Evaluation of sensory testing to measure the effects of tetrodotoxin

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Leiden University Medical Center

Participant type

Healthy volunteers

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10], Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Anesthesia and Analgesia [E03]

Trial duration

30 Aug 2023 → 26 Feb 2024

Decision date (initial)

2023-07-21

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

WEX Pharmaceuticals Inc

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Dose response, Efficacy

To evaluate the effect on the peripheral nervous system using Quantitative Sensory Testing (QST) when two different doses of Halneuron (Tetrodotoxin (TTX) for Injection) are administered to healthy subjects.

Secondary objectives 4

1. To determine key QST tests providing greatest sensitivity of changes using various TTX dose levels.
2. To investigate whether Halneuron administration affects olfaction.
3. To investigate any correlation with QST results to adverse events reported.
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.

Conditions and MedDRA coding

pain

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Willingness to adhere to protocol requirements as evidenced by a valid informed consent form (ICF) duly signed by the subject.
2. Generally healthy males and females, between 18 and 55 years of age (inclusive) with a body mass index (BMI) within 19-30 kg/m2.
3. Minimum weight of 50 kg.
4. Normal renal function (creatinine clearance from 80 to 180 mL/min per Cockroft-Gault equation.
5. Clinical laboratory values within the laboratory's stated normal range. If not within this range, they must be considered not clinically significant by an investigator and must be recorded as such in the CRF.
6. Physical examination within normal limits or considered not clinically significant by an Investigator.
7. Supine blood pressure ≥ 100/60 mmHg and ≤ 160/100 mmHg and pulse rate > 50 bpm and < 100 bpm after 5 minutes of rest, at screening. Repeat measurements are allowed if initial readings are considered unrepresentative by the PI.
8. Nonsmoker or ex-smoker (for a minimum of 6 months).
9. Women of childbearing potential and men must agree to use adequate contraception in the opinion of an investigator (e.g., hormonal or double-barrier method of birth control; abstinence) during the duration of study participation.

Exclusion criteria 24

1. Significant history of hypersensitivity to fish or tetrodotoxin or any related products.
2. History of anaphylaxis to a medication, dietary item, or environmental exposure (including bee stings).
3. History of multiple, clinically significant drug allergies
4. Presence or history of significant gastrointestinal, liver, or kidney disease, or any other conditions known to interfere with the absorption, distribution, metabolism or excretion of drugs or known to potentiate or predispose to undesired effects.
5. History of an obstructive pulmonary disease including asthma, emphysema, or chronic bronchitis.
6. History or presence of any disorder resulting in clinically significant restrictive pulmonary disease.
7. History or presence of Guillain-Barre syndrome, multiple sclerosis, myasthenia gravis, muscular dystrophy, or other neuropathy or myopathy.
8. A clinically significant deficiency on the neurological part of the physical exam prior to enrollment.
9. Diagnosis or symptoms suggesting central nervous system (CNS) disorders and peripheral nervous system disorders.
10. History of seizure disorder, concussion, or other clinically significant head or spine injury.
11. Presence or history of significant cardiovascular, hematologic, psychiatric, endocrine, immunologic or dermatologic disease.
12. History of malignancy.
13. History of alcoholism considered excessive in the opinion of an investigator, within 12 months, or routine use of ethanol averaging > 3 units of alcohol per day.
14. Maintenance therapy with any drug, or significant history of drug dependency, including prescription drug abuse.
15. Any clinically significant illness in the previous 28 days before Day 1 of this study. A significant illness is an illness requiring hospitalization or an event that in the opinion of the Investigator no longer classifies the subject as a “healthy volunteer”.
16. Use of Botox (Botulinum Toxin Type A) in the past 3 months.
17. Local or systemic exposure to lidocaine.
18. The use of antidepressants or anticonvulsants with known voltage-gated sodium channel activity.
19. Participation in another clinical trial with drug or device in the previous 30 days.
20. Positive for human immunodeficiency virus (HIV) infection.
21. Diagnosed with hepatitis B or hepatitis C virus infection.
22. Females with a positive urine pregnancy test at screening, who are lactating, or at risk of pregnancy (i.e., sexually active with fertile males and not using an adequate form of birth control).
23. Subjects with loss or donation of 50 mL or more of blood in the previous 28 days before Day 1 of this study, or 500mL or more of blood in the previous 56 days before Day 1 of this study.
24. Any condition which makes a candidate unsuitable for study participation, in the opinion of the PI.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The change from baseline in all individual QST sensory measurements at 1-hour post-dose for each dose administered.

Secondary endpoints 4

1. To compare the change at 1-hour post-dose from baseline in the different QST sensory test measurements between the two doses administered.
2. The change from baseline of the odor identification and odor threshold test at 1 hour post-dose for each dose administered.
3. The change from baseline in the hypoxic ventilatory response at 1-hour post-dose for each dose administered.
4. To compare adverse events reported to changes in QST measurements

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Leiden University Medical Center

Sponsor organisation

Leiden University Medical Center

Address

Albinusdreef 2

City

Leiden

Postcode

2333 ZA

Country

Netherlands

Scientific contact point

Organisation

Leiden University Medical Center

Contact name

Monique van Velzen

Public contact point

Organisation

Leiden University Medical Center

Contact name

Monique van Velzen

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 2 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications