Parkinson's Disease (PD)Phase 1NCT02778594
Pharmacokinetic-pharmacodynamic Interaction Between BIA 3-202 and Levodopa/Benserazide
A Phase 1 study testing BIA 3-202 and levodopa 100 mg / benserazide 25 mg in people with Parkinson's Disease (PD), run by Bial - Portela C S.A. at 1 site in Portugal.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Parkinson's Disease (PD)
- What is being tested?
- BIA 3-202 and levodopa 100 mg / benserazide 25 mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 17 participants
- Where
- 1 sitePortugal
- Study dates
- Sep 2005to Nov 2005
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
About this study
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
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).
Read the 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.
- Conditions
- Parkinson's Disease (PD)
- Being tested
- BIA 3-202, Placebo, levodopa 100 mg / benserazide 25 mg
- Medical subject headings
- Parkinson Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BIA 3-202Drug
Also called Nebicapone
nebicapone 50 mg tablets; oral use
PlaceboDrug
Nebicapone matching placebo tablets
levodopa 100 mg / benserazide 25 mgDrug
Also called Madopar
Madopar® HBS 125 (levodopa 100 mg / benserazide 25 mg) capsules; oral use
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Placebo (4 tablets) Simultaneously with the placebo dose, subjects were administered 1 capsule of Madopar® HBS 125 Receives: 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 Receives: 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 Receives: 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 Receives: Drug: BIA 3-202; Drug: levodopa 100 mg / benserazide 25 mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: pre-dose, ½, 1, 1½, 2, 3, 4, 6, 8, 12, 16 and 24 h post-dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 May 2016 (estimated)
- Study startSep 2005
- Primary completionNov 2005
- Study completionNov 2005
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Parkinson's Disease (PD)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 17 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bial - Portela C S.A.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02778594
- Sponsor's protocol ID
- BIA-3202-108
- Status last verified
- Jun 2016
- First submitted
- 18 May 2016
- Last updated
- 14 Jun 2016
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 14 Jun 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02778594
- Acronym / sponsor ID
- BIA-3202-108
- Conditions
- Parkinson's Disease (PD)
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 17 participants (actual)
- Lead sponsor
- Bial - Portela C S.A.Industry (pharma, biotech, devices)
- Study start
- Sep 2005
- Primary completion
- Nov 2005 (actual)
- Study completion
- Nov 2005 (actual)
- First posted
- 20 May 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: Placebo, Drug: levodopa 100 mg / benserazide 25 mgPlacebo (4 tablets) Simultaneously with the placebo dose, subjects were administered 1 capsule of Madopar® HBS 125 |
| Nebicapone 50 mg | Experimental | Drug: BIA 3-202, Drug: Placebo, Drug: levodopa 100 mg / benserazide 25 mgNebicapone 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 | Experimental | Drug: BIA 3-202, Drug: Placebo, Drug: levodopa 100 mg / benserazide 25 mgNebicapone 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 | Experimental | Drug: BIA 3-202, Drug: levodopa 100 mg / benserazide 25 mgNebicapone 200 mg (4 tablets of 50 mg). Simultaneously with the nebicapone dose, subjects were administered 1 capsule of Madopar® HBS 125 |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (11 listed)
- 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.
Key exclusion criteria (21 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BIA 3-202Also: Nebicaponenebicapone 50 mg tablets; oral use | Drug | Nebicapone 100 mg, Nebicapone 200 mg, Nebicapone 50 mg |
| PlaceboNebicapone matching placebo tablets | Drug | Nebicapone 100 mg, Nebicapone 50 mg, Placebo |
| levodopa 100 mg / benserazide 25 mgAlso: MadoparMadopar® HBS 125 (levodopa 100 mg / benserazide 25 mg) capsules; oral use | Drug | Nebicapone 100 mg, Nebicapone 200 mg, Nebicapone 50 mg, Placebo |
Primary outcome
Maximum observed plasma drug concentration (Cmax)
Time frame: pre-dose, ½, 1, 1½, 2, 3, 4, 6, 8, 12, 16 and 24 h post-dose
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)
Time frame: pre-dose, ½, 1, 1½, 2, 3, 4, 6, 8, 12, 16 and 24 h post-dose
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)
Time frame: pre-dose, ½, 1, 1½, 2, 3, 4, 6, 8, 12, 16 and 24 h post-dose
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-∞)
Time frame: pre-dose, ½, 1, 1½, 2, 3, 4, 6, 8, 12, 16 and 24 h post-dose
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)
Time frame: pre-dose, ½, 1, 1½, 2, 3, 4, 6, 8, 12, 16 and 24 h post-dose
Mean t1/2 pharmacokinetic parameters of levodopa following oral administration of single-doses of Madopar® HBS 125 concomitantly with placebo or nebicapone
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Jun 2016.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing BIA 3-202 and levodopa 100 mg / benserazide 25 mg in people with Parkinson's Disease (PD), run by Bial - Portela C S.A. at 1 site in Portugal.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Jun 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Portugal. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum observed plasma drug concentration (Cmax) (time frame: pre-dose, ½, 1, 1½, 2, 3, 4, 6, 8, 12, 16 and 24 h post-dose). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Jun 2016.