Trial Outcomes & Findings for A Study of Soticlestat in Healthy Adult Nondependent Recreational Drug Users With Central Nervous System (CNS) Depressant Experience (NCT NCT05602818)

Results Overview

Drug liking ("at this moment") assessed how much a participant likes or dislikes a drug effect at the time the question was being asked. It was scored using a 0 to 100-point bipolar VAS, where 0: Strong disliking, 50: Neither like nor dislike (neutral point), 100: Strong liking. A higher score indicates stronger liking.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

100 participants

Primary outcome timeframe

Day 1 of each Treatment Period: 15, 30, and 45 minutes, and 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, and 24 hours post-dose

Results posted on

2024-12-09

Participant Flow

Participants took part in the study at 1 investigative site in the United States from 15 November 2022 to 07 July 2023. A total of 100 participants participated in the Qualification Phase, of which 69 met the qualification criteria, out of which 68 enrolled in the treatment phase and were randomized to 1 of the 10 sequences of the Treatment Phase.

Participants entered a Qualification Phase to determine if they were able to discriminate the drug effects of the positive control, alprazolam, when compared with placebo. Only participants who could discriminate the drug effects of the positive control were randomized into one of the 10 sequences of Treatment Phase (ABECD, BCADE, CDBEA, DECAB, EADBC, DCEBA, EDACB, AEBDC, BACED or CBDAE) to receive soticlestat, alprazolam or placebo.

Participant milestones

Participant milestones
Measure	Qualification Phase: Sequence 1 All participants received: Day 1: Alprazolam 2 milligrams (mg), Day 2: Alprazolam matching placebo. Orally with a 4-day washout between Qualification Phase and Treatment Phase.	Qualification Phase: Sequence 2 All participants received: Day 1: Alprazolam matching placebo, Day 2: Alprazolam 2 mg. Orally with a 4-day washout between Qualification Phase and Treatment Phase.	Treatment Phase, Sequence 1: ABECD All participants received: Period 1: Soticlestat 300 milligrams (mg) (Treatment A), Period 2: Soticlestat 600 mg (Treatment B), Period 3: Placebo (Treatment E), Period 4: Soticlestat 900 mg (Treatment C), Period 5: Alprazolam 2 mg (Treatment D). Orally with a 7-day washout between doses.	Treatment Phase, Sequence 2: BCADE All participants received: Period 1: Soticlestat 600 mg (Treatment B), Period 2: Soticlestat 900 mg (Treatment C), Period 3: Soticlestat 300 mg (Treatment A), Period 4: Alprazolam 2 mg (Treatment D), Period 5: Placebo (Treatment E). Orally with a 7-day washout between doses.	Treatment Phase, Sequence 3: CDBEA All participants received: Period 1: Soticlestat 900 mg (Treatment C), Period 2: Alprazolam 2 mg (Treatment D), Period 3: Soticlestat 600 mg (Treatment B), Period 4: Placebo (Treatment E), Period 5: Soticlestat 300 mg (Treatment A). Orally with a 7-day washout between doses.	Treatment Phase, Sequence 4: DECAB Period 1: Alprazolam 2 mg (Treatment D), Period 2: Placebo (Treatment E), Period 3: Soticlestat 900 mg (Treatment C), Period 4: Soticlestat 300 mg (Treatment A), Period 5: Soticlestat 600 mg (Treatment B). Orally with a 7-day washout between doses.	Treatment Phase, Sequence 5: EADBC All participants received: Period 1: Placebo (Treatment E), Period 2: Soticlestat 300 mg (Treatment A), Period 3: Alprazolam 2 mg (Treatment D), Period 4: Soticlestat 600 mg (Treatment B), Period 5: Soticlestat 900 mg (Treatment C). Orally with a 7-day washout between doses.	Treatment Phase, Sequence 6: DCEBA All participants received: Period 1: Alprazolam 2 mg (Treatment D), Period 2: Soticlestat 900 mg (Treatment C), Period 3: Placebo, (Treatment E), Period 4: Soticlestat 600 mg, (Treatment B), Period 5: Soticlestat 300 mg (Treatment A). Orally with a 7-day washout between doses.	Treatment Phase, Sequence 7: EDACB All participants received: Period 1: Placebo (Treatment E), Period 2: Alprazolam 2 mg (Treatment D), Period 3: Soticlestat 300 mg (Treatment A), Period 4: Soticlestat 900 mg (Treatment C), Period 5: Soticlestat 600 mg (Treatment B). Orally with a 7-day washout between doses.	Treatment Phase, Sequence 8: AEBDC All participants received: Period 1: Soticlestat 300 mg (Treatment A), Period 2: Placebo (Treatment E), Period 3: Soticlestat 600 mg (Treatment B), Period 4: Alprazolam 2 mg (Treatment D), Period 5: Soticlestat 900 mg (Treatment C). Orally with a 7-day washout between doses.	Treatment Phase, Sequence 9: BACED All participants received: Period 1: Soticlestat 600 mg (Treatment B), Period 2: Soticlestat 300 mg (Treatment A), Period 3: Soticlestat 900 mg (Treatment C), Period 4: Placebo (Treatment E), Period 5: Alprazolam 2 mg (Treatment D). Orally with a 7-day washout between doses.	Treatment Phase, Sequence 10: CBDAE All participants received: Period 1: Soticlestat 900 mg (Treatment C), Period 2: Soticlestat 600 mg (Treatment B), Period 3: Alprazolam 2 mg (Treatment D), Period 4: Soticlestat 300 mg (Treatment A), Period 5: Placebo (Treatment E). Orally with a 7-day washout between doses.
Qualification Phase (3 Days) STARTED	50	50	0	0	0	0	0	0	0	0	0	0
Qualification Phase (3 Days) Qualification Safety Analysis Set (Treated)	49	49	0	0	0	0	0	0	0	0	0	0
Qualification Phase (3 Days) COMPLETED	33	36	0	0	0	0	0	0	0	0	0	0
Qualification Phase (3 Days) NOT COMPLETED	17	14	0	0	0	0	0	0	0	0	0	0
Treatment Phase (29 Days) STARTED	0	0	7	6	6	6	8	8	6	6	8	7
Treatment Phase (29 Days) Safety Analysis Set (Treated)	0	0	7	6	6	6	8	8	6	6	7	7
Treatment Phase (29 Days) COMPLETED	0	0	4	5	5	5	5	6	5	5	4	5
