Methamphetamine Abuse, Methamphetamine-dependence
Conditions
Brief summary
This study evaluates the ability of IXT-m200 to change methamphetamine concentrations in blood and alter the way methamphetamine feels. Participants will receive either placebo, a low or high dose of IXT-m200, in addition to methamphetamine challenge doses.
Detailed description
IXT-m200 is a monoclonal antibody that binds to methamphetamine in the blood. The main purpose of this study is to look at the effects of IXT-m200 on the pharmacokinetics of methamphetamine and on methamphetamine liking effects. Additionally, the study will determine IXT-m200 pharmacokinetics, safety and tolerability in subjects with methamphetamine use disorder. Qualified subjects will receive a single dose of IXT-m200 followed by up to 4 methamphetamine challenge doses.
Interventions
DRUGPlacebo
Normal saline
DRUGIXT-m200
IXT-m200 is an anti-methamphetamine monoclonal antibody
Sponsors
National Institute on Drug Abuse (NIDA)
InterveXion Therapeutics, LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
21 Years to 50 Years
Healthy volunteers
No
Inclusion criteria
* Subject voluntarily agrees to participate in this study and signs an informed consent form. * Subject must be able to verbalize understanding of the consent forms, provide written informed consent, and verbalize willingness to complete study procedures. * Males or females between 21 to 50 years of age, inclusive. Female subjects should be of non-childbearing potential or, they should be nonpregnant, nonlactating, and agree to use medically acceptable forms of birth control from screening to end-of-study follow-up, or have a partner who has had a vasectomy. Male subjects need to have had a vasectomy or agree to use a condom and spermicide in addition to their female partners using a form of birth control. They should agree not to donate sperm for 90 days post IXT-m200 dose. * Body mass index (BMI) between 18.0 and 35.0 kg/m2. Body weight ≥ 50 kg and ≤ 100 kg. * Subjects have hematology and chemistry laboratory tests that are within normal (+/- 10%) limits with the following exceptions: a) liver function tests (total bilirubin, alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase) \< 3 times the upper limit of normal, and b) kidney function tests (creatinine and BUN) \< 2 times the upper limit of normal. * Subjects meet Diagnostic and Statistical Manual of Mental Disorders (DSM)-5 criteria for METH use disorder and are not seeking treatment at the time of the study. * Subjects will be experienced METH users with a history of non-therapeutic METH use for 2 or more years. Subjects must have experience with smoking or IV injection of METH. * Current METH use (past 30 days) less than daily, self-reported and documented by calendar-based timeline follow-back. * Primary current (past 30 days) route of METH self-administration other than IV (ie, smoking, snorting, or oral). * Subjects agree not to take METH from any source outside of the study during their participation in the study. Subjects agree not to take substances that are structurally similar to METH. * Subjects must provide a negative urine sample prior to admission to the unit on Day -1 for the study.
Exclusion criteria
* Subjects who have been treated with a monoclonal antibody (mAb) in the past year. * Known or suspected allergy sensitivity to IXT-m200 based on known allergies to other mAbs. * History of severe allergy (rash, hives, breathing difficulty, etc) to any medications. * History of allergic or environmental bronchial asthma. * Clinically significant history of or current abnormality or disease of any organ system, including renal, hepatic, GI, cardiovascular, pulmonary (including chronic asthma), endocrine (eg, diabetes), central nervous, or hematologic systems, or recent clinically significant surgery. * Current diagnosis or history of major psychiatric illness in the past two years or other current psychiatric condition requiring medication, other than methamphetamine dependence. * Considered by the PI to be at imminent risk of suicide or injury to self, others, or property, or the subject has attempted suicide with the past year. Past year history of, or current evidence for, suicidal ideation or those who were actively suicidal based on the Columbia-Suicide Severity Rating Scale (C-SSRS). * Current dependence on alcohol or heavy use defined as \>28 alcoholic drinks per week if male and \>21 drinks per week if female in last 30 days. * Current dependence on other drugs except amphetamines, or marijuana and nicotine used in moderate amounts. * History of seizure, epilepsy, severe head injury with residual neurologic effects, multiple sclerosis, or stroke. * Abnormal pre-admission vital signs, physical examination, clinical laboratory, ECG, or any safety variable which is considered clinically significant for this population. * History of cardiovascular disease. * Treatment with any prescription medications or over the counter nutritional supplements within 14 days prior to the first dose of study medication. * Ingestion of any approved prescription anti-obesity drug or taken any over-the-counter medication for weight loss within a period of 90 days prior to the first dose of study medication. * Ingestion or use of any investigational medication or device within 30 days prior to the first dose of study medication. * Acute illness within 5 days prior to the first dose of study medication, eg, flu syndrome, GI virus, or clinically significant indigestion (eg, reflux). * Positive result for hepatitis B surface antigen (HBsAG), hepatitis C (HepC) antibody, hepatitis A immunoglobulin M (IgM), or HIV Viral Serology, or nucleic acid testing (NAT) tests at screening. * Positive breath alcohol test or positive urine drug test for illicit substances on Day -1. * Subjects with history of donated blood, plasma, or platelets in last 30 days, and who do not agree to refrain from blood, plasma, platelets, egg or sperm donation during the study period. * Predominant or only route of METH self-administration is IV. * Any subject judged by the PI or Sponsor (or designee) to be inappropriate for the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Plasma Methamphetamine (METH) Area Under the Curve (AUCinf) Resulting From METH Challenge Doses Following Single IV Doses of IXT-m200 | Day 1, 5, 12, 19, and 26 | METH AUCinf following IXT-m200 dosing on each METH Challenge Day. |
| Change in Plasma Methamphetamine (METH) Maximum Concentration (Cmax) Resulting From METH Challenge Doses Following Single IV Doses of IXT-m200 | Day 1, 5, 12, 19, and 26 | METH Cmax following IXT-m200 dosing on each METH Challenge Day. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Subjective Effects for FEEL of METH Challenge Doses | Day 1, 5, 12, 19, and 26 | Drug effects questionnaires (visual analog scales with range from 0 (no effect) to 100 (maximum effect)) were administered following weekly doses of methamphetamine starting on Day 5, one day after IXT-m200 or placebo administration. Participants were asked questions assessing subjective effects for FEEL over 180 minutes. Values were calculated as an area under the curve by using the trapezoidal rule; time 0 was set to 0 on the effect scale (at time of methamphetamine administration) and the area was calculated through 180 min post-dose. Lower values would indicate less drug effect (better) than higher values indicating larger drug effect (worse). |
| Change in Subjective Effects for GOOD of METH Challenge Doses | Day 1, 5, 12, 19, and 26 | Drug effects questionnaires (visual analog scales with range from 0 (no effect) to 100 (maximum effect)) were administered following weekly doses of methamphetamine starting on Day 5, one day after IXT-m200 or placebo administration. Participants were asked questions assessing subjective effects for GOOD over 180 minutes. Values were calculated as an area under the curve by using the trapezoidal rule; time 0 was set to 0 on the effect scale (at time of methamphetamine administration) and the area was calculated through 180 min post-dose. Lower values would indicate less drug effect (better) than higher values indicating larger drug effect (worse). |
| Change in Subjective Effects for HIGH of METH Challenge Doses | Day 1, 5, 12, 19, and 26 | Drug effects questionnaires (visual analog scales with range from 0 (no effect) to 100 (maximum effect)) were administered following weekly doses of methamphetamine starting on Day 5, one day after IXT-m200 or placebo administration. Participants were asked questions assessing subjective effects for HIGH over 180 minutes. Values were calculated as an area under the curve by using the trapezoidal rule; time 0 was set to 0 on the effect scale (at time of methamphetamine administration) and the area was calculated through 180 min post-dose. Lower values would indicate less drug effect (better) than higher values indicating larger drug effect (worse). |
| Change in Subjective Effects for LIKE of METH Challenge Doses | Day 1, 5, 12, 19, and 26 | Drug effects questionnaires (visual analog scales with range from 0 (no effect) to 100 (maximum effect)) were administered following weekly doses of methamphetamine starting on Day 5, one day after IXT-m200 or placebo administration. Participants were asked questions assessing subjective effects for LIKE over 180 minutes. Values were calculated as an area under the curve by using the trapezoidal rule; time 0 was set to 0 on the effect scale (at time of methamphetamine administration) and the area was calculated through 180 min post-dose. Lower values would indicate less drug effect (better) than higher values indicating larger drug effect (worse). |
| Change in Subjective Effects for CRAVE of METH Challenge Doses | Day 1, 5, 12, 19, and 26 | Drug effects questionnaires (visual analog scales with range from 0 (no effect) to 100 (maximum effect)) were administered following weekly doses of methamphetamine starting on Day 5, one day after IXT-m200 or placebo administration. Participants were asked questions assessing subjective effects for CRAVE over 180 minutes. Values were calculated as an area under the curve by using the trapezoidal rule; time 0 was set to 0 on the effect scale (at time of methamphetamine administration) and the area was calculated through 180 min post-dose. Lower values would indicate less drug effect (better) than higher values indicating larger drug effect (worse). |
| Change in Subjective Effects for STIMULATED of METH Challenge Doses | Day 1, 5, 12, 19, and 26 | Drug effects questionnaires (visual analog scales with range from 0 (no effect) to 100 (maximum effect)) were administered following weekly doses of methamphetamine starting on Day 5, one day after IXT-m200 or placebo administration. Participants were asked questions assessing subjective effects for STIMULATED over 180 minutes. Values were calculated as an area under the curve by using the trapezoidal rule; time 0 was set to 0 on the effect scale (at time of methamphetamine administration) and the area was calculated through 180 min post-dose. Lower values would indicate less drug effect (better) than higher values indicating larger drug effect (worse). |
| Safety and Tolerability of IXT-m200 Followed by METH Challenges | 126 days | Number of serious adverse events (SAEs) as identified by physical examinations and vital sign, adverse event, ECG, and clinical laboratory testing, and immune response by measurement of anti-IXT-m200 antibody levels. |
| Pharmacokinetics of IXT-m200 Following Single Administration | 122 days | Measured by serum concentrations of IXT-m200 over time |
| Change in Subjective Effects for MORE of METH Challenge Doses | Day 1, 5, 12, 19, and 26 | Drug effects questionnaires (visual analog scales with range from 0 (no effect) to 100 (maximum effect)) were administered following weekly doses of methamphetamine starting on Day 5, one day after IXT-m200 or placebo administration. Participants were asked questions assessing subjective effects for MORE over 180 minutes. Values were calculated as an area under the curve by using the trapezoidal rule; time 0 was set to 0 on the effect scale (at time of methamphetamine administration) and the area was calculated through 180 min post-dose. Lower values would indicate less drug effect (better) than higher values indicating larger drug effect (worse). |
| Change in Subjective Effects for DISLIKE of METH Challenge Doses | Day 1, 5, 12, 19, and 26 | Drug effects questionnaires (visual analog scales with range from 0 (no effect) to 100 (maximum effect)) were administered following weekly doses of methamphetamine starting on Day 5, one day after IXT-m200 or placebo administration. Participants were asked questions assessing subjective effects for DISLIKE over 180 minutes. Values were calculated as an area under the curve by using the trapezoidal rule; time 0 was set to 0 on the effect scale (at time of methamphetamine administration) and the area was calculated through 180 min post-dose. Lower values would indicate less drug effect (better) than higher values indicating larger drug effect (worse). |
Countries
United States
Participant flow
Recruitment details
Participants were recruited at two clinical research sites in Salt Lake City, UT and Anaheim, CA between April 2018 and October 2020.
Pre-assignment details
Participants underwent drug discrimination testing on Day 1 (30 mg IV methamphetamine vs normal saline). Those who reported appropriate responses on drug effects questionnaires and had no safety concerns following IV methamphetamine dosing were allowed to continue in the study. 77 subjects were enrolled, 10 discontinued or withdrew after Day 1 and 11 did not pass drug discrimination and were disqualified.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Normal saline
Placebo: Normal saline | 20 |
| IXT-m200, 6 mg/kg Single 6 mg/kg intravenous dose of IXT-m200
IXT-m200: IXT-m200 is an anti-methamphetamine monoclonal antibody | 18 |
| IXT-m200, 20 mg/kg Single 20 mg/kg intravenous dose of IXT-m200 | 18 |
| Total | 56 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 2 | 0 | 3 |
| Overall Study | Noncompliance with clinic house rules | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 1 | 0 |
Baseline characteristics
| Characteristic | IXT-m200, 6 mg/kg | Total | Placebo | IXT-m200, 20 mg/kg |
|---|---|---|---|---|
| Age, Continuous | 32.2 years STANDARD_DEVIATION 7.79 | 33.7 years STANDARD_DEVIATION 7.44 | 34.6 years STANDARD_DEVIATION 7.34 | 34.1 years STANDARD_DEVIATION 7.4 |
| BMI | 25.56 kg/m^2 STANDARD_DEVIATION 4.088 | 25.55 kg/m^2 STANDARD_DEVIATION 3.959 | 25.71 kg/m^2 STANDARD_DEVIATION 3.953 | 25.36 kg/m^2 STANDARD_DEVIATION 4.056 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 5 Participants | 2 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 15 Participants | 51 Participants | 18 Participants | 18 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Height | 171.32 cm STANDARD_DEVIATION 8.852 | 173.58 cm STANDARD_DEVIATION 9.34 | 172.23 cm STANDARD_DEVIATION 10.827 | 177.34 cm STANDARD_DEVIATION 7.093 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 2 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 3 Participants | 1 Participants | 1 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 | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) White | 16 Participants | 48 Participants | 17 Participants | 15 Participants |
| Region of Enrollment United States | 18 participants | 56 participants | 20 participants | 18 participants |
| Sex: Female, Male Female | 3 Participants | 10 Participants | 5 Participants | 2 Participants |
| Sex: Female, Male Male | 15 Participants | 46 Participants | 15 Participants | 16 Participants |
| Weight | 75.15 kg STANDARD_DEVIATION 13.832 | 76.92 kg STANDARD_DEVIATION 13.09 | 76.12 kg STANDARD_DEVIATION 13.109 | 79.59 kg STANDARD_DEVIATION 12.624 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 77 | 0 / 20 | 0 / 18 | 0 / 18 |
| other Total, other adverse events | 69 / 77 | 20 / 20 | 17 / 18 | 18 / 18 |
| serious Total, serious adverse events | 0 / 77 | 0 / 20 | 0 / 18 | 0 / 18 |
Outcome results
Primary
Change in Plasma Methamphetamine (METH) Area Under the Curve (AUCinf) Resulting From METH Challenge Doses Following Single IV Doses of IXT-m200
METH AUCinf following IXT-m200 dosing on each METH Challenge Day.
