E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 25.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10055577 |
E.1.2 | Term | Obstructive sleep apnea syndrome |
E.1.2 | System Organ Class | 100000004855 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the efficacy of three different doses of Sulthiame (STM) compared to placebo on sleep apnea activity in adult patients with moderate to severe obstructive sleep apnea after at least 12 weeks of treatment at target dose. |
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E.2.2 | Secondary objectives of the trial |
To evaluate the effect of three different doses of STM after at least 12 weeks of treatment at target dose in patients with moderate to severe obstructive sleep apnea (OSA) on: - apnea/hyponea events - hypoxic burden - sleep quality - daytime sleepiness - patient’s symptoms and well-being - comorbidity-related outcomes - safety and tolerability of STM
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Willing and able to provide written informed consent 2. Male or female aged 18 to 75 years inclusive 3. OSA diagnosis according to the international classification of sleep disorders (ICSD)-3 criteria with an AHI ≥15 documented by PSG or polygraphy (PG) 4. Currently not treated with CPAP or MAD (see further details in the protocol) 5. An AHI of ≥15 to ≤50 (mean from 2 PSG recordings [2 nights] at baseline), AHI of at least 10 on each night 6. BMI ≥18.5 kg/m2 and ≤35 kg/m2 7. Women of childbearing potential (WOCBP) or men whose sexual partners are WOCBP must be able and willing to use at least 1 highly effective method of contraception for at least 2 months prior to the first dose of study drug, throughout the entire study period, and for 30 days after the last dose of study drug 8. Willing and able to comply with the study design schedule and other requirements
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E.4 | Principal exclusion criteria |
1. Any OSA treatment within the last 4 weeks prior to screening 2. Fulfilling criteria for a dominant central sleep apnea syndrome or a dominant Cheyne Stokes respiration 3. Other clinically significant sleep disorder including periodic limb movement disorder, restless leg syndrome, periodic limb movements arousal index (PLMAI) >15, insomnia, parasomnia or narcolepsy 4. Hypoventilation or hypoxemia due to chronic obstructive pulmonary disease or other respiratory condition 5. Clinically relevant craniofacial malformation 6. Any upper airway surgery for OSA within the last 12 months prior to baseline 7. Patients who underwent an obesity surgery within the last 2 years prior to baseline or patients actively participating in any weight loss treatment program or use of any weight loss medication (prescription or over-the-counter) within 2 months prior to the first PSG night 8. Elevated blood pressure or uncontrolled hypertension (systolic blood pressure ≥160 mm Hg and/or diastolic blood pressure ≥100 mm Hg). If treated, patients must have been on the same dose of antihypertensive medication for at least 4 weeks prior to screening 9. Uncontrolled congestive heart failure 10. Myocardial infarction or coronary vessel intervention within the previous 6 months period or unstable angina pectoris 11. Previously diagnosed or treated clinically significant cardiac arrhythmia 12. Episode of major depression, bipolar disorder, or any other significant psychiatric disorder within the last 12 months prior to screening 13. Significant neurological or cognitive disorders as detailed in the protocol 14. Renal or hepatic failure as defined in the protocol 15. History of severe allergy/hypersensitivity or any ongoing allergy/hypersensitivity requiring continuous medical treatment 16. Known allergy/hypersensitivity to STM and ingredients or to sulfonamides 17. Nightshift-workers, professional drivers, patients handling complex machinery or with any other occupation where there may be an increased risk for work or traffic accidents 18. Participation in another clinical study during the last 30 days prior to screening 19. Planned surgery during the study period or major surgery within 6 months prior to first dose of study drug 20. History of alcohol or drug abuse during the last year, substance use disorder, positive urine drug screen for drugs of abuse at screening 21. Intake of any protocol-specified prohibited medication 22. Clinically significant gastrointestinal, metabolic, urinary, or hematological disorder or any other significant condition or infection that, in the opinion of the investigator, could interfere with participation in the study. Note, acute porphyria and untreated hyperthyroidism are excluded. 23. Type 1 diabetes or insulin treated type 2 diabetes or poorly controlled type 2 diabetes 24. Positive COVID-19 polymerase chain reaction (PCR) test result within 30 days prior to screening, history of hospitalization for COVID-19 within 30 days prior to screening, or history of use of oxygen due to COVID-19 within 30 days prior to screening. Note that previous COVID-19 infection alone is not exclusionary and vaccination against SARS-CoV-2 is allowed, but must be documented. 25. Planned COVID-19 vaccination during the trial participation or within 2 weeks prior to screening. Booster vaccinations are allowed. 26. History of actual suicidal behavior or suicidal ideation of type 2 to 5 within one year prior to screening, or current suicidal ideation of any type (i.e. 1 to 5) as assessed by the C-SSRS at screening 27. Female patients who are currently pregnant or breastfeeding Please see the full list of exclusion criteria in the study protocol. 28.Patients who are kept in an institution by an official injunction or by court order or whose willingness to volunteer in a clinical trial may be unduly influenced by a potential relationship of dependency with the Sponsor, the investigator, or the investigational site. Please see the full list of exclusion criteria in the study protocol. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint of this study is the relative change in AHI from baseline to Week 15 (at least 12 weeks of treatment at target dose) measured by PSG. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
As specified in the endpoints. |
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E.5.2 | Secondary end point(s) |
• AHI Responder • Change in Oxygen desaturation Index • Change in overnight Oxygen Saturation • Change in sleep stages • Change in sleep quality parameter • Patient/Clinical global Impression Scale • Change in Epworth Sleepiness Scale • Change in Sleep Apnea Quality of Life • Change in Pittsburg Sleep Quality Index • Change in blood pressure •Change in body weight
For the Efficacy endpoints please refer to section 6.2.2.1. of Final Clinical Study Protocol . |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
As specified in the endpoints, and in the study procedures (section 10 of the Final Clinical Study Protocol). |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 4 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 30 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 4 |