An open-label Phase 2 study to assess the pharmacokinetics of Accordion Pill¿ Carbidopa-Levodopa compared to immediate release carbidopa-levodopa in patients with Parkinson¿s disease
- Conditions
- Parkinson's Disease (PD)MedDRA version: 20.0Level: PTClassification code 10061536Term: Parkinson's diseaseSystem Organ Class: 10029205 - Nervous system disordersTherapeutic area: Diseases [C] - Nervous System Diseases [C10]
- Registration Number
- EUCTR2018-001209-95-IT
- Lead Sponsor
- INTEC PHARMA LTD
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 12
1.Men or women 30 years of age or older at screening
2.Diagnosis of Parkinson’s disease consistent with the UK Brain Bank Criteria
3.Stable doses of levodopa/carbidopa IR for at least 4 weeks prior to entry
4.Taking at least 4 doses of immediate release levodopa during waking hours
5.Taking a total levodopa daily dose of at least 400 mg prior to initial screening assessment
6.All anti-PD medications are permitted during the study but must be maintained on stable doses for at least 30 days prior to study entry (screening visit). COMT inhibitors will be held prior to PK studies on Day 1 and through Day 8.
7.Other than PD, the subject is in satisfactory health in the judgment of the investigator. No clinically significant medical, psychiatric or laboratory abnormality that could compromise safety or interfere with study procedures
8.Subjects must be approved for suitability by an Enrollment Authorization Committee.
9.Able and willing to give written (signed and dated) informed consent, and to comply with study requirements
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 4
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 8
1.Atypical or secondary parkinsonism
2.Clinically significant cardiac, pulmonary, hepatic or renal disease or other condition which contraindicates his/her participation in judgment of the investigator or the EAC
3.Severe dyskinesia as assessed by the PI or the Enrollment Authorization Committee
4.Significant cognitive impairment in the opinion of the Investigator.
5.Clinically significant psychiatric illness in the opinion of the Investigator, including psychotic attacks or major depression
6.Subjects with a history of suicide attempt (including an active attempt, interrupted attempt or aborted attempt) within the last 5 years.
7.Treatment within the past 28 days with a neuroleptic drug (antipsychotic) or any other drug with anti-dopaminergic properties (e.g. metoclopramide).
8.Currently experiencing or any known history of psychosis within the previous 2 years.
9.History of small bowel or gastric surgery (Including PEG-J placement for Duopa/Duodopa) or bowel obstruction, diagnosis of small bowel narrowing, diagnosis of Crohn’s disease, frequent nausea or emesis regardless of etiology, and symptomatic gastroparesis. (Previous appendectomy or hernioplasty will be not be exclusionary)
10.History of GI pathology of clinical significance as determined by the Investigator.
11.Regular use of opioids (Intermittent opioid use is not exclusionary)
12.Allergy to the study drug or any of its excipients or to Yellow Dye #5 (tartrazine)
13.History of drug or alcohol abuse within past 12 months
14.Use of an experimental drug within 30 days or five half-lives of screening
15.Unable to swallow large pills (e.g., large vitamin pills)
16.Active gastroesophageal reflux (GERD) and regular use of proton pump inhibitors (PPIs)
17.Women who are pregnant or nursing and women of childbearing potential (defined as from menarche and until becoming post-menopausal unless permanently sterile) who are not willing to use a highly effective method of contraception. Medically acceptable methods of contraception that may be used by the subject and/or partner include:
•True abstinence when this is in line with the preferred and usual lifestyle of the subject,
•combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation
ooral
ointravaginal
otransdermal (e.g., Ortho Evra),
•Progestogen-only hormonal contraception associated with inhibition of ovulation
ooral
oinjectable (e.g., Dep-Provera),
oimplantable (e.g., Norplant),
•intrauterine device (IUD),
•surgical sterilization (>6 months),
•Vasectomized partner (>6 months)
• Postmenopausal female (no menstrual period for > 2years)
Hormonal contraceptive therapy must be at a stable dose for at least 90 days prior to first study drug administration. The current contraceptive therapy must be maintained through the end of the study (Safety Follow Up Visit or Early Termination Visit).
18.History of Narrow-angle Glaucoma.
19.History of Melanoma or suspicious skin lesion which could be a Melanoma.
20.Treatment with non-selective monoamine oxidase (MAO) inhibitors during the last 28 days prior to initial screening assessment or planning to take during study participation.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To assess the pharmacokinetics of the Accordion Pill¿ carbidopa/levodopa (AP-CD/LD) administered at 500 mg TID compared to immediate release CD/LD administered as 1.5 tablets of Sinemet¿ 25-100 five times per day in Parkinson¿s disease (PD) patients. ;Secondary Objective: To assess the safety and tolerability of AP-CD/LD;Primary end point(s): •Variability in plasma levodopa concentration as assessed by the levodopa fluctuation index (fluctuation index = (Cmax-Cmin)/Caverage) (comparison of AP-CD/LD to IR-CD/LD).;Timepoint(s) of evaluation of this end point: PK blood sampling will be performed at time 0 and every 30 minutes for 16 hours (from approximately 8:00 AM until midnight) and again at 24 hours on Days 1 and 8.
- Secondary Outcome Measures
Name Time Method Secondary end point(s): Variability in plasma levodopa concentration as assessed by Coefficient of variation (CV) (comparison of AP-CD/LD to IR- CD/LD); AEs and SAEs ; Tolerability ; IR-CD/LD and AP-CD/LD Cmax, Tmax, Cmin, AUC, and elimination half life;Timepoint(s) of evaluation of this end point: PK blood sampling will be performed at time 0 and every 30 minutes for 16 hours (from approximately 8:00 AM until midnight) and again at 24 hours on Days 1 and 8; During the trial; During the trial; PK blood sampling will be performed at time 0 and every 30 minutes for 16 hours (from approximately 8:00 AM until midnight) and again at 24 hours on Days 1 and 8.