Intermittent Oral Administration vs. Semi-continuous Intra-oral Administration of Levodopa/Carbidopa in Fluctuating Parkinsonian Patients

NCT02763137 | Completed Phase 2 DMC

• 1 other identifier: RP 12/14
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase IIa study to assess the safety, tolerability, plasma pharmacokinetics and efficacy of intermittent oral administration of standard levodopa/carbidopa (LD/CD) vs.semi-continuous intra-oral administration of levodopa/carbidopa in patients with advanced Parkinson's disease (PD) who suffer motor fluctuations.The objective of this study is to assess the plasma pharmacokinetics (PK) of continuous intra-oral administration of LD/CD vs. intermittent administration of standard oral LD/CD. For purposes of this study continuous intra-oral administration of LD/CD is defined as oral administration of LD/CD at 5-10 minute intervals. Secondary objectives are to assess the safety and tolerability of continuous intra-oral administration of LD/CD and the effect on PD motor function of continuous intra-oral administration of LD/CD vs. intermittent administration of standard oral LD/CD.

Conditions

Parkinson Disease

Outcome Measures

Primary Outcomes (1)

• Variability in the observed plasma concentration of levodopa as assessed with the fluctuation index (Fluctuation index= (Maximum Plasma Concentration (Cmax)-Minimum Plasma Concentration (Cmin))/Concentration average)

  Change in fluctuation index between intermittent administration (Day 2) and intra-oral administration (Day 3)

  Change in fluctuation index between Day 2 and Day 3

Secondary Outcomes (3)

• Assess the safety and tolerability of continuous intra-oral administration of LD/CD: Adverse Events

  From Day 1 to Day 18

• Assess the effect on number of hours of "off" time of continuous intra-oral administration of LD/CD vs. intermittent administration of standard oral LD/CD

  Change in number of hours of "off" time between Day 2 and Day 3

• Assess the effect on UPDRS of continuous intra-oral administration of LD/CD vs. intermittent administration of standard oral LD/CD

  Change in UPDRS between Day 2 and Day 3

Study Arms (2)

Standard LD/CD

ACTIVE COMPARATOR

Standard LD/CD administered at patient's usual dose and frequency

Drug: Standard LD/CD

Semi continuous intra-oral administration of LD/CD

EXPERIMENTAL

Semi continuous intra-oral administration of LD/CD at a dose equivalent to the patient's regular dose of standard LD/CD

Drug: Semi continuous intra-oral administration of LD/CD

Interventions

Standard LD/CD DRUG

LD/CD will be administered at patient's usual dose and frequency during 8 hours interval

Also known as: Sinemet 25 mg/100 mg at patient's usual dose and frequency

Standard LD/CD

Semi continuous intra-oral administration of LD/CD DRUG

Semi continuous intra-oral administration of standard LD/CD at a dose equal to the total dose of standard oral LD/CD that patients would normally consume over 8 hours period.

Also known as: Sinemet 25 mg/100 mg administered at 5-10 minutes intervals

Semi continuous intra-oral administration of LD/CD

Eligibility Criteria

• Age: 35 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• PD diagnosis consistent with United Kingdom Brain Bank Criteria
• Good response to levodopa with at least 2 hours of wearing off episodes in judgment of investigator
• Stable doses of levodopa plus/minus other dopaminergic therapy (minimum of 4 weeks for each drug)
• Mini Mental Score Examination (MMSE): score \> 26
• Capable of providing informed consent
• No clinically significant medical, psychiatric or laboratory abnormalities in the judgment of the investigator.
• No history of psychosis or hallucinations in the past 6 months
• 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.
• Approval for entry into the study by an enrolment steering committee

You may not qualify if:

• Atypical or secondary parkinsonism
• Severe dyskinesia that might interfere with study performance in judgment of investigator
• Patient receiving duodopa, apomorphine infusion or Deep Brain Stimulation (DBS)
• Dysphagia or sialorrhea that might interfere with administration of study intervention
• 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.

Sponsors & Collaborators

• IRCCS San Raffaele Roma: lead
• SynAgile Corporation: collaborator

Study Sites (1)

Irccs San Raffaele Pisana

Rome, 00163, Italy

Location

Related Publications (1)

• Stocchi F, Vacca L, Ruggieri S, Olanow CW. Intermittent vs continuous levodopa administration in patients with advanced Parkinson disease: a clinical and pharmacokinetic study. Arch Neurol. 2005 Jun;62(6):905-10. doi: 10.1001/archneur.62.6.905.

  PMID: 15956161 RESULT

MeSH Terms

Conditions

Parkinson Disease

Interventions

carbidopa, levodopa drug combination

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Study Officials

• FABRIZIO STOCCHI, PROFESSOR

  IRCCS San Raffaele

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 26, 2016
• First Posted: May 5, 2016
• Study Start: July 30, 2014
• Primary Completion: October 1, 2015
• Study Completion: October 1, 2015
• Last Updated: April 10, 2024

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will share

Locations

IT (1)