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

Pharmacokinetic-pharmacodynamic Interaction Between Three Different Single Doses of BIA 9-1067 and a Single-dose of Controlled-release 100/25 mg Levodopa/Benserazide: a Double-blind, Randomized, Four-way Crossover, Placebo-controlled Study in Healthy Male Subjects

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).

Study Overview

• Status: Completed
• Conditions: Parkinson's Disease (PD)
• Intervention / Treatment: Drug: BIA 9-1067; Drug: Placebo; Drug: Madopar® HBS

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 1

Contacts and Locations

Study Locations

• Portugal
  • Trofa
    • S. Mamede do Coronado, Trofa, Portugal, 4745-457
      • BIAL - Portela & Cª - Human Pharmacology Unit (UFH)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: DOUBLE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Group 1; 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.)	Drug: BIA 9-1067; OPC, Opicapone; Other Names: OPC, Opicapone; Drug: Placebo; PLC, Placebo; Other Names: PLC, Placebo; Drug: Madopar® HBS; controlled-release levodopa 100 mg/benserazide 25 mg
EXPERIMENTAL: Group 2; 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.)	Drug: BIA 9-1067; OPC, Opicapone; Other Names: OPC, Opicapone; Drug: Placebo; PLC, Placebo; Other Names: PLC, Placebo; Drug: Madopar® HBS; controlled-release levodopa 100 mg/benserazide 25 mg
EXPERIMENTAL: Group 3; 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.)	Drug: BIA 9-1067; OPC, Opicapone; Other Names: OPC, Opicapone; Drug: Placebo; PLC, Placebo; Other Names: PLC, Placebo; Drug: Madopar® HBS; controlled-release levodopa 100 mg/benserazide 25 mg
EXPERIMENTAL: Group 4; 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.)	Drug: BIA 9-1067; OPC, Opicapone; Other Names: OPC, Opicapone; Drug: Placebo; PLC, Placebo; Other Names: PLC, Placebo; Drug: Madopar® HBS; controlled-release levodopa 100 mg/benserazide 25 mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax - Maximum Observed Plasma Concentration of Levodopa	Primary pharmacokinetic parameter: Levodopa maximum observed plasma concentration (Cmax) (ng/mL)	pre-dose, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 48 and 72 h post-dose.
AUC0-t - Area Under the Plasma Concentration-time Curve	Primary pharmacokinetic parameter: Area under the plasma concentration-time curve for levodopa	pre-dose, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 48 and 72 h post-dose.
AUC0-∞ - AUC From Time Zero to Infinity	Primary pharmacokinetic parameter: Area under the plasma concentration-time curve from time zero to infinity for levodopa	pre-dose, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 48 and 72 h post-dose.
Tmax - Time to Cmax	Primary pharmacokinetic parameter: tmax - time to Cmax	pre-dose, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 48 and 72 h post-dose.

Collaborators and Investigators

• Sponsor: Bial - Portela C S.A.

Study record dates

Study Major Dates

• Study Start: January 1, 2009
• Primary Completion (ACTUAL): May 1, 2009
• Study Completion (ACTUAL): May 1, 2009

Study Registration Dates

• First Submitted: January 20, 2012
• First Submitted That Met QC Criteria: June 19, 2014
• First Posted (ESTIMATE): June 23, 2014

Study Record Updates

• Last Update Posted (ESTIMATE): November 3, 2015
• Last Update Submitted That Met QC Criteria: October 2, 2015
• Last Verified: October 1, 2015

More Information

Terms related to this study

• Keywords: Parkinson's disease (PD); Opicapone; BIA 9-1067
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Parkinson Disease; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Dopamine Agents; Antiparkinson Agents; Anti-Dyskinesia Agents; Catechol O-Methyltransferase Inhibitors; Opicapone; Benserazide, levodopa drug combination
• Other Study ID Numbers: BIA-91067-109