Double-blind, Placebo-control, Study to Evaluate the Safety and Pharmacokinetics of CT-044 HCl, in Healthy Volunteers

Study Overview
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Brief Summary
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This study will be conducted to assess safety, tolerability, and PK of CT-044 HCl in normal healthy volunteers, in a traditional sequential multiple ascending dose paradigm. The multiple-dose escalation is designed to mimic the manner in which the product (CT-044 HCl) would be used to manage ongoing pain in patients (i.e., multiple dosing).

Detailed Description
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Subjects meeting all inclusion and exclusion criteria will be randomized to receive CT-044 HCl or placebo in three successive dose escalating cohorts of 8 subjects each (2 placebo and 6 active drug per dose level). Subjects will receive multiple oral CT-044 HCl doses for 7 days. Subjects will be monitored in-house for vital signs, physical examination, electrocardiogram (ECG), safety laboratory testing and documentation of adverse signs and symptoms. Serial blood and urine samples will be collected to evaluate CT-044 HCl levels in plasma and urine. Eligible subjects will be admitted to the Clinical Trial Unit on the day prior to dosing (Day -1) and remain in house until Day 9 (discharge day). Subjects will return to the Clinical Trial Unit on an outpatient basis for follow-up (Day 13, ± 1 day).

Official Title
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Double-blinded, Placebo-controlled, Sequential Cohort, Multiple-Dose Escalation Study to Evaluate the Safety and Multiple Dose Pharmacokinetics of CT-044 HCl, a Reactive Species Decomposition Accelerant, in Healthy Human Volunteers

Conditions
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Acute Pain, Pain, Acute, Surgery, Neuropathy

Intervention / Treatment
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* Drug: CT-044 HCl


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Body mass index within the range 18.5 to 32.0 kg/m2 (inclusive). Healthy subjects as determined by medical history, physical examination including neurological examination, vital signs, electrocardiogram (ECG), and clinical laboratory tests. Negative tests for hepatitis B surface antigen, hepatitis C virus antibodies and human immunodeficiency virus (HIV-1 or HIV-2) antibody, and syphilis. Nonsmokers (use of any nicotine containing product) or ex-smokers (have ceased smoking for at least 3 months and do not use any drug for smoking cessation. Negative screen for alcohol and drugs of abuse. Women must not be of childbearing potential by reason of surgery or at least 1 year post-menopausal (i.e., 12 months without menstrual period), or menopause. Men must be infertile (at least 3-months post-vasectomy), or truly abstinent of heterosexual intercourse, or heterosexual partner is not of childbearing potential or must agree to use an effective method of contraception. Men must agree to not provide sperm donation during that same period. Able and willing to be available for the duration of the study. Willing and able to give written informed consent to participate. Able to understand and comply with protocol instructions.

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: Other
Allocation: Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: The study is planned to have 3 dose levels (3 study cohorts); the actual dose level cohorts will be decided by the SRC after review of the data from each cohort that was successfully completed in the SAD study. Each dose cohort will include 8 subjects randomized to placebo (2 subjects) or active drug (6 subjects).
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 200 mg CT-044 HCl or Placebo<br>200 mg of CT-044 HCl administered every 8 hours vs placebo | Drug: CT-044 HCl<br>* CT-044 HCl is a reactive species decomposition accelerant<br>|
| Experimental: 400 mg CT-044 HCl or Placebo<br>400 mg of CT-044 HCl administered every 8 hours vs placebo | Drug: CT-044 HCl<br>* CT-044 HCl is a reactive species decomposition accelerant<br>|
| Experimental: 600 mg CT-044 HCl or Placebo<br>600 mg of CT-044 HCl administered every 8 hours vs placebo | Drug: CT-044 HCl<br>* CT-044 HCl is a reactive species decomposition accelerant<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum exposure level of CT-044 | Occurrence of maximum exposure level of Cmax of 80 μg/mL and/or AUC0-24 of 450 hr.μg/mL (corresponding to average values obtained at the NOAEL doses in males rat and dog) has been reached in ≥2 subjects in a cohort or if it is expected to be reached in the planned next cohort. | 49 days | 
| Plasma Pharmacokinetic Concentration of CT-044 | The PK data will be summarized by dose/cohort using appropriate statistics. Actual elapsed time from dosing will be used for the final plasma PK parameter calculations after database lock. Plasma PK samples collected every 8 hours for 32 hours. | 32 Hours | 
| Urine Pharmacokinetic Concentration of CT-044 | The urine PK concentration of CT-044 will use individual data points to determine the concentration of CT-044 in subjects urine. Urine PK samples collected every 8 hours for 24 hours. | 24 Hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PK, Safety, Tolerability, Escalation, Pharmacokinetics, CT-044 HCl, Ascending, Plasma, Surgical Pain, Acute Pain, Non-Opioid, Neuropathy, Chronic Neuropathy