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
Overview
- Phase
- Phase 2
- Intervention
- Placebo
- Conditions
- Parkinson's Disease (PD)
- Sponsor
- Bial - Portela C S.A.
- Enrollment
- 19
- Primary Endpoint
- Maximum plasma concentrations (Cmax)
- Status
- Completed
- Last Updated
- 9 years ago
Overview
Brief Summary
The purpose of this study is to determine the effect of two different multiple-dose regimens of nebicapone in comparison to placebo and entacapone 200 mg on the pharmacokinetics of levodopa in Parkinson's Disease (PD) patients.
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.
Investigators
Eligibility Criteria
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).
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.
Arms & Interventions
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.
Intervention: Placebo
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.
Intervention: Sinemet®
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.
Intervention: BIA 3-202
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.
Intervention: Sinemet®
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.
Intervention: BIA 3-202
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.
Intervention: Sinemet®
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.
Intervention: Comtan®
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.
Intervention: Sinemet®
Outcomes
Primary Outcomes
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®
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®
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®
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®