Pharmacokinetic-pharmacodynamic Interaction Between Three Different Single Doses of BIA 9-1067 and a Single-dose of Controlled-release 100/25 mg Levodopa/Benserazide

BIAL

Status and phase: Completed; Phase 1

Conditions: Parkinson's Disease (PD)

Treatments: Drug: Placebo; Drug: Madopar® HBS; Drug: BIA 9-1067

Study type: Interventional

Funder types: Industry

Identifiers

NCT02169466

BIA-91067-109

Details and patient eligibility

About

To investigate the effect of three single oral doses of BIA 9-1067 (25 mg, 50 mg and 100 mg) on the levodopa pharmacokinetics when administered in combination with a single-dose of controlled-release levodopa 100 mg/benserazide 25 mg (Madopar HBS).

Full description

Single centre, double-blind, randomized, placebo-controlled, crossover study with four consecutive single-dose treatment periods. The washout period between doses was to be at least10 days. On each treatment period (25, 50 and 100 mg BIA 9-1067 or placebo), after completion of pre-dose assessments, BIA 9-1067-Placebo was to be administered concomitantly with the dose of Madopar HBS; post-dose assessments were to be completed and subjects were to be discharged 72 h post-dose.

Enrollment: 22 patients

Sex: Male

Ages: 18 to 45 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Male subjects between 18 and 45 years, inclusive.
• Subjects of body mass index (BMI) between 19 and 30 kg/m2, inclusive.
• Subjects who were healthy as determined by pre-study medical history, physical examination, vital signs, complete neurological examination and 12-lead ECG.
• Subjects who had clinical laboratory test results that were clinically acceptable at screening and admission to first treatment period.
• Subjects who had negative tests for hepatitis B surface antigen (HBsAg), anti-hepatitis C antibodies (HCV Ab), and Human immunodeficiency viruses -1 and -2 antibodies (HIV-1 and HIV-2 Ab) at screening.
• Subjects who had/were negative for drugs of abuse at screening and admission to each treatment period.
• Subjects who were non-smokers or who smoked ≤10 cigarettes or equivalent per day.
• Subjects who were able and willing to give written informed consent.

Exclusion criteria

• Subjects who did not conform to the above inclusion criteria, or
• Subjects who had a 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.
• Subjects who had a clinically relevant surgical history.
• Subjects who had a clinically relevant family history.
• Subjects who had a history of relevant atopy.
• Subjects who had a history of relevant drug hypersensitivity.
• Subjects who had a history of glaucoma.
• Subjects who had a history of alcoholism or drug abuse.
• Subjects who consumed more than 21 units of alcohol a week.
• Subjects who had a significant infection or known inflammatory process on screening or first admission.
• Subjects who had acute gastrointestinal symptoms at the time of screening or first admission (e.g., nausea, vomiting, diarrhoea, heartburn).
• Subjects who used medicines within 2 weeks of first admission that, in the opinion of the investigator, may affect the safety or other study assessments.
• Subjects who used any investigational drug or participated in any clinical trial within 2 months of their first admission.
• Subjects who donated or received any blood or blood products within the previous 2 months prior to screening.
• Subjects who were vegetarians, vegans or have medical dietary restrictions.
• Subjects who could not communicate reliably with the investigator.
• Subjects who were unlikely to co-operate with the requirements of the study.
• Subjects who were unwilling or unable to give written informed consent.
• Subjects who were BIAL - Portela & Cª, SA employees.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Double Blind

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22 participants in 4 patient groups

Group 1

Experimental group

Description:

Period 1: BIA 9-1067 25 mg Period 2: BIA 9-1067 50 mg Period 3: BIA 9-1067 100 mg Period 4: Placebo BIA 9-1067/Placebo was to be administered concomitantly with the dose of Madopar® HBS (Single-dose of controlled-release levodopa/benserazide 100/25 mg: 1 capsule of Madopar® HBS.)

Treatment:

Drug: Madopar® HBS

Drug: BIA 9-1067

Drug: Placebo

Group 2

Experimental group

Description:

Period 1: BIA 9-1067 50 mg Period 2: BIA 9-1067 100 mg Period 3: Placebo Period 4: BIA 9-1067 25 mg BIA 9-1067/Placebo was to be administered concomitantly with the dose of Madopar® HBS (Single-dose of controlled-release levodopa/benserazide 100/25 mg: 1 capsule of Madopar® HBS.)

Treatment:

Drug: Madopar® HBS

Drug: BIA 9-1067

Drug: Placebo

Group 3

Experimental group

Description:

Period 1: BIA 9-1067 100 mg Period 2: Placebo Period 3: BIA 9-1067 25 mg Period 4: BIA 9-1067 50 mg BIA 9-1067/Placebo was to be administered concomitantly with the dose of Madopar® HBS (Single-dose of controlled-release levodopa/benserazide 100/25 mg: 1 capsule of Madopar® HBS.)

Treatment:

Drug: Madopar® HBS

Drug: BIA 9-1067

Drug: Placebo

Group 4

Experimental group

Description:

Period 1: Placebo Period 2: BIA 9-1067 25 mg Period 3: BIA 9-1067 50 mg Period 4: BIA 9-1067 100 mg BIA 9-1067/Placebo was to be administered concomitantly with the dose of Madopar® HBS (Single-dose of controlled-release levodopa/benserazide 100/25 mg: 1 capsule of Madopar® HBS.)

Treatment:

Drug: Madopar® HBS

Drug: BIA 9-1067

Drug: Placebo