Trial Outcomes & Findings for A Study of Soticlestat With Itraconazole and Mefenamic Acid in Healthy Adults (NCT NCT05064449)

Results Overview

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

28 participants

Primary outcome timeframe

Soticlestat alone: Period 1, Day 1 pre-dose and at multiple timepoints (up to 96 hours) post-dose; Soticlestat with itraconazole: Period 2, Day 5 pre-dose and at multiple timepoints (up to 168 hours) post-dose

Results posted on

2023-10-03

Participant Flow

Participants took part in the study at 1 investigative site in the United States from 14 October 2021 to 30 November 2021.

Healthy participants were enrolled in this 2-part study to receive soticlestat tablets alone in Period 1 and soticlestat tablets and itraconazole solution in Period 2 of Part 1; and soticlestat tablets alone in Period 1 and soticlestat tablets and mefenamic acid capsules in Period 2 of Part 2. Both study parts (Parts 1 and 2) were conducted independently from one another, no crossover happened between both parts.

Participant milestones

Participant milestones
Measure	Part 1: Soticlestat 300 mg + Itraconazole 200 mg Soticlestat 300 milligram (mg) administered as 3\100 mg tablets, orally, once on Day 1 of Period 1, followed by 4 days washout period, further followed by itraconazole 200 mg administered as 20 milliliter (mL) of 10 milligram per milliliter (mg/ml) solution, orally, once daily from Day 1 up to Day 11 of Period 2 and soticlestat 300 mg administered as 3\100 mg tablets, orally, once on Day 5 of Period 2.	Part 2: Soticlestat 300 mg + Mefenamic Acid 500 mg and 250 mg Soticlestat 300 mg administered as 3\100 mg tablets, orally, once on Day 1 of Period 1, followed by 4 days washout period, further followed by initial single dose of mefenamic acid 500 mg administered as 2\250 mg capsules, orally on the morning of Day 1 and 250 mg subsequent doses at every six hours from Day 1 up to Day 7 of Period 2, and soticlestat 300 mg administered as 3\*100 mg tablets, orally, once on Day 2 of Period 2.
Period 1 (1 Day) STARTED	14	14
Period 1 (1 Day) COMPLETED	14	14
Period 1 (1 Day) NOT COMPLETED	0	0
Washout Period (4 Days) STARTED	14	14
Washout Period (4 Days) COMPLETED	14	14
Washout Period (4 Days) NOT COMPLETED	0	0
Period 2(Part 1:Day 1-12;Part 2:Day 1-8) STARTED	14	14
Period 2(Part 1:Day 1-12;Part 2:Day 1-8) COMPLETED	14	14
Period 2(Part 1:Day 1-12;Part 2:Day 1-8) NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Study of Soticlestat With Itraconazole and Mefenamic Acid in Healthy Adults

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Part 1: Soticlestat 300 mg + Itraconazole 200 mg n=14 Participants Soticlestat 300 mg administered as 3\100 mg tablets, orally, once on Day 1 of Period 1, followed by 4 days washout period, further followed by itraconazole 200 mg administered as 20 mL of 10 mg/ml solution, orally, once daily from Day 1 up to Day 11 of Period 2 and soticlestat 300 mg administered as 3\100 mg tablets, orally, once on Day 5 of Period 2.	Part 2: Soticlestat 300 mg + Mefenamic Acid 500 mg and 250 mg n=14 Participants Soticlestat 300 mg administered as 3\100 mg tablets, orally, once on Day 1 of Period 1, followed by 4 days washout period, further followed by initial single dose of mefenamic acid 500 mg administered as 2\250 mg capsules, orally on the morning of Day 1 and 250 mg subsequent doses at every six hours from Day 1 up to Day 7 of Period 2, and soticlestat 300 mg administered as 3\*100 mg tablets, orally, once on Day 2 of Period 2.	Total n=28 Participants Total of all reporting groups
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	14 Participants n=5 Participants	14 Participants n=7 Participants	28 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Female	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants
Sex: Female, Male Male	11 Participants n=5 Participants	12 Participants n=7 Participants	23 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	12 Participants n=5 Participants	12 Participants n=7 Participants	24 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized Asian	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	4 Participants n=5 Participants	5 Participants n=7 Participants	9 Participants n=5 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized White	8 Participants n=5 Participants	5 Participants n=7 Participants	13 Participants n=5 Participants
Race/Ethnicity, Customized White, American Indian or Alaska Native	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized White, Black or African American	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized White, Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Region of Enrollment United States of America	14 Participants n=5 Participants	14 Participants n=7 Participants	28 Participants n=5 Participants

PRIMARY outcome

Timeframe: Soticlestat alone: Period 1, Day 1 pre-dose and at multiple timepoints (up to 96 hours) post-dose; Soticlestat with itraconazole: Period 2, Day 5 pre-dose and at multiple timepoints (up to 168 hours) post-dose

Population: All participants who complied sufficiently with the protocol and display an evaluable pharmacokinetic (PK) profile (example, exposure to treatment, availability of measurements and absence of major protocol violations) were included in the PK analysis set.

Outcome measures

Outcome measures
Measure	Part 1: Soticlestat 300 mg Alone n=14 Participants Soticlestat 300 mg administered as 3\*100 mg tablets, orally, once on Day 1 of Period 1.	Part 1: Soticlestat 300 mg + Itraconazole 200 mg n=14 Participants Itraconazole 200 mg administered as 20 mL of 10 mg/ml solution, orally, once daily from Day 1 up to Day 11 of Period 2, and soticlestat 300 mg administered as 3\*100 mg tablets, orally, once on Day 5 of Period 2.	Part 1: Soticlestat 300 mg + Itraconazole 200 mg Soticlestat 300 mg administered as 3\100 mg tablets, orally, once on Day 1 of Period 1, followed by 4 days washout period, further followed by itraconazole 200 mg administered as 20 mL of 10 mg/ml solution, orally, once daily from Day 1 up to Day 11 of Period 2 and soticlestat 300 mg administered as 3\100 mg tablets, orally, once on Day 5 of Period 2.	Part 2: Soticlestat 300 mg Alone Soticlestat 300 mg administered as 3\*100 mg tablets, orally, once on Day 1 of Period 1.	Part 2: Mefenamic Acid 500 mg and 250 mg Initial single dose of mefenamic acid 500 mg administered as 2\*250 mg capsules, orally on the morning of Day 1 and 250 mg subsequent doses at every six hours from Day 1 up to Day 7 of Period 2.	Part 2: Soticlestat 300 mg + Mefenamic Acid 500 mg and 250 mg Soticlestat 300 mg administered as 3\100 mg tablets, orally, once on Day 1 of Period 1, followed by 4 days washout period, further followed by initial single dose of mefenamic acid 500 mg administered as 2\250 mg capsules, orally on the morning of Day 1 and 250 mg subsequent doses at every six hours from Day 1 up to Day 7 of Period 2, and soticlestat 300 mg administered as 3\*100 mg tablets, orally, once on Day 2 of Period 2.
Part 1, Cmax: Maximum Observed Plasma Concentration for Soticlestat When Administered Alone and With Itraconazole	1310 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 80.2	1527 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 65.5	—	—	—	—

PRIMARY outcome

Timeframe: Soticlestat alone: Period 1, Day 1 pre-dose and at multiple timepoints (up to 96 hours) post-dose; Soticlestat with mefenamic acid: Period 2, Day 2 pre-dose and at multiple timepoints (up to 144 hours) post-dose

Population: All participants who complied sufficiently with the protocol and display an evaluable PK profile (example, exposure to treatment, availability of measurements and absence of major protocol violations) were included in the PK analysis set.

Outcome measures

Outcome measures
Measure	Part 1: Soticlestat 300 mg Alone n=14 Participants Soticlestat 300 mg administered as 3\*100 mg tablets, orally, once on Day 1 of Period 1.	Part 1: Soticlestat 300 mg + Itraconazole 200 mg n=14 Participants Itraconazole 200 mg administered as 20 mL of 10 mg/ml solution, orally, once daily from Day 1 up to Day 11 of Period 2, and soticlestat 300 mg administered as 3\*100 mg tablets, orally, once on Day 5 of Period 2.	Part 1: Soticlestat 300 mg + Itraconazole 200 mg Soticlestat 300 mg administered as 3\100 mg tablets, orally, once on Day 1 of Period 1, followed by 4 days washout period, further followed by itraconazole 200 mg administered as 20 mL of 10 mg/ml solution, orally, once daily from Day 1 up to Day 11 of Period 2 and soticlestat 300 mg administered as 3\100 mg tablets, orally, once on Day 5 of Period 2.	Part 2: Soticlestat 300 mg Alone Soticlestat 300 mg administered as 3\*100 mg tablets, orally, once on Day 1 of Period 1.	Part 2: Mefenamic Acid 500 mg and 250 mg Initial single dose of mefenamic acid 500 mg administered as 2\*250 mg capsules, orally on the morning of Day 1 and 250 mg subsequent doses at every six hours from Day 1 up to Day 7 of Period 2.	Part 2: Soticlestat 300 mg + Mefenamic Acid 500 mg and 250 mg Soticlestat 300 mg administered as 3\100 mg tablets, orally, once on Day 1 of Period 1, followed by 4 days washout period, further followed by initial single dose of mefenamic acid 500 mg administered as 2\250 mg capsules, orally on the morning of Day 1 and 250 mg subsequent doses at every six hours from Day 1 up to Day 7 of Period 2, and soticlestat 300 mg administered as 3\*100 mg tablets, orally, once on Day 2 of Period 2.
Part 2, Cmax: Maximum Observed Plasma Concentration for Soticlestat When Administered Alone and With Mefenamic Acid	1414 ng/mL Geometric Coefficient of Variation 58.4	1517 ng/mL Geometric Coefficient of Variation 55.8	—	—	—	—

