Patients with obesity hypoventilation syndrome (OHS) MedDRA version: 20.0 Level: PT Classification code 10035004 Term: Pickwickian syndrome System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders
Conditions
Interventions
Trade Name: Strattera
Product Name: Atomoxetina
Product Code: [Atomoxetina]
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Atomoxetina
Current Sponsor code: Atomoxetina
Concentration unit: mg
Sponsors
ISTITUTO AUXOLOGICO ITALIANO
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Participant must be able to understand the nature of the study and must have the opportunity to have any questions answered. Participant voluntarily agrees to participate in this study and signs an Ethic Committee -approved informed consent prior to performing any of the Screening Visit procedures. 2. Male or female participants between 18 to 75 years of age 3. BMI > 35 kg/m2, inclusive, at the pre-PSG visit 4. Presence of nocturnal hypoventilation defined as mean PtcCO2 >55 mmHg or >50 mmHg if PtcCO2 increases by more than 10 mmHg for more than 10 minutes of sleep compared to awake supine value 5. Previous surgical treatment for OSA is allowed if = 1 year prior to enrollment. 6. Participants known for OHS and having treatment are eligible for screening/baseline PSG if they report CPAP or BPAP or mandibular advancement device or positional therapy intolerance or poor compliance (compliance is defined as use of CPAP or other treatments for 4 hours per night for 70% of nights; per participant self-report). Participants who had been using CPAP at least 4 hours nightly for at least 70% of the nights are eligible for further screening and baseline PSG for this study only if CPAP or other treatments will not have been used for 2 weeks prior to the screening/baseline PSG for this study. 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 9 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 6
Exclusion criteria
Exclusion criteria: 1. History of narcolepsy. 2. Clinically significant craniofacial malformation. 3. Clinically significant respiratory (COPD, ILD) or cardiac (Heart Failure, Atrial fibrillation, established severe peripheral arterial disease) disease or hypertension requiring more than 3 medications for control 4. History of renal failure or history of hepatic insufficiency or history of hepatic cirrhosis. 5. History of schizophrenia, schizoaffective disorder or bipolar disorder according to Diagnostic and Statistical Manual of Mental Disorders-V (DSM V) or International Classification of Disease tenth edition criteria. 6. History of attempted suicide or suicidal ideation within 1 year prior to screening, or current suicidal ideation. 7. Positive screen for drugs of abuse or substance use disorder as defined in DSM-V within 12 months prior to Screening Visit. 8. A significant illness or infection requiring medical treatment in the past 30 days. 9. Clinically significant cognitive dysfunction or serious neurological disorder, including serious epilepsy/convulsions. 10. Untreated narrow angle glaucoma. 11. Women who are pregnant or nursing. 12. History of oxygen therapy. 13. Treatment with strong cytochrome P450 3A4 (CYP3A4) inhibitors, or monoamine oxidase inhibitors (MAOI) or linezolid within 14 days of the start of treatment. 14. History of pheochromocytoma. 15. History of diabetes with unstable glucose control in the past 15 days. 16. Chronic use of more than 500 mg/day of Aspirin, due to the potential for an interaction of acetazolamide and very high doses of Aspirin (acetylsalicylic acid, a salicylate drug). 19 17. Allergies to sulfonamides – e.g. hydrochlorothiazide, furosemide, sulfasalazine, celecoxib, sumatriptan, and zonisamide. 18. History of Adrenocortical insufficiency. 19. Known history of low sodium or potassium or evidence of low sodium (<130mEq\L) or potassium (<3meq\L) at blood tests in the last year (if available). 20. History of hyperchloremic acidosis. 21. Any condition that in the investigator’s opinion would present an unreasonable risk to the participant, or which would interfere with their participation in the study or confound study interpretation. 22. Participant considered by the investigator, for any reason, an unsuitable candidate to receive Ato/Acz treatment or unable or unlikely to understand or comply with the dosing schedule or study evaluations. 23. History of using oral or nasal devices (such as mandibular advancement devices) for the treatment of OSA may enroll as long as the devices are not used during participation in the study for at least 2 weeks prior to study begin. 24. History of using devices to affect participant sleeping position for the treatment of OSA, e.g. to discourage supine sleeping position, may enroll as long as the devices are not used during participation in the study. 25. Use of another investigational agent within 30 days or 5 half-lives, whichever is longer, prior to dosing. 26. Patient currently receiving: MAOIs, Serotonin and Norepinephrine Reuptake Inhibitors, Norepinephrine Reuptake Inhibitors, Lithium, Tricyclic antidepressants, strong CYP2D6 inhibitors, other strong inhibitors cytochrome P450, thiazides diuretics, benzodiazepines, opioids, drugs with clinically significant cardiac QT-interval prolonging effects, drugs known to lower seizure threshold, amphetamines, antiepileptics, modafinil or armodafinil, beta2 agonists (if used more than 3 times/week), antipsychotics, pseudoephe
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the efficacy of atomoxetine/acetazolamide (Ato/Actz) at fixed dose vs placebo in patients with obesity hypoventilation syndrome (OHS);Secondary Objective: •Higher proportion of participants without nocturnal hypoventilation on Ato/Actz vs placebo •Reduction in AHI on Ato/Actz vs placebo;Primary end point(s): The primary efficacy endpoint is the mean nocturnal PtcCO2 level from screening/baseline to final day with study treatment.;Timepoint(s) of evaluation of this end point: 9 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Gli endpoint secondari saranno la percentuale di partecipanti senza ipoventilazione notturna con Ato/Actz rispetto al placebo e la variazione dell'AHI con Ato/Actz rispetto al placebo. I valori P nominali saranno calcolati per i seguenti endpoint di efficacia per il trattamento rispetto al placebo;Timepoint(s) of evaluation of this end point: 9 weeks | — |
Countries
Italy
Contacts
Public ContactDr.ssa Elisa Perger - Centro di Med
ISTITUTO AUXOLOGICO ITALIANO
Outcome results
None listed