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Clinical Trial Results:
A Multisite Randomized Clinical Trial Evaluating BP1.3656 Versus Placebo For Alcohol Use Disorder Treatment

Summary
EudraCT number	2017-000069-57
Trial protocol	BG NL
Global end of trial date	24 Nov 2021

Results information
Results version number	v1(current)
This version publication date	21 Aug 2024
First version publication date	21 Aug 2024
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

P15-01

ISRCTN number

US NCT number

NCT03424824

WHO universal trial number (UTN)

Sponsor organisation name

BIOPROJET PHARMA

Sponsor organisation address

9 rue rameau, Paris, France, 75002

Public contact

Bioprojet Clinical Development department, BIOPROJET PHARMA, 33 147036633, contact@bioprojet.com

Scientific contact

Bioprojet Clinical Development department, BIOPROJET PHARMA, 33 147036633, contact@bioprojet.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

10 Jun 2022

Is this the analysis of the primary completion data?

Yes

Primary completion date

24 Nov 2021

Global end of trial reached?

Yes

Global end of trial date

24 Nov 2021

Was the trial ended prematurely?

Main objective of the trial

To assess tolerance and efficacy of 12 weeks BP1.3656 at 30 μg OD vs 60 μg OD vs 90 μg OD versus placebo to reduce alcohol consumption in alcohol dependent patients

Protection of trial subjects

The study was performed in accordance with the Ethical principles stated in the Declaration of Helsinki, the international recommendation of Good Clinical Practices (ICH-E6) as well as with the local regulation. Written approval/favourable opinion from the IEC and authorization/non-objection from the regulatory authorities were obtained, as well as until other GCP prerequisites were fulfilled prior to the study being implemented in a clinical site. The study was monitored by monitors designated by the Sponsor who regularly checked compliance with the protocol and ethical requirements. The monitors compared selected key data collected in the CRF with source data, and verified Drug Accountability and Informed Consent. The study was as well monitored centrally in order to detect any risk. If new safety information became available, this new information was communicated without delay to the patient, the Investigator, the Ethics Committee, and Regulatory Authorities whenever required. Prior to the initiation of the study at Clinical site level, the study was submitted to the Independent Ethics Committee (IEC) with all the documents required by local regulations and any other documents that were requested. According to local regulations, the appropriate documents were submitted to the relevant competent authority for authorization or non objection. Voluntary written Informed Consent Form (ICF) was obtained from each patient prior to performing any study related procedures in compliance with the recommendations of the Good Clinical Practices.

Background therapy

Evidence for comparator

Actual start date of recruitment

09 Jan 2018

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Russian Federation: 64

Country: Number of subjects enrolled

Bulgaria: 138

Country: Number of subjects enrolled

France: 8

Worldwide total number of subjects

210

EEA total number of subjects

146

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)

210

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

From January 2018 to August 2021, a total of 210 patients were randomized (ITT population) at 18 active study centres in 3 countries (France, Bulgaria, Russia).

Screening details

A total of 237 patients were screened. 210 out of the 237 were randomized to receive either the active drug, BP1.3656 (150 patients), or the placebo (60 patients).

Number of subjects started

210

Number of subjects completed

209

Reason: Number of subjects

Physician decision: 1

Period 1 title

Double-blind period

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Monitor, Data analyst, Carer, Assessor

Blinding implementation details

The following controls were employed to maintain the double-blind status: − The placebo tablets were identical in appearance to the BP1.3656 tablets − Treatment allocation was done through IWRS − Patients, Investigator and sponsor (and their representatives) remained blinded to the treatment randomization code. During each interim analysis the independent third party statistician analyzed the data and decided about continuation or not. He was the only person allowed to receive the rando list

Are arms mutually exclusive

Yes

BP1.3656 30 µg (treatment arm)

Arm description

tablets of 30 μg : per os 1 tablet / day during 12 weeks

Arm type

Experimental

Investigational medicinal product name

BP1.3656

Investigational medicinal product code

BP1.3656

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

30 μg 1 tablet per os / day

BP1.3656 60 µg (treatment arm)

