Clinical Trial Results:
An open-label naturalistic pragmatic study to assess the long-term safety of Pitolisant (BF2.649) in the treatment of Excessive Daytime Sleepiness (EDS) in narcolepsy (“HARMONY III”)
Part I : 12-month analysis
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Summary
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EudraCT number |
2010-023804-28 |
Trial protocol |
HU |
Global end of trial date |
12 Sep 2016
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Results information
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Results version number |
v1(current) |
This version publication date |
15 Dec 2022
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First version publication date |
15 Dec 2022
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Other versions |
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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 |
P09-10
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01399606 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Bioprojet
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Sponsor organisation address |
9, rue Rameau, Paris, France, 75002
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Public contact |
Clinical Development Director, Bioprojet
, +33 1 47 03 66 33, contact@bioprojet.com
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Scientific contact |
Clinical Development Director, Bioprojet
, +33 1 47 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 |
30 May 2018
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
07 Oct 2013
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Global end of trial reached? |
Yes
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Global end of trial date |
12 Sep 2016
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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 |
- To assess the long-term safety of pitolisant (BF2.649) at 5, 10, 20 or 40 mg/d in the treatment of Excessive Daytime Sleepiness (EDS) in narcoleptic patients with or without cataplexy.
The main objective was to get safety data from at least 50 complete patients treated for at least 12 months until BF2.649 commercialization.
- To assess the drug-drug interactions with possible concomitant therapies.
- To assess the efficacy of long-term therapy with pitolisant (BF2.649) on EDS after a prolonged treatment period.
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Protection of trial subjects |
The study was conducted in accordance with International Conference on Harmonisation, Good Clinical Practice (ICH-GCP E6), the ethical principles that have their origins in the Declaration of Helsinki
(revised Edinburgh, 2000), and applicable national and local regulatory requirements. Prior to the performance of any study-specific procedures, written informed consent was obtained from
each patient. The subject was informed about the nature and purpose of the study, as well as of its risks and benefits.
It was explained that the subject could withdraw from the study at any time for any reason and that this would not have any effect on potential future medical care.
An independent Data Safety Monitoring Board (DSMB) was established to assess at intervals the progress of the trial as well as safety data and to recommend whether to continue, modify or terminate the study. It was composed of three independent experts selected by the sponsor, without any direct involvement in the conduct of the trial.
At each meeting, the DSMB members considered study-specific safety data (serious and non-serious AEs) as well as relevant background knowledge about narcolepsy, pitolisant (BF2.649) development (previous and ongoing studies), and patient population under study. DSMB members concluded each review with their recommendations as to whether the study should continue without change, be modified, or terminated.
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Background therapy |
Previous participation in a Bioprojet narcolepsy study testing pitolisant (BF2.649) until completion (P05-03, P06-06, P07-03 HARMONY I or P09-15 HARMONY I bis or P07-07 HARMONY II) OR narcoleptic patients with EDS not able to participate in a double-blind study against placebo but who could benefit from testing a new therapy such as pitolisant in an open label study OR patient receiving pitolisant under condition of temporary authorization of use (ATU) delivered by the French Health Authorities. | ||
Evidence for comparator |
no comparator was included | ||
Actual start date of recruitment |
11 May 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 |
France: 79
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Country: Number of subjects enrolled |
Hungary: 25
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Worldwide total number of subjects |
104
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EEA total number of subjects |
104
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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) |
96
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From 65 to 84 years |
8
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85 years and over |
0
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Recruitment
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Recruitment details |
After a 1-week baseline period without investigational treatments, or at the end of the participation in a previous double blind controlled narcolepsy study testing pitolisant (BF2.649) (e.g., Studies P07-03, P07-07, P09-15), patients who fulfilled selection criteria started a 1-month individual dose titration phase. | ||||||
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Pre-assignment
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Screening details |
Previous participation in a Bioprojet narcolepsy study with pitolisant until completion OR narcoleptic patients with EDS not able to participate in a double-blind study against placebo but who could benefit from testing a new therapy such as pitolisant in an open label study OR patient receiving pitolisant under temporary authorization of use. | ||||||
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Period 1
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Period 1 title |
12-month (Completers) (overall period)
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Is this the baseline period? |
Yes | ||||||
Allocation method |
Non-randomised - controlled
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Blinding used |
Not blinded | ||||||
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Arms
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Arm title
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Baseline (12-month Completers) | ||||||
Arm description |
Subjects who completed the 12-month period with valid measurements at baseline and 12-month time point | ||||||
Arm type |
Experimental | ||||||
Investigational medicinal product name |
BF2.649
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Investigational medicinal product code |
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Other name |
Pitolisant
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Pitolisant hydrochloride (BF2.649)
Dose: 5, 10, 20, 40 mg OD
Mode of administration: Per os
1-month individual dose titration phase: BF2.649 at 5 mg OD (1/4 tablet of BF2.649 at 20 mg) from D1 to D7, BF2.649 at 10 mg OD (1/2 tablet) from D8 to D14 and then increased to 20 mg OD (1 tablet) from D15 to D21 if safety and tolerability were good. At D21, doses could be adjusted according to the individual benefit/risk ratio (5, 10 or 20 mg OD). At 1-month, an individual dose adjustment could be performed again (5, 10, 20 or 40 mg OD if the investigator judged that the efficacy of 20 mg OD was not sufficient). Thereafter, the dose remained stable for a 2-month period. At 3-, 6-, 9-, 12-month visits, an individual dose adjustment could be performed again (5, 10, 20 or 40 mg OD).
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| 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: Subset of patients who completed the 12-month period, with baseline data - for Efficacy Endpoint |
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Baseline characteristics reporting groups
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Reporting group title |
12-month (Completers)
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Reporting group description |
Subjects who completed the 12-month period with baseline data - Efficacy endpoint | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
Safety Population
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Subject analysis set type |
Safety analysis | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Subjects who took at least one dose of study treatment
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Subject analysis set title |
12-month (Completers)
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Subject analysis set type |
Per protocol | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Patients who completed the 12 months of treatment (n=68) with baseline data
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End points reporting groups
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Reporting group title |
Baseline (12-month Completers)
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Reporting group description |
Subjects who completed the 12-month period with valid measurements at baseline and 12-month time point | ||
Subject analysis set title |
Safety Population
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Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
Subjects who took at least one dose of study treatment
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Subject analysis set title |
12-month (Completers)
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Subject analysis set type |
Per protocol | ||
Subject analysis set description |
Patients who completed the 12 months of treatment (n=68) with baseline data
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End point title |
Epworth Sleepiness Score [1] | ||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
Control visit at 12 months (Visit 7)
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| 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: Efficacy was not the primary objective but safety. No formal statistical analysis was planned other than descriptive statistics. See attached Figure and Table with descriptive statistical results. |
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Attachments |
Untitled (Filename: 2010-023804-28_Figure8_Epworth_Sleepiness_Scale_by_Visit_ITT.pdf) Untitled (Filename: 2010-023804-28_Table38_Epworth_Sleepiness_Scale_M12_ITT.pdf) |
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| Notes [2] - Without replacement of missing values – ITT population |
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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 |
From Day 0 and then at Day 21 (Visit, V2), 1 month (V3), 3 month (V4), 6 month (V5), 9 month (V6) and 12 month (V7)
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Adverse event reporting additional description |
Full data collected on the first 12 months period.
For non-serious adverse events, only Treatment Emergent Adverse Events (TEAEs) that were considered related (possibly or likely) to study drug.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
15.1
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Reporting groups
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Reporting group title |
Safety Population
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Reporting group description |
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| Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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 Jun 2012 |
After having completed the first 12-month period, the cohort of French patients had the possibility to continue and receive prolonged treatment and follow-up until pitolisant (BF2.649) marketing authorization (Amendment N°2 of the 6th of June 2012 for France only). |
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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 | |||
Online references |
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| http://www.ncbi.nlm.nih.gov/pubmed/31529094 |
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