Phase IIa Multicentre Study Investigating of VR040 in Parkinson's Disease

Parkinson's Disease Clinical Trial

— VR040/2/003  

Official title:

A Clinic-Based, Phase IIa, Double-Blind, Placebo- Controlled, Ascending-Dose, Multicentre Study of Safety, Tolerability, Efficacy and Pharmacokinetics of VR040 in Parkinson's Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01693081
• Other study ID #: VR040/2/003
• Status: Completed
• Phase: Phase 2
• First received: September 21, 2012
• Last updated: September 25, 2012
• Start date: March 2007
• Est. completion date: July 2009

Study information

• Verified date: September 2012
• Source: South Glasgow University Hospitals NHS Trust
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: National Health Service
• Study type: Interventional

Clinical Trial Summary

'Off periods' where people with Parkinson's disease are slow, stiff and unable to function are disabling, and a treatment which can converts people to a "on", good, able to function state would be extremely useful. We assessed safety, tolerability and efficacy of inhaled dry powder apomorphine (VR040) in a clinic-based study in this setting.

Description:

Background: 'Off' periods increase as Parkinson's disease progresses and the benefits of standard therapy wane. Subcutaneous apomorphine rescues 'off' periods, but patient self-injection and adverse cutaneous effects are sometimes problematic.

Methods: We assessed safety, tolerability and efficacy of inhaled dry powder apomorphine (VR040) in a clinic-based Phase II study. Of 48 patients recruited at 9 sites, 47 were randomized 2:1 inhaled apomorphine:placebo. Respirable doses (drug predicted to reach the lung) ascending through 1.5mg, 2.3mg, 3.0mg, and 4.0mg until efficacy was achieved, were administered to patients in a practically defined 'off' state. The primary endpoint was the response in unified Parkinson's disease rating scale Part 3 (UPDRS 3), at the highest dose received by the patient. Secondary endpoints included time to 'on', the proportion of patients converting from 'off' to 'on', and pharmacokinetics.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 47
• Est. completion date: July 2009
• Est. primary completion date: July 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 30 Years to 90 Years

Eligibility

Inclusion Criteria:

1. Male or female between 30 and 90 years old with idiopathic PD for at least 5 years.

2. Voluntary written informed consent provided.

3. Willing and able to comply with study procedures.

4. Fulfilled steps 1 and 2 of the UK Brain Bank Criteria.

5. Classified as Hoehn and Yahr Stage II to IV in "on" state.

6. Motor fluctuations with recognisable "off" periods in control of motor symptoms, as assessed by the Motor Fluctuation Questionnaire.

7. Optimised oral therapy.

8. Dopaminergic responsiveness as defined by = 30% improvement(reduction) in UPDRS III score compared with pre-dose value.

Exclusion Criteria:

1. Participated in a trial with an investigational product within prior 3 months.

2. Serious uncontrolled disease including serious psychological disorders.

3. Previous intolerance to apomorphine.

4. Previous significant complication from oral dopamine agonist therapy

5. Women lactating, pregnant or of child-bearing potential not using a reliable contraceptive method (eg, barrier, intrauterine device, abstinence).

6. Known HIV or active chronic hepatitis B or C infection.

7. Any clinically significant abnormality following review of screening observations

8. Patients who, in the Investigator's opinion, were unsuitable for the study for any reason.

9. Major ECG abnormalities.

10. Patients with a FEV1 = 65% predicted.

11. Patients showing a postural decrease in systolic blood pressure (BP) of =20 mm Hg or showing significant clinical symptoms associated with orthostatic hypotension.

12. Patients with persistent arterial hypotension, with average systolic readings of =110 mm Hg.

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 apomorphine at any time during these study visits, anabolic steroids,traditional antipsychotics (unless low dose) and vasodilators other than for the treatment of hypertension. The following atypical antipsychotics were permitted: Quetiapine (up to and including 50 mg per day), risperidone (up to and including 1 mg per day) and olanzapine (up to and including 2.5 mg per day).

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(eg, in previous challenge tests or trials).

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 psychosis, dementia, "Parkinson-plus" syndromes or unstable systemic disease.

22. Patients with history of stroke, seizure or other neurological conditions.

23. Patients with dyskinesia rated 4 in Item 32 of UPDRS IV assessment at Screening(dyskinesia present =76% of a waking day).

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Parkinson Disease
• Parkinson's Disease

Intervention

Drug:
• VR040/Aspirair® inhaler
Dry Powder inhaled apomorphine
• placebo

Locations

Country	Name	City	State
Serbia	Institute of Neurology Clinical Center Serbia Dr Subotica 6	Belgrade
Serbia	Neurology Clinical Military Medical Academy, Crnotravska 17	Belgrade
United Kingdom	University Hospital, Wales	Cardiff
United Kingdom	Department of Neurology, Southern General Hospital	Glasgow
United Kingdom	The Walton Centre	Liverpool
United Kingdom	Llandudno Hospital	Llandudno
United Kingdom	Newark Hospital	Newark
United Kingdom	Neurology Dept, Radcliffe Infirmary	Oxford
United Kingdom	Essex Neurosciences, UnitOld Church Hospital, Essex	Romford Essex

Sponsors (2)

Lead Sponsor	Collaborator
South Glasgow University Hospitals NHS Trust	Vectura Limited

Countries where clinical trial is conducted

Serbia,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Safety variables	Safety variables were: the pre- to post-dose change in vital signs, 12-lead ECG and continuous 12-lead Holter ECG, and lung function.	90minutes	Yes
Primary	The maximum UPDRS 3 improvement from pre-dose to post-dose	The primary efficacy endpoint was the maximum UPDRS 3 improvement from pre-dose to post-dose at the highest dose used.	90 minutes	No
Secondary	Time to improvement from 'off' to 'on'	Time to improvement from 'off' to 'on'.	90 minutes	No
Secondary	The duration of 'on'	The duration of 'on', the duration of time when the patient can function well.	90 minutes	No
Secondary	The proportion of patients converting to 'on' any time after treatment administration.	The proportion of patients converting to 'on' any time after treatment administration.	90 minutes	No