A Cardiac Safety Study of an Investigational Drug to See How if Affects the Heart in People With Parkinson's Disease Complicated by Motor Fluctuations "OFF" Episodes
Condition: Parkinson's Disease; Off Episodes of Parkinson Disease
MeSH terms: Parkinson Disease
Intervention: APL-130277; Placebo; Moxifloxacin
Intervention description: APL-130277 single dose; Placebo single dose; moxifloxacin 400mg single dose
Intervention MeSH terms: Moxifloxacin; Apomorphine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking description: Double blind period
Enrollment: 48.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Parkinson's Disease; Off episodes

Summary:

      A cardiac safety study of an investigational drug to see how it affects the heart in people
      with Parkinson's Disease Complicated by Motor Fluctuations ("OFF" Episodes)
    

Eligibility criteria:

        Inclusion Criteria:

          -  1) Male or female ≥ 18 years of age. 2) Clinical diagnosis of Idiopathic PD,
             consistent with UK Brain Bank Criteria (excluding the "more than one affected
             relative" criterion).

             3) Clinically meaningful response to Levodopa (L-Dopa). Subjects with or without well
             defined "OFF" episodes, as determined by the Investigator will be allowed.

             4) Receiving stable doses of L-Dopa/carbidopa (immediate or sustained release)
             administered at least 3 times per day OR Rytary™ administered 3 times per day, for at
             least 4 weeks before the initial Screening Visit (SV1). Subjects receiving
             L-Dopa/carbidopa 3 times a day must also be on stable treatment with adjunctive PD
             medication regimens. These regimens bust me maintained at a stable dose for at least 4
             weeks prior to the initial Screening Visit (SV1) with the exception that MAO-B
             inhibitors must be maintained at a stable level for at least 8 weeks prior to the
             initial Screening Visit (SV1).

             5) No planned medication change(s) or surgical intervention anticipated during the
             course of study.

             6) the subject must be able to have a drug withdrawal induced "OFF" episode.

             7) Stage III or less on the modified Hoehn and Yahr scale in the "ON" state.

             8) Mini-Mental State Examination (MMSE) score > 21.

             9) If female and of childbearing potential, must agree to use one of the following
             methods of birth control throughout the study and until at least 30 days after final
             drug administration:

               -  Oral contraceptive

               -  Contraceptive patch

               -  Barrier (diaphragm, sponge or condom) plus spermicidal preparations

               -  Intrauterine contraceptive system

               -  Levonorgestrel implant

               -  Medroxyprogesterone acetate contraceptive injection

               -  Complete abstinence from sexual intercourse;

               -  Hormonal vaginal contraceptive ring; or

               -  Surgical sterilization or partner sterile (must have documented proof).

                  10)Male subjects must be either surgically sterile, agree to be sexually
                  abstinent or use a barrier method of birth control (e.g., condom) from first
                  study drug administration until at least 30 days after final drug administration

                  11)Willing and able to comply with scheduled visits, treatment plan, laboratory
                  tests, and other study-related procedures to complete the study.

                  12)Able to understand the consent form, and to provide written informed consent.

                  13)Must be approved as a satisfactory candidate by the Enrollment Authorization
                  Committee (EAC) and the Sponsor.

        Exclusion Criteria:

          1. Atypical or secondary parkinsonism

          2. Nausea associated with the use of dopamine agonists that requires treatment with an
             antiemetic.

          3. Previous treatment with any of the following: a neurosurgical procedure for PD;
             continuous subcutaneous (s.c.) apomorphine infusion; or Duodopa/Duopa.

          4. Treatment with any form of s.c. apomorphine within 7 days prior to the initial
             Screening Visit (SV1). Subjects that stopped s.c. apomorphine for any reason other
             than systemic safety concerns or lack of efficacy may be considered.

          5. Contraindications to moxifloxacin or APOKYN®, or hypersensitivity to apomorphine
             hydrochloride or any macrolide antibiotic or any of the ingredients of APOKYN®
             (notably sodium metabisulfite).

          6. Female who is pregnant or lactating.

          7. Participation in a clinical trial within 30 days prior to the initial Screening Visit
             (SV1), with the exception of clinical studies related to APL-13077.

          8. Receipt of any investigational (i.e., unapproved) medication within 30 days prior to
             the initial Screening Visit (SV1), with the exception of APL-13077.

          9. Any selective 5HT3 antagonists (i.e., ondansetron, granisetron, dolasetron,
             palonosetron, alosetron), dopamine antagonists (including Tigan [trimethobenzamide]
             and domperidone, but excluding quetiapine or clozapine) or dopamine depleting agents
             within 30 days prior to initial Screening Visit (SV1).

         10. Drug or alcohol dependency in the past 12 months.

         11. Subject has a history of malignancy within 5 years prior to SV1, except for adequately
             treated basal cell or squamous cell skin cancer or in situ cervical cancer. Pituitary
             tumors of any duration are excluded.

         12. Documented abnormalities with ECGs including, arrhythmias, clinically meaningful
             interval irregularities, structural heart abnormalities ,myocardial infarction,
             presence or history of a pacemaker, or any abnormality of the ECG that in the opinion
             of the Investigator, would interfere with the ability to measure the QT interval, or
             correct the QT interval for heart rate.

         13. Male subjects with a screening corrected QT interval using Fridericia's formula (QTcF)
             of ≥ 450 ms; female subjects with a screening QT interval ≥ 470 ms. Eligibility will
             be based on the core laboratory ECG interpretation report.

         14. HR at screening < 45 bpm or > 100 bpm.

         15. QRS duration at screening >120 ms

         16. PR interval at screening >200 ms.

         17. Subjects with a history of cataplexy, unexplained syncope or seizures.

         18. Family history of sudden cardiac death.

         19. Heart failure (NYHA Class II or greater) and/or a myocardial infarction.

         20. Current use of any concomitant mediations that prolong the QT/QTc interval. Refer to
             https://crediblemeds.org for listing.

         21. History of additional risk factors for TdP (i.e., heart failure, hypokalemia, family
             history of Long QT Syndrome).

         22. Clinically significant medical, surgical, or laboratory abnormality in the opinion of
             the Investigator.

         23. Subject has a positive screening laboratory test result for human immunodeficiency
             virus (HIV).

         24. Subject has a positive screening laboratory test result for hepatitis B surface
             antigen or hepatitis C antibodies and has liver function test results at screening
             above the ULN for the reference laboratory.

         25. Major psychiatric disorder including, but not limited to, dementia, bipolar disorder,
             psychosis (including Parkinson's disease 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.

         26. History of clinically significant impulse control disorder(s).

         27. Dementia that precludes providing informed consent or would interfere with
             participation in the study.

         28. Current suicidal ideation within one year prior to the second Screening Visit (SV2) as
             evidenced by answering "yes" to Questions 4 or 5 on the suicidal ideation portion of
             the Columbia-Suicide Severity Rating Scale (C-SSRS) or attempted suicide within the
             last 5 years.

         29. Donation of blood plasma in the 30 days prior to first dosing.