Mirtazapine and Methamphetamine Drug-drug Interaction Study

NCT04614584 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: 20-30109
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 3

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).

Conditions

Methamphetamine Use Disorder; Drug Interaction; Cardiovascular Abnormalities

Keywords

Methamphetamine; Mirtazapine; Methadone; Drug Interaction

Outcome Measures

Primary Outcomes (2)

• Safety Measures

  QT interval associated with combined use of methamphetamine and mirtazapine with and without concomitant methadone use

  24 Days

• Metabolism of methamphetamine in presence of steady state mirtazapine

  Metabolism of methamphetamine in combination with mirtazapine Pharmacokinetics of methamphetamine in combination with mirtazapine with or without concomitant methadone use

  14 Days

Secondary Outcomes (5)

• Impact of mirtazapine on subjective effects of methamphetamine reinforcement

  14 Days

• Impact of mirtazapine on mood produced by methamphetamine use

  14 days

• Urge for stimulant use in the presence of mirtazapine

  14 days

• Preference for methamphetamine in the presence of mirtazapine

  14 days

• Impact of mirtazapine on discounting in the presence of methamphetamine

  14 days

Study Arms (2)

Mirtazapine

EXPERIMENTAL

Mirtazapine 30 mg PO daily x 4 days

Drug: Mirtazapine; Drug: Methamphetamine

Placebo

PLACEBO COMPARATOR

Placebo 30 mg PO Daily x 4 days

Drug: Methamphetamine

Interventions

Mirtazapine DRUG

Mirtazapine 30 mg PO daily x 4 days

Mirtazapine

Methamphetamine DRUG

Methamphetamine 30 mg IV once

Mirtazapine; Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• San Francisco Department of Public Health: lead
• University of California, Los Angeles: collaborator

Study Sites (3)

UCLA Medical Center

Los Angeles, California, 90095, United States

Location

San Francisco Department of Public Health

San Francisco, California, 94102, United States

Location

Substance Use Research Unit

San Francisco, California, 94102, United States

Location

MeSH Terms

Conditions

Cardiovascular Abnormalities

Interventions

Mirtazapine; Methamphetamine

Condition Hierarchy (Ancestors)

Cardiovascular Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Dibenzazepines; Heterocyclic Compounds, 3-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Amphetamines; Phenethylamines; Ethylamines; Amines; Organic Chemicals

Study Officials

• Phillip Coffin, MD, MIA

  Director, Substance Use Division, San Francisco Department of Public Health

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Substance Use Research

Study Record Dates

• First Submitted: September 14, 2020
• First Posted: November 4, 2020
• Study Start: May 3, 2021
• Primary Completion: May 31, 2024
• Study Completion: May 31, 2024
• Last Updated: September 27, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)