Back to resultsPharmacokinetic-pharmacodynamic Interaction Between BIA 3-202 and Levodopa/Carbidopa
Primary Purpose
Parkinson's Disease
Status
Completed
Phase
Phase 1
Locations
Portugal
Study Type
Interventional
Intervention
BIA 3-202
Placebo
Sinemet®
Sponsored by
About this trial
This is an interventional treatment trial for Parkinson's Disease
Eligibility Criteria
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
Experimental
Experimental
Experimental
Placebo Comparator
Arm Label
Nebicapone 50 mg
Nebicapone 100 mg
Nebicapone 200 mg
Placebo
Arm Description
1 tablet of 50 mg plus 3 tablets of placebo concomitantly with 1 tablet of Sinemet® CR 200/50 (levodopa 200 mg / carbidopa 50 mg)
2 tablets of 50 mg plus 2 tablets of placebo concomitantly with 1 tablet of Sinemet® CR 200/50 (levodopa 200 mg / carbidopa 50 mg)
4 tablets of 50 mg concomitantly with 1 tablet of Sinemet® CR 200/50 (levodopa 200 mg / carbidopa 50 mg)
4 tablets concomitantly with 1 tablet of Sinemet® CR 200/50 (levodopa 200 mg / carbidopa 50 mg)
Outcomes
Primary Outcome Measures
Cmax
Cmax - Maximum observed plasma concentration of levodopa following oral administration of single-doses of Sinemet® CR 200/50 concomitantly with placebo or nebicapone
Tmax
Tmax - Time to occurrence of Cmax of levodopa following oral administration of single-doses of Sinemet® CR 200/50 concomitantly with placebo or nebicapone
AUC0-t
AUC0-t - Area under the plasma concentration-time curve from time 0 to the last sampling time at which concentration were at or above the Limit of quantification of levodopa following oral administration of single-doses of Sinemet® CR 200/50 concomitantly with placebo or nebicapone
AUC0-∞
AUC0-∞ - Area under the plasma concentration-time curve extrapolated to infinity of levodopa following oral administration of single-doses of Sinemet® CR 200/50 concomitantly with placebo or nebicapone
Secondary Outcome Measures
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02774564
Brief Title
Pharmacokinetic-pharmacodynamic Interaction Between BIA 3-202 and Levodopa/Carbidopa
Official Title
Pharmacokinetic-pharmacodynamic Interaction Between Three Different Single Doses of BIA 3-202 and a Single Dose of Controlled-release 200/50 mg Levodopa/Carbidopa (Sinemet® cr 200/50): a Double-blind, Randomised, Four-way Crossover, Placebo-controlled Study in Healthy Volunteers
Study Type
Interventional
2. Study Status
Record Verification Date
May 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
No
5. Study Description
Brief Summary
The purpose of this study is to 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 200 mg/carbidopa 50 mg (Sinemet CR 200/50).
Detailed Description
Single centre, double-blind, randomised, placebo-controlled, 4-way crossover study with four single-dose treatment periods. The washout period between doses was 5 days or more.
Procedures:
Screening: Subjects will be screened for eligibility within 28 and 7 days of first admission. Written informed consent will be obtained before any study procedure is performed. The screening will consist of: medical history; physical examination, vital signs; complete neurological examination; 12-lead ECG; hematology, 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. The results of screening must be known to the investigator prior to the subject's first admission.
Treatment periods: In each of the four consecutive treatment periods, eligible subjects will be 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; hematology and plasma biochemistry; drugs of abuse and alcohol screen; and urine pregnancy test in women of childbearing potential. On the first admission the subjects will have a review of the selection criteria and will be randomized to one of the treatment sequences. On the morning of the dosing day, subjects will receive a dose of BIA 3-202 / Placebo concomitantly with a dose of Sinemet CR 200/50 in fasting conditions (at least 8 hours) and will remain in the UFH until at least 24 h post-dose; then, they will be discharged and will return for the next period or the follow-up visit. At given time-points between pre-dose and discharge, subjects will be submitted to vital signs recording, brief neurological examinations, 12-lead ECG, and blood sampling for plasma drug assays and erythrocyte S-COMT activity. At discharge, vital signs and ECG will be recorded, and hematology and plasma biochemistry tests will be performed.
Follow-up: A follow-up visit will occur approximately 7-10 days after discharge of the last treatment period or early discontinuation for: medical history and physical examination updates; vital signs; 12-lead ECG; hematology, 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
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Crossover Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
16 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Nebicapone 50 mg
Arm Type
Experimental
Arm Description
1 tablet of 50 mg plus 3 tablets of placebo concomitantly with 1 tablet of Sinemet® CR 200/50 (levodopa 200 mg / carbidopa 50 mg)
Arm Title
Nebicapone 100 mg
Arm Type
Experimental
Arm Description
2 tablets of 50 mg plus 2 tablets of placebo concomitantly with 1 tablet of Sinemet® CR 200/50 (levodopa 200 mg / carbidopa 50 mg)
Arm Title
Nebicapone 200 mg
Arm Type
Experimental
Arm Description
4 tablets of 50 mg concomitantly with 1 tablet of Sinemet® CR 200/50 (levodopa 200 mg / carbidopa 50 mg)
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
4 tablets concomitantly with 1 tablet of Sinemet® CR 200/50 (levodopa 200 mg / carbidopa 50 mg)
Intervention Type
Drug
Intervention Name(s)
BIA 3-202
Other Intervention Name(s)
Nebicapone
Intervention Description
Nebicapone tablets 50 mg, oral administration
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Nebicapone matching placebo tablets
Intervention Type
Drug
Intervention Name(s)
Sinemet®
Intervention Description
Sinemet® CR 200/50 (levodopa 200 mg / carbidopa 50 mg) tablets
Primary Outcome Measure Information:
Title
Cmax
Description
Cmax - Maximum observed plasma concentration of levodopa following oral administration of single-doses of Sinemet® CR 200/50 concomitantly with placebo or nebicapone
Time Frame
pre-dose, ½, 1, 1½, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose.
Title
Tmax
Description
Tmax - Time to occurrence of Cmax of levodopa following oral administration of single-doses of Sinemet® CR 200/50 concomitantly with placebo or nebicapone
Time Frame
pre-dose, ½, 1, 1½, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose.
Title
AUC0-t
Description
AUC0-t - Area under the plasma concentration-time curve from time 0 to the last sampling time at which concentration were at or above the Limit of quantification of levodopa following oral administration of single-doses of Sinemet® CR 200/50 concomitantly with placebo or nebicapone
Time Frame
pre-dose, ½, 1, 1½, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose.
Title
AUC0-∞
Description
AUC0-∞ - Area under the plasma concentration-time curve extrapolated to infinity of levodopa following oral administration of single-doses of Sinemet® CR 200/50 concomitantly with placebo or nebicapone
Time Frame
pre-dose, ½, 1, 1½, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
45 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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.
Facility Information:
Facility Name
Human Pharmacology Unit
City
S. Mamede do Coronado
ZIP/Postal Code
4745-457
Country
Portugal
12. IPD Sharing Statement
Plan to Share IPD
Undecided
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Pharmacokinetic-pharmacodynamic Interaction Between BIA 3-202 and Levodopa/Carbidopa
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