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Assessment of Abuse Potential of Rapastinel in Humans

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ClinicalTrials.gov Identifier: NCT03799900
Recruitment Status : Completed
First Posted : January 10, 2019
Last Update Posted : May 16, 2019
Sponsor:
Information provided by (Responsible Party):
Naurex, Inc, an affiliate of Allergan plc

Tracking Information
First Submitted Date  ICMJE November 15, 2018
First Posted Date  ICMJE January 10, 2019
Last Update Posted Date May 16, 2019
Actual Study Start Date  ICMJE November 1, 2018
Actual Primary Completion Date March 24, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 14, 2019)
Maximum effect (Emax) for "At this Moment" Drug Liking visual analog scale (VAS). [ Time Frame: 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".
Original Primary Outcome Measures  ICMJE
 (submitted: January 9, 2019)
Maximum effect (Emax) for "At this Moment" Drug Liking visual analog scale (VAS). [ Time Frame: Treatment Phase: Pre-dose and up to 8 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".
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 14, 2019)
  • Maximum effect (Emax) [ Time Frame: Treatment Phase: Pre-dose and up to 24 hours post-dose ]
  • Minimum effect (Emin) [ Time Frame: Treatment Phase: Pre-dose and up to 24 hours post-dose ]
  • Time to Emax (TEmax) [ Time Frame: Treatment Phase: Pre-dose and up to 24 hours post-dose ]
  • Time to Emin (TEmin) [ Time Frame: Treatment Phase: Pre-dose and up to 24 hours post-dose ]
  • Time averaged area under the effect curve (TA_AUE) [ Time Frame: Treatment Phase: Hour 0 and up to 24 Hours post-dose ]
  • Maximum plasma drug concentration (Cmax) [ Time Frame: 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) [ Time Frame: Treatment Phase: Pre-dose and up to 24 hours post-dose ]
  • Adverse events [ Time Frame: Part 1: 6 weeks, Part 2: 9 weeks ]
  • Proportion of abnormal electrocardiograms [ Time Frame: Part 1: 6 weeks, Part 2: 9 weeks ]
  • Columbia-Suicide Severity Rating Scale [ Time Frame: 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).
Original Secondary Outcome Measures  ICMJE
 (submitted: January 9, 2019)
  • Maximum effect (Emax) [ Time Frame: Treatment Phase: Pre-dose and up to 8 hours post-dose ]
  • Minimum effect (Emin) [ Time Frame: Treatment Phase: Pre-dose and up to 8 hours post-dose ]
  • Time to Emax (TEmax) [ Time Frame: Treatment Phase: Pre-dose and up to 8 hours post-dose ]
  • Time to Emin (TEmin) [ Time Frame: Treatment Phase: Pre-dose and up to 8 hours post-dose ]
  • Time averaged area under the effect curve (TA_AUE) [ Time Frame: Treatment Phase: Hour 0 and up to 4 Hours post-dose ]
  • Maximum plasma drug concentration (Cmax) [ Time Frame: Treatment Phase: Pre-dose and up to 8 hours post-dose ]
  • Area under the plasma concentration versus time curve from time 0 to the last quantifiable concentration (AUClast) [ Time Frame: Treatment Phase: Pre-dose and up to 8 hours post-dose ]
  • Adverse events [ Time Frame: Part 1: 6 weeks, Part 2: 9 weeks ]
  • Proportion of abnormal electrocardiograms [ Time Frame: Part 1: 6 weeks, Part 2: 9 weeks ]
  • Columbia-Suicide Severity Rating Scale [ Time Frame: 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).
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Assessment of Abuse Potential of Rapastinel in Humans
Official Title  ICMJE 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
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 Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Other
Condition  ICMJE Human Abuse Potential
Intervention  ICMJE
  • 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.
  • 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.

  • 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.

Study Arms  ICMJE
  • Experimental: Part 1, Cohort 1: Ketamine Low Dose
    Some participants will be administered a single IV dose of ketamine on Day 1.
    Intervention: Drug: Ketamine
  • Placebo Comparator: Part 1, Cohort 1: Placebo
    Some participants will be administered a single IV dose of placebo on Day 1.
    Intervention: Drug: Placebo
  • Experimental: Part 1, Cohort 2: Ketamine Medium Dose
    Some participants will be administered a single IV dose of ketamine on Day 1.
    Intervention: Drug: Ketamine
  • Placebo Comparator: Part 1, Cohort 2: Placebo
    Some participants will be administered a single IV dose of placebo on Day 1.
    Intervention: Drug: Placebo
  • Experimental: Part 1, Cohort 3 (Optional): Ketamine High Dose
    Optional: some participants will be administered a single IV dose of ketamine on Day 1.
    Intervention: Drug: Ketamine
  • Placebo Comparator: Part 1, Cohort 3 (Optional): Placebo
    Optional: some participants will be administered a single IV dose of placebo on Day 1.
    Intervention: Drug: Placebo
  • Experimental: Part 2, Qualification Phase: Ketamine
    Participants will receive IV ketamine on Day 1 and placebo on Day 2 in a randomized crossover manner.
    Intervention: Drug: Ketamine
  • 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.
    Intervention: Drug: Placebo
  • 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.
    Intervention: Drug: Rapastinel
  • 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.
    Intervention: Drug: Rapastinel
  • 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.
    Intervention: Drug: Rapastinel
  • Active Comparator: Part 2, Treatment Phase: Ketamine
    Participants will be administered single IV doses of rapastinel, ketamine, and placebo in a randomized crossover manner.
    Intervention: Drug: Ketamine
  • Placebo Comparator: Part 2, Treatment Phase: Placebo
    Participants will be administered single IV doses of rapastinel, ketamine, and placebo in a randomized crossover manner.
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: May 14, 2019)
72
Original Estimated Enrollment  ICMJE
 (submitted: January 9, 2019)
98
Actual Study Completion Date  ICMJE March 29, 2019
Actual Primary Completion Date March 24, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 55 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03799900
Other Study ID Numbers  ICMJE RAP-PK-12
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Naurex, Inc, an affiliate of Allergan plc
Study Sponsor  ICMJE Naurex, Inc, an affiliate of Allergan plc
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Sheng Fang Su Allergan
PRS Account Naurex, Inc, an affiliate of Allergan plc
Verification Date May 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP