Efficacy and Safety Proof of Concept Study in Patients With Parkinson's Disease and End-of-dose Motor Fluctuations (PARPOC)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Orion Corporation, Orion Pharma
ClinicalTrials.gov Identifier:
NCT01766258
First received: November 22, 2012
Last updated: November 20, 2013
Last verified: November 2013
  Purpose

The primary objective of the study is to assess the efficacy, carbidopa dose response and safety of ODM-101, a new combination of levodopa, carbidopa and entacapone in the treatment of Parkinson's disease (PD) patients with end-of-dose motor fluctuations.


Condition Intervention Phase
Parkinson's Disease
Drug: ODM-101 65mg Carbidopa
Drug: ODM-101 105mg Carbidopa
Drug: Stalevo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Efficacy and Safety of ODM-101 Compared to a Standard Combination (Stalevo®); a Randomised, Double-blind, Crossover, Proof of Concept Study in Patients With Parkinson's Disease and End-of-dose Motor Fluctuations

Resource links provided by NLM:


Further study details as provided by Orion Corporation, Orion Pharma:

Primary Outcome Measures:
  • Duration of off time [ Time Frame: Average per day (over 3 consecutive days during the last 2 weeks of each treatment period). ] [ Designated as safety issue: No ]
    Duration of off time measured by the diary will be analysed using analysis of variance (ANOVA) model for cross-over design.


Secondary Outcome Measures:
  • Unified Parkinson's disease rating Scale (UPDRS) I-IV and the sum of UPDRS II and III ('total score') [ Time Frame: Weeks 4, 8 and 12 ] [ Designated as safety issue: No ]
    UPDRS I-IV and the sum of UPDRS II and III ('total score') asses by the investigator analysed using ANOVA model for crossover design.


Enrollment: 117
Study Start Date: May 2011
Study Completion Date: September 2012
Primary Completion Date: August 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Stalevo
levodopa/carbidopa/entacapone
Drug: Stalevo
Experimental: ODM-101 65mg Carbidopa
levodopa/carbidopa/entacapone
Drug: ODM-101 65mg Carbidopa
Experimental: ODM-101 105mg Carbidopa
levodopa/carbidopa/entacapone
Drug: ODM-101 105mg Carbidopa

Detailed Description:

This is a randomised, double-blind, double-dummy, active-controlled, crossover, multicentre, phase II proof of concept study in patients with PD and end-of-dose motor fluctuations. The patient's individually optimised daily levodopa regimen must be kept stable for at least 2 weeks before randomisation. The patients will be randomised to receive ODM-101 with 65 mg of carbidopa, ODM-101 with 105 mg of carbidopa and Stalevo® according to a 3-period crossover design.

The study consists of a screening period, 3 treatment periods and a post-treatment period. For each patient,there will be 9 visits: a screening visit performed 7-28 days before randomisation, a randomisation visit (visit 1), 6 visits during the 3 treatment periods (i.e. 2, 4, 6, 8, 10 and 12 weeks after randomisation and the start of the study treatment; visits 2-7), and an end-of-study visit 7-21 days after the last visit of the last treatment period. The duration of study will be 14-23 weeks for each patient.

The patients switch to study drugs after all assessments have been done at visit 1. The strength of the levodopa in the study drug is determined by the patient's individually optimised levodopa regimen before randomisation. During the first 2 weeks of each treatment period, the patient's levodopa strength (but not frequency) in the study drug will be adjusted as necessary by the investigator. For the remaining 2 weeks of each treatment period, the levodopa strengths should be kept stable.

Unscheduled visits maybe performed during the first 2 weeks of each treatment period, if there is a need to adjust the levodopa strength. In case the patient has not contacted the study centre within a week after the start of the treatment period, the study personnel will phone the patient to ensure that the symptoms and possible adverse events (AEs) are sufficiently controlled and captured, and to assess the need to adjust the levodopa treatment.

  Eligibility

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

Inclusion Criteria:

  • Written informed consent (IC) obtained.
  • Male or female patients with idiopathic PD according to the United Kingdom brain bank criteria with end-of-dose -motor fluctuations.
  • Hoehn and Yahr stage 2-4 performed during the on state.
  • An average of 3.0 hours of off time, with a minimum of 0.5 hours of off time on each day (using PD home diary [hereafter diary]) on 3 consecutive days before the decision of entry.
  • Treatment with 3-8 daily doses of levodopa/dopa decarboxylase inhibitor (DDCI) with entacapone (either levodopa/DDCI combined with Comtess®/Comtan® or as Stalevo®) or without entacapone, including daily use of soluble levodopa formulation, with a total daily levodopa dose in the range of 400-1400 mg. One evening dose of controlled-release formulation of levodopa/DDCI is allowed providing that it is included in the total daily levodopa dose in the range of 400-1400 mg mentioned above. Use of additional soluble levodopa formulations as rescue treatment, such as Madopar LT or Quick, up to a maximum of 4 doses per week is allowed; however, its use should be avoided on days during which PD status (diary) is recorded. The levodopa dose from these rescue soluble levodopa formulations is not included in the range of total daily dose of levodopa indicated above.
  • Unchanged levodopa/DDCI with or without entacapone and other antiparkinsonian medication (dopamine agonists, monoamine oxidase [MAO] B inhibitor, amantadine and/or anticholinergics with doses recommended by the manufacturer), if any, for at least 4 weeks prior to the screening visit.
  • Age of 30 years or above.

Exclusion Criteria:

  • Secondary or atypical parkinsonism.
  • Current use of tolcapone (within 6 weeks prior to the first treatment period).
  • Previous tolerability problems with entacapone or tolcapone.
  • Concomitant treatment with apomorphine, MAO-A inhibitors or non-selective MAO inhibitors.
  • Concomitant treatment with drugs having antidopaminergic action including alpha-methyldopa, reserpine and antipsychotic drugs (also dopamine D2 receptor blocking antiemetics except domperidone). As an exception to the prohibition of use of antipsychotic drugs, 1 evening dose of an atypical antipsychotic is allowed.
  • Severe dyskinesias as judged by the investigator; however, mild to moderate dyskinesia not significantly affecting patient's activities of daily living is allowed.
  • Currently active hallucinations.
  • Severe orthostatic hypotension as judged by the investigator.
  • Current dementia (Mini-Mental State Examination [MMSE] score < 24).
  • Problematic impulse control disorders (ICD) such as pathological gambling, hypersexuality or compulsive shopping within 6 months prior to the screening visit.
  • History of neuroleptic malignant syndrome (NMS) and/or non-traumatic (drug-induced) rhabdomyolysis.
  • Past or current treatment with deep brain stimulation (DBS) or other surgical treatment for PD.
  • Narrow-angle glaucoma or pheochromocytoma.
  • Any active malignant cancer.
  • Patients with pre-planned elective surgery that is likely to change or impact on the control of PD symptoms, or involve hospitalisation.
  • Failure to demonstrate acceptable/appropriate use of the diary, despite adequate training, during the screening visit or other separate training sessions during the screening period.
  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: NCT01766258

Sponsors and Collaborators
Orion Corporation, Orion Pharma
Investigators
Principal Investigator: Claudia Trenkwalder, MD Paracelsus-Elena-Klinik, Klinikstr. 16, 34128 Kassel, Germany
  More Information

Additional Information:
No publications provided

Responsible Party: Orion Corporation, Orion Pharma
ClinicalTrials.gov Identifier: NCT01766258     History of Changes
Other Study ID Numbers: 2939135
Study First Received: November 22, 2012
Last Updated: November 20, 2013
Health Authority: Finland: Finnish Medicines Agency
Germany: Federal Institute for Drugs and Medical Devices
Latvia: State Agency of Medicines
Lithuania: State Medicine Control Agency - Ministry of Health
Romania: National Medicines Agency

Keywords provided by Orion Corporation, Orion Pharma:
Parkinson's Disease
Motor-fluctuation
Wearing-off

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

ClinicalTrials.gov processed this record on September 16, 2014