Time frame: Day 1, 5, 12, 19, and 26
Population: This outcome used the pharmacokinetic (PK) set. The PK set consisted of all subjects in the safety analysis set for whom at least 1 PK parameter could be calculated for METH or IXT-m200.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change in Plasma Methamphetamine (METH) Area Under the Curve (AUCinf) Resulting From METH Challenge Doses Following Single IV Doses of IXT-m200 | Day 19, AUCinf | 1219 h*ng/mL | Standard Deviation 346 |
| Placebo | Change in Plasma Methamphetamine (METH) Area Under the Curve (AUCinf) Resulting From METH Challenge Doses Following Single IV Doses of IXT-m200 | Day 12, AUCinf | 1254 h*ng/mL | Standard Deviation 341 |
| Placebo | Change in Plasma Methamphetamine (METH) Area Under the Curve (AUCinf) Resulting From METH Challenge Doses Following Single IV Doses of IXT-m200 | Day 1, AUCinf | 1635 h*ng/mL | Standard Deviation 1345 |
| Placebo | Change in Plasma Methamphetamine (METH) Area Under the Curve (AUCinf) Resulting From METH Challenge Doses Following Single IV Doses of IXT-m200 | Day 5, AUCinf | 1233 h*ng/mL | Standard Deviation 323 |
| Placebo | Change in Plasma Methamphetamine (METH) Area Under the Curve (AUCinf) Resulting From METH Challenge Doses Following Single IV Doses of IXT-m200 | Day 26, AUCinf | 1225 h*ng/mL | Standard Deviation 389 |
| IXT-m200, 6 mg/kg | Change in Plasma Methamphetamine (METH) Area Under the Curve (AUCinf) Resulting From METH Challenge Doses Following Single IV Doses of IXT-m200 | Day 12, AUCinf | 8210 h*ng/mL | Standard Deviation 2184 |
| IXT-m200, 6 mg/kg | Change in Plasma Methamphetamine (METH) Area Under the Curve (AUCinf) Resulting From METH Challenge Doses Following Single IV Doses of IXT-m200 | Day 1, AUCinf | 1433 h*ng/mL | Standard Deviation 555 |
| IXT-m200, 6 mg/kg | Change in Plasma Methamphetamine (METH) Area Under the Curve (AUCinf) Resulting From METH Challenge Doses Following Single IV Doses of IXT-m200 | Day 5, AUCinf | 14042 h*ng/mL | Standard Deviation 3067 |
| IXT-m200, 6 mg/kg | Change in Plasma Methamphetamine (METH) Area Under the Curve (AUCinf) Resulting From METH Challenge Doses Following Single IV Doses of IXT-m200 | Day 19, AUCinf | 5640 h*ng/mL | Standard Deviation 1123 |
| IXT-m200, 6 mg/kg | Change in Plasma Methamphetamine (METH) Area Under the Curve (AUCinf) Resulting From METH Challenge Doses Following Single IV Doses of IXT-m200 | Day 26, AUCinf | 4336 h*ng/mL | Standard Deviation 1021 |
| IXT-m200, 20 mg/kg | Change in Plasma Methamphetamine (METH) Area Under the Curve (AUCinf) Resulting From METH Challenge Doses Following Single IV Doses of IXT-m200 | Day 26, AUCinf | 12411 h*ng/mL | Standard Deviation 2597 |
| IXT-m200, 20 mg/kg | Change in Plasma Methamphetamine (METH) Area Under the Curve (AUCinf) Resulting From METH Challenge Doses Following Single IV Doses of IXT-m200 | Day 19, AUCinf | 16458 h*ng/mL | Standard Deviation 2580 |
| IXT-m200, 20 mg/kg | Change in Plasma Methamphetamine (METH) Area Under the Curve (AUCinf) Resulting From METH Challenge Doses Following Single IV Doses of IXT-m200 | Day 1, AUCinf | 1265 h*ng/mL | Standard Deviation 350 |
| IXT-m200, 20 mg/kg | Change in Plasma Methamphetamine (METH) Area Under the Curve (AUCinf) Resulting From METH Challenge Doses Following Single IV Doses of IXT-m200 | Day 12, AUCinf | 21846 h*ng/mL | Standard Deviation 3915 |
| IXT-m200, 20 mg/kg | Change in Plasma Methamphetamine (METH) Area Under the Curve (AUCinf) Resulting From METH Challenge Doses Following Single IV Doses of IXT-m200 | Day 5, AUCinf | 39379 h*ng/mL | Standard Deviation 8288 |
Comparison: Values were compared by a statistical analysis of change from Day 1 in METH PK parameters following IXT-m200 dosing. Geometric LS Mean change from Day 1 for each treatment on each day were calculated. Geometric LS Means Ratios of change in METH exposure for each dose level of IXT-m200 compared to Placebo on each Day 5 (primary), Day 12, Day 19 and Day 26 were calculated along with the 95% confidence intervals.p-value: <0.0001Mixed Models Analysis
Comparison: Values were compared by a statistical analysis of change from Day 1 in METH PK parameters following IXT-m200 dosing. Geometric LS Mean change from Day 1 for each treatment on each day were calculated. Geometric LS Means Ratios of change in METH exposure for each dose level of IXT-m200 compared to Placebo on each Day 5 (primary), Day 12, Day 19 and Day 26 were calculated along with the 95% confidence intervals.p-value: <0.0001Mixed Models Analysis
Comparison: Values were compared by a statistical analysis of change from Day 1 in METH PK parameters following IXT-m200 dosing. Geometric LS Mean change from Day 1 for each treatment on each day were calculated. Geometric LS Means Ratios of change in METH exposure for each dose level of IXT-m200 compared to Placebo on each Day 5 (primary), Day 12, Day 19 and Day 26 were calculated along with the 95% confidence intervals.p-value: <0.0001Mixed Models Analysis
Comparison: Values were compared by a statistical analysis of change from Day 1 in METH PK parameters following IXT-m200 dosing. Geometric LS Mean change from Day 1 for each treatment on each day were calculated. Geometric LS Means Ratios of change in METH exposure for each dose level of IXT-m200 compared to Placebo on each Day 5 (primary), Day 12, Day 19 and Day 26 were calculated along with the 95% confidence intervals.p-value: <0.0001Mixed Models Analysis
Comparison: Values were compared by a statistical analysis of change from Day 1 in METH PK parameters following IXT-m200 dosing. Geometric LS Mean change from Day 1 for each treatment on each day were calculated. Geometric LS Means Ratios of change in METH exposure for each dose level of IXT-m200 compared to Placebo on each Day 5 (primary), Day 12, Day 19 and Day 26 were calculated along with the 95% confidence intervals.p-value: <0.0001Mixed Models Analysis
Comparison: Values were compared by a statistical analysis of change from Day 1 in METH PK parameters following IXT-m200 dosing. Geometric LS Mean change from Day 1 for each treatment on each day were calculated. Geometric LS Means Ratios of change in METH exposure for each dose level of IXT-m200 compared to Placebo on each Day 5 (primary), Day 12, Day 19 and Day 26 were calculated along with the 95% confidence intervals.p-value: <0.0001Mixed Models Analysis
Comparison: Values were compared by a statistical analysis of change from Day 1 in METH PK parameters following IXT-m200 dosing. Geometric LS Mean change from Day 1 for each treatment on each day were calculated. Geometric LS Means Ratios of change in METH exposure for each dose level of IXT-m200 compared to Placebo on each Day 5 (primary), Day 12, Day 19 and Day 26 were calculated along with the 95% confidence intervals.p-value: <0.0001Mixed Models Analysis
Comparison: Values were compared by a statistical analysis of change from Day 1 in METH PK parameters following IXT-m200 dosing. Geometric LS Mean change from Day 1 for each treatment on each day were calculated. Geometric LS Means Ratios of change in METH exposure for each dose level of IXT-m200 compared to Placebo on each Day 5 (primary), Day 12, Day 19 and Day 26 were calculated along with the 95% confidence intervals.p-value: <0.0001Mixed Models Analysis
Primary
Change in Plasma Methamphetamine (METH) Maximum Concentration (Cmax) Resulting From METH Challenge Doses Following Single IV Doses of IXT-m200
METH Cmax following IXT-m200 dosing on each METH Challenge Day.
Time frame: Day 1, 5, 12, 19, and 26
Population: This outcome used the pharmacokinetic (PK) set. The PK set consisted of all subjects in the safety analysis set for whom at least 1 PK parameter could be calculated for METH or IXT-m200.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change in Plasma Methamphetamine (METH) Maximum Concentration (Cmax) Resulting From METH Challenge Doses Following Single IV Doses of IXT-m200 | Day 19, Cmax | 96 ng/mL | Standard Deviation 36 |
| Placebo | Change in Plasma Methamphetamine (METH) Maximum Concentration (Cmax) Resulting From METH Challenge Doses Following Single IV Doses of IXT-m200 | Day 12, Cmax | 100 ng/mL | Standard Deviation 31 |
| Placebo | Change in Plasma Methamphetamine (METH) Maximum Concentration (Cmax) Resulting From METH Challenge Doses Following Single IV Doses of IXT-m200 | Day 1, Cmax | 111 ng/mL | Standard Deviation 58 |
| Placebo | Change in Plasma Methamphetamine (METH) Maximum Concentration (Cmax) Resulting From METH Challenge Doses Following Single IV Doses of IXT-m200 | Day 5, Cmax | 103 ng/mL | Standard Deviation 56 |
| Placebo | Change in Plasma Methamphetamine (METH) Maximum Concentration (Cmax) Resulting From METH Challenge Doses Following Single IV Doses of IXT-m200 | Day 26, Cmax | 80 ng/mL | Standard Deviation 13 |
| IXT-m200, 6 mg/kg | Change in Plasma Methamphetamine (METH) Maximum Concentration (Cmax) Resulting From METH Challenge Doses Following Single IV Doses of IXT-m200 | Day 12, Cmax | 198 ng/mL | Standard Deviation 24 |
| IXT-m200, 6 mg/kg | Change in Plasma Methamphetamine (METH) Maximum Concentration (Cmax) Resulting From METH Challenge Doses Following Single IV Doses of IXT-m200 | Day 1, Cmax | 98 ng/mL | Standard Deviation 29 |
| IXT-m200, 6 mg/kg | Change in Plasma Methamphetamine (METH) Maximum Concentration (Cmax) Resulting From METH Challenge Doses Following Single IV Doses of IXT-m200 | Day 5, Cmax | 312 ng/mL | Standard Deviation 37 |
| IXT-m200, 6 mg/kg | Change in Plasma Methamphetamine (METH) Maximum Concentration (Cmax) Resulting From METH Challenge Doses Following Single IV Doses of IXT-m200 | Day 19, Cmax | 168 ng/mL | Standard Deviation 24 |
| IXT-m200, 6 mg/kg | Change in Plasma Methamphetamine (METH) Maximum Concentration (Cmax) Resulting From METH Challenge Doses Following Single IV Doses of IXT-m200 | Day 26, Cmax | 145 ng/mL | Standard Deviation 17 |
| IXT-m200, 20 mg/kg | Change in Plasma Methamphetamine (METH) Maximum Concentration (Cmax) Resulting From METH Challenge Doses Following Single IV Doses of IXT-m200 | Day 26, Cmax | 262 ng/mL | Standard Deviation 54 |
| IXT-m200, 20 mg/kg | Change in Plasma Methamphetamine (METH) Maximum Concentration (Cmax) Resulting From METH Challenge Doses Following Single IV Doses of IXT-m200 | Day 19, Cmax | 340 ng/mL | Standard Deviation 57 |
| IXT-m200, 20 mg/kg | Change in Plasma Methamphetamine (METH) Maximum Concentration (Cmax) Resulting From METH Challenge Doses Following Single IV Doses of IXT-m200 | Day 1, Cmax | 90 ng/mL | Standard Deviation 24 |
| IXT-m200, 20 mg/kg | Change in Plasma Methamphetamine (METH) Maximum Concentration (Cmax) Resulting From METH Challenge Doses Following Single IV Doses of IXT-m200 | Day 12, Cmax | 444 ng/mL | Standard Deviation 92 |
| IXT-m200, 20 mg/kg | Change in Plasma Methamphetamine (METH) Maximum Concentration (Cmax) Resulting From METH Challenge Doses Following Single IV Doses of IXT-m200 | Day 5, Cmax | 759 ng/mL | Standard Deviation 135 |
Comparison: Values were compared by a statistical analysis of change from Day 1 in METH PK parameters following IXT-m200 dosing. Geometric LS Mean change from Day 1 for each treatment on each day were calculated. Geometric LS Means Ratios of change in METH exposure for each dose level of IXT-m200 compared to Placebo on each Day 5 (primary), Day 12, Day 19 and Day 26 were calculated along with the 95% confidence intervals.p-value: <0.0001Mixed Models Analysis
Comparison: Values were compared by a statistical analysis of change from Day 1 in METH PK parameters following IXT-m200 dosing. Geometric LS Mean change from Day 1 for each treatment on each day were calculated. Geometric LS Means Ratios of change in METH exposure for each dose level of IXT-m200 compared to Placebo on each Day 5 (primary), Day 12, Day 19 and Day 26 were calculated along with the 95% confidence intervals.p-value: <0.0001Mixed Models Analysis
Comparison: Values were compared by a statistical analysis of change from Day 1 in METH PK parameters following IXT-m200 dosing. Geometric LS Mean change from Day 1 for each treatment on each day were calculated. Geometric LS Means Ratios of change in METH exposure for each dose level of IXT-m200 compared to Placebo on each Day 5 (primary), Day 12, Day 19 and Day 26 were calculated along with the 95% confidence intervals.p-value: <0.0001Mixed Models Analysis
Comparison: Values were compared by a statistical analysis of change from Day 1 in METH PK parameters following IXT-m200 dosing. Geometric LS Mean change from Day 1 for each treatment on each day were calculated. Geometric LS Means Ratios of change in METH exposure for each dose level of IXT-m200 compared to Placebo on each Day 5 (primary), Day 12, Day 19 and Day 26 were calculated along with the 95% confidence intervals.p-value: <0.0001Mixed Models Analysis
Comparison: Values were compared by a statistical analysis of change from Day 1 in METH PK parameters following IXT-m200 dosing. Geometric LS Mean change from Day 1 for each treatment on each day were calculated. Geometric LS Means Ratios of change in METH exposure for each dose level of IXT-m200 compared to Placebo on each Day 5 (primary), Day 12, Day 19 and Day 26 were calculated along with the 95% confidence intervals.p-value: <0.0001Mixed Models Analysis
Comparison: Values were compared by a statistical analysis of change from Day 1 in METH PK parameters following IXT-m200 dosing. Geometric LS Mean change from Day 1 for each treatment on each day were calculated. Geometric LS Means Ratios of change in METH exposure for each dose level of IXT-m200 compared to Placebo on each Day 5 (primary), Day 12, Day 19 and Day 26 were calculated along with the 95% confidence intervals.p-value: <0.0001Mixed Models Analysis
Comparison: Values were compared by a statistical analysis of change from Day 1 in METH PK parameters following IXT-m200 dosing. Geometric LS Mean change from Day 1 for each treatment on each day were calculated. Geometric LS Means Ratios of change in METH exposure for each dose level of IXT-m200 compared to Placebo on each Day 5 (primary), Day 12, Day 19 and Day 26 were calculated along with the 95% confidence intervals.p-value: <0.0001Mixed Models Analysis
Secondary
Change in Subjective Effects for CRAVE of METH Challenge Doses
Drug effects questionnaires (visual analog scales with range from 0 (no effect) to 100 (maximum effect)) were administered following weekly doses of methamphetamine starting on Day 5, one day after IXT-m200 or placebo administration. Participants were asked questions assessing subjective effects for CRAVE over 180 minutes. Values were calculated as an area under the curve by using the trapezoidal rule; time 0 was set to 0 on the effect scale (at time of methamphetamine administration) and the area was calculated through 180 min post-dose. Lower values would indicate less drug effect (better) than higher values indicating larger drug effect (worse).
Time frame: Day 1, 5, 12, 19, and 26
Population: The pharmacodynamic (PD) analysis set included 54 (96.4%) subjects for at least one time point. Two subjects were excluded after IXT-m200 dosing from the PD set due to having no measures for PD data due to early discontinuation. Other subjects were excluded for having no PD data at subsequent timepoints due to leaving the inpatient portion of the study early.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change in Subjective Effects for CRAVE of METH Challenge Doses | Day 19 | 3456 score on a scale * min | Standard Deviation 4406 |
| Placebo | Change in Subjective Effects for CRAVE of METH Challenge Doses | Day 12 | 4587 score on a scale * min | Standard Deviation 4466 |
| Placebo | Change in Subjective Effects for CRAVE of METH Challenge Doses | Day 1 | 6601 score on a scale * min | Standard Deviation 4492 |
| Placebo | Change in Subjective Effects for CRAVE of METH Challenge Doses | Day 5 | 5758 score on a scale * min | Standard Deviation 4642 |
| Placebo | Change in Subjective Effects for CRAVE of METH Challenge Doses | Day 26 | 3044 score on a scale * min | Standard Deviation 3611 |
| IXT-m200, 6 mg/kg | Change in Subjective Effects for CRAVE of METH Challenge Doses | Day 12 | 5544 score on a scale * min | Standard Deviation 6318 |
| IXT-m200, 6 mg/kg | Change in Subjective Effects for CRAVE of METH Challenge Doses | Day 1 | 7040 score on a scale * min | Standard Deviation 6022 |
| IXT-m200, 6 mg/kg | Change in Subjective Effects for CRAVE of METH Challenge Doses | Day 5 | 5837 score on a scale * min | Standard Deviation 5870 |
| IXT-m200, 6 mg/kg | Change in Subjective Effects for CRAVE of METH Challenge Doses | Day 19 | 6457 score on a scale * min | Standard Deviation 6623 |
| IXT-m200, 6 mg/kg | Change in Subjective Effects for CRAVE of METH Challenge Doses | Day 26 | 2374 score on a scale * min | Standard Deviation 2683 |
| IXT-m200, 20 mg/kg | Change in Subjective Effects for CRAVE of METH Challenge Doses | Day 26 | 5716 score on a scale * min | Standard Deviation 9434 |
| IXT-m200, 20 mg/kg | Change in Subjective Effects for CRAVE of METH Challenge Doses | Day 19 | 4426 score on a scale * min | Standard Deviation 4292 |
| IXT-m200, 20 mg/kg | Change in Subjective Effects for CRAVE of METH Challenge Doses | Day 1 | 8658 score on a scale * min | Standard Deviation 5133 |
| IXT-m200, 20 mg/kg | Change in Subjective Effects for CRAVE of METH Challenge Doses | Day 12 | 5532 score on a scale * min | Standard Deviation 3974 |
| IXT-m200, 20 mg/kg | Change in Subjective Effects for CRAVE of METH Challenge Doses | Day 5 | 5980 score on a scale * min | Standard Deviation 4363 |
Secondary
Change in Subjective Effects for DISLIKE of METH Challenge Doses
Drug effects questionnaires (visual analog scales with range from 0 (no effect) to 100 (maximum effect)) were administered following weekly doses of methamphetamine starting on Day 5, one day after IXT-m200 or placebo administration. Participants were asked questions assessing subjective effects for DISLIKE over 180 minutes. Values were calculated as an area under the curve by using the trapezoidal rule; time 0 was set to 0 on the effect scale (at time of methamphetamine administration) and the area was calculated through 180 min post-dose. Lower values would indicate less drug effect (better) than higher values indicating larger drug effect (worse).
Time frame: Day 1, 5, 12, 19, and 26
Population: The pharmacodynamic (PD) analysis set included 54 (96.4%) subjects for at least one time point. Two subjects were excluded after IXT-m200 dosing from the PD set due to having no measures for PD data due to early discontinuation. Other subjects were excluded for having no PD data at subsequent timepoints due to leaving the inpatient portion of the study early.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change in Subjective Effects for DISLIKE of METH Challenge Doses | Day 19 | 2089 score on a scale * min | Standard Deviation 2686 |
| Placebo | Change in Subjective Effects for DISLIKE of METH Challenge Doses | Day 12 | 1998 score on a scale * min | Standard Deviation 2598 |
| Placebo | Change in Subjective Effects for DISLIKE of METH Challenge Doses | Day 1 | 2124 score on a scale * min | Standard Deviation 2173 |
| Placebo | Change in Subjective Effects for DISLIKE of METH Challenge Doses | Day 5 | 2021 score on a scale * min | Standard Deviation 2636 |
| Placebo | Change in Subjective Effects for DISLIKE of METH Challenge Doses | Day 26 | 1610 score on a scale * min | Standard Deviation 2434 |
| IXT-m200, 6 mg/kg | Change in Subjective Effects for DISLIKE of METH Challenge Doses | Day 12 | 3393 score on a scale * min | Standard Deviation 5240 |
| IXT-m200, 6 mg/kg | Change in Subjective Effects for DISLIKE of METH Challenge Doses | Day 1 | 2806 score on a scale * min | Standard Deviation 4517 |
| IXT-m200, 6 mg/kg | Change in Subjective Effects for DISLIKE of METH Challenge Doses | Day 5 | 3331 score on a scale * min | Standard Deviation 3966 |
| IXT-m200, 6 mg/kg | Change in Subjective Effects for DISLIKE of METH Challenge Doses | Day 19 | 3433 score on a scale * min | Standard Deviation 5486 |
| IXT-m200, 6 mg/kg | Change in Subjective Effects for DISLIKE of METH Challenge Doses | Day 26 | 1925 score on a scale * min | Standard Deviation 3679 |
| IXT-m200, 20 mg/kg | Change in Subjective Effects for DISLIKE of METH Challenge Doses | Day 26 | 50520 score on a scale * min | Standard Deviation 6042 |
| IXT-m200, 20 mg/kg | Change in Subjective Effects for DISLIKE of METH Challenge Doses | Day 19 | 2888 score on a scale * min | Standard Deviation 4245 |
| IXT-m200, 20 mg/kg | Change in Subjective Effects for DISLIKE of METH Challenge Doses | Day 1 | 1697 score on a scale * min | Standard Deviation 2446 |
| IXT-m200, 20 mg/kg | Change in Subjective Effects for DISLIKE of METH Challenge Doses | Day 12 | 2292 score on a scale * min | Standard Deviation 3176 |
| IXT-m200, 20 mg/kg | Change in Subjective Effects for DISLIKE of METH Challenge Doses | Day 5 | 2523 score on a scale * min | Standard Deviation 3412 |
Secondary
Change in Subjective Effects for FEEL of METH Challenge Doses
Drug effects questionnaires (visual analog scales with range from 0 (no effect) to 100 (maximum effect)) were administered following weekly doses of methamphetamine starting on Day 5, one day after IXT-m200 or placebo administration. Participants were asked questions assessing subjective effects for FEEL over 180 minutes. Values were calculated as an area under the curve by using the trapezoidal rule; time 0 was set to 0 on the effect scale (at time of methamphetamine administration) and the area was calculated through 180 min post-dose. Lower values would indicate less drug effect (better) than higher values indicating larger drug effect (worse).
Time frame: Day 1, 5, 12, 19, and 26
Population: The pharmacodynamic (PD) analysis set included 54 (96.4%) subjects for at least one time point. Two subjects were excluded after IXT-m200 dosing from the PD set due to having no measures for PD data due to early discontinuation. Other subjects were excluded for having no PD data at subsequent timepoints due to leaving the inpatient portion of the study early.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change in Subjective Effects for FEEL of METH Challenge Doses | Day 19 | 5827 score on a scale * min | Standard Deviation 4723 |
| Placebo | Change in Subjective Effects for FEEL of METH Challenge Doses | Day 12 | 5491 score on a scale * min | Standard Deviation 4370 |
| Placebo | Change in Subjective Effects for FEEL of METH Challenge Doses | Day 1 | 5963 score on a scale * min | Standard Deviation 2731 |
| Placebo | Change in Subjective Effects for FEEL of METH Challenge Doses | Day 5 | 6470 score on a scale * min | Standard Deviation 3886 |
| Placebo | Change in Subjective Effects for FEEL of METH Challenge Doses | Day 26 | 5784 score on a scale * min | Standard Deviation 3992 |
| IXT-m200, 6 mg/kg | Change in Subjective Effects for FEEL of METH Challenge Doses | Day 12 | 9179 score on a scale * min | Standard Deviation 5318 |
| IXT-m200, 6 mg/kg | Change in Subjective Effects for FEEL of METH Challenge Doses | Day 1 | 10640 score on a scale * min | Standard Deviation 4839 |
| IXT-m200, 6 mg/kg | Change in Subjective Effects for FEEL of METH Challenge Doses | Day 5 | 9923 score on a scale * min | Standard Deviation 5441 |
| IXT-m200, 6 mg/kg | Change in Subjective Effects for FEEL of METH Challenge Doses | Day 19 | 10086 score on a scale * min | Standard Deviation 5122 |
| IXT-m200, 6 mg/kg | Change in Subjective Effects for FEEL of METH Challenge Doses | Day 26 | 7405 score on a scale * min | Standard Deviation 4315 |
| IXT-m200, 20 mg/kg | Change in Subjective Effects for FEEL of METH Challenge Doses | Day 26 | 9277 score on a scale * min | Standard Deviation 7464 |
| IXT-m200, 20 mg/kg | Change in Subjective Effects for FEEL of METH Challenge Doses | Day 19 | 6078 score on a scale * min | Standard Deviation 4772 |
| IXT-m200, 20 mg/kg | Change in Subjective Effects for FEEL of METH Challenge Doses | Day 1 | 8116 score on a scale * min | Standard Deviation 4242 |
| IXT-m200, 20 mg/kg | Change in Subjective Effects for FEEL of METH Challenge Doses | Day 12 | 7029 score on a scale * min | Standard Deviation 4597 |
| IXT-m200, 20 mg/kg | Change in Subjective Effects for FEEL of METH Challenge Doses | Day 5 | 6822 score on a scale * min | Standard Deviation 4089 |
Secondary
Change in Subjective Effects for GOOD of METH Challenge Doses
Drug effects questionnaires (visual analog scales with range from 0 (no effect) to 100 (maximum effect)) were administered following weekly doses of methamphetamine starting on Day 5, one day after IXT-m200 or placebo administration. Participants were asked questions assessing subjective effects for GOOD over 180 minutes. Values were calculated as an area under the curve by using the trapezoidal rule; time 0 was set to 0 on the effect scale (at time of methamphetamine administration) and the area was calculated through 180 min post-dose. Lower values would indicate less drug effect (better) than higher values indicating larger drug effect (worse).
Time frame: Day 1, 5, 12, 19, and 26
Population: The pharmacodynamic (PD) analysis set included 54 (96.4%) subjects for at least one time point. Two subjects were excluded after IXT-m200 dosing from the PD set due to having no measures for PD data due to early discontinuation. Other subjects were excluded for having no PD data at subsequent timepoints due to leaving the inpatient portion of the study early.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change in Subjective Effects for GOOD of METH Challenge Doses | Day 19 | 6138 score on a scale * min | Standard Deviation 5393 |
| Placebo | Change in Subjective Effects for GOOD of METH Challenge Doses | Day 12 | 5584 score on a scale * min | Standard Deviation 4498 |
| Placebo | Change in Subjective Effects for GOOD of METH Challenge Doses | Day 1 | 6151 score on a scale * min | Standard Deviation 2872 |
| Placebo | Change in Subjective Effects for GOOD of METH Challenge Doses | Day 5 | 6555 score on a scale * min | Standard Deviation 4260 |
| Placebo | Change in Subjective Effects for GOOD of METH Challenge Doses | Day 26 | 6335 score on a scale * min | Standard Deviation 5099 |
| IXT-m200, 6 mg/kg | Change in Subjective Effects for GOOD of METH Challenge Doses | Day 12 | 9236 score on a scale * min | Standard Deviation 5083 |
| IXT-m200, 6 mg/kg | Change in Subjective Effects for GOOD of METH Challenge Doses | Day 1 | 10984 score on a scale * min | Standard Deviation 5214 |
| IXT-m200, 6 mg/kg | Change in Subjective Effects for GOOD of METH Challenge Doses | Day 5 | 9783 score on a scale * min | Standard Deviation 5185 |
| IXT-m200, 6 mg/kg | Change in Subjective Effects for GOOD of METH Challenge Doses | Day 19 | 10016 score on a scale * min | Standard Deviation 5209 |
| IXT-m200, 6 mg/kg | Change in Subjective Effects for GOOD of METH Challenge Doses | Day 26 | 7468 score on a scale * min | Standard Deviation 3443 |
| IXT-m200, 20 mg/kg | Change in Subjective Effects for GOOD of METH Challenge Doses | Day 26 | 6760 score on a scale * min | Standard Deviation 6967 |
| IXT-m200, 20 mg/kg | Change in Subjective Effects for GOOD of METH Challenge Doses | Day 19 | 5238 score on a scale * min | Standard Deviation 3999 |
| IXT-m200, 20 mg/kg | Change in Subjective Effects for GOOD of METH Challenge Doses | Day 1 | 8378 score on a scale * min | Standard Deviation 3766 |
| IXT-m200, 20 mg/kg | Change in Subjective Effects for GOOD of METH Challenge Doses | Day 12 | 7001 score on a scale * min | Standard Deviation 4211 |
| IXT-m200, 20 mg/kg | Change in Subjective Effects for GOOD of METH Challenge Doses | Day 5 | 6903 score on a scale * min | Standard Deviation 3820 |
Secondary
Change in Subjective Effects for HIGH of METH Challenge Doses
Drug effects questionnaires (visual analog scales with range from 0 (no effect) to 100 (maximum effect)) were administered following weekly doses of methamphetamine starting on Day 5, one day after IXT-m200 or placebo administration. Participants were asked questions assessing subjective effects for HIGH over 180 minutes. Values were calculated as an area under the curve by using the trapezoidal rule; time 0 was set to 0 on the effect scale (at time of methamphetamine administration) and the area was calculated through 180 min post-dose. Lower values would indicate less drug effect (better) than higher values indicating larger drug effect (worse).
Time frame: Day 1, 5, 12, 19, and 26
Population: The pharmacodynamic (PD) analysis set included 54 (96.4%) subjects for at least one time point. Two subjects were excluded after IXT-m200 dosing from the PD set due to having no measures for PD data due to early discontinuation. Other subjects were excluded for having no PD data at subsequent timepoints due to leaving the inpatient portion of the study early.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change in Subjective Effects for HIGH of METH Challenge Doses | Day 19 | 5494 score on a scale * min | Standard Deviation 4916 |
| Placebo | Change in Subjective Effects for HIGH of METH Challenge Doses | Day 12 | 5117 score on a scale * min | Standard Deviation 4420 |
| Placebo | Change in Subjective Effects for HIGH of METH Challenge Doses | Day 1 | 5873 score on a scale * min | Standard Deviation 2671 |
| Placebo | Change in Subjective Effects for HIGH of METH Challenge Doses | Day 5 | 6187 score on a scale * min | Standard Deviation 3744 |
| Placebo | Change in Subjective Effects for HIGH of METH Challenge Doses | Day 26 | 5603 score on a scale * min | Standard Deviation 3980 |
| IXT-m200, 6 mg/kg | Change in Subjective Effects for HIGH of METH Challenge Doses | Day 12 | 9162 score on a scale * min | Standard Deviation 5245 |
| IXT-m200, 6 mg/kg | Change in Subjective Effects for HIGH of METH Challenge Doses | Day 1 | 10599 score on a scale * min | Standard Deviation 4871 |
| IXT-m200, 6 mg/kg | Change in Subjective Effects for HIGH of METH Challenge Doses | Day 5 | 9765 score on a scale * min | Standard Deviation 5441 |
| IXT-m200, 6 mg/kg | Change in Subjective Effects for HIGH of METH Challenge Doses | Day 19 | 9740 score on a scale * min | Standard Deviation 5366 |
| IXT-m200, 6 mg/kg | Change in Subjective Effects for HIGH of METH Challenge Doses | Day 26 | 7562 score on a scale * min | Standard Deviation 4542 |
| IXT-m200, 20 mg/kg | Change in Subjective Effects for HIGH of METH Challenge Doses | Day 26 | 9690 score on a scale * min | Standard Deviation 7217 |
| IXT-m200, 20 mg/kg | Change in Subjective Effects for HIGH of METH Challenge Doses | Day 19 | 6018 score on a scale * min | Standard Deviation 4700 |
| IXT-m200, 20 mg/kg | Change in Subjective Effects for HIGH of METH Challenge Doses | Day 1 | 7947 score on a scale * min | Standard Deviation 4218 |
| IXT-m200, 20 mg/kg | Change in Subjective Effects for HIGH of METH Challenge Doses | Day 12 | 6973 score on a scale * min | Standard Deviation 4583 |
| IXT-m200, 20 mg/kg | Change in Subjective Effects for HIGH of METH Challenge Doses | Day 5 | 6813 score on a scale * min | Standard Deviation 4046 |
Secondary
Change in Subjective Effects for LIKE of METH Challenge Doses
Drug effects questionnaires (visual analog scales with range from 0 (no effect) to 100 (maximum effect)) were administered following weekly doses of methamphetamine starting on Day 5, one day after IXT-m200 or placebo administration. Participants were asked questions assessing subjective effects for LIKE over 180 minutes. Values were calculated as an area under the curve by using the trapezoidal rule; time 0 was set to 0 on the effect scale (at time of methamphetamine administration) and the area was calculated through 180 min post-dose. Lower values would indicate less drug effect (better) than higher values indicating larger drug effect (worse).
Time frame: Day 1, 5, 12, 19, and 26
Population: The pharmacodynamic (PD) analysis set included 54 (96.4%) subjects for at least one time point. Two subjects were excluded after IXT-m200 dosing from the PD set due to having no measures for PD data due to early discontinuation. Other subjects were excluded for having no PD data at subsequent timepoints due to leaving the inpatient portion of the study early.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change in Subjective Effects for LIKE of METH Challenge Doses | Day 1 | 7495 score on a scale * min | Standard Deviation 3870 |
| Placebo | Change in Subjective Effects for LIKE of METH Challenge Doses | Day 19 | 6420 score on a scale * min | Standard Deviation 5633 |
| Placebo | Change in Subjective Effects for LIKE of METH Challenge Doses | Day 12 | 6394 score on a scale * min | Standard Deviation 5089 |
| Placebo | Change in Subjective Effects for LIKE of METH Challenge Doses | Day 26 | 7354 score on a scale * min | Standard Deviation 5345 |
| Placebo | Change in Subjective Effects for LIKE of METH Challenge Doses | Day 5 | 7582 score on a scale * min | Standard Deviation 4437 |
| IXT-m200, 6 mg/kg | Change in Subjective Effects for LIKE of METH Challenge Doses | Day 19 | 10271 score on a scale * min | Standard Deviation 5432 |
| IXT-m200, 6 mg/kg | Change in Subjective Effects for LIKE of METH Challenge Doses | Day 1 | 11322 score on a scale * min | Standard Deviation 4276 |
| IXT-m200, 6 mg/kg | Change in Subjective Effects for LIKE of METH Challenge Doses | Day 5 | 9668 score on a scale * min | Standard Deviation 4997 |
| IXT-m200, 6 mg/kg | Change in Subjective Effects for LIKE of METH Challenge Doses | Day 12 | 9498 score on a scale * min | Standard Deviation 5002 |
| IXT-m200, 6 mg/kg | Change in Subjective Effects for LIKE of METH Challenge Doses | Day 26 | 7713 score on a scale * min | Standard Deviation 2827 |
| IXT-m200, 20 mg/kg | Change in Subjective Effects for LIKE of METH Challenge Doses | Day 5 | 7430 score on a scale * min | Standard Deviation 4126 |
| IXT-m200, 20 mg/kg | Change in Subjective Effects for LIKE of METH Challenge Doses | Day 19 | 6027 score on a scale * min | Standard Deviation 3905 |
| IXT-m200, 20 mg/kg | Change in Subjective Effects for LIKE of METH Challenge Doses | Day 1 | 9858 score on a scale * min | Standard Deviation 3635 |
| IXT-m200, 20 mg/kg | Change in Subjective Effects for LIKE of METH Challenge Doses | Day 26 | 6811 score on a scale * min | Standard Deviation 7344 |
| IXT-m200, 20 mg/kg | Change in Subjective Effects for LIKE of METH Challenge Doses | Day 12 | 7111 score on a scale * min | Standard Deviation 4001 |
Secondary
Change in Subjective Effects for MORE of METH Challenge Doses
Drug effects questionnaires (visual analog scales with range from 0 (no effect) to 100 (maximum effect)) were administered following weekly doses of methamphetamine starting on Day 5, one day after IXT-m200 or placebo administration. Participants were asked questions assessing subjective effects for MORE over 180 minutes. Values were calculated as an area under the curve by using the trapezoidal rule; time 0 was set to 0 on the effect scale (at time of methamphetamine administration) and the area was calculated through 180 min post-dose. Lower values would indicate less drug effect (better) than higher values indicating larger drug effect (worse).
Time frame: Day 1, 5, 12, 19, and 26
Population: The pharmacodynamic (PD) analysis set included 54 (96.4%) subjects for at least one time point. Two subjects were excluded after IXT-m200 dosing from the PD set due to having no measures for PD data due to early discontinuation. Other subjects were excluded for having no PD data at subsequent timepoints due to leaving the inpatient portion of the study early.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change in Subjective Effects for MORE of METH Challenge Doses | Day 26 | 6801 score on a scale * min | Standard Deviation 6021 |
| Placebo | Change in Subjective Effects for MORE of METH Challenge Doses | Day 12 | 6629 score on a scale * min | Standard Deviation 5306 |
| Placebo | Change in Subjective Effects for MORE of METH Challenge Doses | Day 1 | 9469 score on a scale * min | Standard Deviation 4254 |
| Placebo | Change in Subjective Effects for MORE of METH Challenge Doses | Day 19 | 5654 score on a scale * min | Standard Deviation 5911 |
| Placebo | Change in Subjective Effects for MORE of METH Challenge Doses | Day 5 | 8582 score on a scale * min | Standard Deviation 4853 |
| IXT-m200, 6 mg/kg | Change in Subjective Effects for MORE of METH Challenge Doses | Day 12 | 7734 score on a scale * min | Standard Deviation 6017 |
| IXT-m200, 6 mg/kg | Change in Subjective Effects for MORE of METH Challenge Doses | Day 1 | 9404 score on a scale * min | Standard Deviation 5347 |
| IXT-m200, 6 mg/kg | Change in Subjective Effects for MORE of METH Challenge Doses | Day 5 | 7341 score on a scale * min | Standard Deviation 5671 |
| IXT-m200, 6 mg/kg | Change in Subjective Effects for MORE of METH Challenge Doses | Day 19 | 8521 score on a scale * min | Standard Deviation 6584 |
| IXT-m200, 6 mg/kg | Change in Subjective Effects for MORE of METH Challenge Doses | Day 26 | 4059 score on a scale * min | Standard Deviation 4201 |
| IXT-m200, 20 mg/kg | Change in Subjective Effects for MORE of METH Challenge Doses | Day 26 | 5273 score on a scale * min | Standard Deviation 8644 |
| IXT-m200, 20 mg/kg | Change in Subjective Effects for MORE of METH Challenge Doses | Day 19 | 5603 score on a scale * min | Standard Deviation 4593 |
| IXT-m200, 20 mg/kg | Change in Subjective Effects for MORE of METH Challenge Doses | Day 5 | 7796 score on a scale * min | Standard Deviation 4303 |
| IXT-m200, 20 mg/kg | Change in Subjective Effects for MORE of METH Challenge Doses | Day 12 | 7802 score on a scale * min | Standard Deviation 3954 |
| IXT-m200, 20 mg/kg | Change in Subjective Effects for MORE of METH Challenge Doses | Day 1 | 11164 score on a scale * min | Standard Deviation 4365 |
Secondary
Change in Subjective Effects for STIMULATED of METH Challenge Doses
Drug effects questionnaires (visual analog scales with range from 0 (no effect) to 100 (maximum effect)) were administered following weekly doses of methamphetamine starting on Day 5, one day after IXT-m200 or placebo administration. Participants were asked questions assessing subjective effects for STIMULATED over 180 minutes. Values were calculated as an area under the curve by using the trapezoidal rule; time 0 was set to 0 on the effect scale (at time of methamphetamine administration) and the area was calculated through 180 min post-dose. Lower values would indicate less drug effect (better) than higher values indicating larger drug effect (worse).
Time frame: Day 1, 5, 12, 19, and 26
Population: The pharmacodynamic (PD) analysis set included 54 (96.4%) subjects for at least one time point. Two subjects were excluded after IXT-m200 dosing from the PD set due to having no measures for PD data due to early discontinuation. Other subjects were excluded for having no PD data at subsequent timepoints due to leaving the inpatient portion of the study early.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change in Subjective Effects for STIMULATED of METH Challenge Doses | Day 19 | 5643 score on a scale * min | Standard Deviation 4387 |
| Placebo | Change in Subjective Effects for STIMULATED of METH Challenge Doses | Day 12 | 5407 score on a scale * min | Standard Deviation 4279 |
| Placebo | Change in Subjective Effects for STIMULATED of METH Challenge Doses | Day 1 | 6155 score on a scale * min | Standard Deviation 3245 |
| Placebo | Change in Subjective Effects for STIMULATED of METH Challenge Doses | Day 5 | 6108 score on a scale * min | Standard Deviation 3615 |
| Placebo | Change in Subjective Effects for STIMULATED of METH Challenge Doses | Day 26 | 5777 score on a scale * min | Standard Deviation 3498 |
| IXT-m200, 6 mg/kg | Change in Subjective Effects for STIMULATED of METH Challenge Doses | Day 12 | 9502 score on a scale * min | Standard Deviation 5234 |
| IXT-m200, 6 mg/kg | Change in Subjective Effects for STIMULATED of METH Challenge Doses | Day 1 | 11041 score on a scale * min | Standard Deviation 4934 |
| IXT-m200, 6 mg/kg | Change in Subjective Effects for STIMULATED of METH Challenge Doses | Day 5 | 9902 score on a scale * min | Standard Deviation 5445 |
| IXT-m200, 6 mg/kg | Change in Subjective Effects for STIMULATED of METH Challenge Doses | Day 19 | 10314 score on a scale * min | Standard Deviation 5130 |
| IXT-m200, 6 mg/kg | Change in Subjective Effects for STIMULATED of METH Challenge Doses | Day 26 | 7062 score on a scale * min | Standard Deviation 4436 |
| IXT-m200, 20 mg/kg | Change in Subjective Effects for STIMULATED of METH Challenge Doses | Day 26 | 9435 score on a scale * min | Standard Deviation 7499 |
| IXT-m200, 20 mg/kg | Change in Subjective Effects for STIMULATED of METH Challenge Doses | Day 19 | 5764 score on a scale * min | Standard Deviation 4707 |
| IXT-m200, 20 mg/kg | Change in Subjective Effects for STIMULATED of METH Challenge Doses | Day 1 | 8231 score on a scale * min | Standard Deviation 4259 |
| IXT-m200, 20 mg/kg | Change in Subjective Effects for STIMULATED of METH Challenge Doses | Day 12 | 6913 score on a scale * min | Standard Deviation 4448 |
| IXT-m200, 20 mg/kg | Change in Subjective Effects for STIMULATED of METH Challenge Doses | Day 5 | 6885 score on a scale * min | Standard Deviation 3915 |
Secondary
Pharmacokinetics of IXT-m200 Following Single Administration
Measured by serum concentrations of IXT-m200 over time
Time frame: 122 days
Population: All subjects who had quantifiable serum concentrations of IXT-m200 above the lower limit of quantitation (\<1250 ng/mL) starting at the first time point within 2.25 hr post-dose.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Pharmacokinetics of IXT-m200 Following Single Administration | 24 hr | 104920.1213 ng/mL | Standard Deviation 16662.63925 |
| Placebo | Pharmacokinetics of IXT-m200 Following Single Administration | 576 hr | 28816.8833 ng/mL | Standard Deviation 4801.42874 |
| Placebo | Pharmacokinetics of IXT-m200 Following Single Administration | 6 hr | 136095.9889 ng/mL | Standard Deviation 38937.85634 |
| Placebo | Pharmacokinetics of IXT-m200 Following Single Administration | 744 hr | 22375.2957 ng/mL | Standard Deviation 8092.25642 |
| Placebo | Pharmacokinetics of IXT-m200 Following Single Administration | 72 hr | 80955.9851 ng/mL | Standard Deviation 14213.86691 |
| Placebo | Pharmacokinetics of IXT-m200 Following Single Administration | 912 hr | 16793.6838 ng/mL | Standard Deviation 4465.29642 |
| Placebo | Pharmacokinetics of IXT-m200 Following Single Administration | 4 hr | 146618.9207 ng/mL | Standard Deviation 31767.42539 |
| Placebo | Pharmacokinetics of IXT-m200 Following Single Administration | 1080 hr | 12230.3541 ng/mL | Standard Deviation 3819.65649 |
| Placebo | Pharmacokinetics of IXT-m200 Following Single Administration | 192 hr | 52338.2686 ng/mL | Standard Deviation 10831.30591 |
| Placebo | Pharmacokinetics of IXT-m200 Following Single Administration | 1248 hr | 10954.1343 ng/mL | Standard Deviation 3596.63207 |
| Placebo | Pharmacokinetics of IXT-m200 Following Single Administration | 12 hr | 129181.7595 ng/mL | Standard Deviation 34383.49379 |
| Placebo | Pharmacokinetics of IXT-m200 Following Single Administration | 1416 hr | 8321.6347 ng/mL | Standard Deviation 2654.52136 |
| Placebo | Pharmacokinetics of IXT-m200 Following Single Administration | 360 hr | 41457.508 ng/mL | Standard Deviation 6880.32292 |
| Placebo | Pharmacokinetics of IXT-m200 Following Single Administration | 1920 hr | 4493.8091 ng/mL | Standard Deviation 2547.2715 |
| Placebo | Pharmacokinetics of IXT-m200 Following Single Administration | 2.25 hr | 148344.5945 ng/mL | Standard Deviation 36757.72368 |
| Placebo | Pharmacokinetics of IXT-m200 Following Single Administration | 2424 hr | 2093.7292 ng/mL | Standard Deviation 1803.09651 |
| Placebo | Pharmacokinetics of IXT-m200 Following Single Administration | 528 hr | 30996.9615 ng/mL | Standard Deviation 4340.51769 |
| Placebo | Pharmacokinetics of IXT-m200 Following Single Administration | 2928 hr | 1128.2148 ng/mL | Standard Deviation 1846.27013 |
| Placebo | Pharmacokinetics of IXT-m200 Following Single Administration | Pre-dose | 617.1589 ng/mL | Standard Deviation 2310.85995 |
| IXT-m200, 6 mg/kg | Pharmacokinetics of IXT-m200 Following Single Administration | 2928 hr | 5226.7547 ng/mL | Standard Deviation 2209.49318 |
| IXT-m200, 6 mg/kg | Pharmacokinetics of IXT-m200 Following Single Administration | Pre-dose | 101.9665 ng/mL | Standard Deviation 432.60722 |
| IXT-m200, 6 mg/kg | Pharmacokinetics of IXT-m200 Following Single Administration | 2.25 hr | 437078.0551 ng/mL | Standard Deviation 86546.28544 |
| IXT-m200, 6 mg/kg | Pharmacokinetics of IXT-m200 Following Single Administration | 4 hr | 413372.2737 ng/mL | Standard Deviation 86725.33552 |
| IXT-m200, 6 mg/kg | Pharmacokinetics of IXT-m200 Following Single Administration | 6 hr | 399030.4857 ng/mL | Standard Deviation 80456.98764 |
| IXT-m200, 6 mg/kg | Pharmacokinetics of IXT-m200 Following Single Administration | 12 hr | 357523.6776 ng/mL | Standard Deviation 66912.58267 |
| IXT-m200, 6 mg/kg | Pharmacokinetics of IXT-m200 Following Single Administration | 24 hr | 308379.4673 ng/mL | Standard Deviation 51024.44575 |
| IXT-m200, 6 mg/kg | Pharmacokinetics of IXT-m200 Following Single Administration | 72 hr | 261876.2091 ng/mL | Standard Deviation 105541.51539 |
| IXT-m200, 6 mg/kg | Pharmacokinetics of IXT-m200 Following Single Administration | 192 hr | 165650.1889 ng/mL | Standard Deviation 43060.62407 |
| IXT-m200, 6 mg/kg | Pharmacokinetics of IXT-m200 Following Single Administration | 360 hr | 119773.4315 ng/mL | Standard Deviation 26091.50216 |
| IXT-m200, 6 mg/kg | Pharmacokinetics of IXT-m200 Following Single Administration | 528 hr | 84460.7453 ng/mL | Standard Deviation 12052.38197 |
| IXT-m200, 6 mg/kg | Pharmacokinetics of IXT-m200 Following Single Administration | 576 hr | 93827.4756 ng/mL | Standard Deviation 28503.81089 |
| IXT-m200, 6 mg/kg | Pharmacokinetics of IXT-m200 Following Single Administration | 744 hr | 73363.3274 ng/mL | Standard Deviation 22594.3438 |
| IXT-m200, 6 mg/kg | Pharmacokinetics of IXT-m200 Following Single Administration | 912 hr | 61311.3385 ng/mL | Standard Deviation 20125.59405 |
| IXT-m200, 6 mg/kg | Pharmacokinetics of IXT-m200 Following Single Administration | 1080 hr | 45940.3791 ng/mL | Standard Deviation 12826.46281 |
| IXT-m200, 6 mg/kg | Pharmacokinetics of IXT-m200 Following Single Administration | 1248 hr | 38972.226 ng/mL | Standard Deviation 11834.15391 |
| IXT-m200, 6 mg/kg | Pharmacokinetics of IXT-m200 Following Single Administration | 1416 hr | 29865.3018 ng/mL | Standard Deviation 10122.90309 |
| IXT-m200, 6 mg/kg | Pharmacokinetics of IXT-m200 Following Single Administration | 1920 hr | 16676.9182 ng/mL | Standard Deviation 7385.34675 |
| IXT-m200, 6 mg/kg | Pharmacokinetics of IXT-m200 Following Single Administration | 2424 hr | 10002.5426 ng/mL | Standard Deviation 4197.70821 |
Secondary
Safety and Tolerability of IXT-m200 Followed by METH Challenges
Number of serious adverse events (SAEs) as identified by physical examinations and vital sign, adverse event, ECG, and clinical laboratory testing, and immune response by measurement of anti-IXT-m200 antibody levels.
Time frame: 126 days
Population: All subjects who received a dose of IXT-m200 or placebo on Day 4.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Safety and Tolerability of IXT-m200 Followed by METH Challenges | 0 Participants |
| IXT-m200, 6 mg/kg | Safety and Tolerability of IXT-m200 Followed by METH Challenges | 0 Participants |
| IXT-m200, 20 mg/kg | Safety and Tolerability of IXT-m200 Followed by METH Challenges | 0 Participants |