None listed
Conditions
Brief summary
This is a double-blind, placebo-controlled study to assess the safety of ZE75-0267 and how this drug acts in the body in healthy volunteers. ZE75-0267 may be indicated for use in patients with Parkinson's disease, but a trial of the drug in healthy volunteers is needed before trials in Parkinson's disease patients can proceed. Who is it for? You may be eligible for this study if you are aged 18 to 65 years and are in good general health without a clinically significant medical history. Study details All healthy volunteer participants who choose to enrol in this study will be assigned by chance to receive single or multiple doses of ZE75-0267 or placebo. All participants will have their vital signs checked (heart rate, blood pressure, temperature, etc), and will provide blood and urine samples for testing. It is hoped this research will determine the maximum dose of ZE75-0267 that can be administered safely without causing severe reactions. Once the dose of ZE75-0267 has been determined in healthy volunteers, a trial investigating the efficacy of ZE75-0267 as a treatment for patients with Parkinson's disease may proceed.
Interventions
This is a double-blind, randomised, placebo-controlled study evaluating the safety, tolerability, and pharmacokinetics (PK) of ZE75-0267. The study will be conducted in 2 parts: a single ascending dose (SAD) part (Part A) at up to 6 dose levels and a multiple ascending dose (MAD) part (Part B) at up to 4 dose levels. Evaluation of dose levels will be conducted in a sequential fashion with lower dose levels evaluated first in the sequence. Participants will only be allowed to enroll in either Par
This is a double-blind, randomised, placebo-controlled study evaluating the safety, tolerability, and pharmacokinetics (PK) of ZE75-0267. The study will be conducted in 2 parts: a single ascending dose (SAD) part (Part A) at up to 6 dose levels and a multiple ascending dose (MAD) part (Part B) at up to 4 dose levels. Evaluation of dose levels will be conducted in a sequential fashion with lower dose levels evaluated first in the sequence. Participants will only be allowed to enroll in either Part A or B of the study. Part A: Each cohort will enroll 8 participants with 6 participants randomized to receive ZE75-0267 and 2 participants randomized to receive placebo on Day 1. There will be 6 cohorts and ZE75-0267 will be administered at the following dose levels: •SAD Cohort 1: 50 mg oral capsules (under fasted conditions) •SAD Cohort 2: 100 mg oral capsules (under fasted conditions) •SAD Cohort 3: 25 mg oral capsules (under fasted & fed conditions) •SAD Cohort 4: 25mg oral liquid (under fasted conditions) •SAD Cohort 5: TBC oral liquid (under fasted conditions) •SAD Cohort 6 (optional): TBC oral liquid (under fasted conditions) The dose level for SAD Cohorts 5-6 will be decided based on review of the safety data from the current and the previous cohort(s) and trailing PK data by the SRC. SAD Cohort 3 – food effect cohort: Single oral dose of ZE75-0267 or placebo administered on Day 1 under fasted conditions and another single oral dose administered on Day 15 under fed conditions (total of 2 doses). After an overnight fast of 10 hours, a high fat, high calorie meal will be consumed consisting of: 1. Two eggs fried in butter 2. Two rashers of bacon 3. Two slices of toast with 16 g butter per slice 4. 125 g of hash browns 5. 240 mL of full cream milk Part B: MAD Cohort 1 will enrol 8 participants each with 6 participants randomised to receive ZE75-0267 50 mg and 2 participants randomised to receive placebo once daily on Days 1 to 10 (total of 10 doses). MAD Cohort 2 will enrol 8 participants with all participants to receive ZE75-0267 25mg once daily on Days 1 to 10. MAD Cohort 3 and Cohort 4 will enrol 8 participants to receive ZE75-0267 or placebo oral liquid once daily for 10 or 14 days. Following review by the SRC of PK and PD data, it may be decided that MAD Cohort 3 and Cohort 4 participants be randomised to receive ZE75-0267 (6 participants) or placebo (2 participants) or all participants be assigned to receive active ZE75-0267. The dose will not exceed what has previously been studied. Study drug will be administered at the study site by trained study site personnel to ensure compliance.
