A Randomised, Double-Blind, Placebo-Controlled, First-in-Human Study of the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single and Multiple Ascending Doses of ZE46 0134 in Healthy Volunteers

Phase 1

Recruiting

Conditions: Cancer
Cancer - Leukaemia - Acute leukaemia

Registration Number: ACTRN12623000871640

Lead Sponsor: Eilean Therapeutics

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Recruiting

Sex: All

Target Recruitment: 80

Inclusion Criteria

Healthy volunteers will be included in Part A and Part B of the study if they satisfy all of the following 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 55 years of age (inclusive) at screening.
3.Body mass index 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 kg at screening.
4.Medically healthy without clinically significant abnormalities (in the opinion of the PI) at the screening visit and prior to dosing at the timepoints indicated, including:
a.Physical examination without any clinically significant findings.
b.Systolic blood pressure in the range of 90 mm Hg to 140 mm Hg; diastolic blood pressure in the range of 40 mm Hg to 90 mm Hg.
c.Heart rate in the range of 40 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.Serum chemistry, haematology, coagulation and urinalysis tests within normal ranges at screening.
f. Additional inclusion criteria for study Part A (Itraconazole administration in SAD Cohort 6 only): ALT, AST, ALP and gamma-glutamyltransferase (GGT) must be normal (within reference range).
g.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 nonsmokers (including tobacco, e-cigarettes and marijuana) for at least 3 months prior to first study drug administration (self-reported to investigator) at screening visit, on Day -4 (SAD Cohort 6 only) and at check-in on Day -1.
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 level >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 from signing the consent form until at least 30 days after the last dose of the study drug.
7.Male volunteers must agree not to donate sperm and, if engaging in sexual intercourse with a female partner who could become pregnant, must agree to use an acceptable method of contraception from signing the consent form until at least 90 days after the last dose of study drug.
8.Have suitable venous access for blood sampling.
9.Be willing and able to comply with all study assessments and adhere to the protocol schedule and restrictions.

Exclusion Criteria

Healthy volunteers will be excluded from Part A or Part B of this study if there is evidence of any of the following at the screening visit or prior to dosing:
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.Acute infections within 4 weeks prior to the screening or current infection that requires systemically absorbed antibiotic, antifungal, antiparasitic or antiviral medications.
3.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.
4.Any history of malignant disease in the last 10 years (excludes surgically resected skin squamous cell or basal cell carcinoma).
5.Any screening laboratory result outside the normal laboratory reference range and as confirmed upon repeated testing, and deemed clinically significant by the PI.
6.Presence of clinically relevant immunosuppression from, but not limited to, immunodeficiency conditions such as common variable hypogammaglobulinemia.
7.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 prior to enrolment.
8.Use of or plans to use agents that have clinically significant interaction with cytochrome P450 3A4 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 28 days prior to enrolment.
9.History of risk factors for torsade de pointes (including a family history of long QT syndrome or sudden cardiac death) or a known arrythmia.
10.Participant is planning to have surgery between Screening and the end of study visit.
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 (CrCl) < 60 mL/min using the Cockcroft-Gault formula.
14.Creatine kinase >1.5 x ULN at screening visit (SAD Cohort 6 only) or on Day -1.
15.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]) within 12 weeks prior to the screening visit.
16.History of alcohol consumption in the 4 days prior to Screening.
17.Positive drugs of abuse, cotinine or alcohol breath test results at the screening visit, on Day -4 (SAD Cohort 6 only) or at check-in (Day -1).
18.Use of any prescription or over-the-counter medication (including herbal products, diet aids, and hormone supplements) within 14 days prior to the first study drug administration, including oral contraceptives (with the excep