Arm description

tablets of 60 μg : per os 1 tablet / day during 12 weeks

Arm type

Experimental

Investigational medicinal product name

BP1.3656

Investigational medicinal product code

BP1.3656

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

60 μg 1 tablet per os / day

Placebo arm

Arm description

tablets of placebo : per os 1 tablet / day during 12 weeks

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

1 tablet per os / day

BP1.3656 90 µg (treatment arm)

Arm description

tablets of 90 μg : per os 1 tablet / day during 12 weeks

Arm type

Experimental

Investigational medicinal product name

BP1.3656

Investigational medicinal product code

BP1.3656

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

90 μg 1 tablet per os / day

Number of subjects in period 1 ^[1]	BP1.3656 30 µg (treatment arm)	BP1.3656 60 µg (treatment arm)	Placebo arm	BP1.3656 90 µg (treatment arm)
Started	40	45	60	64
Completed	32	39	57	62
Not completed	8	6	3	2
Physician decision	2	1	1	-
Consent withdrawn by subject	3	3	2	2
Adverse event, non-fatal	1	-	-	-
Lost to follow-up	1	-	-	-
Protocol deviation	1	2	-	-

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: 209 patients out of the 210 randomized patients received at least one dose of study drug and have been reported with a baseline value and at least one post-baseline value to compute the primary endpoint (FAS population).

Period 2 title

Single-blind period

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Single blind

Roles blinded

Subject

Placebo arm

Arm description

tablets of placebo : per os 1 tablet / day during 1 week

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

1 tablet per os / day

Number of subjects in period 2	Placebo arm
Started	190
Completed	189
Not completed	1
Consent withdrawn by subject	1

Baseline characteristics

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Reporting group title

BP1.3656 30 µg (treatment arm)

Reporting group description

tablets of 30 μg : per os 1 tablet / day during 12 weeks

Reporting group title

BP1.3656 60 µg (treatment arm)

Reporting group description

tablets of 60 μg : per os 1 tablet / day during 12 weeks

Reporting group title

Placebo arm

Reporting group description

tablets of placebo : per os 1 tablet / day during 12 weeks

Reporting group title

BP1.3656 90 µg (treatment arm)

Reporting group description

tablets of 90 μg : per os 1 tablet / day during 12 weeks

Reporting group values	BP1.3656 30 µg (treatment arm)	BP1.3656 60 µg (treatment arm)	Placebo arm	BP1.3656 90 µg (treatment arm)	Total
Number of subjects	40	45	60	64	209
Age categorical
Units: Subjects
Adults (18-34 years)	5	6	10	12	33
Adults (35-49 years)	26	25	26	34	111
Adults (50-64 years)	9	14	24	18	65
Adults >= 65 years	0	0	0	0	0
Age continuous
Units: years
arithmetic mean (standard deviation)	42.9 ( 8.5 )	44.7 ( 9.2 )	45.7 ( 9.8 )	44.6 ( 10.5 )	-
Gender categorical
Units: Subjects
Female	12	15	21	11	59
Male	28	30	39	53	150
BMI in classes
Units: Subjects
<25 kg/m2	22	22	33	33	110
25 to <30 kg/m2	13	16	24	23	76
>=30 kg/m2	5	7	3	8	23

Subject analysis set title

Full Analysis Set

Subject analysis set type

Full analysis

Subject analysis set description

Subset of the ITT population having taken at least one dose of drug and having been reported with a baseline value and at least one post-baseline value to compute the primary endpoint.

Subject analysis sets values	Full Analysis Set
Number of subjects	209
Age categorical
Units: Subjects
Adults (18-34 years)	33
Adults (35-49 years)	111
Adults (50-64 years)	65
Adults >= 65 years	0
Age continuous
Units: years
arithmetic mean (standard deviation)	44.6 ( 9.6 )
Gender categorical
Units: Subjects
Female	59
Male	150
BMI in classes
Units: Subjects
<25 kg/m2	110
25 to <30 kg/m2	76
>=30 kg/m2	23

End points

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Reporting group title

BP1.3656 30 µg (treatment arm)

Reporting group description

tablets of 30 μg : per os 1 tablet / day during 12 weeks

Reporting group title

BP1.3656 60 µg (treatment arm)

Reporting group description

tablets of 60 μg : per os 1 tablet / day during 12 weeks

Reporting group title

Placebo arm

Reporting group description

tablets of placebo : per os 1 tablet / day during 12 weeks

Reporting group title

BP1.3656 90 µg (treatment arm)

Reporting group description

tablets of 90 μg : per os 1 tablet / day during 12 weeks

Reporting group title

Placebo arm

Reporting group description

tablets of placebo : per os 1 tablet / day during 1 week

Subject analysis set title

Full Analysis Set

Subject analysis set type

Full analysis

Subject analysis set description

Subset of the ITT population having taken at least one dose of drug and having been reported with a baseline value and at least one post-baseline value to compute the primary endpoint.

Primary: Decrease in nHDD (number of monthly heavy drinking days)

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End point title

Decrease in nHDD (number of monthly heavy drinking days)

End point description

The study primary endpoint aimed to assess the decrease in nHDDs (≥ 60 g/day in men and ≥ 40 g/day in women) from baseline to end of the double-blind randomised study treatment period (12-week).

End point type

Primary

End point timeframe

nHDD from baseline to final time (end of Double-Blind period)

End point values	BP1.3656 30 µg (treatment arm)	BP1.3656 60 µg (treatment arm)	Placebo arm	BP1.3656 90 µg (treatment arm)
Number of subjects analysed	40	45	60	64
Units: nHDD at final time
arithmetic mean (standard deviation)	10.96 ( 10.10 )	8.57 ( 8.08 )	10.23 ( 9.49 )	12.27 ( 10.22 )

Adjusted mean difference

Statistical analysis description

a stepdown strategy is used to assess the significance of doses: The highest dose is tested first, and the significance of the lower dosages is only considered conditionally to the significant effect of the previous dose

Comparison groups

BP1.3656 90 µg (treatment arm) v Placebo arm

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

ANCOVA

Parameter type

adjusted mean difference

Point estimate

0.37

Confidence interval

level

90%

sides

2-sided

lower limit

-2.01

upper limit

2.74

Variability estimate

Standard error of the mean

Dispersion value

1.44

Adverse events

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Timeframe for reporting adverse events

AE assessment will be performed throughout the trial once the patient has signed informed consent. During 30 days after patient study discontinuation any relevant AE should be reported by the investigator.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

24.1

Reporting group title

BP1.3656 30 µg (treatment arm)

Reporting group description

tablets of 30 μg per os 1 tablet / day

Reporting group title

BP1.3656 60 µg (treatment arm)

Reporting group description

tablets of 60 μg per os 1 tablet / day

Reporting group title

Placebo arm

Reporting group description

tablets of placebo per os 1 tablet / day

Reporting group title

BP1.3656 90 µg (treatment arm)

Reporting group description

Tablets of 90 μg per os 1 tablet / day

Serious adverse events	BP1.3656 30 µg (treatment arm)	BP1.3656 60 µg (treatment arm)	Placebo arm	BP1.3656 90 µg (treatment arm)
Total subjects affected by serious adverse events
subjects affected / exposed	0 / 43 (0.00%)	0 / 43 (0.00%)	2 / 60 (3.33%)	1 / 64 (1.56%)
number of deaths (all causes)	0	0	0	0
number of deaths resulting from adverse events	0	0	0	0
Injury, poisoning and procedural complications
Facial bones fracture
subjects affected / exposed	0 / 43 (0.00%)	0 / 43 (0.00%)	0 / 60 (0.00%)	1 / 64 (1.56%)
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
Foot fracture
subjects affected / exposed	0 / 43 (0.00%)	0 / 43 (0.00%)	1 / 60 (1.67%)	0 / 64 (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
Hand fracture
subjects affected / exposed	0 / 43 (0.00%)	0 / 43 (0.00%)	0 / 60 (0.00%)	1 / 64 (1.56%)
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
Gastrointestinal disorders
Gastric ulcer
subjects affected / exposed	0 / 43 (0.00%)	0 / 43 (0.00%)	1 / 60 (1.67%)	0 / 64 (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

