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

Study Overview
=================
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.

Official Title
-----------------
An Open-Label, Randomized, Two-Way Crossover Study to Investigate the Potential Pharmacokinetic Interaction of Padsevonil With Oral Contraceptives in Healthy Female Participants

Conditions
-----------------
Healthy Female Participants

Intervention / Treatment
-----------------
* Drug: Padsevonil
* Drug: Microgynon 30®


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 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) Exclusion Criteria: 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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Oral contraceptive<br>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®<br>* Study Medication: Microgynon 30® Dosage formulation: Oral tablets Dose: Ethinyl estradiol 30 µg + levonorgestrel 150 µg<br>|
| Experimental: Oral contraceptive + padsevonil<br>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<br>* Study Medication: Padsevonil Dosage formulation: Oral tablets; 400 mg BID (Part 1) and 200 mg BID (Part 2)<br>Drug: Microgynon 30®<br>* Study Medication: Microgynon 30® Dosage formulation: Oral tablets Dose: Ethinyl estradiol 30 µg + levonorgestrel 150 µg<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) in Part 1 | An adverse event (AE) was any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. TEAEs were defined as AEs with a start date/time on or after the first dose of study medication (OC or PSL) or any unresolved event already present before administration of study medication that worsened in intensity following exposure to the treatment. | 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 | Serious AEs were defined as any untoward medical occurrence that resulted in death, is life threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent disability, is a congenital anomaly, or is an important medical event which based on medical or scientific judgement may jeopardize the participants, or may require medical or surgical intervention to prevent any of the above. | 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 | An AE was any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. TEAEs were defined as AEs with a start date/time on or after the first dose of study medication (OC or PSL) or any unresolved event already present before administration of study medication that worsened in intensity following exposure to the treatment. | 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 | Serious AEs were defined as any untoward medical occurrence that resulted in death, is life threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent disability, is a congenital anomaly, or is an important medical event which based on medical or scientific judgement may jeopardize the participants, or may require medical or surgical intervention to prevent any of the above. | 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 | Maximum observed plasma concentration of padsevonil at steady-state was reported. This outcome measure was planned to be analyzed for 'PSL + Oral contraceptive' and 'PSL Alone' arms. | Day 12 and 13 (Sequence A) and Day 29 and 30 (Sequence B) | 
| Steady State Plasma Concentration (Cmax,ss) of Padsevonil in Part 2 | Cmax,ss is the steady state plasma concentration of padsevonil. | Day 8 and 9 (Sequence A) and Day 25 and 26 (Sequence B) | 
| Area Under the Concentration-time Curve From Time 0 to Time Tau (AUC[0-tau]) of Padsevonil in Part 1 | Area under the concentration-time curve over a dosing interval from time 0 to tau for padsevonil was reported. This outcome measure was planned to be analyzed for 'PSL + Oral contraceptive' and 'PSL Alone' arms. | Day 12 and 13 (Sequence A) and Day 29 and 30 (Sequence B) | 
| Area Under the Concentration-time Curve From Time 0 to Time Tau (AUC[0-tau]) of Padsevonil in Part 2 | AUC0-tau is area under the concentration-time curve over a dosing interval from time 0 to tau of padsevonil. | Day 8 and 9 (Sequence A) and Day 25 and 26 (Sequence B) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Padsevonil, Contraceptives, Healthy female participants