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

NCT01766258 | Completed Phase 2

• 1 other identifier: 2939135
• Study Type: interventional
• Target: 117
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Parkinson's Disease

Keywords

Parkinson's Disease; Motor-fluctuation; Wearing-off

Outcome Measures

Primary Outcomes (1)

• Duration of off time

  Duration of off time measured by the diary will be analysed using analysis of variance (ANOVA) model for cross-over design.

  Average per day (over 3 consecutive days during the last 2 weeks of each treatment period).

Secondary Outcomes (1)

• Unified Parkinson's disease rating Scale (UPDRS) I-IV and the sum of UPDRS II and III ('total score')

  Weeks 4, 8 and 12

Study Arms (3)

Stalevo

ACTIVE COMPARATOR

levodopa/carbidopa/entacapone

Drug: Stalevo

ODM-101 65mg Carbidopa

EXPERIMENTAL

levodopa/carbidopa/entacapone

Drug: ODM-101 65mg Carbidopa

ODM-101 105mg Carbidopa

EXPERIMENTAL

levodopa/carbidopa/entacapone

Drug: ODM-101 105mg Carbidopa

Interventions

ODM-101 65mg Carbidopa DRUG

ODM-101 65mg Carbidopa

ODM-101 105mg Carbidopa DRUG

ODM-101 105mg Carbidopa

Stalevo DRUG

Stalevo

Eligibility Criteria

• Age: 30 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Orion Corporation, Orion Pharma: lead

Related Publications (1)

• Trenkwalder C, Kuoppamaki M, Vahteristo M, Muller T, Ellmen J. Increased dose of carbidopa with levodopa and entacapone improves "off" time in a randomized trial. Neurology. 2019 Mar 26;92(13):e1487-e1496. doi: 10.1212/WNL.0000000000007173. Epub 2019 Mar 1.

  PMID: 30824559 DERIVED

MeSH Terms

Conditions

Parkinson Disease

Interventions

Carbidopa; Stalevo

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Methyldopa; Dihydroxyphenylalanine; Catecholamines; Amines; Organic Chemicals; Hydrazines; Catechols; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons

Study Officials

• Claudia Trenkwalder, MD

  Paracelsus-Elena-Klinik, Klinikstr. 16, 34128 Kassel, Germany

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 22, 2012
• First Posted: January 11, 2013
• Study Start: May 1, 2011
• Primary Completion: August 1, 2012
• Study Completion: September 1, 2012
• Last Updated: November 21, 2013

Record last verified: 2013-11