A Phase 1, Single Ascending Dose, Randomized, Double-Blind, Placebo and Positive Controlled Study to Evaluate the Cardiovascular Effect of Tetrodotoxin in Healthy Adult Subjects

NCT04083833 | Completed Phase 1 FDA Drug

• 1 other identifier: TTX-TQT-101
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

To determine if a single subcutaneous (SC) administration of TTX at various dose levels has an effect on the QT/QTc intervals when assessing concentration QT (C-QT) relationship (i.e., QT/QTc intervals prolongation in relation to plasma levels of TTX) in healthy adult subjects. Secondary:

• Tetrodotoxin matching placebo a sterile 0.9% sodium chloride injection or normal saline for injection, Lot No. 84-093-DK
• 400 mg Avelox® (moxifloxacin hydrochloride) tablets, Lot No. BXHJ1S1
• Moxifloxacin matching placebo film-coated tablets, Id.-No.: K15372, Batch No.: C1606007 Treatments were as follows: Treatment Arm (n = 9) Treatment A: (Period 1) A single TTX dose of 15 μg (0.5 mL of TTX 30 μg/mL injection solution) administered as 1 SC injection with a single oral moxifloxacin matching placebo (1 x placebo tablet) Treatment B: (Period 2) A single TTX dose of 30 μg (1 mL of TTX 30 μg/mL injection solution) administered as 1 SC injection with a single oral moxifloxacin matching placebo (1 x placebo tablet) Treatment C: (Period 3) A single TTX dose of 45 μg (1.5 mL of TTX 30 μg/mL injection solution) administered as 2 SC injections with a single oral moxifloxacin matching placebo (1 x placebo tablet) Subjects randomized to the Control Arm were further randomized to receive 1 of 2 treatment sequences (Treatment Sequence DEF \[n = 8\] and Treatment Sequence GHI \[n = 8\]): Control Arm (n = 16) Treatment D: (Period 1) A single matching-TTX placebo (0.5 mL of placebo injection solution) administered as 1 SC injection with a single oral moxifloxacin matching placebo (1 x placebo tablet) Treatment E: (Period 2) A single matching-TTX placebo (1 mL of placebo injection solution) administered as 1 SC injection with a single oral 400 mg moxifloxacin (1 x 400 mg tablet) Treatment F: (Period 3) A single matching-TTX placebo (1.5 mL of placebo injection solution) administered as 2 SC injections with a single oral moxifloxacin matching placebo (1 x placebo tablet) Treatment G: (Period 1) A single matching-TTX placebo (0.5 mL of placebo injection solution) administered as 1 SC injection with a single oral 400 mg moxifloxacin (1 x 400 mg tablet) Treatment H: (Period 2) A single matching-TTX placebo (1 mL of placebo injection solution) administered as 1 SC injection with a single oral moxifloxacin matching placebo (1 x placebo tablet) Treatment I: (Period 3) A single matching-TTX placebo (1.5 mL of placebo injection solution) administered as 2 SC injections with a single oral 400 mg moxifloxacin (1 x 400 mg tablet) All oral study drugs were administered with approximately 240 mL of water.

Conditions

TQT Study

Keywords

TQT TTX Halneuron cardiac safety

Outcome Measures

Primary Outcomes (1)

• Cardiodynamic

  The primary cardiodynamic endpoint was the effect of TTX plasma concentrations on the QTc interval using linear mixed-effect exposure-response modeling, including the predicted ddQTc at Cmax values corresponding to exposure levels of interest.

  24 hours

Secondary Outcomes (3)

• ECG Paramenters

  24 hours

• ECG Paramenters

  24 hours

• Assay Sensitivity

  24 hours

Study Arms (2)

Treatment Arm

EXPERIMENTAL

(Period 1) A single TTX dose of 15 μg (0.5 mL of TTX 30 μg/mL injection solution) administered as 1 SC injection with a single oral moxifloxacin matching placebo (1 x placebo tablet) (Period 2) A single TTX dose of 30 μg (1 mL of TTX 30 μg/mL injection solution) administered as 1 SC injection with a single oral moxifloxacin matching placebo (1 x placebo tablet) (Period 3) A single TTX dose of 45 μg (1.5 mL of TTX 30 μg/mL injection solution) administered as 2 SC injections with a single oral moxifloxacin matching placebo (1 x placebo tablet)

