A Study of Idazoxan in Healthy Participants

Study Overview
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Brief Summary
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Four-part study of the safety, tolerability and pharmacokinetics of 3 forms of TR-01-XRR, 1 form of TR-01-XRS, and 1 form of TR-01-XR in healthy adults.

Official Title
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A Phase 1 Safety, Tolerability and Pharmacokinetic Study of R-Idazoxan HCl Extended-Release (TR-01-XRR), S-Idazoxan HCl Extended-Release (TR-01-XRS) and Racemic Idazoxan HCl Extended-Release (TR-01-XR) in Healthy Participants

Conditions
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Healthy

Intervention / Treatment
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* Drug: TR-01-XRR (1)
* Drug: TR-01-XRR (2)
* Drug: TR-01-XRR (3)
* Drug: TR-01-XRS
* Drug: TR-01-XR
* Drug: TR-01-IR
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: BMI between 18 and 32 kg/m2 Medically healthy without clinically significant or relevant medical history Exclusion Criteria: Evidence of recurrent disease, physical illness or medical condition that could affect action, absorption or disposition of investigational products Use of any prescription or over-the-counter medication that cannot be discontinued for the duration of the study Impaired renal function Cardiac abnormalities Positive HIV, HBsAg or HCV Positive test for alcohol, drugs of abuse or cotinine

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Part 1: Parallel group comparison, single dose level of 5 forms of the investigational study drug. Part 2: Parallel group comparison, single dose escalation (3 dose levels) of 4 forms investigational study drug and placebo. Part 3: Placebo controlled, multiple dose cross-over within 4 parallel group comparison. Part 4: Single-dose food effect cross-over.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1 Single Dose<br>Parallel group comparison, single dose level of 5 forms of the investigational study drug. | Drug: TR-01-XRR (1)<br>* Extended-release form<br>* Other names: R-Idazoxan HCL Extended Release (medium release rate) Tablet;Drug: TR-01-XRR (2)<br>* Extended-release form<br>* Other names: R-Idazoxan HCL Extended Release (faster release rate) Tablet;Drug: TR-01-XRR (3)<br>* Extended-release form<br>* Other names: R-Idazoxan HCL Extended Release (slower release rate) Tablet;Drug: TR-01-XRS<br>* Extended-release form<br>* Other names: S-Idazoxan Extended Release Tablet;Drug: TR-01-XR<br>* Extended-release form<br>* Other names: Racemic Idazoxan HCL Extended Release Tablet;|
| Experimental: Part 2: Single escalating doses<br>Parallel group comparison, single p.o. dose escalation (3 dose levels) of 4 forms investigational study drug and placebo administered to two sequential cohorts. Dose Level 1 will be administered to the first cohort. Dose Levels 2 and 3 will be administered to a subsequent cohort. Dose levels in this cohort are separated by a 7-day washout period. Doses to be determined by review of data from Part 1. | Drug: TR-01-XRR (1)<br>* Extended-release form<br>* Other names: R-Idazoxan HCL Extended Release (medium release rate) Tablet;Drug: TR-01-XRS<br>* Extended-release form<br>* Other names: S-Idazoxan Extended Release Tablet;Drug: TR-01-XR<br>* Extended-release form<br>* Other names: Racemic Idazoxan HCL Extended Release Tablet;Drug: TR-01-IR<br>* Active comparator<br>* Other names: Idazoxan HCL Immediate Release Tablet;Drug: Placebo<br>* Placebo comparator<br>* Other names: Matching Placebo Tablet;|
| Experimental: Part 3: Multiple Dose<br>Parallel group comparison of 4 active treatments dosed p.o. x 4 days. Each active is dosed in a 2-period placebo-controlled crossover separated by a 5-day washout. Doses to be determined by review of data from Part 2. | Drug: TR-01-XRR (1)<br>* Extended-release form<br>* Other names: R-Idazoxan HCL Extended Release (medium release rate) Tablet;Drug: TR-01-XRS<br>* Extended-release form<br>* Other names: S-Idazoxan Extended Release Tablet;Drug: TR-01-XR<br>* Extended-release form<br>* Other names: Racemic Idazoxan HCL Extended Release Tablet;Drug: TR-01-IR<br>* Active comparator<br>* Other names: Idazoxan HCL Immediate Release Tablet;Drug: Placebo<br>* Placebo comparator<br>* Other names: Matching Placebo Tablet;|
| Experimental: Part 4: Food Effects<br>Two-period single p.o. dose fasted/fed crossover separated by 5-day washout period. Dose to be determined by review of data from Part 2. | Drug: TR-01-XRR (1)<br>* Extended-release form<br>* Other names: R-Idazoxan HCL Extended Release (medium release rate) Tablet;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with treatment-related adverse events based on clinical observation and participant report | Clinically observed adverse events include findings from physical examination, vital sign, ECG and laboratory assessments (hematological and clinical chemistry laboratory panels). Participant report includes any side effect reported by a participant during the study. | Through study completion up to 25 days after initial dose | 
| Area under the plasma concentration-time curve (AUC) | To evaluate drug exposure over specified measurement time frame | Up to 120 hours after dose | 
| Maximum plasma concentration (Cmax) | To evaluate peak drug concentration achieved during specified measurement time frame | Up to 120 hours after dose | 
| Time to maximum plasma concentration (Tmax) | To evaluate time to achieve peak concentration during specified measurement time frame | Up to 120 hours after dose | 
| Terminal elimination rate constant | To evaluate rate of drug elimination | Up to 120 hours after dose | 
| Terminal elimination half-life (T1/2) | To evaluate time over which drug concentration is decreased by half | Up to 120 hours after dose | 
| Apparent total clearance from plasma (CL/F) | To evaluate rate of drug clearance | Up to 120 hours after dose | 
| Apparent volume of distribution (Vz/F) | To evaluate extent of drug distribution in the body | Up to 120 hours after dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relative bioavailability (Frel) | To compare single dose oral bioavailability in fed and fasted states | Over 120 hours after dose |