Methamphetamine Intoxication (Disorder)
Conditions
Brief 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.
Interventions
BIOLOGICALIXT-m200
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.
DRUGLorazepam
Lorazepam is a benzodiazepine that is safe and commonly used to treat agitation and dysphoria in the emergency setting.
DRUGHaloperidol
Haloperidol is commonly used to treat agitation due to psychosis.
Sponsors
National Institute on Drug Abuse (NIDA)
InterveXion Therapeutics, LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With Treatment-related AEs as Measured by Electrocardiogram | 4 hours | Electrocardiogram |
| Number of Patients With Treatment-related Adverse Events (AEs) as Measured by Vital Signs | 28 days | Blood pressure, heart rate, and temperature |
| Number of Patients With Treatment-related AEs as Measured by Physical Examinations | 28 days | Physical examinations |
| Number of Patients With Treatment-related AEs as Measured by Clinical Laboratory Testing | 3 days | Clinical laboratory testing |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time Course and Degree of Normalization of Temperature | Baseline and hours 0.5, 1, 2, 3, 4, and 8 post-dose or until discharge. | Temperature over time |
| Number of Participants Requiring Rescue Medications for Psychiatric or Cardiovascular Manifestations of METH Toxicity | 8 hours | Number of participants that need rescue medications to treat: * agitation, dysphoria, or psychosis (central nervous system toxicity) * hypertension, tachycardia, or other cardiovascular instability (cardiovascular toxicity) |
| Time Course and Degree of Normalization of Agitation | Baseline and hours 0.5, 1, 2, 3, 4, and 8 post-dose or until discharge. | Agitation/sedation scores over time as measured by Agitation/Calmness Evaluation Score (ACES). The minimum value is 1 (highly agitated) and the highest value is 9 (completely sedated). A score of 3-5 is considered normal. |
| Number of Participants at Certain Degrees of Normalization of Blood Pressure Over Time | Baseline and hours 0.5, 1, 2, 3, 4, and 8 post-dose or until discharge. | Blood pressure over time; reported as the number of participants with blood pressure out of normal range (i.e., diastolic \>110 or \<50 mmHg, or systolic \>180 or \<90 mmHg)) |
| Number of Participants at Certain Degrees of Normalization of Heart Rate Over Time | Baseline and hours 0.5, 1, 2, 3, 4, and 8 post-dose or until discharge. | Heart rate over time reported as number of participants with heart rate high (\>120 beats/min), normal, or low (\<40 beats/min). |
Other
| Measure | Time frame | Description |
|---|---|---|
| Length of Patient Stay in the ED | Start of treatment until discharge | ED length of stay as measured by discharge time minus start of treatment time |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| IXT-m200 Low Dose (0.5 g) IXT-m200 is a high-affinity chimeric anti-METH monoclonal antibody that is well-tolerated in healthy volunteers and in non-intoxicated people with METH use disorder. The total dose will be given over 10 min for the 0.5-g dose.
IXT-m200: 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. | 8 |
| IXT-m200 High Dose (2 g) IXT-m200 is a high-affinity chimeric anti-METH monoclonal antibody that is well-tolerated in healthy volunteers and in non-intoxicated people with METH use disorder. The total dose will be given over 20 min for the 2-g doses.
IXT-m200: 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. | 8 |
| Treatment as Usual (TAU) 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.
Lorazepam: Lorazepam is a benzodiazepine that is safe and commonly used to treat agitation and dysphoria in the emergency setting.
Haloperidol: Haloperidol is commonly used to treat agitation due to psychosis. | 4 |
| Total | 20 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 5 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | IXT-m200 Low Dose (0.5 g) | Total | Treatment as Usual (TAU) | IXT-m200 High Dose (2 g) |
|---|---|---|---|---|
| Age, Continuous | 34.3 years STANDARD_DEVIATION 6.23 | 35.5 years STANDARD_DEVIATION 6.1 | 35.3 years STANDARD_DEVIATION 7.17 | 36.8 years STANDARD_DEVIATION 6.48 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 4 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants | 16 Participants | 3 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 2 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 6 Participants | 16 Participants | 4 Participants | 6 Participants |
| Region of Enrollment United States | 8 participants | 20 participants | 4 participants | 8 participants |
| Sex: Female, Male Female | 2 Participants | 6 Participants | 0 Participants | 4 Participants |
| Sex: Female, Male Male | 6 Participants | 14 Participants | 4 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 8 | 0 / 4 |
| other Total, other adverse events | 5 / 8 | 2 / 8 | 2 / 4 |
| serious Total, serious adverse events | 1 / 8 | 0 / 8 | 0 / 4 |
Outcome results
Primary
Number of Patients With Treatment-related Adverse Events (AEs) as Measured by Vital Signs
Blood pressure, heart rate, and temperature
Time frame: 28 days
Population: All participants receiving a dose of IXT-m200 or TAU.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| IXT-m200 Low Dose (0.5 g) | Number of Patients With Treatment-related Adverse Events (AEs) as Measured by Vital Signs | 0 Participants |
| IXT-m200 High Dose (2 g) | Number of Patients With Treatment-related Adverse Events (AEs) as Measured by Vital Signs | 0 Participants |
| Treatment as Usual (TAU) | Number of Patients With Treatment-related Adverse Events (AEs) as Measured by Vital Signs | 0 Participants |
Primary
Number of Patients With Treatment-related AEs as Measured by Clinical Laboratory Testing
Clinical laboratory testing
Time frame: 3 days
Population: All participants receiving a dose of IXT-m200 or TAU.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| IXT-m200 Low Dose (0.5 g) | Number of Patients With Treatment-related AEs as Measured by Clinical Laboratory Testing | 0 Participants |
| IXT-m200 High Dose (2 g) | Number of Patients With Treatment-related AEs as Measured by Clinical Laboratory Testing | 0 Participants |
| Treatment as Usual (TAU) | Number of Patients With Treatment-related AEs as Measured by Clinical Laboratory Testing | 0 Participants |
Primary
Number of Patients With Treatment-related AEs as Measured by Electrocardiogram
Electrocardiogram
Time frame: 4 hours
Population: All participants receiving a dose of IXT-m200 or TAU.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| IXT-m200 Low Dose (0.5 g) | Number of Patients With Treatment-related AEs as Measured by Electrocardiogram | 0 Participants |
| IXT-m200 High Dose (2 g) | Number of Patients With Treatment-related AEs as Measured by Electrocardiogram | 0 Participants |
| Treatment as Usual (TAU) | Number of Patients With Treatment-related AEs as Measured by Electrocardiogram | 0 Participants |
Primary
Number of Patients With Treatment-related AEs as Measured by Physical Examinations
Physical examinations
Time frame: 28 days
Population: All participants receiving a dose of IXT-m200 or TAU
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| IXT-m200 Low Dose (0.5 g) | Number of Patients With Treatment-related AEs as Measured by Physical Examinations | 0 Participants |
| IXT-m200 High Dose (2 g) | Number of Patients With Treatment-related AEs as Measured by Physical Examinations | 0 Participants |
| Treatment as Usual (TAU) | Number of Patients With Treatment-related AEs as Measured by Physical Examinations | 0 Participants |
Secondary
Number of Participants at Certain Degrees of Normalization of Blood Pressure Over Time
Blood pressure over time; reported as the number of participants with blood pressure out of normal range (i.e., diastolic \>110 or \<50 mmHg, or systolic \>180 or \<90 mmHg))
Time frame: Baseline and hours 0.5, 1, 2, 3, 4, and 8 post-dose or until discharge.
