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

NCT ID: NCT02834507

Last Updated: 2016-07-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 19 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-03-31
• Study Completion Date: 2005-11-30

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.

Conditions

Parkinson's Disease (PD)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Matching placebo capsules

Sinemet®

Intervention Type: DRUG

levodopa/carbidopa (Sinemet®) dose patient used to take

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.

Group Type: EXPERIMENTAL

BIA 3-202

Intervention Type: DRUG

Capsules containing nebicapone 75 mg or 150 mg

Sinemet®

Intervention Type: DRUG

levodopa/carbidopa (Sinemet®) dose patient used to take

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.

Group Type: EXPERIMENTAL

BIA 3-202

Intervention Type: DRUG

Capsules containing nebicapone 75 mg or 150 mg

Sinemet®

Intervention Type: DRUG

levodopa/carbidopa (Sinemet®) dose patient used to take

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.

Group Type: ACTIVE_COMPARATOR

Comtan®

Intervention Type: DRUG

Capsules containing entacapone 200 mg

Sinemet®

Intervention Type: DRUG

levodopa/carbidopa (Sinemet®) dose patient used to take

Interventions

Placebo

Matching placebo capsules

Intervention Type: DRUG

BIA 3-202

Capsules containing nebicapone 75 mg or 150 mg

Intervention Type: DRUG

Comtan®

Capsules containing entacapone 200 mg

Intervention Type: DRUG

Sinemet®

levodopa/carbidopa (Sinemet®) dose patient used to take

Intervention Type: DRUG

Other Intervention Names

Nebicapone; Entacapone; levodopa/carbidopa

Eligibility Criteria

Inclusion Criteria

1. Written informed consent signed before screening activities.

2. Male or female aged between 30 and 75 years, inclusive.

3. 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).

4. Predictable signs of end-of-dose "wearing-OFF" phenomenon (end-of-dose deterioration) despite "optimal" levodopa/carbidopa therapy.

5. At least 60 minutes of daily OFF time in the two days prior to the randomisation visit day.

6. Been treated with levodopa/carbidopa for at least 1 year prior to randomisation with clear clinical improvement.

7. 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.

8. Concomitant anti-Parkinsonian medication (other than apomorphine and entacapone) in stable doses for at least 4 weeks prior to randomisation.

9. Able to keep reliable ON/OFF charts (diaries), alone or with caregiver assistance.

10. Laboratory results acceptable by the investigator (not clinically significant for the well-being of the patient or for the purpose of the study).

11. 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

1. Non-idiopathic parkinsonism (atypical parkinsonism, symptomatic parkinsonism, Parkinson-plus syndrome).

2. 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.

3. Major depressive episode within 6 months prior to randomisation.

4. Treated with entacapone, neuroleptics, monoamine oxidase inhibitors (except selegiline not exceeding 10 mg/day) or antiemetics (except domperidone) within one month prior to randomisation.

5. Treated with apomorphine within 7 days prior to randomisation.

6. Treated with any investigational product within 2 months prior to randomisation (or within 5 half-lives, whichever is longer).

7. A psychiatric or any medical condition that might place him/her at increased risk or interfere with assessments.

8. Previous use of nebicapone or participation in a clinical study with nebicapone.

9. Known hypersensitivity to any of the ingredients of the investigational products.

10. A history of abuse of alcohol, drugs or medications within the last 2 years.

11. 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.

12. A history or current evidence of heart disease, including but not limited to myocardial infarction, angina, congestive heart failure and cardiac arrhythmia.

13. Unstable concomitant disease being treated with changing doses of medication.

14. 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.

15. 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).

16. Donated or received blood or blood products within 3 months prior to randomisation.

17. Pregnant or breast feeding.

18. Any other condition or circumstance that, in the opinion of the investigator, may compromise the patient's ability to comply with the study protocol.

• Minimum Eligible Age: 30 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bial - Portela C S.A.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Other Identifiers

BIA-3202-201

Identifier Type: -

Identifier Source: org_study_id