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-HU
• Date of registration: 20/11/2014
• 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: 11/02/2015
• Target sample size: 365
• 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

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 80 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 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, which must include doses at least 4 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.
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 255
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 110

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 (or if a patient is receiving treatment for any of these conditions).
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).



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: 17.1 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.
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 describe the effects of CVT-301, Time course of effect and onset of effect, Magnitude of effect
To characterize the occurrence and severity of examiner rated dyskinesia following treatment of patients experiencing an OFF episode after the initiation of CVT 301 treatment.
To characterize the proportion of patients achieving resolution of an OFF to an ON state within 60 minutes after study drug is administered in the clinic
To characterize the proportion of patients with an ON state at the end of the 60-minute observation period following treatment in the clinic
To evaluate the ability of carbon monoxide diffusing capacity (DLco) maneuver.
To describe the effects of CVT 301 on DLco over a 12 month period.

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

Primary end point(s): Spirometry forced expiratory volume in 1 second [FEV1] and FEV1/forced vital capacity [FVC] ratio

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

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): Mean change from pre-dose in average Unified Parkinson’s Disease Rating Scale (UPDRS) Part 3 motor score at 10 to 60 minutes following treatment of patients experiencing an OFF episode in the clinic at 1, 3, 6, 9, and 12 months after the initiation of CVT-301 treatment.
Time-course of the change in UPDRS Part 3 motor score from pre-dose to 10, 20, 30, and 60 minutes following treatment in the clinic at 1, 3, 6, 9, and 12 months after the initiation of CVT-301 treatment.
Mean change from pre-dose in average UPDRS Part 3 motor score at 10 to 20 minutes following treatment of patients experiencing an OFF episode in the clinic at 1, 3, 6, 9, and 12 months after the initiation of CVT-301 treatment.
Mean best change and best percent change in the UPDRS Part 3 motor score from pre-dose at 10 to 60 minutes following treatment of patients experiencing an OFF episode in the clinic at 1, 3, 6, 9, and 12 months after the initiation of CVT-301 treatment.
Mean change in the UPDRS item 23 (Finger Taps) from pre dose to 10 minutes following treatment of patients experiencing an OFF episode in the clinic at 1, 3, 6, 9 and 12 months after the initiation of CVT-301 treatment.
Mean change in the UPDRS item 31 (Body Bradykinesia and Hypokinesia) from pre-dose to 10 minutes following treatment of patients experiencing an OFF episode in the clinic at 1, 3, 6, 9 and 12 months after the initiation of CVT-301 treatment.
Proportion of patients with a =3 point, =6 point, and =11 point reduction in the UPDRS Part 3 motor score from pre dose to post dose, by assessing the number and proportion of patients achieving on objective motor response overall and at 10, 20, 30, and 60 minutes following treatment in the clinic at 1, 3, 6, 9, and 12 months after the initiation of CVT 301 treatment.
Occurrence and severity of examiner rated dyskinesia following treatment of patients experiencing an OFF episode in the clinic at 1, 3, 6, 9, and 12 months after the initiation of CVT 301 treatment.
Proportion of patients achieving resolution of an OFF to an ON state within 60 minutes after study drug is administered in the clinic (per the examiner’s subjective assessment) at 1, 3, 6, 9, and 12 months after the initiation of CVT 301 treatment.
Proportion of patients with an ON state at the end of the 60-minute observation period (per the examiner’s subjective assessment) following treatment in the clinic at 1, 3, 6, 9, and 12 months after the initiation of CVT 301 treatment.
Patient reported total daily OFF time, total daily ON time without dyskinesia, total daily ON time with non troublesome dyskinesia, and total daily ON time with troublesome dyskinesia, assessed by the patient and recorded in the patient diary for the 3 consecutive days immediately prior to visits at 1, 3, 6, 9, and 12 months after the initiation of CVT-301 treatment.
Mean change from baseline in the 39-Item Parkinson’s Disease Questionnaire (PDQ-39) quality of life instrument measured pre dose at 3, 6, and 12 months after the initiation of CVT 301 treatment.
Patient Global Impression of Change (PGI-C) rating scale measured pre dose at 3, 6, and 12 months after the initiation of CVT 301 treatment.
Mean change from baseline in the Schwab and England (S&E) Activities of Daily Living (ADL) score measured pre dose at 3, 6, and 12 months after the initiation of CVT-301 treatment.
Mean change from baseline in the UPDRS Part 2 score measured pre dose at 3, 6, and 12 months after the initiation of CVT-301 treatment.
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 3, 6, and 12 months after the initiation of CVT-301 treatment.
The ability of Parkinson’s disease (PD) patients to perform American Thoracic Society (ATS) quality carbon monoxide diffusing capacity (DLco) maneuver.
DLco over a 12 month period.

Secondary ID(s)

CVT-301-005

Source(s) of Monetary Support

Civitas Theurapeutics, Inc.