Population: All participants receiving a dose of IXT-m200 or TAU. No further data were collected after participants were discharged. Some time points do not contain results as all participants in that group had been discharged prior to that timepoint or all data were missing.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| IXT-m200 Low Dose (0.5 g) | Number of Participants at Certain Degrees of Normalization of Blood Pressure Over Time | 1 hour | High | 0 Participants |
| IXT-m200 Low Dose (0.5 g) | Number of Participants at Certain Degrees of Normalization of Blood Pressure Over Time | 3 hours | Low | 0 Participants |
| IXT-m200 Low Dose (0.5 g) | Number of Participants at Certain Degrees of Normalization of Blood Pressure Over Time | Baseline | Low | 0 Participants |
| IXT-m200 Low Dose (0.5 g) | Number of Participants at Certain Degrees of Normalization of Blood Pressure Over Time | 1 hour | Normal | 8 Participants |
| IXT-m200 Low Dose (0.5 g) | Number of Participants at Certain Degrees of Normalization of Blood Pressure Over Time | Baseline | Normal | 8 Participants |
| IXT-m200 Low Dose (0.5 g) | Number of Participants at Certain Degrees of Normalization of Blood Pressure Over Time | Baseline | High | 0 Participants |
| IXT-m200 Low Dose (0.5 g) | Number of Participants at Certain Degrees of Normalization of Blood Pressure Over Time | 1 hour | Low | 0 Participants |
| IXT-m200 Low Dose (0.5 g) | Number of Participants at Certain Degrees of Normalization of Blood Pressure Over Time | 3 hours | Normal | 1 Participants |
| IXT-m200 Low Dose (0.5 g) | Number of Participants at Certain Degrees of Normalization of Blood Pressure Over Time | 0.5 hour | Low | 0 Participants |
| IXT-m200 Low Dose (0.5 g) | Number of Participants at Certain Degrees of Normalization of Blood Pressure Over Time | 2 hours | High | 0 Participants |
| IXT-m200 Low Dose (0.5 g) | Number of Participants at Certain Degrees of Normalization of Blood Pressure Over Time | 0.5 hour | Normal | 8 Participants |
| IXT-m200 Low Dose (0.5 g) | Number of Participants at Certain Degrees of Normalization of Blood Pressure Over Time | 0.5 hour | High | 0 Participants |
| IXT-m200 Low Dose (0.5 g) | Number of Participants at Certain Degrees of Normalization of Blood Pressure Over Time | 2 hours | Normal | 7 Participants |
| IXT-m200 Low Dose (0.5 g) | Number of Participants at Certain Degrees of Normalization of Blood Pressure Over Time | 3 hours | High | 0 Participants |
| IXT-m200 Low Dose (0.5 g) | Number of Participants at Certain Degrees of Normalization of Blood Pressure Over Time | 2 hours | Low | 0 Participants |
| IXT-m200 High Dose (2 g) | Number of Participants at Certain Degrees of Normalization of Blood Pressure Over Time | 1 hour | Low | 0 Participants |
| IXT-m200 High Dose (2 g) | Number of Participants at Certain Degrees of Normalization of Blood Pressure Over Time | 2 hours | High | 0 Participants |
| IXT-m200 High Dose (2 g) | Number of Participants at Certain Degrees of Normalization of Blood Pressure Over Time | 2 hours | Normal | 5 Participants |
| IXT-m200 High Dose (2 g) | Number of Participants at Certain Degrees of Normalization of Blood Pressure Over Time | 0.5 hour | High | 1 Participants |
| IXT-m200 High Dose (2 g) | Number of Participants at Certain Degrees of Normalization of Blood Pressure Over Time | 2 hours | Low | 0 Participants |
| IXT-m200 High Dose (2 g) | Number of Participants at Certain Degrees of Normalization of Blood Pressure Over Time | 3 hours | High | 0 Participants |
| IXT-m200 High Dose (2 g) | Number of Participants at Certain Degrees of Normalization of Blood Pressure Over Time | 3 hours | Normal | 2 Participants |
| IXT-m200 High Dose (2 g) | Number of Participants at Certain Degrees of Normalization of Blood Pressure Over Time | 3 hours | Low | 0 Participants |
| IXT-m200 High Dose (2 g) | Number of Participants at Certain Degrees of Normalization of Blood Pressure Over Time | Prior to discharge | High | 1 Participants |
