Efficacy and safety of orally inhaled apomorphine in patients with Parkinson's disease

ISRCTN ISRCTN41929673
DOI https://doi.org/10.1186/ISRCTN41929673
Protocol serial number VR040/2/008
Sponsor Vectura Limited (UK)
Funder Vectura Limited (UK)
Submission date
17/12/2008
Registration date
16/02/2009
Last edited
17/05/2016
Recruitment status
No longer recruiting
Overall study status
Completed
Condition category
Nervous System Diseases
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Record updated in last year

Plain English summary of protocol

Not provided at time of registration

Contact information

Dr Donald Grosset
Scientific

Department of Neurology
Southern General Hospital
1345 Govan Road
Glasgow
G51 4TF
United Kingdom

Study information

Primary study designInterventional
Study designRandomised double-blind placebo-controlled parallel-group study
Secondary study designRandomised controlled trial
Study type Participant information sheet
Scientific titleA phase IIb randomised, double-blind, placebo-controlled, parallel-group study investigating the efficacy and safety of inhaled apomorphine in patients with "on-off" or "wearing-off" effects associated with Parkinson's disease
Study objectivesApomorphine administered by injection or subcutaneous pump is approved for the treatment of disabling motor fluctuations that persist in PD patients, despite treatment with levodopa and/or oral dopamine agonists. Inhaled apomorphine is expected to present a more rapid clinical effect achieved via a convenient and non-invasive route of administration. Treatment consistency will be improved, allowing accurate and precise dose setting, thereby minimising peak-dose dyskinesia incidence. Based upon inhaled apomorphine bioavailability, an improved risk/benefit profile may be established, resulting in a reduced need to administer concomitant domperidone medication.
Ethics approval(s)A favourable opinion was given by Scottish A Research Ethics Committee on 12/11/2008 and by Ricerca Biomedica dell'Universita Degli Studi Gabriele D'Annunzio e della Asl di Chieti, Italy on 27/11/2008. Approval is pending from Ethics Committee of the Dept. of Human Medicine, Philipps University, Marburg, Germany.
Health condition(s) or problem(s) studiedParkinson's disease
InterventionDuring an In-Clinic dosing period patients will be titrated to their optimal delivered dose of Apomorphine HCl or placebo based on tolerance and efficacy, for up to 6 weeks. During the At-Home dosing period, patients will take their study medication for the treatment of sudden "on-off" or "wearing-off" episodes up to 5 times per day for 4 weeks at his or her optimal dose as determined during the In-Clinic dosing period. Patients will be followed-up for a further 3 weeks.
Intervention typeDrug
PhasePhase II
Drug / device / biological / vaccine name(s)Apomorphine
Primary outcome measure(s)

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.

Key secondary outcome measure(s)

1. Proportion of "off" events per day aborted by study treatment
2. Interval between dose administration and onset of "on" state
3. Period from onset of "on" state to return to an "off" state
4. Mean daily duration in "on" without dyskinesias
5. Mean daily duration in "on" with non-troublesome dyskinesias
6. Mean daily duration in "on" with troublesome dyskinesias
7. Time taken for the study medication to start working and the period of time when the study medication was working
8. Mean number of "off" episodes per day
9. Mean daily period in "off" state
10. Mean daily period in any "on" state
11. Mean daily period asleep

Safety parameters:
12. Incidence of treatment-emergent AEs
13. Changes in laboratory tests and physical examination
14. Changes in vital signs, ECG, forced vital capacity (FVC)/FEV1

All measured from screening to the end-of-treatment or close out visit.

Completion date15/11/2009

Eligibility

Participant type(s)Patient
Age groupAdult
SexAll
Target sample size at registration66
Key inclusion criteria1. 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
Key exclusion criteria1. 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
Date of first enrolment15/01/2009
Date of final enrolment15/11/2009

Locations

Countries of recruitment

  • United Kingdom
  • Scotland
  • Germany
  • Italy

Study participating centre

Southern General Hospital
Glasgow
G51 4TF
United Kingdom

Results and Publications

Individual participant data (IPD) Intention to shareNo
IPD sharing plan summaryNot provided at time of registration
IPD sharing plan

Study outputs

Output type Details Date created Date added Peer reviewed? Patient-facing?
Participant information sheet Participant information sheet 11/11/2025 11/11/2025 No Yes

Editorial Notes

17/05/2016: No publications found, verifying study status with principal investigator.

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