Study to Evaluate the Effect of Coadministered Erythromycin on the Pharmacokinetics and Safety of Padsevonil

Pharmacokinetics Clinical Trial

Official title:

An Open-label, Fixed-sequence Study in Healthy Study Participants to Evaluate the Effect of Coadministered Erythromycin on the Pharmacokinetics and Safety of Padsevonil

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03480243
• Other study ID #: UP0057
• Secondary ID: 2017-004694-13
• Status: Completed
• Phase: Phase 1
• Start date: March 27, 2018
• Est. completion date: August 2, 2018

Study information

• Verified date: June 2021
• Source: UCB Pharma
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate and compare the Pharmacokinetics (PK) of concomitant administration of Padsevonil (PSL) in the presence and absence of erythromycin in healthy study participants.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 28
• Est. completion date: August 2, 2018
• Est. primary completion date: August 2, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

Inclusion Criteria:

• Study participant is male or female and between 18 and 55 years of age (inclusive)

• Study participant is of a body weight of at least 50 kg for males and 45 kg for females, as determined by a body mass index (BMI) between 18 and 30 kg/m^2

• Female study participants use an efficient form of contraception for the duration of the study (unless menopausal). Hormonal contraception may be susceptible to an interaction with the Investigational Medicinal Product (IMP), which may reduce the efficacy of the contraception method. The potential for reduced efficacy of any hormonal contraception methods requires that a barrier method (preferably male condom) also be used

• Study participant has clinical laboratory test results within the local reference ranges or values are considered as not clinically relevant by the investigator and approved by the UCB Study Physician

• Study participant has Blood Pressure (BP) and pulse rate within normal range in supine position after 10 minutes of rest

• Male study participant agrees that, during the study period, when having sexual intercourse with a woman of childbearing potential, he will use an efficient barrier contraceptive (condom plus spermicide) AND that the respective partner will use an additional efficient contraceptive method

Exclusion Criteria:

• Study participant has previously received Investigational Medicinal Product (IMP) in this study

• Study participant has participated in another study of an IMP (or a medical device) within the previous 3 months before Screening (or within 5 half-lives for the IMP, whichever is longer) or is currently participating in another study of an IMP (or a medical device)

• Study participant has a history of drug or alcohol dependency within the previous 6 months or tests positive for alcohol (breath test) and/or drugs of abuse (urine test) at the Screening Visit or at any time during confinement

• Study participant has made a blood or plasma donation or has had a comparable blood loss (>400 mL) within the last 3 months prior to the Screening Visit

• Study participant smokes more than 5 cigarettes per day (or equivalent) or has done so within 6 months prior to the Screening Visit

• Study participant is taking any concomitant medication currently or within 2 weeks prior to the first day of dosing with the exception of paracetamol (acetaminophen)

• Study participant has any clinically relevant Electrocardiogram (ECG) finding at the Screening Visit or confinement

• Study participant has a history within the last 5 years or present condition of malignancy, with the exception of basal cell carcinoma

• Female study participant tests positive for pregnancy, plans to get pregnant during the participation in the study, or who is breastfeeding

Related Conditions & MeSH terms

• Pharmacokinetics

Intervention

Drug:
• Padsevonil (UCB0942)
Pharmaceutical Form: film-coated tablet Route of Administration: Oral use
• Erythromycin
Pharmaceutical Form: film-coated tablet Route of Administration: Oral use

Locations

Country	Name	City	State
United Kingdom	Up0057 001	London

Sponsors (1)

Lead Sponsor	Collaborator
UCB Biopharma S.P.R.L.

