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

NCT03187301 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: CTH-2012016-001762-29
• Study Type: interventional
• Target: 48
• Locations: 2 countries
• Sites: 15

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)

Conditions

Parkinson's Disease; Off Episodes of Parkinson Disease

Keywords

Parkinson's Disease; Off episodes

Outcome Measures

Primary Outcomes (2)

• Time-Matched Change From Baseline in QTc, Placebo-Adjusted and Corrected for Heart Rate Based on the Fridericia Correction Method (QTcF) Using Delta Delta Method (ΔΔQTcF): Comparison Between APL-130277 and Placebo (Central Tendency Analysis)

  For the primary central tendency analysis, the changes from baseline (ΔQTcF) were compared between APL-130277 and placebo (ΔΔQTcF). Baseline was defined as the mean of the 9 ECGs (3 sets of triplicate ECGs) recorded at baseline (P1V1). In case any of the 9 ECGs were missing, the baseline was defined as the mean of the available baseline values. The post-dose ECGs were evaluated at 15, 30, 45 and 60 minutes (mins) and 2, 3 and 4 hours post-dose at each of the 3 treatment period dosing visits during the Randomized Crossover Assessment Phase. For each of the time points, an average value was calculated based on the 3 (or all available) ECGs. These average values were used in all change from baseline calculations.

  Baseline to 15, 30, 45, 60 mins and 2, 3, and 4 hours post-dose for each of the 3 treatment period dosing visits.

• Time-Matched Change From Baseline in QTc, Placebo-Adjusted and Corrected for Heart Rate Based on QTcF Using ΔΔQTcF: Comparison Between Moxifloxacin and Placebo (Assay Sensitivity Analysis)

  For the assay sensitivity analysis in support of the primary central tendency analysis, the changes from baseline (ΔQTcF) were compared between moxifloxacin (positive control) and placebo (ΔΔQTcF). Baseline was defined as the mean of the 9 ECGs (3 sets of triplicate ECGs) recorded at baseline (P1V1). In case any of the 9 ECGs were missing, the baseline was defined as the mean of the available baseline values. The post-dose ECGs were evaluated at 60 mins and 2, 3 and 4 hours post-dose for each of the 3 treatment period dosing visits in the Randomized Crossover Assessment Phase. For each of the time points, an average value was calculated based on the 3 (or all available) ECGs. These average values were used in all change from baseline calculations.

  Baseline to 60 mins and 2, 3, and 4 hours post-dose for each of the 3 treatment period dosing visits.

Secondary Outcomes (12)

• Cmax of Apomorphine and Apomorphine Sulfate (Metabolite) Following the Administration of APL-130277

  Blood samples for PK assessments were taken prior to dosing and at 0.5, 0.75, 1, 2, and 4 hours post-dose.

• Tmax of Apomorphine and Apomorphine Sulfate (Metabolite) Following the Administration of APL-130277

  Blood samples for PK assessments were taken prior to dosing and at 0.5, 0.75, 1, 2, and 4 hours post-dose.

• AUClast of Apomorphine and Apomorphine Sulfate (Metabolite) Following the Administration of APL-130277

  Blood samples for PK assessments were taken prior to dosing and at 0.5, 0.75, 1, 2, and 4 hours post-dose.

• Number of Patients With Treatment-Emergent Adverse Events (TEAEs)

  From first dose of study medication up to last study visit for Randomized Crossover Assessment Phase, approximately up to 2 weeks

• ECG Assessments: Mean Change From Baseline to Post-Baseline Value for QTcB Interval During Randomized Crossover Assessment Phase

  Baseline and at 15, 30, 45, 60 minutes and 2, 3, and 4 hours post-dose for each of the 3 treatment period dosing visits during the Randomized Crossover Assessment Phase.

