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

NCT02169453 | Completed Phase 1 Results

• 1 other identifier: BIA-91067-110
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

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/carbidopa 100/25 mg (Sinemet® CR 100/25)

Conditions

Parkinson's Disease (PD)

Keywords

Parkinson's disease (PD); BIA 9-1067; Opicapone

Outcome Measures

Primary Outcomes (6)

• Cmax - Maximum Observed Plasma Concentration

  Cmax - Maximum observed plasma concentration of levodopa

  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 to Last Measurable Time Point

  AUC0-t - Area under the plasma concentration-time curve to last measurable time point for levodopa

  pre-dose, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 48 and 72 h post-dose

• AUC0-∞ - Area Under the Plasma Concentration-time Curve Extrapolated to Infinity

  AUC0-∞ - Area under the plasma concentration-time curve extrapolated 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

• Emax - Maximum Inhibition of COMT Activity

  Emax - Maximum inhibition of Catechol-O-Methyltransferase (COMT) activity

  pre-dose, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 48 and 72 h post-dose

• tEmax - Time of Occurrence of Emax

  pre-dose, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 48 and 72 h post-dose

• AUEC0-24 - Area Under the Effect-time Curve From t=0h to t=24h

  pre-dose, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 48 and 72 h post-dose

Study Arms (4)

Group 1

EXPERIMENTAL

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 Sinemet® CR 100/25 (Single-dose of controlled-release levodopa/carbidopa 100/25 mg: 1 tablet of Sinemet® CR 100/25.)

Drug: BIA 9-1067; Drug: Placebo; Drug: Sinemet® CR 100/25

Group 2

EXPERIMENTAL

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 Sinemet® CR 100/25 (Single-dose of controlled-release levodopa/carbidopa 100/25 mg: 1 tablet of Sinemet® CR 100/25.)

Drug: BIA 9-1067; Drug: Placebo; Drug: Sinemet® CR 100/25

Group 3

EXPERIMENTAL

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 Sinemet® CR 100/25 (Single-dose of controlled-release levodopa/carbidopa 100/25 mg: 1 tablet of Sinemet® CR 100/25.)

Drug: BIA 9-1067; Drug: Placebo; Drug: Sinemet® CR 100/25

Group 4

EXPERIMENTAL

Period 1: Placebo Period 2: BIA 9-1067 25 mg Period 3: BIA 9-1067 50 mg Period 4: BIA 9-1067 100 mg Subjects were to attend four treatment periods and were to receive a different dose of BIA 9-1067 (25 mg, 50 mg and 100 mg) or placebo during each of these treatment periods.

Drug: BIA 9-1067; Drug: Placebo; Drug: Sinemet® CR 100/25

Interventions

BIA 9-1067 DRUG

OPC, Opicapone

Also known as: OPC, Opicapone

Group 1; Group 2; Group 3; Group 4

Placebo DRUG

PLC, Placebo

Also known as: PLC, Placebo

Group 1; Group 2; Group 3; Group 4

Sinemet® CR 100/25 DRUG

Controlled-release levodopa/carbidopa 100/25 mg

Group 1; Group 2; Group 3; Group 4

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Availability for the entire study period and willingness to adhere to the protocol requirements as evidenced by the informed consent form (ICF) duly read, signed and dated by the volunteer prior to participation in the study.
• Male volunteers.
• Volunteers of at least 18 years of age but not older than 45 years.
• Volunteers with body mass index (BMI) greater than or equal to 19 and below 30 kg/m2.
• Volunteers who were non- or ex-smokers. An ex-smoker is defined as someone who completely stopped smoking for at least 12 months before day 1 of this study.
• Volunteers who were healthy as determined by pre-study (at screening) medical history, physical examination, vital signs, complete neurological examination and 12-lead ECG.
• Volunteers who had clinical laboratory test results judged clinically acceptable (within the laboratory's stated normal range; if not within this range, they must had been without any clinical significance) at screening and admission to first treatment period.
• Volunteers 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.
• Volunteers who had negative screen of ethyl alcohol and drugs of abuse at screening.
• Due to unknown risks and potential harm to the unborn fetus, sexually active men must have agreed to use a medically acceptable form of contraception throughout the study.

You may not qualify if:

• Volunteers who had a clinically relevant surgical history.
• Volunteers who had a clinically relevant family history.
• Volunteers who had a history of relevant atopy.
• Volunteers who had a significant infection or known inflammatory process at screening or first admission.
• Volunteers who had acute gastrointestinal symptoms at the time of screening or first admission (e.g., nausea, vomiting, diarrhoea, heartburn).
• Volunteers who were vegetarians, vegans or have medical dietary restrictions.
• Volunteers who could not communicate reliably with the investigator.
• Volunteers who were unlikely to co-operate with the requirements of the study.
• Significant history of hypersensitivity to BIA 9-1067, tolcapone, entacapone, levodopa, carbidopa or any related products (including excipients of the formulations) as well as severe hypersensitivity reactions (like angioedema) to any drugs.
• Presence of significant gastrointestinal, liver or kidney disease, or any other conditions known to interfere with the absorption, distribution, metabolism or excretion of drugs or known to potentiate or predispose to undesired effects.
• History of significant gastrointestinal, liver or kidney disease that may affect drug bioavailability.
• Presence or history of significant cardiovascular, pulmonary, hematologic, neurologic, psychiatric, lymphatic, musculoskeletal, genitourinary, endocrine, immunologic, dermatologic or connective tissue disease.
• Suicidal tendency, history of or disposition to seizures, state of confusion, clinically relevant psychiatric diseases.
• Presence of significant heart disease or disorder according to ECG.
• Presence of suspicious undiagnosed skin lesions or a history of melanoma.

Sponsors & Collaborators

• Bial - Portela C S.A.: lead

Study Sites (1)

Algorithme Pharma Inc

Mount Royal, Quebec, H3P 3P1, Canada

Location

MeSH Terms

Conditions

Parkinson Disease

Interventions

opicapone

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Results Point of Contact

• Title: Head of Clinical Research
• Organization: Bial - Portela & Cª, S.A.

jose.rocha@bial.com

+351 229 866 100

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 20, 2012
• First Posted: June 23, 2014
• Study Start: October 1, 2008
• Primary Completion: January 1, 2009
• Study Completion: January 1, 2009
• Last Updated: January 21, 2015
• Results First Posted: January 21, 2015

Record last verified: 2015-01

Locations

CA (1)