| IXT-m200 High Dose (2 g) | Number of Participants at Certain Degrees of Normalization of Blood Pressure Over Time | Prior to discharge | Normal | 0 Participants |
| IXT-m200 High Dose (2 g) | Number of Participants at Certain Degrees of Normalization of Blood Pressure Over Time | 0.5 hour | Normal | 7 Participants |
| IXT-m200 High Dose (2 g) | Number of Participants at Certain Degrees of Normalization of Blood Pressure Over Time | Prior to discharge | Low | 0 Participants |
| IXT-m200 High Dose (2 g) | Number of Participants at Certain Degrees of Normalization of Blood Pressure Over Time | Baseline | Normal | 5 Participants |
| IXT-m200 High Dose (2 g) | Number of Participants at Certain Degrees of Normalization of Blood Pressure Over Time | 0.5 hour | Low | 0 Participants |
| IXT-m200 High Dose (2 g) | Number of Participants at Certain Degrees of Normalization of Blood Pressure Over Time | Baseline | High | 2 Participants |
| IXT-m200 High Dose (2 g) | Number of Participants at Certain Degrees of Normalization of Blood Pressure Over Time | 1 hour | High | 1 Participants |
| IXT-m200 High Dose (2 g) | Number of Participants at Certain Degrees of Normalization of Blood Pressure Over Time | 1 hour | Normal | 7 Participants |
| IXT-m200 High Dose (2 g) | Number of Participants at Certain Degrees of Normalization of Blood Pressure Over Time | Baseline | Low | 1 Participants |
| Treatment as Usual (TAU) | Number of Participants at Certain Degrees of Normalization of Blood Pressure Over Time | Prior to discharge | Low | 0 Participants |
| Treatment as Usual (TAU) | Number of Participants at Certain Degrees of Normalization of Blood Pressure Over Time | Baseline | High | 0 Participants |
| Treatment as Usual (TAU) | Number of Participants at Certain Degrees of Normalization of Blood Pressure Over Time | Baseline | Normal | 4 Participants |
| Treatment as Usual (TAU) | Number of Participants at Certain Degrees of Normalization of Blood Pressure Over Time | Baseline | Low | 0 Participants |
| Treatment as Usual (TAU) | Number of Participants at Certain Degrees of Normalization of Blood Pressure Over Time | 0.5 hour | High | 0 Participants |
| Treatment as Usual (TAU) | Number of Participants at Certain Degrees of Normalization of Blood Pressure Over Time | 0.5 hour | Normal | 3 Participants |
| Treatment as Usual (TAU) | Number of Participants at Certain Degrees of Normalization of Blood Pressure Over Time | 0.5 hour | Low | 0 Participants |
| Treatment as Usual (TAU) | Number of Participants at Certain Degrees of Normalization of Blood Pressure Over Time | 1 hour | High | 0 Participants |
| Treatment as Usual (TAU) | Number of Participants at Certain Degrees of Normalization of Blood Pressure Over Time | 1 hour | Normal | 4 Participants |
| Treatment as Usual (TAU) | Number of Participants at Certain Degrees of Normalization of Blood Pressure Over Time | 1 hour | Low | 0 Participants |
| Treatment as Usual (TAU) | Number of Participants at Certain Degrees of Normalization of Blood Pressure Over Time | 2 hours | High | 0 Participants |
| Treatment as Usual (TAU) | Number of Participants at Certain Degrees of Normalization of Blood Pressure Over Time | 2 hours | Normal | 1 Participants |
| Treatment as Usual (TAU) | Number of Participants at Certain Degrees of Normalization of Blood Pressure Over Time | 2 hours | Low | 1 Participants |
| Treatment as Usual (TAU) | Number of Participants at Certain Degrees of Normalization of Blood Pressure Over Time | Prior to discharge | High | 0 Participants |
| Treatment as Usual (TAU) | Number of Participants at Certain Degrees of Normalization of Blood Pressure Over Time | Prior to discharge | Normal | 1 Participants |
Secondary
Number of Participants at Certain Degrees of Normalization of Heart Rate Over Time
Heart rate over time reported as number of participants with heart rate high (\>120 beats/min), normal, or low (\<40 beats/min).
Time frame: Baseline and hours 0.5, 1, 2, 3, 4, and 8 post-dose or until discharge.
Population: All participants receiving a dose of IXT-m200 or TAU. No further data were collected after participants were discharged. Some time points do not contain results as all participants in that group had been discharged prior to that timepoint or all data were missing.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| IXT-m200 Low Dose (0.5 g) | Number of Participants at Certain Degrees of Normalization of Heart Rate Over Time | 0.5 hour | Normal | 7 Participants |
| IXT-m200 Low Dose (0.5 g) | Number of Participants at Certain Degrees of Normalization of Heart Rate Over Time | Baseline | Normal | 8 Participants |
| IXT-m200 Low Dose (0.5 g) | Number of Participants at Certain Degrees of Normalization of Heart Rate Over Time | Baseline | Low | 0 Participants |
| IXT-m200 Low Dose (0.5 g) | Number of Participants at Certain Degrees of Normalization of Heart Rate Over Time | 0.5 hour | High | 1 Participants |
| IXT-m200 Low Dose (0.5 g) | Number of Participants at Certain Degrees of Normalization of Heart Rate Over Time | Baseline | High | 0 Participants |
| IXT-m200 Low Dose (0.5 g) | Number of Participants at Certain Degrees of Normalization of Heart Rate Over Time | 0.5 hour | Low | 0 Participants |
| IXT-m200 Low Dose (0.5 g) | Number of Participants at Certain Degrees of Normalization of Heart Rate Over Time | 1 hour | High | 1 Participants |
| IXT-m200 Low Dose (0.5 g) | Number of Participants at Certain Degrees of Normalization of Heart Rate Over Time | 1 hour | Normal | 7 Participants |
| IXT-m200 Low Dose (0.5 g) | Number of Participants at Certain Degrees of Normalization of Heart Rate Over Time | 1 hour | Low | 0 Participants |
| IXT-m200 Low Dose (0.5 g) | Number of Participants at Certain Degrees of Normalization of Heart Rate Over Time | 2 hours | High | 1 Participants |
| IXT-m200 Low Dose (0.5 g) | Number of Participants at Certain Degrees of Normalization of Heart Rate Over Time | 2 hours | Normal | 6 Participants |
| IXT-m200 Low Dose (0.5 g) | Number of Participants at Certain Degrees of Normalization of Heart Rate Over Time | 2 hours | Low | 0 Participants |
| IXT-m200 Low Dose (0.5 g) | Number of Participants at Certain Degrees of Normalization of Heart Rate Over Time | 3 hours | High | 0 Participants |
| IXT-m200 Low Dose (0.5 g) | Number of Participants at Certain Degrees of Normalization of Heart Rate Over Time | 3 hours | Normal | 1 Participants |
| IXT-m200 Low Dose (0.5 g) | Number of Participants at Certain Degrees of Normalization of Heart Rate Over Time | 3 hours | Low | 0 Participants |
| IXT-m200 High Dose (2 g) | Number of Participants at Certain Degrees of Normalization of Heart Rate Over Time | Prior to discharge | Low | 0 Participants |
| IXT-m200 High Dose (2 g) | Number of Participants at Certain Degrees of Normalization of Heart Rate Over Time | 0.5 hour | Low | 0 Participants |
| IXT-m200 High Dose (2 g) | Number of Participants at Certain Degrees of Normalization of Heart Rate Over Time | 1 hour | High | 0 Participants |
| IXT-m200 High Dose (2 g) | Number of Participants at Certain Degrees of Normalization of Heart Rate Over Time | 1 hour | Normal | 8 Participants |
| IXT-m200 High Dose (2 g) | Number of Participants at Certain Degrees of Normalization of Heart Rate Over Time | 3 hours | Low | 0 Participants |
| IXT-m200 High Dose (2 g) | Number of Participants at Certain Degrees of Normalization of Heart Rate Over Time | 1 hour | Low | 0 Participants |
| IXT-m200 High Dose (2 g) | Number of Participants at Certain Degrees of Normalization of Heart Rate Over Time | Prior to discharge | High | 0 Participants |
| IXT-m200 High Dose (2 g) | Number of Participants at Certain Degrees of Normalization of Heart Rate Over Time | 2 hours | High | 0 Participants |
| IXT-m200 High Dose (2 g) | Number of Participants at Certain Degrees of Normalization of Heart Rate Over Time | 2 hours | Normal | 5 Participants |
| IXT-m200 High Dose (2 g) | Number of Participants at Certain Degrees of Normalization of Heart Rate Over Time | Prior to discharge | Normal | 1 Participants |
| IXT-m200 High Dose (2 g) | Number of Participants at Certain Degrees of Normalization of Heart Rate Over Time | Baseline | High | 0 Participants |
| IXT-m200 High Dose (2 g) | Number of Participants at Certain Degrees of Normalization of Heart Rate Over Time | 2 hours | Low | 0 Participants |
| IXT-m200 High Dose (2 g) | Number of Participants at Certain Degrees of Normalization of Heart Rate Over Time | Baseline | Normal | 8 Participants |
| IXT-m200 High Dose (2 g) | Number of Participants at Certain Degrees of Normalization of Heart Rate Over Time | Baseline | Low | 0 Participants |
| IXT-m200 High Dose (2 g) | Number of Participants at Certain Degrees of Normalization of Heart Rate Over Time | 0.5 hour | High | 0 Participants |
| IXT-m200 High Dose (2 g) | Number of Participants at Certain Degrees of Normalization of Heart Rate Over Time | 3 hours | High | 0 Participants |
| IXT-m200 High Dose (2 g) | Number of Participants at Certain Degrees of Normalization of Heart Rate Over Time | 0.5 hour | Normal | 8 Participants |
| IXT-m200 High Dose (2 g) | Number of Participants at Certain Degrees of Normalization of Heart Rate Over Time | 3 hours | Normal | 2 Participants |
| Treatment as Usual (TAU) | Number of Participants at Certain Degrees of Normalization of Heart Rate Over Time | 0.5 hour | Low | 0 Participants |
| Treatment as Usual (TAU) | Number of Participants at Certain Degrees of Normalization of Heart Rate Over Time | 2 hours | Normal | 2 Participants |
| Treatment as Usual (TAU) | Number of Participants at Certain Degrees of Normalization of Heart Rate Over Time | 0.5 hour | High | 0 Participants |
| Treatment as Usual (TAU) | Number of Participants at Certain Degrees of Normalization of Heart Rate Over Time | 1 hour | High | 0 Participants |
| Treatment as Usual (TAU) | Number of Participants at Certain Degrees of Normalization of Heart Rate Over Time | Prior to discharge | Low | 0 Participants |
| Treatment as Usual (TAU) | Number of Participants at Certain Degrees of Normalization of Heart Rate Over Time | Baseline | Low | 0 Participants |
| Treatment as Usual (TAU) | Number of Participants at Certain Degrees of Normalization of Heart Rate Over Time | 1 hour | Normal | 4 Participants |
| Treatment as Usual (TAU) | Number of Participants at Certain Degrees of Normalization of Heart Rate Over Time | Baseline | High | 0 Participants |
| Treatment as Usual (TAU) | Number of Participants at Certain Degrees of Normalization of Heart Rate Over Time | Prior to discharge | Normal | 1 Participants |
| Treatment as Usual (TAU) | Number of Participants at Certain Degrees of Normalization of Heart Rate Over Time | 1 hour | Low | 0 Participants |
| Treatment as Usual (TAU) | Number of Participants at Certain Degrees of Normalization of Heart Rate Over Time | 0.5 hour | Normal | 3 Participants |
| Treatment as Usual (TAU) | Number of Participants at Certain Degrees of Normalization of Heart Rate Over Time | Baseline | Normal | 4 Participants |
| Treatment as Usual (TAU) | Number of Participants at Certain Degrees of Normalization of Heart Rate Over Time | 2 hours | High | 0 Participants |
| Treatment as Usual (TAU) | Number of Participants at Certain Degrees of Normalization of Heart Rate Over Time | Prior to discharge | High | 0 Participants |
| Treatment as Usual (TAU) | Number of Participants at Certain Degrees of Normalization of Heart Rate Over Time | 2 hours | Low | 0 Participants |
Secondary
Number of Participants Requiring Rescue Medications for Psychiatric or Cardiovascular Manifestations of METH Toxicity
Number of participants that need rescue medications to treat: * agitation, dysphoria, or psychosis (central nervous system toxicity) * hypertension, tachycardia, or other cardiovascular instability (cardiovascular toxicity)
Time frame: 8 hours
Population: All participants receiving a dose of IXT-m200 or TAU.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| IXT-m200 Low Dose (0.5 g) | Number of Participants Requiring Rescue Medications for Psychiatric or Cardiovascular Manifestations of METH Toxicity | Required rescue medications | 0 Participants |
