A Randomized, Participant- and Investigator-blinded, Placebo-controlled, Parallel-group Study to Assess the Safety, Tolerability, and Pharmacokinetics of Oral TMP-301 Given Concurrently With Cocaine
Overview
- Phase
- Phase 1
- Intervention
- TMP-301
- Conditions
- Cocaine Use Disorder
- Sponsor
- Tempero Bio, Inc.
- Enrollment
- 18
- Locations
- 1
- Primary Endpoint
- To evaluate the safety and tolerability of TMP-301 in combination with cocaine via peak change from baseline of heart rate (CFBmax).
- Status
- Completed
- Last Updated
- 11 months ago
Overview
Brief Summary
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.
Detailed Description
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Males and females between 18 and 55 years of age, inclusive.
- •Understand the study procedures, follow instructions, and provide written informed consent.
- •Have a body mass index (BMI) within a range of 18.0 to 34.0 kg/m2 and body weight ≥50.0 kg at Screening.
- •Healthy, as determined by no clinically significant medical history, physical examination, 12-lead ECG, vital signs, and clinical laboratory results (including hematology, clinical chemistry, urinalysis, and serology) at Screening, as judged by the investigator.
- •≥6 uses of cocaine by the smoked or IV route in the 12 months prior to Screening
- •Provide a positive urine drug screen (UDS) for cocaine at least once during the screening period or at admission. Repeat or rescheduled testing will be allowed at the investigator's discretion.
- •Have BP and Heart Rate (HR) within the following ranges after 5 minutes' rest at Screening and admission:
- •SBP: 90 to 139 mmHg, inclusive
- •DBP: 50 to 89 mmHg, inclusive
- •HR: 45 to 99 bpm, inclusive
Exclusion Criteria
- •Meet current Diagnostic and Statistical Manual of Mental Disorders - Fifth Edition (DSM-5) criteria for any SUDs other than cocaine, cannabis, or nicotine. Diagnosis of mild to moderate alcohol use disorder will not be considered exclusionary.
- •Have a DSM-5 psychiatric disorder other than SUD, including but not limited to, Bipolar Disorder, Major Depressive Disorder, or Schizophrenia, or have a neurological disorder requiring ongoing treatment and/or making study participation unsafe.
- •Have any previous medically adverse reaction to cocaine, including loss of consciousness, chest pain, paranoid reaction, or epileptic seizure.
- •Have a 12-lead ECG with repeated demonstration of corrected QT interval (QTcF) ≥470 msec in female participants or ≥450 msec in male participants at Screening.
- •Unable to tolerate a 20 mg cocaine IV infusion (Day -2) or a 40 mg cocaine IV infusion (Day -1) during the Baseline Phase, as judged by the investigator or designee and per criteria in protocol;
- •History or clinical manifestation of any metabolic, allergic, dermatological, hepatic, renal, hematological, pulmonary, gastrointestinal, neurological, respiratory, or endocrine disorder, which would preclude safe or successful completion of the study, as determined by an investigator.
- •Have a history of any illness, or a family history of early significant cardiovascular disease that, in the opinion of the investigator, might confound the results of the study or pose additional risk in administering the study drugs to the participant.
- •Have a significant risk of developing psychosis (assessed by Prevention through Risk Identification, Management, and Education \[PRIME\] screen) or have a personal history of psychotic symptoms (hallucinations or delusions), with or without a formal psychiatric diagnosis.
- •Have a family history of significant mental, behavioral, or neurodevelopmental disorders, unless determined by the investigator to be not clinically significant (NCS).
- •Have a current or past history of seizures, including alcohol- or stimulant-related seizures (excluding childhood febrile seizures), or significant family history of idiopathic seizure disorder or clinically significant (CS) head injury.
Arms & Interventions
TMP-301
Once daily \[QD\] × 14 days
Intervention: TMP-301
Placebo
Once daily \[QD\] × 14 days
Intervention: Placebo
Outcomes
Primary Outcomes
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 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 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
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
Secondary Outcomes
- To evaluate the safety and tolerability of TMP-301 as assessed by heart rate.(Baseline to Day 23)
- To assess the area under the plasma concentration-time curve from time 0 to the last measured concentration (AUC0-t) of cocaine alone.(Days 7 and 14)
- To assess the maximum observed plasma concentration (Cmax) of cocaine alone.(Days 7 and 14)
- To assess the maximum observed plasma concentration (Cmax) of cocaine with TMP-301.(Days 7 and 14)
- To assess the Tmax of cocaine alone.(Days 7 and 14)
- To assess the Tmax of cocaine with TMP-301.(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.(Days 7 and 14)
- To assess the AUC from time 0 to infinity (AUC0-inf) of cocaine alone.(Days 7 and 14)
- To assess the AUC from time 0 to infinity (AUC0-inf) of cocaine alone in combination with TMP-301.(Days 7 and 14)
- To assess the elimination rate constant (λz) of cocaine alone.(Days 7 and 14)
- To assess the elimination rate constant (λz) of cocaine in combination with TMP-301.(Days 7 and 14)
- To assess the t1/2 of cocaine alone.(Days 7 and 14)
- To assess the t1/2 of cocaine in combination with TMP-301.(Days 7 and 14)
- To assess the apparent clearance (CL; if data permit) of cocaine alone.(Days 7 and 14)
- To assess the apparent clearance (CL; if data permit) of cocaine in combination with TMP-301.(Days 7 and 14)
- To assess the apparent volume of distribution (Vd; if data permit) of cocaine alone.(Days 7 and 14)
- To assess the apparent volume of distribution (Vd; if data permit) of cocaine in combination with TMP-301.(Days 7 and 14)
- To assess the metabolite-to-parent ratio (Cmax) of cocaine alone.(Days 7 and 14)
- To assess the metabolite-to-parent ratio (area under the plasma concentration versus time curve) of cocaine alone.(Days 7 and 14)
- To assess the metabolite-to-parent ratio (Cmax) of cocaine in combination with TMP-301.(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.(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.(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.(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.(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.(Days 7 and 14)
- To assess the Brief Substance Craving Scale (BSCS) scores over time of cocaine alone.(Days 7 and 14)
- To assess the Brief Substance Craving Scale (BSCS) scores over time of cocaine in combination with TMP-301.(Days 7 and 14)
- To assess the Cmax of TMP-301.(Days 7 and 14)
- To assess the Tmax of TMP-301.(Days 7 and 14)
- To assess the AUC during a dosing interval (AUC0-τ) of TMP-301.(Days 7 and 14)
- To assess the λz of TMP-301.(Days 7 and 14)
- To assess the t1/2 of TMP-301.(Days 7 and 14)
- To assess the CL/F (if data permit) of TMP-301.(Days 7 and 14)
- To assess the Vd/F (if data permit) of TMP-301.(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).(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.(Baseline to Day 23)
- To evaluate the safety and tolerability of TMP-301 as assessed by systolic blood pressure.(Baseline to Day 23)
- To evaluate the safety and tolerability of TMP-301 as assessed by diastolic blood pressure.(Baseline to Day 23)
- To evaluate the safety and tolerability of TMP-301 as assessed by electrocardiogram PR interval.(Baseline to Day 23)
- To evaluate the safety and tolerability of TMP-301 as assessed by electrocardiogram QRS complex.(Baseline to Day 23)
- To evaluate the safety and tolerability of TMP-301 as assessed by number of participants with abnormal laboratory test results.(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.(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.(Baseline to Day 23)
- To evaluate the safety and tolerability of TMP-301 as assessed by number of participants with abnormal physical examination findings.(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)(Baseline to Day 23)