Clinical Trial Results:
Efficacy and safety of BF2.649 in the treatment of Excessive Daytime Sleepiness in patients with Obstructive Sleep Apnoea syndrome (OSA), refusing the nasal continuous positive airway pressure (nCPAP) therapy
Summary
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EudraCT number |
2009-017251-94 |
Trial protocol |
DE BE ES FI SE DK BG |
Global end of trial date |
07 May 2014
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Results information
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Results version number |
v1(current) |
This version publication date |
02 Mar 2022
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First version publication date |
02 Mar 2022
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Other versions |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
P 09-09
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
Bioprojet Pharma
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Sponsor organisation address |
9 rue Rameau, Paris, France, 75002
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Public contact |
Clinical Development Director, Bioprojet Pharma, 33 147 03 66 33, contact@bioprojet.com
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Scientific contact |
Clinical Development Director, Bioprojet Pharma, 33 147 03 66 33, contact@bioprojet.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
21 Dec 2018
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
29 Jul 2013
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Global end of trial reached? |
Yes
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Global end of trial date |
07 May 2014
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
The first objective of this study was to demonstrate the efficacy and safety of BF2.649 given at 5, 10, or 20 mg per day versus placebo during 12 weeks for the double blind phase, to treat the excessive diurnal sleepiness in patients with moderate to severe Obstructive Sleep Apnoea (OSA) refusing the nasal Continuous Positive Airway Pressure (nCPAP) therapy.
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Protection of trial subjects |
In order to avoid useless patient exposure, 2 futility analyses were planned when 60 and 120 patients had completed the double-blind phase of the study.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
06 Oct 2011
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
North Macedonia: 71
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Country: Number of subjects enrolled |
Spain: 2
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Country: Number of subjects enrolled |
Sweden: 7
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Country: Number of subjects enrolled |
Belgium: 8
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Country: Number of subjects enrolled |
Bulgaria: 137
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Country: Number of subjects enrolled |
Denmark: 1
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Country: Number of subjects enrolled |
Finland: 10
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Country: Number of subjects enrolled |
France: 8
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Country: Number of subjects enrolled |
Germany: 2
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Country: Number of subjects enrolled |
Serbia: 22
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Worldwide total number of subjects |
268
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EEA total number of subjects |
175
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
236
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From 65 to 84 years |
32
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85 years and over |
0
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Recruitment
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Recruitment details |
- | |||||||||||||||||||||
Pre-assignment
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Screening details |
During the screening visit, the investigator checked the inclusion and exclusion criteria and performed all required screening assessments. From this visit, a 14-day wash-out period started. 298 patients were screened for inclusion. Of those, 268 patients (89.9%) were eligible for entry into the study | |||||||||||||||||||||
Period 1
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Period 1 title |
Double-blind period (overall period)
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Is this the baseline period? |
Yes | |||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | |||||||||||||||||||||
Roles blinded |
Subject, Investigator, Monitor, Data analyst, Carer, Assessor | |||||||||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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BF2.649 Treatment Arm (Double-blind) | |||||||||||||||||||||
Arm description |
12-week double-blind period starting with an escalating dose period with BF2.649 given at 5-, 10-, or 20 mg per day, followed by treatment with the selected dose. | |||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||
Investigational medicinal product name |
Pitolisant
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Investigational medicinal product code |
BF2.649
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Other name |
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Pharmaceutical forms |
Capsule
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Routes of administration |
Oral use
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Dosage and administration details |
1 capsule / day, containing ¼, ½, or one 20 mg tablet of BF2.649
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Arm title
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Placebo Arm (Double-blind) | |||||||||||||||||||||
Arm description |
12-week double-blind period with placebo. | |||||||||||||||||||||
Arm type |
Placebo | |||||||||||||||||||||
Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Capsule
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Routes of administration |
Oral use
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Dosage and administration details |
1 capsule / day, containing placebo (lactose)
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Baseline characteristics reporting groups
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Reporting group title |
BF2.649 Treatment Arm (Double-blind)
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Reporting group description |
12-week double-blind period starting with an escalating dose period with BF2.649 given at 5-, 10-, or 20 mg per day, followed by treatment with the selected dose. | ||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo Arm (Double-blind)
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Reporting group description |
12-week double-blind period with placebo. | ||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
BF2.649 Treatment Arm (Double-blind)
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Reporting group description |
12-week double-blind period starting with an escalating dose period with BF2.649 given at 5-, 10-, or 20 mg per day, followed by treatment with the selected dose. | ||
Reporting group title |
Placebo Arm (Double-blind)
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Reporting group description |
12-week double-blind period with placebo. |
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End point title |
Epworth Sleepiness Scale (ESS) - Double-blind period | ||||||||||||
End point description |
ESS score measured persistent daytime sleepiness or sleep propensity for adult patients in ITT (Intention-to-treat) population.
The ESS score was the sum of the eight sub-scores and can range from 0 to 24 with higher scores representing greater sleepiness.
A score greater than 10 was considered as abnormal sleepiness.
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End point type |
Primary
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End point timeframe |
Between baseline and end of double-blind period
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Statistical analysis title |
Primary analysis | ||||||||||||
Statistical analysis description |
For the ITT Population this model showed a statistically significant treatment effect of -2.8 (95% CI: [-4.0;-1.5]) (p<0.001). This indicated a statistically significant diference between the two treatment groups in reduction of excessive daytime sleepiness in patients with OSA.
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Comparison groups |
BF2.649 Treatment Arm (Double-blind) v Placebo Arm (Double-blind)
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Number of subjects included in analysis |
268
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
< 0.001 | ||||||||||||
Method |
ANCOVA | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Confidence interval |
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95% | ||||||||||||
sides |
2-sided
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lower limit |
- | ||||||||||||
upper limit |
- |
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End point title |
Epworth Response (R1) | ||||||||||||
End point description |
Reaching an absolute value of the ESS inferior to 11 in ITT population
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End point type |
Secondary
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End point timeframe |
from beginning of treatment to end of double-blind (treatment and placebo arms)
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No statistical analyses for this end point |
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End point title |
Epworth Response (R2) | ||||||||||||
End point description |
Either reaching an absolute ESS inferior to 11 or an improvement from baseline of at least 3 in ITT
population
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End point type |
Secondary
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End point timeframe |
From beginning of treatment to end of double-blind (treatment and placebo arms)
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No statistical analyses for this end point |
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End point title |
Pichot Fatigue Scale | ||||||||||||
End point description |
EndThe Pichot questionnaire was a practical 24-item self-rating account with three homogeneous subscales
of 8 items each which measure depressive mood, asthenia-fatigue, and anxiety parameters,
respectively. A score > 22 indicates excessive fatigue. It was measured in the ITT population.
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End point type |
Secondary
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End point timeframe |
This scale was measured at V2 to V6 (end of double-blind period)
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No statistical analyses for this end point |
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End point title |
Clinical Global Impression (CGI) | ||||||||||||
End point description |
The CGI was a 3-item observer-rated scale which measures illness severity (CGI-S), global improvement
or change (CGI-C), and therapeutic response.
The CGI was measured in the ITT population.
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End point type |
Secondary
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End point timeframe |
The CGI-S (illness severity) was performed at V1 and V2, CGI-C (global improvement or change) at V6, V7 (end of double-blind period).
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No statistical analyses for this end point |
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Adverse events information
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Timeframe for reporting adverse events |
The period of observation for the double-blind period extended from the time the patient gave informed consent (Visit 1; D0) until one month after the last visit (Visit 7; D91).
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Assessment type |
Systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
20.0
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Reporting groups
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Reporting group title |
Double-blind - BF2.649 Treatment Arm
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Reporting group description |
Patients receiving BF2.649during double-blind period. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Double-blind - Placebo Arm
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Reporting group description |
Patients receiving placebo during double-blind period. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 2% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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06 Apr 2011 |
Amendment 1: Addition of the amphetamine-like withdrawal symptom questionnaire to be completed 3 days after V6 for the subjects who terminate the study by the placebo wash out period and minor
modification of the sleep diary (non-substantial modification) and update of the Investigator’s Brochure with preclinical data (substantial modification). |
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05 Oct 2011 |
Amendment 2: Rules to assess the primary endpoint (ESS) were modified (substantial modification): The baseline ESS to be taken in consideration is the ESS score at V2 instead of the mean of ESS values at V1 and V2, since the patients had to stop their previous medication at V1. For the sleep diary, the possibility was foreseen to collect data electronically via telephone (3 first days of the week before the next visit) if the patient accepts. Patients who preferred the paper solution could still use it. These patients were to complete a paper diary during 3 days prior to the next visit (non substantial modification). |
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Interruptions (globally) |
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Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported |