Pharmacokinetics of Rising Single-doses of BIA 6-512 and Their Effect on the Levodopa Pharmacokinetics

NCT03091868 | Completed Phase 1

• 1 other identifier: BIA-6512-102
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

To investigate the effect of rising oral single-doses of BIA 6-512 (25 mg, 50 mg, 100 mg and 200 mg) on levodopa pharmacokinetics when administered in combination with a single-dose of immediate release levodopa/carbidopa 100/25 mg (Sinemet® 100/25) or with a single-dose of Sinemet® 100/25 plus a single-dose of entacapone (Comtan®) 200 mg and to assess the tolerability and safety of rising single oral doses of BIA 6-512 when administered in combination with a single-dose of Sinemet® 100/25 or with a single-dose of Sinemet® 100/25 plus a single-dose of Comtan® 200 mg.

Conditions

Parkinson Disease

Outcome Measures

Primary Outcomes (12)

• Maximum observed plasma drug concentration (Cmax) - Day 1

  Pharmacokinetic parameters for BIA 6-512, levodopa, 3-O-methyldopa (3-OMD) on Day 1 - Day of administration of BIA 6-512/Placebo concomitantly with 1 tablet of levodopa/carbidopa 100/25 mg (Sinemet® 100/25)

  pre-dose, ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose

• Time at which the Cmax occurred (tmax) - Day 1

  Pharmacokinetic parameters for BIA 6-512, levodopa, 3-O-methyldopa (3-OMD) on Day 1 - Day of administration of BIA 6-512/Placebo concomitantly with 1 tablet of levodopa/carbidopa 100/25 mg (Sinemet® 100/25)

  pre-dose, ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose

• Area under the plasma concentration versus time curve (AUC) from time zero to the last sampling time at which concentrations were at or above the limit of quantification (AUC0-t) - Day 1

  Pharmacokinetic parameters for BIA 6-512, levodopa, 3-O-methyldopa (3-OMD) on Day 1 - Day of administration of BIA 6-512/Placebo concomitantly with 1 tablet of levodopa/carbidopa 100/25 mg (Sinemet® 100/25)

  pre-dose, ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose

• AUC from time zero to the infinity (AUC0-∞) - Day 1

  Pharmacokinetic parameters for BIA 6-512, levodopa, 3-O-methyldopa (3-OMD) on Day 1 - Day of administration of BIA 6-512/Placebo concomitantly with 1 tablet of levodopa/carbidopa 100/25 mg (Sinemet® 100/25)

  pre-dose, ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose

• Elimination rate constant (λz) - Day 1

  Pharmacokinetic parameters for BIA 6-512, levodopa, 3-O-methyldopa (3-OMD) on Day 1 - Day of administration of BIA 6-512/Placebo concomitantly with 1 tablet of levodopa/carbidopa 100/25 mg (Sinemet® 100/25)

  pre-dose, ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose

• Apparent elimination half-life (t1/2) - Day 1

  Pharmacokinetic parameters for BIA 6-512, levodopa, 3-O-methyldopa (3-OMD) on Day 1 - Day of administration of BIA 6-512/Placebo concomitantly with 1 tablet of levodopa/carbidopa 100/25 mg (Sinemet® 100/25)

  pre-dose, ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose

• Maximum observed plasma drug concentration (Cmax) - Day 2

  Pharmacokinetic parameters for BIA 6-512, levodopa, 3-O-methyldopa (3-OMD) and entacapone on day 2 - Day of administration of BIA 6-512/Placebo concomitantly with 1 tablet of levodopa/carbidopa 100/25 mg (Sinemet® 100/25) plus 1 tablet of entacapone 200 mg (Comtan®). Administration occurred 24 h after the time of administration in Day 1.

  ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose

• Time at which the Cmax occurred (tmax) - Day 2

  Pharmacokinetic parameters for BIA 6-512, levodopa, 3-O-methyldopa (3-OMD) and entacapone on day 2 - Day of administration of BIA 6-512/Placebo concomitantly with 1 tablet of levodopa/carbidopa 100/25 mg (Sinemet® 100/25) plus 1 tablet of entacapone 200 mg (Comtan®). Administration occurred 24 h after the time of administration in Day 1.

  ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose

• Area under the plasma concentration versus time curve (AUC) from time zero to the last sampling time at which concentrations were at or above the limit of quantification (AUC0-t) - Day 2

  Pharmacokinetic parameters for BIA 6-512, levodopa, 3-O-methyldopa (3-OMD) and entacapone on day 2 - Day of administration of BIA 6-512/Placebo concomitantly with 1 tablet of levodopa/carbidopa 100/25 mg (Sinemet® 100/25) plus 1 tablet of entacapone 200 mg (Comtan®). Administration occurred 24 h after the time of administration in Day 1.

  ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose

• AUC from time zero to the infinity (AUC0-∞) - Day 2

  Pharmacokinetic parameters for BIA 6-512, levodopa, 3-O-methyldopa (3-OMD) and entacapone on day 2 - Day of administration of BIA 6-512/Placebo concomitantly with 1 tablet of levodopa/carbidopa 100/25 mg (Sinemet® 100/25) plus 1 tablet of entacapone 200 mg (Comtan®). Administration occurred 24 h after the time of administration in Day 1.

  ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose

• Elimination rate constant (λz) - Day 2

  Pharmacokinetic parameters for BIA 6-512, levodopa, 3-O-methyldopa (3-OMD) and entacapone on day 2 - Day of administration of BIA 6-512/Placebo concomitantly with 1 tablet of levodopa/carbidopa 100/25 mg (Sinemet® 100/25) plus 1 tablet of entacapone 200 mg (Comtan®). Administration occurred 24 h after the time of administration in Day 1.

  ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose

• Apparent elimination half-life (t1/2) - Day 2

  Pharmacokinetic parameters for BIA 6-512, levodopa, 3-O-methyldopa (3-OMD) and entacapone on day 2 - Day of administration of BIA 6-512/Placebo concomitantly with 1 tablet of levodopa/carbidopa 100/25 mg (Sinemet® 100/25) plus 1 tablet of entacapone 200 mg (Comtan®). Administration occurred 24 h after the time of administration in Day 1.

  ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose

Study Arms (4)

Group 1 (BIA 6-512 25 mg + Placebo)

EXPERIMENTAL

Single-doses were prepared as follows: BIA 6-512 25 mg dose = 1 capsule of 25 mg plus 1 capsule of placebo In all groups, placebo recipients received 2 capsules of placebo. BIA 6-512/Placebo capsules and Sinemet® 100/25 and Comtan® tablets were administered simultaneously, by oral route, in fasting conditions.

Drug: Placebo oral capsule; Drug: Sinemet® 100/25; Drug: Comtan®; Drug: BIA 6-512 25 mg

Group 2 (BIA 6-512 50 mg + Placebo)

EXPERIMENTAL

Single-doses were prepared as follows: BIA 6-512 50 mg dose = 2 capsules of 25 mg In all groups, placebo recipients received 2 capsules of placebo. BIA 6-512/Placebo capsules and Sinemet® 100/25 and Comtan® tablets were administered simultaneously, by oral route, in fasting conditions.

Drug: Placebo oral capsule; Drug: Sinemet® 100/25; Drug: Comtan®; Drug: BIA 6-512 25 mg

Group 3 (BIA 6-512 100 mg + Placebo)

EXPERIMENTAL

Single-doses were prepared as follows: BIA 6-512 100 mg dose = 1 capsule of 100 mg plus 1 capsule of placebo In all groups, placebo recipients received 2 capsules of placebo. BIA 6-512/Placebo capsules and Sinemet® 100/25 and Comtan® tablets were administered simultaneously, by oral route, in fasting conditions.

