A Phase I, Randomised, Double Blind, Placebo-Controlled, Single and Multiple Ascending Dose Study to Evaluate the Safety, Tolerability and Pharmacokinetics of OXT-328 in Healthy Adult Volunteers
- Conditions
- Neurological - Other neurological disordersChemotherapy-Induced Peripheral Neuropathy (CIPN)
- Registration Number
- ACTRN12624000374561
- Lead Sponsor
- Cleothena Enterprises Pty Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 56
Participants will be included in Part A and B of the study only if they satisfy all 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. Healthy male or female, aged between 18 and 65 years, inclusive at screening.
3. Body mass index (BMI) of 18 to 35 kg/m2, inclusive at screening, with body weight greater than or equal to 50.0 kg (males) or greater than or equal to 45.0 kg (females), at screening.
4. Participant is medically healthy (in the opinion of the Investigator [or delegate]), as determined by pre-study medical history and without clinically significant abnormalities including:
a. Physical examination without any additional clinically relevant findings
b. Systolic blood pressure (BP) in the range of 90 to 160 mmHg and diastolic BP in the range of 50 to 95 mmHg after 5 minutes in supine or semi-supine position.
c. Pulse rate in the range of 40 to 100 beats/minute after 5 minutes rest in supine or semi-supine position.
d. Body temperature between 35.5°C and 37.7°C.
e. Electrocardiogram without clinically significant abnormalities including QT interval corrected for Fredericia (QTcF) < 450 msec for male subjects and < 470 msec for female subjects.
f. No clinically significant findings in serum chemistry, haematology or urinalysis (in the opinion of the Investigator).
Note: The above assessments may be repeated, if abnormal values were recorded in the first instance, at the discretion of the Investigator (or delegate).
5. Participant is willing to refrain from consuming food or beverages containing caffeine and/or xanthene products, within 24 hours prior to check-in on Day -1 and while confined to the study clinic.
6. Female participants 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, if of childbearing potential:
a. Must have a negative serum pregnancy test at the screening visit and a negative urine pregnancy test on Day -1, prior to dose administration.
b. Must agree not to donate ova or attempt to become pregnant from the time of signing consent until at least 30 days after the last dose of study drug.
c. If not exclusively in a same-sex relationship, must agree to use adequate contraception (which is 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.
7. Male participants must:
a. Agree not to donate sperm from the time of signing consent 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 plus a highly effective method of contraception) from the time of signing consent 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 con
Participants will be excluded from Part A and B of the study if there is evidence of any of the following:
1. Current, active infection that requires systemically absorbed antibiotic, antifungal, antiparasitic or antiviral medications.
2. Suffers from frequent or recurrent infections (defined as greater than or equal to 3 recurrent or separate occurrences in the 12 months preceding first study drug administration or 2 recurrent or separate occurrences in the 6 months preceding first study drug administration).
3. Use of antioxidant-containing medications, supplements or products within 30 days prior to the first study drug administration.
4. Use of systemic corticosteroid, sulindac, or any other NSAID within 7 days or 5 half-lives of the medication (whichever is longer) prior to the first study drug administration.
5. Use of tricyclics, serotonin and norepinephrine reuptake inhibitors (SNRIs) (e.g., duloxetine, venlafaxine), sodium channel blockers, and gabapentinoids within 30 days or 5 half-lives of the medication (whichever is longer) prior to first study drug administration.
6. Use of selective serotonin reuptake inhibitors (SSRIs) (citalopram, escitalopram, sertraline, etc.) within 30 days prior to the first study drug administration.
Note: Participant on stable doses of SSRIs is permitted.
7. Experienced myocardial infarction or undergone coronary artery bypass grafting within 6 months of Screening.
8. Diagnosis with congestive heart failure, defined as New York Heart Association (NYHA) Class II-IV.
9. History of hypersensitivity reaction, anaphylaxis or other clinically significant reactions or known allergy to any of the study drug ingredients (including any of its metabolic derivatives – sulindac, sulindac sulfone and sulindac sulfide), or any other NSAIDs.
10. History of or currently existing aspirin-induced asthma, gastric ulcers, non-iatrogenic intestinal perforation, or GI bleeding from NSAID usage for which intervention was required.
11. History of any clinically significant disorder (which, in the opinion of the Investigator [or delegate] would make implementation of the protocol or interpretation of study results difficult, or that would put the subject at risk by participating in the study), including cardiovascular, haematologic, pulmonary, hepatic, renal, GI, connective tissue, uncontrolled endocrine/metabolic (including but not limited to diabetes), oncologic (within the last 5 years), neurologic, and psychiatric (including substance abuse disorder), or any disorder that may prevent the successful completion of the study or influence the absorption, distribution, metabolism, excretion, or action of the study drug (including any of its metabolic derivatives – sulindac, sulindac sulfone and sulindac sulfide).
Note: Participants with history of resolved childhood asthma, history of migraine (if less than or equal to 1 monthly episode and not on preventative medication), or history of non-hospitalised depression (if not on any anti-depressant) will be allowed to participate in the study.
12. History of surgery or hospitalisation within 12 weeks prior to screening, or surgery planned during the study.
13. Lack of suitable veins for multiple venepunctures/cannulations as assessed by the Investigator or delegate at screening.
14. Presence of any tattoos, scarring or active skin infection or other condition (including open sores, pressure ulcers, stasis ulcers, or other dermatitides), which (in the opinion of
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method