E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Alleviation of acute episodes of motor symptoms associated with Parkinson's Disease |
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MedDRA Classification |
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 determine the safety and local tolerability of repeated once daily dosing with Apomorphine Nasal Powder 2 and 4 mg over a period of 12 weeks, in subjects with Parkinson’s disease. |
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E.2.2 | Secondary objectives of the trial |
- To determine the effect of once daily dosing with Apomorphine Nasal Powder 2 and 4 mg in comparison with Placebo Nasal Powder based on time to alleviate a daily acute episode of Parkinsonian motor symptoms (’off’ episode) over a period of 7 days for each blinded week and compared to Baseline, in subjects with Parkinson’s disease.
- To determine the effect of once daily dosing with Apomorphine Nasal Powder 2 and 4 mg in comparison with Placebo Nasal Powder based on the UPDRS (Sections 18-31) rating scale recorded in the clinic at 15 and 30 min post dose at Visits 1, 2 and 3, in subjects with Parkinson’s disease.
- To determine the efficacy, safety and local tolerability of repeated once daily dosing with Apomorphine Nasal Powder 2 and 4 mg over a period of 48 weeks, in subjects with Parkinson’s disease.
- To assess changes in quality of life at Visit 7 and Visit 16 and compared to Baseline in subjects with Parkinson’s disease. |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
At Screening Visit:
1. Ability and willingness to give written informed consent
2. Males and females aged 18 years and over
3. History of Parkinson’s disease for at least 1 year prior to screening
4. Documented medication for Parkinson’s disease for at least 6 months prior to screening
5. Currently on established, stable treatment for Parkinson’s disease (i.e. unchanged in the last 4 weeks)
6. Subjects naïve to subcutaneous apomorphine
7. At least one documented predictable or unpredictable daily acute episode of Parkinsonian motor symptoms (’off’ episode) that persists for longer than 30 minutes and resolves the same day
8. Willingness to take oral domperidone as anti-emesis prophylaxis for the duration of the blinded phase of the study and if required during open label
9. Willingness to agree not to change the dose of their usual Parkinsonian medication for the duration of blinded phase (except in the event of an emergency such as hospitalisation)
10. Ability to communicate well with the Investigator and comply with the requirements of the study
At Baseline Visit:
1. Ability to complete the diary card satisfactorily
At Visit 1:
1. One documented predictable or unpredictable daily acute episode of Parkinsonian motor symptoms (’off’ episode) that persists for longer than 30 minutes and resolves the same day - as demonstrated by the mean duration of the monitored acute episode of motor symptoms for the last 6 days in the completed Screening and Baseline diary cards, respectively
2. No clinically significant abnormal laboratory values or ECG findings which the Investigator considers would make the subject unsuitable for the study
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E.4 | Principal exclusion criteria |
At Screening and Baseline Visit:
1. Participation in any clinical study within the 12 weeks prior to screening
2. Subjects with respiratory depression, dementia, psychotic disease or hepatic insufficiency
3. Subjects with known hypersensitivity to apomorphine, its derivatives or any excipients of the product (mannitol and ascorbic acid)
4. Subjects who have an ‘on’ response to levodopa, which is marred by severe dyskinesia or dystonia
5. Pregnant or lactating females, or those likely to become pregnant
Additional Advice: The Investigator should exercise caution when administering apomorphine to subjects:
· With renal, pulmonary or cardiovascular disease · Prone to nausea and vomiting · If elderly or debilitated · With pre-existing cardiac disease or taking vasoactive medicinal products · With Postural hypotension · Who have neuropsychiatric disturbances
Apomorphine has been associated with somnolence, therefore subjects who experience somnolence must refrain from driving or operating machines. Coombs positive haemolytic anaemia has been reported in patients treated with levodopa. Haematology tests will therefore be performed regularly during the study.
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E.5 End points |
E.5.1 | Primary end point(s) |
The main efficacy endpoint is:· The time to initial improvement in the acute ‘off’ episode of Parkinsonian motor symptoms, as recorded in the diary card. The mean time for each subject in each treatment period will be calculated from the available data. |
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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 | No |
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 | Information not present in EudraCT |
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 | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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 | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | Yes |
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 | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
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 | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
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 | 6 |