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum Observed Plasma Concentration (Cmax) of Padsevonil for Single Dose	Cmax: The maximum observed plasma concentration of padsevonil for single dose . Cmax was expressed in nanograms per milliliter (ng/mL).	Predose and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8, and 12 hours postdose on Day 1, 12, and 26
Primary	Area Under the Plasma Concentration-time Curve From Time Zero to 12 Hours (AUC(0-12)) of Padsevonil for Single Dose	AUC(0-12): The area under the plasma concentration-time curve from time zero to 12 hours of padsevonil for single dose . AUC(0-12) was expressed in hours times nanograms per milliliter (hours*ng/mL).	Predose and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8, and 12 hours postdose on Day 1, 12, and 26
Primary	Maximum Observed Steady-state Plasma Concentration (Cmax, ss) of Padsevonil for Multiple Doses	Cmax, ss: The maximum observed steady-state plasma concentration of padsevonil for multiple doses. Cmax, ss was expressed in nanograms per millilitre (ng/mL).	Blood samples were taken at specific time points from pre-dose to 72 hours post last dose of Padsevonil (PSL) (Treatment Period 1 and 2); from pre-dose to 120 hours post last dose of PSL (Treatment Period 3)
Primary	Area Under the Plasma Concentration-time Curve Over a Dosing Interval (12 Hours) (AUCtau) of Padsevonil for Multiple Doses	AUCtau: The area under the plasma concentration-time curve over a dosing interval (12 hours) of padsevonil for multiple doses. AUC(tau) was expressed in hours times nanograms per millilitre (hours*ng/mL).	Blood samples were taken at specific time points from pre-dose to 72 hours post last dose of Padsevonil (PSL) (Treatment Period 1 and 2); from pre-dose to 120 hours post last dose of PSL (Treatment Period 3)
Secondary	Time of Maximum Plasma Concentration (Tmax) of Padsevonil for Single Dose	Tmax: The time of maximum plasma concentration of padsevonil for single dose. Tmax was expressed in hours (h).	Blood samples were taken at specific time points from pre-dose to 12 hours post first dose of Padsevonil for each Treatment Period
Secondary	Minimum Observed Plasma Concentration (Cmin) of Padsevonil for Single Dose	Cmin: The minimum observed plasma concentration of padsevonil for single dose. Cmin was expressed in nanograms per millilitre (ng/mL).	Blood samples were taken at specific time points from pre-dose to 12 hours post first dose of Padsevonil for each Treatment Period
Secondary	Time of Maximum Plasma Concentration (Tmax) of Padsevonil for Multiple Doses	Tmax: The time of maximum plasma concentration of padsevonil for multiple doses. Tmax was expressed in hours (h).	Blood samples were taken at specific time points from pre-dose to 72 hours post last dose of Padsevonil (PSL) (Treatment Period 1 and 2); from pre-dose to 120 hours post last dose of PSL (Treatment Period 3)
Secondary	Apparent Terminal Elimination Half-life at Steady-state (t1/2,ss) of Padsevonil for Multiple Doses in Plasma	t½,ss: The apparent terminal elimination half-life at steady-state of padsevonil for multiple doses in plasma. t1/2, ss was expressed in hours (h).	Blood samples were taken at specific time points from pre-dose to 72 hours post last dose of Padsevonil (PSL) (Treatment Period 1 and 2); from pre-dose to 120 hours post last dose of PSL (Treatment Period 3)
Secondary	Predose Observed Plasma Concentration (Ctrough) of Padsevonil for Multiple Doses	Ctrough: The predose observed plasma concentration of padsevonil for multiple doses. Ctrough was expressed in nanograms per millilitre (ng/mL).	Blood samples were taken at specific time points from pre-dose to 72 hours post last dose of Padsevonil (PSL) (Treatment Period 1 and 2); from pre-dose to 120 hours post last dose of PSL (Treatment Period 3)
Secondary	Apparent Total Clearance at Steady-state (CL/Fss) of Padsevonil for Multiple Doses in Plasma	CL/Fss: The apparent total clearance at steady-state of padsevonil for multiple doses in plasma. CL/Fss was expressed in milliliters per hour (mL/hour).	Blood samples were taken at specific time points from pre-dose to 72 hours post last dose of Padsevonil (PSL) (Treatment Period 1 and 2); from pre-dose to 120 hours post last dose of PSL (Treatment Period 3)
Secondary	Apparent Elimination Rate Constant (Lambdaz) of Padsevonil for Multiple Doses in Plasma	lambdaz: The apparent elimination rate constant of padsevonil for multiple doses in plasma. Lambdaz was expressed in liters per hour (l/hour).	Blood samples were taken at specific time points from pre-dose to 72 hours post last dose of Padsevonil (PSL) (Treatment Period 1 and 2); from pre-dose to 120 hours post last dose of PSL (Treatment Period 3)
Secondary	Maximum Observed Plasma Concentration (Cmax) of Padsevonil Metabolites (1 and 2) for Single Dose	Cmax: The maximum plasma concentration of padsevonil metabolites (1 and 2) for single dose. Cmax was expressed in nanograms per milliliter (ng/mL).	Blood samples were taken at specific time points from pre-dose to 12 hours post first dose of Padsevonil for each Treatment Period
Secondary	Area Under the Plasma Concentration-time Curve From Time Zero to 12 Hours (AUC(0-12)) of Padsevonil Metabolites (1 and 2) for Single Dose	AUC(0-12): The area under the plasma concentration-time curve from time zero to 12 hours of padsevonil metabolites (1 and 2) for single dose. AUC(0-12) was expressed in hours times nanograms per milliliter (hours*ng/mL).	Blood samples were taken at specific time points from pre-dose to 12 hours post first dose of Padsevonil for each Treatment Period
Secondary	Area Under the Plasma Concentration-time Curve Over a Dosing Interval (12 Hours) (AUCtau) of Padsevonil Metabolites (1 and 2) for Multiple Doses	AUCtau: The area under the plasma concentration-time curve over a dosing interval (12 hours) of padsevonil metabolites (1 and 2) for multiple doses. AUCtau was expressed in hours times nanograms per milliliter (hours*ng/mL).	Blood samples were taken at specific time points from pre-dose to 72 hours post last dose of Padsevonil (PSL) (Treatment Period 1 and 2); from pre-dose to 120 hours post last dose of PSL (Treatment Period 3)
Secondary	Maximum Observed Steady-state Plasma Concentration (Cmax, ss) of Padsevonil Metabolites (1 and 2) for Multiple Doses	Cmax, ss: The maximum observed steady-state plasma concentration of padsevonil metabolites (1 and 2) for multiple doses. Cmax, ss was expressed in nanograms per millilitre (ng/mL).	Blood samples were taken at specific time points from pre-dose to 72 hours post last dose of Padsevonil (PSL) (Treatment Period 1 and 2); from pre-dose to 120 hours post last dose of PSL (Treatment Period 3)
Secondary	Metabolite-to-parent Ratio for Cmax of Padsevonil Metabolites (1 and 2) in Plasma	Metabolite-to-parent ratio calculated as: Cmax of padsevonil metabolites (1 and 2) divided by Cmax of padsevonil following a single dose in plasma. Metabolite-to-parent ratio for Cmax was expressed as ratio.	Blood samples were taken at specific time points from pre-dose to 12 hours post dose of Padsevonil for each Treatment Period
Secondary	Metabolite-to-parent Ratio for AUC(0-12) of Padsevonil Metabolites (1 and 2) in Plasma	Metabolite-to-parent ratio calculated as: AUC(0-12)of padsevonil metabolites (1 and 2) divided by AUC(0-12) of padsevonil following a single dose in plasma. Metabolite-to-parent ratio for AUC(0-12) was expressed as ratio.	Blood samples were taken at specific time points from pre-dose to 12 hours post first dose of Padsevonil for each Treatment Period
Secondary	Metabolite-to-parent Ratio for AUCtau of Padsevonil Metabolites (1 and 2) in Plasma	Metabolite-to-parent ratio calculated as: AUCtau of padsevonil metabolites (1 and 2) divided by AUCtau of padsevonil following multiple dosing in plasma. Metabolite-to-parent ratio for AUCtau was expressed as ratio.	Blood samples were taken at specific time points from pre-dose to 72 hours post last dose of Padsevonil (PSL) (Treatment Period 1 and 2); from pre-dose to 120 hours post last dose of PSL (Treatment Period 3)
Secondary	Renal Clearance (CLr) of Padsevonil and Metabolites (1 and 2) for Single Dose in Urine	CLr: The renal clearance of padsevonil and its metabolites (1 and 2) for single dose in urine. CLr was expressed in milliliters per hour (mL/hour).	Urine samples were taken 0 to 12 hours post first dose of Padsevonil during each Treatment Period
Secondary	Renal Clearance (CLr) of Padsevonil and Metabolites (1 and 2) for Multiple Doses in Urine	CLr: The renal clearance of padsevonil and its metabolites (1 and 2) for multiple doses in urine. CLr was expressed in milliliters per hour (mL/hour).	Urine samples were taken 0 to 12 hours, 12 to 24 hours,and 24 to 48 hours post last PSL dose during Treatment Period 1 and 2; 0 to 12 hours, 12 to 24 hours, 24 to 48 hours, 48 to 72 hours, and 72 to 96 hours post last dose of PSL during Treatment Period 3
Secondary	Cumulative Amount (Ae) of Padsevonil and Metabolites (1, 2, and 3) Excreted Into the Urine for Single Dose	Ae: The cumulative amount of padsevonil and its metabolites (1, 2, and 3) excreted into the urine for single dose. Ae was expressed in milligrams (mg).	Urine samples were taken 0 to 12 hours post first dose of Padsevonil during each Treatment Period
Secondary	Cumulative Amount (Ae) of Padsevonil and Metabolites (1, 2, and 3) Excreted Into the Urine for Multiple Doses	Ae: The cumulative amount of padsevonil and its metabolites (1, 2, and 3) excreted into the urine for multiple doses. Ae was expressed in milligrams (mg).	Urine samples were taken 0 to 12 hours, 12 to 24 hours,and 24 to 48 hours post last PSL dose during Treatment Period 1 and 2; 0 to 12 hours, 12 to 24 hours, 24 to 48 hours, 48 to 72 hours, and 72 to 96 hours post last dose of PSL during Treatment Period 3
Secondary	Fraction (fe) of Padsevonil and Metabolites (1, 2, and 3) Excreted Into the Urine for Single Dose	fe: The fraction of padsevonil or metabolites (1, 2, and 3) excreted into the urine for single dose. fe was expressed in percentage (%).	Urine samples were taken 0 to 12 hours post first dose of Padsevonil during each Treatment Period
Secondary	Fraction (fe) of Padsevonil and Metabolites (1, 2, and 3) Excreted Into the Urine for Multiple Doses	fe: The fraction of padsevonil and its metabolites (1, 2, and 3) excreted into the urine for multiple doses. fe was expressed in percentage (%).	Urine samples were taken 0 to 12 hours, 12 to 24 hours,and 24 to 48 hours post last PSL dose during Treatment Period 1 and 2; 0 to 12 hours, 12 to 24 hours, 24 to 48 hours, 48 to 72 hours, and 72 to 96 hours post last dose of PSL during Treatment Period 3
Secondary	Formation Clearance (CLform) of Padsevonil Metabolites (1, 2, and 3) in the Urine for Single Dose	CLform: The formation clearance of padsevonil metabolites (1, 2, and 3) in the urine for single dose. CLform was expressed in milliliters per hour (mL/hour).	Urine samples were taken 0 to 12 hours post first dose of Padsevonil during each Treatment Period
Secondary	Formation Clearance (CLform) of Padsevonil Metabolites (1, 2, and 3) in the Urine for Multiple Doses	CLform: The formation clearance of padsevonil metabolites (1, 2, and 3) in the urine for multiple doses. CLform was expressed in milliliters per hour (mL/hour).	Urine samples were taken 0 to 12 hours, 12 to 24 hours,and 24 to 48 hours post last PSL dose during Treatment Period 1 and 2; 0 to 12 hours, 12 to 24 hours, 24 to 48 hours, 48 to 72 hours, and 72 to 96 hours post last dose of PSL during Treatment Period 3
Secondary	Percentage of Participants Experiencing Treatment-Emergent Serious Adverse Events (SAEs) During the Study	An SAE is any untoward medical occurrence that at any dose: Results in death; Is life-threatening; Requires in patient hospitalization or prolongation of existing hospitalization; Is a congenital anomaly or birth defect; Is an infection that requires treatment parenteral antibiotics; Other important medical events which based on medical or scientific judgement may jeopardize the patients, or may require medical or surgical intervention to prevent any of the above.	From beginning of the first Treatment Period (Day 1) to the Safety Follow-up Visit (up to 48 days )
Secondary	Percentage of Participants Experiencing Treatment-Emergent Non-serious Adverse Events (AEs) During the Study	Treatment-emergent Adverse Events (TEAEs) were defined as those events which started on or after the date of first dose of UP0057 IMP, or events in which severity worsened on or after the date of first dose of UP0057 study medication.	From beginning of the first Treatment Period (Day 1) to the Safety Follow-up Visit (up to 48 days )