A Study to Evaluate the Safety and Efficacy of IPX203 in Parkinson's Disease Patients With Motor Fluctuations

• ClinicalTrials.gov Identifier: NCT03670953
• Recruitment Status: Active, not recruiting
• First Posted: September 14, 2018
• Last Update Posted: January 25, 2021
• Sponsor: Impax Laboratories, LLC
• Information provided by (Responsible Party): Impax Laboratories, LLC

Tracking Information

• First Submitted Date: September 12, 2018
• First Posted Date: September 14, 2018
• Last Update Posted Date: January 25, 2021
• Actual Study Start Date: November 6, 2018
• Estimated Primary Completion Date: April 30, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 12, 2018)

Change in "Good on" time [ Time Frame: 13 weeks ]

Change from baseline in "Good on" time in hours per day, at the end of double-blind treatment period. "Good on" time is defined as the sum of "On" time without dyskinesia and "On" time with nontroublesome dyskinesia.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: March 5, 2019)

• Change in "Off" time [ Time Frame: 13 weeks ]
  Change from baseline in "Off" time in hours per day, at the end of double-blind treatment period.
• Patients with "much improved" or "very much improved" on PGI-C [ Time Frame: 13 weeks ]
  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 in MDS-UPDRS Part III [ Time Frame: 13 weeks ]
  Change from baseline in the MDS-UPDRS Part III at the end of double-blind treatment period.
• Change in MDS-UPDRS Parts II and III [ Time Frame: 13 weeks ]
  Change from baseline in the sum of MDS-UPDRS Parts II and III at the end of double-blind treatment period.

Original Secondary Outcome Measures (submitted: September 12, 2018)

• Change in "Off" time [ Time Frame: 13 weeks ]
  Change from baseline in "Off" time in hours per day, at the end of double-blind treatment period.
• Patients with "much improved" or "very much improved" on PGI-C [ Time Frame: 13 weeks ]
  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 in MDS-UPSDRS Part III [ Time Frame: 13 weeks ]
  Change from baseline in the MDS-UPDRS Part III at the end of double-blind treatment period.
• Change in MDS-UPDRS Parts II and III [ Time Frame: 13 weeks ]
  Change from baseline in the sum of MDS-UPDRS Parts II and III at the end of double-blind treatment period.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study to Evaluate the Safety and Efficacy of IPX203 in Parkinson's Disease Patients With Motor Fluctuations
• Official 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
• Brief Summary: To evaluate the safety and efficacy of IPX203 (carbidopa and levodopa) extended-release capsules (IPX203 ER CD-LD) in comparison to immediate release (IR) CD-LD in the treatment of CD-LD-experienced subjects with Parkinson's disease (PD) who have motor fluctuations.
• Detailed Description: This is a multicenter, randomized, double-blind, double-dummy, active-controlled, parallel-group study. The study will consist of a 3-week, open-label IR CD-LD dose adjustment period; a 4-week, open-label period for conversion to IPX203; followed by a 13-week double-blind treatment period with subjects randomized in a 1:1 ratio, stratified by center, to receive either IPX203 (with matching IR CD-LD placebo) or IR CD-LD (with matching IPX203 placebo). Approximately 510 subjects will be enrolled to randomize 420 subjects.
• Study Type: Interventional
• Study Phase: Phase 3

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

Multicenter, randomized, double-blind, double-dummy, active-controlled, parallel-group study.

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:

Double dummy, blinded drug

Primary Purpose: Treatment

• Condition: Parkinson's Disease (Disorder)

Intervention

• Drug: IR CD-LD
  Active comparator - IR CD-LD
  Other Name: Generic for Sinemet tablets
• Drug: IPX203 ER CD-LD
  Investigational formulation - ER CD-LD
  Other Name: IPX203 extended-release capsules
• Other: IPX203 placebo
  Double dummy placebo capsules
  Other Name: IPX203 placebo capsules
• Other: IR CD-LD placebo
  Double dummy placebo tablets
  Other Name: IR CD-LD placebo tablets

Study Arms

• Experimental: IPX203 ER CD-LD

  Following IR CD-LD dose adjustment and conversion to IPX203 ER CD-LD, subjects will be randomized to investigational product IPX203 ER CD-LD and IR CD-LD placebo.

