster of Differentiation 4 Positive (CD4+) T-cell count through Weeks 24, 48, and 96

Secondary: Mean Change from Baseline in Cluster of Differentiation 4 Positive (CD4+) T-cell count through Weeks 24, 48, and 96

Secondary: Number of subjects with virologic failure who exhibited genotypic substitutions in viral RNA through Weeks 24, 48, and 96

Secondary: Number of subjects with virologic failure who exhibited genotypic substitutions in viral RNA through Weeks 24, 48, and 96

Adverse events

Adverse events

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Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

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Clinical trials

Clinical Trial Results: A Phase IIb Randomized, Controlled, Partially Blinded Clinical Trial to Investigate Safety, Efficacy and Dose-response of BMS-986001 in Treatment-naive HIV-1-infected Subjects, Followed by an Open-label Period on the Recommended Dose.

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Proportion of subjects with HIV-1 RNA < 50 c/mL at Week 24

Primary: Proportion of subjects with HIV-1 RNA < 50 c/mL at Week 24

Primary: Number of Subjects with SAEs, AEs leading to discontinuation, Death through Week 24

Primary: Number of Subjects with SAEs, AEs leading to discontinuation, Death through Week 24

Secondary: Proportion of subjects with HIV-1 RNA < 50 c/mL through Weeks 48 and 96

Secondary: Proportion of subjects with HIV-1 RNA < 50 c/mL through Weeks 48 and 96

Secondary: Number of Subjects with SAEs, AEs leading to discontinuation, Death through Week 96

Secondary: Number of Subjects with SAEs, AEs leading to discontinuation, Death through Week 96

Secondary: Mean Change from Baseline in Cluster of Differentiation 4 Positive (CD4+) T-cell count through Weeks 24, 48, and 96

Secondary: Mean Change from Baseline in Cluster of Differentiation 4 Positive (CD4+) T-cell count through Weeks 24, 48, and 96

Secondary: Number of subjects with virologic failure who exhibited genotypic substitutions in viral RNA through Weeks 24, 48, and 96

Secondary: Number of subjects with virologic failure who exhibited genotypic substitutions in viral RNA through Weeks 24, 48, and 96

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
A Phase IIb Randomized, Controlled, Partially Blinded Clinical Trial to Investigate Safety, Efficacy and Dose-response of BMS-986001 in Treatment-naive HIV-1-infected Subjects, Followed by an Open-label Period on the Recommended Dose.