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

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:

1. To determine if a single SC administration of TTX at various dose levels has an effect on other important electrocardiogram (ECG) parameters in healthy adult subjects.
2. To demonstrate sensitivity of this QTc assay using moxifloxacin as a positive control.
3. To confirm plasma pharmacokinetic (PK) of a single SC administration of TTX at various dose levels when administered to healthy adult subjects.
4. To determine the overall safety and tolerability of a single SC administration of TTX at various dose levels when administered to healthy adult subjects.

Test Product, Dose, Duration, Mode of Administration, and Batch Number:

The test product was 30 µg/mL tetrodotoxin (TTX) for injection, Lot No. F141124-001.

Subjects were also administered:

* 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

Interventions

DRUG

Tetrodotoxin

A single TTX dose in a dose ascending study

DRUG

Placebos

matching placebo comparator

Sponsors & Collaborators

• Celerion

  collaborator INDUSTRY

• Wex Pharmaceuticals Inc.

  lead INDUSTRY

Study Design

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

QUADRUPLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

55 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2018-02-07

Primary Completion

2018-03-24

Completion

2018-03-24

FDA Drug

Yes

Countries

• United States

Study Locations