Drug: Placebo oral capsule; Drug: Sinemet® 100/25; Drug: Comtan®; Drug: BIA 6-512 100 mg

Group 4 (BIA 6-512 200 mg + Placebo)

EXPERIMENTAL

Single-doses were prepared as follows: BIA 6-512 200 mg dose = 2 capsules of 100 mg In all groups, placebo recipients received 2 capsules of placebo. BIA 6-512/Placebo capsules and Sinemet® 100/25 and Comtan® tablets were administered simultaneously, by oral route, in fasting conditions.

Drug: Placebo oral capsule; Drug: Sinemet® 100/25; Drug: Comtan®; Drug: BIA 6-512 100 mg

Interventions

Placebo oral capsule DRUG

Matching placebo capsules. Oral administration.

Group 1 (BIA 6-512 25 mg + Placebo); Group 2 (BIA 6-512 50 mg + Placebo); Group 3 (BIA 6-512 100 mg + Placebo); Group 4 (BIA 6-512 200 mg + Placebo)

Sinemet® 100/25 DRUG

Single-dose of immediate release levodopa/carbidopa 100/25 mg consisted of 1 tablet of Sinemet® 100/25. Route of administration: Oral.

Group 1 (BIA 6-512 25 mg + Placebo); Group 2 (BIA 6-512 50 mg + Placebo); Group 3 (BIA 6-512 100 mg + Placebo); Group 4 (BIA 6-512 200 mg + Placebo)

Comtan® DRUG

Single-dose of entacapone 200 mg consisted of 1 tablet of Comtan®. Route of administration: Oral.

Group 1 (BIA 6-512 25 mg + Placebo); Group 2 (BIA 6-512 50 mg + Placebo); Group 3 (BIA 6-512 100 mg + Placebo); Group 4 (BIA 6-512 200 mg + Placebo)

BIA 6-512 25 mg DRUG

BIA 6-512 capsules strengths 25 mg. Oral administration.

Group 1 (BIA 6-512 25 mg + Placebo); Group 2 (BIA 6-512 50 mg + Placebo)

BIA 6-512 100 mg DRUG

BIA 6-512 capsules strengths 100 mg. Oral administration.

Group 3 (BIA 6-512 100 mg + Placebo); Group 4 (BIA 6-512 200 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 clinical laboratory tests clinically acceptable at screening and admission.
• Subjects who had negative tests for HBsAg, anti-HCVAb and anti-HIV-1 and anti-HIV-2 Ab at screening.
• Subjects who had a negative screen for alcohol and drugs of abuse at screening and admission.
• Subjects who were non-smokers or who smoked less than 10 cigarettes or equivalent per day.
• Subjects who were able and willing to give written informed consent.
• (If female) She was sterile 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 21 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 at the time of screening or admission (e.g., nausea, vomiting, diarrhoea, heartburn).
• Subjects who had used prescription or over-the-counter medication within 2 weeks of admission.
• Subjects who had used any investigational drug or participated in any clinical trial within 3 months prior to screening.
• Subjects who had donated or received any blood or blood products within 3 months prior to screening.
• Subjects who were vegetarians, vegans or have medical dietary restrictions.
• Subjects who cannot communicate reliably with the investigator.
• Subjects who were unlikely to co-operate with the requirements of the study.

Sponsors & Collaborators

• Bial - Portela C S.A.: lead

Study Sites (1)

Human Pharmacology Unit (UFH)

S. Mamede Do Coronado, 4745-457, Portugal

Location

MeSH Terms

Conditions

Parkinson Disease

Interventions

entacapone

Condition Hierarchy (Ancestors)

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

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 21, 2017
• First Posted: March 27, 2017
• Study Start: November 3, 2004
• Primary Completion: February 28, 2005
• Study Completion: February 28, 2005
• Last Updated: March 27, 2017

Record last verified: 2017-03

Locations

PT (1)