- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02834507
Effect of Two Multiple-dose Regimens of BIA 3-202 on the Pharmacokinetics and Motor Response of Levodopa, and on the Erythrocyte Comt Activity in Parkinson's Disease Patients
A Double-blind, Randomised, Placebo- and Active-controlled, Cross-over Study to Investigate the Effect of Two Multiple-dose Regimens of BIA 3-202 on the Pharmacokinetics and Motor Response of Levodopa, and on the Erythrocyte Comt Activity in Parkinson's Disease Patients
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
STUDY DESIGN AND METHODOLOGY:
This was a multicentre, randomised, double-blind, placebo- and active-controlled, four-way crossover study. The study consisted of 4 treatment periods in at least 16 patients with PD treated with standard release levodopa/carbidopa (Sinemet®). Patients were randomly assigned to treatment with placebo, nebicapone 75 mg, nebicapone 150 mg or entacapone 200 mg (Comtan®) in 4 different sequences.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Written informed consent signed before screening activities.
- Male or female aged between 30 and 75 years, inclusive.
- A diagnosis of PD according to the UK PDS Brain Bank diagnostic criteria (bradykinesia and at least one of the following: muscular rigidity, rest tremor and postural instability).
- Predictable signs of end-of-dose "wearing-OFF" phenomenon (end-of-dose deterioration) despite "optimal" levodopa/carbidopa therapy.
- At least 60 minutes of daily OFF time in the two days prior to the randomisation visit day.
- Been treated with levodopa/carbidopa for at least 1 year prior to randomisation with clear clinical improvement.
- Been treated with a stable regimen of 3 to 6 daily doses of standard release levodopa/carbidopa (4:1 ratio) per day within at least 4 weeks prior to randomisation, although a bedtime dose of slow-release formulation is permitted.
- Concomitant anti-Parkinsonian medication (other than apomorphine and entacapone) in stable doses for at least 4 weeks prior to randomisation.
- Able to keep reliable ON/OFF charts (diaries), alone or with caregiver assistance.
- Laboratory results acceptable by the investigator (not clinically significant for the well-being of the patient or for the purpose of the study).
- Women: Post-menopausal or otherwise incapable of becoming pregnant by reason of surgery or tubal ligation. In case of woman of childbearing potential, patient had to present a serum B-hCG test consistent with a non-gravid state and had to agree to remain abstinent or use effective contraceptive methods.
Exclusion Criteria:
- Non-idiopathic parkinsonism (atypical parkinsonism, symptomatic parkinsonism, Parkinson-plus syndrome).
- Treated with levodopa/benserazide, or with levodopa/carbidopa in a 10:1 ratio, or with levodopa/carbidopa in a controlled-release form during day-time.
- Major depressive episode within 6 months prior to randomisation.
- Treated with entacapone, neuroleptics, monoamine oxidase inhibitors (except selegiline not exceeding 10 mg/day) or antiemetics (except domperidone) within one month prior to randomisation.
- Treated with apomorphine within 7 days prior to randomisation.
- Treated with any investigational product within 2 months prior to randomisation (or within 5 half-lives, whichever is longer).
- A psychiatric or any medical condition that might place him/her at increased risk or interfere with assessments.
- Previous use of nebicapone or participation in a clinical study with nebicapone.
- Known hypersensitivity to any of the ingredients of the investigational products.
- A history of abuse of alcohol, drugs or medications within the last 2 years.
- A clinically relevant ECG abnormality. Patient could only be randomised if the ECG was normal or, if abnormal, the abnormality was mild and not considered to be clinically relevant.
- A history or current evidence of heart disease, including but not limited to myocardial infarction, angina, congestive heart failure and cardiac arrhythmia.
- Unstable concomitant disease being treated with changing doses of medication.
- A history or current evidence of any relevant disease in the context of this study, i.e., with respect to the safety of the subject (e.g., hepatic impairment) or related to the study conditions.
- A test positive for the human immunodeficiency viruses (HIV) 1 or 2 antibodies, hepatitis B surface antigen (HBs Ag) or hepatitis C antibody (HCV Ab).
- Donated or received blood or blood products within 3 months prior to randomisation.
- Pregnant or breast feeding.
- Any other condition or circumstance that, in the opinion of the investigator, may compromise the patient's ability to comply with the study protocol.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Placebo Comparator: Placebo
In each treatment period, patients received, in a double-blind manner, 1 capsule of investigational product (nebicapone 75 mg, nebicapone 150 mg, entacapone 200 mg or placebo, according to the treatment sequence), concomitantly with each levodopa/carbidopa (Sinemet®) dose patient used to take.
|
Matching placebo capsules
levodopa/carbidopa (Sinemet®) dose patient used to take
Other Names:
|
Experimental: Nebicapone 75 mg
In each treatment period, patients received, in a double-blind manner, 1 capsule of investigational product (nebicapone 75 mg, nebicapone 150 mg, entacapone 200 mg or placebo, according to the treatment sequence), concomitantly with each levodopa/carbidopa (Sinemet®) dose patient used to take.
|
levodopa/carbidopa (Sinemet®) dose patient used to take
Other Names:
Capsules containing nebicapone 75 mg or 150 mg
Other Names:
|
Experimental: Nebicapone 150 mg
In each treatment period, patients received, in a double-blind manner, 1 capsule of investigational product (nebicapone 75 mg, nebicapone 150 mg, entacapone 200 mg or placebo, according to the treatment sequence), concomitantly with each levodopa/carbidopa (Sinemet®) dose patient used to take.
|
levodopa/carbidopa (Sinemet®) dose patient used to take
Other Names:
Capsules containing nebicapone 75 mg or 150 mg
Other Names:
|
Active Comparator: Entacapone 200 mg
In each treatment period, patients received, in a double-blind manner, 1 capsule of investigational product (nebicapone 75 mg, nebicapone 150 mg, entacapone 200 mg or placebo, according to the treatment sequence), concomitantly with each levodopa/carbidopa (Sinemet®) dose patient used to take.
|
levodopa/carbidopa (Sinemet®) dose patient used to take
Other Names:
Capsules containing entacapone 200 mg
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Maximum plasma concentrations (Cmax)
Time Frame: pre-dose, 30 min, 60 min, 90 min, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 18 h and 24 h post dose
|
Levodopa pharmacokinetic parameters following administration of nebicapone 75 mg (n=16), nebicapone 150 mg (n=18), entacapone 200 mg (n=18) or placebo (n=17) concomitantly with Sinemet®
|
pre-dose, 30 min, 60 min, 90 min, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 18 h and 24 h post dose
|
time to Cmax (tmax)
Time Frame: pre-dose, 30 min, 60 min, 90 min, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 18 h and 24 h post dose
|
Levodopa pharmacokinetic parameters following administration of nebicapone 75 mg (n=16), nebicapone 150 mg (n=18), entacapone 200 mg (n=18) or placebo (n=17) concomitantly with Sinemet®
|
pre-dose, 30 min, 60 min, 90 min, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 18 h and 24 h post dose
|
Area under the plasma concentration-time curve from dosing until 6 h after (AUC0-6)
Time Frame: pre-dose, 30 min, 60 min, 90 min, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 18 h and 24 h post dose
|
Levodopa pharmacokinetic parameters following administration of nebicapone 75 mg (n=16), nebicapone 150 mg (n=18), entacapone 200 mg (n=18) or placebo (n=17) concomitantly with Sinemet®
|
pre-dose, 30 min, 60 min, 90 min, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 18 h and 24 h post dose
|
Apparent elimination half-life (t1/2)
Time Frame: pre-dose, 30 min, 60 min, 90 min, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 18 h and 24 h post dose
|
Levodopa pharmacokinetic parameters following administration of nebicapone 75 mg (n=16), nebicapone 150 mg (n=18), entacapone 200 mg (n=18) or placebo (n=17) concomitantly with Sinemet®
|
pre-dose, 30 min, 60 min, 90 min, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 18 h and 24 h post dose
|
Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
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
- Catechol O-Methyltransferase Inhibitors
- Aromatic Amino Acid Decarboxylase Inhibitors
- Levodopa
- Carbidopa
- Carbidopa, levodopa drug combination
- Entacapone
Other Study ID Numbers
- BIA-3202-201
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
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