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

• Register: ClinicalTrials.gov
• Last refreshed on: 8 August 2016
• Main ID: NCT02834507
• Date of registration: 13/07/2016
• Prospective Registration: No
• Primary sponsor: Bial - Portela C S.A.
• Public title: 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
• Scientific title: 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
• Date of first enrolment: March 2005
• Target sample size: 19
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02834507
• Study type: Interventional
• Study design: Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment
• Phase: Phase 2

Key inclusion & exclusion 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.



Age minimum: 30 Years
Age maximum: 75 Years
Gender: Both

Health Condition(s) or Problem(s) studied

Parkinson's Disease (PD)

Intervention(s)

Drug: Sinemet®

Drug: Comtan®

Drug: BIA 3-202

Drug: Placebo

Primary Outcome(s)

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]

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]

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]

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]

Secondary ID(s)

BIA-3202-201

Source(s) of Monetary Support

Please refer to primary and secondary sponsors