TQT StudyPhase 1NCT04083833
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
A Phase 1 study testing Tetrodotoxin in people with TQT Study, run by Wex Pharmaceuticals Inc. at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- TQT Study
- What is being tested?
- Tetrodotoxin
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 25 participants
- Where
- 1 siteUnited States
- Study dates
- 7 Feb 2018to 24 Mar 2018
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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.
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- 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.
- A non vasectomized, male subject must agree to use a condom with spermicide or abstain from sexual intercourse during the study until 90 days beyond the last dose of study drug. (No restrictions are required for a vasectomized male provided his vasectomy has been performed 4 months or more prior to first dose of study drug. A male who has been vasectomized less than 4 months prior to study first dose must follow the same restrictions as a non vasectomized male).
- If male, must agree not to donate sperm from the first dose until 90 days after last dosing.
- No clinically significant history or presence of ECG findings as judged by the PI at screening and check-in of Period 1, including each criterion as listed below:
- Normal sinus rhythm (heart rate between 50 bpm and 100 bpm inclusive);
- QTcF interval ≤ 450 msec;
- QRS interval ≤ 110 msec; if > 110 msec, result will be confirmed by a manual over read;
- PR interval ≤ 220 msec.
- Normal renal function (creatinine clearance from 80 to 180 mL/minute per Cockcroft-Gault equation; 24-hour urinary creatinine collection may be used for borderline cases).
- PEF of ≥ 80% per handheld meter and oxygen saturation of ≥ 95% by pulse oximetry.
- Understands the study procedures in the informed consent form (ICF), and be willing and able to comply with the protocol.
Who cannot join
- 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);
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- 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.
- Positive urine drug, cotinine, or alcohol results at screening or check in of Period 1.
- Positive results at screening for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV).
- Seated blood pressure is less than 90/40 mmHg or greater than 140/90 mmHg at screening.
- Seated heart rate is lower than 50 bpm or higher than 99 bpm at screening.
- Unable to refrain from or anticipates the use of any drug, including prescription and non prescription medications, herbal remedies, or vitamin supplements beginning 14 days prior to the first dose and throughout the study.
- Has been on a diet incompatible with the on study diet, in the opinion of the PI or designee, within the 30 days prior to the first dose and throughout the study.
- Donation of blood or significant blood loss within 56 days prior to the first dose.
- Plasma donation within 7 days prior to the first dose.
- Participation in another clinical study within 30 days prior to the first dose. The 30 day window will be derived from the date of the last blood collection or dosing, whichever is later, in the previous study to Day 1 of Period 1 of the current study.
Trial locations and contacts
1 site in 1 country.
About this study
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:
Read more
- 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.
- To demonstrate sensitivity of this QTc assay using moxifloxacin as a positive control.
- To confirm plasma pharmacokinetic (PK) of a single SC administration of TTX at various dose levels when administered to healthy adult subjects.
- 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
- Being tested
- Tetrodotoxin, Placebos
- Keywords
- TQT TTX Halneuron cardiac safety
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TetrodotoxinDrug
Also called Halneuron
A single TTX dose in a dose ascending study
PlacebosDrug
matching placebo comparator
| Study group | Role | What they receive |
|---|---|---|
| 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) Receives: 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 Receives: Drug: Placebos |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 24 hours
Secondary outcomes (3)
ECG Paramenters
Other ECG parameters such as QTc, QT, PR, and RR intervals, QRS duration, and HR
Measured: 24 hours
ECG Paramenters
Abnormalities in T wave morphology and pathologic U waves will be reported when identified by the cardiologist reviewer, as appropriate.
Measured: 24 hours
Assay Sensitivity
- Assay sensitivity assessment with ddQTc at the geometric mean Cmax value predicted from a linear mixed-effect model evaluating the relationship between QTc and moxifloxacin plasma concentrations (exposure-response modeling).
Measured: 24 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Sep 2019
- Study start7 Feb 2018
- Primary completion24 Mar 2018
- Study completion24 Mar 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for TQT StudyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- Wex Pharmaceuticals Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Celerion
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04083833
- Sponsor's protocol ID
- TTX-TQT-101
- Status last verified
- Sep 2019
- First submitted
- 6 Sep 2019
- Last updated
- 10 Sep 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Sep 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT04083833
- Acronym / sponsor ID
- TTX-TQT-101
- Conditions
- TQT Study
- Keywords
- TQT TTX Halneuron cardiac safety
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- Wex Pharmaceuticals Inc.Industry (pharma, biotech, devices)
- Collaborators
- Celerion
- Study start
- 7 Feb 2018 (actual)
- Primary completion
- 24 Mar 2018 (actual)
- Study completion
- 24 Mar 2018 (actual)
- First posted
- 10 Sep 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- 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.
- To demonstrate sensitivity of this QTc assay using moxifloxacin as a positive control.
- To confirm plasma pharmacokinetic (PK) of a single SC administration of TTX at various dose levels when administered to healthy adult subjects.
- 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.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Treatment Arm | Experimental | Drug: Tetrodotoxin(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) |
| Control | Placebo comparator | Drug: PlacebosTreatment 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 |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (25 listed)
- 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:
Key exclusion criteria (24 listed)
- 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:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TetrodotoxinAlso: HalneuronA single TTX dose in a dose ascending study | Drug | Treatment Arm |
| Placebosmatching placebo comparator | Drug | Control |
Primary outcome
Cardiodynamic
Time frame: 24 hours
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.
3 secondary outcomes
ECG Paramenters
Time frame: 24 hours
ECG Paramenters
Time frame: 24 hours
Assay Sensitivity
Time frame: 24 hours
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Sep 2019.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Tetrodotoxin in people with TQT Study, run by Wex Pharmaceuticals Inc. at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 25 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Sep 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Cardiodynamic (time frame: 24 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Sep 2019.