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

NCT02834507 | Completed Phase 2

• 1 other identifier: BIA-3202-201
• Study Type: interventional
• Target: 19
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Parkinson's Disease (PD)

Outcome Measures

Primary Outcomes (4)

• Maximum plasma concentrations (Cmax)

  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)

  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)

  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)

  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

Study Arms (4)

Placebo

PLACEBO COMPARATOR

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.

Drug: Placebo; Drug: Sinemet®

Nebicapone 75 mg

EXPERIMENTAL

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.

Drug: BIA 3-202; Drug: Sinemet®

Nebicapone 150 mg

EXPERIMENTAL

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.

Drug: BIA 3-202; Drug: Sinemet®

Entacapone 200 mg

ACTIVE COMPARATOR

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.

Drug: Comtan®; Drug: Sinemet®

Interventions

Placebo DRUG

Matching placebo capsules

Placebo

BIA 3-202 DRUG

Capsules containing nebicapone 75 mg or 150 mg

Also known as: Nebicapone

Nebicapone 150 mg; Nebicapone 75 mg

Comtan® DRUG

Capsules containing entacapone 200 mg

Also known as: Entacapone

Entacapone 200 mg

Sinemet® DRUG

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

Also known as: levodopa/carbidopa

Entacapone 200 mg; Nebicapone 150 mg; Nebicapone 75 mg; Placebo

Eligibility Criteria

• Age: 30 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Bial - Portela C S.A.: lead

MeSH Terms

Conditions

Parkinson Disease

Interventions

nebicapone; entacapone; carbidopa, levodopa drug combination

Condition Hierarchy (Ancestors)

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 13, 2016
• First Posted: July 15, 2016
• Study Start: March 1, 2005
• Primary Completion: November 1, 2005
• Study Completion: November 1, 2005
• Last Updated: July 15, 2016

Record last verified: 2016-07