Parkinson's Disease (PD) MedDRA version: 20.0 Level: PT Classification code 10061536 Term: Parkinson's disease System Organ Class: 10029205 - Nervous system disorders
Conditions
Interventions
Product Name: APL-130277
Product Code: APL-130277
Pharmaceutical Form: Sublingual film
INN or Proposed INN: Apomorphine Hydrocloride Hemihydrate
CAS Number: 41372-20-7
Current Sponsor code: Apomorphin
Sponsors
SUNOVION PHARMACEUTICALS
Eligibility
Sex/Gender
All
Inclusion 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) with well-defined early morning “OFF” episodes, as determined by the Investigator. 4.Receiving stable doses of L-Dopa/carbidopa (immediate or sustained release) administered at least 4 times per day OR Rytary™ administered 3 times per day, for at least 4 weeks before the initial Screening Visit (SV1). Adjunctive PD medication regimens must be 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.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. 7.Stage III or less on the modified Hoehn and Yahr scale in the “ON” state. 8.Mini–Mental State Examination (MMSE) score > 25. 9.If female and of childbearing potential, must agree to use one of the following methods of birth control: • 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 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). Are the trial subjects under 18? no Number of subjects for this age range: 1 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 15 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 30
Exclusion criteria
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). Patients 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). 8.Receipt of any investigational (i.e., unapproved) medication within 30 days prior to the initial Screening Visit (SV1). 9.Any selective 5HT3 antagonists (i.e., ondansetron, granisetron, dolasetron, palonosetron, alosetron), dopamine antagonists (excluding quetiapine and 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.History of malignant melanoma. 12.Documented abnormalities with ECGs including, arrhythmias, clinically meaningful interval irregularities, structural heart abnormalities, 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 patients with a screening QT interval > 450 ms; female patients with a screening QT interval > 470 ms. 14.HR at screening 100 bpm. 15.QRS duration at screening >120 ms. 16.PR interval at screening >200 ms. 17.Patients 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.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. 24.History of clinically significant hallucinations during the past 6 months. 25.History of clinically significant impulse control disorder(s). 26.Dementia that precludes providing informed consent or would interfere with participation in the study. 27.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. 28.Donation of blood or plasma in the 30 days prior to first dosing.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is to evaluate the effect of APL-130277 compared to placebo on QTc intervals in subjects with Parkinson’s disease (PD) complicated by motor fluctuations.;Secondary Objective: The secondary objectives include the evaluation of safety and pharmacokinetics of APL-130277 and the comparison of efficacy of the highest tolerated dose level and the lowest APL-130277 dose resulting in a full “ON” during the Dose Titration Phase.;Primary end point(s): Time-matched change from baseline in QTc, placebo-adjusted and corrected for HR based on the Fridericia correction method (QTcF) method (??QTcF). Assay sensitivity will be demonstrated by inclusion of a positive control, moxifloxacin.;Timepoint(s) of evaluation of this end point: 12-lead ECG (Triplicate; Holter): Period 1: 3 sets of triplicate ECGs over approximately 1-hour (prior to dosing) as the baseline assessment; and triplicate ECG at t = 15, 30, 45, 60 minutes and 2, 3, 4, 8, 12, 24 hours after dosing. Period 2 and Period 3: triplicate ECG at t = 0 (just prior to dosing), 15, 30, 45, 60 minutes and 2, 3, 4, 8, 12, 24 hours after dosing. 2 and Period 3: triplicate ECG at t = 0 (just prior to dosing), 15, 30, 45, 60 minutes and 2, 3, 4, 8, 12, 24 hours after dosing. EOS: triplicate ECG. 12-lead ECG (Single; Resting): At the Screening Visit in triplicate (SV2). TV1 to TV9: ECG at t = 0 (just prior to dosing) and 45 minutes after dosing. Period 1, Period 2 and Period 3 at 60 minutes after dosing. ECGs will be assessed by the Investigator at each visit. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Pharmacodynamic assessments including QTc with Bazett correction (QTcB), heart rate, PR interval, QRS interval, uncorrected QT interval, ECG morphology and correlation between the QTcF change from baseline and plasma concentrations of APL-130277.;Timepoint(s) of evaluation of this end point: PK will be assessed dosing days at t = 0 (just prior to dosing), 30, 45, 60 minutes and 2, 4 hours after dosing. PK will be assessed on the moxifloxacin dosing day at t = 0 (just prior to dosing), 30, 60 minutes and 2, 3, 4, 6, 8 hours after dosing. | — |
Countries
Italy
Contacts
Public ContactCMO
SUNOVION PHARMACEUTICALS
Outcome results
None listed