Effect of BIA 6-512 at Steady-state on the Levodopa Pharmacokinetics

Parkinson Disease Clinical Trial

Official title:

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 Entacapone 200 mg

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03094156
• Other study ID #: BIA-6512-106
• Status: Completed
• Phase: Phase 1
• First received: March 23, 2017
• Last updated: March 29, 2017
• Start date: April 26, 2006
• Est. completion date: July 11, 2006

Study information

• Verified date: March 2017
• Source: Bial - Portela C S.A.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of the study was to To investigate 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 entacapone 200 mg.

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 (UFHBIAL - Portela & Cª, SA) 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 entacapone 200 mg (Comtan®) 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 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 39
• Est. completion date: July 11, 2006
• Est. primary completion date: July 11, 2006
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 45 Years

Eligibility

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.

Related Conditions & MeSH terms

• Parkinson Disease

Intervention

Drug:
• Placebo
1 capsule of placebo [to be taken orally, with 240 mL of potable water]
• BIA 6-512
1 capsule of BIA 6-512 25mg or 1 capsule of BIA 6-512 50 mg or 1 capsule of BIA 6-512 75 mg or 1 capsule of BIA 6-512 100 mg [to be taken orally, with 240 mL of potable water]
• Madopar® 250
Levodopa/benserazide immediate release tablets 200mg/50mg [to be taken orally, with 240 mL of potable water]
• Comtan®
Entacapone 200 mg tablets [to be taken orally, with 240 mL of potable water]

Locations

Country	Name	City	State
Portugal	Human Pharmacology Unit (UFH) - BIAL - Portela & Cª, SA	S. Mamede do Coronado

Sponsors (1)

Lead Sponsor	Collaborator
Bial - Portela C S.A.

Country where clinical trial is conducted

Portugal, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Day 4 - Maximum observed plasma drug concentration (Cmax)	BIA 6-512, levodopa, 3-OMD and entacapone pharmacokinetic parameters on day 4	pre-dose, ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8 and 16 hours post-dose
Primary	Day 4 - Time of occurrence of Cmax (tmax)	BIA 6-512, levodopa, 3-OMD and entacapone pharmacokinetic parameters on day 4	pre-dose, ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8 and 16 hours post-dose
Primary	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)	BIA 6-512, levodopa, 3-OMD and entacapone pharmacokinetic parameters on day 4	pre-dose, ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8 and 16 hours post-dose
Primary	Day 4 - AUC from time zero to 8 h post-dose (AUC0-t)	BIA 6-512, levodopa, 3-OMD and entacapone pharmacokinetic parameters on day 4	pre-dose, ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8 and 16 hours post-dose
Primary	Day 4 - Apparent terminal elimination half-life, calculated from ln 2/?z (t1/2)	BIA 6-512, levodopa, 3-OMD and entacapone pharmacokinetic parameters on day 4	pre-dose, ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8 and 16 hours post-dose
Primary	Day 4 - Area under the plasma concentration versus time curve from time zero to infinity (AUC0-8)	BIA 6-512, levodopa, 3-OMD and entacapone pharmacokinetic parameters on day 4	pre-dose, ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8 and 16 hours post-dose
Primary	Day 5 - Maximum observed plasma drug concentration (Cmax)		pre-dose, ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8, 16 and 24 hours post-dose
Primary	Day 5 - Time of occurrence of Cmax (tmax)	BIA 6-512, levodopa, 3-OMD and entacapone pharmacokinetic parameters on day 5	pre-dose, ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8, 16 and 24 hours post-dose
Primary	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)	BIA 6-512, levodopa, 3-OMD and entacapone pharmacokinetic parameters on day 5	pre-dose, ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8, 16 and 24 hours post-dose
Primary	Day 5 - AUC from time zero to 8 h post-dose (AUC0-t)	BIA 6-512, levodopa, 3-OMD and entacapone pharmacokinetic parameters on day 5	pre-dose, ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8, 16 and 24 hours post-dose
Primary	Day 5 - Apparent terminal elimination half-life, calculated from ln 2/?z (t1/2)	BIA 6-512, levodopa, 3-OMD and entacapone pharmacokinetic parameters on day 5	pre-dose, ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8, 16 and 24 hours post-dose
Primary	Day 5 - Area under the plasma concentration versus time curve from time zero to infinity (AUC0-8)	BIA 6-512, levodopa, 3-OMD and entacapone pharmacokinetic parameters on day 5	pre-dose, ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8, 16 and 24 hours post-dose