Efficacy, Safety and Tolerability Study of APL-130277 for the Acute Treatment of OFF Episodes in Patients With Parkinson's Disease
Condition: Parkinson Disease, Off Episodes
MeSH terms: Parkinson Disease
Intervention: APL-130277; Placebo
Intervention description: Use to treat up to 5 "OFF" episodes per day; placebo
Intervention MeSH terms: Apomorphine
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 141.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Parkinson Disease, off episodes

Summary:

      A 12-week, prospective, multi-center, randomized, double-blind, placebo controlled, Phase 3
      study in L-Dopa responsive PD patients with motor fluctuations ("OFF" episodes), designed to
      determine the efficacy, safety and tolerability of APL-130277.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male or female ≥ 18 years of age.

          -  Clinical diagnosis of Idiopathic PD, consistent with UK Brain Bank Criteria.

          -  Clinically meaningful response to L-Dopa with well-defined early morning "OFF"
             episodes, as determined by the Investigator.

          -  Receiving stable doses of L-Dopa/carbidopa (immediate or CR) administered at least 4
             times per day OR Rytary™ administered 3 times per day, for at least 4 weeks before the
             initial Screening Visit

          -  No planned medication change(s) or surgical intervention anticipated during the course
             of study.

          -  Patients must experience at least one well defined "OFF" episode per day with a total
             daily "OFF" time duration of ≥ 2 hours during the waking day, based on patient
             self-assessment.

          -  Stage III or less on the modified Hoehn and Yahr scale in the "ON" state.

          -  MMSE score > 25.

        Exclusion Criteria:

        A patient will not be eligible for study entry if any of the following exclusion criteria
        are met:

          -  Atypical or secondary parkinsonism.

          -  Previous treatment with any of the following: a neurosurgical procedure for PD;
             continuous s.c. apomorphine infusion; or Duodopa/Duopa.

          -  Treatment with any form of s.c. apomorphine within 7 days prior to the initial
             Screening Visit (SV1). Patients that stopped s.c. apomorphine for any reason other
             than systemic safety concerns or lack of efficacy may be considered.

          -  Contraindications to APOKYN®, or hypersensitivity to apomorphine hydrochloride or any
             of the ingredients of APOKYN® (notably sodium metabisulfite); Tigan®
             (trimethobenzamide hydrochloride; patients from US sites only); or domperidone
             (patients from non-US sites only).

          -  Participation in a clinical trial within 30 days prior to the initial Screening Visit
             (SV1).

          -  Currently taking selective 5HT3 antagonists (i.e., ondansetron, granisetron,
             dolasetron, palonosetron, alosetron), dopamine antagonists (excluding quetiapine or
             clozapine) or dopamine depleting agents.

          -  Drug or alcohol dependency in the past 12 months.

          -  History of malignant melanoma.

          -  Clinically significant medical, surgical, or laboratory abnormality in the opinion of
             the Investigator.

          -  Major psychiatric disorder including, but not limited to, dementia, bipolar disorder,
             psychosis, or any disorder that, in the opinion of the Investigator, requires ongoing
             treatment that would make study participation unsafe or make treatment compliance
             difficult.

          -  History of clinically significant hallucinations during the past 6 months.

          -  History of clinically significant impulse control disorder(s).

          -  Dementia that precludes providing informed consent or would interfere with
             participation in the study.