A Phase IIa study to assess the safety, tolerability, plasma pharmacokinetics and efficacy of intermittent oral administration of standard levodopa/carbidopa vs. semi-continuous intra-oral administration of levodopa/carbidopa in patients with advanced Parkinson’s disease who suffer motor fluctuations.

• Register: EUCTR
• Last refreshed on: 19 February 2018
• Main ID: EUCTR2014-002295-87-IT
• Date of registration: 29/09/2014
• Prospective Registration: Yes
• Primary sponsor: SynAgile Corporation
• Public title: A Phase IIa study to assess the safety, tolerability, plasma pharmacokinetics and efficacy of intermittent oral administration of standard levodopa/carbidopa vs. semi-continuous intra-oral administration of levodopa/carbidopa in patients with advanced Parkinson’s disease who suffer motor fluctuations.
• Scientific title: A Phase IIa study to assess the safety, tolerability, plasma pharmacokinetics and efficacy of intermittent oral administration of standard levodopa/carbidopa vs. semi-continuous intra-oral administration of levodopa/carbidopa in patients with advanced Parkinson’s disease who suffer motor fluctuations.
• Date of first enrolment: 13/10/2014
• Target sample size: 18
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-002295-87
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: no; Open: yes; Single blind: no; Double blind: no; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: yes; Other specify the comparator: same drug, administered in different ways; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Italy

Contacts

• Name: Michela Pilone
• Affiliation: CIRM

• Name: Michela Pilone
• Affiliation: CIRM

Key inclusion & exclusion criteria

Inclusion criteria:
1. PD diagnosis consistent with UK Brain Bank Criteria
2. Good response to levodopa with at least 2 hours of wearing off
episodes in judgment of investigator
3. Stable doses of levodopa plus/minus other dopaminergic therapy
(minimum of 4 weeks for each drug)
4. MMSE score > 26
5. Capable of providing informed consent
6. No clinically significant medical, psychiatric or laboratory
abnormalities in the judgment of the investigator.
7. No history of psychosis or hallucinations in the past 6 months
8. Women who are capable of child bearing must have a negative urine
pregnancy test at screening visit and use an adequate contraceptive
method throughout the study.

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 13
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 5

Exclusion criteria:
1. Atypical or secondary parkinsonism
2. Severe dyskinesia that might interfere with study performance in
judgment of investigator
3. Patient receiving duodopa, apomorphine infusion or DBS
4. Dysphagia or sialorrhea that might interfere with administration of
study intervention
5. Any relevant medical, surgical, or psychiatric condition, laboratory
value, or concomitant medication which, in the opinion of the
Investigator, would interfere with performing a pharmacokinetic study
or would interfere with drug absorption.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Parkinson's disease patients who suffer motor fluctuations will participate in the study
MedDRA version: 17.0 Level: SOC Classification code 10029205 Term: Nervous system disorders System Organ Class: 10029205 - Nervous system disorders

Intervention(s)

Trade Name: SINEMET 100 mg + 25 mg compresse
Product Name: SINEMET 100 mg + 25 mg compresse
Product Code: NA
Pharmaceutical Form: Oral suspension

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: The hourly time points are as follows: 0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5,
5, 5.5, 6, 6.5, 7, 7.5, and 8, on Days 2 and 3

Main Objective: To assess the plasma pharmacokinetics of continuous intra-oral administration of LD/CD vs. intermittent administration of standard oral LD/CD

Primary end point(s): Pharmacokinetic: The primary outcome measure will be the variability in
the observed plasma concentration of levodopa as assessed with the
fluctuation index (Fluctuation index = (Cmax-Cmin)/Caverage).

Secondary Objective: To assess the safety and tolerability of continuous intra-oral administration of
LD/CD
To assess the effect on PD motor function of continuous intra-oral
infusion of LD/CD vs. intermittent administration of standard oral LD/CD

Secondary Outcome(s)

Secondary end point(s): Pharmacokinetic: Secondary outcome measures will include assessment
of variability using the coefficient of variation (CV). Exploratory
measures will include assessments of levodopa Cmax, Tmax, and AUC.
Plasma PK of carbidopa, HVA, DOPAC, and 3-OMD will also be assessed.
Safety: Safety will be assessed by descriptive reporting of adverse
events (frequency and severity)
Tolerability: Tolerability will be assessed by percentage of subjects that
complete the trial on given treatment assignment.
Efficacy: Efficacy will be measured by the number of off hours in 8-hour
day as determined by physician evaluations and in the change in the
UPDRS between the baseline and mean of 2, 4, and 8-hour evaluations

Timepoint(s) of evaluation of this end point: Pharmacokinetic :The hourly time points are as follows: 0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5 and 8, on Days 2 and 3
Safety: descriptively by D2, D3, and D4 and cumulative safety
Tolerability: Baseline to D2, Baseline to D3 and Baseline to D4
Efficacy: every half hour over 8 hour period and at hours 2,4, and 8

Secondary ID(s)

LDCD-001

Source(s) of Monetary Support

SynAgile Corporation