Clinical Study Aiming to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of a Single Administration of ZE50-0134 at 5 Dose Levels in Healthy Volunteers

NCT06787131 | Completed Phase 1

• 1 other identifier: ZE50-0134-0001
• Study Type: interventional
• Target: 104
• Locations: 1 country
• Sites: 1

Brief Summary

A first-in-human study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of single and multiple ascending doses of ZE50-0134 administered orally in healthy volunteers.

Conditions

Healthy

Keywords

Chronic lymphocytic leukemia; refractory chronic lymphocytic leukaemia; relapsed chronic lymphocytic leukaemia

Outcome Measures

Primary Outcomes (2)

• Plasma pharmacokinetics of ZE50-0134

  Plasma concentration, ng/mL

  Within 15 min prior to dosing with ZE50-0134/placebo to 168 hours post-dose

• Plasma pharmacokinetics of ZE50-0134 with and without rabeprazole (PPI)

  To evaluate and compare the PK profile of ZE50-0134 after single dose administration with and without rabeprazole (PPI) pre-dosing in healthy adult volunteers

  Within 60 min prior to dosing with ZE50-0134/placebo to 168 hours post-dose

Secondary Outcomes (1)

• Safety of ZE50-0134

  From the signing of the consent form until day 8 for all dose levels except level 2 + Itraconazole and until day 11 for dose level 2 + Itraconazole.

Study Arms (13)

Level 1 Single dose

EXPERIMENTAL

Dose level 1: 6 participants will receive 100 mg ZE50-0134 and 2 participants will receive placebo under fasted conditions.

Drug: ZE50-0134 or placebo

Level 2 Single dose

EXPERIMENTAL

Dose level 2: 6 participants will receive 200 mg ZE50-0134 and 2 participants will receive placebo under fasted conditions.

Drug: ZE50-0134 or placebo

Level 3 Single dose

EXPERIMENTAL

Dose level 3: 6 participants will receive 400 mg ZE50-0134 and 2 participants will receive placebo under fasted conditions.

Drug: ZE50-0134 or placebo

Level 4 Single dose

EXPERIMENTAL

Dose level 4: 6 participants will receive 800 mg ZE50-0134 and 2 participants will receive placebo under fasted conditions.

Drug: ZE50-0134 or placebo

Level 5 Single dose

EXPERIMENTAL

Dose level 5: 6 participants will receive 1600 mg ZE50-0134 and 2 participants will receive placebo under fasted conditions.

Drug: ZE50-0134 or placebo

Level 1 Single dose optional

EXPERIMENTAL

Dose level 1: 6 participants will receive 100 mg ZE50-0134 and 2 participants will receive placebo under fed conditions.

Drug: ZE50-0134 or placebo

Level 2 Single dose optional

EXPERIMENTAL

Dose level 2: 6 participants will receive 200 mg ZE50-0134 and 2 participants will receive placebo under fed conditions.

Drug: ZE50-0134 or placebo

Level 3 Single dose optional

EXPERIMENTAL

Dose level 3: 6 participants will receive 400 mg ZE50-0134 and 2 participants will receive placebo under fed conditions.

Drug: ZE50-0134 or placebo

Level 4 Single dose optional

EXPERIMENTAL

Dose level 4: 6 participants will receive 800 mg ZE50-0134 and 2 participants will receive placebo under fed conditions.

Drug: ZE50-0134 or placebo

Level 5 Single dose optional

EXPERIMENTAL

Dose level 5: 6 participants will receive 1600 mg ZE50-0134 and 2 participants will receive placebo under fed conditions.

Drug: ZE50-0134 or placebo

Level 2 Single dose + itraconazole

EXPERIMENTAL

Dose level 2: 6 participants will receive 200 mg ZE50-0134 and 2 participants will receive placebo under fasted conditions (to be administered in conjunction with itraconazole \[200 mg itraconazole to be administered twice per day \[BID\] on Day -4 and once per day \[QD\] on Days -3 to 8, inclusive)

Drug: ZE50-0134 or placebo; Drug: Itraconazole (200 mg)

Level 3 BID dosing

EXPERIMENTAL

Dose level 3 BID dosing: 6 participants will receive 400 mg of ZE50-0134 administered BID and 2 participants will receive placebo under fasted conditions.

Drug: ZE50-0134 or placebo

Level 3 Single dose + Rabeprazole

EXPERIMENTAL

Dose level 3: 6 participants will receive 400 mg ZE50-0134 and 2 participants will receive placebo under fasted conditions (to be administered in conjunction with rabeprazole \[rabeprazole 20 mg once daily (QD) on Day 1 and Day 2\]).

Drug: ZE50-0134 or placebo; Drug: Rabeprazole 20 mg

Interventions

ZE50-0134 or placebo DRUG

The patients will receive ZE50-0134 or placebo.

Level 1 Single dose; Level 1 Single dose optional; Level 2 Single dose; Level 2 Single dose + itraconazole; Level 2 Single dose optional; Level 3 BID dosing; Level 3 Single dose; Level 3 Single dose + Rabeprazole; Level 3 Single dose optional; Level 4 Single dose; Level 4 Single dose optional; Level 5 Single dose; Level 5 Single dose optional

Rabeprazole 20 mg DRUG

Rabeprazole 20 mg once daily (QD) on Day 1 and Day 2.

Level 3 Single dose + Rabeprazole

Itraconazole (200 mg) DRUG

Itraconazole 200 mg twice per day.

Level 2 Single dose + itraconazole

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.
• Adult males and females, 18 to 55 years of age (inclusive) at screening.
• Body mass index (BMI) ≥ 18.0 and ≤ 32.0 kg/m2, with a body weight (to 1 decimal place) ≥ 50.0 kg (males) or 45.0 kg (females) at screening.
• 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:
• Physical examination without any clinically significant findings.
• Systolic blood pressure in the range of 90 mm Hg to 160 mm Hg; diastolic blood pressure in the range of 40 mm Hg to 95 mm Hg.
• Heart rate (HR) in the range of 40 to 100 bpm after 5 minutes in a supine or semi-supine position
• Body temperature (tympanic or oral) in the range 35.5°C to 37.7°C (inclusive).
• No clinically significant findings in serum chemistry, hematology, coagulation and urinalysis tests as judged by the Investigator, including the following specific findings:
• i. Hemoglobin and platelet 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/semi-supine for at least 10 minutes) with average QTcF ≤ 450 msec for males and ≤ 470 msec for females and no clinically significant abnormalities.
• Female volunteers must:
• 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
• 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.
• 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.

You may not qualify if:

• History or presence of significant cardiovascular, pulmonary, hepatic, renal, hematological, 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. Note: participants with a history of fully resolved childhood asthma are permitted.
• Acute infections within 4 weeks prior to Day -1 (nominal Cohorts 1-10) or Day -4 (nominal Cohort 11), or current infection that requires systemically absorbed antibiotic, antifungal, antiparasitic or antiviral medications.
• 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. Note: participants with Gilbert's syndrome may be permitted, at the discretion of the PI (or delegate). Participants with a history of cholecystectomy may be permitted at the discretion of the PI (or delegate).
• Any history of malignant disease in the last 5 years (excludes surgically resected skin squamous cell or basal cell carcinoma)
• Any screening laboratory result outside the normal laboratory reference range (as confirmed upon repeated testing) and deemed clinically significant by the PI.
• Presence of clinically relevant immunosuppression from, but not limited to, immunodeficiency conditions such as common variable hypogammaglobulinemia.
• 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 first study drug administration.
• 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 28 days (whichever is longer) prior to first study drug administration. Note: timeframe = 3 days for grapefruit and grapefruit products or other foods/drinks (e.g. pomelo) that may have a clinically significant interaction with CYP3A4.
• History of risk factors for torsade de pointes (including a family history of long QT syndrome or sudden cardiac death) or clinically significant arrythmia.
• Participant is planning to have surgery between Screening and the EoS visit.
• Positive test results for active human immunodeficiency virus (HIV-1 or HIV-2), hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibodies, or tuberculosis (TB) at the screening visit.
• History of latent or active TB infection, or signs or symptoms suggestive of active TB infection upon medical history and/or physical examination.
• Estimated creatinine clearance \< 60 mL/min using the Cockcroft-Gault formula.
• 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.
• History of alcohol consumption in the 4 days prior to dosing.

Sponsors & Collaborators

• Lomond Therapeutics Holdings, Inc.: lead

Study Sites (1)

Scientia Clinical Research

Sydney, Randwick NSW, 2031, Australia

Location

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, B-Cell

Interventions

Rabeprazole; Itraconazole

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

2-Pyridinylmethylsulfinylbenzimidazoles; Sulfoxides; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Triazoles; Azoles; Piperazines

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 16, 2025
• First Posted: January 22, 2025
• Study Start: May 21, 2024
• Primary Completion: July 4, 2025
• Study Completion: July 4, 2025
• Last Updated: December 5, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)