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

A Double-blind, Randomised, Placebo- and Active-controlled Multiple-dose Study of BIA 9-1067 to Investigate Its Effect on Levodopa Pharmacokinetics Following a Levodopa/Carbidopa 100/25 mg Single-dose in Healthy Subjects

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

Study Overview

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

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 82
• Phase: Phase 1

Contacts and Locations

Study Locations

• Portugal
  • S. Mamede do Coronado, Portugal, 4745-457
    • Bial - Portela & Cª, S.A.

Participation Criteria

Eligibility Criteria

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

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Group 1; Placebo at all the dosing times	Drug: Placebo; placebo (four times a day); Other Names: PLC, placebo
Experimental: Group 2; 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	Drug: Placebo; placebo (four times a day); Other Names: PLC, placebo; Drug: BIA 9-1067 5 mg; BIA 9-1067 OPC, Opicapone 5 mg; Other Names: OPC, Opicapone; Drug: levodopa/carbidopa; standard release levodopa/carbidopa 100/25 mg (single-dose)
Experimental: Group 3; 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	Drug: Placebo; placebo (four times a day); Other Names: PLC, placebo; Drug: levodopa/carbidopa; standard release levodopa/carbidopa 100/25 mg (single-dose); Drug: BIA 9-1067 15 mg; BIA 9-1067 OPC, Opicapone 15 mg; Other Names: OPC, Opicapone
Experimental: Group 4; 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	Drug: Placebo; placebo (four times a day); Other Names: PLC, placebo; Drug: levodopa/carbidopa; standard release levodopa/carbidopa 100/25 mg (single-dose); Drug: BIA 9-1067 30 mg; BIA 9-1067 OPC, Opicapone 30 mg; Other Names: OPC, Opicapone
Experimental: Group 5; 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	Drug: Placebo; placebo (four times a day); Other Names: PLC, placebo; Drug: levodopa/carbidopa; standard release levodopa/carbidopa 100/25 mg (single-dose); Drug: Entacapone; Entacapone 200 mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax - Maximum Plasma Concentration of Levodopa	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	8 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tmax - Time to Reach Maximum Plasma Concentration of Levodopa	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.	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.	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	8 days
AUC0-∞ - Area Under the Plasma Concentration-time Curve (AUC) of Levodopa From Time Zero to Infinity	AUC0-∞ - Area under the plasma concentration-time curve (AUC) of levodopa from time zero to infinity.	8 days

Collaborators and Investigators

• Sponsor: Bial - Portela C S.A.

Study record dates

Study Major Dates

• Study Start: November 1, 2009
• Primary Completion (Actual): February 1, 2010
• Study Completion (Actual): June 1, 2011

Study Registration Dates

• First Submitted: January 23, 2012
• First Submitted That Met QC Criteria: January 23, 2012
• First Posted (Estimate): January 26, 2012

Study Record Updates

• Last Update Posted (Estimate): August 20, 2015
• Last Update Submitted That Met QC Criteria: July 22, 2015
• Last Verified: July 1, 2015

More Information

Terms related to this study

• Keywords: Parkinson Disease; 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; Aromatic Amino Acid Decarboxylase Inhibitors; Levodopa; Carbidopa; Opicapone; Entacapone
• Other Study ID Numbers: BIA-91067-114