This is a double-blind, randomised, placebo-controlled study evaluating the safety, tolerability, and pharmacokinetics (PK) of ZE75-0267. The study will be conducted in 2 parts: a single ascending dose (SAD) part (Part A) at up to 8 dose levels and a multiple ascending dose (MAD) part (Part B) at up to 4 dose levels. Evaluation of dose levels will be conducted in a sequential fashion with lower dose levels evaluated first in the sequence. Participants will only be allowed to enroll in either Par
This is a double-blind, randomised, placebo-controlled study evaluating the safety, tolerability, and pharmacokinetics (PK) of ZE75-0267. The study will be conducted in 2 parts: a single ascending dose (SAD) part (Part A) at up to 8 dose levels and a multiple ascending dose (MAD) part (Part B) at up to 4 dose levels. Evaluation of dose levels will be conducted in a sequential fashion with lower dose levels evaluated first in the sequence. Participants will only be allowed to enroll in either Part A or B of the study. Part A: Each cohort will enroll 8 participants with 6 participants randomized to receive ZE75-0267 and 2 participants randomized to receive placebo on Day 1. There will be 8 cohorts and ZE75-0267 will be administered at the following dose levels: •SAD Cohort 1: 50 mg oral capsules (under fasted conditions) •SAD Cohort 2: 100 mg oral capsules (under fasted conditions) •SAD Cohort 3: 25 mg oral capsules (under fasted & fed conditions) •SAD Cohort 4: 25mg oral liquid (under fasted conditions) •SAD Cohort 5: 100 mg oral liquid (under fasted conditions) •SAD Cohort 6: 30 mg oral tablet (under fasted conditions) •SAD Cohort 7 (optional): TBC* oral tablet (under fasted conditions) •SAD Cohort 8 (optional): TBC* oral tablet (under fasted conditions) *Nominal dose levels The dose level for SAD Cohorts 7-8 will be decided based on review of the safety data from the current and the previous cohort(s) and trailing PK data by the SRC. SAD Cohort 3 – food effect cohort: Single oral dose of ZE75-0267 or placebo administered on Day 1 under fasted conditions and another single oral dose administered on Day 15 under fed conditions (total of 2 doses). After an overnight fast of 10 hours, a high fat, high calorie meal will be consumed consisting of: 1. Two eggs fried in butter 2. Two rashers of bacon 3. Two slices of toast with 16 g butter per slice 4. 125 g of hash browns 5. 240 mL of full cream milk Part B: MAD Cohort 1 will enrol 8 participants each with 6 participants randomised to receive ZE75-0267 50 mg and 2 participants randomised to receive placebo once daily on Days 1 to 10 (total of 10 doses). MAD Cohort 2 will enrol 8 participants with all participants to receive ZE75-0267 25mg once daily on Days 1 to 10. MAD Cohort 3 and Cohort 4 will enrol 8 participants to receive ZE75-0267 or placebo oral tablet once daily for 10 or 14 days. Following review by the SRC of PK and PD data, it may be decided that MAD Cohort 3 and Cohort 4 participants be randomised to receive ZE75-0267 (6 participants) or placebo (2 participants) or all participants be assigned to receive active ZE75-0267. The dose will not exceed what has previously been studied. Study drug will be administered at the study site by trained study site personnel to ensure compliance.
Sponsors
Brenig Therapeutics AU Pty Ltd. (subsidiary of Brenig Therapeutics )
Study design
Allocation
Randomised controlled trial
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver)
Eligibility
Sex/Gender
All
Age
18 Years to 65 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 65 years of age (inclusive) at screening. 3. Body mass index (BMI) greater than or equal to 18.0 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 for males or greater than or equal to 45 kg for females at screening. 4. Medically healthy without clinically significant abnormalities (in the opinion of the PI [or delegate]) 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 149 mm Hg; diastolic blood pressure in the range of 50 mm Hg to 90 mm Hg. c. HR in the range of 40 to 100 bpm after 5 minutes in a supine or semi-supine position d. Body temperature (tympanic or oral) in the range 35.5°C to 37.5°C (inclusive). e. Triplicate 12-lead ECG (taken after the volunteer has been supine or semi-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. f. No clinically significant findings in serum chemistry, haematology, coagulation, and urinalysis tests. 5. Female volunteers, must: a. Must be of non-childbearing potential i.e., surgically sterilised (hysterectomy, bilateral salpingectomy, bilateral oophorectomy) at least 6 weeks before the screening visit or postmenopausal (where postmenopausal is defined as no menses for 12 months without an alternative medical cause and a follicle-stimulating hormone (FSH) level consistent with postmenopausal status, per local laboratory guidelines), or b. If of childbearing potential, must: i. Have a negative pregnancy test at the screening visit and on admission to the study site 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 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 6. Male volunteers, must: a. Agree not to donate sperm from signing the consent form until at least 90 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 dose of study drug. c. If engaging in sexual intercourse with a female partner who is not of childbearing potential or a same-sex partner, agree to use a condom from signing the consent form until at least 3 days after the last dose of study drug. 7. Have suitable venous access for blood sampling. 8. Be willing and able to comply with all study assessments and adhere to the protocol schedule and restrictions. 9. [Part A SAD and Part B MAD, select cohorts undergoing CSF collection] Participant is willing and able to undergo lumbar puncture and have no contraindications to the procedure.
Exclusion criteria
1. Known hypersensitivity to the study drug or any of the study drug ingredients. 2. History of anaphylaxis or other significant allergy which, in the opinion of the PI (or delegate), would interfere with the volunteer’s ability to participate in the study. 3. History or presence of clinically significant cardiovascular, pulmonary, hepatic, renal, haematological, gastrointestinal, endocrine, immunologic, dermatologic, psychiatric, or neurological disease/disorder, including any acute illness, within the past 3 months determined by the PI (or delegate) to be clinically relevant. 4. History of surgery or hospitalisation within 3 months prior to screening, or surgery planned during the study. 5. Any history of malignant disease in the last 10 years (excludes surgically resected skin squamous cell or basal cell carcinoma). 6. Presence of clinically relevant immunosuppression from, but not limited to, immunodeficiency conditions such as common variable hypogammaglobulinemia. 7. History of risk factors for torsade de pointes (including a family history of long QT syndrome or sudden cardiac death) or a known arrythmia. 8. Presence or having sequelae of gastrointestinal, liver (including Gilbert’s syndrome), kidney, or other conditions known to interfere with the absorption, distribution, metabolism, or excretion of drugs. 9. Liver function test results elevated >1.5-fold above the ULN for gamma glutamyl transferase (GGT), bilirubin (total, conjugated and unconjugated), ALP, AST or ALT. Participants with elevated GGT, ALP, AST and/or ALT above the limits specified may be included, at the discretion of the PI (or delegate), if the levels are unaccompanied by clinical signs and are determined to be normal variants. 10. Estimated creatinine clearance (CrCl) < 60 mL/min using the Cockcroft-Gault formula or serum creatinine >1.5-fold above the ULN. 11. A history of or positive test results for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV) antibodies at the screening visit. 12. Positive drugs of abuse test, carbon monoxide breath test or alcohol breath test results at the screening visit and/or on admission to the study site on Day -1. 13. Regular consumption of more than 10 standard alcoholic drinks/week and/or more than 4 standard alcoholic 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], or 30 mL spirit [40% Alc/Vol]). 14. Volunteer smokes more than 5 cigarettes or equivalent nicotine-containing products per week, and/or the volunteer is unwilling to abstain from smoking or the use of nicotine-containing products for 72 hours prior to check-in on Day -1 and throughout the study. Note: 1 average cigar equals approx. 5 average cigarettes; 1 average pipe session equals approx. 5 average cigarettes, 1 average nicotine liquid vape session equals 1 average e-cigarette equals 1 average cigarette. 15. Females who are breastfeeding or planning to breastfeed. 16. Unable to swallow oral medication. 17. Use of any prescription or over-the-counter medication (including herbal products, diet aids, vitamins, and hormone supplements) within 10 days or 5 half-lives of the medication (whichever is longer) prior to the first dose of study drug, except use of contraceptives, the use of paracetamol (up to 2 g per day) for no more than 3 consecutive days and the use of ibuprofen (up to 1.2 g per day) for no more than 3 consecutive days. 18. In addition, participants must not take systemic immunosuppressive (e.g., corticosteroids, methotrexate, azathioprine, cyclosporine) or immunomodulating medications (e.g., interferon) within 28 days or 5 half-lives of individual agent (whichever is longer) prior to dosing and during the study. 19. 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. 20. Current infection that requires systemically absorbed antibiotic, antifungal, antiparasitic or antiviral medication within 10 days prior to first dose of study drug. 21. Use of any vaccinations within 30 days prior to screening. 22. Donation of blood or plasma within 30 days prior to first dose of study drug, or loss of whole blood of more than 500 mL within 30 days prior to first dose of study drug, or receipt of a blood transfusion within 1 year of the first dose of study drug. 23. Participation in any clinical study of an investigational drug or investigational device within 30 days or 5 half-lives of the investigational drug (whichever is longer) prior to screening. 24. Any other condition or prior therapy that in the opinion of the PI (or delegate) 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