A Study to Evaluate the Safety and Efficacy of IPX203 in Parkinson's Disease Participants With Motor Fluctuations
Condition: Parkinson's Disease (Disorder)
MeSH terms: Parkinson Disease; Disease
Intervention: IR CD-LD; IPX203 ER CD-LD; Placebo Matching IPX203; Placebo Matching IR CD-LD
Intervention description: Active comparator - IR CD-LD; Investigational formulation - ER CD-LD; Double dummy placebo capsules; Double dummy placebo tablets
Intervention MeSH terms: Carbidopa, levodopa drug combination
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
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
Enrollment: 630.0
Sex: All
Minimum age: 40 Years
Healthy volunteers: No
Keywords: Idiopathic Parkinson's Disease; Lewy Body Parkinson's Disease; Paralysis Agitans; Primary Parkinsonism

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 participants with Parkinson's disease (PD) who have motor fluctuations.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male or female participants 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 participants 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 participant 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 participant 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 participants 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 participants 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.

          -  Participant 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.

          -  Participants who have previously participated in an IPX203 study.

          -  Participants who, in the opinion of the clinical investigator, should not participate
             in the study.

          -  Based on clinical assessment, participant does not adequately comprehend the
             terminology needed to complete the PD diary.