Clinical trial NCT03799900: Assessment of Abuse Potential of Rapastinel in Humans
Official title: A Two-part, Single-dose, Randomized, Double-blind, Placebo and Active-Controlled Crossover Study to Evaluate the Abuse Potential of Rapastinel in Healthy, Non-dependent, Adult Recreational Polydrug Users
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Human Abuse Potential
Lead sponsor: Naurex, Inc, an affiliate of Allergan plc
Sponsor class: INDUSTRY
First posted: 2019-01-10
Enrollment: 72
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: OTHER

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Maximum effect (Emax) for "At this Moment" Drug Liking visual analog scale (VAS).
timeFrame: Treatment Phase: Pre-dose and up to 24 hours post-dose
Secondary outcomes:
measure: Maximum effect (Emax)
timeFrame: Treatment Phase: Pre-dose and up to 24 hours post-dose
measure: Minimum effect (Emin)
timeFrame: Treatment Phase: Pre-dose and up to 24 hours post-dose
measure: Time to Emax (TEmax)
timeFrame: Treatment Phase: Pre-dose and up to 24 hours post-dose
measure: Time to Emin (TEmin)
timeFrame: Treatment Phase: Pre-dose and up to 24 hours post-dose
measure: Time averaged area under the effect curve (TA_AUE)
timeFrame: Treatment Phase: Hour 0 and up to 24 Hours post-dose
measure: Maximum plasma drug concentration (Cmax)
timeFrame: Treatment Phase: Pre-dose and up to 24 hours post-dose
measure: Area under the plasma concentration versus time curve from time 0 to the last quantifiable concentration (AUClast)
timeFrame: Treatment Phase: Pre-dose and up to 24 hours post-dose
measure: Adverse events
timeFrame: Part 1: 6 weeks, Part 2: 9 weeks
measure: Proportion of abnormal electrocardiograms
timeFrame: Part 1: 6 weeks, Part 2: 9 weeks
measure: Columbia-Suicide Severity Rating Scale
timeFrame: Part 1: 6 weeks, Part 2: 9 weeks
Other outcomes:
Locations:
city: Overland Park
country: United States
facility: Vince and Associates Clinical Research Inc
state: Kansas
Study officials:
affiliation: Allergan
name: Sheng Fang Su
role: STUDY_DIRECTOR
References: