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

NCT03480243 | Completed Phase 1 Results

• 2 other identifiers: UP00572017-004694-13
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

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.

Conditions

Pharmacokinetics

Keywords

Padsevonil

Outcome Measures

Primary Outcomes (4)

• 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

• 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

• 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)

• 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 Outcomes (24)

• 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

• 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

• 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)

• 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)

• 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)

Study Arms (1)

Padsevonil and Erythromycin

EXPERIMENTAL

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

Drug: Padsevonil (UCB0942); Drug: Erythromycin

Interventions

Padsevonil (UCB0942) DRUG

* Pharmaceutical Form: film-coated tablet * Route of Administration: Oral use

Padsevonil and Erythromycin

Erythromycin DRUG

* Pharmaceutical Form: film-coated tablet * Route of Administration: Oral use

Padsevonil and Erythromycin

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• UCB Biopharma S.P.R.L.: lead

Study Sites (1)

Up0057 001

London, United Kingdom

Location

Related Publications (1)

• Chanteux H, MacPherson M, Kramer H, Otoul C, Okagaki T, Rospo C, De Bruyn S, Watling M, Bani M, Sciberras D. Overview of preclinical and clinical studies investigating pharmacokinetics and drug-drug interactions of padsevonil. Expert Opin Drug Metab Toxicol. 2024 Aug;20(8):841-855. doi: 10.1080/17425255.2024.2373108. Epub 2024 Jul 9.

  PMID: 38932723 DERIVED

MeSH Terms

Interventions

padsevonil; Erythromycin

Intervention Hierarchy (Ancestors)

Macrolides; Polyketides; Lactones; Organic Chemicals

Results Point of Contact

• Title: UCB
• Organization: Cares

UCBCares@ucb.com

+1844 599

Study Officials

• UCB Cares

  001 844 599 2273 (UCB)

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 21, 2018
• First Posted: March 29, 2018
• Study Start: March 27, 2018
• Primary Completion: August 2, 2018
• Study Completion: August 2, 2018
• Last Updated: July 12, 2021
• Results First Posted: July 12, 2021

Record last verified: 2021-06

Locations

GB (1)