Efficacy, Safety, and Pharmacokinetics/Pharmacodynamic Study of L-Dopa/Carbidopa To Treat Parkinson's Disease

An Efficacy, Safety, and Pharmacokinetics/Pharmacodynamic Relationship Study of L-Dopa/Carbidopa in a Novel Release Formulation in Parkinson's Disease Patients

Determine if a novel levodopa/carbidopa formulation results in a better clinical response on Parkinson's Disease patients compared to the reference formulation of levodopa/carbidopa in terms of motor complications, onset of action and response duration.

Study Overview

• Status: Completed
• Conditions: Parkinson's Disease
• Intervention / Treatment: Drug: levodopa-carbidopa

Detailed Description

Primary objective is to demonstrate a better clinical response profile of novel levodopa/carbidopa formulation vs. the reference formulation of levodopa/carbidopa in patients with Parkinson's Disease as judged by motor performance and to describe pharmacokinetic profile for the novel formulation compared to the reference.

• Study Type: Interventional
• Enrollment (Actual): 78
• Phase: Phase 2

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina
    • Hospital Sirio Libanes
  • Buenos Aires, Argentina
    • Fundacion Alfredo Thomson
  • Buenos Aires, Argentina
    • Hospital Posadas
  • Buenos Aires, Argentina
    • Hospital Ramos Mejia
  • Buenos Aires, Argentina
    • Instituto Frenopático
  • Buenos Aires, Argentina
    • nstituto INEBA
  • Buenos Aires, Argentina
    • Policlinica Bancaria
  • Rosario, Argentina
    • Fundación Rosarina de Neuro-Rehabilitación
  • Salta, Argentina
    • Hospital San Bernardo

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Clinical diagnostic of Parkinson's Disease, with a Hoehn and Yahr Staging within 2-4, and L-Dopa therapy complications
• at least 2years of L-Dopa therapy
• Patients with the ability to differentiate between "ON" and "OFF" periods
• Patients who have been receiving stable doses of L-Dopa between 600 and 1600 mg/day, for at least 2 months prior to the screening visit using a dosing regimen not higher that 5 times a day, and not expected in the investigator's opinion to need any dose modifications over the duration of the study
• Patients presenting a score of at least 2 in the UPDRS IVa, item 32 and/or a score of at least 2 in the UPDRS IVb, item 39, at screening and randomization visits based on clinical records for the first visit and daily diary cards at randomization time.
• Willing and able to understand and sign Informed Consent form

Exclusion Criteria:

• Patients with a diagnosis of any known secondary Parkinsonian syndrome, (vascular, toxin or drug-induced, metabolic or infectious, etc) or other neurodegenerative disorder with parkinsonism (Progressive Supranuclear Palsy, Corticobasal Degeneration, Multiple System Atrophy, etc).
• Patients receiving other concomitant anti-Parkinsonian pharmacological therapies affecting L-dopa or dopamine metabolisom (COMT inhibitors or MAO inhibitors)
• Subjects who have undergone prior functional neurosurgical treatment for PD (ablation or Deep Brain Stimulation).
• Patient with a L-dopa dosage regimen greater than 5 times a day which is not able to be adapted to a q.i.d. regimen.
• Patients having received L-dopa / Decarboxylase inhibitors therapy for less than 2 years.
• Patients needing nightly doses of L-dopa / Decarboxylase inhibitors apart from the four daily doses.
• Any medical condition or past medical history that, in the investigator's judgment, would increase the risk of exposure to L-dopa / Carbidopa or interfere with the evaluation of the study objectives.
• Patients with unstable or clinically significant known medical illness; such as cardiac, pulmonary, kidney, hepatic and/or gastrointestinal disease that would, in the investigator's judgment, interfere with the safe course of the study.
• Cognitive impaired patients, as determined by a score of lesser than 26 on the Mini-Mental Score Status Examination. (MMSE < 26).
• Alcohol or illegal drugs abuse.
• Pregnant or lactating patients.
• Hypersensitivity to any of the investigational drugs, based on known allergies to drugs of the same class.
• Patients having taken any research drugs over the last 30 days prior to the beginning of the study.
• Blood donation, or blood products, or participation to a clinical trial with serial blood withdrawals, within twelve weeks prior to the start of the trial, or intention to donate blood or blood products within three months following the study completion.
• Patients who have received some of the following medications with an anticipation of no more than 7 treatment-drug elimination half-lives of entry time: Dopamine D2 receptor antagonists , isoniazid, anti-epileptic drugs, IMAO A or B, pyridoxine, ferrous salts or methyldopa.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: A	Drug: levodopa-carbidopa; novel levodopa/carbidopa formulation or a reference levodopa/carbidopa formulation
Active Comparator: B	Drug: levodopa-carbidopa; novel levodopa/carbidopa formulation or a reference levodopa/carbidopa formulation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Evidence of a novel levodopa/carbidopa formulation providing a better clinical profile than reference levodopa/carbidopa formulation using Unified Parkinson's Disease Rating Scale (UPDRS III) and patient's diary cards	every half hour for the first 8 hours after dosing

Secondary Outcome Measures

Outcome Measure	Time Frame
Other measurements to be used for demonstrating clinical profile is UPDRS II and IV, Clinical Global Impression Scale (CGI)/Patient's Global Improvement Scale (PGI), and the Abnormal Involuntary Movement Scale (AIMS)	over the course of the study

Collaborators and Investigators

• Sponsor: Osmotica Pharmaceutical US LLC
• Investigators: Study Director: Gustavo Fischbein, M.D., Osmotica Pharmaceutical Argentina S.A.

Study record dates

Study Major Dates

• Study Start: November 1, 2007
• Primary Completion (Actual): December 1, 2008
• Study Completion (Actual): December 1, 2008

Study Registration Dates

• First Submitted: November 12, 2007
• First Submitted That Met QC Criteria: November 13, 2007
• First Posted (Estimate): November 14, 2007

Study Record Updates

• Last Update Posted (Estimate): January 14, 2009
• Last Update Submitted That Met QC Criteria: January 13, 2009
• Last Verified: January 1, 2009

More Information

Terms related to this study

• Keywords: Treatment of Parkinson's Disease
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Parkinson Disease; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Immunologic Factors; Dopamine Agonists; Dopamine Agents; Adjuvants, Immunologic; Antiparkinson Agents; Anti-Dyskinesia Agents; Aromatic Amino Acid Decarboxylase Inhibitors; Levodopa; Carbidopa; Carbidopa, levodopa drug combination
• Other Study ID Numbers: OS353-CTP 01