PRIMARY outcome

Timeframe: Soticlestat alone: Period 1, Day 1 pre-dose and at multiple timepoints (up to 96 hours) post-dose; Soticlestat with itraconazole: Period 2, Day 5 pre-dose and at multiple timepoints (up to 168 hours) post-dose

Population: All participants who complied sufficiently with the protocol and display an evaluable PK profile (example, exposure to treatment, availability of measurements and absence of major protocol violations) were included in the PK analysis set. Here, "overall number of participants analyzed" signified those who were evaluable for this outcome measure.

Outcome measures

Outcome measures
Measure	Part 1: Soticlestat 300 mg Alone n=12 Participants Soticlestat 300 mg administered as 3\*100 mg tablets, orally, once on Day 1 of Period 1.	Part 1: Soticlestat 300 mg + Itraconazole 200 mg n=9 Participants Itraconazole 200 mg administered as 20 mL of 10 mg/ml solution, orally, once daily from Day 1 up to Day 11 of Period 2, and soticlestat 300 mg administered as 3\*100 mg tablets, orally, once on Day 5 of Period 2.	Part 1: Soticlestat 300 mg + Itraconazole 200 mg Soticlestat 300 mg administered as 3\100 mg tablets, orally, once on Day 1 of Period 1, followed by 4 days washout period, further followed by itraconazole 200 mg administered as 20 mL of 10 mg/ml solution, orally, once daily from Day 1 up to Day 11 of Period 2 and soticlestat 300 mg administered as 3\100 mg tablets, orally, once on Day 5 of Period 2.	Part 2: Soticlestat 300 mg Alone Soticlestat 300 mg administered as 3\*100 mg tablets, orally, once on Day 1 of Period 1.	Part 2: Mefenamic Acid 500 mg and 250 mg Initial single dose of mefenamic acid 500 mg administered as 2\*250 mg capsules, orally on the morning of Day 1 and 250 mg subsequent doses at every six hours from Day 1 up to Day 7 of Period 2.	Part 2: Soticlestat 300 mg + Mefenamic Acid 500 mg and 250 mg Soticlestat 300 mg administered as 3\100 mg tablets, orally, once on Day 1 of Period 1, followed by 4 days washout period, further followed by initial single dose of mefenamic acid 500 mg administered as 2\250 mg capsules, orally on the morning of Day 1 and 250 mg subsequent doses at every six hours from Day 1 up to Day 7 of Period 2, and soticlestat 300 mg administered as 3\*100 mg tablets, orally, once on Day 2 of Period 2.
Part 1, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Soticlestat When Administered Alone and With Itraconazole	1483 nanogramhours per milliliter(nghr/mL) Geometric Coefficient of Variation 56.1	1914 nanogramhours per milliliter(nghr/mL) Geometric Coefficient of Variation 42.8	—	—	—	—

PRIMARY outcome

Timeframe: Soticlestat alone: Period 1, Day 1 pre-dose and at multiple timepoints (up to 96 hours) post-dose; Soticlestat with mefenamic acid: Period 2, Day 2 pre-dose and at multiple timepoints (up to 144 hours) post-dose

Population: All participants who complied sufficiently with the protocol and display an evaluable PK profile (example, exposure to treatment, availability of measurements and absence of major protocol violations) were included in the PK analysis set. Here, "overall number of participants analyzed" signified those who were evaluable for this outcome measure.

Outcome measures

Outcome measures
Measure	Part 1: Soticlestat 300 mg Alone n=11 Participants Soticlestat 300 mg administered as 3\*100 mg tablets, orally, once on Day 1 of Period 1.	Part 1: Soticlestat 300 mg + Itraconazole 200 mg n=9 Participants Itraconazole 200 mg administered as 20 mL of 10 mg/ml solution, orally, once daily from Day 1 up to Day 11 of Period 2, and soticlestat 300 mg administered as 3\*100 mg tablets, orally, once on Day 5 of Period 2.	Part 1: Soticlestat 300 mg + Itraconazole 200 mg Soticlestat 300 mg administered as 3\100 mg tablets, orally, once on Day 1 of Period 1, followed by 4 days washout period, further followed by itraconazole 200 mg administered as 20 mL of 10 mg/ml solution, orally, once daily from Day 1 up to Day 11 of Period 2 and soticlestat 300 mg administered as 3\100 mg tablets, orally, once on Day 5 of Period 2.	Part 2: Soticlestat 300 mg Alone Soticlestat 300 mg administered as 3\*100 mg tablets, orally, once on Day 1 of Period 1.	Part 2: Mefenamic Acid 500 mg and 250 mg Initial single dose of mefenamic acid 500 mg administered as 2\*250 mg capsules, orally on the morning of Day 1 and 250 mg subsequent doses at every six hours from Day 1 up to Day 7 of Period 2.	Part 2: Soticlestat 300 mg + Mefenamic Acid 500 mg and 250 mg Soticlestat 300 mg administered as 3\100 mg tablets, orally, once on Day 1 of Period 1, followed by 4 days washout period, further followed by initial single dose of mefenamic acid 500 mg administered as 2\250 mg capsules, orally on the morning of Day 1 and 250 mg subsequent doses at every six hours from Day 1 up to Day 7 of Period 2, and soticlestat 300 mg administered as 3\*100 mg tablets, orally, once on Day 2 of Period 2.
Part 2, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Soticlestat When Administered Alone and With Mefenamic Acid	1533 ng*hr/mL Geometric Coefficient of Variation 42.2	1594 ng*hr/mL Geometric Coefficient of Variation 45.6	—	—	—	—

PRIMARY outcome

Timeframe: Soticlestat alone: Period 1, Day 1 pre-dose and at multiple timepoints (up to 96 hours) post-dose; Soticlestat with itraconazole: Period 2, Day 5 pre-dose and at multiple timepoints (up to 168 hours) post-dose

Population: All participants who complied sufficiently with the protocol and display an evaluable PK profile (example, exposure to treatment, availability of measurements and absence of major protocol violations) were included in the PK analysis set.

Outcome measures

Outcome measures
Measure	Part 1: Soticlestat 300 mg Alone n=14 Participants Soticlestat 300 mg administered as 3\*100 mg tablets, orally, once on Day 1 of Period 1.	Part 1: Soticlestat 300 mg + Itraconazole 200 mg n=14 Participants Itraconazole 200 mg administered as 20 mL of 10 mg/ml solution, orally, once daily from Day 1 up to Day 11 of Period 2, and soticlestat 300 mg administered as 3\*100 mg tablets, orally, once on Day 5 of Period 2.	Part 1: Soticlestat 300 mg + Itraconazole 200 mg Soticlestat 300 mg administered as 3\100 mg tablets, orally, once on Day 1 of Period 1, followed by 4 days washout period, further followed by itraconazole 200 mg administered as 20 mL of 10 mg/ml solution, orally, once daily from Day 1 up to Day 11 of Period 2 and soticlestat 300 mg administered as 3\100 mg tablets, orally, once on Day 5 of Period 2.	Part 2: Soticlestat 300 mg Alone Soticlestat 300 mg administered as 3\*100 mg tablets, orally, once on Day 1 of Period 1.	Part 2: Mefenamic Acid 500 mg and 250 mg Initial single dose of mefenamic acid 500 mg administered as 2\*250 mg capsules, orally on the morning of Day 1 and 250 mg subsequent doses at every six hours from Day 1 up to Day 7 of Period 2.	Part 2: Soticlestat 300 mg + Mefenamic Acid 500 mg and 250 mg Soticlestat 300 mg administered as 3\100 mg tablets, orally, once on Day 1 of Period 1, followed by 4 days washout period, further followed by initial single dose of mefenamic acid 500 mg administered as 2\250 mg capsules, orally on the morning of Day 1 and 250 mg subsequent doses at every six hours from Day 1 up to Day 7 of Period 2, and soticlestat 300 mg administered as 3\*100 mg tablets, orally, once on Day 2 of Period 2.
Part 1, AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Soticlestat When Administered Alone and With Itraconazole	1391 ng*hr/mL Geometric Coefficient of Variation 54.9	1697 ng*hr/mL Geometric Coefficient of Variation 45.3	—	—	—	—

PRIMARY outcome

Timeframe: Soticlestat alone: Period 1, Day 1 pre-dose and at multiple timepoints (up to 96 hours) post-dose; Soticlestat with mefenamic acid: Period 2, Day 2 pre-dose and at multiple timepoints (up to 144 hours) post-dose

Population: All participants who complied sufficiently with the protocol and display an evaluable PK profile (example, exposure to treatment, availability of measurements and absence of major protocol violations) were included in the PK analysis set.

Outcome measures

Outcome measures
Measure	Part 1: Soticlestat 300 mg Alone n=14 Participants Soticlestat 300 mg administered as 3\*100 mg tablets, orally, once on Day 1 of Period 1.	Part 1: Soticlestat 300 mg + Itraconazole 200 mg n=14 Participants Itraconazole 200 mg administered as 20 mL of 10 mg/ml solution, orally, once daily from Day 1 up to Day 11 of Period 2, and soticlestat 300 mg administered as 3\*100 mg tablets, orally, once on Day 5 of Period 2.	Part 1: Soticlestat 300 mg + Itraconazole 200 mg Soticlestat 300 mg administered as 3\100 mg tablets, orally, once on Day 1 of Period 1, followed by 4 days washout period, further followed by itraconazole 200 mg administered as 20 mL of 10 mg/ml solution, orally, once daily from Day 1 up to Day 11 of Period 2 and soticlestat 300 mg administered as 3\100 mg tablets, orally, once on Day 5 of Period 2.	Part 2: Soticlestat 300 mg Alone Soticlestat 300 mg administered as 3\*100 mg tablets, orally, once on Day 1 of Period 1.	Part 2: Mefenamic Acid 500 mg and 250 mg Initial single dose of mefenamic acid 500 mg administered as 2\*250 mg capsules, orally on the morning of Day 1 and 250 mg subsequent doses at every six hours from Day 1 up to Day 7 of Period 2.	Part 2: Soticlestat 300 mg + Mefenamic Acid 500 mg and 250 mg Soticlestat 300 mg administered as 3\100 mg tablets, orally, once on Day 1 of Period 1, followed by 4 days washout period, further followed by initial single dose of mefenamic acid 500 mg administered as 2\250 mg capsules, orally on the morning of Day 1 and 250 mg subsequent doses at every six hours from Day 1 up to Day 7 of Period 2, and soticlestat 300 mg administered as 3\*100 mg tablets, orally, once on Day 2 of Period 2.
Part 2, AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Soticlestat When Administered Alone and With Mefenamic Acid	1423 ng*hr/mL Geometric Coefficient of Variation 41.6	1528 ng*hr/mL Geometric Coefficient of Variation 46.2	—	—	—	—

PRIMARY outcome

Timeframe: Soticlestat alone: Period 1, Day 1 pre-dose and at multiple timepoints (up to 96 hours) post-dose; Soticlestat with itraconazole: Period 2, Day 5 pre-dose and at multiple timepoints (up to 168 hours) post-dose

Population: All participants who complied sufficiently with the protocol and display an evaluable PK profile (example, exposure to treatment, availability of measurements and absence of major protocol violations) were included in the PK analysis set.

Outcome measures

Outcome measures
Measure	Part 1: Soticlestat 300 mg Alone n=14 Participants Soticlestat 300 mg administered as 3\*100 mg tablets, orally, once on Day 1 of Period 1.	Part 1: Soticlestat 300 mg + Itraconazole 200 mg n=14 Participants Itraconazole 200 mg administered as 20 mL of 10 mg/ml solution, orally, once daily from Day 1 up to Day 11 of Period 2, and soticlestat 300 mg administered as 3\*100 mg tablets, orally, once on Day 5 of Period 2.	Part 1: Soticlestat 300 mg + Itraconazole 200 mg Soticlestat 300 mg administered as 3\100 mg tablets, orally, once on Day 1 of Period 1, followed by 4 days washout period, further followed by itraconazole 200 mg administered as 20 mL of 10 mg/ml solution, orally, once daily from Day 1 up to Day 11 of Period 2 and soticlestat 300 mg administered as 3\100 mg tablets, orally, once on Day 5 of Period 2.	Part 2: Soticlestat 300 mg Alone Soticlestat 300 mg administered as 3\*100 mg tablets, orally, once on Day 1 of Period 1.	Part 2: Mefenamic Acid 500 mg and 250 mg Initial single dose of mefenamic acid 500 mg administered as 2\*250 mg capsules, orally on the morning of Day 1 and 250 mg subsequent doses at every six hours from Day 1 up to Day 7 of Period 2.	Part 2: Soticlestat 300 mg + Mefenamic Acid 500 mg and 250 mg Soticlestat 300 mg administered as 3\100 mg tablets, orally, once on Day 1 of Period 1, followed by 4 days washout period, further followed by initial single dose of mefenamic acid 500 mg administered as 2\250 mg capsules, orally on the morning of Day 1 and 250 mg subsequent doses at every six hours from Day 1 up to Day 7 of Period 2, and soticlestat 300 mg administered as 3\*100 mg tablets, orally, once on Day 2 of Period 2.
Part 1, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Soticlestat When Administered Alone and With Itraconazole	0.500 hour Interval 0.5 to 0.76	0.503 hour Interval 0.5 to 1.0	—	—	—	—

