Open Actively Recruiting

Mirtazapine and Methamphetamine Drug-drug Interaction Study

About

Brief Summary

This is a drug-drug interaction (DDI) study of mirtazapine for methamphetamine (MA) use disorder (MUD) to ensure the safety of this medication in the presence of a relevant dose of MA for people actively-using MA.

Aim 1: To determine if mirtazapine alters the cardiovascular response to IV MA. Aim 2: To determine if the pharmacokinetics of IV MA are altered by mirtazapine administration. Aim 3: To evaluate the above aims in the setting of concomitant administration of methadone. This study involves two simultaneous within-subject drug-drug interaction studies, each comprised of 12 participants. A total of 24 subjects will be enrolled who have methamphetamine use disorder who will be classified into 2 groups: (Group 1: no opioids; Group 2: opioid use disorder on methadone maintenance). Subjects will be randomized to the order of mirtazapine and placebo (i.e. one-half will receive mirtazapine first, then placebo; one-half will receive placebo first, then mirtazapine).

Primary Purpose

Treatment

Study Type

Interventional

Phase

Phase 1

Eligibility

Gender

All

Healthy Volunteers

Yes

Minimum Age

18 Years

Maximum Age

N/A

Inclusion Criteria:

English-speaking;
age 18-55 years inclusive;
meet DSM-V criteria for MA use disorder, as diagnosed via SCID;
provide MA-positive urine during screening;
have a resting heart rate of 50-90
have a systolic blood pressure ≤ of 100-150 mm Hg, and diastolic blood pressure of 45-90 Hg within two days prior to admission;
have a baseline EKG that demonstrates normal sinus rhythm, QTc < 440 msec in men or QTc < 450 msec in women;
have acceptable safety lab data, ALT / AST<3x upper limit nL; est GFR >50;
if female (except females of non-childbearing potential-e.g., at least 1 year post-menopausal or surgically sterile), not pregnant confirmed by negative pregnancy test nor lactating and willing to use a medically approved method of birth control to prevent pregnancy during the trial and for 7 days after the last dose of study medication.

For those who also use opioids and are on methadone maintenance treatment (Group 2), urine positive for methadone and negative for buprenorphine on admission.

Exclusion Criteria:

Have current cocaine, cannabis, or alcohol use disorder by DSM-V SCID;
current or past history of seizure disorder;
current ongoing treatment with psychotropic medications (e.g. antidepressants, antipsychotics, antiepileptics, sedative/hypnotics, narcotic analgesics);
urine positive for MA and other unplanned drugs on the day of admission and breathalyzer results negative for alcohol;
any prior adverse reaction to MA; including chest pain or epileptic seizure;
major psychiatric disorder not due to substance abuse (e.g., schizophrenia, bipolar illness but excepting stable major depressive disorder, generalized anxiety disorder, etc.) as assessed by the SCID;
have a current neurological disorder (e.g., organic brain disease, dementia) or medical condition which would make study compliance difficult or compromise informed consent;
history of suicide attempt(s) in the past 90 days or current suicidal intent or plan by SCID;
evidence of untreated or unstable serious medical illness including: neuroendocrine, autoimmune, renal, hepatic, or active infectious disease including active tuberculosis infection;
seeking treatment for MA problems at the time of the study;
any serious medical or psychiatric AE after test infusion of MA 30mg IV (e.g. sustained SBP>200 or DBP>100; sustained pulse >(220-0.85xAge).
any other circumstances that, in the opinion of the investigators, would compromise participant safety and/or successful completion of the trial.