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

NCT ID: NCT03187301

Last Updated: 2020-08-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 48 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-08-03
• Study Completion Date: 2017-12-21

Brief 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)

Detailed Description

This multi-center, Phase 2, Randomized, Double-Blind, Placebo Controlled, 3-Period Crossover, Positive Control study designed to evaluate the QT interval prolongation potential of 10 mg to 60 mg doses of APL-130277 compared to placebo and the positive control, 400mg moxifloxacin in subjects with Parkinson's Disease (PD) who experience motor fluctuations ("OFF" episodes) The patient is titrated to the highest tolerated dose from 10mg to 60mg, and then is randomized to one of six crossover sequences. Each sequence includes treatment with the following:

1. Treatment A: APL-130277 at the dose determined in the Dose Titration Phase,

2. Treatment B: Matched placebo,

3. Treatment C: A single 400 mg dose of moxifloxacin

Conditions

Parkinson's Disease; Off Episodes of Parkinson Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

APL-130277

APL-130277 at the dose determined in the dose titration phase

Group Type: EXPERIMENTAL

APL-130277

Intervention Type: DRUG

APL-130277 single dose

Placebo

Placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo single dose

moxifloxacin

moxifloxacin at a single 400mg dose

Group Type: ACTIVE_COMPARATOR

Moxifloxacin

Intervention Type: DRUG

moxifloxacin 400mg single dose

Interventions

APL-130277

APL-130277 single dose

Intervention Type: DRUG

Placebo

Placebo single dose

Intervention Type: DRUG

Moxifloxacin

moxifloxacin 400mg single dose

Intervention Type: DRUG

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sumitomo Pharma America, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

CNS Medical Director

Role: STUDY_CHAIR

Sunovion Pharmacetuicals Inc.

Locations

Movement Disorders Center of Arizona

Scottsdale, Arizona, United States

Clinical Trials, Inc.

Little Rock, Arkansas, United States

The Parkinson's and Movement Disorder Institute

Fountain Valley, California, United States

Parkinson's Disease and Movement Disorders Center of Boca Raton

Boca Raton, Florida, United States

MD Clinical

Hallandale, Florida, United States

Bioclinica Reserach

Orlando, Florida, United States

Atlanta Center for Medical Research

Atlanta, Georgia, United States

The NeuroMedical Center, PC

Baton Rouge, Louisiana, United States

QUEST Research Institute

Farmington Hills, Michigan, United States

Central Texas Neurology Consultants

Round Rock, Texas, United States

Casa di Cura villa Margherita (Neurologia)

Arcugnano, , Italy

Centro Ricerche San Raffaele

Cassino, , Italy

Agine Research Center, University Foundahon Chica-Pescara, Behavioral Neurology and Movement Disorders Unit

Chieti, , Italy

Neurologia, Policlinico Tor Vergata

Rome, , Italy

IRCCS San Raffaele Pisana,Clinical Trial Center

Rome, , Italy

Countries

United States; Italy

References

Stocchi F, Peckham EL, De Pandis MF, Sciarappa K, Kleiman R, Agbo F, Olanow CW, Blum D, Navia B. A Randomized Thorough QT Study of Apomorphine Sublingual Film in Patients With Parkinson's Disease. Clin Pharmacol Drug Dev. 2022 Sep;11(9):1068-1077. doi: 10.1002/cpdd.1147. Epub 2022 Jul 28.

Reference Type: DERIVED

PMID: 35899977 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2016-001762-29

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CTH-201

Identifier Type: -

Identifier Source: org_study_id