Effect of BIA 9-1067 at Steady-state on the Pharmacokinetics of Levodopa/Carbidopa and Levodopa/Benserazide

NCT01533116 | Completed Phase 1 Results

• 1 other identifier: BIA-91067-118
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 1

Brief Summary

To investigate the effect of BIA 9-1067 in steady-state conditions on the levodopa pharmacokinetics

Conditions

Parkinson Disease

Keywords

Parkinson Disease; BIA 9-1067

Outcome Measures

Primary Outcomes (5)

• Cmax - Maximum Plasma Concentration

  Cmax - maximum plasma concentration Cmax (Levodopa) Sinemet® or Prolopa® - following administration of Sinemet® or Prolopa® Cmax (3-OMD) Sinemet® or Prolopa® - following administration of Sinemet® or Prolopa® Cmax (BIA 9-1067) Sinemet® or Prolopa® - following administration of Sinemet® or Prolopa®

  pre-dose and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 h

• Tmax - Time to Maximum Plasma Concentration

  Tmax - time to maximum plasma concentration Tmax (Levodopa) Sinemet® or Prolopa® - following administration of Sinemet® or Prolopa® Tmax (3-OMD) Sinemet® or Prolopa® - following administration of Sinemet® or Prolopa® Tmax (BIA 9-1067) Sinemet® or Prolopa® - following administration of Sinemet® or Prolopa®

  pre-dose and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 h

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

  AUC0-t - area under the plasma concentration-time curve from time 0 to last observed concentration 3-OMD - 3-O-methyl-dopa - metabolite of L-DOPA (levodopa) AUC0-t (Levodopa) Sinemet® or Prolopa® - following administration of Sinemet® or Prolopa® AUC0-t (3-OMD) Sinemet® or Prolopa® - following administration of Sinemet® or Prolopa® AUC0-t (BIA 9-1067) Sinemet® or Prolopa® - following administration of Sinemet® or Prolopa®

  pre-dose and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 h

• tEmax - Time of Occurrence of Maximum Observed Effect on S-COMT Activity

  tEmax - time of occurrence of maximum observed effect on S-COMT activity COMT - Catechol-O-Methyltransferase

  pre-dose and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 h

• AUEC0-24 - Area Under the Effect-time Curve (AUEC) to 24 h Post-dose

  AUEC0-24 - Area under the effect-time curve (AUEC) to 24 h post-dose.

  pre-dose and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 h

Study Arms (4)

5 mg BIA 9-1067

EXPERIMENTAL

5 mg BIA 9-1067 once-daily for 28 days single-dose of levodopa/carbidopa 100/25 mg on Day 21 single-dose of levodopa/benserazide 100/25 mg on Day 28

Drug: BIA 9-1067; Drug: levodopa/carbidopa; Drug: levodopa/benserazide

Placebo

EXPERIMENTAL

Placebo once-daily for 28 days single-dose of levodopa/carbidopa 100/25 mg on Day 21 single-dose of levodopa/benserazide 100/25 mg on Day 28.

Drug: Placebo; Drug: levodopa/carbidopa; Drug: levodopa/benserazide

15 mg BIA 9-1067

EXPERIMENTAL

15 mg BIA 9-1067 once-daily for 28 days single-dose of levodopa/carbidopa 100/25 mg on Day 21 single-dose of levodopa/benserazide 100/25 mg on Day 28

Drug: BIA 9-1067; Drug: levodopa/carbidopa; Drug: levodopa/benserazide

30 mg BIA 9-1067

EXPERIMENTAL

30 mg BIA 9-1067 once-daily for 28 days single-dose of levodopa/carbidopa 100/25 mg on Day 21 single-dose of levodopa/benserazide 100/25 mg on Day 28

Drug: BIA 9-1067; Drug: levodopa/carbidopa; Drug: levodopa/benserazide

Interventions

BIA 9-1067 DRUG

Also known as: OPC, Opicapone

15 mg BIA 9-1067; 30 mg BIA 9-1067; 5 mg BIA 9-1067

Placebo DRUG

Also known as: PLC, Placebo

Placebo

levodopa/carbidopa DRUG

Also known as: Sinemet® 100/25

15 mg BIA 9-1067; 30 mg BIA 9-1067; 5 mg BIA 9-1067; Placebo

levodopa/benserazide DRUG

Also known as: Prolopa® 100/25

15 mg BIA 9-1067; 30 mg BIA 9-1067; 5 mg BIA 9-1067; Placebo

Eligibility Criteria

• Age: 25 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 25 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 and admission to the treatment period.
• 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; benserazide, levodopa drug combination

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

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: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• 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: August 1, 2009
• Study Completion: March 1, 2010
• Last Updated: November 16, 2015
• Results First Posted: November 16, 2015

Record last verified: 2015-10

Locations

CA (1)