Hypomobility (off or freezing) episodes associated with advanced Parkinson's disease
Conditions
Interventions
Product Name: Apomorphine hydrochloride
Product Code: VR040
Pharmaceutical Form: Inhalation powder
Pharmaceutical form of the placebo: Inhalation powder
Route of administration of the placebo: Inhalat
Sponsors
Vectura Group plc
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: In order to be eligible to enter the study, patients must meet all of the following criteria: 1.Male and female patients between 30 and 90 years of age with a clinical diagnosis of idiopathic PD for at least 5 years duration 2.Fulfilment of steps 1 & 2 of the UK brain bank criteria (Appendix 3) 3.Patients classified as Hoehn & Yahr stage II-IV in “on” state (Appendix 4) 4.Suffered motor fluctuations associated with late-stage PD, and a minimum of 2-hour average daily “off” time (to be confirmed by the baseline diary card at Visit 2) (Appendix 5) 5.Received optimised oral therapy including LD 300-1500 mg/day (in combination with decarboxylase inhibitors) at least 30 days before screening. For patients receiving controlled-release (CR) formulations, the dose range is based on a 70% bioavailability adjustment (ie, 100 mg CR = 70 mg non-CR). 6.Written informed consent 7.Willing and able to comply with study procedures. 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: Patients will be excluded from the study if they meet any of the following criteria: 1.Participation in a trial with an investigational product within 3 months prior to Visit 1. 2.Previous exposure to subcutaneous apomorphine (except for use as a diagnostic challenge). 3.Serious uncontrolled disease, including serious psychological disorders likely to interfere with the study and/or likely to cause death within 6 months of the study completion. 4.Previous intolerance to apomorphine (in testing such as by nasal or inhalational route in prior clinical trials, or by subcutaneous route used during challenge testing). 5.Previous significant complication from oral DA therapy including hospitalisation following DA introduction and/or the development of hallucinations or other adverse neuropsychiatric features. Specific severe mental side effects include compulsive behaviour, psychosis, or hallucination that led to withdrawal of oral DA therapy. 6.Women during the lactation period, pregnancy or of childbearing potential not using a reliable contraceptive method. 7.Known HIV or active chronic hepatitis B or C infection. 8.Any clinically significant abnormality following review of screening laboratory data and full physical examination. 9.In the Investigator’s opinion, the patient is unsuitable for the study for any reason. 10.Clinically significant blood test abnormalities (to be confirmed by laboratory results at Visit 2) and previous medical history/intercurrent illnesses, which may compromise the safety of the patient in the study. 11.ECG abnormalities that, in the opinion of the Investigator, would preclude study entry. 12.FEV1 = 65% will not be enrolled in the study. 13.A postural decrease in systolic blood pressure of = 20 mmHg, or showing significant clinical symptoms associated with orthostatic hypotension. 14.Persistent arterial hypotension, with average systolic readings of =110 mmHg. 15.Persistent elevation of blood pressure, with average systolic readings of =160 mmHg or average diastolic readings of =100 mmHg. 16.Taking prohibited concomitant medications (Section 7.2). 17.Consumption of anabolic steroids or antipsychotics (except quetiapine at low dose). 18.Consumption of the 5HT3 antagonist class including ondansetron, granisetron, dolasetron, palonosetron, and alosetron. 19.Existing cancer and those in remission for less than 5 years. 20.Evidence as ascertained from examination, tests or history to indicate cardiovascular, gastrointestinal (GI) tract, liver, kidneys, central nervous system (CNS), pulmonary system or bone marrow disorders that, in the Investigator’s opinion, compromises patient safety. 21.Known non-responders to apomorphine treatment for “off” episodes, eg, in previous trials. 22.History of drug or alcohol abuse in the 12 months prior to entry. 23.A history of clinically significant allergies to VR040 formulation constituents (including lactose and opioids) or domperidone (for patients who will be taking it). 24.Signs or symptoms suggestive of psychosis, dementia, “Parkinson-plus” syndromes, or unstable systemic disease. 25.History of stroke, seizure, or other neurological conditions. 26.Patients with dyskinesia rated =2 in Item 32 of UPDRS IV assessment at screening (dyskinesia present =26% of a 24-h day).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: •To explore in patients with advanced idiopathic PD the efficacy and safety of VR040 as measured by primary and secondary endpoints. •To compare the efficacy of up to 3 doses of VR040 with that of placebo in controlling the “off” periods in patients with advanced idiopathic PD. •To determine the extent of patient acceptance of the Aspirair® inhaler as measured by the Patient Acceptability Questionnaire. •To verify the ability of patients with PD to use the Aspirair® inhaler as measured by the need for retraining. •To verify the suitability of the Aspirair® inhaler for use at home by the patient or the carer. The mechanical robustness and the drug delivery performance of the inhaler will be verified in the laboratory by examination and testing of the returned devices at the end of the study. ;Secondary Objective: ;Primary end point(s): The primary efficacy endpoint, the total UPDRS III score, is calculated for each patient as the change from pre-dose score to post-dose score captured at each dose escalation visit. The UPDRS III data will be collected during the dose titration procedures conducted at Visits 3-5. | — |
Countries
United Kingdom
Outcome results
None listed