A study investigating the safety of CVT-301 in patients with Parkinson's Disease

• Register: EUCTR
• Last refreshed on: 21 January 2013
• Main ID: EUCTR2012-000181-37-GB
• Date of registration: 27/02/2012
• Prospective Registration: Yes
• Primary sponsor: Civitas Therapeutics, Inc.
• Public title: A study investigating the safety of CVT-301 in patients with Parkinson's Disease
• Scientific title: A Randomized, Placebo-Controlled Phase 2 Study of the Safety, Pharmacokinetics, and Pharmacodynamics of CVT-301 (Levodopa Inhalation Powder) in Patients with Parkinson’s Disease and Motor Response Fluctuations (“Off” Episodes)
• Date of first enrolment: 25/04/2012
• Target sample size: 24
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2012-000181-37
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: yes Other: no Number of treatment arms in the trial: 6

Countries of recruitment

Israel, Serbia, United Kingdom

Contacts

• Name: Global Regulatory Start-up Manager
• Affiliation: i3 International (UK) Limited

• Name: Global Regulatory Start-up Manager
• Affiliation: i3 International (UK) Limited

Key inclusion & exclusion criteria

Inclusion criteria:
1. Has signed and dated an IEC-approved informed consent form before any protocol specific screening procedures are performed.
2. Has a clinical diagnosis of idiopathic PD (i.e., not induced by drugs or other diseases) as defined by fulfilling Steps 1 and 2 of the UK Brain Bank criteria, diagnosed at an age of 30 to 80 years, inclusive.
3. Is a male or female over the age of 30 years. Women of child-bearing potential must use protocol-defined contraceptive measures and must have a negative serum human chorionic gonadotropin (hCG) test at screening. These patients must be willing to remain on their current form of contraception for the duration of the study.
4. Is classified as Stage 1 to 3 (in the “on” state) on the modified Hoehn and Yahr scale for staging of PD severity.
5. Is levodopa-responsive (as documented by the investigator) with a PD medication regimen that includes a levodopa/DDI-containing regimen at least 4 times during the waking day. Levodopa-containing regimens must be stable for at least 2 weeks prior to
screening.
6. If treated with dopamine agonists, COMT inhibitors, MAO-B inhibitors, or other nonlevodopa-containing PD medications, must be on a stable dose for at least 4 weeks prior to screening and must remain stable throughout the study.
7. Has not received apomorphine for at least 2 weeks prior to screening and agrees not to be treated with apomorphine for the duration of the study.
8. Experiences motor fluctuations with recognizable and predictable “off” periods and has an average of at least 2 hours of “off” time per waking day, exclusive of early morning “off” time (by self-report). Patients should be able to recognize their “wearing off” symptoms and verify that they usually improve after their next dose of PD medication.
9. If a current smoker, is able to comply with the following guidelines: agrees not to smoke on the mornings of study dosing days and for the entire study dosing day until completion of all study procedures.
10. Is willing and able to complete all study assessments and procedures.
11. Has an FEV1 greater than 70% of predicted for race, age, sex, and height, and FEV1/FVC (forced vital capacity) ratio greater than or equal to 75%, in the “on” state.
12. Patients may be taking anti-depressant medication, but the dose must be stable for at least 4 weeks prior to screening.
13. Understands (with or without carer assistance) his/her daily PD medications.
14. Is able (with or without carer assistance) to attend all study visits.
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 12
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 12

