Pharmacokinetic-pharmacodynamic Interaction Between BIA 3-202 and Levodopa/Benserazide

NCT02778594 | Completed Phase 1

• 1 other identifier: BIA-3202-108
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine the effect of three single oral doses of nebicapone (50 mg, 100 mg and 200 mg) on the levodopa pharmacokinetics when administered in combination with a single-dose of controlled release levodopa 100 mg/benserazide 25 mg (Madopar® HBS 125).

Conditions

Parkinson's Disease (PD)

Outcome Measures

Primary Outcomes (5)

• Maximum observed plasma drug concentration (Cmax)

  Mean Cmax pharmacokinetic parameters of levodopa following oral administration of single-doses of Madopar® HBS 125 concomitantly with placebo or nebicapone

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

• Time of occurrence of Cmax (tmax)

  Mean tmax pharmacokinetic parameters of levodopa following oral administration of single-doses of Madopar® HBS 125 concomitantly with placebo or nebicapone

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

• 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)

  Mean AUC0-t pharmacokinetic parameters of levodopa following oral administration of single-doses of Madopar® HBS 125 concomitantly with placebo or nebicapone

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

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

  Mean AUC0-00 pharmacokinetic parameters of levodopa following oral administration of single-doses of Madopar® HBS 125 concomitantly with placebo or nebicapone

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

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

  Mean t1/2 pharmacokinetic parameters of levodopa following oral administration of single-doses of Madopar® HBS 125 concomitantly with placebo or nebicapone

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

Study Arms (4)

Placebo

PLACEBO COMPARATOR

Placebo (4 tablets) Simultaneously with the placebo dose, subjects were administered 1 capsule of Madopar® HBS 125

Drug: Placebo; Drug: levodopa 100 mg / benserazide 25 mg

Nebicapone 50 mg

EXPERIMENTAL

Nebicapone 50 mg (1 tablet of 50 mg plus 3 tablets of placebo). Simultaneously with the nebicapone dose, subjects were administered 1 capsule of Madopar® HBS 125

Drug: BIA 3-202; Drug: Placebo; Drug: levodopa 100 mg / benserazide 25 mg

Nebicapone 100 mg

EXPERIMENTAL

Nebicapone 100 mg (2 tablets of 50 mg plus 2 tablets of placebo). Simultaneously with the nebicapone dose, subjects were administered 1 capsule of Madopar® HBS 125

Drug: BIA 3-202; Drug: Placebo; Drug: levodopa 100 mg / benserazide 25 mg

Nebicapone 200 mg

EXPERIMENTAL

Nebicapone 200 mg (4 tablets of 50 mg). Simultaneously with the nebicapone dose, subjects were administered 1 capsule of Madopar® HBS 125

Drug: BIA 3-202; Drug: levodopa 100 mg / benserazide 25 mg

Interventions

BIA 3-202 DRUG

nebicapone 50 mg tablets; oral use

Also known as: Nebicapone

Nebicapone 100 mg; Nebicapone 200 mg; Nebicapone 50 mg

Placebo DRUG

Nebicapone matching placebo tablets

Nebicapone 100 mg; Nebicapone 50 mg; Placebo

levodopa 100 mg / benserazide 25 mg DRUG

Madopar® HBS 125 (levodopa 100 mg / benserazide 25 mg) capsules; oral use

Also known as: Madopar

Nebicapone 100 mg; Nebicapone 200 mg; Nebicapone 50 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 test results clinically acceptable at screening and admission to first treatment period.
• Subjects who had negative tests for HBsAg, anti-HCVAb and HIV-1 and HIV-2 Ab at screening.
• Subjects who had a negative screen for alcohol and drugs of abuse at screening and admission to each treatment period.
• Subjects who were non-smokers or who smoked ≤ 10 cigarettes or equivalent per day.
• Subjects who were able and willing to give 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 to each treatment period.

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 glaucoma.
• 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 first admission.
• Subjects who had acute gastrointestinal symptoms at the time of screening or first admission (e.g., nausea, vomiting, diarrhoea, heartburn).
• Subjects who had used medicines within 2 weeks of first admission that, in the opinion of the investigator, may affect the safety or other study assessments.
• Subjects who had used any investigational drug or participated in any clinical trial within 2 months of their first admission.
• Subjects who had donated or received any blood or blood products within the previous 2 months prior to screening.
• Subjects who were vegetarians, vegans or have medical dietary restrictions.
• Subjects who could not communicate reliably with the investigator.

Sponsors & Collaborators

• Bial - Portela C S.A.: lead

Study Sites (1)

Human Pharmacology Unit

S. Mamede Do Coronado, 4745-457, Portugal

Location

MeSH Terms

Conditions

Parkinson Disease

Interventions

nebicapone; Levodopa; Benserazide; 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

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; Hydrazines

Study Design

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

Study Record Dates

• First Submitted: May 18, 2016
• First Posted: May 20, 2016
• Study Start: September 1, 2005
• Primary Completion: November 1, 2005
• Study Completion: November 1, 2005
• Last Updated: June 14, 2016

Record last verified: 2016-06

Locations

PT (1)