This will be a randomized, double-blind, placebo-controlled, parallel-group study to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of oral TMP-301, given concurrently with cocaine. The study will consist of 4 phases: Screening, Baseline, Treatment, and Follow-up.
This will be a randomized, double-blind, placebo-controlled, parallel-group study to assess the safety, tolerability, PK, and PD of oral TMP-301, given concurrently with cocaine. The study will consist of 4 phases: Screening, Baseline, Treatment, and Follow-up. The Screening Phase will be completed as an outpatient visit within 24 days of the Baseline Phase and will consist of a standard medical screen. Within 24 days of a standard medical screening, eligible participants will return to the clinical site as inpatients to complete the Baseline Phase. All participants will remain in-clinic for the duration of the 7-day Treatment Phase. Following confirmation of eligibility, participants will be randomized to one of two treatment groups, either TMP-301 or. A safety follow-up visit will be conducted on Day 23.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
18
Dr. Vince Clinical Research
Overland Park, Kansas, United States
To evaluate the safety and tolerability of TMP-301 alone via incidence and severity of treatment-emergent adverse events (TEAEs) with cocaine infusions.
Time frame: Baseline to Day 23
To evaluate the safety and tolerability of TMP-301 in combination with cocaine via incidence and severity of treatment-emergent adverse events (TEAEs) with cocaine infusions.
Time frame: Baseline to Day 23
To evaluate the safety and tolerability of TMP-301 alone via peak change from baseline of heart rate (CFBmax).
Time frame: Baseline to Day 23
To evaluate the safety and tolerability of TMP-301 in combination with cocaine via peak change from baseline of heart rate (CFBmax).
Time frame: Baseline to Day 23
To evaluate the safety and tolerability of TMP-301 alone via peak change from baseline of systolic blood pressure (SBP).
Time frame: Baseline to Day 23
To evaluate the safety and tolerability of TMP-301 in combination with cocaine via peak change from baseline of systolic blood pressure (SBP).
Time frame: Baseline to Day 23
To evaluate the safety and tolerability of TMP-301 alone via peak change from baseline of diastolic blood pressure (DBP).
Time frame: Baseline to Day 23
To evaluate the safety and tolerability of TMP-301 in combination with cocaine via peak change from baseline of diastolic blood pressure (DBP).
Time frame: Baseline to Day 23
To evaluate the safety and tolerability of TMP-301 alone via peak change from baseline of quantitative electrocardiogram PR interval
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Time frame: Baseline to Day 23
To evaluate the safety and tolerability of TMP-301 alone via peak change from baseline of quantitative electrocardiogram QRS complex.
Time frame: Baseline to Day 23
To evaluate the safety and tolerability of TMP-301 in combination with cocaine via peak change from baseline of quantitative electrocardiogram PR interval.
Time frame: Baseline to Day 23
To evaluate the safety and tolerability of TMP-301 in combination with cocaine via peak change from baseline of quantitative electrocardiogram QRS complex.
Time frame: Baseline to Day 23
To assess the maximum observed plasma concentration (Cmax) of cocaine alone.
Time frame: Days 7 and 14
To assess the maximum observed plasma concentration (Cmax) of cocaine with TMP-301.
Time frame: Days 7 and 14
To assess the Tmax of cocaine alone.
Time frame: Days 7 and 14
To assess the Tmax of cocaine with TMP-301.
Time frame: Days 7 and 14
To assess the area under the plasma concentration-time curve from time 0 to the last measured concentration (AUC0-t) of cocaine alone.
Time frame: Days 7 and 14
To assess the area under the plasma concentration-time curve from time 0 to the last measured concentration (AUC0-t) of cocaine with TMP-301.
Time frame: Days 7 and 14
To assess the AUC from time 0 to infinity (AUC0-inf) of cocaine alone.
Time frame: Days 7 and 14
To assess the AUC from time 0 to infinity (AUC0-inf) of cocaine alone in combination with TMP-301.
Time frame: Days 7 and 14
To assess the elimination rate constant (λz) of cocaine alone.
Time frame: Days 7 and 14
To assess the elimination rate constant (λz) of cocaine in combination with TMP-301.
Time frame: Days 7 and 14
To assess the t1/2 of cocaine alone.
Time frame: Days 7 and 14
To assess the t1/2 of cocaine in combination with TMP-301.
Time frame: Days 7 and 14
To assess the apparent clearance (CL; if data permit) of cocaine alone.
Time frame: Days 7 and 14
To assess the apparent clearance (CL; if data permit) of cocaine in combination with TMP-301.
Time frame: Days 7 and 14
To assess the apparent volume of distribution (Vd; if data permit) of cocaine alone.
