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
Condition: TQT Study
Study type: Interventional
Phase: Phase 1

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.
    


Intervention name(s): Tetrodotoxin; Placebos
Intervention type(s): Drug; Drug
Intervention description(s): A single TTX dose in a dose ascending study; matching placebo comparator
Other intervention name(s): Halneuron
Intervention MeSH terms: Tetrodotoxin
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Basic Science
Keywords: TQT TTX Halneuron cardiac safety