Evaluate the safety and efficacy of IPX203 carbidopa-levodopa extended release capsules compared to carbidopa-levodopa immediate release tablets in patients with Parkinson’s with motor fluctuations.
- Conditions
- Parkinson's diseaseMedDRA version: 20.0Level: PTClassification code 10061536Term: Parkinson's diseaseSystem Organ Class: 10029205 - Nervous system disordersMedDRA version: 20.0Level: SOCClassification code 10029205Term: Nervous system disordersSystem Organ Class: 10029205 - Nervous system disordersMedDRA version: 20.0Level: PTClassification code 10028035Term: Movement disorderSystem Organ Class: 10029205 - Nervous system disordersTherapeutic area: Diseases [C] - Nervous System Diseases [C10]
- Registration Number
- EUCTR2018-002233-37-GB
- Lead Sponsor
- Impax Laboratories, LLC
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 510
• Male or female subjects diagnosed at age = 40 years with PD, consistent with the United Kingdom Parkinson’s Disease Society Brain Bank Diagnostic Criteria and who are being treated with stable regimens of CD-LD but experiencing motor fluctuations.
• Hoehn and Yahr Stages 1, 2, 3, or 4 in the On” state (part of Movement Disorders Society version of the Unified Parkinson’s Disease Rating Scale [MDS-UPDRS] Part III)
• Montreal Cognitive Assessment (MoCA) score = 24 at Screening Visit in On” state.
• By history, for the 4 weeks prior to Screening, the subject experiences daily wearing-off” episodes with periods of bradykinesia in combination with at least one of rest tremor or rigidity, experiences an Off” state upon awakening on most mornings, and reports an average of at least 2.5 cumulative hours per day of Off” time during the waking hours.
• Able to differentiate On” state from Off” state as determined by at least 75% concordance with a trained rater in On/Off” ratings for 8 ratings over a 4-hour training period. The concordance must include at least 1 On” and 1 Off” rating and must be achieved within two 4-hour training sessions.
• At Visit 1, review of the 3-day PD Diaries confirms the following: that the subject is able to properly complete the Diaries with valid entries; and that the subject has an average of at least 2.5 hours per day of Off” time during waking hours over the 3 days with at least 1.5 hours of cumulative Off” time on each day.
• Responsive to CD-LD therapy and currently being treated on a stable regimen with CD-LD for at least 4 weeks prior to Visit 1 and:
- Requires at least 100 mg of LD from IR CD-LD for the first morning dose;
- Requires a total daily dose of at least 400 mg of LD and takes a maximum total daily dose of 2400 mg LD, from IR CD-LD alone or IR CD-LD in combination with a single daily bedtime dose of CR CD-LD;
- Has a dosing frequency of 4 to 9 times daily of CD-LD;
- By history, typically experiences an On” response with the first dose of IR CD-LD of the day, but the efficacy of this dose typically lasts less than 4 hours.
• At Screening, the subject has predictable Off” periods defined by a score of 1 or 2 on Item #4.5 (Complexity of Motor Fluctuations) of the MDS-UPDRS Part IV B (Motor Fluctuations).
• At Screening, the MDS-UPDRS Part III total score in the Off” state is at least 20 units.
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 265
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 245
• Used any doses of controlled-release (CR) CD-LD apart from a single daily bedtime dose within 4 weeks prior to Visit 1.
• Used any dose of Rytary for the past 4 weeks prior to Visit 1 or were considered IPX066 or Rytary failures for reasons of efficacy or safety.
• Had prior neurosurgical treatment for PD or if such procedure is planned or anticipated during the study period.
• Allergic to any excipient in the study drugs.
• History of glaucoma with intraocular pressures that are elevated despite appropriate medical management.
• History of seizure or epilepsy and experienced at least 1 seizure during the past 12 months or has not been compliant with medically recommended therapy or visits.
• History of myocardial infarction with residual atrial, nodal, or ventricular arrhythmias that are not controlled with medical and/or surgical interventions. A recent (= 12 months) history of myocardial infarction with secondary arrhythmias is exclusionary regardless of the therapeutic control.
• Received within 4 weeks of Screening or planning to take during participation in the clinical study:
- Any doses of a CR CD-LD apart from a single daily bedtime dose, any doses of Rytary, additional CD (eg, Lodosyn) or benserazide (eg, Serazide), or catechol-O-methyl transferase inhibitors (entacapone or tolcapone) or medications containing these inhibitors (Stalevo);
- Nonselective monoamine oxidase inhibitors (MAOI), apomorphine, or antidopaminergic agents, including antiemetics.
• Subjects who have previously participated in an IPX203 study.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To evaluate the safety and efficacy of IPX203 in comparison to IR CD-LD in the treatment of CD-LD-experienced subjects with Parkinson’s disease who have motor fluctuations.;Secondary Objective: Not applicable;Primary end point(s): Change from baseline in Good on” time in hours per day, averaged over the PD Diary days, at the end of double-blind treatment period (Visit 7 or early termination). Good on” time is derived from the 3-day PD Diaries and is defined as the sum of On” time without dyskinesia and On” time with nontroublesome dyskinesia.;Timepoint(s) of evaluation of this end point: Visit 7 or early termination
- Secondary Outcome Measures
Name Time Method Secondary end point(s): - Change from baseline in Off” time in hours per day, averaged over the PD Diary days at the end of double-blind treatment period;<br><br>- Proportion of subjects with either much improved” or very much improved” in Patient Global Impression of Change (PGI-C) scores at the end of double-blind treatment period;<br><br>- Change from baseline in the MDS-UPDRS Part III at the end of double-blind treatment period;<br><br>- Change from baseline in the sum of MDS-UPDRS Parts II and III at the end of double-blind treatment period.;Timepoint(s) of evaluation of this end point: Visit 7 or early termination