Effect of BIA 6-512 at Steady-state on the Levodopa Pharmacokinetics

NCT03094156 | Completed Phase 1

• 1 other identifier: BIA-6512-106
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of the study was to To investigate whether the administration of BIA 6-512 (25 mg, 50 mg, 75 mg and 100 mg) at steady-state affects the pharmacokinetics of levodopa when administered in combination with a single-dose of immediate release levodopa/benserazide 200/50 mg or with a single-dose of immediate release levodopa/benserazide 200/50 mg plus a single-dose of entacapone 200 mg.

Conditions

Parkinson Disease

Outcome Measures

Primary Outcomes (12)

• Day 4 - Maximum observed plasma drug concentration (Cmax)

  BIA 6-512, levodopa, 3-OMD and entacapone pharmacokinetic parameters on day 4

  pre-dose, ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8 and 16 hours post-dose

• Day 4 - Time of occurrence of Cmax (tmax)

  BIA 6-512, levodopa, 3-OMD and entacapone pharmacokinetic parameters on day 4

  pre-dose, ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8 and 16 hours post-dose

• Day 4 - Area under the plasma concentration-time curve (AUC) from time zero to the last sampling time at which concentrations were at or above the limit of quantification (AUC0-t)

  BIA 6-512, levodopa, 3-OMD and entacapone pharmacokinetic parameters on day 4

  pre-dose, ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8 and 16 hours post-dose

• Day 4 - AUC from time zero to 8 h post-dose (AUC0-τ)

  BIA 6-512, levodopa, 3-OMD and entacapone pharmacokinetic parameters on day 4

  pre-dose, ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8 and 16 hours post-dose

• Day 4 - Apparent terminal elimination half-life, calculated from ln 2/λz (t1/2)

  BIA 6-512, levodopa, 3-OMD and entacapone pharmacokinetic parameters on day 4

  pre-dose, ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8 and 16 hours post-dose

• Day 4 - Area under the plasma concentration versus time curve from time zero to infinity (AUC0-∞)

  BIA 6-512, levodopa, 3-OMD and entacapone pharmacokinetic parameters on day 4

  pre-dose, ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8 and 16 hours post-dose

• Day 5 - Maximum observed plasma drug concentration (Cmax)

  pre-dose, ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8, 16 and 24 hours post-dose

• Day 5 - Time of occurrence of Cmax (tmax)

  BIA 6-512, levodopa, 3-OMD and entacapone pharmacokinetic parameters on day 5

  pre-dose, ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8, 16 and 24 hours post-dose

• Day 5 - Area under the plasma concentration-time curve (AUC) from time zero to the last sampling time at which concentrations were at or above the limit of quantification (AUC0-t)

  BIA 6-512, levodopa, 3-OMD and entacapone pharmacokinetic parameters on day 5

  pre-dose, ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8, 16 and 24 hours post-dose

• Day 5 - AUC from time zero to 8 h post-dose (AUC0-τ)

  BIA 6-512, levodopa, 3-OMD and entacapone pharmacokinetic parameters on day 5

  pre-dose, ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8, 16 and 24 hours post-dose

• Day 5 - Apparent terminal elimination half-life, calculated from ln 2/λz (t1/2)

  BIA 6-512, levodopa, 3-OMD and entacapone pharmacokinetic parameters on day 5

  pre-dose, ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8, 16 and 24 hours post-dose

• Day 5 - Area under the plasma concentration versus time curve from time zero to infinity (AUC0-∞)

  BIA 6-512, levodopa, 3-OMD and entacapone pharmacokinetic parameters on day 5

  pre-dose, ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8, 16 and 24 hours post-dose

Study Arms (5)

Placebo

EXPERIMENTAL

Subjects were administered with those investigational products at approximately 8-h intervals, starting in the morning (approximately at 8h00) of Day 1 and finishing in the morning of Day 5 (last dose). On Day 4, concomitantly with the Placebo morning dose, one tablet of Madopar® 250 was administered. On Day 5, concomitantly with the Placebo morning dose, one tablet of Madopar® 250 and one tablet of Comtan® were administered.

Drug: Placebo; Drug: Madopar® 250; Drug: Comtan®

BIA 6-512 25 mg

EXPERIMENTAL

Subjects were administered with those investigational products at approximately 8-h intervals, starting in the morning (approximately at 8h00) of Day 1 and finishing in the morning of Day 5 (last dose). On Day 4, concomitantly with the BIA 6-512 25 mg morning dose, one tablet of Madopar® 250 was administered. On Day 5, concomitantly with the BIA 6-512 25 mg morning dose, one tablet of Madopar® 250 and one tablet of Comtan® were administered.

Drug: BIA 6-512; Drug: Madopar® 250; Drug: Comtan®

BIA 6-512 50 mg

EXPERIMENTAL

Subjects were administered with those investigational products at approximately 8-h intervals, starting in the morning (approximately at 8h00) of Day 1 and finishing in the morning of Day 5 (last dose). On Day 4, concomitantly with the BIA 6-512 50 mg morning dose, one tablet of Madopar® 250 was administered. On Day 5, concomitantly with the BIA 6-512 50 mg morning dose, one tablet of Madopar® 250 and one tablet of Comtan® were administered.

