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

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

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).

Study Overview

• Status: Unknown
• Conditions: Surgery; Pain, Acute; Acute Pain; Neuropathy
• Intervention / Treatment: Drug: CT-044 HCl

Detailed Description

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).

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Pasadena, California, United States, 91105
      • Lotus Clinical Resarch,LLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: OTHER
• Allocation: RANDOMIZED
• Interventional Model: SEQUENTIAL
• Masking: DOUBLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: 200 mg CT-044 HCl or Placebo; 200 mg of CT-044 HCl administered every 8 hours vs placebo	Drug: CT-044 HCl; CT-044 HCl is a reactive species decomposition accelerant
EXPERIMENTAL: 400 mg CT-044 HCl or Placebo; 400 mg of CT-044 HCl administered every 8 hours vs placebo	Drug: CT-044 HCl; CT-044 HCl is a reactive species decomposition accelerant
EXPERIMENTAL: 600 mg CT-044 HCl or Placebo; 600 mg of CT-044 HCl administered every 8 hours vs placebo	Drug: CT-044 HCl; CT-044 HCl is a reactive species decomposition accelerant

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Lotus Clinical Research, LLC
• Collaborators: CerSci Therapeutics

Publications and helpful links

General Publications

• Squillace S, Salvemini D. Nitroxidative stress in pain and opioid-induced adverse effects: therapeutic opportunities. Pain. 2022 Feb 1;163(2):205-213. doi: 10.1097/j.pain.0000000000002347. No abstract available.

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 4, 2019
• Primary Completion (ANTICIPATED): August 1, 2020
• Study Completion (ANTICIPATED): September 1, 2020

Study Registration Dates

• First Submitted: November 6, 2019
• First Submitted That Met QC Criteria: November 21, 2019
• First Posted (ACTUAL): November 25, 2019

Study Record Updates

• Last Update Posted (ACTUAL): July 23, 2020
• Last Update Submitted That Met QC Criteria: July 21, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Keywords: Safety; Pharmacokinetics; PK; Tolerability; Neuropathy; Plasma; Acute Pain; Escalation; Surgical Pain; Non-Opioid; CT-044 HCl; Ascending; Chronic Neuropathy
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Acute Pain
• Other Study ID Numbers: CT044-002

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No