E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Obstructive Sleep Apnoea (OSA) |
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E.1.1.1 | Medical condition in easily understood language |
OSA is caused by intermittent pauses in breathing due to repetitive narrowing or collapse of the upper airway during sleep leading to a drop in blood oxygen. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Respiratory Tract Diseases [C08] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10029983 |
E.1.2 | Term | Obstructive sleep apnoea 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 |
What is the effect of morphine on the severity of Obstructive Sleep Apnoea (OSA) measured by Apnoea Hypopnoea Index (AHI - the number of pauses in breathing) in patients with known moderate OSA? |
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E.2.2 | Secondary objectives of the trial |
1. To assess the effect of intravenous (iv) morphine on arterial oxygen desaturation index (the number of times per hour of sleep that the blood's oxygen level drops by 4 percent or more from baseline, ODI) of ≥ 4% per hour measured during overnight sleep study (respiratory polygraphy, rPSG) 2. To assess the frequency of central apnoeas (due to a problem either in the drive to breathe which is generated within the brain or to weakness of the breathing muscles) obstructive apnoeas (due to the obstruction of the upper airway) and mixed apnoeic events (a combination of both central and obstructive apnoeic events) measured during the study rPSG 3. To measure the percentage of time spent with an arterial oxygen saturation (the amount of oxygen in the blood) of less than 90% during the study rPSG 4. To assess the safety endpoints of morphine administration.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.Age ≥ 18 years 2.Patients with a diagnosis of moderate OSA diagnosed by nocturnal oximetry, rPSG or PSG (defined as AHI or ODI of 15-29 events/hour) established on Continuous Positive Airway Pressure (CPAP) 3.Patients with confirmed moderate OSA by rPSG 6 nights after withdrawal of CPAP (baseline rPSG)
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E.4 | Principal exclusion criteria |
1.Inability to give informed consent or comply with the protocol 2.History of acute respiratory tract infection or chronic respiratory disease, symptomatic ischemic heart disease 3.Pregnancy or suspected pregnancy/breast feeding 4.Current or recent (within last week) use of hypnotic, opioid or sedative drugs 5.A known allergy to the IMP or NIMP(s) 6.Patients with an inadequate command of English and requiring an interpreter overnight 7.Change in weight of > 5% since the baseline rPSG 8.Vital signs recordings (oxygen saturations, blood pressure, pulse rate) that in clinician's opinion make it unsafe for the patient to participate in the trial 9.Clinician deems patient unsafe to participate in the trial (e.g. severely sleepy patients who cannot withdraw from CPAP) 10.CPAP intolerant/poor responder 11.History of Intravenous (iv) drug abuse 12.Patient unable to organise transport home following the study visit 13.Professional driver
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E.5 End points |
E.5.1 | Primary end point(s) |
Change in Apnoea Hypopnoea Index (AHI) – change in mean number of apnoeas and hypopneas per hour of sleep from subject's baseline rPSG to the study rPSG. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
AHI is monitored during the overnight sleep study (rPSG). Patients will be monitored by rPSG during the treatment night when they receive either IMP. |
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E.5.2 | Secondary end point(s) |
Change in the following parameters from subject’s baseline rPSG study rPSG:
1.Arterial oxygen desaturation of ≥ 4% per hour (Oxygen Desaturation Index, ODI) measured by pulse oximetry during the rPSG 2.Percentage of time with nocturnal saturations of ≤ 90%- (SpO2≤ 90%) measured by pulse oximetry during the rPSG 3.To assess the number and severity of any adverse events associated with the IMP (morphine).
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
All secondary variables are monitored during the overnight study (rPSG). Patients will be monitored by rPSG during the treatment night when they receive the IMP (morphine). |
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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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
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 | 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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
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) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | No |
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 | No |
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 | 5 |
E.8.9.1 | In the Member State concerned days | 28 |
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 | 5 |
E.8.9.2 | In all countries concerned by the trial days | 28 |