Trial Outcomes & Findings for A Study to Test the Interaction of Padsevonil With Oral Contraceptives in Healthy Female Participants (NCT NCT04131517)

Last Updated: 2021-06-24

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE1

Target enrollment

14 participants

Primary outcome timeframe

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

Results posted on

2021-06-24

Participant Flow

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.

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.

Participant milestones

Participant milestones
Measure	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.	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.
Overall Study STARTED	7	7
Overall Study COMPLETED	7	7
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Part 1 Sequence A n=7 Participants 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.	Part 1 Sequence B n=7 Participants 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.	Total Title n=14 Participants
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	7 Participants n=5 Participants	7 Participants n=7 Participants	14 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Continuous	40.6 years STANDARD_DEVIATION 7.3 • n=5 Participants	30.0 years STANDARD_DEVIATION 9.2 • n=7 Participants	35.3 years STANDARD_DEVIATION 9.7 • n=5 Participants
Sex: Female, Male Female	7 Participants n=5 Participants	7 Participants n=7 Participants	14 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized Black	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized White	7 Participants n=5 Participants	6 Participants n=7 Participants	13 Participants n=5 Participants
Race/Ethnicity, Customized Other/Mixed	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Part 1 Oral Contraceptive Alone (PKS) n=14 Participants After OC intake on Day 34 through Day 41 at Sequence A and OC intake on Day 1 through Day 18 (prior to PSL intake) at Sequence B attributed to OC Alone Treatment Period. Participants formed the PKS.	Part 1 PSL + Oral Contraceptive (PKS) n=14 Participants After OC intake on Day 13 with PSL through Day 34 (prior to OC intake) at Sequence A and after OC intake on Day 30 with PSL through Day 43 at Sequence B attributed to PSL + OC Treatment Period. Participants formed the Pharmacokinetic Set (PKS).	Part 1 PSL Alone (SS) First intake of PSL through Day 13 (prior to OC intake) at Sequence A and PSL intake on Day 18 through Day 30 (prior to OC intake) at Sequence B attributed to PSL Alone Treatment Period. Participants formed the SS.
Maximum Observed Plasma Concentration (Cmax) of Ethinylestradiol in Part 1	41.17 picograms per milliliter (pg/mL) Interval 34.07 to 49.76	42.83 picograms per milliliter (pg/mL) Interval 36.23 to 50.65	—

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Part 1 Oral Contraceptive Alone (PKS) n=14 Participants After OC intake on Day 34 through Day 41 at Sequence A and OC intake on Day 1 through Day 18 (prior to PSL intake) at Sequence B attributed to OC Alone Treatment Period. Participants formed the PKS.	Part 1 PSL + Oral Contraceptive (PKS) n=14 Participants After OC intake on Day 13 with PSL through Day 34 (prior to OC intake) at Sequence A and after OC intake on Day 30 with PSL through Day 43 at Sequence B attributed to PSL + OC Treatment Period. Participants formed the Pharmacokinetic Set (PKS).	Part 1 PSL Alone (SS) First intake of PSL through Day 13 (prior to OC intake) at Sequence A and PSL intake on Day 18 through Day 30 (prior to OC intake) at Sequence B attributed to PSL Alone Treatment Period. Participants formed the SS.
Maximum Observed Plasma Concentration (Cmax) of Levonorgestrel in Part 1	2868 pg/mL Interval 2204.0 to 3733.0	2560 pg/mL Interval 2045.0 to 3206.0	—

PRIMARY outcome

Timeframe: 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.

Cmax is maximum observed plasma concentration of ethinylestradiol.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: 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.

Cmax is maximum observed plasma concentration of levonorgestrel.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Part 1 Oral Contraceptive Alone (PKS) n=13 Participants After OC intake on Day 34 through Day 41 at Sequence A and OC intake on Day 1 through Day 18 (prior to PSL intake) at Sequence B attributed to OC Alone Treatment Period. Participants formed the PKS.	Part 1 PSL + Oral Contraceptive (PKS) n=13 Participants After OC intake on Day 13 with PSL through Day 34 (prior to OC intake) at Sequence A and after OC intake on Day 30 with PSL through Day 43 at Sequence B attributed to PSL + OC Treatment Period. Participants formed the Pharmacokinetic Set (PKS).	Part 1 PSL Alone (SS) First intake of PSL through Day 13 (prior to OC intake) at Sequence A and PSL intake on Day 18 through Day 30 (prior to OC intake) at Sequence B attributed to PSL Alone Treatment Period. Participants formed the SS.
Area Under the Concentration-time Curve From Time 0 to Infinity (AUC[0-inf]) of Ethinylestradiol in Part 1	614.6 hourspicograms per milliliter (hpg/mL) Interval 513.7 to 735.5	629.5 hourspicograms per milliliter (hpg/mL) Interval 535.3 to 740.4	—

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Part 1 Oral Contraceptive Alone (PKS) n=5 Participants After OC intake on Day 34 through Day 41 at Sequence A and OC intake on Day 1 through Day 18 (prior to PSL intake) at Sequence B attributed to OC Alone Treatment Period. Participants formed the PKS.	Part 1 PSL + Oral Contraceptive (PKS) n=8 Participants After OC intake on Day 13 with PSL through Day 34 (prior to OC intake) at Sequence A and after OC intake on Day 30 with PSL through Day 43 at Sequence B attributed to PSL + OC Treatment Period. Participants formed the Pharmacokinetic Set (PKS).	Part 1 PSL Alone (SS) First intake of PSL through Day 13 (prior to OC intake) at Sequence A and PSL intake on Day 18 through Day 30 (prior to OC intake) at Sequence B attributed to PSL Alone Treatment Period. Participants formed the SS.
Area Under the Concentration-time Curve From Time 0 to Infinity (AUC[0-inf]) of Levonorgestrel in Part 1	NA h*pg/mL As pre-specified in the Protocol/Statistical Analysis Plan, Geometric Means, SDs and CVs are only calculated if at least 2/3 of the parameters are properly determined parameters (i.e. calculated and non-flagged). Statistical analysis of ANOVA does not have a data limitation and was pre-specified to be calculated on all available data.	NA h*pg/mL As pre-specified in the Protocol/Statistical Analysis Plan, Geometric Means, SDs and CVs are only calculated if at least 2/3 of the parameters are properly determined parameters (i.e. calculated and non-flagged). Statistical analysis of ANOVA does not have a data limitation and was pre-specified to be calculated on all available data.	—

PRIMARY outcome

Timeframe: 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.

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

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: 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.

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

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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).

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.

Outcome measures

Outcome measures
Measure	Part 1 Oral Contraceptive Alone (PKS) n=14 Participants After OC intake on Day 34 through Day 41 at Sequence A and OC intake on Day 1 through Day 18 (prior to PSL intake) at Sequence B attributed to OC Alone Treatment Period. Participants formed the PKS.	Part 1 PSL + Oral Contraceptive (PKS) n=14 Participants After OC intake on Day 13 with PSL through Day 34 (prior to OC intake) at Sequence A and after OC intake on Day 30 with PSL through Day 43 at Sequence B attributed to PSL + OC Treatment Period. Participants formed the Pharmacokinetic Set (PKS).	Part 1 PSL Alone (SS) n=14 Participants First intake of PSL through Day 13 (prior to OC intake) at Sequence A and PSL intake on Day 18 through Day 30 (prior to OC intake) at Sequence B attributed to PSL Alone Treatment Period. Participants formed the SS.
Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) in Part 1	85.7 percentage of participants	50.0 percentage of participants	100.0 percentage of participants

SECONDARY outcome

Timeframe: 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).

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.

