Healthy Volunteers
Conditions
Keywords
Drug Therapy
Brief summary
The main aim is to evaluate the relative abuse potential of soticlestat in healthy adults who has used central nervous system (CNS) depressants for recreational nontherapeutic reasons.
Detailed description
The drug being tested in this study is called soticlestat. Soticlestat is being tested in healthy participants. This study will assess the relative abuse potential of soticlestat compared to alprazolam and placebo in healthy adult, nondependent recreational drug users with CNS depressant experience. The study will enroll approximately 110 participants. Participants will be randomly (by chance, like flipping a coin) assigned to treatments of the study. Treatment order will remain undisclosed to the participants and study doctor (unless there is an urgent medical need). This single center trial will be conducted in the United States. Participants will be followed up for up to 7 days after the last dose of study drug for a follow-up assessment. The overall time to participate in this study is approximately 11 weeks.
Interventions
DRUGSoticlestat 300 mg
Administered orally.
DRUGSoticlestat 600 mg
Administered orally.
DRUGSoticlestat 900 mg
Administered orally.
DRUGAlprazolam
Administered orally.
DRUGPlacebo
Administered orally.
Sponsors
Takeda
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
1. Healthy as determined by the investigator. 2. Current CNS depressant user who has used CNS depressants (example, benzodiazepines, barbiturates, zolpidem, eszopiclone, zopiclone, propofol/fospropofol, gamma-hydroxybutyrate) for recreational, nontherapeutic reasons at least 10 times in their lifetime and at least once in the 12 weeks prior to screening. Participant must also have recreational experience with at least 1 other drug class associated with abuse (example, opioids, stimulants, cannabinoids, hallucinogens, dissociatives) at least 10 times in their lifetime. 3. Body mass index (BMI) of 18.5 to 35.0 kilogram per square meter (kg/m\^2), inclusive, and a minimum body weight of 50.0 Kilogram (kg) at screening.
Exclusion criteria
1. Self-reported history of drug or alcohol dependence (within the past 1 year, except caffeine or nicotine, prior to the screening visit). 2. Positive alcohol breathalyzer or urine drug screen (UDS) for substances of abuse at admission, excluding tetrahydrocannabinol (THC). 3. Heavy smoker or user of other types of nicotine products (greater than \[\>\] 20 cigarettes equivalent per day). 4. Unable to abstain from smoking for at least 2 hours before and at least 8 hours after dosing. 5. Consumes excessive amounts, defined as greater than 4 servings (1 serving is approximately equivalent to 120 mg of caffeine) of coffee, tea, cola, energy drinks, or other caffeinated beverages per day.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Treatment Phase: Drug Liking (Maximum Effect [Emax]) "At This Moment" as Assessed Using Bipolar Visual Analogue Scale (VAS) | 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 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Treatment Phase: Overall Drug Liking (Emax) Assessed Using Bipolar VAS | Day 1 of each Treatment Period: 12 and 24 hours post-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. |
| Treatment Phase: Take Drug Again (Emax) Assessed "Overall" by Using Bipolar VAS | Day 1 of each Treatment Period: 12 and 24 hours post-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. |
| Treatment Phase: Bad Drug Effects (Emax) Assessed "At This Moment" by Using Unipolar VAS | 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 | 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. |
| Treatment Phase: Good Drug Effects (Emax) Assessed "At This Moment" by Using Unipolar VAS | 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 | 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. |
| Treatment Phase: High (Emax) Assessed "At This Moment" by Using Unipolar VAS | 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 | 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. |
| Treatment Phase: Number of Participants With One or More Treatment-emergent Adverse Events (TEAEs) | From start of study drug administration (Day 1) up to Day 37 | 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. |
Countries
United States
Contacts
STUDY_DIRECTORStudy Director
Takeda (Note: This product was divested to Mistrau Bio, Inc. in 2026)
Participant flow
Recruitment details
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.
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| Qualification Phase: All 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. | 98 |
| Total | 98 |
Baseline characteristics
| Characteristic | Qualification Phase: All Participants |
|---|---|
| Age, Continuous | 33.1 years STANDARD_DEVIATION 7.16 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 90 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 3 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 74 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 23 Participants |
| Sex: Female, Male Female | 11 Participants |
| Sex: Female, Male Male | 87 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 96 | 0 / 98 | 0 / 63 | 0 / 63 | 0 / 61 | 0 / 59 | 0 / 62 |
| other Total, other adverse events | 2 / 96 | 83 / 98 | 14 / 63 | 10 / 63 | 9 / 61 | 50 / 59 | 8 / 62 |
| serious Total, serious adverse events | 0 / 96 | 0 / 98 | 0 / 63 | 0 / 63 | 0 / 61 | 0 / 59 | 0 / 62 |
Outcome results
Primary
Treatment Phase: Drug Liking (Maximum Effect [Emax]) At This Moment as Assessed Using Bipolar Visual Analogue Scale (VAS)
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.
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment Phase: Soticlestat 300 mg | 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 |
| Treatment Phase: Soticlestat 600 mg | Treatment Phase: Drug Liking (Maximum Effect [Emax]) At This Moment as Assessed Using Bipolar Visual Analogue Scale (VAS) | 57.3 score on a scale | Standard Error 1.89 |
| Treatment Phase: Soticlestat 900 mg | Treatment Phase: Drug Liking (Maximum Effect [Emax]) At This Moment as Assessed Using Bipolar Visual Analogue Scale (VAS) | 56.5 score on a scale | Standard Error 1.55 |
| Treatment Phase: Alprazolam 2 mg | Treatment Phase: Drug Liking (Maximum Effect [Emax]) At This Moment as Assessed Using Bipolar Visual Analogue Scale (VAS) | 88.5 score on a scale | Standard Error 1.58 |
| Treatment Phase: Placebo | Treatment Phase: Drug Liking (Maximum Effect [Emax]) At This Moment as Assessed Using Bipolar Visual Analogue Scale (VAS) | 55.6 score on a scale | Standard Error 1.63 |
Secondary
Treatment Phase: Bad Drug Effects (Emax) Assessed At This Moment by Using Unipolar VAS
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.
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment Phase: Soticlestat 300 mg | Treatment Phase: Bad Drug Effects (Emax) Assessed At This Moment by Using Unipolar VAS | 2.3 score on a scale | Standard Error 1.58 |
| Treatment Phase: Soticlestat 600 mg | Treatment Phase: Bad Drug Effects (Emax) Assessed At This Moment by Using Unipolar VAS | 1.4 score on a scale | Standard Error 1.06 |
| Treatment Phase: Soticlestat 900 mg | Treatment Phase: Bad Drug Effects (Emax) Assessed At This Moment by Using Unipolar VAS | 2.5 score on a scale | Standard Error 2.08 |
| Treatment Phase: Alprazolam 2 mg | Treatment Phase: Bad Drug Effects (Emax) Assessed At This Moment by Using Unipolar VAS | 28.5 score on a scale | Standard Error 4.71 |
| Treatment Phase: Placebo | Treatment Phase: Bad Drug Effects (Emax) Assessed At This Moment by Using Unipolar VAS | 1.2 score on a scale | Standard Error 0.93 |
Secondary
Treatment Phase: Good Drug Effects (Emax) Assessed At This Moment by Using Unipolar VAS
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.
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment Phase: Soticlestat 300 mg | Treatment Phase: Good Drug Effects (Emax) Assessed At This Moment by Using Unipolar VAS | 10.9 score on a scale | Standard Error 3.18 |
| Treatment Phase: Soticlestat 600 mg | Treatment Phase: Good Drug Effects (Emax) Assessed At This Moment by Using Unipolar VAS | 10.1 score on a scale | Standard Error 2.78 |
| Treatment Phase: Soticlestat 900 mg | Treatment Phase: Good Drug Effects (Emax) Assessed At This Moment by Using Unipolar VAS | 11.6 score on a scale | Standard Error 3.1 |
| Treatment Phase: Alprazolam 2 mg | Treatment Phase: Good Drug Effects (Emax) Assessed At This Moment by Using Unipolar VAS | 74.0 score on a scale | Standard Error 3.42 |
| Treatment Phase: Placebo | Treatment Phase: Good Drug Effects (Emax) Assessed At This Moment by Using Unipolar VAS | 8.1 score on a scale | Standard Error 2.74 |
Secondary
Treatment Phase: High (Emax) Assessed At This Moment by Using Unipolar VAS
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.
