E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Obstructive sleep apnea/hypopnea syndrome |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 8.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10055577 |
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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 assess the efficacy of Org 4419-2 in decreasing the Apnea Hypopnea Index (AHI) as compared to placebo. |
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E.2.2 | Secondary objectives of the trial |
• to explore the efficacy of Org 4419-2 in improving secondary PSG parameters, clinical global impression, MSLT, snoring frequency, daytime sleepiness, functional status and quality of life in OSAHS as compared to placebo; • to explore a dose-response and/or plasma concentration-response relationship in the efficacy of Org 4419-2; • to assess the plasma concentration of Org 4419-2, Org 4420, Org 31602 and Org 31603 in OSAHS subjects; • to assess the safety and tolerability of Org 4419-2, including the key safety aspects of weight gain and sedation; • to assess whether in-vivo conversion of Org 4419 into Org 4420 and/or invivo conversion of Org 31602 into Org 31603 occurs. |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
• must provide written informed consent after the scope and nature of the investigation have been explained to them, before screening evaluations; • must be able to speak, read and understand the local language and possess the ability to respond to questions, follow instructions and complete questionnaires; • fulfill AASM (1999) criteria for OSAHS; • have an AHI ≥10 (events/h) at the screening PSG; • screening PSG is based on ≥ 6 h time in bed and ≥ 4 h total sleep time; • males and females aged 18-65 years; • no current treatment with CPAP or oral appliances (if treated with prior CPAP or oral appliances, this must have been discontinued ≥3 weeks prior to trial baseline); • no current treatment with modafinil, methylphenidate or other psychostimulant drugs (such prior psychostimulant treatment must have been discontinued ≥3 weeks prior to trial baseline). |
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E.4 | Principal exclusion criteria |
• subjects with unstable or insufficiently treated co-morbid disease (except obesity, mild hypertension (WHO 1999 criteria: systolic BP<160 mmHg and/or diastolic BP <100 mmHg) or impaired glucose tolerance); • subjects who are institutionalized; • subjects with a current episode or history of depression or bipolar disorder or a family history of suicide; • subjects who currently fulfill criteria for central sleep apnea-hypopnea syndrome or Cheyne-Stokes syndrome, periodic limb movement disorder or other dyssomnias or parasomnias (ICSD 1997); • subjects who had UPPP or other type of surgery for OSAHS; • subjects who are working on shift times; • subjects with a BMI > 45 kg/m2; • subjects who are currently treated, or had prior treatment within 3 weeks of baseline, with any antidepressant, 5HT3 antagonists (ondansetron, granisetron, tropisetron etc), 5HT1 agonists (triptans, buspirone), 5HT4 agonists (IBS treatments), antipsychotics, benzodiazepines and nonbenzodiazepine hypnotics and sedatives (including the use of sedative antihistaminergic drugs), opiates, acetazolamide and theophylline; • subjects who are treated with progestagens, of which the dose regimen of the progestagen was changed from 28 days before baseline until baseline; • subjects who have enrolled in experimental trials for the treatment of OSAHS within 3 months of screening or have ever participated in a Org 3770 or Org 50081 clinical trial; • laboratory evidence of hypothyroidism; • subjects with Marfan’s syndrome, acromegaly, congestive heart failure, congenital or hereditary disorders with cranial or maxillary abnormalities or hereditary metabolic disorders; • subjects with moderate and severe renal impairment (GFR <40 ml/min/1.73 m2) or hepatic impairment; • subjects with prior intolerance or hypersensitivity to mirtazapine; • subject who in the judgment of the investigator are unwilling or unable to adequately comply with trial procedures or adequately communicate with the investigator; • pregnancy, lactation or females of childbearing potential not practicing adequate contraceptive measures (using oral contraceptive, a barrier method in combination with a spermicidal agent or who are surgically sterilized); • subjects with documented alcohol- or drug abuse within one year of screening; a positive result for drugs of abuse and disallowed medications in their screening lab results; or subjects drinking more than 14 units of alcohol per week; • subjects who have any clinically significant abnormal laboratory data (e.g., aspartate amino transferase (ASAT) and/or alanine amino transferase (ALAT) values > 2x normal range upper limit) or ECG results, or a clinically significant abnormal outcome at the physical examination at the screening visit; • subjects who had a car accident in the 12 months before the screening period or for whom prolonged daytime sleepiness would be an unacceptable risk (e.g. professional drivers); • subjects with COPD or respiratory insufficiency from any cause (e.g. waking oxygen saturation < 90% or >10% of sleeping time at a saturation <75% in the screening PSG); • subjects with asystoles >3 sec on the screening PSG. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The change from baseline in overall Apnea Hypopnea Index (AHI) at Day 28. |
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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 | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | Yes |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | Yes |
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.8.3 |
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.8.5 | The trial involves multiple Member States | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
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 | |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 7 |