PRIMARY outcome

Timeframe: Soticlestat alone: Period 1, Day 1 pre-dose and at multiple timepoints (up to 96 hours) post-dose; Soticlestat with mefenamic acid: Period 2, Day 2 pre-dose and at multiple timepoints (up to 144 hours) post-dose

Population: All participants who complied sufficiently with the protocol and display an evaluable PK profile (example, exposure to treatment, availability of measurements and absence of major protocol violations) were included in the PK analysis set.

Outcome measures

Outcome measures
Measure	Part 1: Soticlestat 300 mg Alone n=14 Participants Soticlestat 300 mg administered as 3\*100 mg tablets, orally, once on Day 1 of Period 1.	Part 1: Soticlestat 300 mg + Itraconazole 200 mg n=14 Participants Itraconazole 200 mg administered as 20 mL of 10 mg/ml solution, orally, once daily from Day 1 up to Day 11 of Period 2, and soticlestat 300 mg administered as 3\*100 mg tablets, orally, once on Day 5 of Period 2.	Part 1: Soticlestat 300 mg + Itraconazole 200 mg Soticlestat 300 mg administered as 3\100 mg tablets, orally, once on Day 1 of Period 1, followed by 4 days washout period, further followed by itraconazole 200 mg administered as 20 mL of 10 mg/ml solution, orally, once daily from Day 1 up to Day 11 of Period 2 and soticlestat 300 mg administered as 3\100 mg tablets, orally, once on Day 5 of Period 2.	Part 2: Soticlestat 300 mg Alone Soticlestat 300 mg administered as 3\*100 mg tablets, orally, once on Day 1 of Period 1.	Part 2: Mefenamic Acid 500 mg and 250 mg Initial single dose of mefenamic acid 500 mg administered as 2\*250 mg capsules, orally on the morning of Day 1 and 250 mg subsequent doses at every six hours from Day 1 up to Day 7 of Period 2.	Part 2: Soticlestat 300 mg + Mefenamic Acid 500 mg and 250 mg Soticlestat 300 mg administered as 3\100 mg tablets, orally, once on Day 1 of Period 1, followed by 4 days washout period, further followed by initial single dose of mefenamic acid 500 mg administered as 2\250 mg capsules, orally on the morning of Day 1 and 250 mg subsequent doses at every six hours from Day 1 up to Day 7 of Period 2, and soticlestat 300 mg administered as 3\*100 mg tablets, orally, once on Day 2 of Period 2.
Part 2, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Soticlestat When Administered Alone and With Mefenamic Acid	0.505 hour Interval 0.5 to 1.5	0.522 hour Interval 0.51 to 0.56	—	—	—	—

SECONDARY outcome

Timeframe: Part 1: from Day 1 of Period 1 up to 15 days after the last dose of soticlestat in Period 2 (up to Day 20 in Period 2); Part 2: from Day 1 of Period 1 up to 15 days after the last dose of soticlestat in Period 2 (up to Day 17 in Period 2)

Population: All participants who received at least one dose of the study drug(s) were included in the safety analysis set.

