Assessment of Abuse Potential of Rapastinel in Humans
Phase 1
Completed
- Conditions
- Human Abuse Potential
- Interventions
- Registration Number
- NCT03799900
- Lead Sponsor
- Naurex, Inc, an affiliate of Allergan plc
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 72
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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Part 1, Cohort 1: Placebo Placebo Some participants will be administered a single IV dose of placebo on Day 1. Part 1, Cohort 2: Placebo Placebo Some participants will be administered a single IV dose of placebo on Day 1. Part 1, Cohort 3 (Optional): Placebo Placebo Optional: some participants will be administered a single IV dose of placebo on Day 1. Part 2, Qualification Phase: Placebo Placebo Participants will receive IV ketamine on Day 2 and placebo on Day 1 in a randomized crossover manner. Part 2, Treatment Phase: Rapastinel Low Dose Rapastinel Participants will be administered single IV doses of rapastinel, ketamine, and placebo in a randomized crossover manner. Part 2, Treatment Phase: Rapastinel Medium Dose Rapastinel Participants will be administered single IV doses of rapastinel, ketamine, and placebo in a randomized crossover manner. Part 2, Treatment Phase: Rapastinel High Dose Rapastinel Participants will be administered single IV doses of rapastinel, ketamine, and placebo in a randomized crossover manner. Part 2, Treatment Phase: Placebo Placebo Participants will be administered single IV doses of rapastinel, ketamine, and placebo in a randomized crossover manner. Part 1, Cohort 1: Ketamine Low Dose Ketamine Some participants will be administered a single IV dose of ketamine on Day 1. Part 1, Cohort 2: Ketamine Medium Dose Ketamine Some participants will be administered a single IV dose of ketamine on Day 1. Part 1, Cohort 3 (Optional): Ketamine High Dose Ketamine Optional: some participants will be administered a single IV dose of ketamine on Day 1. Part 2, Qualification Phase: Ketamine Ketamine Participants will receive IV ketamine on Day 1 and placebo on Day 2 in a randomized crossover manner. Part 2, Treatment Phase: Ketamine Ketamine Participants will be administered single IV doses of rapastinel, ketamine, and placebo in a randomized crossover manner.
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method Maximum effect (Emax) Treatment Phase: Pre-dose and up to 24 hours post-dose Maximum plasma drug concentration (Cmax) 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 Emin (TEmin) 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 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 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
Trial Locations
- Locations (1)
Vince and Associates Clinical Research Inc
🇺🇸Overland Park, Kansas, United States