| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated | | Hypomobility (“off” or “freezing”) episodes associated with advanced Parkinson’s disease | |
| MedDRA Classification |
| E.1.3 | Condition being studied is a rare disease | Yes |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial | | To investigate the safety, tolerability, efficacy, and pharmacokinetics of VR040 in patients with established idiopathic Parkinson’s Disease | |
| E.2.2 | Secondary objectives of the trial | ·To explore the efficacy and dose response of VR040 in controlling “off” periods at 3 different doses, as measured by the primary and secondary efficacy criteria;
·To compare the efficacy of 3 doses of VR040 with that of placebo;
·To confirm the maximum tolerated dose (MTD) by examining the safety/tolerability profile and pharmacokinetics of VR040 as measured by the incidence and severity of spontaneously reported adverse events (AEs), vital signs, lung function and abnormal laboratory test results;
·To identify optimal doses for the next clinical study in patients;
·To verify that patients with idiopathic Parkinson’s Disease have sufficient dexterity and inspiratory effort to operate the Aspirair® inhaler satisfactorily. | |
| E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
| E.3 | Principal inclusion criteria | In order to be eligible to enter the protocol, patients must meet the following criteria:
1.Patients with established idiopathic PD (via fulfilment of Steps 1 and 2 of the UK Brain Bank Criteria), of at least 3 years duration prior to study entry, who are on specific and optimised anti-Parkinson medication (levodopa and/or dopamine agonists), and with motor fluctuations will be eligible to participate in the study.
2.A modified Hoehn and Yahr disease severity scoring of between 2 and 4 in an “on” state.
3.Men or women aged over 30 years.
4.A signed and dated written valid consent obtained prior to participation.
5.A woman is eligible to enter and participate in the study if she is of non-childbearing potential (ie, physiologically incapable of becoming pregnant, including any female who is post-menopausal) or child-bearing potential and has a negative pregnancy test (urine or serum) at screening.
6.Experiences motor fluctuations with recognisable “off” periods in control of motor symptoms, as assessed by the motor fluctuation questionnaire. – Patients should report at least 1 “Yes” response to the questions in the motor fluctuation questionnaire.
7.Patient willing and able to comply with study procedures.
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| E.4 | Principal 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 randomisation at Visit 2.
2.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.
3.Previous intolerance to apomorphine.
4.Previous significant complication from oral dopamine agonist therapy including hospitalisation following dopamine agonist introduction and/or the development of hallucinations or other adverse neuropsychiatric features following introduction of subcutaneous apomorphine.
5.Women during the lactation period, pregnancy or of childbearing potential not using a reliable contraceptive method.
6.Known HIV or active chronic hepatitis B or C infection.
7.Patients with any clinically significant abnormality following review of screening laboratory data and full physical examination.
8.In the Investigator’s opinion the patient is unsuitable for the study for any reason.
9.Patients with clinically significant blood test abnormalities and previous medical history/intercurrent illnesses, which may compromise the safety of the patient in the study.
10.Patients with major ECG abnormalities (as judged by the Investigator).
11.Patients with a FEV1 ≤ 65% will not be enrolled in the study.
12.Patients showing a postural decrease in systolic blood pressure of ≥ 20 mmHg, or showing significant clinical symptoms associated with orthostatic hypotension.
13.Patients with persistent elevation of blood pressure, with average systolic readings of ≥ 160 mmHg or average diastolic readings of ≥ 100 mmHg.
14.Patients taking anabolic steroids, traditional antipsychotics (unless low dose), and antiemetics other than domperidone.
15.Patients taking agents of the 5HT3 antagonist class including ondansetron, granisetron, dolasetron, palonosetron, and alosetron.
16.Patients with existing cancer and those in remission for less than 5 years.
17.Patients with 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 which in the Investigator’s opinion compromises patient safety.
18.Patients who are known non-responders to apomorphine treatment for “off” episodes.
19.History of drug or alcohol abuse in the 12 months prior to entry.
20.Patients with a history of clinically significant allergies to VR040 formulation constituents (including lactose and opioids) and domperidone.
21.All patients with signs or symptoms suggestive of schizophrenia, dementia, “Parkinson-plus” syndromes or unstable systemic disease.
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| E.5 End points |
| E.5.1 | Primary end point(s) | The primary efficacy endpoints in this study are as follows:
·The proportion of patients in an “on” disease state at any time after dosing;
·Time to improvement from “off” to “on” disease state.
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| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | Yes |
| E.6.10 | Pharmacogenetic | Information not present in EudraCT |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.3 | The trial involves single site in the Member State concerned | Yes |
| E.8.4 | The trial involves multiple sites in the Member State concerned | No |
| E.8.5 | The trial involves multiple Member States | No |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
| E.8.8 | Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial | | Last patient to complete visit 4. | |
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 0 |
| E.8.9.1 | In the Member State concerned months | 6 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 0 |
| E.8.9.2 | In all countries concerned by the trial months | 6 |
