Assessment of Abuse Potential of Rapastinel in Humans

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

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.

Study Overview

• Status: Completed
• Conditions: Human Abuse Potential
• Intervention / Treatment: Drug: Ketamine; Drug: Placebo; Drug: Rapastinel

• Study Type: Interventional
• Enrollment (Actual): 72
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Kansas
    • Overland Park, Kansas, United States, 66212
      • Vince and Associates Clinical Research Inc

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

13

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1, Cohort 1: Ketamine Low Dose; Some participants will be administered a single IV dose of ketamine on Day 1.	Drug: Ketamine; 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.
Placebo Comparator: Part 1, Cohort 1: Placebo; Some participants will be administered a single IV dose of placebo on Day 1.	Drug: Placebo; 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.
Experimental: Part 1, Cohort 2: Ketamine Medium Dose; Some participants will be administered a single IV dose of ketamine on Day 1.	Drug: Ketamine; 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.
Placebo Comparator: Part 1, Cohort 2: Placebo; Some participants will be administered a single IV dose of placebo on Day 1.	Drug: Placebo; 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.
Experimental: Part 1, Cohort 3 (Optional): Ketamine High Dose; Optional: some participants will be administered a single IV dose of ketamine on Day 1.	Drug: Ketamine; 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.
Placebo Comparator: Part 1, Cohort 3 (Optional): Placebo; Optional: some participants will be administered a single IV dose of placebo on Day 1.	Drug: Placebo; 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.
Experimental: Part 2, Qualification Phase: Ketamine; Participants will receive IV ketamine on Day 1 and placebo on Day 2 in a randomized crossover manner.	Drug: Ketamine; 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.
Placebo Comparator: Part 2, Qualification Phase: Placebo; Participants will receive IV ketamine on Day 2 and placebo on Day 1 in a randomized crossover manner.	Drug: Placebo; 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.
Experimental: Part 2, Treatment Phase: Rapastinel Low Dose; Participants will be administered single IV doses of rapastinel, ketamine, and placebo in a randomized crossover manner.	Drug: Rapastinel; During the Treatment Phase in Part 2, participants will be administered single IV doses of rapastinel, ketamine, and placebo in a randomized crossover manner.
Experimental: Part 2, Treatment Phase: Rapastinel Medium Dose; Participants will be administered single IV doses of rapastinel, ketamine, and placebo in a randomized crossover manner.	Drug: Rapastinel; During the Treatment Phase in Part 2, participants will be administered single IV doses of rapastinel, ketamine, and placebo in a randomized crossover manner.
Experimental: Part 2, Treatment Phase: Rapastinel High Dose; Participants will be administered single IV doses of rapastinel, ketamine, and placebo in a randomized crossover manner.	Drug: Rapastinel; During the Treatment Phase in Part 2, participants will be administered single IV doses of rapastinel, ketamine, and placebo in a randomized crossover manner.
Active Comparator: Part 2, Treatment Phase: Ketamine; Participants will be administered single IV doses of rapastinel, ketamine, and placebo in a randomized crossover manner.	Drug: Ketamine; 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.
Placebo Comparator: Part 2, Treatment Phase: Placebo; Participants will be administered single IV doses of rapastinel, ketamine, and placebo in a randomized crossover manner.	Drug: Placebo; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum effect (Emax) for "At this Moment" Drug Liking visual analog scale (VAS).	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".	Treatment Phase: Pre-dose and up to 24 hours post-dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 to Emin (TEmin)		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
Maximum plasma drug concentration (Cmax)		Treatment Phase: Pre-dose 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	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).	Part 1: 6 weeks, Part 2: 9 weeks

Collaborators and Investigators

• Sponsor: Naurex, Inc, an affiliate of Allergan plc
• Investigators: Study Director: Sheng Fang Su, Allergan

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2018
• Primary Completion (Actual): March 24, 2019
• Study Completion (Actual): March 29, 2019

Study Registration Dates

• First Submitted: November 15, 2018
• First Submitted That Met QC Criteria: January 9, 2019
• First Posted (Actual): January 10, 2019

Study Record Updates

• Last Update Posted (Actual): May 16, 2019
• Last Update Submitted That Met QC Criteria: May 14, 2019
• Last Verified: May 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Dissociative; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Ketamine
• Other Study ID Numbers: RAP-PK-12

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

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