Meth-OD: A Study of IXT-m200 in Patients With Toxicity From Methamphetamine Overdose
Condition: Methamphetamine Intoxication (Disorder)
MeSH terms: Drug Overdose
Intervention: IXT-m200; Lorazepam; Haloperidol
Intervention description: IXT-m200 binds METH with high selectivity and affinity. The product contains a murine METH-binding variable region and the constant domains of a human immunoglobulin G (IgG) 2κ. This antibody isotype was chosen because of the lower risk of immune response compared to an IgG1 or IgG3. IXT-m200 targets METH, does not rely on binding to any endogenous target for its action, and has been well-tolerated in previous clinical studies.; Lorazepam is a benzodiazepine that is safe and commonly used to treat agitation and dysphoria in the emergency setting.; Haloperidol is commonly used to treat agitation due to psychosis.
Intervention MeSH terms: Lorazepam; Haloperidol; Haloperidol decanoate
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 20.0
Sex: All
Minimum age: 18 Years
Maximum age: 45 Years
Healthy volunteers: No

Summary:

      The hypothesis of this multisite Phase 2a study is that IXT-m200 will be well-tolerated in
      patients with acute mild to moderate METH toxicity. A randomized, open label design will be
      used in which one dose of IXT-m200 will be compared to treatment-as-usual (TAU).
      Approximately 40 participants will be enrolled in 4 cohorts. A dose escalation approach will
      be used so that progressively higher IXT-m200 doses will be evaluated in each cohort. In
      conjunction with safety monitoring, this design assures the opportunity to observe early
      safety findings before any participants are exposed to the next higher dose. The
      randomization ratio for IXT-m200 versus TAU is defined as 4:1 for each cohort so that the
      number of participants receiving TAU equals the number receiving each dose of IXT-m200 at the
      end of the study.

      Agitation scales and vital signs will be recorded to track effect of the antibody treatment
      versus TAU over time on agitation associated with METH use. While in the emergency department
      (ED), detailed and pertinent medical and psychiatric histories, and physical exam will be
      obtained, along with laboratory assessments and ECGs. In the ED, participants will give blood
      samples for analysis of METH and IXT-m200 concentrations and followed for development of
      adverse events. Participants will be evaluated at 2 days and 4 weeks after discharge from the
      ED for adverse events and drug use history. Cohort escalation reviews will be performed by
      the Sponsor, Medical Monitor, and Data and Safety Monitoring Board (DSMB) between cohorts and
      the next group will not start until after completion of this review.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Be aged 18 to 45 years, inclusive;

          2. Present to the ED with METH toxicity as defined in protocol;

          3. Have a PANSS-EC score of 14-28, inclusive;

          4. Have or agrees to have an intravenous (IV) line placed;

          5. Give a history of METH use in the past 24 hours, with participant or observer
             attribution of symptoms to METH, or have a positive METH drug screen;

          6. Be accompanied or readily represented by a legally authorized representative
             (surrogate) who can consent to participation on behalf of the participant; and

          7. Assent to participation in the study.

        Exclusion Criteria:

          1. Present with concomitant opioid overdose requiring ventilatory support;

          2. Be self-reported to be pregnant or lactating;

          3. Be considered to have significant concomitant medical illness or trauma, or symptoms
             of severe METH toxicity including

               1. sepsis or febrile illness;

               2. myocardial infarction, cardiac decompensation or arrhythmias including
                  tachycardia that is not sinus; severe hypertension (>180/110 mmHg); inadequately
                  treated hypertension on chronic medication; history of vasculitis

               3. coma, stroke or severe head injury; new or ongoing seizure activity

               4. acute pulmonary decompensation or severe chronic obstructive pulmonary disease;

               5. any hepatic impairment and/or acute hepatitis or renal impairment due to
                  concomitant medical illness; or

               6. current, or history of, neuroleptic malignant syndrome

          4. Be considered to be at imminent risk of suicide or have disqualifying answers to the
             following two questions. Disqualifying answers would be 1b2 or 2b. 1. In the past 30
             days, have you considered killing yourself? a) No; b) Yes - if Yes, how often? b1) Not
             often (twice or less), b2) Somewhat often (more than twice). 2. In the past year, have
             you attempted to kill yourself? a) No; b) Yes;

          5. Be considered to be at imminent risk of injury or danger to self, others or property;

          6. Have a history of severe allergy (rash, hives, breathing difficulty, etc.), known
             hypersensitivity or infusion reaction to any antibody medications, lorazepam or
             haloperidol; or

          7. Be judged by the treating ED physician, investigator, or Sponsor (or designee) to be
             inappropriate for the study, including people whom the investigator determines cannot
             reasonably be consulted for assent to participation.