| IXT-m200 Low Dose (0.5 g) | Number of Participants Requiring Rescue Medications for Psychiatric or Cardiovascular Manifestations of METH Toxicity | Did not require rescue medications | 8 Participants |
| IXT-m200 High Dose (2 g) | Number of Participants Requiring Rescue Medications for Psychiatric or Cardiovascular Manifestations of METH Toxicity | Required rescue medications | 0 Participants |
| IXT-m200 High Dose (2 g) | Number of Participants Requiring Rescue Medications for Psychiatric or Cardiovascular Manifestations of METH Toxicity | Did not require rescue medications | 8 Participants |
| Treatment as Usual (TAU) | Number of Participants Requiring Rescue Medications for Psychiatric or Cardiovascular Manifestations of METH Toxicity | Required rescue medications | 0 Participants |
| Treatment as Usual (TAU) | Number of Participants Requiring Rescue Medications for Psychiatric or Cardiovascular Manifestations of METH Toxicity | Did not require rescue medications | 4 Participants |
Secondary
Time Course and Degree of Normalization of Agitation
Agitation/sedation scores over time as measured by Agitation/Calmness Evaluation Score (ACES). The minimum value is 1 (highly agitated) and the highest value is 9 (completely sedated). A score of 3-5 is considered normal.
Time frame: Baseline and hours 0.5, 1, 2, 3, 4, and 8 post-dose or until discharge.
Population: All participants receiving a dose of IXT-m200 or TAU. No further data were collected after participants were discharged. Some time points do not contain results as all participants in that group had been discharged prior to that timepoint or all data were missing.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| IXT-m200 Low Dose (0.5 g) | Time Course and Degree of Normalization of Agitation | 3 hours | 7.0 score on a scale | — |
| IXT-m200 Low Dose (0.5 g) | Time Course and Degree of Normalization of Agitation | 1 hour | 4.6 score on a scale | Standard Deviation 1.92 |
| IXT-m200 Low Dose (0.5 g) | Time Course and Degree of Normalization of Agitation | 0.5 hour | 4.1 score on a scale | Standard Deviation 1.81 |
| IXT-m200 Low Dose (0.5 g) | Time Course and Degree of Normalization of Agitation | 2 hours | 4.0 score on a scale | Standard Deviation 1.91 |
| IXT-m200 Low Dose (0.5 g) | Time Course and Degree of Normalization of Agitation | Baseline | 2.1 score on a scale | Standard Deviation 0.64 |
| IXT-m200 High Dose (2 g) | Time Course and Degree of Normalization of Agitation | 4 hours | 1.0 score on a scale | — |
| IXT-m200 High Dose (2 g) | Time Course and Degree of Normalization of Agitation | Baseline | 2. score on a scale | Standard Deviation 0.53 |
| IXT-m200 High Dose (2 g) | Time Course and Degree of Normalization of Agitation | 0.5 hour | 3.6 score on a scale | Standard Deviation 1.6 |
| IXT-m200 High Dose (2 g) | Time Course and Degree of Normalization of Agitation | 1 hour | 3.9 score on a scale | Standard Deviation 1.81 |
| IXT-m200 High Dose (2 g) | Time Course and Degree of Normalization of Agitation | 2 hours | 4.0 score on a scale | Standard Deviation 2.08 |
| IXT-m200 High Dose (2 g) | Time Course and Degree of Normalization of Agitation | 3 hours | 3.0 score on a scale | Standard Deviation 2.83 |
| Treatment as Usual (TAU) | Time Course and Degree of Normalization of Agitation | 2 hours | 4.8 score on a scale | Standard Deviation 0.5 |
| Treatment as Usual (TAU) | Time Course and Degree of Normalization of Agitation | 0.5 hour | 3.9 score on a scale | Standard Deviation 1.67 |
| Treatment as Usual (TAU) | Time Course and Degree of Normalization of Agitation | 1 hour | 5.8 score on a scale | Standard Deviation 1.89 |
| Treatment as Usual (TAU) | Time Course and Degree of Normalization of Agitation | Baseline | 2.8 score on a scale | Standard Deviation 0.5 |
Secondary
Time Course and Degree of Normalization of Temperature
Temperature over time
Time frame: Baseline and hours 0.5, 1, 2, 3, 4, and 8 post-dose or until discharge.
Population: All participants receiving a dose of IXT-m200 or TAU. No further data were collected after participants were discharged. Some time points do not contain results as all participants in that group had been discharged prior to that timepoint or all data were missing.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| IXT-m200 Low Dose (0.5 g) | Time Course and Degree of Normalization of Temperature | Baseline | 98.2 degrees Fahrenheit | Standard Deviation 0.62 |
| IXT-m200 Low Dose (0.5 g) | Time Course and Degree of Normalization of Temperature | 0.5 hour | 98.05 degrees Fahrenheit | Standard Deviation 0.495 |
| IXT-m200 Low Dose (0.5 g) | Time Course and Degree of Normalization of Temperature | 1 hour | 98.45 degrees Fahrenheit | Standard Deviation 0.778 |
| IXT-m200 Low Dose (0.5 g) | Time Course and Degree of Normalization of Temperature | 2 hours | 98.50 degrees Fahrenheit | Standard Deviation 1.414 |
| IXT-m200 Low Dose (0.5 g) | Time Course and Degree of Normalization of Temperature | 3 hours | 99.10 degrees Fahrenheit | — |
| IXT-m200 Low Dose (0.5 g) | Time Course and Degree of Normalization of Temperature | Discharge | 97.40 degrees Fahrenheit | Standard Deviation 0.141 |
| IXT-m200 High Dose (2 g) | Time Course and Degree of Normalization of Temperature | 3 hours | 99.50 degrees Fahrenheit | — |
| IXT-m200 High Dose (2 g) | Time Course and Degree of Normalization of Temperature | Baseline | 98.25 degrees Fahrenheit | Standard Deviation 0.345 |
| IXT-m200 High Dose (2 g) | Time Course and Degree of Normalization of Temperature | Discharge | 98.0 degrees Fahrenheit | — |
| IXT-m200 High Dose (2 g) | Time Course and Degree of Normalization of Temperature | 0.5 hour | 98.52 degrees Fahrenheit | Standard Deviation 0.476 |
| IXT-m200 High Dose (2 g) | Time Course and Degree of Normalization of Temperature | 1 hour | 98.48 degrees Fahrenheit | Standard Deviation 0.562 |
| IXT-m200 High Dose (2 g) | Time Course and Degree of Normalization of Temperature | 2 hours | 98.38 degrees Fahrenheit | Standard Deviation 0.907 |
| Treatment as Usual (TAU) | Time Course and Degree of Normalization of Temperature | 1 hour | 97.7 degrees Fahrenheit | — |
| Treatment as Usual (TAU) | Time Course and Degree of Normalization of Temperature | Discharge | 98.10 degrees Fahrenheit | — |
| Treatment as Usual (TAU) | Time Course and Degree of Normalization of Temperature | Baseline | 98.10 degrees Fahrenheit | Standard Deviation 0.424 |
| Treatment as Usual (TAU) | Time Course and Degree of Normalization of Temperature | 2 hours | 97.7 degrees Fahrenheit | — |
Other Pre-specified
Length of Patient Stay in the ED
ED length of stay as measured by discharge time minus start of treatment time
Time frame: Start of treatment until discharge
Population: All participants receiving a dose of IXT-m200 or TAU.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IXT-m200 Low Dose (0.5 g) | Length of Patient Stay in the ED | 8.940 hours | Standard Deviation 5.6843 |
| IXT-m200 High Dose (2 g) | Length of Patient Stay in the ED | 8.031 hours | Standard Deviation 6.0973 |
| Treatment as Usual (TAU) | Length of Patient Stay in the ED | 10.196 hours | Standard Deviation 8.0826 |