- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03097211
Effect of BIA 6-512 at Steady-state on the Levodopa Pharmacokinetics With a Single-dose of Levodopa/Benserazide 200/50 mg or With a Single-dose of Levodopa/Benserazide 200/50 mg Plus a Single-dose of Nebicapone 150 mg
March 27, 2017 updated by: Bial - Portela C S.A.
A Double-blind, Randomised, Placebo-controlled, Rising Multiple Dose Study in Healthy Volunteers to Investigate the Effect of BIA 6-512 at Steady-state on the Levodopa Pharmacokinetics When Administered in Combination With a Single-dose of Levodopa/Benserazide 200/50 mg or With a Single-dose of Levodopa/Benserazide 200/50 mg Plus a Single-dose of Nebicapone 150 mg
The purpose of this study was to determine 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 nebicapone 150 mg.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Detailed Description
Single centre, double-blind, randomised, placebo-controlled, rising multiple dose study in four sequential groups of healthy male and female subjects.
Eligible subjects were admitted to the Human Pharmacology Unit (UFH)on the day prior to receiving the first study medication.
Starting in the morning of Day 1 (first dose), subjects received BIA 6-512/Placebo thrice daily until the morning of Day 5 (last dose).
Concomitantly with the morning dose of BIA 6-512/Placebo on Day 4, a levodopa/benserazide 200/50 mg (Madopar® 250) single-dose was administered.
On Day 5, a Madopar® 250 single-dose and a nebicapone 150 mg single-dose were administered concomitantly with the morning dose of BIA 6-512/Placebo.
In the morning of Day 4 and Day 5, products were administered in fasting conditions of at least 8 hours and subjects remained fasted until 2 h post-dose.
Subjects were resident in the UFH from admission (Day 0) until at least 24 h post last dose (Day 6); then, they were discharged and returned for the follow-up visit.
Study Type
Interventional
Enrollment (Actual)
38
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
-
S. Mamede do Coronado, Portugal, 4745-457
- Human Pharmacology Unit (UFH) - BIAL - Portela & Cª, SA
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 45 years (ADULT)
Accepts Healthy Volunteers
Yes
Genders Eligible for Study
All
Description
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 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.
Exclusion Criteria:
- 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.
- Subjects who cannot 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 effective contraceptive method (double-barrier, intra-uterine device or abstinence) or she used oral contraceptives.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: RANDOMIZED
- Interventional Model: SEQUENTIAL
- Masking: DOUBLE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: Group 1: BIA 6-512 25 mg or placebo
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/Placebo morning dose, one tablet of Madopar® 250 was administered.
On Day 5, concomitantly with the BIA 6-512/Placebo morning dose, one tablet of Madopar® 250 and one tablet of nebicapone 150 mg were administered
|
Placebo capsules.
Orally, with 240 mL of potable water.
The investigational products consisted of capsules containing BIA 6-512 25 mg, 50 mg, 75 mg, 100 mg.
Orally, with 240 mL of potable water.
Other Names:
Levodopa/benserazide immediate release tablets 200mg/50mg.
Orally, with 240 mL of potable water.
Other Names:
Nebicapone 150 mg tablets.
Orally, with 240 mL of potable water.
Other Names:
|
EXPERIMENTAL: Group 2: BIA 6-512 50 mg or placebo
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/Placebo morning dose, one tablet of Madopar® 250 was administered.
On Day 5, concomitantly with the BIA 6-512/Placebo morning dose, one tablet of Madopar® 250 and one tablet of nebicapone 150 mg were administered
|
Placebo capsules.
Orally, with 240 mL of potable water.
The investigational products consisted of capsules containing BIA 6-512 25 mg, 50 mg, 75 mg, 100 mg.
Orally, with 240 mL of potable water.
Other Names:
Levodopa/benserazide immediate release tablets 200mg/50mg.
Orally, with 240 mL of potable water.
Other Names:
Nebicapone 150 mg tablets.
Orally, with 240 mL of potable water.
Other Names:
|
EXPERIMENTAL: Group 3: BIA 6-512 75 mg or placebo
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/Placebo morning dose, one tablet of Madopar® 250 was administered.
On Day 5, concomitantly with the BIA 6-512/Placebo morning dose, one tablet of Madopar® 250 and one tablet of nebicapone 150 mg were administered
|
Placebo capsules.
Orally, with 240 mL of potable water.
The investigational products consisted of capsules containing BIA 6-512 25 mg, 50 mg, 75 mg, 100 mg.
Orally, with 240 mL of potable water.
Other Names:
Levodopa/benserazide immediate release tablets 200mg/50mg.
Orally, with 240 mL of potable water.
Other Names:
Nebicapone 150 mg tablets.
Orally, with 240 mL of potable water.
Other Names:
|
EXPERIMENTAL: Group 4: BIA 6-512 100 mg or placebo
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/Placebo morning dose, one tablet of Madopar® 250 was administered.
On Day 5, concomitantly with the BIA 6-512/Placebo morning dose, one tablet of Madopar® 250 and one tablet of nebicapone 150 mg were administered
|
Placebo capsules.
Orally, with 240 mL of potable water.
The investigational products consisted of capsules containing BIA 6-512 25 mg, 50 mg, 75 mg, 100 mg.
Orally, with 240 mL of potable water.
Other Names:
Levodopa/benserazide immediate release tablets 200mg/50mg.
Orally, with 240 mL of potable water.
Other Names:
Nebicapone 150 mg tablets.
Orally, with 240 mL of potable water.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Day 4 - Maximum observed plasma drug concentration (Cmax)
Time Frame: pre-dose, ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8 and 16 hours post-dose.
|
Pharmacokinetic parameters of BIA 6-512, levodopa, and nebicapone 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)
Time Frame: pre-dose, ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8 and 16 hours post-dose.
|
Pharmacokinetic parameters of BIA 6-512, levodopa, and nebicapone 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)
Time Frame: pre-dose, ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8 and 16 hours post-dose.
|
Pharmacokinetic parameters of BIA 6-512, levodopa, and nebicapone 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)
Time Frame: pre-dose, ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8 and 16 hours post-dose.
|
Pharmacokinetic parameters of BIA 6-512, levodopa, and nebicapone 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-∞)
Time Frame: pre-dose, ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8 and 16 hours post-dose.
|
Pharmacokinetic parameters of BIA 6-512, levodopa, and nebicapone 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)
Time Frame: pre-dose, ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8 and 16 hours post-dose.
|
Pharmacokinetic parameters of BIA 6-512, levodopa, and nebicapone 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)
Time Frame: pre-dose, ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8, 16 and 24 hours post-dose
|
Pharmacokinetic parameters of BIA 6-512, levodopa, and nebicapone on day 5
|
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)
Time Frame: pre-dose, ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8, 16 and 24 hours post-dose
|
Pharmacokinetic parameters of BIA 6-512, levodopa, and nebicapone 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)
Time Frame: pre-dose, ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8, 16 and 24 hours post-dose
|
Pharmacokinetic parameters of BIA 6-512, levodopa, and nebicapone 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)
Time Frame: pre-dose, ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8, 16 and 24 hours post-dose
|
Pharmacokinetic parameters of BIA 6-512, levodopa, and nebicapone 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-∞)
Time Frame: pre-dose, ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8, 16 and 24 hours post-dose
|
Pharmacokinetic parameters of BIA 6-512, levodopa, and nebicapone 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)
Time Frame: pre-dose, ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8, 16 and 24 hours post-dose
|
Pharmacokinetic parameters of BIA 6-512, levodopa, and nebicapone on day 5
|
pre-dose, ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8, 16 and 24 hours post-dose
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (ACTUAL)
July 17, 2006
Primary Completion (ACTUAL)
October 20, 2006
Study Completion
October 20, 2006
Study Registration Dates
First Submitted
March 27, 2017
First Submitted That Met QC Criteria
March 27, 2017
First Posted (ACTUAL)
March 31, 2017
Study Record Updates
Last Update Posted (ACTUAL)
March 31, 2017
Last Update Submitted That Met QC Criteria
March 27, 2017
Last Verified
March 1, 2017
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Brain Diseases
- Central Nervous System Diseases
- Nervous System Diseases
- Parkinsonian Disorders
- Basal Ganglia Diseases
- Movement Disorders
- Synucleinopathies
- Neurodegenerative Diseases
- Parkinson Disease
- Physiological Effects of Drugs
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Platelet Aggregation Inhibitors
- Protective Agents
- Dopamine Agents
- Antioxidants
- Antiparkinson Agents
- Anti-Dyskinesia Agents
- Levodopa
- Resveratrol
- Benserazide
- Benserazide, levodopa drug combination
Other Study ID Numbers
- BIA-6512-107
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
UNDECIDED
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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