Study of BIA 9-1067 to Investigate Its Effect on Levodopa Pharmacokinetic

Phase 1

Completed

• Conditions: Parkinson Disease
• Interventions: Drug: BIA 9-1067 5 mg; Drug: Entacapone; Drug: Placebo; Drug: BIA 9-1067 30 mg; Drug: levodopa/carbidopa; Drug: BIA 9-1067 15 mg

• Registration Number: NCT01519284
• Lead Sponsor: Bial - Portela C S.A.

Brief Summary

To investigate the effect of repeated dosing of BIA 9-1067 on the levodopa pharmacokinetics, in comparison to placebo and entacapone.

Detailed Description

Single-centre, double-blind, randomised, parallel-group study in 80 young male and female healthy subjects.

Study Timeline

• Study Start: 2009-11
• Primary Completion: 2010-02
• Study Completion: 2011-06
• Study First Submitted: 2012-01-23
• Study First Submitted QC: 2012-01-23
• Study First Posted: 2012-01-26
• Status Verified: 2015-07
• Results First Submitted: 2015-07-22
• Results First Submitted QC: 2015-07-22
• Last Update Submitted: 2015-07-22
• Results First Posted: 2015-08-20
• Last Update Posted: 2015-08-20

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 82

Inclusion Criteria

• Able and willing to give written informed consent.
• Male or female subjects aged between 18 and 45 years, inclusive.
• Subjects of body mass index (BMI) between 19 and 30 kg/m2, inclusive.
• Healthy as determined by pre-study medical history, physical examination, vital signs, complete neurological examination and 12-lead ECG.
• Negative tests for HBsAg, anti-HCVAb and HIV-1 and HIV-2 Ab at screening.
• Clinical laboratory test results clinically acceptable at screening and admission to the treatment period.
• Negative screen for alcohol and drugs of abuse at screening and admission to the treatment period.
• Non-smokers or ex-smokers for at least 3 months.
• (If female) She was not of childbearing potential by reason of surgery or, if of childbearing potential, she used one of the following methods of contraception: intrauterine device (by the subject) and condoms (by the partner) or diaphragm (by the subject) and condoms (by the partner) or spermicide (by the subject) and condoms (by the partner).
• (If female) She had a negative urine pregnancy test at screening and admission to the treatment period.

Exclusion Criteria

• Clinically relevant history or presence of respiratory, gastrointestinal, renal, hepatic, haematological, lymphatic, neurological, cardiovascular, psychiatric, musculoskeletal, genitourinary, immunological, dermatological, endocrine, connective tissue diseases or disorders.
• Clinically relevant surgical history.
• Any abnormality in the coagulation tests.
• Any abnormality in the liver function tests.
• A history of relevant atopy or drug hypersensitivity.
• A history or presence of narrow-angle glaucoma.
• A suspicious undiagnosed skin lesions or a history of melanoma.
• History of alcoholism or drug abuse.
• Consumed more than 14 units of alcohol a week.
• Significant infection or known inflammatory process at screening or admission to the treatment period.
• Acute gastrointestinal symptoms (e.g., nausea, vomiting, diarrhoea, heartburn) at the time of screening or admission to the treatment period.
• Had used non-selective monoamine oxidase (MAO) inhibitors within 2 weeks of admission to the treatment period.
• Had used medicines within 2 weeks of admission to the treatment period that may have affected the safety or other study assessments, in the investigator's opinion.
• Had previously received BIA 9-1067.
• Had used any investigational drug or participated in any clinical trial within 6 months prior to screening.
• Had participated in more than 2 clinical trials within the 12 months prior to screening.
• Had donated or received any blood or blood products within the 3 months prior to screening.
• Vegetarians, vegans or had medical dietary restrictions.
• Cannot communicate reliably with the investigator.
• Unlikely to co-operate with the requirements of the study.
• Unwilling or unable to gave written informed consent.
• (If female) She was pregnant or breast-feeding.
• (If female) She was of childbearing potential and she did not use an approved effective contraceptive method or she used oral contraceptives.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group 4	BIA 9-1067 30 mg	Day 1 to 7: BIA 9-1067 30 mg: 7 AM dose Placebo: 8 AM; 4 PM; 12 PM dose Day 8: BIA 9-1067 30 mg: 7 AM dose Placebo + levodopa/carbidopa 100/25 mg: 8 AM dose
Group 5	Placebo	Day 1 to 7: Placebo: 7 AM dose; Entacapone 200 mg: 8 AM; 4 PM; 12 PM dose Day 8: Placebo: 7 AM dose Entacapone 200 mg + levodopa/carbidopa 100/25 mg: 8 AM dose
Group 5	levodopa/carbidopa	Day 1 to 7: Placebo: 7 AM dose; Entacapone 200 mg: 8 AM; 4 PM; 12 PM dose Day 8: Placebo: 7 AM dose Entacapone 200 mg + levodopa/carbidopa 100/25 mg: 8 AM dose
Group 1	Placebo	Placebo at all the dosing times
Group 2	Placebo	Day 1 to 7: BIA 9-1067 5 mg: 7 AM dose Placebo: 8 AM; 4 PM; 12 PM dose Day 8: BIA 9-1067 5 mg: 7 AM dose Placebo+ levodopa/carbidopa 100/25 mg: 8 AM dose
Group 2	levodopa/carbidopa	Day 1 to 7: BIA 9-1067 5 mg: 7 AM dose Placebo: 8 AM; 4 PM; 12 PM dose Day 8: BIA 9-1067 5 mg: 7 AM dose Placebo+ levodopa/carbidopa 100/25 mg: 8 AM dose
Group 3	Placebo	Day 1 to 7: BIA 9-1067 15 mg: 7 AM dose Placebo: 8 AM; 4 PM; 12 PM dose Day 8: BIA 9-1067 15 mg: 7 AM dose Placebo+ levodopa/carbidopa 100/25 mg: 8 AM dose
Group 3	levodopa/carbidopa	Day 1 to 7: BIA 9-1067 15 mg: 7 AM dose Placebo: 8 AM; 4 PM; 12 PM dose Day 8: BIA 9-1067 15 mg: 7 AM dose Placebo+ levodopa/carbidopa 100/25 mg: 8 AM dose
Group 3	BIA 9-1067 15 mg	Day 1 to 7: BIA 9-1067 15 mg: 7 AM dose Placebo: 8 AM; 4 PM; 12 PM dose Day 8: BIA 9-1067 15 mg: 7 AM dose Placebo+ levodopa/carbidopa 100/25 mg: 8 AM dose
Group 4	Placebo	Day 1 to 7: BIA 9-1067 30 mg: 7 AM dose Placebo: 8 AM; 4 PM; 12 PM dose Day 8: BIA 9-1067 30 mg: 7 AM dose Placebo + levodopa/carbidopa 100/25 mg: 8 AM dose
Group 4	levodopa/carbidopa	Day 1 to 7: BIA 9-1067 30 mg: 7 AM dose Placebo: 8 AM; 4 PM; 12 PM dose Day 8: BIA 9-1067 30 mg: 7 AM dose Placebo + levodopa/carbidopa 100/25 mg: 8 AM dose
Group 2	BIA 9-1067 5 mg	Day 1 to 7: BIA 9-1067 5 mg: 7 AM dose Placebo: 8 AM; 4 PM; 12 PM dose Day 8: BIA 9-1067 5 mg: 7 AM dose Placebo+ levodopa/carbidopa 100/25 mg: 8 AM dose
Group 5	Entacapone	Day 1 to 7: Placebo: 7 AM dose; Entacapone 200 mg: 8 AM; 4 PM; 12 PM dose Day 8: Placebo: 7 AM dose Entacapone 200 mg + levodopa/carbidopa 100/25 mg: 8 AM dose

Primary Outcome Measures

Name	Time	Method
Cmax - Maximum Plasma Concentration of Levodopa	8 days	Cmax - Maximum plasma concentration of levodopa following a single oral administration of Sinemet® 100/25 on Day 8, and 5 mg, 15 mg and 30 mg BIA 9-1067 once-daily (QD), 200 mg entacapone thrice-daily (TID), and placebo, for 8 days

Secondary Outcome Measures

Name	Time	Method
Tmax - Time to Reach Maximum Plasma Concentration of Levodopa	8 days	Tmax - Time to Reach maximum plasma concentration of levodopa following a single oral administration of Sinemet® 100/25 on Day 8, and 5 mg, 15 mg and 30 mg BIA 9-1067 once-daily (QD), 200 mg entacapone thrice-daily (TID), and placebo, for 8 days.
AUC0-t - Area Under the Plasma Concentration-time Curve (AUC) of Levodopa From Time Zero to the Last Sampling Time at Which the Drug Concentration Was at or Above the Lower Limit of Quantification.	8 days	AUC0-t - Area under the plasma concentration-time curve (AUC) of levodopa from time zero to the last sampling time following a single oral administration of Sinemet® 100/25 on Day 8, and 5 mg, 15 mg and 30 mg BIA 9-1067 once-daily (QD), 200 mg entacapone thrice-daily (TID), and placebo, for 8 days
AUC0-∞ - Area Under the Plasma Concentration-time Curve (AUC) of Levodopa From Time Zero to Infinity	8 days	AUC0-∞ - Area under the plasma concentration-time curve (AUC) of levodopa from time zero to infinity.

Trial Locations

Locations (1)

Bial - Portela & Cª, S.A.; 🇵🇹 S. Mamede do Coronado, Portugal