Exclusion criteria:
1. Is a pregnant or lactating woman.
2. Has severe dyskinesia that would significantly interfere with the patient’s ability to perform study assessments.
3. Has any condition that in the investigator’s opinion would make the patient unsuitable for participation in the study and/or medical condition that, in the opinion of the investigator, would interfere with participation in this study.
4. Has a history of chronic obstructive pulmonary disease (COPD), asthma, or other chronic respiratory diseases within the last 5 years, or is currently receiving treatment for any of these conditions.
5. Has used neuroleptics, reserpine, or catecholaminergic blocking agents within the last 3 months.
6. Has received dopamine agonist blocking agents and/or non-specific monoamine oxidase inhibitors (MAOIs) within the last 3 months; however, domperidone is allowed if the maximum daily dose does not exceed 60 mg and if the dose has been stable for at least 4 weeks prior to screening.
7. Has a history of psychotic symptoms requiring treatment with an antipsychotic medication within the past 12 months; however, certain low-dose atypical antipsychotic agents (prescribed for conditions other than psychosis) are allowed if the dose has been
stable for at least 8 weeks prior to screening (quetiapine =50 mg/day, risperidone =1 mg/day, and olanzipine =2.5 mg/day).
8. Has a history of suicidal ideation or suicide attempt within the past 12 months.
9. Has had previous surgery for PD or is planning stereotactic surgery during the study period.
10. In the opinion of the investigator (or carer, as applicable), has signs/symptoms suggestive of clinically significant cognitive impairment that would interfere with the ability to comply with study procedures.
11. Has a history of any primary malignancy, with the exception of basal cell or squamous cell carcinomas of the skin or cervical carcinoma in situ or other malignancies curatively treated and with no evidence of disease for at least 3 years.
12. Has a history within 12 months prior to screening of substance-related disorders (with the exception of caffeine-related and nicotine-related disorders) as defined in the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR).
13. Has a QTcF interval of =450 msec for males or =470 msec for females, or has a clinically significant abnormal ECG as assessed by a qualified physician at screening.
14. Has any clinically significant abnormality following review of screening laboratory data, previous medical history or intercurrent illness, and physical examination data that, in the investigator’s opinion, may compromise the safety of the patient in the study.
15. Has been treated with an investigational drug within 4 weeks or 5 half-lives (whichever is longer) prior to the beginning of the screening period (this includes investigational formulations of marketed products).
16. Has had >500 mL of blood collected within 8 weeks prior to screening.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Parkinson's Disease
MedDRA version: 14.1 Level: LLT Classification code 10034007 Term: Parkinson's disease NOS System Organ Class: 10029205 - Nervous system disorders

Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Intervention(s)

Product Name: CVT-301
Product Code: CVT-301
Pharmaceutical Form: Inhalation powder, hard capsule
INN or Proposed INN: LEVODOPA
CAS Number: 59-92-7
Current Sponsor code: CVT-301
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 12.5-
Pharmaceutical form of the placebo: Inhalation powder, hard capsule
Route of administration of the placebo: Inhalation use

Trade Name: Sinemet®
Product Name: SINEMET® Plus 25 mg/100 mg Tablets
Pharmaceutical Form: Tablet
INN or Proposed INN: LEVODOPA
CAS Number: 59-92-7
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-
CAS Number: 38821-49-7
Other descriptive name: CARBIDOPA MONOHYDRATE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 25-

Primary Outcome(s)

Main Objective: To characterize the safety and tolerability of inhaled CVT 301 in Parkinson’s disease patients experiencing “off” episodes

Secondary Objective: To characterize the input phase pharmacokinetic (PK) profile of single, inhaled doses of levodopa in patients with Parkinson’s disease experiencing “off” episodes

To evaluate the pharmacodynamics of single, inhaled doses of levodopa or a standard oral dose of levodopa in patients with Parkinson’s disease experiencing “off” episodes

Exploratory Objective
To describe and model the relationship of levodopa plasma concentration to motor response

Timepoint(s) of evaluation of this end point: Pharmacokinetic Endpoints:
5 and 10 minutes post-dosing

Pharmacodynamic Endpoints:
Up to 3 hours post-dosing

Primary end point(s): Pharmacokinetics
Baseline-adjusted maximum concentration (?Cmax = Cmax - C0), time to maximum concentration (tmax), and baseline-adjusted partial area under the concentration-time curve (pAUC), e.g. at 5 0 (pAUC0-5) and 10 (pAUC0-10) minutes postdosing.

Pharmacodynamics
• Areas under the curve (AUC) from 0 - 3 hours.
• Average response for all assessments at 0 to 3 hours after the dose of study medication

• Best response for all assessments at 0-3 hours after the dose of study medication
• Early effect, defined as average response of assessments at 0-30 minutes after the dose of study medication

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Not Applicable

Secondary end point(s): Not Applicable

Secondary ID(s)

CVT-301-002

Source(s) of Monetary Support

Civitas Therapeutics, Inc.