None listed
Conditions
Brief summary
This is a first-in-human, single-centre, randomised, double blind, three-part multiple dose study to assess the safety and tolerability of OXT-328 and how this drug acts in the body in patients with chemotherapy induced peripheral neuropathy (CIPN). Who is it for? You may be eligible for this study if you are over 18 years of age and have moderate-to-severe CIPN. Study details: All patients with CIPN who choose to enrol in this study will be assigned by chance to receive multiple doses of OXT-328 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. The data generated in this study will inform the design of future clinical studies and to select the dose(s) for future studies in patients with CIPN.
Interventions
This is a Phase Ia/b, randomised double blind, placebo-controlled, multiple dose, multi-cohort study.
Part C: (Multiple Doses) in patients with chemotherapy-induced peripheral neuropathy (CIPN).
Part C may commence following completion of SRC review of Part B (ACTRN12624000374561).
Twenty five patients with CIPN will be enrolled to 1 of 2 treatment area groups according to the extremity where patients experience CIPN: Hand (Group 1) or Foot (Group 2). Following enrolment to either Group 1 or 2
This is a Phase Ia/b, randomised double blind, placebo-controlled, multiple dose, multi-cohort study. Part C: (Multiple Doses) in patients with chemotherapy-induced peripheral neuropathy (CIPN). Part C may commence following completion of SRC review of Part B (ACTRN12624000374561). Twenty five patients with CIPN will be enrolled to 1 of 2 treatment area groups according to the extremity where patients experience CIPN: Hand (Group 1) or Foot (Group 2). Following enrolment to either Group 1 or 2, patients will be randomised to receive doses of OXT-328 or placebo administered as a topical gel. Group 1: For patients administered treatment on hand: Dose level of 50 mg (1 mL of 5.0% w/w strength study drug) is planned to be evaluated. Group 2: For patients administered treatment on foot: Dose level of 100 mg (2 mL of 5.0% w/w strength study drug) is planned to be evaluated Doses will be administered on Days 1 to 28 (inclusive), with the dosing schedule three times daily. Site staff will administer the first dose on Day 1 and subsequently supply all patients with study drug (OXT-328 or placebo). Patients will be instructed to administer the first dose on Days 2, 7, 14 and 28 in the clinic (under the supervision of site staff) following completion of study assessments, with all other doses will be self-administered at home . Adherence to Intervention will be managed via recording in appropriate drug accountability records.
Sponsors
Cleothena Enterprises Pty Ltd
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver)
Eligibility
Sex/Gender
All
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
Participants will be included in Part C 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. Male or female, aged greater than or equal to 18 years, inclusive at Screening. 3. Have moderate-to-severe CIPN as defined by a NRS score of greater than or equal to 4 and less than or equal to 9 on a 0 – 10 scale for the participant’s experience of all CIPN-related symptoms. 4. Presence of CIPN for more than 3 months and less than 24 months at the time of Screening. 5. Participant is otherwise 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. Heart rate in the range of 40 to 100 beats/minute after 5 minutes rest in supine or semi-supine position. c. Body temperature (tympanic), between 35.5°C and 37.7°C. d. Electrocardiogram without clinically significant abnormal findings. e. No clinically significant findings in serum chemistry, haematology, or urinalysis. 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 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 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 condom from the time of signing consent until at least 90 days after the last dose of study drug. 8. Negative urine drugs of abuse test at Screening or pre-dose on Day 1. Note: Patients with positive drug screen for a known prescribed concomitant medication that is not otherwise exclusionary (e.g., benzodiazepines) may be permitted. 9. Willing and able to comply with all scheduled visits, treatment plans, laboratory tests and other study procedures. 10. Must be able to comprehend the language used in the quality of life and CIPN disease assessments in this clinical study, as assessed by the Investigator (or delegate).
Exclusion criteria
Participants will be excluded from Part C of the study if there is evidence of any of the following: 1. Experienced myocardial infarction or undergone coronary artery bypass grafting within 6 months of Screening. 2. Diagnosed with New York Heart Association (NYHA) Class III or IV heart failure. 3. 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. 4. Recent history (within 3 months of Screening) or currently existing gastric ulcers, non-iatrogenic intestinal perforation, or GI bleeding from NSAID usage for which intervention was required. 5. 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, gastrointestinal (GI), connective tissue, uncontrolled endocrine/metabolic (including but not limited to diabetes), neurologic, and psychiatric, alcohol abuse or addiction 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). 6. History of surgery within 8 weeks prior to Screening, or surgery planned during the study. Note: history of, or planned dental surgery, eye surgery, and/or minor cosmetic procedures not in the hands or feet within the above timeframes are permitted. 7. Currently receiving chemotherapy for the treatment of neoplasia. 8. Experience neuropathic pain due to conditions other than CIPN, including postherpetic neuralgia, diabetes mellitus, human immunodeficiency virus (HIV) infection, spinal cord injury, tumor or metastasis affecting the cervical/lumbosacral plexus with evidence of tumor-associated pain, and other neurological diseases. 9. 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 the Investigator [or delegate]) would interfere with skin local tolerability assessments at the study drug application site. 10. Laboratory results at Screening that indicate inadequate renal function (estimated creatinine clearance of < 60 mL/min calculated by the Cockcroft and Gault formula). 11. Liver function test results elevated more than 2-fold above the upper limit of normal (ULN) for gamma glutamyl transferase (GGT), alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine transaminase (ALT) or total bilirubin. Participants with GGT, ALP and/or ALT/AST above the limits specified may be included, at the discretion of the Investigator, if the levels are unaccompanied by clinical signs and are determined to be normal variants. 12. Any clinically relevant laboratory finding or medical condition that, in the opinion of the Investigator, could place the patient at risk for participation in the study. 13. Use of topical, non traditional, or non-pharmacological therapy for the treatment of their pain (e.g., chiropractic therapies, alternative medicine therapies, or acupuncture) from 7 days prior to first dose of study drug to End of Study. These treatments are not to be used throughout the study. Note: Use of paracetamol (less than or equal to 3 doses per week) is allowed for management of headaches or minor pains unrelated to CIPN. 14. Patient currently using antipsychotics, opiates/opioids, cannabinoids, hypnotics, antidepressants, mood stabilizers, stimulants or gabapentinoids. Patient may be permitted to participate in the study if they are using any of these medications on a chronic basis, with stable regimen for at least four weeks prior to Screening (and regimen to remain unchanged throughout the study). Up to 8 patients in total may be permitted to use EACH of the above group of medications throughout the study. Note: For patients permitted to use the above medications throughout the study: • Patient is not permitted to change medication throughout the study • If using cannabinoids, must be supplied by medical dispensary and permitted by local laws to be used for medical reasons as instructed by the patient’s physician. • If using opioids, dose must not exceed a morphine equivalent daily dose of 100mg. 15. Participation in another 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. 16. Participant is breastfeeding or pregnant, or planning to breastfeed or become pregnant during the study. 17. Known substance or alcohol abuse or medical, psychological, or social conditions that, in the opinion of the PI (or delegate), may interfere with the participants inclusion in the clinical study or evaluation of the clinical study results. 18. Any other condition or prior therapy that in the opinion of the Investigator (or delegate) would make the participant 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