Treatment Phase (29 Days) NOT COMPLETED	0	0	3	1	1	1	3	2	1	1	4	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Qualification Phase: Sequence 1 All participants received: Day 1: Alprazolam 2 milligrams (mg), Day 2: Alprazolam matching placebo. Orally with a 4-day washout between Qualification Phase and Treatment Phase.	Qualification Phase: Sequence 2 All participants received: Day 1: Alprazolam matching placebo, Day 2: Alprazolam 2 mg. Orally with a 4-day washout between Qualification Phase and Treatment Phase.	Treatment Phase, Sequence 1: ABECD All participants received: Period 1: Soticlestat 300 milligrams (mg) (Treatment A), Period 2: Soticlestat 600 mg (Treatment B), Period 3: Placebo (Treatment E), Period 4: Soticlestat 900 mg (Treatment C), Period 5: Alprazolam 2 mg (Treatment D). Orally with a 7-day washout between doses.	Treatment Phase, Sequence 2: BCADE All participants received: Period 1: Soticlestat 600 mg (Treatment B), Period 2: Soticlestat 900 mg (Treatment C), Period 3: Soticlestat 300 mg (Treatment A), Period 4: Alprazolam 2 mg (Treatment D), Period 5: Placebo (Treatment E). Orally with a 7-day washout between doses.	Treatment Phase, Sequence 3: CDBEA All participants received: Period 1: Soticlestat 900 mg (Treatment C), Period 2: Alprazolam 2 mg (Treatment D), Period 3: Soticlestat 600 mg (Treatment B), Period 4: Placebo (Treatment E), Period 5: Soticlestat 300 mg (Treatment A). Orally with a 7-day washout between doses.	Treatment Phase, Sequence 4: DECAB Period 1: Alprazolam 2 mg (Treatment D), Period 2: Placebo (Treatment E), Period 3: Soticlestat 900 mg (Treatment C), Period 4: Soticlestat 300 mg (Treatment A), Period 5: Soticlestat 600 mg (Treatment B). Orally with a 7-day washout between doses.	Treatment Phase, Sequence 5: EADBC All participants received: Period 1: Placebo (Treatment E), Period 2: Soticlestat 300 mg (Treatment A), Period 3: Alprazolam 2 mg (Treatment D), Period 4: Soticlestat 600 mg (Treatment B), Period 5: Soticlestat 900 mg (Treatment C). Orally with a 7-day washout between doses.	Treatment Phase, Sequence 6: DCEBA All participants received: Period 1: Alprazolam 2 mg (Treatment D), Period 2: Soticlestat 900 mg (Treatment C), Period 3: Placebo, (Treatment E), Period 4: Soticlestat 600 mg, (Treatment B), Period 5: Soticlestat 300 mg (Treatment A). Orally with a 7-day washout between doses.	Treatment Phase, Sequence 7: EDACB All participants received: Period 1: Placebo (Treatment E), Period 2: Alprazolam 2 mg (Treatment D), Period 3: Soticlestat 300 mg (Treatment A), Period 4: Soticlestat 900 mg (Treatment C), Period 5: Soticlestat 600 mg (Treatment B). Orally with a 7-day washout between doses.	Treatment Phase, Sequence 8: AEBDC All participants received: Period 1: Soticlestat 300 mg (Treatment A), Period 2: Placebo (Treatment E), Period 3: Soticlestat 600 mg (Treatment B), Period 4: Alprazolam 2 mg (Treatment D), Period 5: Soticlestat 900 mg (Treatment C). Orally with a 7-day washout between doses.	Treatment Phase, Sequence 9: BACED All participants received: Period 1: Soticlestat 600 mg (Treatment B), Period 2: Soticlestat 300 mg (Treatment A), Period 3: Soticlestat 900 mg (Treatment C), Period 4: Placebo (Treatment E), Period 5: Alprazolam 2 mg (Treatment D). Orally with a 7-day washout between doses.	Treatment Phase, Sequence 10: CBDAE All participants received: Period 1: Soticlestat 900 mg (Treatment C), Period 2: Soticlestat 600 mg (Treatment B), Period 3: Alprazolam 2 mg (Treatment D), Period 4: Soticlestat 300 mg (Treatment A), Period 5: Placebo (Treatment E). Orally with a 7-day washout between doses.
Qualification Phase (3 Days) Adverse Event	1	0	0	0	0	0	0	0	0	0	0	0
Qualification Phase (3 Days) Did Not Meet Qualification Criteria	13	13	0	0	0	0	0	0	0	0	0	0
Qualification Phase (3 Days) Withdrawal by Subject	2	0	0	0	0	0	0	0	0	0	0	0
Qualification Phase (3 Days) Other	1	0	0	0	0	0	0	0	0	0	0	0
Qualification Phase (3 Days) Failure to Meet Continuation Criteria	0	1	0	0	0	0	0	0	0	0	0	0
Treatment Phase (29 Days) Protocol Violation	0	0	2	1	1	1	2	2	1	1	2	1
Treatment Phase (29 Days) Withdrawal by Subject	0	0	0	0	0	0	0	0	0	0	1	1
Treatment Phase (29 Days) Physician Decision	0	0	1	0	0	0	1	0	0	0	1	0

Baseline Characteristics

A Study of Soticlestat in Healthy Adult Nondependent Recreational Drug Users With Central Nervous System (CNS) Depressant Experience

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Qualification Phase: All Participants n=98 Participants All participants who received at least 1 dose of study drug in the Qualification phase.: Sequence 1, Day 1: Alprazolam 2 mg, Day 2: Alprazolam matching placebo. Sequence 2, Day 1: Alprazolam matching placebo, Day 2: Alprazolam 2 mg. Orally with a 4-day washout between Qualification Phase and Treatment Phase.
Age, Continuous	33.1 years STANDARD_DEVIATION 7.16 • n=5 Participants
Sex: Female, Male Female	11 Participants n=5 Participants
Sex: Female, Male Male	87 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	5 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	90 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	3 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	74 Participants n=5 Participants
Race (NIH/OMB) White	23 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: Day 1 of each Treatment Period: 15, 30, and 45 minutes, and 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, and 24 hours post-dose

Population: The Modified Completer Analysis Set consisted of all participants in the Completer Analysis Set, excluding those whose Drug Liking "at this moment" VAS Emax scores met the elimination criteria defined in the SAP. As pre-specified in SAP, the pharmacodynamic data was planned to be collected and reported as per the treatment dose.

Drug liking ("at this moment") assessed how much a participant likes or dislikes a drug effect at the time the question was being asked. It was scored using a 0 to 100-point bipolar VAS, where 0: Strong disliking, 50: Neither like nor dislike (neutral point), 100: Strong liking. A higher score indicates stronger liking.

Outcome measures

Outcome measures
Measure	Treatment Phase: Soticlestat 300 mg n=48 Participants Soticlestat 300 mg as a single oral dose in one of five treatment periods.	Treatment Phase: Soticlestat 600 mg n=48 Participants Soticlestat 600 mg as a single oral dose in one of five treatment periods.	Treatment Phase: Soticlestat 900 mg n=48 Participants Soticlestat 900 mg as a single oral dose in one of five treatment periods.	Treatment Phase: Alprazolam 2 mg n=48 Participants Alprazolam 2 mg as a single oral dose in one of five treatment periods.	Treatment Phase: Placebo n=48 Participants Placebo as a single oral dose in one of five treatment periods.
Treatment Phase: Drug Liking (Maximum Effect [Emax]) "At This Moment" as Assessed Using Bipolar Visual Analogue Scale (VAS)	56.7 score on a scale Standard Error 1.87	57.3 score on a scale Standard Error 1.89	56.5 score on a scale Standard Error 1.55	88.5 score on a scale Standard Error 1.58	55.6 score on a scale Standard Error 1.63

SECONDARY outcome

Timeframe: Day 1 of each Treatment Period: 12 and 24 hours post-dose

Population: The Modified Completer Analysis Set consisted of all participants in the Completer Analysis Set, excluding those whose Drug Liking "at this moment" VAS Emax scores met the elimination criteria defined in the SAP. As pre-specified in SAP, the pharmacodynamic data was planned to be collected and reported as per the treatment dose.

Overall drug liking assesses participant's overall experience with the drug by assessing the participant's overall liking for the drug. It was scored using a 100-point bipolar VAS, where 0: Strong disliking, 50: Neither like nor dislike (neutral point), 100: Strong liking. A higher score indicates better liking. The "overall drug liking" was an independent measure and not an "at this moment" assessment.

Outcome measures

Outcome measures
Measure	Treatment Phase: Soticlestat 300 mg n=48 Participants Soticlestat 300 mg as a single oral dose in one of five treatment periods.	Treatment Phase: Soticlestat 600 mg n=48 Participants Soticlestat 600 mg as a single oral dose in one of five treatment periods.	Treatment Phase: Soticlestat 900 mg n=48 Participants Soticlestat 900 mg as a single oral dose in one of five treatment periods.	Treatment Phase: Alprazolam 2 mg n=48 Participants Alprazolam 2 mg as a single oral dose in one of five treatment periods.	Treatment Phase: Placebo n=48 Participants Placebo as a single oral dose in one of five treatment periods.
Treatment Phase: Overall Drug Liking (Emax) Assessed Using Bipolar VAS	58.2 score on a scale Standard Error 2.40	58.5 score on a scale Standard Error 2.32	59.5 score on a scale Standard Error 2.45	90.0 score on a scale Standard Error 1.82	58.0 score on a scale Standard Error 2.17

SECONDARY outcome

Timeframe: Day 1 of each Treatment Period: 12 and 24 hours post-dose

Population: The Modified Completer Analysis Set consisted of all participants in the Completer Analysis Set, excluding those whose Drug Liking "at this moment" VAS Emax scores met the elimination criteria defined in the SAP. As pre-specified in SAP, the pharmacodynamic data was planned to be collected and reported as per the treatment dose.

Take drug again was a subjective assessment of the degree to which a participant would desire to take the drug again if given the opportunity. It was scored using a 0 to 100-point bipolar VAS, where 0: Definitely not, 50: Neutral, 100: Definitely so. A higher score indicates stronger desire.

Outcome measures

Outcome measures
Measure	Treatment Phase: Soticlestat 300 mg n=48 Participants Soticlestat 300 mg as a single oral dose in one of five treatment periods.	Treatment Phase: Soticlestat 600 mg n=48 Participants Soticlestat 600 mg as a single oral dose in one of five treatment periods.	Treatment Phase: Soticlestat 900 mg n=48 Participants Soticlestat 900 mg as a single oral dose in one of five treatment periods.	Treatment Phase: Alprazolam 2 mg n=48 Participants Alprazolam 2 mg as a single oral dose in one of five treatment periods.	Treatment Phase: Placebo n=48 Participants Placebo as a single oral dose in one of five treatment periods.
Treatment Phase: Take Drug Again (Emax) Assessed "Overall" by Using Bipolar VAS	58.5 score on a scale Standard Error 2.80	57.6 score on a scale Standard Error 2.56	58.4 score on a scale Standard Error 2.72	92.0 score on a scale Standard Error 1.46	57.1 score on a scale Standard Error 2.14

SECONDARY outcome

Timeframe: Day 1 of each Treatment Period: 15, 30, and 45 minutes, and 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, and 24 hours post-dose

Population: The Modified Completer Analysis Set consisted of all participants in the Completer Analysis Set, excluding those whose Drug Liking "at this moment" VAS Emax scores met the elimination criteria defined in the SAP. As pre-specified in SAP, the pharmacodynamic data was planned to be collected and reported as per the treatment dose.

Bad drug effects assessed the bad effect of drug experienced by the participant at the time the question is being asked. It was scored using a 100-point unipolar VAS, where responses were unidirectional and ranged from 0 (Not at all) to 100 (Extremely). A higher score indicated a stronger bad drug effect.

Outcome measures

Outcome measures
Measure	Treatment Phase: Soticlestat 300 mg n=48 Participants Soticlestat 300 mg as a single oral dose in one of five treatment periods.	Treatment Phase: Soticlestat 600 mg n=48 Participants Soticlestat 600 mg as a single oral dose in one of five treatment periods.	Treatment Phase: Soticlestat 900 mg n=48 Participants Soticlestat 900 mg as a single oral dose in one of five treatment periods.	Treatment Phase: Alprazolam 2 mg n=48 Participants Alprazolam 2 mg as a single oral dose in one of five treatment periods.	Treatment Phase: Placebo n=48 Participants Placebo as a single oral dose in one of five treatment periods.
Treatment Phase: Bad Drug Effects (Emax) Assessed "At This Moment" by Using Unipolar VAS	2.3 score on a scale Standard Error 1.58	1.4 score on a scale Standard Error 1.06	2.5 score on a scale Standard Error 2.08	28.5 score on a scale Standard Error 4.71	1.2 score on a scale Standard Error 0.93

SECONDARY outcome

Timeframe: Day 1 of each Treatment Period: 15, 30, and 45 minutes, and 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, and 24 hours post-dose

Population: The Modified Completer Analysis Set consisted of all participants in the Completer Analysis Set, excluding those whose Drug Liking "at this moment" VAS Emax scores met the elimination criteria defined in the SAP. As pre-specified in SAP, the pharmacodynamic data was planned to be collected and reported as per the treatment dose.