Time frame: Days 7 and 14
To assess the apparent volume of distribution (Vd; if data permit) of cocaine in combination with TMP-301.
Time frame: Days 7 and 14
To assess the metabolite-to-parent ratio (Cmax) of cocaine alone.
Time frame: Days 7 and 14
To assess the metabolite-to-parent ratio (area under the plasma concentration versus time curve) of cocaine alone.
Time frame: Days 7 and 14
To assess the metabolite-to-parent ratio (Cmax) of cocaine in combination with TMP-301.
Time frame: Days 7 and 14
To assess the metabolite-to-parent ratio (area under the plasma concentration versus time curve) of cocaine in combination with TMP-301.
Time frame: Days 7 and 14
To assess the visual analog scale (0-100): maximum effect (Emax) from time 0 to 60 minutes post-cocaine infusion of cocaine alone.
Higher score is worse
Time frame: Days 7 and 14
To assess the visual analog scale (0-100): Area Under the Effect Curve (AUE) from time 0 to 60 minutes post-cocaine infusion of cocaine alone.
Higher score is worse
Time frame: Days 7 and 14
To assess the visual analog scale (0-100): maximum effect (Emax) from time 0 to 60 minutes post-cocaine infusion of cocaine in combination with TMP-301.
Higher score is worse
Time frame: Days 7 and 14
To assess the visual analog scale (0-100): AUE from time 0 to 60 minutes post-cocaine infusion of cocaine in combination with TMP-301.
Higher score is worse
Time frame: Days 7 and 14
To assess the Brief Substance Craving Scale (BSCS) scores over time of cocaine alone.
The BSCS is a self-administered assessment that asks the participant to rate his or her craving for cocaine. The BSCS used for this study is a modification of the State of Feelings and Cravings Questionnaire.
Time frame: Days 7 and 14
To assess the Brief Substance Craving Scale (BSCS) scores over time of cocaine in combination with TMP-301.
The BSCS is a self-administered assessment that asks the participant to rate his or her craving for cocaine. The BSCS used for this study is a modification of the State of Feelings and Cravings Questionnaire.
Time frame: Days 7 and 14
To assess the Cmax of TMP-301.
Time frame: Days 7 and 14
To assess the Tmax of TMP-301.
Time frame: Days 7 and 14
To assess the AUC during a dosing interval (AUC0-τ) of TMP-301.
Time frame: Days 7 and 14
To assess the λz of TMP-301.
Time frame: Days 7 and 14
To assess the t1/2 of TMP-301.
Time frame: Days 7 and 14
To assess the CL/F (if data permit) of TMP-301.
Time frame: Days 7 and 14
To assess the Vd/F (if data permit) of TMP-301.
Time frame: Days 7 and 14
To evaluate the safety and tolerability of TMP-301 as assessed by the incidence and severity of Treatments Emergent Adverse Events (TEAEs).
Time frame: Baseline to Day 23
To evaluate the safety and tolerability of TMP-301 as assessed by number of participants taking concomitant medications taken during study participation.
Time frame: Baseline to Day 23
To evaluate the safety and tolerability of TMP-301 as assessed by systolic blood pressure.
Time frame: Baseline to Day 23
To evaluate the safety and tolerability of TMP-301 as assessed by diastolic blood pressure.
Time frame: Baseline to Day 23
To evaluate the safety and tolerability of TMP-301 as assessed by heart rate.
Time frame: Baseline to Day 23
To evaluate the safety and tolerability of TMP-301 as assessed by electrocardiogram PR interval.
Time frame: Baseline to Day 23
To evaluate the safety and tolerability of TMP-301 as assessed by electrocardiogram QRS complex.
Time frame: Baseline to Day 23
To evaluate the safety and tolerability of TMP-301 as assessed by number of participants with abnormal laboratory test results.
Time frame: Baseline to Day 23
To evaluate the safety and tolerability of TMP-301 as assessed by Beck Depression Inventory (BDI) scores (0-63) over time.
Score of 63 is worse.
Time frame: Baseline to Day 23
To evaluate the safety and tolerability of TMP-301 as assessed by the Brief Psychiatric Rating Scale (BPRS) scores (0-126) over time.
Score of 126 is worse.
Time frame: Baseline to Day 23
To evaluate the safety and tolerability of TMP-301 as assessed by number of participants with abnormal physical examination findings.
Time frame: Baseline to Day 23
To evaluate the safety and tolerability of TMP-301 as assessed by Columbia-Suicide Severity Rating Scale (C-SSRS) score (0-5)
Score of 5 is worse.
Time frame: Baseline to Day 23