A clinical trial to compare APL-130277 sublingual film to Subcutaneous Apomorphine in Parkinson’s Disease patients

Phase 1

• Conditions: evodopa Responsive Patients with Parkinson’s Disease Complicated by Motor Fluctuations (OFF episodes); MedDRA version: 20.0Level: LLTClassification code 10034006Term: Parkinson's disease aggravatedSystem Organ Class: 100000004852; Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

• Registration Number: EUCTR2016-003456-70-ES
• Lead Sponsor: Sunovion Pharmaceuticals Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2017-12-07
• Last Update Posted: 12 February 2018

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 85

Inclusion Criteria

1) Male or female = 18 years of age.
2) Clinical diagnosis of Idiopathic PD, consistent with UK Brain Bank Criteria.1
3) Clinically meaningful response to L Dopa as determined by the Investigator.
4) Receiving stable doses of L Dopa/carbidopa and/or L Dopa/benserazide and/or L Dopa/carbidopa/entacapone (immediate or chronic release) administered at least 4 times per day OR Rytary™ administered at least 3 times per day, and on stable doses for at least 4 weeks before the initial Screening Visit (SV1). Adjunctive PD medication regimens are permitted but must be maintained at a stable dose for at least 4 weeks prior to SV1 with the exception of monoamine oxidase B (MAO B) inhibitors, which must be maintained at a stable level for at least 8 weeks prior to SV1.
5) No planned medication change(s) or surgical intervention anticipated during the course of study.
6) Subjects 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 judgment of physician and subject self assessment.
7) Subject must have predictable morning OFF” periods.
8) Subject and where appropriate, caregiver, must be trained in completing the home dosing diary and able to recognize ON” and OFF” states.
9) Stage III or less on the modified Hoehn and Yahr scale in the ON state.
10) Mini–Mental State Examination (MMSE) score >25.
11) Female subject of childbearing potential and male subject with female partner of childbearing potential, must agree to use an effective and medically acceptable form of birth control (see Section 10.3.1) throughout the study period. Note: Continued use of an effective and medically acceptable form of birth control is recommended through 30 days after study completion
12) Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study related procedures to complete the study.
13) Able to understand the consent form, and to provide written informed consent.
14) Must be approved as a satisfactory candidate by the Enrollment Adjudication Committee (EAC).
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 51
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 34

Exclusion Criteria

1. Atypical or secondary parkinsonism.
2. Previous treatment with any of the following: a neurosurgical procedure for PD; continuous subcutaneous (s.c.) apomorphine infusion; subcutaneous (s.c.) apomorphine injection; Duodopa/Duopa; or APL-130277.
3. Contraindications to domperidone, subcutaneous apomorphine, or hypersensitivity to apomorphine hydrochloride or any of the ingredients of subcutaneous apomorphine (notably sodium metabisulfite).
4. Female who is pregnant or lactating.
5. Participation in a clinical trial within 30 days prior to SV1.
6. Receipt of any investigational (ie, unapproved) medication within 30 days prior to SV1.
7. Currently taking selective 5HT3 antagonists (ie, ondansetron, granisetron, dolasetron, palonosetron, alosetron), dopamine antagonists (excluding quetiapine or clozapine) or dopamine depleting agents. Subjects receiving anti-depressants must be on a stable daily dose for at least 8 weeks before SV1.
8. The subject has a current diagnosis or history of substance abuse (excluding cannabinoids, nicotine, and caffeine) or alcohol abuse (in the opinion of the investigator) < 6 months prior to SV1.
9. 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.
10. Subject has a clinically significant abnormality on screening evaluation including physical examination, vital signs, ECG, or laboratory tests that the Investigator considers to be inappropriate to allow participation in the study.
11. Subject has screening laboratory test results of: blood urea nitrogen (BUN) value = 1.5 times the upper limit of normal (ULN) for the reference range; serum creatinine > 1.5 times the ULN for the reference range; or alanine aminotransferase (ALT) or aspartate aminotransferase (AST) value = 2 times the ULN for the reference laboratory.
12. Subject is on injectable medication for the treatment of Type 2 diabetes. A subject with Type 2 diabetes is eligible for study inclusion if considered clinically stable, which is defined as
• Random (non-fasting) screening glucose is < 200 mg/dl (11.1 mmol/L); and
• HbA1c = 6.5%; and
• If a subject is currently being treated with oral anti-diabetic medication(s), the dose must have been stable for at least 4 weeks prior to screening. Such medication may be adjusted or discontinued during the study, as clinically indicated.
Note: If the subject's random (non-fasting) screening glucose is = 200 mg/dL (11.1 mmol/L), glucose must be retested in a fasted state. If the retested fasted value is = 126 mg/dL (7.0 mmol/L), the subject will be excluded.
13. The subject’s screening ECG at SV1 or SV2 shows a corrected QT interval using Fridericia’s formula (QTcF) of = 450 msec for male subjects or = 470 msec for female subjects. Eligibility will be based on the core laboratory ECG interpretation report.
14. Subject has a positive screening laboratory test result for human immunodeficiency virus (HIV).
15. 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.
16. Subject has major psychiatric disorder, including but not limited to in the last 12 months: bipolar disorder, psychosis (including hallucinations), major depressive episode, or any disorder that, in the opinion of the Inve

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified