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

A Phase 1, Randomized, Double-Blind, Double-Dummy, Active- and Placebo-Controlled, 5-Way Crossover Study Evaluating the Abuse Potential of Soticlestat (TAK-935) in Healthy Adult Nondependent Recreational Drug Users With Central Nervous System Depressant Experience

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.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: Placebo; Drug: Soticlestat 300 mg; Drug: Soticlestat 600 mg; Drug: Soticlestat 900 mg; Drug: Alprazolam

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.

• Study Type: Interventional
• Enrollment (Actual): 100
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Kansas
    • Overland Park, Kansas, United States, 66212
      • Altasciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 51 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Soticlestat 300 mg; Participants will receive a single oral dose of soticlestat 300 milligrams (mg).	Drug: Soticlestat 300 mg; Administered orally.
Experimental: Soticlestat 600 mg; Participants will receive a single oral dose of soticlestat 600 mg.	Drug: Soticlestat 600 mg; Administered orally.
Experimental: Soticlestat 900 mg; Participants will receive a single oral dose of soticlestat 900 mg.	Drug: Soticlestat 900 mg; Administered orally.
Active Comparator: Alprazolam 2 mg; Participants will receive a single oral dose of over encapsulated alprazolam 2 mg.	Drug: Alprazolam; Administered orally.
Placebo Comparator: Placebo; Participants will receive a single oral dose of matching placebo.	Drug: Placebo; Administered orally.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Day 1 of each Treatment Period: 12 and 24 hours post-dose
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.	Day 1 of each Treatment Period: 12 and 24 hours post-dose
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.	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
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.	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
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.	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
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.	From start of study drug administration (Day 1) up to Day 37

Collaborators and Investigators

• Sponsor: Takeda
• Investigators: Study Director: Study Director, Takeda

Publications and helpful links

Helpful Links

• To obtain more information on the study, click here/on this link.

Study record dates

Study Major Dates

• Study Start (Actual): November 15, 2022
• Primary Completion (Actual): June 29, 2023
• Study Completion (Actual): July 7, 2023

Study Registration Dates

• First Submitted: October 28, 2022
• First Submitted That Met QC Criteria: October 28, 2022
• First Posted (Actual): November 2, 2022

Study Record Updates

• Last Update Posted (Estimated): December 9, 2024
• Last Update Submitted That Met QC Criteria: October 24, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: Drug Therapy
• Additional Relevant MeSH Terms: Mental Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Drug Misuse; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Neurotransmitter Agents; Hypnotics and Sedatives; Anti-Anxiety Agents; Tranquilizing Agents; Psychotropic Drugs; GABA Modulators; GABA Agents; Alprazolam
• Other Study ID Numbers: TAK-935-1012; 2018-002484-25 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
• IPD Sharing Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/ For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No