Efficacy and safety of orally inhaled apomorphine in patients with Parkinson's disease
- Conditions
- Parkinson's diseaseNervous System Diseases
- Registration Number
- ISRCTN41929673
- Lead Sponsor
- Vectura Limited (UK)
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- All
- Target Recruitment
- 66
1. Male and female patients between the ages of 30 and 90 years
2. A clinical diagnosis of PD of at least 5 years duration
3. Fulfilled Steps 1 and 2 of the UK Brain Bank Criteria
4. Classified as Hoehn and Yahr Stage II - IV in on state
5. Have suffered from motor fluctuations associated with fluctuating idiopathic PD and a minimum of a 2-hour average daily off time
6. Showed dopaminergic responsiveness as defined by equal to or more than 30% change (reduction) in Unified Parkinson's Disease Rating Scale (UPDRS III) score compared to the pre-dose value
7. Optimised on oral therapy, including levodopa not greater than 1500 mg/day (in combination with decarboxylase inhibitors) at least 30 days before screening
8. Receiving (for at least 30 days), or have received in the past, but discontinued due to adverse events (AEs), at least one of the following types of medications:
8.1. Dopamine agonist
8.2. Catechol-o-methyltransferase inhibitor
8.3. Monoamine oxidase B inhibitor
9. Understand (with carer assistance) their daily medications
1. Very serious or advanced disease
2. Dyskinesias rated as severe, i.e. equal to 2 in Item 32 of the UPDRS IV assessment and equal to 2 in Item 33 of the UPDRS IV assessment, at screening
3. Previous intolerance or allergy to apomorphine or any of its constituents, or any previous significant historic complication from oral dopamine agonist (DA) therapy
4. Pregnant or lactating females, and patients with known human immunodeficiency virus or active chronic hepatitis B or C infection
5. Any clinically significant abnormality or finding from examination, tests, or history that may compromise patient safety, specifically any history of renal or hepatic impairment
6. Relevant electrocardiogram (ECG) abnormalities
7. Forced expiratory volume in one second (FEV1) equals 65% predicted
8. Evidence of orthostatic or persistent arterial hypotension
9. Hypertension
10. Cancer
11. Those taking certain prohibited medications or anabolic steroids or antipsychotics (some exceptions apply)
12. Those taking 5HT3 antagonists or clozapine
13. History of drug or alcohol abuse
14. Current, or a history of, hypersensitivity to domperidone, pituitary tumour (prolactinoma), or gastrointestinal blockage or haemorrhage
15. Known non-responders to apomorphine treatment for off episodes, e.g. in previous challenge tests or trials
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Change in off time per day compared with the baseline value derived from the three-consecutive-day patient diary card information completed prior to visit 1 and prior to visits 5 and 6 during the At-Home dosing period and the maximum change in total UPDRS III score from pre-dose to post-dose during the In-Clinic dosing titration period.
- Secondary Outcome Measures
Name Time Method 1. Proportion of off events per day aborted by study treatment<br>2. Interval between dose administration and onset of on state<br>3. Period from onset of on state to return to an off state<br>4. Mean daily duration in on without dyskinesias<br>5. Mean daily duration in on with non-troublesome dyskinesias<br>6. Mean daily duration in on with troublesome dyskinesias<br>7. Time taken for the study medication to start working and the period of time when the study medication was working<br>8. Mean number of off episodes per day<br>9. Mean daily period in off state<br>10. Mean daily period in any on state<br>11. Mean daily period asleep<br><br>Safety parameters:<br>12. Incidence of treatment-emergent AEs<br>13. Changes in laboratory tests and physical examination<br>14. Changes in vital signs, ECG, forced vital capacity (FVC)/FEV1 <br><br>All measured from screening to the end-of-treatment or close out visit.