None listed
Conditions
Brief summary
This research project is being conducted to look at the safety, tolerability and pharmacokinetics (PK, how the human body processes a substance) of TTI-0102 when given to healthy volunteers orally as a single dose, compared with a single oral dose of the marketed product Cystagon (registered trademark). It is proposed that TTI-0102 could be used as a treatment for acute respiratory distress syndrome (ARDS) related to COVID-19 infection.
Interventions
TTI-0102 will be given as an oral solution, TTI-0102 drug product (powder) dissolved in 240mL sterile water.
The planned treatments are:
Cohort 1: Cystagon (registered trademark) 600mg once on Day 1, then TTI-0102 1300mg once on Day 3.
Cohort 2: Cystagon (registered trademark) 600mg once on Day 1, then TTI-0102 2600mg once on Day 3.
Cohort 3: Cystagon (registered trademark) 600mg once on Day 1, then TTI-0102 2600mg given as 1300mg in the morning and 1300mg 12 hours later on
Day 3.
The decision
TTI-0102 will be given as an oral solution, TTI-0102 drug product (powder) dissolved in 240mL sterile water. The planned treatments are: Cohort 1: Cystagon (registered trademark) 600mg once on Day 1, then TTI-0102 1300mg once on Day 3. Cohort 2: Cystagon (registered trademark) 600mg once on Day 1, then TTI-0102 2600mg once on Day 3. Cohort 3: Cystagon (registered trademark) 600mg once on Day 1, then TTI-0102 2600mg given as 1300mg in the morning and 1300mg 12 hours later on Day 3. The decision to dose escalate to Cohort 2 will be made by the Safety Review Committee (SRC). The decision to move to twice daily TTI-0102 dosing in Cohort 3 will be made by the SRC. Adherence to the study treatments will be monitored by inpatient stay and observation; participants will be confined to the study unit from check-in on Day -1 through to discharge on Day 4 (24 hours post last dose).
Sponsors
Thiogenesis Therapeutics, Inc.
Study design
Allocation
Non-randomised trial
Intervention model
Other
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to 64 Years
Healthy volunteers
Yes
Inclusion criteria
1. Must have given written informed consent before any study-related activities are carried out and must be able to understand the full nature and purpose of the trial, including possible risks and adverse effects. 2. Adult males and females, 18 to 64 years of age (inclusive) at screening. 3. Body mass index greater than or equal to 19.0 and less than or equal to 31.0 kg/metres squared, with a body weight greater than or equal to 60.0 and less than or equal to 85.0 kg at screening. 4. Be nonsmokers (including tobacco, e-cigarettes and marijuana) for at least 1 month prior to first study drug administration. 5. Medically healthy without clinically significant (in the opinion of the Investigator) abnormalities at screening and pre-dose on Day 1, including: a. Physical examination without any clinically relevant findings; b. Systolic blood pressure in the range of 90 to 160 mmHg and diastolic blood pressure in the range of 50 to 95 mmHg after 5 minutes in supine position; c. Heart rate (HR) in the range of 45 to 100 bpm after 5 minutes rest in supine position; d. Body temperature, between 35.5°C and 37.7°C; e. No clinically significant findings in serum chemistry, hematology, coagulation and urinalysis tests as judged by the investigator. 6. Conventional 12-lead electrocardiogram (ECG) recording in triplicate (the mean of triplicate measurements will be used to determine eligibility at screening and pre-dose on Day 1) consistent with the PI assessment of a normal cardiac conduction and function, including the following criteria: a. Normal sinus rhythm with HR between 45 and 100 bpm, inclusive; b. QT interval corrected using the Fridericia method (QTcF) less than or equal to 450 msec for males or less than or equal to 470 msec for females; c. QRS duration of less than 120 msec; d. PR interval of less than or equal to 220 msec; e. Electrocardiogram morphology consistent with healthy cardiac ventricular conduction and normal rhythm, and with measurement of the QT interval; f. No family history of short or long QT syndrome; g. No history of risk factors for torsade de pointes or the diagnosis; 7. Female participants must: a. Be of nonchildbearing potential (i.e., surgically sterilised [hysterectomy, bilateral salpingectomy, bilateral oophorectomy at least 6 weeks before screening]) or postmenopausal (where postmenopausal is defined as no menses for 12 months without an alternative medical cause, and a follicle-stimulating hormone [FSH] level greater than 40 IU/L at the screening visit), or b. If of childbearing potential, must agree not to donate ova, not to attempt to become pregnant and, if engaging in sexual intercourse with a male partner, must agree to use an acceptable method of contraception (refer to Appendix 5) from signing the consent form until at least 30 days after the last dose of the study drug. 8. Male participants, if not surgically sterilized, must be willing not to donate sperm and, if engaging in sexual intercourse with a female partner who could become pregnant, must be willing to use a condom in addition to having the female partner use a highly effective contraceptive method from signing the consent form until at least 90 days after the last dose of study drug. 9. Have suitable venous access for blood sampling. 10. Be willing and able to comply with all study assessments and adhere to the protocol schedule and restrictions.
