A Single-Dose, Double-Blind, Placebo-Controlled, Randomized, Crossover Study to Determine the Abuse Potential of Single Oral Dose of Seltorexant Compared To Suvorexant and Zolpidem
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Enrollment
- 127
- Locations
- 1
- Primary Endpoint
- Peak Maximum Effect (Emax) for Drug Liking (At this Moment) Visual Analog Scale (VAS)
Study Overview
Brief Summary
The purpose of this study is to evaluate the abuse potential of seltorexant compared to placebo and two active comparators (zolpidem and suvorexant) in non-dependent, recreational sedative users.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Crossover
- Primary Purpose
- Treatment
- Masking
- Double (Participant, Investigator)
Eligibility Criteria
- Ages
- 18 Years to 60 Years (Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Be a current, recreational, not physically dependent, drug user
- •Participant must be medically stable
- •All female participants must have a negative serum beta-human chorionic gonadotropin (beta-hCG) pregnancy test at screening and a negative urine pregnancy test on Day -1 of the qualification phase and on Day -1 of each treatment period of the treatment Phase
- •Blood pressure (after the participant is in a sitting position for 5 minutes) between 90 millimeters of mercury (mmHg) and 160 mmHg systolic, inclusive, and no higher than 100 mmHg diastolic at screening and Day -1 prior to qualification phase randomization
- •A 12-lead ECG consistent with normal cardiac conduction and function, including: sinus rhythm, pulse rate between 40 and 100 beats per minute (bpm), QTc interval less than or equal to (<=) 450 milliseconds (ms) for males, <=470 for females, QRS interval of less than (<) 120 ms, PR interval <210 ms, Morphology consistent with healthy cardiac conduction and function
Exclusion Criteria
- •Known allergies to seltorexant, zolpidem, and suvorexant
- •Previous history of recurrent fainting, collapses, syncope, orthostatic hypotension, or vasovagal reactions
- •Prescription medications except for stable medical problems such as hypertension, elevated cholesterol, and non-insulin-dependent diabetes mellitus with stable medications for at least 1 month prior to screening
- •Participants who have ever been in treatment for substance use disorders (except smoking cessation) or are currently seeking treatment for substance use disorders. In addition, currently seeking or participating in a substance rehabilitation program should be excluded
- •Preplanned surgery or procedures that would interfere with the conduct of the study
Arms & Interventions
Qualification Phase: Treatment Sequence YXZ
Participants will receive a single oral dose of suvorexant (Treatment Y) in qualification period 1, followed by single oral dose of placebo (Treatment X) in qualification period 2 and then single oral dose of zolpidem (Treatment Z) in qualification period 3 on Day 1 during each qualification phase. Each treatment will be separated by washout of at least 3 days.
Intervention: Suvorexant (Drug)
Qualification Phase: Treatment Sequence YXZ
Participants will receive a single oral dose of suvorexant (Treatment Y) in qualification period 1, followed by single oral dose of placebo (Treatment X) in qualification period 2 and then single oral dose of zolpidem (Treatment Z) in qualification period 3 on Day 1 during each qualification phase. Each treatment will be separated by washout of at least 3 days.
Intervention: Zolpidem (Drug)
Qualification Phase: Treatment Sequence YXZ
Participants will receive a single oral dose of suvorexant (Treatment Y) in qualification period 1, followed by single oral dose of placebo (Treatment X) in qualification period 2 and then single oral dose of zolpidem (Treatment Z) in qualification period 3 on Day 1 during each qualification phase. Each treatment will be separated by washout of at least 3 days.
Intervention: Placebo (Drug)
Qualification Phase: Treatment Sequence ZYX
Participants will receive Treatment Z in qualification period 1, followed by Treatment Y in qualification period 2, and then Treatment X in qualification period 3 on Day 1 during each qualification phase. Each treatment will be separated by washout of at least 3 days.
Intervention: Suvorexant (Drug)
Qualification Phase: Treatment Sequence ZYX
Participants will receive Treatment Z in qualification period 1, followed by Treatment Y in qualification period 2, and then Treatment X in qualification period 3 on Day 1 during each qualification phase. Each treatment will be separated by washout of at least 3 days.
Intervention: Zolpidem (Drug)
Qualification Phase: Treatment Sequence ZYX
Participants will receive Treatment Z in qualification period 1, followed by Treatment Y in qualification period 2, and then Treatment X in qualification period 3 on Day 1 during each qualification phase. Each treatment will be separated by washout of at least 3 days.
Intervention: Placebo (Drug)
Qualification Phase: Treatment Sequence XZY
Participants will receive Treatment X in qualification period 1, followed by Treatment Z in qualification period 2, and then Treatment Y in qualification period 3 on Day 1 during each qualification phase. Each treatment will be separated by washout of at least 3 days.
Intervention: Suvorexant (Drug)
Qualification Phase: Treatment Sequence XZY
Participants will receive Treatment X in qualification period 1, followed by Treatment Z in qualification period 2, and then Treatment Y in qualification period 3 on Day 1 during each qualification phase. Each treatment will be separated by washout of at least 3 days.
Intervention: Zolpidem (Drug)
Qualification Phase: Treatment Sequence XZY
Participants will receive Treatment X in qualification period 1, followed by Treatment Z in qualification period 2, and then Treatment Y in qualification period 3 on Day 1 during each qualification phase. Each treatment will be separated by washout of at least 3 days.
Intervention: Placebo (Drug)
Qualification Phase: Treatment Sequence YZX
Participants will receive Treatment Y in qualification period 1, followed by Treatment Z in qualification period 2, and then Treatment X in qualification period 3 on Day 1 during each qualification phase. Each treatment will be separated by washout of at least 3 days.
Intervention: Suvorexant (Drug)
Qualification Phase: Treatment Sequence YZX
Participants will receive Treatment Y in qualification period 1, followed by Treatment Z in qualification period 2, and then Treatment X in qualification period 3 on Day 1 during each qualification phase. Each treatment will be separated by washout of at least 3 days.
Intervention: Zolpidem (Drug)
Qualification Phase: Treatment Sequence YZX
Participants will receive Treatment Y in qualification period 1, followed by Treatment Z in qualification period 2, and then Treatment X in qualification period 3 on Day 1 during each qualification phase. Each treatment will be separated by washout of at least 3 days.
Intervention: Placebo (Drug)
Qualification Phase: Treatment Sequence ZXY
Participants will receive Treatment Z in qualification period 1, followed by Treatment X in qualification period 2, and then Treatment Y in qualification period 3 on Day 1 during qualification phase. Each treatment will be separated by washout of at least 3 days.
Intervention: Suvorexant (Drug)
Qualification Phase: Treatment Sequence ZXY
Participants will receive Treatment Z in qualification period 1, followed by Treatment X in qualification period 2, and then Treatment Y in qualification period 3 on Day 1 during qualification phase. Each treatment will be separated by washout of at least 3 days.
Intervention: Zolpidem (Drug)
Qualification Phase: Treatment Sequence ZXY
Participants will receive Treatment Z in qualification period 1, followed by Treatment X in qualification period 2, and then Treatment Y in qualification period 3 on Day 1 during qualification phase. Each treatment will be separated by washout of at least 3 days.
Intervention: Placebo (Drug)
Qualification Phase: Treatment Sequence XYZ
Participants will receive Treatment X in qualification period 1, followed by Treatment Y in qualification period 2, and then Treatment Z in qualification period 3 on Day 1 during each qualification phase. Each treatment will be separated by washout of at least 3 days.
Intervention: Suvorexant (Drug)
Qualification Phase: Treatment Sequence XYZ
Participants will receive Treatment X in qualification period 1, followed by Treatment Y in qualification period 2, and then Treatment Z in qualification period 3 on Day 1 during each qualification phase. Each treatment will be separated by washout of at least 3 days.
Intervention: Zolpidem (Drug)
Qualification Phase: Treatment Sequence XYZ
Participants will receive Treatment X in qualification period 1, followed by Treatment Y in qualification period 2, and then Treatment Z in qualification period 3 on Day 1 during each qualification phase. Each treatment will be separated by washout of at least 3 days.
Intervention: Placebo (Drug)
Treatment Phase: Treatment Sequence ABFCED
Participants will receive a single oral dose of placebo (Treatment A) in treatment period 1, followed by single oral dose of suvorexant (Treatment B) in treatment period 2, single oral Dose 3 of seltorexant (Treatment F) in treatment period 3, single oral dose of zolpidem (Treatment C) in treatment period 4, single oral Dose 2 of seltorexant (Treatment E) in treatment period 5 and then a single oral Dose 1 of seltorexant (Treatment D) in treatment period 6 on Day 1 during each treatment phase. Each treatment will be separated by washout of at least 5 days.
Intervention: Suvorexant (Drug)
Treatment Phase: Treatment Sequence ABFCED
Participants will receive a single oral dose of placebo (Treatment A) in treatment period 1, followed by single oral dose of suvorexant (Treatment B) in treatment period 2, single oral Dose 3 of seltorexant (Treatment F) in treatment period 3, single oral dose of zolpidem (Treatment C) in treatment period 4, single oral Dose 2 of seltorexant (Treatment E) in treatment period 5 and then a single oral Dose 1 of seltorexant (Treatment D) in treatment period 6 on Day 1 during each treatment phase. Each treatment will be separated by washout of at least 5 days.
Intervention: Zolpidem (Drug)
Treatment Phase: Treatment Sequence ABFCED
Participants will receive a single oral dose of placebo (Treatment A) in treatment period 1, followed by single oral dose of suvorexant (Treatment B) in treatment period 2, single oral Dose 3 of seltorexant (Treatment F) in treatment period 3, single oral dose of zolpidem (Treatment C) in treatment period 4, single oral Dose 2 of seltorexant (Treatment E) in treatment period 5 and then a single oral Dose 1 of seltorexant (Treatment D) in treatment period 6 on Day 1 during each treatment phase. Each treatment will be separated by washout of at least 5 days.
Intervention: Seltorexant (Drug)
Treatment Phase: Treatment Sequence ABFCED
Participants will receive a single oral dose of placebo (Treatment A) in treatment period 1, followed by single oral dose of suvorexant (Treatment B) in treatment period 2, single oral Dose 3 of seltorexant (Treatment F) in treatment period 3, single oral dose of zolpidem (Treatment C) in treatment period 4, single oral Dose 2 of seltorexant (Treatment E) in treatment period 5 and then a single oral Dose 1 of seltorexant (Treatment D) in treatment period 6 on Day 1 during each treatment phase. Each treatment will be separated by washout of at least 5 days.
Intervention: Placebo (Drug)
Treatment Phase: Treatment Sequence BCADFE
Participants will receive Treatment B in treatment period 1, followed by Treatment C in treatment period 2, Treatment A in treatment period 3, Treatment D in treatment period 4, Treatment F in treatment period 5 and then Treatment E in treatment period 6 on Day 1 during each treatment phase. Each treatment will be separated by washout of at least 5 days.
Intervention: Suvorexant (Drug)
Treatment Phase: Treatment Sequence BCADFE
Participants will receive Treatment B in treatment period 1, followed by Treatment C in treatment period 2, Treatment A in treatment period 3, Treatment D in treatment period 4, Treatment F in treatment period 5 and then Treatment E in treatment period 6 on Day 1 during each treatment phase. Each treatment will be separated by washout of at least 5 days.