  IR CD-LD active and placebo are tablets and IPX203 ER CD-LD active is capsules. Dosage and frequency is patient specific.

  Interventions:

  • Drug: IR CD-LD
  • Drug: IPX203 ER CD-LD
  • Other: IR CD-LD placebo
• Active Comparator: IR CD-LD

  Following IR CD-LD dose adjustment and conversion to IPX203 ER CD-LD, subjects will be randomized to IPX203 placebo and IR CD-LD active comparator.

  IR CD-LD active is tablets and IPX203 active and placebo are capsules. Dosage and frequency is patient specific.

  Interventions:

  • Drug: IR CD-LD
  • Drug: IPX203 ER CD-LD
  • Other: IPX203 placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Estimated Enrollment (submitted: September 12, 2018): 510
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: May 31, 2021
• Estimated Primary Completion Date: April 30, 2021 (Final data collection date for primary outcome measure)

Eligibility 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.
• Able to provide written informed consent prior to the conduct of any study-specific procedures.
• Female subjects of childbearing potential must have a negative urine pregnancy test at Screening Visit.
• Negative urine screen for drugs of abuse and negative alcohol breath test at Screening.
• 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)
• Agrees to use a medically acceptable method of contraception throughout the study and for 6 weeks after completing the study. Medically acceptable methods of contraception that may be used by the subject and/or partner include but are not limited to: abstinence, oral contraception, NuvaRing or transdermal systems, diaphragm with vaginal spermicide, intrauterine device, condom and partner using vaginal spermicide, surgical sterilization (6 months), progestin implant or injection, or postmenopausal female (no menstrual period for ˃ 2 years) or vasectomy (˃ 6 months).
• Montreal Cognitive Assessment (MoCA) score ≥ 24 at Screening Visit in "On" state.
• 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.
• Able and willing to comply with the protocol, including completion of diaries and availability for all study visits.
• 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.
• At Screening, the subject has predictable "Off" periods.

Exclusion Criteria:

• Received any investigational medications within 30 days or 5 times the half-life, whichever is longer, prior to Visit 1.
• Female subjects who are currently breastfeeding or lactating.
• 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 medical conditions or of a prior surgical procedure that would interfere with LD absorption, such as gastrectomy, proximal small-bowel resection, or bariatric surgery.
• History of upper gastrointestinal hemorrhage in patients with peptic ulcer disease within the past 5 years.
• 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.
• History of neuroleptic malignant syndrome or of nontraumatic rhabdomyolysis.
• Liver enzyme values ≥ 2.5 times the upper limit of normal; or history of severe hepatic impairment.
• Serum creatinine level ≥ 1.75 times the upper limit of normal; or requires dialysis at the time of Screening.
• Subject with a history of malignant melanoma or with a suspicious undiagnosed skin lesion which in the opinion of the investigator could be melanoma.
• History of drug or alcohol abuse within the 12 months prior to Screening.
• 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.
• Employees or family members of the investigator, study site, or sponsor.
• Subjects who have previously participated in an IPX203 study.
• Subjects who, in the opinion of the clinical investigator, should not participate in the study.
• Based on clinical assessment, subject does not adequately comprehend the terminology needed to complete the PD diary.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 40 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Czechia, France, Germany, Italy, Poland, Spain, United Kingdom, United States

Administrative Information

• NCT Number: NCT03670953
• Other Study ID Numbers: IPX203-B16-02; 2018-002233-37 ( EudraCT Number )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: Impax Laboratories, LLC
• Study Sponsor: Impax Laboratories, LLC
• Collaborators: Not Provided

Investigators

• Study Director: Impax Study Director; Impax Laboratories, LLC

• PRS Account: Impax Laboratories, LLC
• Verification Date: May 2020