- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02170376
The Effect of BIA 9-1067 at Steady-state on the Levodopa Pharmacokinetics
July 29, 2016 updated by: Bial - Portela C S.A.
The Effect of BIA 9-1067 at Steady-state on the Levodopa Pharmacokinetics When Administered With Immediate-release 100/25 mg Levodopa/Carbidopa in Healthy Subjects
The purpose of this study is to determine the effect of repeated dosing of once-daily 25, 50 and 75 mg opicapone (OPC, development code BIA 9-1067) on the levodopa pharmacokinetics (PK), in comparison to placebo and 200 mg entacapone (ENT).
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Detailed Description
This study was a single-centre, randomized, double-blind, gender-balanced, placebo-controlled study in 4 groups of 20 healthy subjects each (10 male and 10 female).
The clinical part included a screening examination within 3 weeks before the first institutionalization, an ambulatory period of 11 days (from Day 1 evening to Day 11 evening), during which the subjects returned to the clinical unit every evening, followed by an institutionalization of 1.5 days (from Day 11 evening to Day 13 morning (i.e. 14 h after the third administration of levodopa/carbidopa).
Then, a follow-up visit at 5 to 9 days after collection of the last PK blood sample (i.e.
Day 13).
The maximum total duration of the clinical study, including the 21-day screening period and the post-study follow-up, was expected to be about 39 to 43 days.
Study Type
Interventional
Enrollment (Actual)
80
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
-
-
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Paris, France, 75015
- SGS Aster
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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:
- Healthy male and female volunteers 18 to 45 years old (inclusive),
- Body Mass Index (BMI) in normal range (18-30 kg/m²),
- Healthy as determined by the Investigator on the basis of medical history, physical examination, clinical laboratory test results, vital signs, complete neurological examination and 12-lead ECG (electrocardiogram),
- Negative tests for Hepatitis B surface antigen (HBsAG), anti-Hepatitis C virus (HCV) antibodies and Human immunodeficiency virus (HIV) -1 and HIV-2 antibodies at screening,
- Negative screen for drugs of abuse and alcohol at screening and admission to the treatment period,
- If of childbearing potential (i.e. except if they had been sterilized for at least 3 months or postmenopausal for at least one year - the menopause was defined by a follicule stimulating hormone (FSH) level > 30 IU/L): used a non hormonal acceptable contraception method, i.e. intra-uterine device, condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository for all the duration of the study,
- If female of childbearing potential, had a negative human chorionic gonadotropin (HCG) beta serum pregnancy test at screening and urinary pregnancy test at admission to both ambulatory and confinement periods,
- Non-smokers or ex-smokers for at least 3 months,
- Able to communicate well with the Investigator and research staff and to comply with the requirements of the entire study,
- Provision of written informed consent to participate as shown by a signature on the volunteer consent form,
- Registered with the French Social Security in agreement with the French law on biomedical experimentation
Exclusion Criteria:
- Did not conform to the above inclusion criteria, or in case of volunteers who had a clinically relevant surgical history, a clinically relevant family history; had a history of relevant atopy,
- Had a significant infection or known inflammatory process at screening or admission to the treatment period; acute gastrointestinal symptoms (e.g., nausea, vomiting, diarrhoea, heartburn) at the time of screening or admission to the treatment period,
- Were vegetarians, vegans or had medical dietary restrictions,
- Could not communicate reliably with the Investigator,
- Were unlikely to co-operate with the requirements of the study; history of hypersensitivity to OPC, tolcapone, ENT, levodopa, carbidopa, benserazide or any related products (including excipients of the formulations) as well as severe hypersensitivity reactions (like angioedema) to any drugs,
- Had any significant cardiovascular (e.g. hypertension), hepatic, renal, respiratory (e.g. childhood asthma), gastrointestinal, endocrine (e.g. diabetes, dyslipidemia), immunologic, dermatological, hematological, neurological, or psychiatric disease,
- Presented any clinically significant illness in the previous 28 days before Day 1 of this study; history of drug abuse within 1 year before study Day 1; history of alcoholism within 1 year before Day 1,
- Had taken any prescribed or over the counter drug (including antacid drug), with the exception of paracetamol (up to 3 g per day) within 2 weeks prior to the dose administration,
- Consumed more than 50 g of ethanol per day (12.5 cL glass of 10° [10%] wine = 12 g; 4 cL of aperitif, 42° [42%] whiskey = 17 g; 25 cL glass of 3° [3%] beer = 7.5 g; 25 cL glass of 6° [6%] beer = 15 g,
- Drank more than 8 cups daily of beverage containing caffeine,
- Had poor motivation, intellectual problems likely to limit the validity of consent to participate in the study or limit the ability to comply with the protocol requirements or inability to cooperate adequately, inability to understand and to observe the instructions of the physician,
- Had received any experimental drug within the exclusion period defined in the National Register for Healthy Volunteers of the French Ministry of Health,
- Forfeited their freedom by administrative or legal award or were under guardianship,
- Had undergone surgery or had donated blood (i.e. 450 mL) within 12 weeks before study Day 1,
- Had positive urine screening of ethyl alcohol or drugs of abuse upon admission to the treatment period,
- Had any history of tuberculosis and/or prophylaxis for tuberculosis; positive results to HIV, HBsAg or anti-HCV tests; participation in any previous clinical study with OPC,
- If female, was pregnant or breast-feeding.
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: Parallel Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Group 1
Placebo once-daily for 11 days 200 mg entacapone concomitantly with levodopa/carbidopa on Day 12
|
Entacapone (ENT), over-encapsulated tablet 200 mg
Other Names:
PLC, placebo
Other Names:
Levodopa/carbidopa, tablet 100/25 mg
Other Names:
|
Experimental: Group 2
25 mg BIA 9-1067 once-daily for 11 days Placebo concomitantly with levodopa/carbidopa on Day 12
|
PLC, placebo
Other Names:
Levodopa/carbidopa, tablet 100/25 mg
Other Names:
BIA 9-1067 25 mg and 50 mg
Other Names:
|
Experimental: Group 3
50 mg 9-1067 once-daily for 11 days Placebo concomitantly with levodopa/carbidopa on Day 12
|
PLC, placebo
Other Names:
Levodopa/carbidopa, tablet 100/25 mg
Other Names:
BIA 9-1067 25 mg and 50 mg
Other Names:
|
Experimental: Group 4
75 mg 9-1067 once-daily for 11 days placebo concomitantly with levodopa/carbidopa on Day 12
|
PLC, placebo
Other Names:
Levodopa/carbidopa, tablet 100/25 mg
Other Names:
BIA 9-1067 25 mg and 50 mg
Other Names:
|
Placebo Comparator: Group 5
placebo once-daily for 11 days placebo concomitantly with levodopa/carbidopa on Day 12
|
PLC, placebo
Other Names:
Levodopa/carbidopa, tablet 100/25 mg
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Cmax - Maximum Plasma Concentration of Levodopa
Time Frame: pre-first dose and at 0.5, 1.0, 1.5, 2.0, 3.0, 4.0 and 5.0 h post-first and -second levodopa/carbidopa administration, and at 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 5.0, 8.0 and 14.0 h post-third levodopa/carbidopa administration
|
Cmax - Maximum plasma concentration of levodopa (mean pharmacokinetic parameter) following first oral administration of 100/25 mg levodopa/carbidopa on Day 12 with 25, 50 and 75 mg OPC or placebo and 200 mg Entacapone.
|
pre-first dose and at 0.5, 1.0, 1.5, 2.0, 3.0, 4.0 and 5.0 h post-first and -second levodopa/carbidopa administration, and at 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 5.0, 8.0 and 14.0 h post-third levodopa/carbidopa administration
|
Tmax - Time of Occurrence of Maximum Plasma Concentration
Time Frame: pre-first dose and at 0.5, 1.0, 1.5, 2.0, 3.0, 4.0 and 5.0 h post-first and -second levodopa/carbidopa administration, and at 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 5.0, 8.0 and 14.0 h post-third levodopa/carbidopa administration
|
Tmax - Time to Reach maximum plasma concentration of levodopa (mean pharmacokinetic parameter) following first oral administration of 100/25 mg levodopa/carbidopa on Day 12 with 25, 50 and 75 mg OPC or placebo and 200 mg Entacapone
|
pre-first dose and at 0.5, 1.0, 1.5, 2.0, 3.0, 4.0 and 5.0 h post-first and -second levodopa/carbidopa administration, and at 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 5.0, 8.0 and 14.0 h post-third levodopa/carbidopa administration
|
AUC0-∞ - Area Under the Concentration-time Curve From Time Zero up to Infinity With Extrapolation of the Terminal Phase
Time Frame: pre-first dose and at 0.5, 1.0, 1.5, 2.0, 3.0, 4.0 and 5.0 h post-first and -second levodopa/carbidopa administration, and at 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 5.0, 8.0 and 14.0 h post-third levodopa/carbidopa administration
|
AUC0-∞ of levodopa (mean pharmacokinetic parameter) following first oral administration of 100/25 mg levodopa/carbidopa on Day 12 with 25, 50 and 75 mg OPC or placebo and 200 mg Entacapone.
|
pre-first dose and at 0.5, 1.0, 1.5, 2.0, 3.0, 4.0 and 5.0 h post-first and -second levodopa/carbidopa administration, and at 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 5.0, 8.0 and 14.0 h post-third levodopa/carbidopa administration
|
AUC0-t - Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Time (t) Corresponding to the Last Quantifiable Concentration.
Time Frame: pre-first dose and at 0.5, 1.0, 1.5, 2.0, 3.0, 4.0 and 5.0 h post-first and -second levodopa/carbidopa administration, and at 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 5.0, 8.0 and 14.0 h post-third levodopa/carbidopa administration
|
AUC0-t - of levodopa (mean pharmacokinetic parameter) following first oral administration of 100/25 mg levodopa/carbidopa on Day 12 with 25, 50 and 75 mg OPC or placebo and 200 mg Entacapone.
|
pre-first dose and at 0.5, 1.0, 1.5, 2.0, 3.0, 4.0 and 5.0 h post-first and -second levodopa/carbidopa administration, and at 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 5.0, 8.0 and 14.0 h post-third levodopa/carbidopa administration
|
AUC0-5 - AUC Over 5 Hours
Time Frame: pre-first dose and at 0.5, 1.0, 1.5, 2.0, 3.0, 4.0 and 5.0 h post-first and -second levodopa/carbidopa administration, and at 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 5.0, 8.0 and 14.0 h post-third levodopa/carbidopa administration
|
AUC0-5 - of levodopa (mean pharmacokinetic parameter) following first oral administration of 100/25 mg levodopa/carbidopa on Day 12 with 25, 50 and 75 mg OPC or placebo and 200 mg Entacapone.
|
pre-first dose and at 0.5, 1.0, 1.5, 2.0, 3.0, 4.0 and 5.0 h post-first and -second levodopa/carbidopa administration, and at 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 5.0, 8.0 and 14.0 h post-third levodopa/carbidopa administration
|
t1/2 - Terminal Plasma Half-life
Time Frame: pre-first dose and at 0.5, 1.0, 1.5, 2.0, 3.0, 4.0 and 5.0 h post-first and -second levodopa/carbidopa administration, and at 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 5.0, 8.0 and 14.0 h post-third levodopa/carbidopa administration
|
t1/2 - Terminal plasma half-life of levodopa (mean pharmacokinetic parameter) following first oral administration of 100/25 mg levodopa/carbidopa on Day 12 with 25, 50 and 75 mg OPC or placebo and 200 mg Entacapone.
|
pre-first dose and at 0.5, 1.0, 1.5, 2.0, 3.0, 4.0 and 5.0 h post-first and -second levodopa/carbidopa administration, and at 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 5.0, 8.0 and 14.0 h post-third levodopa/carbidopa administration
|
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
September 1, 2011
Primary Completion (Actual)
January 1, 2012
Study Completion (Actual)
January 1, 2012
Study Registration Dates
First Submitted
June 19, 2014
First Submitted That Met QC Criteria
June 19, 2014
First Posted (Estimate)
June 23, 2014
Study Record Updates
Last Update Posted (Estimate)
September 20, 2016
Last Update Submitted That Met QC Criteria
July 29, 2016
Last Verified
July 1, 2016
More Information
Terms related to this study
Keywords
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
- Dopamine Agents
- Antiparkinson Agents
- Anti-Dyskinesia Agents
- Catechol O-Methyltransferase Inhibitors
- Aromatic Amino Acid Decarboxylase Inhibitors
- Levodopa
- Carbidopa
- Opicapone
- Entacapone
Other Study ID Numbers
- BIA-91067-124
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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