Moderate to severe obstructive sleep apnea. Males and females
Conditions
Interventions
Trade Name: Aricept
Product Name: donepezil
Product Code: donepezil
Pharmaceutical Form: Capsule*
INN or Proposed INN: Donepezil
CAS Number: 120014-06-4
Concentration unit: mg/g milligram(s)/gram
Conc
Sponsors
Pharmapnea AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Eligible for this study are patients who meet each one of the following criteria at the screening visit. - Males and females; age 25 to 65 years - Previously diagnosed OSA defined as an oxygen desaturation (4%) index of 15 or more obtained from a preceding routine outpatient screening recording. The screening study had to encompass at least 6 hours overnight recording of SaO2, respiratory movements (impedance), heart rate, nasal and oral airflow, breathing sounds, and body position. - The patient is able to read and understand the patient information sheet. - The patient has given signed informed consent before any study specific procedures are carried out. - The patient is willing to attend the study appoints in the correct time window. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Patients who meet one or more of the following criteria at the screening visit or at Visit 2 on Day 1 cannot be selected: 1. Previous exposure to continuous positive airway pressure (CPAP treatment) or oral devices is allowed but treatment has to be interrupted at least one week before the first study night and throughout the whole study period 2. Coronary heart disease 3. Previously known or treated cardiac arrhythmia of any type 4. Myocardial infarction or stroke within 12 months before study enrolment 5. A body weight exceeding Body Mass Index of 32 kgm-2 6. Patient has a history of or current abuse or dependence on any substance with abuse potential according to DSM-IV-TRTM. This includes alcohol, hypnotics, and drugs of abuse, but excludes nicotine dependence. A patient who fulfils DSM-IV-TRTM criteria for sustained full remission can be included if he/she, in the investigator’s opinion, is not at risk for drug dependence or abuse. 7. Patient has any of the following conditions: a. restless leg syndrome b. severe or acute respiratory failure c. myasthenia gravis d. proneness to muscle spasm or epileptic seizure. 8. Use of disallowed recent/concomitant therapy: a. An investigational drug within 3 months prior to screening visit. b. Use of any psychoactive or hypnotic drug (including herbal remedies) or benzodiazepines within 1 week prior to screening visit. c. Depot antipsychotics within 6 months prior to screening. d. Use of antihistamines with sedative properties within 2 weeks prior to screening visit. e. Use of any drug containing opiate or opiate derivatives. f. Use of antiepileptics within 14 days prior to screen visit. g. Serotonin reuptake inhibitors h. Mirtazepin i. Flurazepam or diazepam within 2 weeks prior to screening visit. j. Weight reducing drugs. k. Hormone replacement therapy is allowed when given at least under the last three months with constant dosage 9. The patient consumes on average more than 14 units (females) or more than 21 units (males) of alcohol per week on a regular basis (glasses of wine/beer and its equivalent). 10. History of severe drug allergy or hypersensitivity, or known hypersensitivity to donepezil. 11. Patient has a known positive HIV test or chronic hepatitis B/C. 12. Diseases/medication, which, judged by the investigator, could interfere with the assessments of safety, tolerability or efficacy. 13. Unstable serious illness and/or serious sequelae thereof, including liver or renal insufficiency, cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurological, infectious, neoplastic, or metabolic disturbances. (If there is history of such disease but the condition has been stable for at least one year and is judged by the investigator not to lead to an unsafe inclusion and not to interfere with the patient’s participation in the study, the patient may be included). 14. The patient, in the opinion of the investigator, is unlikely to comply with the clinical study protocol or is unsuitable for any other reasons. 15. Laboratory values at screening outside the normal ranges, considered by the investigator to be clinically significant. If urine creatinine is out of range, impaired renal function has to be considered.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The objective of the study is to determine the effective dose range of donepezil in patients with moderate to severe obstructive sleep apnea. These effects will be operationalized by the following outcome variables. Primary outcome variables: • Change from baseline in the REM sleep Apnea Index (REM-AI) assessed by overnight home polysomnography between each donepezil treatment period (1, 5, 10 mg) and placebo. ;Secondary Objective: Secondary outcome variables: • Change in total AI index compared to placebo • Change in AI/nonREM index compared to placebo • Pharmacokinetic determination of trough Cpss [donepezil] • Change in cognitive test scores compared to placebo • Change in Quality of Life assessed by questionnaires compared to placebo • Weekly investigator assessments of global clinical impression (CGI-I and CGI-S). Other Efficacy variables: • Change in total Apnea Hypopnea Index (AHI) index compared to placebo • Change in hypopnea index (non REM and REM sleep) • Change in sleep stage distribution • Change in autonomic indices like heart rate/finger pulse wave amplitude Safety variables: • Adverse events • Physical examination • Haematology, biochemistry and urine analyses ;Primary end point(s): Primary outcome variables: • Change from baseline in the REM sleep Apnea Index (REM-AI) assessed by overnight home polysomnography between each donepezil treatment period (1, 5, 10 mg) and placebo. | — |
Countries
Sweden
Outcome results
None listed