PK, PD and Safety of Multiple Doses of V1512 Tablets in PD Patients Compared to Standard Levodopa/Carbidopa Oral Tablets

This study has been completed.
Sponsor:
Collaborators:
Cita NeuroPharmaceuticals
INC Research
Information provided by:
Vernalis (R&D) Ltd
ClinicalTrials.gov Identifier:
NCT00491998
First received: June 26, 2007
Last updated: July 21, 2011
Last verified: July 2011
  Purpose

The purpose of the study is to determine if the pharmacokinetic profile of V1512 is similar or better than existing medications for the treatment of Parkinson's Disease


Condition Intervention Phase
Parkinson's Disease
Drug: V1512
Drug: V1512 and Entacapone
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Crossover Assignment
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: Randomised, Double-blind, Double-dummy, Two-period, Cross-over Study to Determine the PK, PD and Safety of Multiple Doses of V1512 Effervescent Tablets in Parkinson's Disease Patients Compared to Sinemet® Oral Tablets

Resource links provided by NLM:


Further study details as provided by Vernalis (R&D) Ltd:

Primary Outcome Measures:
  • to characterise the plasma concentrations of L-dopa after repeated doses of V1512 in fluctuating PD patients compared to standard L-dopa/carbidopa (Sinemet) over the course of the day [ Time Frame: 4 weeks ]

Secondary Outcome Measures:
  • correlate plasma concentrations with response to therapy; [ Time Frame: 4 weeks ]
  • further characterise the safety and tolerability profile for each treatment [ Time Frame: 4 weeks ]

Estimated Enrollment: 27
Study Start Date: November 2006
Study Completion Date: November 2007
Primary Completion Date: November 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 2-hourly dosing
6 Doses of IMP at 2-hourly intervals
Drug: V1512
6 doses of IMP at 2-hourly intervals
Experimental: 3-hourly dosing
4 doses of IMP at 3-hourly intervals
Drug: V1512
3-hourly dosing
Active Comparator: 3-hourly dosing plus Entacapone
4 doses of IMP plus Entacapone at 3-hourly intervals
Drug: V1512 and Entacapone
4 doses of IMP and Entacapone at 3-hourly intervals

Detailed Description:

The pharmacokinetics of V1512 effervescent tablet has been evaluated in healthy volunteers, however not fully in PD patients. This study aims to evaluate the PK profiles in PD patients of different dosing schedules of V1512 effervescent tablet compared to the profiles after standard L-dopa/carbidopa (Sinemet) over the course of the day. Two dosing schedules have been chosen to evaluate a possible relation between dosing interval and 'ON' time, with and without associated dyskinesia. Similar dosing schedules with the comparator Sinemet are commonly employed in the treatment of fluctuating PD patients. Patients assigned to cohort 3 will also take a dose of entacapone concomitantly with each dose of V1512 or Sinemet, thereby allowing the kinetics and dynamics of.V1512 and Sinemet to be compared in the presence of COMT inhibition.

Safety and tolerability of the dosing regimens in patients will also be assessed further in this double-blind study

  Eligibility

Ages Eligible for Study:   30 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male or female, >30 years of age of any race;
  2. A Body Mass Index between 18.5 and 29.9 kg/m2 (inclusive);
  3. Clinical diagnosis according to the Brain Bank diagnostic criteria of idiopathic Parkinson's Disease (2 of 3 cardinal symptoms - bradykinesia, rigidity, tremor -must be present, with a positive response to L-dopa);
  4. Presence of fluctuations in motor performance with >2 hours inclusive of daytime OFF episodes (not applicable for cohort 1 patients);
  5. At least 1 hour delay to ON time with afternoon doses;
  6. Discontinued use of COMT inhibitors (cathecol-o-methyl transferase) for at least 2 weeks prior to study entry (not applicable for cohort 3 patients);
  7. Stable doses of dopamine agonists or selegiline for at least 2 weeks before entry into the study;
  8. Stable comorbidity for 4 weeks;
  9. Female patients must be of non-childbearing potential (post-menopausal or physically incapable of childbearing);
  10. Willing and able to give informed consent according to national legal requirements prior to initiation of any study-related procedures

Exclusion Criteria:

  1. Clinically relevant abnormal vital sign values or safety laboratory data.
  2. Patients who smoke and are unable to refrain from smoking during the in-clinic period
  3. Diagnosis of atypical parkinsonism;
  4. A history and/or the presence of gastro-intestinal disorders (or surgery) that could interfere with absorption of the test medication;
  5. A history of intolerance or clinically relevant allergy to L-dopa and/or carbidopa taken in any formulation or combination;
  6. A history of intolerance or clinically relevant allergy to entacapone or any ingredients of Comtan (cohort 3 patients only)
  7. Any other condition which, in the opinion of the Investigator, would interfere with optimal participation in the study e.g. inability to complete patient diary;
  8. Participation in any clinical study or receiving treatment with another investigational drug within 30 days or 5 half lives (whichever is longer) before the screening visit;
  9. Blood donation within 3 months before study participation;
  10. History of neuroleptic malignant syndrome (NMS) or NMS-like syndromes, or non-traumatic rhabdomyolysis;
  11. Patients taking non-selective MAO inhibitors;
  12. Patients with a history of, or clinical indication of, narrow angle glaucoma;
  13. Patients with a history of, or clinical indication of, malignant melanoma;
  14. Patients with a history of, or clinical indication of, depression or psychosis;
  15. Patients taking iron containing medications (ferrous sulphate, ferrous gluconate)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00491998

Locations
Italy
IRCCS San Raffaele Pisana
Roma, Rome, Italy, 00163
Sponsors and Collaborators
Vernalis (R&D) Ltd
Cita NeuroPharmaceuticals
INC Research
Investigators
Principal Investigator: Fabrizio Stocchi, MD, PhD IRCCS San Raffaele
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT00491998     History of Changes
Other Study ID Numbers: V1512-2PD01
Study First Received: June 26, 2007
Last Updated: July 21, 2011
Health Authority: Italy: Ministry of Health

Additional relevant MeSH terms:
Parkinson Disease
Parkinsonian Disorders
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Movement Disorders
Neurodegenerative Diseases
Entacapone
Antiparkinson Agents
Anti-Dyskinesia Agents
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on October 01, 2014