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

Non-serious adverse events	BP1.3656 30 µg (treatment arm)	BP1.3656 60 µg (treatment arm)	Placebo arm	BP1.3656 90 µg (treatment arm)
Total subjects affected by non serious adverse events
subjects affected / exposed	0 / 43 (0.00%)	9 / 43 (20.93%)	8 / 60 (13.33%)	19 / 64 (29.69%)
Nervous system disorders
Headache
subjects affected / exposed	0 / 43 (0.00%)	3 / 43 (6.98%)	2 / 60 (3.33%)	1 / 64 (1.56%)
occurrences all number	0	3	2	1
Gastrointestinal disorders
Nausea
subjects affected / exposed	0 / 43 (0.00%)	2 / 43 (4.65%)	3 / 60 (5.00%)	5 / 64 (7.81%)
occurrences all number	0	2	3	5
Psychiatric disorders
Insomnia
subjects affected / exposed	0 / 43 (0.00%)	4 / 43 (9.30%)	3 / 60 (5.00%)	5 / 64 (7.81%)
occurrences all number	0	4	3	6
Abnormal dreams
subjects affected / exposed	0 / 43 (0.00%)	0 / 43 (0.00%)	0 / 60 (0.00%)	4 / 64 (6.25%)
occurrences all number	0	0	0	4
Dysphoria
subjects affected / exposed	0 / 43 (0.00%)	0 / 43 (0.00%)	0 / 60 (0.00%)	4 / 64 (6.25%)
occurrences all number	0	0	0	4

More information

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Were there any global substantial amendments to the protocol? Yes

28 Sep 2017

This amendment changed the protocol initially approved on the following topics: - Suppression of the Netherlands clinical investigation centre - Change of Coordinator lnvestigator - Correction of the randomization ratio - Inclusion of additional exams at screening visit - Modification of exams time-points from visit 0 (baseline) to the screening visit - Inclusion of additional liver function tests at each visit from screening visit to visit 6 (end of double-blind period) - Addition of BP1.3656 pharmacokinetic (PK) assessment - Modification of Time Line Follow Back presentation - Modification of M.I.N .I utilization in the study - Modification of AUDIT frequency utilization - Modification of PSQI frequency utilization - Modification of SF-12 frequency utilization - Addition of information related to preclinical and clinical data of BP1.3656 compound - Correction of typo errors

11 Jun 2018

Following the participation of a new country in the study and the possibility for patients to not be involved in the pharmacokinetics dosing, we revised the protocol version 2.0 dated September 28th 2017. The version 3.0 was created on this occasion. The modifications introduced in the version 3.0 allowed us to update protocol according new versions of Investigator’s Brochure (version 7.0, May 30th 2018) and Investigational Medicinal Product Dossier (version 5.0, May 23rd 2018) and to add clarifications of some processes.

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.

None reported

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Clinical trials

Clinical Trial Results:
A Multisite Randomized Clinical Trial Evaluating BP1.3656 Versus Placebo For Alcohol Use Disorder Treatment

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Decrease in nHDD (number of monthly heavy drinking days)

Primary: Decrease in nHDD (number of monthly heavy drinking days)

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

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Clinical trials

Clinical Trial Results: A Multisite Randomized Clinical Trial Evaluating BP1.3656 Versus Placebo For Alcohol Use Disorder Treatment

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Decrease in nHDD (number of monthly heavy drinking days)

Primary: Decrease in nHDD (number of monthly heavy drinking days)

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
A Multisite Randomized Clinical Trial Evaluating BP1.3656 Versus Placebo For Alcohol Use Disorder Treatment