Parkinson's Disease With Motor Response Fluctuations (OFF Phenomena) MedDRA version: 20.0 Level: LLT Classification code 10034007 Term: Parkinson's disease NOS System Organ Class: 100000004852
Conditions
Sponsors
Civitas Therapeutics, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Inclusion Criteria (not assessed for the CVT-301-004 study patients): • 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 86 years, inclusive. 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. • Patients who have idiopathic PD (i.e., not induced by drugs or other diseases) as defined by fulfilling Steps 1 and 2 of the United Kingdom (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 • 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 (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 patients with an FEV1 that is = 50% to 60% to 60% to =65 years) yes F.1.3.1 Number of subjects for this age range 123
Exclusion criteria
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 cell transplantation) or plan to have stereotactic surgery during the study period. Patients who have had deep brain stimulation [DBS] will also be excluded unless the procedure was performed more than 6 months prior to study enrollment. • Patients with a history of psychotic symptoms requiring treatment, or suicidal ideation or attempt within the prior 12 months. • 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. • 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. • 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 unable to comply with study procedures or make them unsuitable for their participation in the study. • Patients who have any clinically significant abnormality or finding from examination, tests, or history that may compromise patient safety. Potential issues of concern should be raised to the medical monitor during eligibility review. • For new CVT-301 naïve patients, patients who have been treated with an investigational drug within 4 weeks or 5 halflives (whichever is longer) prior to the beginning of the screening period (this includes investigational formulations of marketed products).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To characterize the effects of CVT-301 on 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.;Secondary Objective: • Proportion of patients achieving resolution of an OFF to an ON state within 60 minutes after study drug is administered in the clinic, maintaining the ON state at 60 minutes after study drug administration (per examiner’s subjective assessment) 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 • Change from baseline visit 39-Item PD Questionnaire (PDQ-39) • Proportion of patients who improved based on the Patient Global Impression of Change (PGI-C) rating scale measured pre-dose • Change from baseline visit Schwab and England (S&E) Activities of Daily Living (ADL) score • Change from baseline visit 9-Item Patient Health Questionnaire (PHQ-9) • Change from baseline visit Impact of Parkinson’s OFF Episodes Patient Survey • Change from baseline visit UPDRS Part 2 score;Primary end point(s): The primary endpoints related to the primary objective of the study are the pulmonary safety measures, FEV1, FVC and FEV1/ FVC ratio, assessed over a 12 month period. FEV1, FVC and FEV1/FVC ratio will be recorded from the single “best test” (based on effort with highest summed FEV1 and FVC). Variables will include the absolute FEV1, FVC, and FEV1/FVC ratio and FEV1 and FVC expressed as % of predicted value. Percent Predicted = 100 * (Observed) / Predicted, where predicted is calculated and provided to INC by Biomedical Systems (BMS).;Timepoint(s) of evaluation of this end point: Changes from baseline (TV1) for each variable will be calculated at each subsequent visit. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): •Proportion of patients achieving resolution of an OFF to an ON state within 60 minutes after study drug is administered in the clinic and maintaining the ON at 60 minutes after study drug administration (per the examiner’s subjective assessment). This endpoint will be based on the examiner’s subjective assessment. In case the assessment of turning on within 60 minutes is missing but the assessment of maintaining the ON at 60 minutes has been done, the patient will be classified based on the available assessment. In case the assessment of maintenance of ON at 60 minutes is missing, the patient will be classified as having missing data. •Change from baseline (3 consecutive days prior to TV1, or in case of missing data, the last 3 recorded days before TV1) in patient-recorded total daily OFF time, assessed by the patient and recorded in the PD Diary for 3 consecutive days prior to in-clinic visits (or in case of missing data, the last 3 recorded days before the visit). The validity of the PD diary entries will be checked prior to including a diary day in the summary calculations. Only valid diary days will be included in the diary summarizations. Change from baseline in total daily ON time without dyskinesia, total daily ON time with non-troublesome dyskinesia, and total daily ON time with troublesome dyskinesia will be calculated similarly. •A day will be considered as being valid if at least 80% of the entries during the day have been completed per instructions. That is, for each half hour period, only one entry among the responses (Asleep, OFF, ON without dyskinesia, ON with non-troublesome dyskinesia, or ON with troublesome dyskinesia) has been checked. The entry will not be used if no responses are checked or more than one response is checked. However, if the proportion of entries rejected due to multiple checked responses is large, sensitivity analysis will be performed by using the worst case out of the entries that had been check | — |
Countries
Canada, Czech Republic, Poland, Spain, United States
Contacts
Public ContactRegulatory Affairs
INC Research
Outcome results
None listed