Single and Multiple Rising Dose Study of Safety and PK of Metyrapone/Oxazepam Combination (EMB-001)
Condition: Cocaine Use Disorder; Tobacco Use Disorder
MeSH terms: Tobacco Use Disorder
Study type: Interventional
Phase: Phase 1

Summary: 
      This is a study of EMB-001 (a combination of two FDA-approved drugs, metyrapone and oxazepam)
      in otherwise healthy adults who are regular cigarette smokers. There will be 3 groups of 8
      subjects; in each group, 6 subjects will get the drug combination and 2 will get placebo.
      Neither the subjects nor the study personnel will know who got drug and who got placebo
      (double-blind). In the first group the drug doses will be low, and they will be increased in
      the second and third groups. Subjects will receive a single dose on Day 1, followed 24 hours
      later by the start of doses twice daily for 7 days, and then a final morning dose on the last
      day. The levels of the drugs in the blood will be assessed by repeated blood draws after the
      first day and after the end of dosing. Safety will be assessed after the single dose and
      repeated dosing. Effects of study drug on smoking and craving cigarettes will be assessed at
      the end of repeated dosing. The hypothesis is that this drug combination will be safe, with
      relatively few side effects.
    

Detailed description: 
      This study is a Phase 1, double blind, single and multiple rising dose tolerance study of
      EMB-001 (metyrapone/oxazepam combination) in otherwise healthy adults who have tobacco use
      disorder. There will be 3 cohorts, each with 8 subjects (6 active: 2 placebo), for a total of
      24 subjects. During the treatment period, subjects will receive a single dose of EMB 001 on
      Day 1, followed 24 hours later by the start of multiple doses twice daily for 7 days, and
      then a final morning dose on the last dosing day (Day 9). This design allows for
      characterization of EMB-001 single dose PK for 24 hours, followed by assessment of repeat
      dose PK in the multiple-dose phase. Safety will be assessed after the single dose and
      repeated dosing. Effects of study drug on smoking and craving cigarettes will be assessed at
      the end of repeated dosing. Later studies may also assess the efficacy of this drug
      combination in treating cocaine use disorder, tobacco use disorder, and/or other disorders.
    

Intervention name(s): metyrapone & oxazepam; metyrapone & oxazepam; metyrapone & oxazepam; Placebo
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): 6 subjects will receive active study drug (a low dose combination of metyrapone & oxazepam) and 2 subjects will receive placebo.; 6 subjects will receive active study drug (a medium dose combination of metyrapone & oxazepam) and 2 subjects will receive placebo.; 6 subjects will receive active study drug (a high dose combination of metyrapone & oxazepam) and 2 subjects will receive placebo.; Each cohort will have 2 subjects receiving placebo
Other intervention name(s): Cohort 1; Cohort 2; Cohort 3; All Cohorts
Intervention MeSH terms: Oxazepam; Metyrapone
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment