A Randomised, Double-Blind, Placebo-Controlled, First-in-Human Study of Orally Administered 83-0060 to Evaluate the Safety, Tolerability, and Pharmacokinetics of Single and Multiple Ascending Doses of 83-0060 in Healthy Volunteers

Phase 1

Recruiting

Conditions: SARS-CoV-2
Respiratory - Other respiratory disorders / diseases

Registration Number: ACTRN12624000220561

Lead Sponsor: Trawsfynydd Therapeutics AU Pty Ltd

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Recruiting

Sex: All

Target Recruitment: 64

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 65 years of age (inclusive) at screening.
3. Body mass index (BMI) greater than or equal to 18.5 and less than or equal to 32.0 kg/m2, with a body weight (to 1 decimal place) greater than or equal to 50.0 kg at screening.
4. Medically healthy without clinically significant abnormalities (in the opinion of the Investigator) at the screening visit and prior to dosing at the timepoints indicated in the Schedule of Assessments, including:
a. Physical examination without any clinically significant findings in the opinion of the investigator.
b. Systolic blood pressure in the range of 90 mm Hg to 160 mm Hg; diastolic blood pressure in the range of 50 mm Hg to 95 mm Hg.
c. HR in the range of 45 to 100 bpm after 5 minutes in a supine position
d. Body temperature (tympanic or oral) in the range 35.5°C to 37.5°C (inclusive).
e. No clinically significant findings in serum chemistry, haematology, coagulation and urinalysis tests as judged by the Investigator, including the following specific findings:
i. Haemoglobin, platelet count, WBC count, lymphocyte count, and neutrophil count within normal ranges (as per local laboratory standard ranges), WBC count (> 3.0 x 109/L), lymphocyte count (> 1.0 x 109/L), and neutrophil count (> 1.5 x 109/L)
ii. AST, ALT and total bilirubin < 1.5 x ULN (note: for participants with Gilbert’s syndrome, ULN is considered to be 2.9 mg/ml).
f. Triplicate 12-lead ECG (taken after the volunteer has been supine for at least 5 minutes) with a QTcF less than or equal to 450 msec for males and less than or equal to 470 msec for females and no clinically significant abnormalities.
5. Be willing to refrain from smoking (including tobacco, nicotine replacement therapy, e-cigarettes and marijuana) between the Screening visit and discharge from the clinic.
6. Female volunteers, 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 >40 IU/L at the screening visit), or
b. If of childbearing potential, must:
i. Have a negative pregnancy test at the screening visit and on admission to the clinic on Day-1.
ii. Agree not to attempt to become pregnant or donate ova from signing the consent form until at least 30 days after the last dose of the study drug.
iii. Agree to use adequate contraception (defined as use of a condom by the male partner combined with use of a highly effective method of contraception) from one month prior to screening until at least 30 days after the last dose of study drug, if not exclusively in a same-sex relationship or abstinent as a committed lifestyle
7. Male volunteers, must:
a. Agree not to donate sperm from signing the consent form until at least 90 days days after the last dose of study drug.
b. If engaging in sexual intercourse with a female partner who could become pregnant, agree to use adequate contraception (defined as use of a condom combined with use of a highly effective method of contraception) from signing the consent form until at least 90 days after the last d

Exclusion Criteria

1. History or presence of significant cardiovascular, pulmonary, hepatic, renal, haematological, gastrointestinal, endocrine, immunologic, dermatologic or neurological disease, including any acute illness or major surgery within the past 3 months determined by the PI to be clinically significant.
2. History of surgery or hospitalisation within 30 days prior to screening, or surgery planned during the study.
3. Acute infections within 4 weeks prior to screening or current infection that requires systemically absorbed antibiotic, antifungal, antiparasitic or antiviral medications.
4. Presence or history of any abnormality or illness, including gastrointestinal surgery, which in the opinion of the PI may affect absorption, distribution, metabolism or elimination of the study drug.
5. Any history of malignant disease in the last 5 years (excludes surgically resected skin squamous cell or basal cell carcinoma).
6. Any screening laboratory result outside the normal laboratory reference range (as confirmed upon repeated testing) and deemed clinically significant by the PI.
7. Presence of clinically relevant immunosuppression from, but not limited to, immunodeficiency conditions such as common variable hypogammaglobulinemia.
8. Use of or plans to use systemic immunosuppressive (e.g., corticosteroids by any route, methotrexate, azathioprine, cyclosporine) or immunomodulating medications (e.g., interferon) during the study or within 5 half-lives of individual agent or within 28 days (whichever is longer) prior to dosing.
9. Use of or plans to use agents (e.g., grapefruit and grapefruit products) that have clinically significant interaction with CYP3A4 or the use of any medications that could have a significantly impact on organ function (e.g., barbiturates, omeprazole, cimetidine) during the study or within 5 half-lives of individual agent or within 7 days (whichever is longer) prior to dosing.
10. History of risk factors for torsade de pointes (including a family history of long QT syndrome or sudden cardiac death) or clinically significant arrythmia.
11. Positive test results for active human immunodeficiency virus (HIV-1 or HIV-2), hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibodies at the screening visit.
12. Presence or having sequelae of gastrointestinal, liver, kidney, or other conditions known to interfere with the absorption, distribution, metabolism, or excretion of drugs.
13. Estimated creatinine clearance < 60 mL/min using the Cockcroft-Gault formula.
14. Creatine kinase >2.0 x ULN at Day -1. If abnormal values are obtained, the assessment may be repeated once.
15. History of any drug or alcohol abuse in the past 2 years defined as >21 units of alcohol per week for males and >14 units of alcohol per week for females. Where 1 unit = 360 mL of beer, 150 mL wine, or 30 mL of spirits.
16. History of alcohol consumption in the 4 days prior to dosing.
17. Positive drugs of abuse, or alcohol breath test results at the screening visit or at check-in (Day -1).
18. Use of any prescription medications within 14 days or at least 5 half-lives of the medication (whichever is longer) prior to the first study drug administration, and use of any over-the-counter medication (including herbal products, nutritional, diet aids, vitamin supplements, minerals and hormone supplements) within 7 days or at least 5 half-lives of the medication (whichever is longer) prior to the first study drug administration, with the excep