Clinical trial NCT03480243: Study to Evaluate the Effect of Coadministered Erythromycin on the Pharmacokinetics and Safety of Padsevonil
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Pharmacokinetics
Keywords: Padsevonil
Lead sponsor: UCB Pharma
Sponsor class: INDUSTRY
First posted: 2018-03-29
Enrollment: 28
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: BASIC_SCIENCE

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.


Eligibility criteria: 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

Primary outcomes:
measure: Maximum Observed Plasma Concentration (Cmax) of Padsevonil for Single Dose
timeFrame: 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
measure: Area Under the Plasma Concentration-time Curve From Time Zero to 12 Hours (AUC(0-12)) of Padsevonil for Single Dose
timeFrame: 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
measure: Maximum Observed Steady-state Plasma Concentration (Cmax, ss) of Padsevonil for Multiple Doses
timeFrame: 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)
measure: Area Under the Plasma Concentration-time Curve Over a Dosing Interval (12 Hours) (AUCtau) of Padsevonil for Multiple Doses
timeFrame: 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 outcomes:
measure: Time of Maximum Plasma Concentration (Tmax) of Padsevonil for Single Dose
timeFrame: Blood samples were taken at specific time points from pre-dose to 12 hours post first dose of Padsevonil for each Treatment Period
measure: Minimum Observed Plasma Concentration (Cmin) of Padsevonil for Single Dose
timeFrame: Blood samples were taken at specific time points from pre-dose to 12 hours post first dose of Padsevonil for each Treatment Period
measure: Time of Maximum Plasma Concentration (Tmax) of Padsevonil for Multiple Doses
timeFrame: 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)
measure: Apparent Terminal Elimination Half-life at Steady-state (t1/2,ss) of Padsevonil for Multiple Doses in Plasma
timeFrame: 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)
measure: Predose Observed Plasma Concentration (Ctrough) of Padsevonil for Multiple Doses
timeFrame: 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)
measure: Apparent Total Clearance at Steady-state (CL/Fss) of Padsevonil for Multiple Doses in Plasma
timeFrame: 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)
measure: Apparent Elimination Rate Constant (Lambdaz) of Padsevonil for Multiple Doses in Plasma
timeFrame: 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)
measure: Maximum Observed Plasma Concentration (Cmax) of Padsevonil Metabolites (1 and 2) for Single Dose
timeFrame: Blood samples were taken at specific time points from pre-dose to 12 hours post first dose of Padsevonil for each Treatment Period
measure: 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
timeFrame: Blood samples were taken at specific time points from pre-dose to 12 hours post first dose of Padsevonil for each Treatment Period
measure: Area Under the Plasma Concentration-time Curve Over a Dosing Interval (12 Hours) (AUCtau) of Padsevonil Metabolites (1 and 2) for Multiple Doses
timeFrame: 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)
measure: Maximum Observed Steady-state Plasma Concentration (Cmax, ss) of Padsevonil Metabolites (1 and 2) for Multiple Doses
timeFrame: 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)
measure: Metabolite-to-parent Ratio for Cmax of Padsevonil Metabolites (1 and 2) in Plasma
timeFrame: Blood samples were taken at specific time points from pre-dose to 12 hours post dose of Padsevonil for each Treatment Period
measure: Metabolite-to-parent Ratio for AUC(0-12) of Padsevonil Metabolites (1 and 2) in Plasma
timeFrame: Blood samples were taken at specific time points from pre-dose to 12 hours post first dose of Padsevonil for each Treatment Period
measure: Metabolite-to-parent Ratio for AUCtau of Padsevonil Metabolites (1 and 2) in Plasma
timeFrame: 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)
measure: Renal Clearance (CLr) of Padsevonil and Metabolites (1 and 2) for Single Dose in Urine
timeFrame: Urine samples were taken 0 to 12 hours post first dose of Padsevonil during each Treatment Period
measure: Renal Clearance (CLr) of Padsevonil and Metabolites (1 and 2) for Multiple Doses in Urine
timeFrame: 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
measure: Cumulative Amount (Ae) of Padsevonil and Metabolites (1, 2, and 3) Excreted Into the Urine for Single Dose
timeFrame: Urine samples were taken 0 to 12 hours post first dose of Padsevonil during each Treatment Period
measure: Cumulative Amount (Ae) of Padsevonil and Metabolites (1, 2, and 3) Excreted Into the Urine for Multiple Doses
timeFrame: 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
measure: Fraction (fe) of Padsevonil and Metabolites (1, 2, and 3) Excreted Into the Urine for Single Dose
timeFrame: Urine samples were taken 0 to 12 hours post first dose of Padsevonil during each Treatment Period
measure: Fraction (fe) of Padsevonil and Metabolites (1, 2, and 3) Excreted Into the Urine for Multiple Doses
timeFrame: 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
measure: Formation Clearance (CLform) of Padsevonil Metabolites (1, 2, and 3) in the Urine for Single Dose
timeFrame: Urine samples were taken 0 to 12 hours post first dose of Padsevonil during each Treatment Period
measure: Formation Clearance (CLform) of Padsevonil Metabolites (1, 2, and 3) in the Urine for Multiple Doses
timeFrame: 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
measure: Percentage of Participants Experiencing Treatment-Emergent Serious Adverse Events (SAEs) During the Study
timeFrame: From beginning of the first Treatment Period (Day 1) to the Safety Follow-up Visit (up to 48 days )
measure: Percentage of Participants Experiencing Treatment-Emergent Non-serious Adverse Events (AEs) During the Study
timeFrame: From beginning of the first Treatment Period (Day 1) to the Safety Follow-up Visit (up to 48 days )
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Up0057 001
Study officials:
affiliation: 001 844 599 2273 (UCB)
name: UCB Cares
role: STUDY_DIRECTOR
References: