Phase 1
Completed N=28
Study to Evaluate the Effect of Coadministered Erythromycin on the Pharmacokinetics and Safety of Padsevonil
Pharmacokinetics
Source: ClinicalTrials.gov NCT03480243 ↗
Enrolled (actual)
28
Serious AEs
0.0%
Results posted
Jul 2021
Primary outcomePrimary: Maximum Observed Plasma Concentration (Cmax) of Padsevonil for Single Dose — 366.6; 385.3; 697.4 ng/mL
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Maximum Observed Plasma Concentration (Cmax) of Padsevonil for Single Dose |
366.6; 385.3; 697.4 | — |
| PRIMARY Area Under the Plasma Concentration-time Curve From Time Zero to 12 Hours (AUC(0-12)) of Padsevonil for Single Dose |
1428; 1571; 2576 | — |
| PRIMARY Maximum Observed Steady-state Plasma Concentration (Cmax, ss) of Padsevonil for Multiple Doses |
475.0; 473.9; 1010 | — |
| PRIMARY Area Under the Plasma Concentration-time Curve Over a Dosing Interval (12 Hours) (AUCtau) of Padsevonil for Multiple Doses |
2049; 2274; 5073 | — |
| SECONDARY Time of Maximum Plasma Concentration (Tmax) of Padsevonil for Single Dose |
3.000; 1.500; 1.500 | — |
| SECONDARY Minimum Observed Plasma Concentration (Cmin) of Padsevonil for Single Dose |
2.857; 5.643; 4.286 | — |
| SECONDARY Time of Maximum Plasma Concentration (Tmax) of Padsevonil for Multiple Doses |
1.750; 1.500; 2.000 | — |
| SECONDARY Apparent Terminal Elimination Half-life at Steady-state (t1/2,ss) of Padsevonil for Multiple Doses in Plasma |
6.465; 6.649; 8.548 | — |
| SECONDARY Predose Observed Plasma Concentration (Ctrough) of Padsevonil for Multiple Doses |
57.03; 68.57; 182.6 | — |
| SECONDARY Apparent Total Clearance at Steady-state (CL/Fss) of Padsevonil for Multiple Doses in Plasma |
48810; 43970; 19710 | — |
| SECONDARY Apparent Elimination Rate Constant (Lambdaz) of Padsevonil for Multiple Doses in Plasma |
0.1049; 0.1006; 0.07975 | — |
| SECONDARY Maximum Observed Plasma Concentration (Cmax) of Padsevonil Metabolites (1 and 2) for Single Dose |
166.6; 158.7; 189.5; 110.5; 94.47; 108.3 | — |
| 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 |
828.3; 824.3; 905.6; 596.5; 534.4; 599.5 | — |
| SECONDARY Area Under the Plasma Concentration-time Curve Over a Dosing Interval (12 Hours) (AUCtau) of Padsevonil Metabolites (1 and 2) for Multiple Doses |
1748; 1993; 2625; 775.1; 813.1; 799.0 | — |
| SECONDARY Maximum Observed Steady-state Plasma Concentration (Cmax, ss) of Padsevonil Metabolites (1 and 2) for Multiple Doses |
232.3; 258.3; 310.3; 118.6; 113.3; 101.8 | — |
| SECONDARY Metabolite-to-parent Ratio for Cmax of Padsevonil Metabolites (1 and 2) in Plasma |
0.4544; 0.4119; 0.2717; 0.3015; 0.2452; 0.1552 | — |
| SECONDARY Metabolite-to-parent Ratio for AUC(0-12) of Padsevonil Metabolites (1 and 2) in Plasma |
0.5799; 0.5246; 0.3515; 0.4176; 0.3401; 0.2327 | — |
| SECONDARY Metabolite-to-parent Ratio for AUCtau of Padsevonil Metabolites (1 and 2) in Plasma |
0.8533; 0.8766; 0.5174; 0.3783; 0.3576; 0.1575 | — |
| SECONDARY Renal Clearance (CLr) of Padsevonil and Metabolites (1 and 2) for Single Dose in Urine |
27.40; 25.80; 19.36; 253.7; 283.0; 255.0 | — |
| SECONDARY Renal Clearance (CLr) of Padsevonil and Metabolites (1 and 2) for Multiple Doses in Urine |
28.43; 25.24; 25.12; 335.0; 325.4; 311.4 | — |
| SECONDARY Cumulative Amount (Ae) of Padsevonil and Metabolites (1, 2, and 3) Excreted Into the Urine for Single Dose |
0.03914; 0.04054; 0.04987; 0.2101; 0.2333; 0.2309 | — |
| SECONDARY Cumulative Amount (Ae) of Padsevonil and Metabolites (1, 2, and 3) Excreted Into the Urine for Multiple Doses |
0.05825; 0.05741; 0.1274; 0.6188; 0.6657; 0.8797 | — |
| SECONDARY Fraction (fe) of Padsevonil and Metabolites (1, 2, and 3) Excreted Into the Urine for Single Dose |
0.03914; 0.04054; 0.04987; 0.2170; 0.2410; 0.2385 | — |
| SECONDARY Fraction (fe) of Padsevonil and Metabolites (1, 2, and 3) Excreted Into the Urine for Multiple Doses |
0.05825; 0.05741; 0.1274; 0.6049; 0.6700; 0.8443 | — |
| SECONDARY Formation Clearance (CLform) of Padsevonil Metabolites (1, 2, and 3) in the Urine for Single Dose |
151.9; 153.4; 92.59; 7365; 5994; 3788 | — |
| SECONDARY Formation Clearance (CLform) of Padsevonil Metabolites (1, 2, and 3) in the Urine for Multiple Doses |
295.3; 294.6; 166.4; 7331; 6622; 2593 | — |
| SECONDARY Percentage of Participants Experiencing Treatment-Emergent Serious Adverse Events (SAEs) During the Study |
0; 0; 0; 0 | — |
| SECONDARY Percentage of Participants Experiencing Treatment-Emergent Non-serious Adverse Events (AEs) During the Study |
100; 11.1; 96.3; 19.2 | — |
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
Data sourced from ClinicalTrials.gov (NCT03480243). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.