Excessive Daytime SleepinessPhase 3HAROSA3NCT02739568
Pitolisant (BF2.649) in the Treatment of EDS in Patients With OSA
A Phase 3 study testing Pitolisant (BF2.649) in people with Excessive Daytime Sleepiness and Obstructive Sleep Apnea, run by Bioprojet at 6 sites in 2 countries.
Trial summary
The first objective of this study is to demonstrate the efficacy and safety of pitolisant given at 10, 20, or 40 mg per day versus placebo during 12 weeks of the Double Blind period, to treat the Excessive Daytime Sleepiness (EDS) in patients with Obstructive Sleep Apnea (OSA) refusing the nasal Continuous Positive… Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- Excessive Daytime Sleepiness, Obstructive Sleep Apnea
- What is being tested?
- Pitolisant (BF2.649)
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 389 participants
- Where
- 6 sitesin 2 countries
- Study dates
- Apr 2016to Apr 2020
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male and/or female outpatients aged from at least 18 years
- Patients complaining of EDS refusing to be treated by nCPAP therapy or having been submitted to nCPAP therapy for a minimum period of 3 months, and still complaining of EDS despite the efforts made beforehand to obtain an efficient nCPAP therapy
- Polysomnography performed (for patients submitted to nCPAP therapy - under nCPAP) between V1 and V2 or during the last 12 months with Apnea-Hypopnea Index (AHI): for patients without nCPAP therapy ≥ 15; for patients under nCPAP therapy less or equal to 10
- For patients submitted to nCPAP therapy: nCPAP ≥ 4 hours / day (compliance checked on the clock-time counter of the CPAP machine)
- Mini Mental State Examination (MMSE) ≥ 28
- Beck Depression Inventory - 13 items (BDI-13) score < 16 and item G (suicidal ideation) of BDI-13 = 0
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- Body Mass Index (BMI )less or equal to 40 kg/m²
- Epworth Sleepiness Scale (ESS) ≥ 12
- Female patients with child-bearing potential using a medically accepted method of birth control (i.e. oral contraceptives of normal average dosage) agreeing to continue this method throughout the study, and during the month following treatment discontinuation, being negative to serum pregnancy test performed at the screening visit
- If specified by the investigator, the patient must be willing not to operate a car (if sleepy at wheel) or heavy machinery for the duration of the trial or as long as the investigator deems it clinically indicated. In addition, the patient should be willing to maintain during the study their usual behaviors which could affect their diurnal sleepiness (e.g. circadian rhythm, caffeine consumption, nocturnal sleep duration)
- Patients having signed and dated the informed consent form
Who cannot join
- Patients suffering from chronic severe insomnia in accordance with the International Classification of Sleep Disorders (ICSD 2005) without OSA
- Patients with co-existing narcolepsy (ICSD 2005), judged on clinical criteria
- Patients with sleep debt not due to OSA (according to the physician' s judgment)
- Patients with non-respiratory sleep fragmentation (restless leg syndrome…)
- Shift work, professional drivers
- Refusal from the patient to stop any current therapy for EDS or predictable risk for the patient to stop the therapy
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- Patients suffering from a psychiatric disease
- Acute or chronic disease preventing the improvement assessment, e.g. severe chronic obstructive pulmonary disease (COPD)
- Current or recent (within one year) history of drug, alcohol, narcotic or other substance abuse or dependence
- Any significant serious abnormality of the cardiovascular system, e.g. recent myocardial infarction, angina, hypertension or dysrhythmias (within the previous 6 months), Electrocardiogram Fridericia corrected QT interval higher than 450 ms, history of left ventricular hypertrophy or mitral valve prolapse
- Severe co-morbid medical or biological conditions that may jeopardize study participation at the discretion of the investigator (particularly in the cardiovascular system and the instable diabetes)
- Positive serology tests (HIV, HCV and HBsAg)
- Pregnant or breast-feeding women
- Women with child-bearing potential and no efficient birth-control method
- Patients unable to understand the study protocol
- Patients with suspected or known hypersensitivity to study medication
- Patients with a dominant arm deficiency impeding the achievement of the tests
- Patients using a prohibited medication
- Congenital galactose poisoning, glucose and galactose malabsorption, deficit in lactase
- Patients participating in another study or being in a follow-up period for another study
Trial locations and contacts
6 sites in 2 countries.
6 sites in 2 countries
Bulgaria5 sites
Specialised Hospital for Active Treatment of pneumo-phthisiatric diseases - Burgas" EOOD, Pneumology ward
Burgas, 8000
Multiprofile Hospital for Active Treatment "Sv. Ivan Rilski" EOOD
Kozloduy, 3320
Multiprofile Hospital for Active Treatment "Sv. Paraskeva" OOD
Pleven, 5800
University Multiprofile Hospital for Active Treatment "Kaspela" EOOD Clinic of thoracic surgery
Plovdiv, 5000
University Multiprofile Hospital for Active Treatment "Aleksandrovska" EAD
Sofia, 1432
About this study
Official title: Efficacy and Safety of Pitolisant (BF2.649) in the Treatment of Excessive Daytime Sleepiness in Patients With Obstructive Sleep Apnea Syndrome, Treated or Not by Nasal Continuous Positive Airway Pressure, But Still Complaining of Excessive Daytime Sleepiness
The first objective of this study is to demonstrate the efficacy and safety of pitolisant given at 10, 20, or 40 mg per day versus placebo during 12 weeks of the Double Blind period, to treat the Excessive Daytime Sleepiness (EDS) in patients with Obstructive Sleep Apnea (OSA) refusing the nasal Continuous Positive Airway Pressure (nCPAP) therapy or treated by nCPAP but still complaining of EDS.
The secondary objectives of the study include assessing the long-term tolerance as well as the maintenance of efficacy of pitolisant given at 10, 20 or 40 mg per day during 39 weeks of Open Label Extension period and further investigating the co-variates or co-medications that affect the pharmacokinetics of pitolisant in the target population.
- Being tested
- Pitolisant (BF2.649), Placebo
- Keywords
- EDS, OSA
- Medical subject headings
- Disorders of Excessive Somnolence, Sleep Apnea, Obstructive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Pitolisant (BF2.649)Drug
PlaceboDrug
| Study group | Role | What they receive |
|---|---|---|
| Pitolisant (BF2.6449 | Experimental | Histamine H3 receptor H3R antagonist/ inverse agonist Receives: Drug: Pitolisant (BF2.649) |
| Placebo | Placebo comparator | Placebo Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Epworth sleepiness scale (ESS)
Change from Baseline of ESS
Measured: at weeks 12 and 52
Secondary outcomes (9)
Percentage of ESS responders
Percentage of ESS responders
Measured: at weeks 12 and 52
Reduction of sleepiness and sleep episodes on the sleep diary
Reduction of sleepiness and sleep episodes
Measured: at weeks 12 and 52
Improvement in vigilance according to Oxford Sleep Resistance (OSleR) test
Improvement in vigilance according to Oxford Sleep Resistance (OSleR) test
Measured: at weeks 12 and 52
European Quality of Life Questionnaire (EQ-5D)
EQ-5D improvement (mobility, self-care, usual activities, pain/discomfort and anxiety/depression)
Measured: at weeks 12 and 52
Leeds Sleep Evaluation Questionnaire (LSEQ)
LSEQ improvement (changes in sleep and next morning behaviour during disease/pharmacological investigations)
Measured: at weeks 12 and 52
The Pichot Fatigue Scale
Pichot Fatigue scale improvement (assessment of the level of discomfort caused by a state of fatigue)
Measured: at weeks 12 and 52
Trail Making Test parts (A and B)
TMT test improvement
Measured: at weeks 12 and 52
Improvement in Clinical Global Impression (CGI)
CGI improvement (patient progress and treatment response over time)
Measured: at weeks 12 and 52
Aggregate Z-score of secondary endpoints.
Aggregate Z-score of secondary endpoints improvement
Measured: at weeks 12 and 52
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Apr 2016 (estimated)
- Study startApr 2016
- Primary completionApr 2020
- Study completionApr 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Excessive Daytime SleepinessStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 389 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bioprojet
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02739568
- Sponsor's protocol ID
- P15 13/ BF2.649
- Acronym
- HAROSA3
- Status last verified
- Jul 2020
- First submitted
- 31 Mar 2016
- Last updated
- 8 Jul 2020
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 8 Jul 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy and Safety of Pitolisant (BF2.649) in the Treatment of Excessive Daytime Sleepiness in Patients With Obstructive Sleep Apnea Syndrome, Treated or Not by Nasal Continuous Positive Airway Pressure, But Still Complaining of Excessive Daytime Sleepiness
- ClinicalTrials.gov ID
- NCT02739568
- Acronym / sponsor ID
- HAROSA3 / P15 13/ BF2.649
- Keywords
- EDS, OSA
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 389 participants (actual)
- Lead sponsor
- BioprojetUniversity, hospital or other
- Study start
- Apr 2016 (actual)
- Primary completion
- Apr 2020 (actual)
- Study completion
- Apr 2020 (actual)
- First posted
- 15 Apr 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The first objective of this study is to demonstrate the efficacy and safety of pitolisant given at 10, 20, or 40 mg per day versus placebo during 12 weeks of the Double Blind period, to treat the Excessive Daytime Sleepiness (EDS) in patients with Obstructive Sleep Apnea (OSA) refusing the nasal Continuous Positive Airway Pressure (nCPAP) therapy or treated by nCPAP but still complaining of EDS.
The secondary objectives of the study include assessing the long-term tolerance as well as the maintenance of efficacy of pitolisant given at 10, 20 or 40 mg per day during 39 weeks of Open Label Extension period and further investigating the co-variates or co-medications that affect the pharmacokinetics of pitolisant in the target population.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Pitolisant (BF2.6449 | Experimental | Drug: Pitolisant (BF2.649)Histamine H3 receptor H3R antagonist/ inverse agonist |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Male and/or female outpatients aged from at least 18 years
- Patients complaining of EDS refusing to be treated by nCPAP therapy or having been submitted to nCPAP therapy for a minimum period of 3 months, and still complaining of EDS despite the efforts made beforehand to obtain an efficient nCPAP therapy
- Polysomnography performed (for patients submitted to nCPAP therapy - under nCPAP) between V1 and V2 or during the last 12 months with Apnea-Hypopnea Index (AHI): for patients without nCPAP therapy ≥ 15; for patients under nCPAP therapy less or equal to 10
- For patients submitted to nCPAP therapy: nCPAP ≥ 4 hours / day (compliance checked on the clock-time counter of the CPAP machine)
- Mini Mental State Examination (MMSE) ≥ 28
Key exclusion criteria (20 listed)
- Patients suffering from chronic severe insomnia in accordance with the International Classification of Sleep Disorders (ICSD 2005) without OSA
- Patients with co-existing narcolepsy (ICSD 2005), judged on clinical criteria
- Patients with sleep debt not due to OSA (according to the physician' s judgment)
- Patients with non-respiratory sleep fragmentation (restless leg syndrome…)
- Shift work, professional drivers
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Pitolisant (BF2.649) | Drug | Pitolisant (BF2.6449 |
| Placebo | Drug | Placebo |
Primary outcome
Epworth sleepiness scale (ESS)
Time frame: at weeks 12 and 52
Change from Baseline of ESS
9 secondary outcomes
Percentage of ESS responders
Time frame: at weeks 12 and 52
Reduction of sleepiness and sleep episodes on the sleep diary
Time frame: at weeks 12 and 52
Improvement in vigilance according to Oxford Sleep Resistance (OSleR) test
Time frame: at weeks 12 and 52
European Quality of Life Questionnaire (EQ-5D)
Time frame: at weeks 12 and 52
Leeds Sleep Evaluation Questionnaire (LSEQ)
Time frame: at weeks 12 and 52
The Pichot Fatigue Scale
Time frame: at weeks 12 and 52
Trail Making Test parts (A and B)
Time frame: at weeks 12 and 52
Improvement in Clinical Global Impression (CGI)
Time frame: at weeks 12 and 52
Aggregate Z-score of secondary endpoints.
Time frame: at weeks 12 and 52
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jul 2020.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
6 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Pitolisant (BF2.649) in people with Excessive Daytime Sleepiness and Obstructive Sleep Apnea, run by Bioprojet at 6 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Jul 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in Bulgaria, North Macedonia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Epworth sleepiness scale (ESS) (time frame: at weeks 12 and 52). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Jul 2020.