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.

• Register: EUCTR
• Last refreshed on: 17 August 2021
• Main ID: EUCTR2018-002233-37-CZ
• Date of registration: 11/12/2018
• Prospective Registration: Yes
• Primary sponsor: Impax Laboratories, LLC
• Public title: 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.
• Scientific title: A randomized controlled study to compare the safety and efficacy of IPX203 with immediate-release carbidopa-levodopa in Parkinson's disease patients with motor fluctuations.
• Date of first enrolment: 18/03/2019
• Target sample size: 510
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2018-002233-37
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: yes; Cross over: no; Other: yes; Other trial design description: double-dummy; If controlled, specify comparator, Other Medicinial Product: yes; Placebo: yes; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Czech Republic, France, Germany, Italy, Poland, Spain, United Kingdom, United States

Contacts

• Name: Drug Safety Dept. Attn: Dr. Sanwo
• Affiliation: Impax Laboratories, LLC

• Name: Drug Safety Dept. Attn: Dr. Sanwo
• Affiliation: Impax Laboratories, LLC

Key inclusion & exclusion criteria

Inclusion criteria:
• 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

Exclusion criteria:
• 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.


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

Health Condition(s) or Problem(s) studied

Parkinson's disease
MedDRA version: 20.0 Level: PT Classification code 10061536 Term: Parkinson's disease System Organ Class: 10029205 - Nervous system disorders
MedDRA version: 20.0 Level: SOC Classification code 10029205 Term: Nervous system disorders System Organ Class: 10029205 - Nervous system disorders
MedDRA version: 20.0 Level: PT Classification code 10028035 Term: Movement disorder System Organ Class: 10029205 - Nervous system disorders

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

Intervention(s)

Product Name: IPX203
Product Code: IPX203
Pharmaceutical Form: Modified-release capsule, hard
INN or Proposed INN: Levodopa
CAS Number: 59-92-7
Current Sponsor code: LD
Other descriptive name: LEVODOPA
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 140-
INN or Proposed INN: Carbidopa
Current Sponsor code: CD
Other descriptive name: ANHYDROUS CARBIDOPA
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 35-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Trade Name: Carbidopa and Levodopa Tablets, USP
Product Name: IR CD-LD (carbidopa-levodopa) tablets
Product Code: IR CD-LD
Pharmaceutical Form: Tablet
INN or Proposed INN: Levodopa
CAS Number: 59-92-7
Current Sponsor code: LD
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-
INN or Proposed INN: Carbidopa
Current Sponsor code: CD
Other descriptive name: ANHYDROUS CARBIDOPA
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 25-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

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

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 Outcome(s)

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;

- 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;

- Change from baseline in the MDS-UPDRS Part III at the end of double-blind treatment period;

- 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

Secondary ID(s)

IPX203-B16-02

NCT03670953

Source(s) of Monetary Support

Impax Laboratories, LLC

Ethics review

Status: Approved
Approval date: 16/01/2019
Contact: