Healthy Female Participants
Conditions
Keywords
Padsevonil, Contraceptives, Healthy female participants
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.
Interventions
DRUGPadsevonil
Study Medication: Padsevonil Dosage formulation: Oral tablets; 400 mg BID (Part 1) and 200 mg BID (Part 2)
DRUGMicrogynon 30®
Study Medication: Microgynon 30® Dosage formulation: Oral tablets Dose: Ethinyl estradiol 30 µg + levonorgestrel 150 µg
Sponsors
UCB Biopharma SRL
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
Yes
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: 1. Oral contraceptive or oral hormone replacement therapy within prior 30 days 2. Implanted hormonal contraceptives within prior 6 months 3. Injectable contraceptives within prior 12 months 4. Topical controlled-delivery contraceptives within prior 3 months 5. 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: 1. QT interval corrected for heart rate using Bazett's formula (QTcB) or Fridericia's formula (QTcF) \>450 ms in 2 of 3 ECG recordings; 2. other conduction abnormalities (defined as PR interval ≥220 ms); 3. 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Concentration-time Curve From Time 0 to Infinity (AUC[0-inf]) of Levonorgestrel in Part 2 | 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 | AUC0-inf is the area under the concentration time curve from time 0 extrapolated to infinity of levonorgestrel. |
| Maximum Observed Plasma Concentration (Cmax) of Ethinylestradiol in Part 1 | 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 | 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. |
| Maximum Observed Plasma Concentration (Cmax) of Levonorgestrel in Part 1 | 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 | 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. |
| Maximum Observed Plasma Concentration (Cmax) of Ethinylestradiol in Part 2 | 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 | Cmax is maximum observed plasma concentration of ethinylestradiol. |
| Maximum Observed Plasma Concentration (Cmax) of Levonorgestrel in Part 2 | 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 | Cmax is maximum observed plasma concentration of levonorgestrel. |
| Area Under the Concentration-time Curve From Time 0 to Infinity (AUC[0-inf]) of Ethinylestradiol in Part 1 | 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 extrapolated to infinity for ethinylestradiol was reported. This outcome measure was planned to be analyzed for 'Oral Contraceptive Alone' and 'PSL + Oral Contraceptive' arms. |
| Area Under the Concentration-time Curve From Time 0 to Infinity (AUC[0-inf]) of Levonorgestrel in Part 1 | 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 | 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. |
| Area Under the Concentration-time Curve From Time 0 to Infinity (AUC[0-inf]) of Ethinylestradiol in Part 2 | 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 | AUC0-inf is the area under the concentration time curve from time 0 extrapolated to infinity of ethinylestradiol. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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) | 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. |
| 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) | 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. |
| 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) | 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. |
| 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) | 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. |
| Steady State Plasma Concentration (Cmax,ss) of Padsevonil in Part 1 | Day 12 and 13 (Sequence A) and Day 29 and 30 (Sequence B) | 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. |
| Steady State Plasma Concentration (Cmax,ss) of Padsevonil in Part 2 | Day 8 and 9 (Sequence A) and Day 25 and 26 (Sequence B) | Cmax,ss is the steady state plasma concentration of padsevonil. |
| Area Under the Concentration-time Curve From Time 0 to Time Tau (AUC[0-tau]) of Padsevonil in Part 1 | Day 12 and 13 (Sequence A) and Day 29 and 30 (Sequence B) | 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. |
| Area Under the Concentration-time Curve From Time 0 to Time Tau (AUC[0-tau]) of Padsevonil in Part 2 | Day 8 and 9 (Sequence A) and Day 25 and 26 (Sequence B) | AUC0-tau is area under the concentration-time curve over a dosing interval from time 0 to tau of padsevonil. |
Countries
United Kingdom
Participant flow
Recruitment details
The study started to enroll study participants in October 2019 and concluded in May 2020. No study participants started Part 2 due to the COVID-19 pandemic. Later, the program developing PSL in focal-onset seizures was stopped and the study was terminated.
Pre-assignment details
Participant flow refers to the Safety Set (SS). No study participants started Part 2 due to the COVID-19 pandemic. Later, the program developing PSL in focal-onset seizures was stopped and the study was terminated.
