Single-Centre Study of VR040(Inhaled Apomorphine) in Idiopathic Parkinson's Disease

An Ascending-Dose, Single-Centre Study Investigating the Safety, Tolerability, Efficacy, and Pharmacokinetics of VR040(Inhaled Apomorphine)in Parkinson's Disease

In this first study of inhaled apomorphine in Parkinson's disease patients, the primary objective is to find the minimum efficacious dose of apomorphine that is useful in rescuing patients during 'off' periods. Safety, tolerability and pharmacokinetics of inhaled apomorphine will be assessed during the study.

Study Overview

• Status: Completed
• Conditions: Parkinson's Disease
• Intervention / Treatment: Drug: Inhaled VR040; Drug: Placebo for VR040

Detailed Description

Objectives:

• Study Type: Interventional
• Enrollment (Actual): 29
• Phase: Phase 2

Contacts and Locations

Study Locations

• United Kingdom
  • Glasgow, United Kingdom, G51 4TF
    • Southern General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion 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 were on specific and optimised anti-Parkinson medication (levodopa and/or dopamine agonists), and with motor fluctuations.
2. Patients with 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. Patients with a signed and dated written valid consent obtained prior to participation.
5. Female patients must have been of non-childbearing potential (ie, physiologically incapable of becoming pregnant, including any female who was post-menopausal) or of child-bearing potential with a negative pregnancy test (urine or serum) at screening.
6. Patients who experienced motor fluctuations with recognisable "off" periods in control of motor symptoms, as assessed by the motor fluctuation questionnaire (patients were to have reported at least 1 "Yes" response to the questions in the motor fluctuation questionnaire).
7. Patient willing and able to comply with study procedures.-

Exclusion Criteria:

1. Patients who had participated in a trial with an investigational product within 3 months prior to randomisation at Visit 2.
2. Patients with 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. Patients with previous intolerance to apomorphine.
4. Patients with a 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 sc apomorphine.
5. Women lactating, pregnant, or of child-bearing potential not using a reliable contraceptive method.
6. Patients with 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. Patients who, in the Investigator's opinion, were unsuitable for the study for any reason.
9. Patients with clinically significant blood test abnormalities and previous medical history/intercurrent illnesses that may have compromised 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%.
12. Patients showing a postural decrease in systolic blood pressure (BP) of > 20 mm Hg, or showing significant clinical symptoms associated with orthostatic hypotension.
13. Patients with persistent elevation of BP, with average systolic readings of 160 mm Hg or average diastolic readings of 100 mm Hg.
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 tract, liver, kidney, central nervous system, pulmonary system, or bone marrow disorders that in the Investigator's opinion compromised patient safety.
18. Patients who were known non-responders to apomorphine treatment for "off" episodes.
19. Patients with a 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. Patients with signs or symptoms suggestive of schizophrenia, dementia, "Parkinson plus" syndromes, or unstable systemic disease

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Inhaled VR040; Inhaled apomorphine, dry powder, VR040 at fine particle doses (FPD) of 0.2mg, 0.5mg and 0.8mg. A single dose, followed by a second dose at 12 minutes if efficacy end point was not attained.	Drug: Inhaled VR040; Other Names: Inhaled apomorphine
Placebo Comparator: Placebo; Inhaled dry powder. A single dose, followed by a second dose at 12 minutes if efficacy end point was not attained.	Drug: Placebo for VR040; Placebo arm

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The proportion of patients "on" at any time post-dosing.	Parkinson's motor severity assessed by a clinician, and disease state assessment by the patient, were performed at baseline during an 'off' state, and at specified times after test drug administration.	up to 80 minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration that patients remain in an "on" state.	Time from when patient switched "on" after inhalation of study product, until patient returned to "off" state.	until return to "off" up to 3 hours

Collaborators and Investigators

• Sponsor: South Glasgow University Hospitals NHS Trust
• Collaborators: Vectura Limited

Study record dates

Study Major Dates

• Study Start: January 1, 2006
• Primary Completion (Actual): June 1, 2006
• Study Completion (Actual): May 1, 2007

Study Registration Dates

• First Submitted: September 7, 2012
• First Submitted That Met QC Criteria: September 7, 2012
• First Posted (Estimate): September 11, 2012

Study Record Updates

• Last Update Posted (Estimate): September 11, 2012
• Last Update Submitted That Met QC Criteria: September 7, 2012
• Last Verified: September 1, 2012

More Information

Terms related to this study

• Keywords: inhaled; motor fluctuations; apomorphine
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Parkinson Disease; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Gastrointestinal Agents; Dopamine Agonists; Dopamine Agents; Emetics; Apomorphine
• Other Study ID Numbers: VR040/001