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

Primary Purpose

Parkinson's Disease (PD)

Status

Completed

Phase

Phase 1

Locations

Portugal

Study Type

Interventional

Intervention

BIA 3-202

Placebo

levodopa 100 mg / benserazide 25 mg

About this trial

This is an interventional treatment trial for Parkinson's Disease (PD)

Eligibility Criteria

18 Years - 45 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

Subjects were eligible for entry into the study if they fulfilled the following inclusion criteria:

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.

Exclusion Criteria:

Subjects were not eligible for entry into the study if they fulfilled the following exclusion criteria:

Subjects who did not conform to the above inclusion criteria, or
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.
Subjects who were unlikely to co-operate with the requirements of the study.
Subjects who were unwilling or unable to give written informed consent.
(If female) She was pregnant or breast-feeding.
(If female) She was of childbearing potential and she did not use an approved effective contraceptive method (double-barrier, intra-uterine device or abstinence) or she used oral contraceptives.

Sites / Locations

Human Pharmacology Unit

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Placebo Comparator

Experimental

Arm Label

Placebo

Nebicapone 50 mg

Nebicapone 100 mg

Nebicapone 200 mg

Arm Description

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

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

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

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

Outcomes

Primary Outcome Measures

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

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

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

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

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

Secondary Outcome Measures

Full Information

NCT ID

NCT02778594

First Posted

May 18, 2016

Last Updated

June 13, 2016

Sponsor

Bial - Portela C S.A.

1. Study Identification

Unique Protocol Identification Number

NCT02778594

Brief Title

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

Official Title

Pharmacokinetic-pharmacodynamic Interaction Between Three Different Single Doses of BIA 3-202 and a Single-dose of Controlled-release 100/25 mg Levodopa/Benserazide (Madopar® HBS 125): a Double-blind, Randomised, Four-way Crossover, Placebo-controlled Study in Healthy Volunteers

Study Type

Interventional

2. Study Status

Record Verification Date

June 2016

Overall Recruitment Status

Completed

Study Start Date

September 2005 (undefined)

Primary Completion Date

November 2005 (Actual)

Study Completion Date

November 2005 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Bial - Portela C S.A.

4. Oversight

Data Monitoring Committee

5. Study Description

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).

Detailed Description

STUDY DESIGN AND METHODOLOGY: Single centre, double-blind, randomised, placebo-controlled, 4-way crossover study with 4 single-dose treatment periods. The washout period between doses was 5 days or more. Screening: Subjects were screened for eligibility within 28 and 7 days before first admission. The screening consisted of: medical history; physical examination, vital signs; complete neurological examination; 12-lead ECG; haematology, coagulation, plasma biochemistry and urinalysis tests; HIV, hepatitis B and hepatitis C serology; drugs of abuse and alcohol screen; urine pregnancy test in women of childbearing potential; and review of the selection criteria. Treatment periods: In each treatment period, eligible subjects were admitted to the UFH on the day prior to receiving the study medication for: vital signs; medical history and physical examination updates; 12-lead ECG; haematology and plasma biochemistry; drugs of abuse and alcohol screen; and urine pregnancy test in women of childbearing potential. On first admission, subjects had a review of the selection criteria and were randomly assigned to one of the treatment sequences. On the morning of the dosing day, subjects received a dose of nebicapone/placebo concomitantly with a dose of Madopar® HBS 125 in fasting conditions (at least 8 hours) and remained in the UFH until at least 24 h post-dose; then, they left and returned for the next period or the follow-up visit. At given time-points between pre-dose and discharge, subjects were submitted to vital signs recording, brief neurological examination, 12-lead ECG, and blood sampling for plasma drug determination and erythrocyte S-COMT activity assay. At discharge, vital signs and ECG were recorded, and haematology and plasma biochemistry tests were performed. Blood samples (7 mL) for the determination of plasma concentration of levodopa, 3-O-methyldopa (3-OMD) and nebicapone, and for the assay of the erythrocyte S-COMT activity were taken at the following times: pre-dose, ½, 1, 1½, 2, 3, 4, 6, 8, 12, 16 and 24 h post-dose. Follow-up: A follow-up visit occurred approximately 7-10 days after discharge of last treatment period or early discontinuation for: medical history and physical examination updates; vital signs; 12-lead ECG; haematology, plasma biochemistry and urinalysis tests; and pregnancy test in women of childbearing potential.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Parkinson's Disease (PD)

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Crossover Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

17 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

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

Arm Title

Nebicapone 50 mg

Arm Type

Experimental

Arm Description

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

Arm Title

Nebicapone 100 mg

Arm Type

Experimental

Arm Description

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

Arm Title

Nebicapone 200 mg

Arm Type

Experimental

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

BIA 3-202

Other Intervention Name(s)

Nebicapone

Intervention Description

nebicapone 50 mg tablets; oral use

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Nebicapone matching placebo tablets

Intervention Type

Drug

Intervention Name(s)

levodopa 100 mg / benserazide 25 mg

Other Intervention Name(s)

Madopar

Intervention Description

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

Primary Outcome Measure Information:

Title

Maximum observed plasma drug concentration (Cmax)

Description

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

Time Frame