A study of the safety and drug effects of levodopa inhalation powder (CVT-301) compared to Standard of Care Observational Cohort in patients with Parkinson’s disease

• Register: EUCTR
• Last refreshed on: 3 July 2017
• Main ID: EUCTR2014-003799-22-CZ
• Date of registration: 26/11/2014
• Prospective Registration: Yes
• Primary sponsor: Civitas Therapeutics, Inc.
• Public title: A study of the safety and drug effects of levodopa inhalation powder (CVT-301) compared to Standard of Care Observational Cohort in patients with Parkinson’s disease
• Scientific title: A Phase 3, Randomized Study Investigating the Safety of CVT-301 (Levodopa Inhalation Powder) in Parkinson’s Disease Patients With Motor Response Fluctuations (OFF Phenomena) Compared to an Observational Cohort Control
• Date of first enrolment: 26/02/2015
• Target sample size: 408
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-003799-22
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: yes Other specify the comparator: Standard of Care Treatment Number of treatment arms in the trial: 1
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Austria, Belgium, Czech Republic, France, Germany, Hungary, Israel, Italy, Poland, Romania, Serbia, Spain, United Kingdom, United States

Contacts

• Name: Regulatory Affairs
• Affiliation: INC Research

• Name: Regulatory Affairs
• Affiliation: INC Research

Key inclusion & exclusion criteria

Inclusion criteria:
Has signed and dated an IRB/IEC-approved informed consent form before any protocol-specific screening procedures are performed.
Is a male or female aged 30 to 85 years, inclusive. Women of child-bearing potential must use protocol-defined contraceptive measures (see Section 11.1.5) 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.
Patients who have 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 after the age of 30 years.
Patients who are classified as Stage 1 to 3 (in the ON state) on the modified Hoehn and Yahr scale for staging of PD severity.
Patients who have experienced motor fluctuations for a minimum of 2 hours of average daily OFF time per waking day (excluding early morning OFF time) by self-report and confirmed by the PD Diary (on 3 consecutive days) during the screening period.
Patients who are on a LD-containing therapy, not including Rytary (or equivalent), must be stable on oral LD-containing therapy for at least 2 weeks prior to SV1 with a LD/dopamine decarboxylase inhibitor (DDI) containing regimen.
Patients who are on a LD containing therapy, when including Rytary (or equivalent), should be on a stable dose for at least 6 weeks prior to SV1. The frequency of L-dopa administrations must be at least 3 times during the waking day and a total daily LD dose of =1600 mg (exclusive of PRN LD-containing medications).
Patients should be stable on other PD medications for at least 4 weeks prior to SV1.
Patients must have a =25% difference between UPDRS Part 3 scores recorded in their ON and OFF states at screening.
Patients must have normal cognition as confirmed by a score of =25 on the MMSE, performed in the ON state.
Patients must be able to perform a spirometry maneuver in the ON and OFF states, and must have a screening FEV1 =50% of predicted and an FEV1/FVC ratio >60% in the ON state at screening. (A pulmonologist will review the spirometry tracings/morphology of any patient with an FEV1 that is =50% to <60% of predicted or an FEV1/FVC ratio that is >60% to <70% in order to determine potential eligibility. All CVT 301 naïve patients with an FEV1/FVC ratio of >60% to <70% will be required to undergo a bronchodilator challenge and the results must be reviewed prior to entry into the study. Patients with an FEV1/FVC ratio that is >60% to <70% will complete spirometry before and after the administration of a bronchodilator in a pulmonary function laboratory. Testing will be performed in accordance with the 2005 ATS/European Respiratory Society [ERS] criteria prior to randomization. The results of the bronchodilator challenge will be reviewed by a pulmonologist prior to potential randomization.)

