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

Phase 1

Completed

Conditions: Pharmacokinetics

Interventions: Drug: Padsevonil (UCB0942)
Drug: Erythromycin

Registration Number: NCT03480243

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

Brief 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 28

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Padsevonil and Erythromycin	Padsevonil (UCB0942)	Treatment Period 1 (Day 1 to Day 11): * Padsevonil 100 mg twice daily (bid) on Day 1 to Day 4 * Padsevonil 100 mg single dose on Day 5 * 1 week of wash-out (from evening of Day 5 to Day 11) Treatment Period 2 (Day 12 to 22): * Padsevonil 100 mg twice daily (bid) on Day 12 to Day 15 * Padsevonil 100 mg single dose on Day 16 * 1 week of wash-out (from evening of Day 16 to Day 22) Treatment Period 3 (Day 23 to Day 38): * Erythromycin 500 mg twice daily (bid) on Day 23 to Day 25 * Padsevonil 100 mg bid and erythromycin 500 mg bid on Day 26 to Day 32 * Padsevonil 100 mg single dose on Day 33 * Erythromycin 500 mg twice daily (bid) on Day 33 to Day 36 * Erythromycin 500 mg single dose on Day 37
Padsevonil and Erythromycin	Erythromycin	Treatment Period 1 (Day 1 to Day 11): * Padsevonil 100 mg twice daily (bid) on Day 1 to Day 4 * Padsevonil 100 mg single dose on Day 5 * 1 week of wash-out (from evening of Day 5 to Day 11) Treatment Period 2 (Day 12 to 22): * Padsevonil 100 mg twice daily (bid) on Day 12 to Day 15 * Padsevonil 100 mg single dose on Day 16 * 1 week of wash-out (from evening of Day 16 to Day 22) Treatment Period 3 (Day 23 to Day 38): * Erythromycin 500 mg twice daily (bid) on Day 23 to Day 25 * Padsevonil 100 mg bid and erythromycin 500 mg bid on Day 26 to Day 32 * Padsevonil 100 mg single dose on Day 33 * Erythromycin 500 mg twice daily (bid) on Day 33 to Day 36 * Erythromycin 500 mg single dose on Day 37

Primary Outcome Measures

Name	Time	Method
Area Under the Plasma Concentration-time Curve From Time Zero to 12 Hours (AUC(0-12)) of Padsevonil for Single Dose	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	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).
Maximum Observed Steady-state Plasma Concentration (Cmax, ss) of Padsevonil for Multiple Doses	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)	Cmax, ss: The maximum observed steady-state plasma concentration of padsevonil for multiple doses. Cmax, ss was expressed in nanograms per millilitre (ng/mL).
Area Under the Plasma Concentration-time Curve Over a Dosing Interval (12 Hours) (AUCtau) of Padsevonil for Multiple Doses	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)	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).
Maximum Observed Plasma Concentration (Cmax) of Padsevonil for Single Dose	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	Cmax: The maximum observed plasma concentration of padsevonil for single dose . Cmax was expressed in nanograms per milliliter (ng/mL).

Secondary Outcome Measures

Name	Time	Method
Time of Maximum Plasma Concentration (Tmax) of Padsevonil for Single Dose	Blood samples were taken at specific time points from pre-dose to 12 hours post first dose of Padsevonil for each Treatment Period	Tmax: The time of maximum plasma concentration of padsevonil for single dose. Tmax was expressed in hours (h).
Minimum Observed Plasma Concentration (Cmin) of Padsevonil for Single Dose	Blood samples were taken at specific time points from pre-dose to 12 hours post first dose of Padsevonil for each Treatment Period	Cmin: The minimum observed plasma concentration of padsevonil for single dose. Cmin was expressed in nanograms per millilitre (ng/mL).
Time of Maximum Plasma Concentration (Tmax) of Padsevonil for Multiple Doses	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)	Tmax: The time of maximum plasma concentration of padsevonil for multiple doses. Tmax was expressed in hours (h).
Apparent Terminal Elimination Half-life at Steady-state (t1/2,ss) of Padsevonil for Multiple Doses in Plasma	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)	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).
Predose Observed Plasma Concentration (Ctrough) of Padsevonil for Multiple Doses	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)	Ctrough: The predose observed plasma concentration of padsevonil for multiple doses. Ctrough was expressed in nanograms per millilitre (ng/mL).
Apparent Total Clearance at Steady-state (CL/Fss) of Padsevonil for Multiple Doses in Plasma	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)	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).
Apparent Elimination Rate Constant (Lambdaz) of Padsevonil for Multiple Doses in Plasma	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)	lambdaz: The apparent elimination rate constant of padsevonil for multiple doses in plasma. Lambdaz was expressed in liters per hour (l/hour).
Maximum Observed Plasma Concentration (Cmax) of Padsevonil Metabolites (1 and 2) for Single Dose	Blood samples were taken at specific time points from pre-dose to 12 hours post first dose of Padsevonil for each Treatment Period	Cmax: The maximum plasma concentration of padsevonil metabolites (1 and 2) for single dose. Cmax was expressed in nanograms per milliliter (ng/mL).
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	Blood samples were taken at specific time points from pre-dose to 12 hours post first dose of Padsevonil for each Treatment Period	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).
Percentage of Participants Experiencing Treatment-Emergent Serious Adverse Events (SAEs) During the Study	From beginning of the first Treatment Period (Day 1) to the Safety Follow-up Visit (up to 48 days )	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.
Percentage of Participants Experiencing Treatment-Emergent Non-serious Adverse Events (AEs) During the Study	From beginning of the first Treatment Period (Day 1) to the Safety Follow-up Visit (up to 48 days )	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.
Area Under the Plasma Concentration-time Curve Over a Dosing Interval (12 Hours) (AUCtau) of Padsevonil Metabolites (1 and 2) for Multiple Doses	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)	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).
Maximum Observed Steady-state Plasma Concentration (Cmax, ss) of Padsevonil Metabolites (1 and 2) for Multiple Doses	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)	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).
Metabolite-to-parent Ratio for Cmax of Padsevonil Metabolites (1 and 2) in Plasma	Blood samples were taken at specific time points from pre-dose to 12 hours post dose of Padsevonil for each Treatment Period	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.
Metabolite-to-parent Ratio for AUC(0-12) of Padsevonil Metabolites (1 and 2) in Plasma	Blood samples were taken at specific time points from pre-dose to 12 hours post first dose of Padsevonil for each Treatment Period	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.
Metabolite-to-parent Ratio for AUCtau of Padsevonil Metabolites (1 and 2) in Plasma	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)	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.
Renal Clearance (CLr) of Padsevonil and Metabolites (1 and 2) for Single Dose in Urine	Urine samples were taken 0 to 12 hours post first dose of Padsevonil during each Treatment Period	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).
Renal Clearance (CLr) of Padsevonil and Metabolites (1 and 2) for Multiple Doses in Urine	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	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).
Cumulative Amount (Ae) of Padsevonil and Metabolites (1, 2, and 3) Excreted Into the Urine for Single Dose	Urine samples were taken 0 to 12 hours post first dose of Padsevonil during each Treatment Period	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).
Cumulative Amount (Ae) of Padsevonil and Metabolites (1, 2, and 3) Excreted Into the Urine for Multiple Doses	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	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).
Fraction (fe) of Padsevonil and Metabolites (1, 2, and 3) Excreted Into the Urine for Single Dose	Urine samples were taken 0 to 12 hours post first dose of Padsevonil during each Treatment Period	fe: The fraction of padsevonil or metabolites (1, 2, and 3) excreted into the urine for single dose. fe was expressed in percentage (%).
Fraction (fe) of Padsevonil and Metabolites (1, 2, and 3) Excreted Into the Urine for Multiple Doses	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	fe: The fraction of padsevonil and its metabolites (1, 2, and 3) excreted into the urine for multiple doses. fe was expressed in percentage (%).
Formation Clearance (CLform) of Padsevonil Metabolites (1, 2, and 3) in the Urine for Single Dose	Urine samples were taken 0 to 12 hours post first dose of Padsevonil during each Treatment Period	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).
Formation Clearance (CLform) of Padsevonil Metabolites (1, 2, and 3) in the Urine for Multiple Doses	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	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).