Multicenter, parallel-group, double-blind, placebo-controlled phase III study to evaluate the efficacy and safety of apomorphine subcutaneous infusion in Parkinson's disease patients with motor complications not well controlled on medical treatment.
- Conditions
- parkinsonismParkinson's disease10028037
- Registration Number
- NL-OMON41299
- Lead Sponsor
- Britannia Pharmaceuticals Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 20
- Male or female patients aged >=30;
- Diagnosis of idiopathic Parkinson*s disease of >3 years* duration, defined by the UK Brain Bank criteria (with the exception of >1 affected relative being allowed), without any other known or suspected cause of Parkinsonism;
- Hoehn & Yahr stage up to 3 in the ON and 2 to 5 in the OFF state;
- Motor fluctuations not adequately controlled on medical treatment including L-dopa which was judged by the treating physician to be optimal;
- Average of OFF time >= 3 h/day based on screening and baseline diary entries with no day with < 2 hours of OFF time recorded;
- Stable medication regimen, with a stable dose of L-dopa administered in at least 4 intakes, for at least 28 days prior to baseline. All oral or transdermal antiparkinsonian drugs are permitted, with the exception of budipine. This regimen may include the use of L-dopa /DDCI rescue medication if this occurs up to 2 times a day, at doses of up to 200 mg L-dopa/day;
- Patients must be able to differentiate between the ON and OFF state and between troublesome and non-troublesome dyskinesias;
- Male and female patients must be compliant with a highly effective contraceptive method (oral hormonal contraception alone is not considered highly effective and must be used in combination with a barrier method) during the study and for 12 months long-term follow-up period, if sexually active;
- Females of childbearing potential must have a negative serum hCG or urine pregnancy test at screening;
- Ability to accurately complete a paper diary on designated days (with assistance from caregivers, if required), recording periods when they are *ON without troublesome dyskinesia*, *ON with troublesome dyskinesia*, OFF, and sleeping;
- Written informed consent prior to enrollment, after being provided with detailed information about the nature, risks, and scope of the clinical trial as well as the expected desirable and adverse effects of the study treatments;
- Patients considered reliable and capable of adhering to the protocol, visit schedule, and medication intake according to the judgment of the investigator.
- History of respiratory depression;
- Hypersensitivity to apomorphine or any excipients of the medicinal product
- High suspicion of other parkinsonian syndromes;
- Presence of severe freezing or clinically relevant postural instability leading to falls during the ON state;
- Concomitant therapy or within 28 days prior to baseline with: apomorphine pen injections; alpha-methyl dopa, metoclopramide, reserpine, neuroleptics, methylphenidate, or amphetamine; intrajejunal L-dopa;
- Previous use of apomorphine pump treatment;
- History of deep brain stimulation or lesional surgery for PD;
- Any medical condition that is likely to interfere with an adequate participation in the study, including e.g. current diagnosis of unstable epilepsy; clinically relevant cardiac dysfunction and/or myocardial infarction or stroke within the last 12 months;
- Symptomatic, clinically relevant and medically uncontrolled orthostatic hypotension;
- Patients with a borderline QT interval corrected for heart rate according to Bazett*s formula (QTc) of >450 ms for male and >470 ms for female at screening or history of long QT syndrome; or >450 ms absolute duration;
- Clinically relevant hepatic dysfunction (total bilirubin >2.0 mg/dL, ALT and AST >2 times the upper limit of normal);
- Clinically relevant renal dysfunction (serum creatinine >2.0 mg/dL);
- Pregnant and breastfeeding women;
- Clinically relevant cognitive decline, defined as MMSE <=24 or according to DSM IV criteria for dementia;
- Active psychosis or history of at least moderate psychosis in the past year, or with medically uncontrolled severe depression; very mild illusions or hallucinations in the sense of *feelings of passage or presence* with fully retained insight are not an exclusion criterion;
- Known history of melanoma;
- Any investigational therapy in the 4 weeks prior to randomization;
- History or current drug or alcohol abuse or dependencies.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Primary efficacy variable is the absolute change in time spent *OFF* from<br /><br>baseline to the end of 12 weeks treatment period based on patient diaries.</p><br>
- Secondary Outcome Measures
Name Time Method