Crossover Study to Evaluate the Abuse Potential of Intranasal Esketamine Compared to Racemic Intravenous Ketamine in Nondependent, Recreational Drug Users
Condition: Drug Abuse
MeSH terms: Substance-Related Disorders
Study type: Interventional
Phase: Phase 1

Summary: 
      The primary objective of this study is to evaluate the abuse potential of intranasal
      esketamine (112 milligram and 84 mg) compared to racemic intravenous ketamine (0.5 mg/kg) in
      nondependent, recreational polydrug users of perception-altering drugs.
    

Detailed description: 
      This is a single-center, single-dose, double-blind, double-dummy, placebo-controlled
      (participants are randomly assigned to a test treatment or to an identical-appearing
      treatment that does not contain the test drug), randomized (study medication assigned to
      participants by chance), crossover study in up to 120 men and women self-identifying as
      current, recreational, nondependent polydrug users. The study has a Screening Phase
      (consisting of a Screening Visit and a Qualification Session) and a Treatment Phase. In the
      Qualification Session participants will be randomized to receive Sequence 1: intravenous
      placebo and intranasal placebo concurrently (Treatment A) on Day 1 and an intravenous dose
      (0.5 mg/kg) of racemic ketamine and intranasal placebo concurrently (Treatment B) on Day 2,
      or the participants will receive Sequence 2: Treatment B on Day 1 and Treatment A on Day 2.
      In the Treatment Phase eligible participants will be administered 4 treatments: A, B, C
      (intravenous placebo and intranasal 84 mg esketamine as 3 devices, each with 28 mg esketamine
      followed by 1 device with placebo) and D (intravenous placebo and intranasal 112 mg of
      esketamine as 4 devices, each with 28 mg esketamine) in a cross-over manner (1 treatment per
      period) in Sequence 3, 4, 5, or 6. Periods 1, 2, 3, and 4 will be separated by 7 to 14 days.
      Primarily the drug abuse potential will be evaluated. Safety of the participants will be
      monitored throughout the study.
    

Intervention name(s): Intravenous placebo; Intranasal placebo; Intravenous racemic ketamine; Esketamine 112 mg; Esketamine 84 mg
Intervention type(s): Drug; Drug; Drug; Drug; Drug
Intervention description(s): Participants will receive placebo, 40-minute, intravenous infusion on Day 1 of Sequence 1, on Day 2 of Sequence 2, on Day 1 of Period 1 in Sequence 3, 5 and 6, on Day 1 of Period 2 in Sequence 3, 4 and 6, on Day 1 of Period 3 in Sequence 4, 5 and 6, and on Day 1 of Period 4 in Sequence 3, 4 and 5.; Participants will receive placebo, intranasally, on Day 1 or Day 2 in Sequence 1 and 2, on Day 1 of Period 1 in Sequence 3 and 4, on Day 1 of Period 2 in Sequence 4 and 5, on Day 1 of Period 3 in Sequence 3 and 6 and on Day 1 of Period 4 in Sequence 5 and 6.; Participants will receive 0.5 mg/kg racemic ketamine, intranasally, on Day 2 in sequence 1, on Day 1 in sequence 2, on Day 1 of Period 1 in Sequence 4, on Day 1 of Period 2 in Sequence 5, on Day 1 of Period 3 in Sequence 3, and on Day 1 of Period 4 in Sequence 6.; Participants will receive 112 mg of Esketamine, intranasally, on Day 1 of Period 1 in Sequence 6, on Day 1 of Period 2 in Sequence 3, on Day 1 of Period 3 in Sequence 5, and on Day 1 of Period 4 in Sequence 4.; Participants will receive 84 mg of Esketamine, intranasally, on Day 1 of Period 1 in Sequence 5, on Day 1 of Period 2 in Sequence 6, on Day 1 of Period 3 in Sequence 4, and on Day 1 of Period 4 in Sequence 3.
Intervention MeSH terms: Ketamine; Esketamine
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: Esketamine; Placebo; Racemic ketamine; Pharmacokinetics