A clinical trial to compare APL-130277 sublingual film to Subcutaneous Apomorphine in Parkinson’s Disease patients
- Conditions
- evodopa Responsive Patients with Parkinson’s Disease Complicated by Motor Fluctuations (OFF episodes)MedDRA version: 21.1Level: LLTClassification code 10034006Term: Parkinson's disease aggravatedSystem Organ Class: 100000004852Therapeutic area: Diseases [C] - Nervous System Diseases [C10]
- Registration Number
- EUCTR2016-003456-70-GB
- Lead Sponsor
- Sunovion Pharmaceuticals Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 106
1 The subject (and caregiver, if applicable) must be fully informed of and understand the objectives, procedures, and possible benefits and risks of the study, and give written informed consent prior to performing any study-related activities.
2 Male or female = 18 years of age.
3 Clinical diagnosis of Idiopathic PD, consistent with UK Brain Bank
Criteria (excluding the more than one affected relative criterion).
4 Clinically meaningful response to levodopa (L-Dopa), as determined by
the Investigator.
5 Subjects at Screening must demonstrate an adequate L-Dopa response on the MDS-UPDRS Part III in the ON state compared to the MDSUPDRS Part III in the OFF state and on the Hoehn and Yahr, as
determined during the review by Enrollment Adjudication Committee
(EAC), Sponsor, and Medical Monitor.
6 Receiving stable doses of L-Dopa/carbidopa and/or LDopa/
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 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. Use of Madopar PRN in the 4 weeks prior to
screening is permitted.
7 No planned medication change(s) or surgical intervention anticipated
during the course of study.
8 Subjects must experience at least one well defined OFF episode per
day and have a total daily OFF time duration of > 2 hours during the
waking day, based on judgment of physician and subject self assessment.
9 Subject must have predictable morning OFF periods, based on
judgment of physician and subject self-assessment.
10 Subject, and where appropriate caregiver, must be trained in
completing the home dosing diaries and able to recognize ON and
OFF states.
11 Stage III or less on the modified Hoehn and Yahr scale in the ON
state.
12 Mini–Mental State Examination (MMSE) score > 25.
13 Female subject of childbearing potential and male subject with
female partner of childbearing potential must agree to either remain
abstinent or use adequate and reliable contraception (see Section 10.4.1
for additional information on acceptable methods of birth control)
throughout the study and for at least 7 days after the last dose of study
drug has been taken. Note: Continued use of adequate and reliable
contraception is recommended through 30 days after study completion.
14 Willing and able to comply with scheduled visits, treatment plan,
laboratory tests, and other study-related procedures to complete the
study.
15 Must be approved as a satisfactory candidate by the Enrollment
Adjudication Committee (EAC), Medical Monitor, and Sponsor.
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 64
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 42
1 Atypical or secondary parkinsonism.
2 Major focal brain disorders including malignancy or stroke.
3 Prior treatment with any of the following: a neurosurgical procedure
for PD; continuous subcutaneous (sc) apomorphine infusion; sc
apomorphine injection; Duodopa/Duopa; or APL-130277.
4. Subjects who have permanently stopped use of s.c. apomorphine (injection).
5 Contraindications to domperidone, subcutaneous apomorphine, or
hypersensitivity to apomorphine hydrochloride or any of the ingredients
of subcutaneous apomorphine (notably sodium metabisulfite).
6 Female who is pregnant or lactating.
7 Participation in an interventional clinical study and/or receipt of any
investigational (ie, unapproved) medication within 30 days prior to SV1.
8 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 prior to SV1.
9 current diagnosis or history of substance abuse (excluding nicotine
and caffeine) or alcohol abuse (in the opinion of the investigator) < 6
months prior to SV1.
10 positive urine drug screen result. NOTE: Benzodiazepines, opiates, and
oxycodone will be allowed provided the subject has been on a stable
dose for 4 weeks prior to SV1, provided the subject has a valid
prescription. Cotinine is not exclusionary.
11 The recreational use of cannabinoids and hallucinogenic(including
formulations of CBD) and hallucinogenics are excluded, as well any use
of a sublingual formulation of any drug.
12 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.
13 clinically significant abnormality on screening evaluation including
physical examination, vital signs, electrocardiogram (ECG), or laboratory
tests that the Investigator considers to be inappropriate to allow
participation in the study.
14 screening laboratory test results of: 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 ALT or AST value = 2 times the
ULN for the reference laboratory.
15 random (non-fasting) screening glucose of = 200 mg/dL (11.1
mmol/L) or HbA1c > 7.0%.
16 Subjects with type 1 diabetes, or insulin-dependent diabetics are
excluded. Subjects with type 2 diabetes are eligible for study inclusion if
the following conditions are met:
• Subject's screening glucose is < 200 mg/dL (11.1 mmol/L). Note:
Subjects with random (non-fasting) blood glucose at screening = 200
mg/dL (11.1 mmol/L) must be retested in a fasted state; and
• Subject's HbA1c = 7.0%; and
• If the subject is currently being treated with oral anti-diabetic
medication(s), the dose must have been stable for at least 4 weeks prior
to SV1. Such medication may be adjusted or discontinued during the
study, as clinically indicated.
17 The subject's screening ECG results of corrected QT interval using
Fridericia's formula (QTcF) = 450 msec for male subjects or = 470 msec
for female subjects. Eligibility will be based on the core laboratory ECG
interpretation report.
18 positive screening laboratory test result for HIV.
19 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 labo
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method