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment Phase: Soticlestat 300 mg | Treatment Phase: High (Emax) Assessed At This Moment by Using Unipolar VAS | 10.3 score on a scale | Standard Error 2.95 |
| Treatment Phase: Soticlestat 600 mg | Treatment Phase: High (Emax) Assessed At This Moment by Using Unipolar VAS | 12.0 score on a scale | Standard Error 2.94 |
| Treatment Phase: Soticlestat 900 mg | Treatment Phase: High (Emax) Assessed At This Moment by Using Unipolar VAS | 11.3 score on a scale | Standard Error 3.16 |
| Treatment Phase: Alprazolam 2 mg | Treatment Phase: High (Emax) Assessed At This Moment by Using Unipolar VAS | 72.8 score on a scale | Standard Error 3.49 |
| Treatment Phase: Placebo | Treatment Phase: High (Emax) Assessed At This Moment by Using Unipolar VAS | 8.1 score on a scale | Standard Error 2.62 |
Secondary
Treatment Phase: Number of Participants With One or More Treatment-emergent Adverse Events (TEAEs)
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.
Time frame: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment Phase: Soticlestat 300 mg | Treatment Phase: Number of Participants With One or More Treatment-emergent Adverse Events (TEAEs) | 17 Participants |
| Treatment Phase: Soticlestat 600 mg | Treatment Phase: Number of Participants With One or More Treatment-emergent Adverse Events (TEAEs) | 12 Participants |
| Treatment Phase: Soticlestat 900 mg | Treatment Phase: Number of Participants With One or More Treatment-emergent Adverse Events (TEAEs) | 13 Participants |
| Treatment Phase: Alprazolam 2 mg | Treatment Phase: Number of Participants With One or More Treatment-emergent Adverse Events (TEAEs) | 52 Participants |
| Treatment Phase: Placebo | Treatment Phase: Number of Participants With One or More Treatment-emergent Adverse Events (TEAEs) | 15 Participants |
Secondary
Treatment Phase: Overall Drug Liking (Emax) Assessed Using Bipolar VAS
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.
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment Phase: Soticlestat 300 mg | Treatment Phase: Overall Drug Liking (Emax) Assessed Using Bipolar VAS | 58.2 score on a scale | Standard Error 2.4 |
| Treatment Phase: Soticlestat 600 mg | Treatment Phase: Overall Drug Liking (Emax) Assessed Using Bipolar VAS | 58.5 score on a scale | Standard Error 2.32 |
| Treatment Phase: Soticlestat 900 mg | Treatment Phase: Overall Drug Liking (Emax) Assessed Using Bipolar VAS | 59.5 score on a scale | Standard Error 2.45 |
| Treatment Phase: Alprazolam 2 mg | Treatment Phase: Overall Drug Liking (Emax) Assessed Using Bipolar VAS | 90.0 score on a scale | Standard Error 1.82 |
| Treatment Phase: Placebo | Treatment Phase: Overall Drug Liking (Emax) Assessed Using Bipolar VAS | 58.0 score on a scale | Standard Error 2.17 |
Secondary
Treatment Phase: Take Drug Again (Emax) Assessed Overall by Using Bipolar VAS
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.
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment Phase: Soticlestat 300 mg | Treatment Phase: Take Drug Again (Emax) Assessed Overall by Using Bipolar VAS | 58.5 score on a scale | Standard Error 2.8 |
| Treatment Phase: Soticlestat 600 mg | Treatment Phase: Take Drug Again (Emax) Assessed Overall by Using Bipolar VAS | 57.6 score on a scale | Standard Error 2.56 |
| Treatment Phase: Soticlestat 900 mg | Treatment Phase: Take Drug Again (Emax) Assessed Overall by Using Bipolar VAS | 58.4 score on a scale | Standard Error 2.72 |
| Treatment Phase: Alprazolam 2 mg | Treatment Phase: Take Drug Again (Emax) Assessed Overall by Using Bipolar VAS | 92.0 score on a scale | Standard Error 1.46 |
| Treatment Phase: Placebo | Treatment Phase: Take Drug Again (Emax) Assessed Overall by Using Bipolar VAS | 57.1 score on a scale | Standard Error 2.14 |