Outcome measures

Outcome measures
Measure	Part 1: Soticlestat 300 mg Alone n=14 Participants Soticlestat 300 mg administered as 3\*100 mg tablets, orally, once on Day 1 of Period 1.	Part 1: Soticlestat 300 mg + Itraconazole 200 mg n=14 Participants Itraconazole 200 mg administered as 20 mL of 10 mg/ml solution, orally, once daily from Day 1 up to Day 11 of Period 2, and soticlestat 300 mg administered as 3\*100 mg tablets, orally, once on Day 5 of Period 2.	Part 1: Soticlestat 300 mg + Itraconazole 200 mg n=14 Participants Soticlestat 300 mg administered as 3\100 mg tablets, orally, once on Day 1 of Period 1, followed by 4 days washout period, further followed by itraconazole 200 mg administered as 20 mL of 10 mg/ml solution, orally, once daily from Day 1 up to Day 11 of Period 2 and soticlestat 300 mg administered as 3\100 mg tablets, orally, once on Day 5 of Period 2.	Part 2: Soticlestat 300 mg Alone n=14 Participants Soticlestat 300 mg administered as 3\*100 mg tablets, orally, once on Day 1 of Period 1.	Part 2: Mefenamic Acid 500 mg and 250 mg n=14 Participants Initial single dose of mefenamic acid 500 mg administered as 2\*250 mg capsules, orally on the morning of Day 1 and 250 mg subsequent doses at every six hours from Day 1 up to Day 7 of Period 2.	Part 2: Soticlestat 300 mg + Mefenamic Acid 500 mg and 250 mg n=14 Participants Soticlestat 300 mg administered as 3\100 mg tablets, orally, once on Day 1 of Period 1, followed by 4 days washout period, further followed by initial single dose of mefenamic acid 500 mg administered as 2\250 mg capsules, orally on the morning of Day 1 and 250 mg subsequent doses at every six hours from Day 1 up to Day 7 of Period 2, and soticlestat 300 mg administered as 3\*100 mg tablets, orally, once on Day 2 of Period 2.
Parts 1 and 2: Number of Participants Reported One or More Treatment-emergent Adverse Event (TEAE)	1 Participants	2 Participants	3 Participants	1 Participants	0 Participants	3 Participants

SECONDARY outcome

Timeframe: Part 1: Day 1 of Period 1 up to Day 12 of Period 2; Part 2: Day 1 of Period 1 up to Day 8 of Period 2

Population: All participants who received at least one dose of the study drug(s) were included in the safety analysis set.

Outcome measures

Outcome measures
Measure	Part 1: Soticlestat 300 mg Alone n=14 Participants Soticlestat 300 mg administered as 3\*100 mg tablets, orally, once on Day 1 of Period 1.	Part 1: Soticlestat 300 mg + Itraconazole 200 mg n=14 Participants Itraconazole 200 mg administered as 20 mL of 10 mg/ml solution, orally, once daily from Day 1 up to Day 11 of Period 2, and soticlestat 300 mg administered as 3\*100 mg tablets, orally, once on Day 5 of Period 2.	Part 1: Soticlestat 300 mg + Itraconazole 200 mg n=14 Participants Soticlestat 300 mg administered as 3\100 mg tablets, orally, once on Day 1 of Period 1, followed by 4 days washout period, further followed by itraconazole 200 mg administered as 20 mL of 10 mg/ml solution, orally, once daily from Day 1 up to Day 11 of Period 2 and soticlestat 300 mg administered as 3\100 mg tablets, orally, once on Day 5 of Period 2.	Part 2: Soticlestat 300 mg Alone n=14 Participants Soticlestat 300 mg administered as 3\*100 mg tablets, orally, once on Day 1 of Period 1.	Part 2: Mefenamic Acid 500 mg and 250 mg n=14 Participants Initial single dose of mefenamic acid 500 mg administered as 2\*250 mg capsules, orally on the morning of Day 1 and 250 mg subsequent doses at every six hours from Day 1 up to Day 7 of Period 2.	Part 2: Soticlestat 300 mg + Mefenamic Acid 500 mg and 250 mg n=14 Participants Soticlestat 300 mg administered as 3\100 mg tablets, orally, once on Day 1 of Period 1, followed by 4 days washout period, further followed by initial single dose of mefenamic acid 500 mg administered as 2\250 mg capsules, orally on the morning of Day 1 and 250 mg subsequent doses at every six hours from Day 1 up to Day 7 of Period 2, and soticlestat 300 mg administered as 3\*100 mg tablets, orally, once on Day 2 of Period 2.
Parts 1 and 2: Number of Participants With Clinically Significant Abnormal Values for Laboratory Evaluations	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Part 1: Day 1 of Period 1 up to Day 12 of Period 2; Part 2: Day 1 of Period 1 up to Day 8 of Period 2

Population: All participants who received at least one dose of the study drug(s) were included in the safety analysis set.

Outcome measures

Outcome measures
Measure	Part 1: Soticlestat 300 mg Alone n=14 Participants Soticlestat 300 mg administered as 3\*100 mg tablets, orally, once on Day 1 of Period 1.	Part 1: Soticlestat 300 mg + Itraconazole 200 mg n=14 Participants Itraconazole 200 mg administered as 20 mL of 10 mg/ml solution, orally, once daily from Day 1 up to Day 11 of Period 2, and soticlestat 300 mg administered as 3\*100 mg tablets, orally, once on Day 5 of Period 2.	Part 1: Soticlestat 300 mg + Itraconazole 200 mg n=14 Participants Soticlestat 300 mg administered as 3\100 mg tablets, orally, once on Day 1 of Period 1, followed by 4 days washout period, further followed by itraconazole 200 mg administered as 20 mL of 10 mg/ml solution, orally, once daily from Day 1 up to Day 11 of Period 2 and soticlestat 300 mg administered as 3\100 mg tablets, orally, once on Day 5 of Period 2.	Part 2: Soticlestat 300 mg Alone n=14 Participants Soticlestat 300 mg administered as 3\*100 mg tablets, orally, once on Day 1 of Period 1.	Part 2: Mefenamic Acid 500 mg and 250 mg n=14 Participants Initial single dose of mefenamic acid 500 mg administered as 2\*250 mg capsules, orally on the morning of Day 1 and 250 mg subsequent doses at every six hours from Day 1 up to Day 7 of Period 2.	Part 2: Soticlestat 300 mg + Mefenamic Acid 500 mg and 250 mg n=14 Participants Soticlestat 300 mg administered as 3\100 mg tablets, orally, once on Day 1 of Period 1, followed by 4 days washout period, further followed by initial single dose of mefenamic acid 500 mg administered as 2\250 mg capsules, orally on the morning of Day 1 and 250 mg subsequent doses at every six hours from Day 1 up to Day 7 of Period 2, and soticlestat 300 mg administered as 3\*100 mg tablets, orally, once on Day 2 of Period 2.
Parts 1 and 2: Number of Participants With Clinically Significant Abnormal Values for Vital Signs	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Part 1: Day 1 of Period 1 up to Day 12 of Period 2; Part 2: Day 1 of Period 1 up to Day 8 of Period 2

Population: All participants who received at least one dose of the study drug(s) were included in the safety analysis set.

Outcome measures

Outcome measures
Measure	Part 1: Soticlestat 300 mg Alone n=14 Participants Soticlestat 300 mg administered as 3\*100 mg tablets, orally, once on Day 1 of Period 1.	Part 1: Soticlestat 300 mg + Itraconazole 200 mg n=14 Participants Itraconazole 200 mg administered as 20 mL of 10 mg/ml solution, orally, once daily from Day 1 up to Day 11 of Period 2, and soticlestat 300 mg administered as 3\*100 mg tablets, orally, once on Day 5 of Period 2.	Part 1: Soticlestat 300 mg + Itraconazole 200 mg n=14 Participants Soticlestat 300 mg administered as 3\100 mg tablets, orally, once on Day 1 of Period 1, followed by 4 days washout period, further followed by itraconazole 200 mg administered as 20 mL of 10 mg/ml solution, orally, once daily from Day 1 up to Day 11 of Period 2 and soticlestat 300 mg administered as 3\100 mg tablets, orally, once on Day 5 of Period 2.	Part 2: Soticlestat 300 mg Alone n=14 Participants Soticlestat 300 mg administered as 3\*100 mg tablets, orally, once on Day 1 of Period 1.	Part 2: Mefenamic Acid 500 mg and 250 mg n=14 Participants Initial single dose of mefenamic acid 500 mg administered as 2\*250 mg capsules, orally on the morning of Day 1 and 250 mg subsequent doses at every six hours from Day 1 up to Day 7 of Period 2.	Part 2: Soticlestat 300 mg + Mefenamic Acid 500 mg and 250 mg n=14 Participants Soticlestat 300 mg administered as 3\100 mg tablets, orally, once on Day 1 of Period 1, followed by 4 days washout period, further followed by initial single dose of mefenamic acid 500 mg administered as 2\250 mg capsules, orally on the morning of Day 1 and 250 mg subsequent doses at every six hours from Day 1 up to Day 7 of Period 2, and soticlestat 300 mg administered as 3\*100 mg tablets, orally, once on Day 2 of Period 2.
Parts 1 and 2: Number of Participants With Clinically Significant Abnormal Values for Electrocardiogram (ECG)	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Part 1: Day 1 of Period 1 up to Day 12 of Period 2; Part 2: Day 1 of Period 1 up to Day 8 of Period 2

Population: All participants who received at least one dose of the study drug(s) were included in the safety analysis set.

The C-SSRS is an interview-based rating scale to systematically assess any suicidality, suicidal behavior, or suicidal ideation. Any suicidality is emergence of any suicidal ideation or suicidal behavior. Any suicidal behavior was indicated when response was "yes" for any these questions- actual attempted to suicide, engaged in non-suicidal self-injurious behavior, interrupted attempt, aborted attempt, preparatory acts. Any suicidal ideation was indicated when response was "yes" for any of these questions- wish to be dead, non-specific active suicidal thoughts, active suicidal ideation with methods without intent to act or some intended to act, without specific plan or with specific plan and intended to suicide.