Drug: Tetrodotoxin

Control

PLACEBO COMPARATOR

Treatment D: (Period 1)A single matching-TTX placebo administered with a single oral moxifloxacin matching placebo Treatment E: (Period 2)A single matching-TTX placebo with a single oral 400 mg moxifloxacin Treatment F: (Period 3)A single matching-TTX placebo with a single oral moxifloxacin matching placebo Treatment G: (Period 1)A single matching-TTX placebo with a single oral 400 mg moxifloxacin Treatment H: (Period 2)A single matching-TTX placebo with a single oral moxifloxacin matching placebo Treatment I: (Period 3)A single matching-TTX placebo with a single oral 400 mg moxifloxacin

Drug: Placebos

Interventions

Tetrodotoxin DRUG

A single TTX dose in a dose ascending study

Also known as: Halneuron

Treatment Arm

Placebos DRUG

matching placebo comparator

Control

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy, adult, male or female 18 55 years of age, inclusive, at screening.
• Continuous non smoker who has not used nicotine containing products for at least 3 months prior to the first dose and throughout the study.
• Body mass index (BMI) ≥ 18.5 and ≤ 32.0 kg/m2 at screening.
• Medically healthy with no clinically significant medical history, physical examination, neurologic examinations, laboratory profiles, vital signs, or ECGs, as deemed by the PI or designee.
• For a female of childbearing potential: either be sexually inactive (abstinent) for 14 days prior to the first dose and throughout the study or be using one of the following acceptable birth control methods:
• non-hormone releasing intrauterine device for at least 3 months prior to the first dose and throughout the study.
• surgical sterilization of the partner (vasectomy for 4 months minimum prior to the first dose).
• physical barrier method (e.g., condom, diaphragm) with spermicide for at least 14 days prior to the first dose and throughout the study.
• A female subject who claims to be sexually inactive, but becomes sexually active during the course of the study must agree to use a physical barrier method (e.g., condom, diaphragm) with spermicide from the time of the start of sexual activity and throughout the study.
• In addition, female subjects of childbearing potential will be advised to remain sexually inactive or to keep the same birth control method for at least 28 days following the last dose.
• For a female of non childbearing potential: must have undergone one of the following sterilization procedures at least 6 months prior to the first dose:
• hysteroscopic sterilization;
• bilateral tubal ligation or bilateral salpingectomy;
• hysterectomy;
• bilateral oophorectomy; or be postmenopausal with amenorrhea for at least 1 year prior to the first dose and follicle stimulating hormone (FSH) serum levels consistent with postmenopausal status.

You may not qualify if:

• Subject is mentally or legally incapacitated or has significant emotional problems at the time of the screening visit or expected during the conduct of the study.
• History or presence of clinically significant medical or psychiatric condition or disease in the opinion of the PI or designee.
• History of any illness that, in the opinion of the PI or designee, might confound the results of the study or poses an additional risk to the subject by their participation in the study.
• History or presence of alcoholism or drug abuse within the past 2 years prior to the first dose.
• History or presence of:
• risk factors for Torsade de Pointes (e.g., heart failure, cardiomyopathy, or family history of Long QT Syndrome);
• sick sinus syndrome, second or third degree atrioventricular block, myocardial infarction, pulmonary congestion, symptomatic or significant cardiac arrhythmia, prolonged QTcF interval, or conduction abnormalities.
• Any acute or chronic pain conditions requiring ongoing treatment or limiting daily activities.
• History of fainting upon blood sampling or needle puncture.
• Findings during the screening neurological examination that could interfere with or preclude neurological assessments during the study, in the opinion of the PI or designee.
• History or presence of neurologic or neuromuscular disease.
• Allergy to band aids, adhesive dressing or medical tape.
• History or presence of hypersensitivity or idiosyncratic reaction to the study drug(s), related compounds, or fish.
• History of anaphylaxis to a medication, dietary item, or environment exposures (including bee stings).
• Female subjects with a positive pregnancy test or lactating.

Sponsors & Collaborators

• Wex Pharmaceuticals Inc.: lead
• Celerion: collaborator

Study Sites (1)

Celerion

Tempe, Arizona, 85283, United States

Location

MeSH Terms

Interventions

Tetrodotoxin

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Marine Toxins; Toxins, Biological; Biological Factors

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 6, 2019
• First Posted: September 10, 2019
• Study Start: February 7, 2018
• Primary Completion: March 24, 2018
• Study Completion: March 24, 2018
• Last Updated: September 10, 2019

Record last verified: 2019-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)