Pharmacokinetic Interaction Between BIA 9-1067 and Standard-release Levodopa/Carbidopa

NCT01533077 | Completed Phase 1 Results

• 1 other identifier: BIA-91067-117
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

To investigate the pharmacokinetics of levodopa when administered concomitantly with BIA 9-1067 or 1 hour after.

Conditions

Parkinson Disease

Keywords

Parkinson Disease; BIA 9-1067

Outcome Measures

Primary Outcomes (16)

• Cmax - Maximum Observed Plasma Concentration (L-DOPA)

  Mean pharmacokinetic parameters of L-beta-3,4-dihydroxyphenylalanine (levodopa) (L-DOPA)

  pre-dose, ½, 1, 1½, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 and 72 h after dose.

• Tmax - Time of Occurrence of Cmax Maximum Observed Plasma Concentration (L-DOPA)

  Pharmacokinetic parameters of L-beta-3,4-dihydroxyphenylalanine (levodopa) (L-DOPA). For tmax = time to Cmax values are presented as median with range values.

  pre-dose, ½, 1, 1½, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 and 72 h after dose.

• AUC0-t - Area Under the Plasma Concentration-time Curve to Last Measurable Time Point (L-DOPA)

  Mean pharmacokinetic parameters of L-beta-3,4-dihydroxyphenylalanine (levodopa) (L-DOPA)

  pre-dose, ½, 1, 1½, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 and 72 h after dose.

• AUC0-∞ - Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to Infinity (L-DOPA)

  Mean pharmacokinetic parameters of L-beta-3,4-dihydroxyphenylalanine (levodopa) (L-DOPA)

  pre-dose, ½, 1, 1½, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 and 72 h after dose.

• Cmax - Maximum Observed Plasma Concentration (3-OMD)

  Mean pharmacokinetic parameters of 3-O-methyl-levodopa (3-OMD)

  Pre-dose, ½, 1, 1½, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 and 72 h after dose

• Tmax - Time to Occurrence of Cmax (3-OMD)

  Pharmacokinetic parameters of 3-O-methyl-levodopa (3-OMD). For tmax = time to Cmax values are presented as median with range values.

  Pre-dose, ½, 1, 1½, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 and 72 h after dose

• AUC0-t - Area Under the Plasma Concentration-time Curve to Last Measurable Time Point (3-OMD)

  Mean pharmacokinetic parameters of 3-O-methyl-levodopa (3-OMD)

  Pre-dose, ½, 1, 1½, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 and 72 h after dose.

• AUC0-∞ - Area Under the Plasma Concentration-time Curve Extrapolated to Infinity (3-OMD)

  Mean pharmacokinetic parameters of 3-O-methyl-levodopa (3-OMD)

  Pre-dose, ½, 1, 1½, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 and 72 h after dose.

• Cmax - Maximum Observed Plasma Concentration (Carbidopa)

  Mean pharmacokinetic parameters of carbidopa

  Pre-dose, ½, 1, 1½, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 and 72 h after dose.

• Tmax - Time to Occurrence of Cmax (Carbidopa)

  Pharmacokinetic parameters of carbidopa. For tmax = time to Cmax values are presented as median with range values.

  Pre-dose, ½, 1, 1½, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 and 72 h after dose.

• AUC0-t - Area Under the Plasma Concentration-time Curve to Last Measurable Time Point (Carbidopa)

  Mean pharmacokinetic parameters of carbidopa

  Pre-dose, ½, 1, 1½, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 and 72 h after dose.

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

  Pharmacokinetic parameters of carbidopa. For tmax = time to Cmax values are presented as median with range values.

  Pre-dose, ½, 1, 1½, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 and 72 h after dose

• Cmax - Maximum Observed Plasma Concentration (BIA 9-1067)

  Mean pharmacokinetic parameters of BIA 9-1067

  Pre-dose, ½, 1, 1½, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 and 72 h after dose.

• Tmax - Time to Occurrence of Cmax (BIA 9-1067)

  Pharmacokinetic parameters of BIA 9-1067. For tmax = time to Cmax values are presented as median with range values.

  Pre-dose, ½, 1, 1½, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 and 72 h after dose.

• AUC0-t - Area Under the Plasma Concentration-time Curve to Last Measurable Time Point (BIA 9-1067)

  Mean pharmacokinetic parameters of BIA 9-1067

  Pre-dose, ½, 1, 1½, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 and 72 h after dose.

• AUC0-∞ - Area Under the Plasma Concentration-time Curve Extrapolated to Infinity (BIA 9-1067)

  Mean pharmacokinetic parameters of BIA 9-1067

  Pre-dose, ½, 1, 1½, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 and 72 h after dose.

Study Arms (4)

Group 1

EXPERIMENTAL

Period 1: BIA 9-1067 50 mg Period 2: Sinemet® 100/25 1 h after the BIA 9-1067 50 mg Period 3: BIA 9-1067 50 mg + Sinemet® 100/25 Period 4: Sinemet® 100/25

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

Group 2

EXPERIMENTAL

Period 1: Sinemet® 100/25 Period 2: BIA 9-1067 50 mg Period 3: Sinemet® 100/25 1 h after the BIA 9-1067 50 mg Period 4: BIA 9-1067 50 mg + Sinemet® 100/25

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

Group 3

EXPERIMENTAL

Period 1: BIA 9-1067 50 mg + Sinemet® 100/25 Period 2: Sinemet® 100/25 Period 3: BIA 9-1067 50 mg Period 4: Sinemet® 100/25 1 h after the BIA 9-1067 50 mg

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

Group 4

EXPERIMENTAL

Period 1: Sinemet® 100/25 1 h after the BIA 9-1067 50 mg Period 2: BIA 9-1067 50 mg + Sinemet® 100/25 Period 3: Sinemet® 100/25 Period 4: BIA 9-1067 50 mg

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

Interventions

BIA 9-1067 DRUG

50 mg of BIA 9-1067 (single-dose)

Also known as: OPC, Opicapone

Group 1; Group 2; Group 3; Group 4

Sinemet® 100/25 mg DRUG

immediate-release levodopa/carbidopa 100/25 (single-dose).

Also known as: levodopa 100 mg /carbidopa 25 mg

Group 1; Group 2; Group 3; Group 4

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• 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 or female 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 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.
• Volunteers who were non- or ex-smokers. For the purpose of this study, an ex-smoker is defined as someone who completely stopped smoking for at least 3 months before day 1 of this study.
• Due to unknown risks and potential harm to the unborn fetus, sexually active men or women must have agreed to use a medically acceptable form of contraception throughout the study.
• If female of childbearing potential, she had a negative HCG beta serum pregnancy test at screening and admission to each treatment period
• The informed consent form must have been signed by all volunteers, prior to their participation in 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 admission to the treatment period.
• Volunteers who had acute gastrointestinal symptoms at the time of screening or admission to the treatment period (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.
• History of hypersensitivity to BIA 9-1067, tolcapone, entacapone, levodopa, benserazide 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; carbidopa, levodopa drug combination; Levodopa; Carbidopa

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Dihydroxyphenylalanine; Catecholamines; Amines; Organic Chemicals; Catechols; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Tyrosine; Methyldopa; Hydrazines

Results Point of Contact

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

jose.rocha@bial.com

+351 229 866 100

Study Officials

• Eric Sicard, MD

  Algorithme Pharma Inc

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 24, 2012
• First Posted: February 15, 2012
• Study Start: March 1, 2009
• Primary Completion: October 1, 2009
• Study Completion: February 1, 2010
• Last Updated: December 22, 2015
• Results First Posted: December 22, 2015

Record last verified: 2015-11

Locations

CA (1)