Pharmacokinetic Interaction Between BIA 9-1067 and Standard-release Levodopa/Carbidopa

Phase 1

Completed

• Conditions: Parkinson Disease
• Interventions: Drug: BIA 9-1067; Drug: Sinemet® 100/25 mg

• Registration Number: NCT01533077
• Lead Sponsor: Bial - Portela C S.A.

Brief Summary

To investigate the pharmacokinetics of levodopa when administered concomitantly with BIA 9-1067 or 1 hour after.

Detailed Description

Single-centre, open-label, randomized, gender-balanced, crossover study with four consecutive single-dose treatment periods.

Study Timeline

• Study Start: 2009-03
• Primary Completion: 2009-10
• Study Completion: 2010-02
• Study First Submitted: 2012-01-24
• Study First Submitted QC: 2012-02-10
• Study First Posted: 2012-02-15
• Results First Submitted: 2015-07-22
• Status Verified: 2015-11
• Results First Submitted QC: 2015-11-18
• Last Update Submitted: 2015-11-18
• Results First Posted: 2015-12-22
• Last Update Posted: 2015-12-22

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 18

Inclusion Criteria

• Availability for the entire study period and willingness to adhere to the protocol requirements as evidenced by the informed consent form (ICF) duly read, signed and dated by the volunteer prior to participation in the study.
• Male or female volunteers.
• Volunteers of at least 18 years of age but not older than 45 years.
• Volunteers with body mass index (BMI) greater than or equal to 19 and below 30 kg/m2.
• Volunteers who were healthy as determined by pre-study (at screening) medical history, physical examination, vital signs, complete neurological examination and 12-lead ECG.
• Volunteers who had clinical laboratory test results judged clinically acceptable (within the laboratory's stated normal range; if not within this range, they must had been without any clinical significance) at screening and admission to first treatment period.
• Volunteers who had negative tests for hepatitis B surface antigen (HBsAg), anti-hepatitis C antibodies (HCV Ab), and Human immunodeficiency viruses -1 and -2 antibodies (HIV-1 and HIV-2 Ab) at screening.
• Volunteers who had negative screen of ethyl alcohol and drugs of abuse at screening.
• Volunteers who were non- or ex-smokers. For the purpose of this study, an ex-smoker is defined as someone who completely stopped smoking for at least 3 months before day 1 of this study.
• Due to unknown risks and potential harm to the unborn fetus, sexually active men or women must have agreed to use a medically acceptable form of contraception throughout the study.
• If female of childbearing potential, she had a negative HCG beta serum pregnancy test at screening and admission to each treatment period
• The informed consent form must have been signed by all volunteers, prior to their participation in the study.