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 213
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 195

Exclusion criteria:
Patients who have dyskinesia of a severity that would significantly interfere with their ability to participate or perform study procedures.
Pregnant or lactating females or females wishing to become pregnant.
Patients who have any known contraindication to the use of LD, including a history of malignant melanoma or a history of narrow-angle glaucoma.
Patients who have had previous surgery for PD (including but not limited to deep brain stimulation [DBS] or cell transplantation).
Patients with a history of psychotic symptoms requiring treatment, or suicide ideation or attempt within the prior 12 months (stable regimens [for at least 4 weeks prior to SV1] of anti-depressant and certain low-dose atypical antipsychotic medications are permitted).
Patients who have cancer with the exception of the following: basal cell carcinoma or successfully treated squamous cell carcinoma of the skin; cervical carcinoma in situ; prostatic carcinoma in situ; or other malignancies curatively treated and with no evidence of disease recurrence for at least 3 years.
Patients taking certain prohibited medications (see Section 9.4.2).
Patients with a history of drug or alcohol abuse within the prior 12 months.
Patients with chronic obstructive pulmonary disease (COPD), asthma, or other chronic respiratory disease within the last 5 years.
Patients with any contraindication to performing routine spirometry or who are unable to perform a spirometry maneuver (see Appendix 20 for a list of contraindications).
Patients with a current history of symptomatic orthostatic hypotension despite adequate treatment.
Patients with any condition that in the investigator’s opinion would make patients unsuitable or interfere with their participation in the study. Potential issues of concern should be raised to the medical monitor during eligibility review.
Patients who have any clinically significant abnormality or finding from examination, tests, or history that may compromise patient safety.
Patients who have 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).
Prior exposure to CVT-301.


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

Health Condition(s) or Problem(s) studied

Parkinson's Disease With Motor Response Fluctuations (OFF Phenomena)
MedDRA version: 19.0 Level: LLT Classification code 10034007 Term: Parkinson's disease NOS System Organ Class: 100000004852

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
Other descriptive name: LEVODOPA
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 30-

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
Other descriptive name: LEVODOPA
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 42-

Primary Outcome(s)

Secondary Objective: - To characterize the pulmonary safety, as assessed by spirometry (FEV1, FVC, and FEV1/FVC ratio), over a 12-month period in the observational ('standard of care') cohort.
- To estimate the difference between the CVT-301-treated patients and the observational cohort on measures of pulmonary safety.
- To characterize the effects of CVT-301 on safety over a 12-month period
- To evaluate the effects of CVT-301 on mean change from baseline in the UPDRS Part 4 measures of motor fluctuations
- To characterize the occurrence and severity of examiner-rated dyskinesia following treatment of patients experiencing an OFF episode in the clinic over a 12-month period
- To describe the effects of CVT 301 on DLco over a 12-month period.

Primary end point(s): Spirometry (forced expiratory volume in 1 second [FEV1], forced vital capacity (FVC), and FEV1/ FVC ratio), over a 12-month period within the CVT-301-treated patients.

Timepoint(s) of evaluation of this end point: At each patient visit throughout the study

Main Objective: To characterize the pulmonary safety, as assessed by spirometry (forced expiratory volume in 1 second [FEV1], forced vital capacity [FVC], and FEV1 / FVC ratio), over a 12 month period within the CVT 301 treated patients.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: These will be repeated throughout the study where necessary as indicated above

Secondary end point(s): • Spirometry (FEV1, FVC, and FEV1/FVC ratio), over a 12-month period in the observational ('standard of care') cohort.
• Safety over a 12-month period: safety will be assessed by adverse event (AE) reports, physical examination, standard and orthostatic vital signs (blood pressure [BP], heart rate [HR], and respiratory rate [RR]), clinical laboratory tests, 12-lead electrocardiograms (ECGs), the Parkinson's Disease Impulsive-Compulsive Disorders Questionnaire (QUIP), the Epworth Sleepiness Scale, and the Columbia-Suicide SeverityRating Scale (C-SSRS).
• Mean change from baseline in the UPDRS Part 4 measures of motor fluctuations (dyskinesias [Q32-35] and wearing off [Q36-39]) measured pre-dose at 6 and 12 months after theinitiation of CVT-301 treatment.
• Examiner-rated dyskinesia following treatment of patients experiencing an OFF episode in the clinic over a 12-month period
• DLco over a 12-month period.

Secondary ID(s)

CVT-301-005

NCT02352363

2014-003799-22-HU

Source(s) of Monetary Support

Civitas Theurapeutics, Inc.