Alleviation of acute episodes of motor symptoms associated with Parkinson's Disease MedDRA version: 8.1 Level: LLT Classification code 10061536 Term: Parkinson's disease
Conditions
Interventions
Product Name: Apomorphine Nasal Powder
Pharmaceutical Form: Nasal powder
Other descriptive name: 6aß - apomorphine-10,11-diol hydrochloride hemihydrate
Concentration unit: % (W/W) percent weight/weigh
Sponsors
Britannia Pharmaceuticals Limited
Eligibility
Sex/Gender
All
Inclusion criteria
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 therapy. Subjects who have undergone apomorphine challenge for diagnostic purposes (but who have not used subcutaneous apomorphine therapy) may be included. 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 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 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
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. Women of child bearing potential entered into the the study should be using adequate contraception and instructed to inform the Investigator if at any time they suspect they are pregnant or intend to become pregnant.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 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. ;Secondary Objective: - To determine the effect of once daily dosing with Apomorphine (APO) 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 (PD). - To determine the effect of once daily dosing with APO 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 PD. - To determine the efficacy, safety and local tolerability of repeated once daily dosing with APO Nasal Powder 2 and 4 mg over a period of 48 weeks, in subjects with PD. - To assess changes in quality of life at Visit 7 and Visit 16 and compared to Baseline in subjects with PD. - To assess changes in non-motor symptoms between Baseline, Visit 7 and Visit 16 in subjects with PD.;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 and in clinical assessments. The mean time for each subject in each treatment period will be calculated from the available data. | — |
Countries
Germany, Netherlands, United Kingdom
Outcome results
None listed