Exclusion criteria
1. Allergy to any medicine containing mercaptamine, penicillamine or known hypersensitivity to any of the study drug ingredients. 2. Evidence of or verbal attestation of Helicobacter pylori infection, presently, or within the last 90 days prior to Screening. 3. Participants who have had a kidney transplant or are planning or are a registered candidate for a kidney transplant within 3 months of the Screening or have a serum creatinine that is not within local lab normal range or less than or equal to 1.5x ULN. 4. Participants with known hypersensitivity to cysteamine. 5. Patients with a haemoglobin level that is not within local lab normal range or less than or equal to 1.5x ULN. 6. History or presence of significant cardiovascular, pulmonary, hepatic, renal, hematological, gastrointestinal, endocrine, immunologic, dermatologic or neurological disease, including any acute illness or surgery within the past 3 months determined by the PI to be clinically relevant. 7. Current infection that requires antibiotic, antifungal, antiparasitic or antiviral medications. 8. Any history of malignant disease in the last 10 years (excludes surgically resected skin squamous cell or basal cell carcinoma). 9. Liver function test results (ie, aspartate aminotransferase [AST], alanine aminotransferase [ALT], and gamma glutamyl transferase [GGT]) and total bilirubin must not be elevated more than within local lab normal range or more than 1.5-fold above the upper limit of normal (ULN). 10. Positive test results for active human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV) antibodies. 11. Presence or having sequelae of gastrointestinal, liver, kidney, or other conditions known to interfere with the absorption, distribution, metabolism, or excretion of drugs. 12. Estimated creatinine clearance (CrCl) less than 60 mL/min using the Cockcroft-Gault formula. 13. History of substance abuse or alcohol abuse (defined as more than 10 standard drinks per week or regularly consuming more than 4 standard drinks on any one day; where 1 standard drink is 10 g of pure alcohol and is equivalent to 285 mL beer [4.9% Alc./Vol], 100 mL wine [12% Alc./Vol], 30 mL spirit [40% Alc./Vol]) during less than or equal to 12 months prior to the screening visit. 14. Positive drug or alcohol test results at the screening visit or at check-in (Day -1) (may be repeated once, if a positive test was recorded in the first instance, at the discretion of the PI). 15. Use of any prescription or over-the-counter medication (including herbal products, diet aids, and hormone supplements) within 10 days or 5 half-lives of the medication (whichever is longer) prior to the first study drug administration, except occasional use of paracetamol. 16. Use of any live vaccinations within 30 days prior to the first study drug administration except for the influenza vaccine. 17. For women of childbearing potential, a positive serum pregnancy test at screening or a positive urine pregnancy test with confirmatory serum pregnancy test on Day -1. 18. Donation of blood or plasma within 30 days prior to first study drug administration, or loss of whole blood of more than 500 mL within 30 days prior to randomization, or receipt of a blood transfusion within 1 year of first study drug administration. 19. Participation in another investigational clinical trial within 60 days prior to the first study drug administration. 20. Any other condition or prior therapy that in the opinion of the PI would make the volunteer unsuitable for this study, including inability to cooperate fully with the requirements of the study protocol or likelihood of noncompliance with any study requirements.
Outcome results
None listed