Participants by arm
| Arm | Count |
|---|---|
| Part 1 Sequence A Participants received padsevonil (PSL) tablets 100 milligrams (mg) up-titrated to 400 mg, orally twice daily (bid) from Day 1 to 6 followed by padsevonil 400 mg bid on Day 7 to 14 along with a single dose of oral contraceptive (OC) Microgynon® 30 (ethinylestradiol 30 microgram \[mcg\] + levonorgestrel 150 mcg) tablet on Day 13 and, then padsevonil down-titrated from 400 mg to 100 mg bid from Day 15 to 19 during first Treatment Period. Participants received a single dose of OC tablet on Day 34 during second Treatment Period. There was a Washout Period of 14 days between the two Treatment Periods. | 7 |
| Part 1 Sequence B Participants received a single dose of OC tablet on Day 1 during first Treatment Period. Participants received padsevonil tablets 100 mg up-titrated to 400 mg, bid on Day 18 to 23 followed by padsevonil 400 mg bid on Day 24 to 31 along with a single dose of OC tablet on Day 30 and, then padsevonil down-titrated from 400 mg to 100 mg bid from Day 32 to 36 during second Treatment Period. There was a Washout Period of 14 days between the two Treatment Periods. | 7 |
| Total Title | 14 |
| Total | 28 |
Baseline characteristics
| Characteristic | Part 1 Sequence A | Part 1 Sequence B | Total Title |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 7 Participants | 7 Participants | 14 Participants |
| Age, Continuous | 40.6 years STANDARD_DEVIATION 7.3 | 30.0 years STANDARD_DEVIATION 9.2 | 35.3 years STANDARD_DEVIATION 9.7 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Black | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Other/Mixed | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 7 Participants | 6 Participants | 13 Participants |
| Sex: Female, Male Female | 7 Participants | 7 Participants | 14 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 14 | 0 / 14 | 0 / 14 |
| other Total, other adverse events | 12 / 14 | 7 / 14 | 14 / 14 |
| serious Total, serious adverse events | 0 / 14 | 0 / 14 | 0 / 14 |
Outcome results
Primary
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.
Time frame: 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
Population: Pharmacokinetic Set included all study participants who had no important protocol deviations affecting the PK of EE, LN, or PSL and its metabolite and for whom at least 1 measurable concentration existed. Here, Number of participants analyzed signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Part 1 Oral Contraceptive Alone (PKS) | Area Under the Concentration-time Curve From Time 0 to Infinity (AUC[0-inf]) of Ethinylestradiol in Part 1 | 614.6 hours*picograms per milliliter (h*pg/mL) |
| Part 1 PSL + Oral Contraceptive (PKS) | Area Under the Concentration-time Curve From Time 0 to Infinity (AUC[0-inf]) of Ethinylestradiol in Part 1 | 629.5 hours*picograms per milliliter (h*pg/mL) |
Comparison: The ANOVA model included Treatment, Period, and Sequence as fixed effects and participant within Sequence as a random effect.90% CI: [0.95544, 1.1052]
Primary
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.
Time frame: 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
Population: Analysis of this outcome measure was not performed because no study participants started Part 2 due to the COVID-19 pandemic. Later, the study was terminated.
Primary
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.
Time frame: 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
Population: Pharmacokinetic Set included all study participants who had no important protocol deviations affecting the PK of EE, LN, or PSL and its metabolite and for whom at least 1 measurable concentration existed. Here, Number of participants analyzed signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Part 1 Oral Contraceptive Alone (PKS) | Area Under the Concentration-time Curve From Time 0 to Infinity (AUC[0-inf]) of Levonorgestrel in Part 1 | NA h*pg/mL |
| Part 1 PSL + Oral Contraceptive (PKS) | Area Under the Concentration-time Curve From Time 0 to Infinity (AUC[0-inf]) of Levonorgestrel in Part 1 | NA h*pg/mL |
Comparison: The ANOVA model included Treatment, Period, and Sequence as fixed effects and participant within Sequence as a random effect.90% CI: [0.52185, 1.5113]
Primary
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.
Time frame: 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
Population: Analysis of this outcome measure was not performed because no study participants started Part 2 due to the COVID-19 pandemic. Later, the study was terminated.
Primary
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.
Time frame: 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
Population: Pharmacokinetic Set (PKS) included all study participants who had no important protocol deviations affecting the PK of EE, LN, or PSL and its metabolite and for whom at least 1 measurable concentration existed.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Part 1 Oral Contraceptive Alone (PKS) | Maximum Observed Plasma Concentration (Cmax) of Ethinylestradiol in Part 1 | 41.17 picograms per milliliter (pg/mL) |
| Part 1 PSL + Oral Contraceptive (PKS) | Maximum Observed Plasma Concentration (Cmax) of Ethinylestradiol in Part 1 | 42.83 picograms per milliliter (pg/mL) |
Comparison: The analysis of variance model (ANOVA) included Treatment, Period, and Sequence as fixed effects and participant within Sequence as a random effect.90% CI: [0.94156, 1.1497]
Primary
Maximum Observed Plasma Concentration (Cmax) of Ethinylestradiol in Part 2
Cmax is maximum observed plasma concentration of ethinylestradiol.
Time frame: 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
Population: Analysis of this outcome measure was not performed because no study participants started Part 2 due to the COVID-19 pandemic. Later, the study was terminated.
Primary
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.