Drug: BIA 6-512; Drug: Madopar® 250; Drug: Comtan®

BIA 6-512 75 mg

EXPERIMENTAL

Subjects were administered with those investigational products at approximately 8-h intervals, starting in the morning (approximately at 8h00) of Day 1 and finishing in the morning of Day 5 (last dose). On Day 4, concomitantly with the BIA 6-512 75 mg morning dose, one tablet of Madopar® 250 was administered. On Day 5, concomitantly with the BIA 6-512 75 mg morning dose, one tablet of Madopar® 250 and one tablet of Comtan® were administered.

Drug: BIA 6-512; Drug: Madopar® 250; Drug: Comtan®

BIA 6-512 100 mg

EXPERIMENTAL

Subjects were administered with those investigational products at approximately 8-h intervals, starting in the morning (approximately at 8h00) of Day 1 and finishing in the morning of Day 5 (last dose). On Day 4, concomitantly with the BIA 6-512 100 mg morning dose, one tablet of Madopar® 250 was administered. On Day 5, concomitantly with the BIA 6-512 100 mg morning dose, one tablet of Madopar® 250 and one tablet of Comtan® were administered.

Drug: BIA 6-512; Drug: Madopar® 250; Drug: Comtan®

Interventions

Placebo DRUG

1 capsule of placebo \[to be taken orally, with 240 mL of potable water\]

Placebo

BIA 6-512 DRUG

1 capsule of BIA 6-512 25mg or 1 capsule of BIA 6-512 50 mg or 1 capsule of BIA 6-512 75 mg or 1 capsule of BIA 6-512 100 mg \[to be taken orally, with 240 mL of potable water\]

Also known as: Trans-resveratrol

BIA 6-512 100 mg; BIA 6-512 25 mg; BIA 6-512 50 mg; BIA 6-512 75 mg

Madopar® 250 DRUG

Levodopa/benserazide immediate release tablets 200mg/50mg \[to be taken orally, with 240 mL of potable water\]

BIA 6-512 100 mg; BIA 6-512 25 mg; BIA 6-512 50 mg; BIA 6-512 75 mg; Placebo

Comtan® DRUG

Entacapone 200 mg tablets \[to be taken orally, with 240 mL of potable water\]

BIA 6-512 100 mg; BIA 6-512 25 mg; BIA 6-512 50 mg; BIA 6-512 75 mg; Placebo

Eligibility Criteria

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

You may qualify if:

• Male or female subjects aged between 18 and 45 years, inclusive.
• Subjects of body mass index (BMI) between 19 and 30 kg/m2, inclusive.
• Subjects who were healthy as determined by pre-study medical history, physical examination, vital signs, complete neurological examination and 12-lead ECG.
• Subjects who had negative tests for HBsAg, anti-HCVAb and HIV-1 and HIV-2 Ab at screening
• Subjects who had clinical laboratory test results clinically acceptable at screening and admission.
• Subjects who had a negative screen for alcohol and drugs of abuse at screening and admission.
• Subjects who were non-smokers or who smoked ≤ 10 cigarettes or equivalent per day.
• Subjects who were able and willing to gave written informed consent.
• (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: double barrier, intrauterine device or abstinence.
• (If female) She had a negative urine pregnancy test at screening and admission.

You may not qualify if:

• Subjects who had a 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.
• Subjects who had a clinically relevant surgical history.
• Subjects who had a clinically relevant family history.
• Subjects who had a history of relevant atopy.
• Subjects who had a history of relevant drug hypersensitivity.
• Subjects who had a history of alcoholism or drug abuse.
• Subjects who consumed more than 14 units of alcohol a week.
• Subjects who had a significant infection or known inflammatory process on screening or admission.
• Subjects who had acute gastrointestinal symptoms (e.g., nausea, vomiting, diarrhoea, heartburn) at the time of screening or admission.
• Subjects who had used medicines within 2 weeks of admission that may affect the safety or other study assessments, in the investigator's opinion.
• Subjects who had previously participated in a clinical trial with BIA 6-512.
• Subjects who had used any investigational drug or participated in any clinical trial within 6 months prior to screening.
• Subjects who had participated in more than 2 clinical trials within the 12 months prior to screening.
• Subjects who had donated or received any blood or blood products within the 3 months prior to screening.
• Subjects who were vegetarians, vegans or have medical dietary restrictions.

Sponsors & Collaborators

• Bial - Portela C S.A.: lead

Study Sites (1)

Human Pharmacology Unit (UFH) - BIAL - Portela & Cª, SA

S. Mamede Do Coronado, 4745-457, Portugal

Location

MeSH Terms

Conditions

Parkinson Disease

Interventions

Resveratrol; entacapone

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)

Stilbestrols; Stilbenes; Benzylidene Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polyphenols; Phenols

Study Design

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

Study Record Dates

• First Submitted: March 23, 2017
• First Posted: March 29, 2017
• Study Start: April 26, 2006
• Primary Completion: July 11, 2006
• Study Completion: July 11, 2006
• Last Updated: March 30, 2017

Record last verified: 2017-03

Locations

PT (1)