Exclusion Criteria

• Volunteers who did not conform to the above inclusion criteria, or in case of
• Volunteers who had a clinically relevant surgical history.
• Volunteers who had a clinically relevant family history.
• Volunteers who had a history of relevant atopy.
• Volunteers who had a significant infection or known inflammatory process at screening or admission to the treatment period.
• Volunteers who had acute gastrointestinal symptoms at the time of screening or admission to the treatment period (e.g., nausea, vomiting, diarrhoea, heartburn).
• Volunteers who were vegetarians, vegans or have medical dietary restrictions.
• Volunteers who could not communicate reliably with the investigator.
• Volunteers who were unlikely to co-operate with the requirements of the study.
• History of hypersensitivity to BIA 9-1067, tolcapone, entacapone, levodopa, benserazide or any related products (including excipients of the formulations) as well as severe hypersensitivity reactions (like angioedema) to any drugs.
• Presence of significant gastrointestinal, liver or kidney disease, or any other conditions known to interfere with the absorption, distribution, metabolism or excretion of drugs or known to potentiate or predispose to undesired effects.
• History of significant gastrointestinal, liver or kidney disease that may affect drug bioavailability.
• Presence or history of significant cardiovascular, pulmonary, hematologic, neurologic, psychiatric, lymphatic, musculoskeletal, genitourinary, endocrine, immunologic, dermatologic or connective tissue disease.
• Suicidal tendency, history of or disposition to seizures, state of confusion, clinically relevant psychiatric diseases.
• Presence of significant heart disease or disorder according to ECG.
• Presence of suspicious undiagnosed skin lesions or a history of melanoma.
• Previous history of Neuroleptic Malignant Syndrome (NMS) and/or nontraumatic rhabdomyolysis.
• History of significant glaucoma.
• Used of prescription medications including monoamine oxidase (MAO) inhibitors within 28 days before day 1 of the study.
• Used of over-the-counter (OTC) products within 7 days before day 1 of the study.
• Maintenance therapy with any drug, or significant history of drug dependency (drug abuse) or alcohol abuse (> 3 units of alcohol per day, intake of excessive alcohol, acute or chronic).
• Any clinically significant illness in the previous 28 days before day 1 of this study.
• Volunteers who took an Investigational Product (in another clinical trial) or donated 50 mL or more of blood in the previous 28 days before day 1 of this study.
• 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.
• Donation of 500 mL or more of blood (Canadian Blood Services, Hema-Quebec, clinical studies, etc.) in the previous 56 days before day 1 of this study.
• Positive urine screening of ethyl alcohol or drugs of abuse at admission to the treatment period.
• 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 BIA 9-1067 within 84 days before day 1 of the study.
• Females who were pregnant according to a positive serum pregnancy test or were lactating.
• Females of childbearing potential who refused to use an acceptable contraceptive regimen throughout the study.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Group 4	BIA 9-1067	Period 1: Sinemet® 100/25 1 h after the BIA 9-1067 50 mg Period 2: BIA 9-1067 50 mg + Sinemet® 100/25 Period 3: Sinemet® 100/25 Period 4: BIA 9-1067 50 mg
Group 1	Sinemet® 100/25 mg	Period 1: BIA 9-1067 50 mg Period 2: Sinemet® 100/25 1 h after the BIA 9-1067 50 mg Period 3: BIA 9-1067 50 mg + Sinemet® 100/25 Period 4: Sinemet® 100/25
Group 2	Sinemet® 100/25 mg	Period 1: Sinemet® 100/25 Period 2: BIA 9-1067 50 mg Period 3: Sinemet® 100/25 1 h after the BIA 9-1067 50 mg Period 4: BIA 9-1067 50 mg + Sinemet® 100/25
Group 2	BIA 9-1067	Period 1: Sinemet® 100/25 Period 2: BIA 9-1067 50 mg Period 3: Sinemet® 100/25 1 h after the BIA 9-1067 50 mg Period 4: BIA 9-1067 50 mg + Sinemet® 100/25
Group 3	BIA 9-1067	Period 1: BIA 9-1067 50 mg + Sinemet® 100/25 Period 2: Sinemet® 100/25 Period 3: BIA 9-1067 50 mg Period 4: Sinemet® 100/25 1 h after the BIA 9-1067 50 mg
Group 1	BIA 9-1067	Period 1: BIA 9-1067 50 mg Period 2: Sinemet® 100/25 1 h after the BIA 9-1067 50 mg Period 3: BIA 9-1067 50 mg + Sinemet® 100/25 Period 4: Sinemet® 100/25
Group 4	Sinemet® 100/25 mg	Period 1: Sinemet® 100/25 1 h after the BIA 9-1067 50 mg Period 2: BIA 9-1067 50 mg + Sinemet® 100/25 Period 3: Sinemet® 100/25 Period 4: BIA 9-1067 50 mg
Group 3	Sinemet® 100/25 mg	Period 1: BIA 9-1067 50 mg + Sinemet® 100/25 Period 2: Sinemet® 100/25 Period 3: BIA 9-1067 50 mg Period 4: Sinemet® 100/25 1 h after the BIA 9-1067 50 mg