Intervention: Zolpidem (Drug)
Treatment Phase: Treatment Sequence BCADFE
Participants will receive Treatment B in treatment period 1, followed by Treatment C in treatment period 2, Treatment A in treatment period 3, Treatment D in treatment period 4, Treatment F in treatment period 5 and then Treatment E in treatment period 6 on Day 1 during each treatment phase. Each treatment will be separated by washout of at least 5 days.
Intervention: Seltorexant (Drug)
Treatment Phase: Treatment Sequence BCADFE
Participants will receive Treatment B in treatment period 1, followed by Treatment C in treatment period 2, Treatment A in treatment period 3, Treatment D in treatment period 4, Treatment F in treatment period 5 and then Treatment E in treatment period 6 on Day 1 during each treatment phase. Each treatment will be separated by washout of at least 5 days.
Intervention: Placebo (Drug)
Treatment Phase: Treatment Sequence CDBEAF
Participants will receive Treatment C in treatment period 1, followed by Treatment D in treatment period 2, Treatment B in treatment period 3, Treatment E in treatment period 4, Treatment A in treatment period 5 and then Treatment F in treatment period 6 on Day 1 during each treatment phase. Each treatment will be separated by washout of at least 5 days.
Intervention: Suvorexant (Drug)
Treatment Phase: Treatment Sequence CDBEAF
Participants will receive Treatment C in treatment period 1, followed by Treatment D in treatment period 2, Treatment B in treatment period 3, Treatment E in treatment period 4, Treatment A in treatment period 5 and then Treatment F in treatment period 6 on Day 1 during each treatment phase. Each treatment will be separated by washout of at least 5 days.
Intervention: Zolpidem (Drug)
Treatment Phase: Treatment Sequence CDBEAF
Participants will receive Treatment C in treatment period 1, followed by Treatment D in treatment period 2, Treatment B in treatment period 3, Treatment E in treatment period 4, Treatment A in treatment period 5 and then Treatment F in treatment period 6 on Day 1 during each treatment phase. Each treatment will be separated by washout of at least 5 days.
Intervention: Seltorexant (Drug)
Treatment Phase: Treatment Sequence CDBEAF
Participants will receive Treatment C in treatment period 1, followed by Treatment D in treatment period 2, Treatment B in treatment period 3, Treatment E in treatment period 4, Treatment A in treatment period 5 and then Treatment F in treatment period 6 on Day 1 during each treatment phase. Each treatment will be separated by washout of at least 5 days.
Intervention: Placebo (Drug)
Treatment Phase: Treatment Sequence DECFBA
Participants will receive Treatment D in treatment period 1, followed by Treatment E in treatment period 2, Treatment C in treatment period 3, Treatment F in treatment period 4, Treatment B in treatment period 5 and then Treatment A in treatment period 6 on Day 1 during each treatment phase. Each treatment will be separated by washout of at least 5 days.
Intervention: Suvorexant (Drug)
Treatment Phase: Treatment Sequence DECFBA
Participants will receive Treatment D in treatment period 1, followed by Treatment E in treatment period 2, Treatment C in treatment period 3, Treatment F in treatment period 4, Treatment B in treatment period 5 and then Treatment A in treatment period 6 on Day 1 during each treatment phase. Each treatment will be separated by washout of at least 5 days.
Intervention: Zolpidem (Drug)
Treatment Phase: Treatment Sequence DECFBA
Participants will receive Treatment D in treatment period 1, followed by Treatment E in treatment period 2, Treatment C in treatment period 3, Treatment F in treatment period 4, Treatment B in treatment period 5 and then Treatment A in treatment period 6 on Day 1 during each treatment phase. Each treatment will be separated by washout of at least 5 days.
Intervention: Seltorexant (Drug)
Treatment Phase: Treatment Sequence: EFDACB
Participants will receive Treatment E in treatment period 1, followed by Treatment F in treatment period 2, Treatment D in treatment period 3, Treatment A in treatment period 4, Treatment C in treatment period 5 and then Treatment B in treatment period 6 on Day 1 during each treatment phase. Each treatment will be separated by washout of at least 5 days.
Intervention: Zolpidem (Drug)
Treatment Phase: Treatment Sequence DECFBA
Participants will receive Treatment D in treatment period 1, followed by Treatment E in treatment period 2, Treatment C in treatment period 3, Treatment F in treatment period 4, Treatment B in treatment period 5 and then Treatment A in treatment period 6 on Day 1 during each treatment phase. Each treatment will be separated by washout of at least 5 days.
Intervention: Placebo (Drug)
Treatment Phase: Treatment Sequence: EFDACB
Participants will receive Treatment E in treatment period 1, followed by Treatment F in treatment period 2, Treatment D in treatment period 3, Treatment A in treatment period 4, Treatment C in treatment period 5 and then Treatment B in treatment period 6 on Day 1 during each treatment phase. Each treatment will be separated by washout of at least 5 days.
Intervention: Suvorexant (Drug)
Treatment Phase: Treatment Sequence: EFDACB
Participants will receive Treatment E in treatment period 1, followed by Treatment F in treatment period 2, Treatment D in treatment period 3, Treatment A in treatment period 4, Treatment C in treatment period 5 and then Treatment B in treatment period 6 on Day 1 during each treatment phase. Each treatment will be separated by washout of at least 5 days.
Intervention: Seltorexant (Drug)
Treatment Phase: Treatment Sequence: EFDACB
Participants will receive Treatment E in treatment period 1, followed by Treatment F in treatment period 2, Treatment D in treatment period 3, Treatment A in treatment period 4, Treatment C in treatment period 5 and then Treatment B in treatment period 6 on Day 1 during each treatment phase. Each treatment will be separated by washout of at least 5 days.
Intervention: Placebo (Drug)
Treatment Phase: Treatment Sequence FAEBDC
Participants will receive Treatment F in treatment period 1, followed by Treatment A in treatment period 2, Treatment E in treatment period 3, Treatment B in treatment period 4, Treatment D in treatment period 5 and Treatment C in treatment period 6 on Day 1 during each treatment phase. Each treatment will be separated by washout of at least 5 days.
Intervention: Suvorexant (Drug)
Treatment Phase: Treatment Sequence FAEBDC
Participants will receive Treatment F in treatment period 1, followed by Treatment A in treatment period 2, Treatment E in treatment period 3, Treatment B in treatment period 4, Treatment D in treatment period 5 and Treatment C in treatment period 6 on Day 1 during each treatment phase. Each treatment will be separated by washout of at least 5 days.
Intervention: Zolpidem (Drug)
Treatment Phase: Treatment Sequence FAEBDC
Participants will receive Treatment F in treatment period 1, followed by Treatment A in treatment period 2, Treatment E in treatment period 3, Treatment B in treatment period 4, Treatment D in treatment period 5 and Treatment C in treatment period 6 on Day 1 during each treatment phase. Each treatment will be separated by washout of at least 5 days.
Intervention: Seltorexant (Drug)
Treatment Phase: Treatment Sequence FAEBDC
Participants will receive Treatment F in treatment period 1, followed by Treatment A in treatment period 2, Treatment E in treatment period 3, Treatment B in treatment period 4, Treatment D in treatment period 5 and Treatment C in treatment period 6 on Day 1 during each treatment phase. Each treatment will be separated by washout of at least 5 days.
Intervention: Placebo (Drug)
Outcomes
Primary Outcomes
Peak Maximum Effect (Emax) for Drug Liking (At this Moment) Visual Analog Scale (VAS)
Time Frame: Up to 24 hour post-dose (up to Day 2)
Emax for drug liking VAS will be reported. Drug liking VAS is a bipolar scale designed to assess a participant's liking for a given study intervention at the time the question is being asked (that is, at this moment). It is scored as an integer ranging from 0 (strong disliking) to 100 (strong liking).
Secondary Outcomes
- Overall Drug Liking VAS (Emax)(12 hour and 24 hour post-dose)
- Take Drug Again VAS (Emax)(12 hour and 24 hour post-dose)
- Subjective Drug Value (Emax)(12 hour and 24 hour post-dose)
- High VAS (Emax)(Pre-dose up to 24 hours post-dose (up to Day 2))
- Time to Peak Effect (TEmax) for Drug Liking (At this Moment) VAS(Up to 24 hour post-dose (up to Day 2))
- Minimum Effect (Emin) for Drug Liking (At this Moment) VAS(Up to 24 hour post-dose (up to Day 2))
- Time to Minimum Effect (TEmin) for Drug Liking (At this Moment) VAS(Up to 24 hour post-dose (up to Day 2))
- Time-averaged Area Under the Effects Curve (TA_AUE) for Drug Liking (At This Moment) VAS(Up to 24 hour post-dose (up to Day 2))
- TEmax of High VAS(Pre-dose up to 24 hours post-dose (up to Day 2))
- TA_AUE of High VAS(Pre-dose up to 24 hours post-dose (up to Day 2))
- Emax of Good Effect VAS(Up to 24 hour post-dose (up to Day 2))
- TEmax of Good Effects VAS(Up to 24 hour post-dose (up to Day 2))
- TA_AUE of Good Effects VAS(Up to 24 hour post-dose (up to Day 2))
- Emax of Bad Effects VAS(Up to 24 hour post-dose (up to Day 2))
- TA_AUE of Bad Effects VAS(Up to 24 hour post-dose (up to Day 2))
- TEmax of Bad Effects VAS(Up to 24 hour post-dose (up to Day 2))
- Emin of Drowsiness/Alertness VAS(Pre-dose up to 24 hours post-dose (up to Day 2))
- TEmin of Drowsiness/Alertness VAS(Pre-dose up to 24 hours post-dose (up to Day 2))
- Time-averaged Area Over the Effect Time Curve (TA_AOE) of Drowsiness/Alertness VAS(Pre-dose up to 24 hours post-dose (up to Day 2))
- Emin of Relaxation/Agitation VAS(Pre-dose up to 24 hours post-dose (up to Day 2))
- TEmin of Relaxation/Agitation VAS(Pre-dose up to 24 hours post-dose (up to Day 2))
- TA_AOE of Relaxation/Agitation VAS(Pre-dose up to 24 hours post-dose (up to Day 2))
- TEmax of Dizziness VAS(Pre-dose up to 24 hour post-dose (up to Day 2))
- Emax of Dizziness VAS(Pre-dose up to 24 hour post-dose (up to Day 2))
- TA_AUE of Dizziness VAS(Pre-dose up to 24 hour post-dose (up to Day 2))
- Emax of Any Effects VAS(Up to 24 hour post-dose (up to Day 2))
- TEmax of Any Effects VAS(Up to 24 hour post-dose (up to Day 2))
- TA_AUE of Any Effects VAS(Up to 24 hour post-dose (up to Day 2))
- Drug Similarity VAS(24 hour post-dose)
- Percentage of Participants with Adverse Events (AEs)(Up to Week 20)
- Percentage of Participants with Serious Adverse Events (SAEs)(Up to Week 20)
- Percentage of Participants with Abnormalities in Clinical Laboratory Parameters(Up to 24 hour post-dose (up to Day 2))
- Percentage of Participants with Abnormalities in Vital Signs(Up to 24 hour post-dose (up to Day 2))
- Emin of Modified Observer's Assessment of Alertness/Sedation (MOAA/S) of Composite and Sum Score(Up to 24 hour post-dose (up to Day 2))
- TA_AOE of MOAA/S of composite and sum score(Up to 24 hour post-dose (up to Day 2))