Study Arms (3)

APL-130277

EXPERIMENTAL

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

Drug: APL-130277

Placebo

PLACEBO COMPARATOR

Placebo

Drug: Placebo

moxifloxacin

ACTIVE COMPARATOR

moxifloxacin at a single 400mg dose

Drug: Moxifloxacin

Interventions

APL-130277 DRUG

APL-130277 single dose

APL-130277

Placebo DRUG

Placebo single dose

Placebo

Moxifloxacin DRUG

moxifloxacin 400mg single dose

moxifloxacin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \) 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).
• \) Clinically meaningful response to Levodopa (L-Dopa). Subjects with or without well defined "OFF" episodes, as determined by the Investigator will be allowed.
• \) 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).
• \) No planned medication change(s) or surgical intervention anticipated during the course of study.
• \) the subject must be able to have a drug withdrawal induced "OFF" episode.
• \) Stage III or less on the modified Hoehn and Yahr scale in the "ON" state.
• \) Mini-Mental State Examination (MMSE) score \> 21.
• \) 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;

You may not qualify if:

• Atypical or secondary parkinsonism
• Nausea associated with the use of dopamine agonists that requires treatment with an antiemetic.
• Previous treatment with any of the following: a neurosurgical procedure for PD; continuous subcutaneous (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). Subjects that stopped s.c. apomorphine for any reason other than systemic safety concerns or lack of efficacy may be considered.
• Contraindications to moxifloxacin or APOKYN®, or hypersensitivity to apomorphine hydrochloride or any macrolide antibiotic or any of the ingredients of APOKYN® (notably sodium metabisulfite).
• Female who is pregnant or lactating.
• 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.
• Receipt of any investigational (i.e., unapproved) medication within 30 days prior to the initial Screening Visit (SV1), with the exception of APL-13077.
• 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).
• Drug or alcohol dependency in the past 12 months.
• 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.
• 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.
• 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.
• HR at screening \< 45 bpm or \> 100 bpm.
• QRS duration at screening \>120 ms

Sponsors & Collaborators

• Sumitomo Pharma America, Inc.: lead

Study Sites (15)

Movement Disorders Center of Arizona

Scottsdale, Arizona, 85258, United States

Location

Clinical Trials, Inc.

Little Rock, Arkansas, 72205, United States

Location

The Parkinson's and Movement Disorder Institute

Fountain Valley, California, 92708, United States

Location

Parkinson's Disease and Movement Disorders Center of Boca Raton

Boca Raton, Florida, 33486, United States

Location

MD Clinical

Hallandale, Florida, 33009, United States

Location

Bioclinica Reserach

Orlando, Florida, 32806, United States

Location

Atlanta Center for Medical Research

Atlanta, Georgia, 30331, United States

Location

The NeuroMedical Center, PC

Baton Rouge, Louisiana, 70810, United States

Location

QUEST Research Institute

Farmington Hills, Michigan, 48334, United States

Location

Central Texas Neurology Consultants

Round Rock, Texas, 78681, United States

Location

Casa di Cura villa Margherita (Neurologia)

Arcugnano, 36057, Italy

Location

Centro Ricerche San Raffaele

Cassino, 03043, Italy

Location

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

Chieti, Italy

Location

Neurologia, Policlinico Tor Vergata

Rome, 00133, Italy

Location

IRCCS San Raffaele Pisana,Clinical Trial Center

Rome, 00163, Italy

Location

Related Publications (1)

• 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.

  PMID: 35899977 DERIVED

MeSH Terms

Conditions

Parkinson Disease

Interventions

Apomorphine; Moxifloxacin

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Intervention Hierarchy (Ancestors)

Aporphines; Benzylisoquinolines; Alkaloids; Heterocyclic Compounds; Isoquinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds, 4 or More Rings; Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines

Results Point of Contact

• Title: CNS Medical Director
• Organization: Sunovion Pharmaceuticals Inc.

ClinicalTrialDisclosure@sunovion.com

1-866-503-6351

Study Officials

• CNS Medical Director

  Sunovion Pharmacetuicals Inc.

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double blind period
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 7, 2017
• First Posted: June 14, 2017
• Study Start: August 3, 2017
• Primary Completion: December 21, 2017
• Study Completion: December 21, 2017
• Last Updated: August 10, 2020
• Results First Posted: August 10, 2020

Record last verified: 2020-07

Locations

IT (5); US (10)