Assessment of Abuse Potential of Rapastinel in Humans

NCT03799900 | Completed Phase 1 FDA Drug

• 1 other identifier: RAP-PK-12
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 1

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.

Conditions

Human Abuse Potential

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (10)

• 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

Study Arms (13)

Part 1, Cohort 1: Ketamine Low Dose

EXPERIMENTAL

Some participants will be administered a single IV dose of ketamine on Day 1.

Drug: Ketamine

Part 1, Cohort 1: Placebo

PLACEBO COMPARATOR

Some participants will be administered a single IV dose of placebo on Day 1.

Drug: Placebo

Part 1, Cohort 2: Ketamine Medium Dose

EXPERIMENTAL

Some participants will be administered a single IV dose of ketamine on Day 1.

Drug: Ketamine

Part 1, Cohort 2: Placebo

PLACEBO COMPARATOR

Some participants will be administered a single IV dose of placebo on Day 1.

Drug: Placebo

Part 1, Cohort 3 (Optional): Ketamine High Dose

EXPERIMENTAL

Optional: some participants will be administered a single IV dose of ketamine on Day 1.

Drug: Ketamine

Part 1, Cohort 3 (Optional): Placebo

PLACEBO COMPARATOR

Optional: some participants will be administered a single IV dose of placebo on Day 1.

Drug: Placebo

Part 2, Qualification Phase: Ketamine

EXPERIMENTAL

Participants will receive IV ketamine on Day 1 and placebo on Day 2 in a randomized crossover manner.

Drug: Ketamine

Part 2, Qualification Phase: Placebo

PLACEBO COMPARATOR

Participants will receive IV ketamine on Day 2 and placebo on Day 1 in a randomized crossover manner.

Drug: Placebo

Part 2, Treatment Phase: Rapastinel Low Dose

EXPERIMENTAL

Participants will be administered single IV doses of rapastinel, ketamine, and placebo in a randomized crossover manner.

Drug: Rapastinel

Part 2, Treatment Phase: Rapastinel Medium Dose

EXPERIMENTAL

Participants will be administered single IV doses of rapastinel, ketamine, and placebo in a randomized crossover manner.

Drug: Rapastinel

Part 2, Treatment Phase: Rapastinel High Dose

EXPERIMENTAL

Participants will be administered single IV doses of rapastinel, ketamine, and placebo in a randomized crossover manner.

Drug: Rapastinel

Part 2, Treatment Phase: Ketamine

ACTIVE COMPARATOR

Participants will be administered single IV doses of rapastinel, ketamine, and placebo in a randomized crossover manner.

Drug: Ketamine

Part 2, Treatment Phase: Placebo

PLACEBO COMPARATOR

Participants will be administered single IV doses of rapastinel, ketamine, and placebo in a randomized crossover manner.

Drug: Placebo

Interventions

Rapastinel DRUG

During the Treatment Phase in Part 2, participants will be administered single IV doses of rapastinel, ketamine, and placebo in a randomized crossover manner.

Part 2, Treatment Phase: Rapastinel High Dose; Part 2, Treatment Phase: Rapastinel Low Dose; Part 2, Treatment Phase: Rapastinel Medium Dose

Ketamine DRUG

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.

Part 1, Cohort 1: Ketamine Low Dose; Part 1, Cohort 2: Ketamine Medium Dose; Part 1, Cohort 3 (Optional): Ketamine High Dose; Part 2, Qualification Phase: Ketamine; Part 2, Treatment Phase: Ketamine

Placebo DRUG

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.

Part 1, Cohort 1: Placebo; Part 1, Cohort 2: Placebo; Part 1, Cohort 3 (Optional): Placebo; Part 2, Qualification Phase: Placebo; Part 2, Treatment Phase: Placebo

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Naurex, Inc, an affiliate of Allergan plc: lead

Study Sites (1)

Vince and Associates Clinical Research Inc

Overland Park, Kansas, 66212, United States

Location

MeSH Terms

Interventions

GLYX-13 peptide; Ketamine

Intervention Hierarchy (Ancestors)

Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Study Officials

• Sheng Fang Su

  Allergan

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 15, 2018
• First Posted: January 10, 2019
• Study Start: November 1, 2018
• Primary Completion: March 24, 2019
• Study Completion: March 29, 2019
• Last Updated: May 16, 2019

Record last verified: 2019-05

Locations

US (1)