A Study to Test the Interaction of Padsevonil With Oral Contraceptives in Healthy Female Participants

NCT04131517 | Terminated Phase 1 Results FDA Drug

• 2 other identifiers: UP00352019-002194-54
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of the study is to investigate the effect of steady-state padsevonil on the pharmacokinetic of a single dose oral contraceptive.

Conditions

Healthy Female Participants

Keywords

Padsevonil; Contraceptives; Healthy female participants

Outcome Measures

Primary Outcomes (8)

• Maximum Observed Plasma Concentration (Cmax) of Ethinylestradiol in Part 1

  Cmax is maximum observed plasma concentration of ethinylestradiol (EE). Values were determined from the observed concentration and time data. This outcome measure was planned to be analyzed for 'Oral Contraceptive Alone' and 'PSL + Oral Contraceptive' arms.

  Day 13, 14, 15, 34, 35, 36 during Treatment Sequence A and on Day 1, 2, 3, 30, 31 and 32 during Treatment Sequence B

• Maximum Observed Plasma Concentration (Cmax) of Levonorgestrel in Part 1

  Cmax is maximum observed plasma concentration of levonorgestrel. Values were determined from the observed concentration and time data. This outcome measure was planned to be analyzed for 'Oral Contraceptive Alone' and 'PSL + Oral Contraceptive' arms.

  Day 13, 14, 15, 34, 35, 36 during Treatment Sequence A and on Day 1, 2, 3, 30, 31 and 32 during Treatment Sequence B

• Maximum Observed Plasma Concentration (Cmax) of Ethinylestradiol in Part 2

  Cmax is maximum observed plasma concentration of ethinylestradiol.

  Day 9, 10, 11, 26, 27 and 28 during Treatment Sequence A and on Day 1, 2, 3, 26, 27 and 28 during Treatment Sequence B

• Maximum Observed Plasma Concentration (Cmax) of Levonorgestrel in Part 2

  Cmax is maximum observed plasma concentration of levonorgestrel.

  Day 9, 10, 11, 26, 27 and 28 during Treatment Sequence A and on Day 1, 2, 3, 26, 27 and 28 during Treatment Sequence B

• Area Under the Concentration-time Curve From Time 0 to Infinity (AUC[0-inf]) of Ethinylestradiol in Part 1

  Area under the concentration time curve from time 0 extrapolated to infinity for ethinylestradiol was reported. This outcome measure was planned to be analyzed for 'Oral Contraceptive Alone' and 'PSL + Oral Contraceptive' arms.

  Day 13, 14, 15, 34, 35, 36 during Treatment Sequence A and on Day 1, 2, 3, 30, 31 and 32 during Treatment Sequence B

• Area Under the Concentration-time Curve From Time 0 to Infinity (AUC[0-inf]) of Levonorgestrel in Part 1

  AUC0-inf is the area under the concentration time curve from time 0 extrapolated to infinity for levonorgestrel was reported. This outcome measure was planned to be analyzed for 'Oral Contraceptive Alone' and 'PSL + Oral Contraceptive' arms.

  Day 13, 14, 15, 34, 35, 36 during Treatment Sequence A and on Day 1, 2, 3, 30, 31 and 32 during Treatment Sequence B

• Area Under the Concentration-time Curve From Time 0 to Infinity (AUC[0-inf]) of Ethinylestradiol in Part 2

  AUC0-inf is the area under the concentration time curve from time 0 extrapolated to infinity of ethinylestradiol.

  Day 9, 10, 11, 26, 27 and 28 during Treatment Sequence A and on Day 1, 2, 3, 26, 27 and 28 during Treatment Sequence B

• Area Under the Concentration-time Curve From Time 0 to Infinity (AUC[0-inf]) of Levonorgestrel in Part 2

  AUC0-inf is the area under the concentration time curve from time 0 extrapolated to infinity of levonorgestrel.

  Day 9, 10, 11, 26, 27 and 28 during Treatment Sequence A and on Day 1, 2, 3, 26, 27 and 28 during Treatment Sequence B

Secondary Outcomes (8)

• Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) in Part 1

  From Baseline up to Safety Follow-Up during Treatment Sequences A and B (up to Day 46)

• Percentage of Participants With Serious TEAEs in Part 1

  From Baseline up to Safety Follow-Up during Treatment Sequences A and B (up to Day 46)

• Percentage of Participants With TEAEs in Part 2

  From Baseline up to Safety Follow-Up during Treatment Sequences A and B (up to Day 42)

• Percentage of Participants With Serious TEAEs in Part 2

  From Baseline up to Safety Follow-Up during Treatment Sequences A and B (up to Day 42)

• Steady State Plasma Concentration (Cmax,ss) of Padsevonil in Part 1

  Day 12 and 13 (Sequence A) and Day 29 and 30 (Sequence B)

Study Arms (2)

Oral contraceptive

EXPERIMENTAL

Participants will receive oral contraceptive in Period 2 of Sequence A and Period 1 of Sequence B of Part 1 and Part 2.

Drug: Microgynon 30®

Oral contraceptive + padsevonil

EXPERIMENTAL

Participants will receive padsevonil + oral contraceptive in Period 1 of Sequence A and Period 2 of Sequence B of Part 1 and Part 2.

Drug: Padsevonil; Drug: Microgynon 30®

Interventions

Padsevonil DRUG

Study Medication: Padsevonil Dosage formulation: Oral tablets; 400 mg BID (Part 1) and 200 mg BID (Part 2)

Oral contraceptive + padsevonil

Microgynon 30® DRUG

Study Medication: Microgynon 30® Dosage formulation: Oral tablets Dose: Ethinyl estradiol 30 µg + levonorgestrel 150 µg

Oral contraceptive; Oral contraceptive + padsevonil

Eligibility Criteria

• Age: 18 Years+
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participant must be aged 18 years of age or greater, at the time of signing the informed consent
• Participant must be a premenopausal female with no indication of abnormal or gestational/lactational hypothalamic-pituitary-ovarian function. Menopause will be defined for the purpose of this study as amenorrhea of ≥12 months for which no other reason has been identified
• Participant must not be pregnant or breastfeeding. Participant must agree to use an effective form of contraception (other than hormonal methods) for the duration of the Treatment Period and for at least 90 days (or 5 terminal half-lives) after the last dose of study medication
• Participant must be in good physical and mental health as determined by medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring
• Participant must have body weight of at least 45 kg and body mass index within the range 18 to 30 kg/m\^2 (inclusive)

You may not qualify if:

• Participant has a history of discontinued use of oral contraceptives (OC) for medical reasons
• Participant has any medical reason that would contraindicate the administration of OC (per label)
• Participant has used any of the following within the specified time period prior to first dose of study medication:
• Oral contraceptive or oral hormone replacement therapy within prior 30 days
• Implanted hormonal contraceptives within prior 6 months
• Injectable contraceptives within prior 12 months
• Topical controlled-delivery contraceptives within prior 3 months
• Hormone-releasing intrauterine devices ('coils') within prior 3 months
• Participant has other relevant gynecological disorders (such as premature ovarian failure or endometriosis)
• Participant has any clinically relevant electrocardiogram (ECG) finding at the Screening Visit or at Baseline (Day -1) that, in the opinion of the Investigator, increases the risks associated with participating in the study. In addition, any study participant with any of the following findings will be excluded:
• QT interval corrected for heart rate using Bazett's formula (QTcB) or Fridericia's formula (QTcF) \>450 ms in 2 of 3 ECG recordings;
• other conduction abnormalities (defined as PR interval ≥220 ms);
• irregular rhythms other than sinus arrhythmia or occasional, rare supraventricular or rare ventricular ectopic beats. In case of an out-of-range result, 1 repeat will be allowed. If the result is out-of-range again, the study participant cannot be included

Sponsors & Collaborators

• UCB Biopharma SRL: lead

Study Sites (1)

Up0035 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

Limitations and Caveats

The study was terminated on 22 May 2020 because the program developing padsevonil in focal-onset seizures was stopped.

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: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 16, 2019
• First Posted: October 18, 2019
• Study Start: October 23, 2019
• Primary Completion: May 22, 2020
• Study Completion: May 22, 2020
• Last Updated: June 24, 2021
• Results First Posted: June 24, 2021

Record last verified: 2021-06

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)