Clinical trial NCT03091868: Pharmacokinetics of Rising Single-doses of BIA 6-512 and Their Effect on the Levodopa Pharmacokinetics
Official title: A Double-blind, Randomised, Placebo-controlled Study in Healthy Volunteers to Investigate the Tolerability and Pharmacokinetics of Rising Single-doses of BIA 6-512 and Their Effect on the Levodopa Pharmacokinetics When Administered in Combination With a Single-dose of Levodopa/Carbidopa 100/25 mg or With a Single-dose of Levodopa/Carbidopa 100/25 mg Plus a Single-dose of Entacapone 200 mg
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Parkinson Disease
Lead sponsor: Bial - Portela C S.A.
Sponsor class: INDUSTRY
First posted: 2017-03-27
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: To investigate the effect of rising oral single-doses of BIA 6-512 (25 mg, 50 mg, 100 mg and 200 mg) on levodopa pharmacokinetics when administered in combination with a single-dose of immediate release levodopa/carbidopa 100/25 mg (Sinemet® 100/25) or with a single-dose of Sinemet® 100/25 plus a single-dose of entacapone (Comtan®) 200 mg and to assess the tolerability and safety of rising single oral doses of BIA 6-512 when administered in combination with a single-dose of Sinemet® 100/25 or with a single-dose of Sinemet® 100/25 plus a single-dose of Comtan® 200 mg.

Detailed description: Single centre, double-blind, randomised, placebo-controlled study in four sequential groups of healthy subjects. Eligible subjects were admitted to the UFH on the day prior to receiving the first study medication. On the morning of the first dosing day (Day 1), subjects received BIA 6-512/Placebo concomitantly with Sinemet® 100/25; on the morning of the second dosing day (Day 2), subjects received BIA 6-512/Placebo concomitantly with Sinemet® 100/25 and Comtan® 200 mg. Products were administered in fasting conditions (at least 8 hours). Subjects remained confined in the UFH from admission (Day 0) until at least 24 h post last dose (Day 3); then, they were discharged and will return for the follow-up visit.

Eligibility criteria: 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 tests clinically acceptable at screening and admission.
* Subjects who had negative tests for HBsAg, anti-HCVAb and anti-HIV-1 and anti-HIV-2 Ab at screening.
* Subjects who had a negative screen for alcohol and drugs of abuse at screening and admission.
* Subjects who were non-smokers or who smoked less than 10 cigarettes or equivalent per day.
* Subjects who were able and willing to give written informed consent.
* (If female) She was sterile 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 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 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 admission.
* Subjects who had acute gastrointestinal symptoms at the time of screening or admission (e.g., nausea, vomiting, diarrhoea, heartburn).
* Subjects who had used prescription or over-the-counter medication within 2 weeks of admission.
* Subjects who had used any investigational drug or participated in any clinical trial within 3 months prior to screening.
* Subjects who had donated or received any blood or blood products within 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.
* (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 or she used oral contraceptives.

Primary outcomes:
measure: Maximum observed plasma drug concentration (Cmax) - Day 1
timeFrame: pre-dose, ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose
measure: Time at which the Cmax occurred (tmax) - Day 1
timeFrame: pre-dose, ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose
measure: Area under the plasma concentration versus time curve (AUC) from time zero to the last sampling time at which concentrations were at or above the limit of quantification (AUC0-t) - Day 1
timeFrame: pre-dose, ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose
measure: AUC from time zero to the infinity (AUC0-∞) - Day 1
timeFrame: pre-dose, ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose
measure: Elimination rate constant (λz) - Day 1
timeFrame: pre-dose, ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose
measure: Apparent elimination half-life (t1/2) - Day 1
timeFrame: pre-dose, ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose
measure: Maximum observed plasma drug concentration (Cmax) - Day 2
timeFrame: ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose
measure: Time at which the Cmax occurred (tmax) - Day 2
timeFrame: ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose
measure: Area under the plasma concentration versus time curve (AUC) from time zero to the last sampling time at which concentrations were at or above the limit of quantification (AUC0-t) - Day 2
timeFrame: ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose
measure: AUC from time zero to the infinity (AUC0-∞) - Day 2
timeFrame: ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose
measure: Elimination rate constant (λz) - Day 2
timeFrame: ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose
measure: Apparent elimination half-life (t1/2) - Day 2
timeFrame: ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose
Secondary outcomes:
Other outcomes:
Locations:
city: S. Mamede do Coronado
country: Portugal
facility: Human Pharmacology Unit (UFH)
Study officials:
References: