A Study to Evaluate the Pharmacokinetics and Safety of Brivaracetam in Healthy Chinese Subjects

Healthy Participants Clinical Trial

Official title:

An Open-label, Single-arm Study to Evaluate the Pharmacokinetics and Safety of a Single and Multiple Oral Doses of Brivaracetam in Healthy Adult Chinese Subjects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04882540
• Other study ID #: EP0101
• Status: Completed
• Phase: Phase 1
• Start date: May 19, 2021
• Est. completion date: June 8, 2021

Study information

• Verified date: May 2022
• Source: UCB Pharma
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of the study is to assess the pharmacokinetics, safety, and tolerability of brivaracetam after a single dose and multiple doses in healthy adult Chinese Study Participants.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: June 8, 2021
• Est. primary completion date: June 8, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 45 Years

Eligibility

Inclusion Criteria:

• An Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved written Informed Consent form is signed and dated by the subject

• Subject is considered reliable and capable of adhering to the protocol (eg, able to understand and complete diaries), visit schedule, or medication intake according to the judgment of the Investigator

• Subjects are Chinese males and females born in China between 18 and 45 years of age (both inclusive) whose parents are of Chinese origin

• Subjects with body mass index (BMI) from 19 to 24 kg/m^2 (both inclusive). Minimum body weight is equal to or more than 50 kg

• Subjects with supine blood pressure levels of between 90 to 150 and 60 to 90 mmHg (inclusive) for systolic and diastolic, respectively, with pulse rate of 50 to 100 beats per minute (bpm) (supine position, inclusive) at Screening Visit

• Subjects without clinically relevant abnormalities in a standard 12-lead Electrocardiogram (ECG) at Screening Visit judged by the Investigators

• Subjects with laboratory values within the reference range at Screening Visit, or those with values exceeding the reference range but judged by the Investigators to be not clinically significant to their participation in the study

Exclusion Criteria:

• Subject has participated in another study of an investigational medicinal product (IMP) (or a medical device) within the previous 30 days or is currently participating in another study of an IMP (or a medical device)

• Subject has any medical or psychiatric condition that, in the opinion of the Investigator, could jeopardize or would compromise the subject's ability to participate in this study

• Pregnant, lactating, or sexually active women with childbearing potential who are not using a medically accepted birth control method

• Subject has a known hypersensitivity to any components of the IMP or any of its excipients

• Subjects with any previous or current cardiovascular, respiratory, hepatic, renal, digestive, endocrine, or nervous system disorder that may affect absorption, secretion, metabolism, or excretion of the investigational product per Investigator judgement

• Subjects showing a positive result for hepatitis B surface antigen, hepatitis C virus antibody, human immunodeficiency virus antibody, or syphilis test at Screening Visit

Related Conditions & MeSH terms

• Healthy Participants

Intervention

Drug:
• brivaracetam
Pharmaceutical form: Film-coated tablets Concentration: 100 mg tablets Route of administration: Oral use

Locations

Country	Name	City	State
China	Ep0101 101	Shanghai	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
UCB Biopharma SRL

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Plasma Concentration of BRV and Its Metabolites (Ucb-42145, Ucb-100406-1, ucb107092-1) After Single Dose		Day 1: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48, and 72 hours postdose
Primary	Plasma Concentration of BRV and Its Metabolites (Ucb-42145, Ucb-100406-1, ucb107092-1) After Multiple Dose		Predose on Day 5, 6, 7, 8, and 9; Day 10: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48, and 72 hours postdose
Primary	Area Under the Plasma Concentration-time Curve From Zero to the Time of the Last Measured Concentration Above the Limit of Quantification (AUC(0-t)) of Brivaracetam for Single Dose	AUC(0-t) was defined as the area under the plasma concentration-time curve from zero to the time of the last measured concentration above the limit of quantification.	Day 1: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48, and 72 hours postdose
Primary	Maximum Observed Plasma Concentration (Cmax) of Brivaracetam for Single Dose	Cmax was defined as the maximum observed plasma concentration.	Day 1: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48, and 72 hours postdose
Primary	Area Under the Plasma Concentration-time Curve From 0 to 12 Hours at Steady State (AUC(0-12),ss) of Brivaracetam for Multiple Dose	AUC(0-12),ss was defined as the area under the plasma concentration-time curve from 0 to 12 hours at steady state.	Day 10: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 9, and 12 hours postdose
Primary	Maximum Plasma Concentration at Steady State (Cmax,ss) of Brivaracetam for Multiple Dose	Cmax,ss was defined as the maximum plasma concentration at steady state.	Day 10: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48, and 72 hours postdose
Primary	Number of Participants With Treatment-emergent Adverse Events (TEAEs) During the Study	An adverse event (AE) is any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. Treatment-emergent AEs (TEAEs) were defined as those events that start on or after the time of first investigational medicinal product (IMP) administration, or whose severity worsens on or after the date of first administration of the IMP.	From Baseline to the end of Safety Follow-up (approximately 6 weeks)
Secondary	Time to Reach Maximum Concentration (Tmax) of Brivaracetam, Ucb-42145, Ucb-100406-1 and ucb107092-1 in Plasma for Single Dose	Tmax was defined as the time to reach maximum concentration. ucb-42145, ucb-100406-1, and ucb107092-1 are the metabolites of brivaracetam.	Day 1: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48, and 72 hours postdose
Secondary	Terminal Elimination Half-life (t1/2) of Brivaracetam, Ucb-42145, Ucb-100406-1 and ucb107092-1 in Plasma for Single Dose	t1/2 was defined as the terminal elimination half-life. ucb-42145, ucb-100406-1, and ucb107092-1 are the metabolites of brivaracetam.	Day 1: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48, and 72 hours postdose
Secondary	Rate Constant of Elimination (?z) of Brivaracetam, Ucb-42145, Ucb-100406-1 and ucb107092-1 in Plasma for Single Dose	?z was defined as the rate constant of elimination. ucb-42145, ucb-100406-1, and ucb107092-1 are the metabolites of brivaracetam.	Day 1: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48, and 72 hours postdose
Secondary	Mean Residence Time (MRT) of Brivaracetam in Plasma for Single Dose	MRT was defined as the mean residence time.	Day 1: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48, and 72 hours postdose
Secondary	Area Under the Plasma Concentration-time Curve From 0 to Infinite Time (AUC) of Brivaracetam, Ucb-42145, Ucb-100406-1 and ucb107092-1 for Single Dose	AUC was defined as the area under the plasma concentration-time curve from 0 to infinite time. ucb-42145, ucb-100406-1, and ucb107092-1 are the metabolites of brivaracetam.	Day 1: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48, and 72 hours postdose
Secondary	Apparent Total Body Clearance (CL/F) of Brivaracetam in Plasma for Single Dose	CL/F was defined as the apparent total body clearance.	Day 1: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48, and 72 hours postdose
Secondary	Apparent Volume of Distribution (Vz/F) of Brivaracetam in Plasma for Single Dose	Vz/F was defined as the apparent volume of distribution.	Day 1: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48, and 72 hours postdose
Secondary	Cmax of Ucb-42145, Ucb-100406-1 and ucb107092-1 for Single Dose	Cmax was defined as the maximum plasma concentration. ucb-42145, ucb-100406-1, and ucb107092-1 are the metabolites of brivaracetam.	Day 1: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48, and 72 hours postdose
Secondary	AUC (0-t) of Ucb-42145, Ucb-100406-1 and ucb107092-1 in Plasma for Single Dose	AUC(0-t) was defined as the area under the plasma concentration-time curve from zero to the time of the last measured concentration above the limit of quantification. ucb-42145, ucb-100406-1, and ucb107092-1 are the metabolites of brivaracetam.	Day 1: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48, and 72 hours postdose
Secondary	Tmax of Brivaracetam, Ucb-42145, Ucb-100406-1 and ucb107092-1 in Plasma for Multiple Dose	tmax is the time to reach maximum plasma concentration. ucb-42145, ucb-100406-1, and ucb107092-1 are the metabolites of brivaracetam.	Day 10: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48, and 72 hours postdose
Secondary	t1/2 of Brivaracetam, Ucb-42145, Ucb-100406-1 and ucb107092-1 in Plasma for Multiple Dose	t1/2 is the terminal elimination half-life. ucb-42145, ucb-100406-1, and ucb107092-1 are the metabolites of brivaracetam.	Day 10: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48, and 72 hours postdose
Secondary	?z of Brivaracetam, Ucb-42145, Ucb-100406-1 and ucb107092-1 in Plasma for Multiple Dose	?z is the rate constant of elimination. ucb-42145, ucb-100406-1, and ucb107092-1 are the metabolites of brivaracetam.	Day 10: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48, and 72 hours postdose
Secondary	Minimum Plasma Concentration at Steady State (Cmin,ss) of Brivaracetam in Plasma for Multiple Dose	Cmin,ss is the minimum plasma concentration at steady state.	Day 10: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48, and 72 hours postdose
Secondary	Average Plasma Concentration at Steady State (Cav,ss) of Brivaracetam in Plasma for Multiple Dose	Cav,ss is the average plasma concentration at steady state.	Day 10: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48, and 72 hours postdose
Secondary	Apparent Total Body Clearance at Steady State (CLss/F) of Brivaracetam in Plasma for Multiple Dose	CLss/F is the apparent total body clearance at steady state.	Day 10: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48, and 72 hours postdose
Secondary	Vz/F of Brivaracetam in Plasma for Multiple Dose	Vz/F is the apparent volume of distribution.	Day 10: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48, and 72 hours postdose
Secondary	Cmax,ss of Ucb-42145, Ucb-100406-1, and ucb107092-1 in Plasma for Multiple Dose	Cmax,ss is the maximum plasma concentration at steady state. ucb-42145, ucb-100406-1, and ucb107092-1 are the metabolites of brivaracetam.	Day 10: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48, and 72 hours postdose
Secondary	Area Under the Curve From 0 to 12 Hours at Steady State (AUC(0-12),ss) of Ucb-42145, Ucb-100406-1 and ucb107092-1 in Plasma for Multiple Dose	AUC(0-12),ss is the area under the curve from 0 to 12 hours at steady state. ucb-42145, ucb-100406-1, and ucb107092-1 are the metabolites of brivaracetam.	Day 10: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 9, and 12 hours postdose
Secondary	Peak Trough Fluctuation (PTF) of Brivaracetam in Steady-state for Multiple Dose	PTF was calculated as (Cmax,ss-Cmin,ss)/Cav,ss.	Day 10: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48, and 72 hours postdose
Secondary	Accumulation Ratio Calculated From AUC at Steady State and AUC After Single Dose (RAUC) of Brivaracetam for Multiple Dose	Accumulation ratio (RAUC) was calculated as AUC(0-12),ss divided by AUC(0-12).	Day 10: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 9, and 12 hours postdose
Secondary	Accumulation Ratio Calculated From Cmax at Steady State and Cmax After Single Dose (Rmax) of Brivaracetam for Multiple Dose	Accumulation ratio (Rmax) was calculated as Cmax,ss divided by Cmax.	Day 10: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48, and 72 hours postdose