The Effect of BIA 9-1067 at Steady-state on the Levodopa Pharmacokinetics

NCT02170376 | Completed Phase 1 Results

• 1 other identifier: BIA-91067-124
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine the effect of repeated dosing of once-daily 25, 50 and 75 mg opicapone (OPC, development code BIA 9-1067) on the levodopa pharmacokinetics (PK), in comparison to placebo and 200 mg entacapone (ENT).

Conditions

Parkinson's Disease (PD)

Keywords

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

Outcome Measures

Primary Outcomes (6)

• Cmax - Maximum Plasma Concentration of Levodopa

  Cmax - Maximum plasma concentration of levodopa (mean pharmacokinetic parameter) following first oral administration of 100/25 mg levodopa/carbidopa on Day 12 with 25, 50 and 75 mg OPC or placebo and 200 mg Entacapone.

  pre-first dose and at 0.5, 1.0, 1.5, 2.0, 3.0, 4.0 and 5.0 h post-first and -second levodopa/carbidopa administration, and at 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 5.0, 8.0 and 14.0 h post-third levodopa/carbidopa administration

• Tmax - Time of Occurrence of Maximum Plasma Concentration

  Tmax - Time to Reach maximum plasma concentration of levodopa (mean pharmacokinetic parameter) following first oral administration of 100/25 mg levodopa/carbidopa on Day 12 with 25, 50 and 75 mg OPC or placebo and 200 mg Entacapone

  pre-first dose and at 0.5, 1.0, 1.5, 2.0, 3.0, 4.0 and 5.0 h post-first and -second levodopa/carbidopa administration, and at 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 5.0, 8.0 and 14.0 h post-third levodopa/carbidopa administration

• AUC0-∞ - Area Under the Concentration-time Curve From Time Zero up to Infinity With Extrapolation of the Terminal Phase

  AUC0-∞ of levodopa (mean pharmacokinetic parameter) following first oral administration of 100/25 mg levodopa/carbidopa on Day 12 with 25, 50 and 75 mg OPC or placebo and 200 mg Entacapone.

  pre-first dose and at 0.5, 1.0, 1.5, 2.0, 3.0, 4.0 and 5.0 h post-first and -second levodopa/carbidopa administration, and at 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 5.0, 8.0 and 14.0 h post-third levodopa/carbidopa administration

• AUC0-t - Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Time (t) Corresponding to the Last Quantifiable Concentration.

  AUC0-t - of levodopa (mean pharmacokinetic parameter) following first oral administration of 100/25 mg levodopa/carbidopa on Day 12 with 25, 50 and 75 mg OPC or placebo and 200 mg Entacapone.

  pre-first dose and at 0.5, 1.0, 1.5, 2.0, 3.0, 4.0 and 5.0 h post-first and -second levodopa/carbidopa administration, and at 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 5.0, 8.0 and 14.0 h post-third levodopa/carbidopa administration

• AUC0-5 - AUC Over 5 Hours

  AUC0-5 - of levodopa (mean pharmacokinetic parameter) following first oral administration of 100/25 mg levodopa/carbidopa on Day 12 with 25, 50 and 75 mg OPC or placebo and 200 mg Entacapone.

  pre-first dose and at 0.5, 1.0, 1.5, 2.0, 3.0, 4.0 and 5.0 h post-first and -second levodopa/carbidopa administration, and at 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 5.0, 8.0 and 14.0 h post-third levodopa/carbidopa administration

• t1/2 - Terminal Plasma Half-life

  t1/2 - Terminal plasma half-life of levodopa (mean pharmacokinetic parameter) following first oral administration of 100/25 mg levodopa/carbidopa on Day 12 with 25, 50 and 75 mg OPC or placebo and 200 mg Entacapone.

  pre-first dose and at 0.5, 1.0, 1.5, 2.0, 3.0, 4.0 and 5.0 h post-first and -second levodopa/carbidopa administration, and at 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 5.0, 8.0 and 14.0 h post-third levodopa/carbidopa administration

Study Arms (5)

Group 1

EXPERIMENTAL

Placebo once-daily for 11 days 200 mg entacapone concomitantly with levodopa/carbidopa on Day 12

Drug: Entacapone; Drug: Placebo; Drug: Levodopa/carbidopa

Group 2

EXPERIMENTAL

25 mg BIA 9-1067 once-daily for 11 days Placebo concomitantly with levodopa/carbidopa on Day 12

Drug: BIA 9-1067; Drug: Placebo; Drug: Levodopa/carbidopa

Group 3

EXPERIMENTAL

50 mg 9-1067 once-daily for 11 days Placebo concomitantly with levodopa/carbidopa on Day 12

Drug: BIA 9-1067; Drug: Placebo; Drug: Levodopa/carbidopa

Group 4

EXPERIMENTAL

75 mg 9-1067 once-daily for 11 days placebo concomitantly with levodopa/carbidopa on Day 12

Drug: BIA 9-1067; Drug: Placebo; Drug: Levodopa/carbidopa

Group 5

PLACEBO COMPARATOR

placebo once-daily for 11 days placebo concomitantly with levodopa/carbidopa on Day 12

Drug: Placebo; Drug: Levodopa/carbidopa

Interventions

BIA 9-1067 DRUG

BIA 9-1067 25 mg and 50 mg

Also known as: Opicapone, OPC

Group 2; Group 3; Group 4

Entacapone DRUG

Entacapone (ENT), over-encapsulated tablet 200 mg

Also known as: Comtan®, ENT

Group 1

Placebo DRUG

PLC, placebo

Also known as: PLC, placebo

Group 1; Group 2; Group 3; Group 4; Group 5

Levodopa/carbidopa DRUG

Levodopa/carbidopa, tablet 100/25 mg

Also known as: Sinemet®

Group 1; Group 2; Group 3; Group 4; Group 5

Eligibility Criteria

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

You may qualify if:

• Healthy male and female volunteers 18 to 45 years old (inclusive),
• Body Mass Index (BMI) in normal range (18-30 kg/m²),
• Healthy as determined by the Investigator on the basis of medical history, physical examination, clinical laboratory test results, vital signs, complete neurological examination and 12-lead ECG (electrocardiogram),
• Negative tests for Hepatitis B surface antigen (HBsAG), anti-Hepatitis C virus (HCV) antibodies and Human immunodeficiency virus (HIV) -1 and HIV-2 antibodies at screening,
• Negative screen for drugs of abuse and alcohol at screening and admission to the treatment period,
• If of childbearing potential (i.e. except if they had been sterilized for at least 3 months or postmenopausal for at least one year - the menopause was defined by a follicule stimulating hormone (FSH) level \> 30 IU/L): used a non hormonal acceptable contraception method, i.e. intra-uterine device, condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository for all the duration of the study,
• If female of childbearing potential, had a negative human chorionic gonadotropin (HCG) beta serum pregnancy test at screening and urinary pregnancy test at admission to both ambulatory and confinement periods,
• Non-smokers or ex-smokers for at least 3 months,
• Able to communicate well with the Investigator and research staff and to comply with the requirements of the entire study,
• Provision of written informed consent to participate as shown by a signature on the volunteer consent form,
• Registered with the French Social Security in agreement with the French law on biomedical experimentation

You may not qualify if:

• Had a 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,
• Were vegetarians, vegans or had medical dietary restrictions,
• Could not communicate reliably with the Investigator,
• Were unlikely to co-operate with the requirements of the study; history of hypersensitivity to OPC, tolcapone, ENT, levodopa, carbidopa, benserazide or any related products (including excipients of the formulations) as well as severe hypersensitivity reactions (like angioedema) to any drugs,
• Had any significant cardiovascular (e.g. hypertension), hepatic, renal, respiratory (e.g. childhood asthma), gastrointestinal, endocrine (e.g. diabetes, dyslipidemia), immunologic, dermatological, hematological, neurological, or psychiatric disease,
• Presented any clinically significant illness in the previous 28 days before Day 1 of this study; history of drug abuse within 1 year before study Day 1; history of alcoholism within 1 year before Day 1,
• Had taken any prescribed or over the counter drug (including antacid drug), with the exception of paracetamol (up to 3 g per day) within 2 weeks prior to the dose administration,
• Consumed more than 50 g of ethanol per day (12.5 cL glass of 10° \[10%\] wine = 12 g; 4 cL of aperitif, 42° \[42%\] whiskey = 17 g; 25 cL glass of 3° \[3%\] beer = 7.5 g; 25 cL glass of 6° \[6%\] beer = 15 g,
• Drank more than 8 cups daily of beverage containing caffeine,
• Had poor motivation, intellectual problems likely to limit the validity of consent to participate in the study or limit the ability to comply with the protocol requirements or inability to cooperate adequately, inability to understand and to observe the instructions of the physician,
• Forfeited their freedom by administrative or legal award or were under guardianship,
• Had undergone surgery or had donated blood (i.e. 450 mL) within 12 weeks before study Day 1,
• Had positive urine screening of ethyl alcohol or drugs of abuse upon admission to the treatment period,
• Had any history of tuberculosis and/or prophylaxis for tuberculosis; positive results to HIV, HBsAg or anti-HCV tests; participation in any previous clinical study with OPC,
• If female, was pregnant or breast-feeding.

Sponsors & Collaborators

• Bial - Portela C S.A.: lead

Study Sites (1)

SGS aster

Paris, 75015, France

Location

MeSH Terms

Conditions

Parkinson Disease

Interventions

opicapone; entacapone; carbidopa, 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

Publication Agreements

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

Study Design

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

Study Record Dates

• First Submitted: June 19, 2014
• First Posted: June 23, 2014
• Study Start: September 1, 2011
• Primary Completion: January 1, 2012
• Study Completion: January 1, 2012
• Last Updated: September 20, 2016
• Results First Posted: September 20, 2016

Record last verified: 2016-07

Locations

FR (1)