Good drug effects assessed the good effect of drug experienced by the participant at the time the question was being asked. It was scored using a 100-point unipolar VAS, where responses were unidirectional and range from 0 (Not at all) to 100 (extremely). A higher score indicated a stronger good drug effect.

Outcome measures

Outcome measures
Measure	Treatment Phase: Soticlestat 300 mg n=48 Participants Soticlestat 300 mg as a single oral dose in one of five treatment periods.	Treatment Phase: Soticlestat 600 mg n=48 Participants Soticlestat 600 mg as a single oral dose in one of five treatment periods.	Treatment Phase: Soticlestat 900 mg n=48 Participants Soticlestat 900 mg as a single oral dose in one of five treatment periods.	Treatment Phase: Alprazolam 2 mg n=48 Participants Alprazolam 2 mg as a single oral dose in one of five treatment periods.	Treatment Phase: Placebo n=48 Participants Placebo as a single oral dose in one of five treatment periods.
Treatment Phase: Good Drug Effects (Emax) Assessed "At This Moment" by Using Unipolar VAS	10.9 score on a scale Standard Error 3.18	10.1 score on a scale Standard Error 2.78	11.6 score on a scale Standard Error 3.10	74.0 score on a scale Standard Error 3.42	8.1 score on a scale Standard Error 2.74

SECONDARY outcome

Timeframe: Day 1 of each Treatment Period: 15, 30, and 45 minutes, and 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, and 24 hours post-dose

Population: The Modified Completer Analysis Set consisted of all participants in the Completer Analysis Set, excluding those whose Drug Liking "at this moment" VAS Emax scores met the elimination criteria defined in the SAP. As pre-specified in SAP, the pharmacodynamic data was planned to be collected and reported as per the treatment dose.

High assessed the degree that a participant feels a good effect (that is, euphoria) at the time the question was being asked. It was scored using a 100-point unipolar VAS, where responses were unidirectional and ranged from 0 (Not at all) to 100 (Extremely). A higher score indicated a stronger high effect.

Outcome measures

Outcome measures
Measure	Treatment Phase: Soticlestat 300 mg n=48 Participants Soticlestat 300 mg as a single oral dose in one of five treatment periods.	Treatment Phase: Soticlestat 600 mg n=48 Participants Soticlestat 600 mg as a single oral dose in one of five treatment periods.	Treatment Phase: Soticlestat 900 mg n=48 Participants Soticlestat 900 mg as a single oral dose in one of five treatment periods.	Treatment Phase: Alprazolam 2 mg n=48 Participants Alprazolam 2 mg as a single oral dose in one of five treatment periods.	Treatment Phase: Placebo n=48 Participants Placebo as a single oral dose in one of five treatment periods.
Treatment Phase: High (Emax) Assessed "At This Moment" by Using Unipolar VAS	10.3 score on a scale Standard Error 2.95	12.0 score on a scale Standard Error 2.94	11.3 score on a scale Standard Error 3.16	72.8 score on a scale Standard Error 3.49	8.1 score on a scale Standard Error 2.62

SECONDARY outcome

Timeframe: From start of study drug administration (Day 1) up to Day 37

Population: The Safety Analysis Set consisted of all participants who received at least 1 dose of study drug in the Treatment phase. As pre-specified in SAP, the safety data was planned to be collected and reported as per treatment dose. Here, "overall number of participants analyzed" signified participants who received the specified treatment.

An AE was defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A TEAE was defined as an adverse event that started or worsened during or after the first dose of study drug.