Time frame: 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
Population: Pharmacokinetic Set included all study participants who had no important protocol deviations affecting the PK of EE, LN, or PSL and its metabolite and for whom at least 1 measurable concentration existed.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Part 1 Oral Contraceptive Alone (PKS) | Maximum Observed Plasma Concentration (Cmax) of Levonorgestrel in Part 1 | 2868 pg/mL |
| Part 1 PSL + Oral Contraceptive (PKS) | Maximum Observed Plasma Concentration (Cmax) of Levonorgestrel in Part 1 | 2560 pg/mL |
Comparison: The ANOVA model included Treatment, Period, and Sequence as fixed effects and participant within Sequence as a random effect.90% CI: [0.76892, 1.0364]
Primary
Maximum Observed Plasma Concentration (Cmax) of Levonorgestrel in Part 2
Cmax is maximum observed plasma concentration of levonorgestrel.
Time frame: 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
Population: No study participants started Part 2 due to the COVID-19 pandemic. Later, the program developing PSL in focal-onset seizures was stopped and the study was terminated.
Secondary
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.
Time frame: Day 12 and 13 (Sequence A) and Day 29 and 30 (Sequence B)
Population: Pharmacokinetic Set included all study participants who had no important protocol deviations affecting the PK of EE, LN, or PSL and its metabolite and for whom at least 1 measurable concentration existed.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Part 1 Oral Contraceptive Alone (PKS) | Area Under the Concentration-time Curve From Time 0 to Time Tau (AUC[0-tau]) of Padsevonil in Part 1 | 9612 hours*nanograms per milliliter (h*ng/mL) |
| Part 1 PSL + Oral Contraceptive (PKS) | Area Under the Concentration-time Curve From Time 0 to Time Tau (AUC[0-tau]) of Padsevonil in Part 1 | 9925 hours*nanograms per milliliter (h*ng/mL) |
Comparison: The ANOVA model included Treatment, Period, and Sequence as fixed effects and participant within Sequence as a random effect.90% CI: [0.91888, 1.0206]
Secondary
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.
Time frame: Day 8 and 9 (Sequence A) and Day 25 and 26 (Sequence B)
Population: Analysis of this outcome measure was not performed because no study participants started Part 2 due to the COVID-19 pandemic. Later, the study was terminated.
Secondary
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.
Time frame: From Baseline up to Safety Follow-Up during Treatment Sequences A and B (up to Day 46)
Population: Safety Set included study participants who received at least 1 dose of study medication (PSL or OC).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1 Oral Contraceptive Alone (PKS) | Percentage of Participants With Serious TEAEs in Part 1 | 0 percentage of participants |
| Part 1 PSL + Oral Contraceptive (PKS) | Percentage of Participants With Serious TEAEs in Part 1 | 0 percentage of participants |
| Part 1 PSL Alone (SS) | Percentage of Participants With Serious TEAEs in Part 1 | 0 percentage of participants |
Secondary
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.
Time frame: From Baseline up to Safety Follow-Up during Treatment Sequences A and B (up to Day 42)
Population: Analysis of this outcome measure was not performed because no study participants started Part 2 due to the COVID-19 pandemic. Later, the study was terminated.
Secondary
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.
Time frame: From Baseline up to Safety Follow-Up during Treatment Sequences A and B (up to Day 42)
Population: Analysis of this outcome measure was not performed because no study participants started Part 2 due to the COVID-19 pandemic. Later, the study was terminated.
Secondary
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.
Time frame: From Baseline up to Safety Follow-Up during Treatment Sequences A and B (up to Day 46)
Population: Safety Set included study participants who received at least 1 dose of study medication (PSL or OC).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1 Oral Contraceptive Alone (PKS) | Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) in Part 1 | 85.7 percentage of participants |
| Part 1 PSL + Oral Contraceptive (PKS) | Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) in Part 1 | 50.0 percentage of participants |
| Part 1 PSL Alone (SS) | Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) in Part 1 | 100.0 percentage of participants |
Secondary
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.
Time frame: Day 12 and 13 (Sequence A) and Day 29 and 30 (Sequence B)
Population: Pharmacokinetic Set included all study participants who had no important protocol deviations affecting the PK of EE, LN, or PSL and its metabolite and for whom at least 1 measurable concentration existed.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Part 1 Oral Contraceptive Alone (PKS) | Steady State Plasma Concentration (Cmax,ss) of Padsevonil in Part 1 | 2008 nanograms per milliliter (ng/mL) |
| Part 1 PSL + Oral Contraceptive (PKS) | Steady State Plasma Concentration (Cmax,ss) of Padsevonil in Part 1 | 2083 nanograms per milliliter (ng/mL) |
Comparison: The ANOVA model included Treatment, Period, and Sequence as fixed effects and participant within Sequence as a random effect.90% CI: [0.85043, 1.0922]
Secondary
Steady State Plasma Concentration (Cmax,ss) of Padsevonil in Part 2
Cmax,ss is the steady state plasma concentration of padsevonil.
Time frame: Day 8 and 9 (Sequence A) and Day 25 and 26 (Sequence B)
Population: Analysis of this outcome measure was not performed because no study participants started Part 2 due to the COVID-19 pandemic. Later, the study was terminated.