Outcome measures

Outcome measures
Measure	Part 1 Oral Contraceptive Alone (PKS) n=14 Participants After OC intake on Day 34 through Day 41 at Sequence A and OC intake on Day 1 through Day 18 (prior to PSL intake) at Sequence B attributed to OC Alone Treatment Period. Participants formed the PKS.	Part 1 PSL + Oral Contraceptive (PKS) n=14 Participants After OC intake on Day 13 with PSL through Day 34 (prior to OC intake) at Sequence A and after OC intake on Day 30 with PSL through Day 43 at Sequence B attributed to PSL + OC Treatment Period. Participants formed the Pharmacokinetic Set (PKS).	Part 1 PSL Alone (SS) n=14 Participants First intake of PSL through Day 13 (prior to OC intake) at Sequence A and PSL intake on Day 18 through Day 30 (prior to OC intake) at Sequence B attributed to PSL Alone Treatment Period. Participants formed the SS.
Percentage of Participants With Serious TEAEs in Part 1	0 percentage of participants	0 percentage of participants	0 percentage of participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Part 1 Oral Contraceptive Alone (PKS) n=14 Participants After OC intake on Day 34 through Day 41 at Sequence A and OC intake on Day 1 through Day 18 (prior to PSL intake) at Sequence B attributed to OC Alone Treatment Period. Participants formed the PKS.	Part 1 PSL + Oral Contraceptive (PKS) n=14 Participants After OC intake on Day 13 with PSL through Day 34 (prior to OC intake) at Sequence A and after OC intake on Day 30 with PSL through Day 43 at Sequence B attributed to PSL + OC Treatment Period. Participants formed the Pharmacokinetic Set (PKS).	Part 1 PSL Alone (SS) First intake of PSL through Day 13 (prior to OC intake) at Sequence A and PSL intake on Day 18 through Day 30 (prior to OC intake) at Sequence B attributed to PSL Alone Treatment Period. Participants formed the SS.
Steady State Plasma Concentration (Cmax,ss) of Padsevonil in Part 1	2008 nanograms per milliliter (ng/mL) Interval 1768.0 to 2281.0	2083 nanograms per milliliter (ng/mL) Interval 1899.0 to 2286.0	—

SECONDARY outcome

Timeframe: 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.

Cmax,ss is the steady state plasma concentration of padsevonil.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Part 1 Oral Contraceptive Alone (PKS) n=14 Participants After OC intake on Day 34 through Day 41 at Sequence A and OC intake on Day 1 through Day 18 (prior to PSL intake) at Sequence B attributed to OC Alone Treatment Period. Participants formed the PKS.	Part 1 PSL + Oral Contraceptive (PKS) n=14 Participants After OC intake on Day 13 with PSL through Day 34 (prior to OC intake) at Sequence A and after OC intake on Day 30 with PSL through Day 43 at Sequence B attributed to PSL + OC Treatment Period. Participants formed the Pharmacokinetic Set (PKS).	Part 1 PSL Alone (SS) First intake of PSL through Day 13 (prior to OC intake) at Sequence A and PSL intake on Day 18 through Day 30 (prior to OC intake) at Sequence B attributed to PSL Alone Treatment Period. Participants formed the SS.
Area Under the Concentration-time Curve From Time 0 to Time Tau (AUC[0-tau]) of Padsevonil in Part 1	9612 hoursnanograms per milliliter (hng/mL) Interval 8273.0 to 11170.0	9925 hoursnanograms per milliliter (hng/mL) Interval 8769.0 to 11230.0	—

SECONDARY outcome

Timeframe: 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.

AUC0-tau is area under the concentration-time curve over a dosing interval from time 0 to tau of padsevonil.

Outcome measures

Outcome data not reported

Adverse Events

Part 1 PSL + Oral Contraceptive (SS)

Serious events: 0 serious events

Other events: 12 other events

Deaths: 0 deaths

Part 1 Oral Contraceptive Alone (SS)

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

Part 1 PSL Alone (SS)

Serious events: 0 serious events

Other events: 14 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

UCB

Cares

Phone: +1844 599

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60