Primary Outcome Measures

Name	Time	Method
Cmax - Maximum Observed Plasma Concentration (L-DOPA)	pre-dose, ½, 1, 1½, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 and 72 h after dose.	Mean pharmacokinetic parameters of L-beta-3,4-dihydroxyphenylalanine (levodopa) (L-DOPA)
Tmax - Time to Occurrence of Cmax (3-OMD)	Pre-dose, ½, 1, 1½, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 and 72 h after dose	Pharmacokinetic parameters of 3-O-methyl-levodopa (3-OMD). For tmax = time to Cmax values are presented as median with range values.
Tmax - Time of Occurrence of Cmax Maximum Observed Plasma Concentration (L-DOPA)	pre-dose, ½, 1, 1½, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 and 72 h after dose.	Pharmacokinetic parameters of L-beta-3,4-dihydroxyphenylalanine (levodopa) (L-DOPA). For tmax = time to Cmax values are presented as median with range values.
AUC0-t - Area Under the Plasma Concentration-time Curve to Last Measurable Time Point (L-DOPA)	pre-dose, ½, 1, 1½, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 and 72 h after dose.	Mean pharmacokinetic parameters of L-beta-3,4-dihydroxyphenylalanine (levodopa) (L-DOPA)
AUC0-∞ - Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to Infinity (L-DOPA)	pre-dose, ½, 1, 1½, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 and 72 h after dose.	Mean pharmacokinetic parameters of L-beta-3,4-dihydroxyphenylalanine (levodopa) (L-DOPA)
AUC0-t - Area Under the Plasma Concentration-time Curve to Last Measurable Time Point (3-OMD)	Pre-dose, ½, 1, 1½, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 and 72 h after dose.	Mean pharmacokinetic parameters of 3-O-methyl-levodopa (3-OMD)
AUC0-∞ - Area Under the Plasma Concentration-time Curve Extrapolated to Infinity (Carbidopa)	Pre-dose, ½, 1, 1½, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 and 72 h after dose	Pharmacokinetic parameters of carbidopa. For tmax = time to Cmax values are presented as median with range values.
Tmax - Time to Occurrence of Cmax (Carbidopa)	Pre-dose, ½, 1, 1½, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 and 72 h after dose.	Pharmacokinetic parameters of carbidopa. For tmax = time to Cmax values are presented as median with range values.
AUC0-t - Area Under the Plasma Concentration-time Curve to Last Measurable Time Point (Carbidopa)	Pre-dose, ½, 1, 1½, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 and 72 h after dose.	Mean pharmacokinetic parameters of carbidopa
Cmax - Maximum Observed Plasma Concentration (3-OMD)	Pre-dose, ½, 1, 1½, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 and 72 h after dose	Mean pharmacokinetic parameters of 3-O-methyl-levodopa (3-OMD)
AUC0-∞ - Area Under the Plasma Concentration-time Curve Extrapolated to Infinity (3-OMD)	Pre-dose, ½, 1, 1½, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 and 72 h after dose.	Mean pharmacokinetic parameters of 3-O-methyl-levodopa (3-OMD)
Cmax - Maximum Observed Plasma Concentration (Carbidopa)	Pre-dose, ½, 1, 1½, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 and 72 h after dose.	Mean pharmacokinetic parameters of carbidopa
Cmax - Maximum Observed Plasma Concentration (BIA 9-1067)	Pre-dose, ½, 1, 1½, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 and 72 h after dose.	Mean pharmacokinetic parameters of BIA 9-1067
AUC0-∞ - Area Under the Plasma Concentration-time Curve Extrapolated to Infinity (BIA 9-1067)	Pre-dose, ½, 1, 1½, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 and 72 h after dose.	Mean pharmacokinetic parameters of BIA 9-1067
Tmax - Time to Occurrence of Cmax (BIA 9-1067)	Pre-dose, ½, 1, 1½, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 and 72 h after dose.	Pharmacokinetic parameters of BIA 9-1067. For tmax = time to Cmax values are presented as median with range values.
AUC0-t - Area Under the Plasma Concentration-time Curve to Last Measurable Time Point (BIA 9-1067)	Pre-dose, ½, 1, 1½, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 and 72 h after dose.	Mean pharmacokinetic parameters of BIA 9-1067

Trial Locations

Locations (1)

Algorithme Pharma Inc.; 🇨🇦 Mount-Royal, Quebec, Canada