Assessment of Abuse Potential of Rapastinel in Humans

Human Abuse Potential Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03799900
• Other study ID #: RAP-PK-12
• Status: Completed
• Phase: Phase 1
• Start date: November 1, 2018
• Est. completion date: March 29, 2019

Study information

• Verified date: May 2019
• Source: Naurex, Inc, an affiliate of Allergan plc
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 72
• Est. completion date: March 29, 2019
• Est. primary completion date: March 24, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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.

Related Conditions & MeSH terms

• Human Abuse Potential

Intervention

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.
• 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
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.

Locations

Country	Name	City	State
United States	Vince and Associates Clinical Research Inc	Overland Park	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
Naurex, Inc, an affiliate of Allergan plc

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Maximum effect (Emax)		Treatment Phase: Pre-dose and up to 24 hours post-dose
Secondary	Minimum effect (Emin)		Treatment Phase: Pre-dose and up to 24 hours post-dose
Secondary	Time to Emax (TEmax)		Treatment Phase: Pre-dose and up to 24 hours post-dose
Secondary	Time to Emin (TEmin)		Treatment Phase: Pre-dose and up to 24 hours post-dose
Secondary	Time averaged area under the effect curve (TA_AUE)		Treatment Phase: Hour 0 and up to 24 Hours post-dose
Secondary	Maximum plasma drug concentration (Cmax)		Treatment Phase: Pre-dose and up to 24 hours post-dose
Secondary	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
Secondary	Adverse events		Part 1: 6 weeks, Part 2: 9 weeks
Secondary	Proportion of abnormal electrocardiograms		Part 1: 6 weeks, Part 2: 9 weeks
Secondary	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