Human Abuse Potential
Conditions
Brief summary
Based on the pharmacological class of rapastinel, this study will be conducted to evaluate the abuse potential of single doses of rapastinel as compared with ketamine, a NMDAR antagonist that is a Schedule III dissociative anesthetic, and placebo in recreational polydrug users.
Interventions
DRUGRapastinel
During the Treatment Phase in Part 2, participants will be administered single IV doses of rapastinel, ketamine, and placebo in a randomized crossover manner.
DRUGKetamine
Part 1 Part 2, Qualification Phase: Participants will be administered single IV doses of ketamine and placebo in a randomized crossover manner Part 2, Treatment Phase: Participants will be administered single IV doses of rapastinel, ketamine, and placebo in a randomized crossover manner.
DRUGPlacebo
Part 1 Part 2, Qualification Phase: Participants will be administered single IV doses of ketamine and placebo in a randomized crossover manner Part 2, Treatment Phase: Participants will be administered single IV doses of rapastinel, ketamine, and placebo in a randomized crossover manner.
Sponsors
Naurex, Inc, an affiliate of Allergan plc
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
* Participant must be a current recreational polydrug user * Have a supine systolic blood pressure (BP) ≥ 95 mm Hg and ≤ 145 mg Hg, or supine diastolic BP ≥ 50 mm Hg and ≤ 90 mm Hg at the Screening Visit. * Have negative test results for benzoylecgonine (cocaine), methadone, barbiturates, amphetamines, benzodiazepines, alcohol, oxycodone and other opioids, and phencyclidine at any admission * Able, as assessed by the investigator, and willing to follow study instructions and likely to complete all required study visits
Exclusion criteria
* Evidence of drug or alcohol dependence (excluding nicotine and caffeine) within the past 2 years * Suicidal risk based on the opinion of the principal investigator (or appropriately trained designee) * History of violent or psychotic behavior when taking psychedelic drugs, or unwilling to take a drug that might alter perception in a controlled setting * Have taken or require concomitant treatment with any CNS depressants, or cannot safely discontinue these medications within 14 days (or 5 half-lives, whichever is longer) before study treatment administration * Previously participated in an investigational study of rapastinel. * Participation in any other clinical investigation using an experimental drug within 30 days, 5 half-lives or twice the duration of the biological effect of the study treatment (whichever is longer), prior to study treatment administration or is concurrently enrolled in any clinical trial, judged not to be scientifically or medically compatible with this study * Consumption of alcohol within 72 hours before administration of study treatment * Breastfeeding * Unable to refrain from consuming caffeine or xanthine-containing compounds such as tea, coffee, soft drinks, energy sports drinks or chocolate (more than 48 oz/day) from 48 hours before administration of study treatment. * Have consumed dietary supplements or other foods or beverages that may affect various drug metabolizing enzymes and transporters (eg, grapefruit, grapefruit juice, grapefruit-containing beverages), vegetables from the mustard green family (eg, kale, broccoli, watercress, collard greens, kohlrabi, Brussels sprouts, mustard), and charbroiled meats within 14 days prior to dosing or unable to refrain from consumption during the study. * The ability to tolerate IV ketamine as judged by the Investigator, based on available safety data, as well as pharmacodynamic data.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum effect (Emax) for At this Moment Drug Liking visual analog scale (VAS). | Treatment Phase: Pre-dose and up to 24 hours post-dose | The drug liking VAS measures the participant's liking for the drug and is scored from 0 to 100, with 0 reflecting Strong disliking and 100 reflecting Strong liking. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum plasma drug concentration (Cmax) | Treatment Phase: Pre-dose and up to 24 hours post-dose | — |
| Maximum effect (Emax) | Treatment Phase: Pre-dose and up to 24 hours post-dose | — |
| Minimum effect (Emin) | Treatment Phase: Pre-dose and up to 24 hours post-dose | — |
| Time to Emax (TEmax) | Treatment Phase: Pre-dose and up to 24 hours post-dose | — |
| Time averaged area under the effect curve (TA_AUE) | Treatment Phase: Hour 0 and up to 24 Hours post-dose | — |
| Area under the plasma concentration versus time curve from time 0 to the last quantifiable concentration (AUClast) | Treatment Phase: Pre-dose and up to 24 hours post-dose | — |
| Adverse events | Part 1: 6 weeks, Part 2: 9 weeks | — |
| Proportion of abnormal electrocardiograms | Part 1: 6 weeks, Part 2: 9 weeks | — |
| Columbia-Suicide Severity Rating Scale | Part 1: 6 weeks, Part 2: 9 weeks | The C-SSRS is a clinician-rated instrument that reports the severity of both suicidal ideation and behavior. Suicidal ideation is classified on a 5-item scale: 1 (least severe) to 5 (most severe). |
| Time to Emin (TEmin) | Treatment Phase: Pre-dose and up to 24 hours post-dose | — |
Countries
United States
Outcome results
None listed