None listed
Conditions
Brief summary
SIR1-365 is a potent and selective allosteric kinase inhibitor of RIP1 with favorable drug-like properties in vitro and in vivo. RIP1 inhibitors may be beneficial for the treatments of degenerative diseases including neurodegenerative and systemic inflammatory diseases. The primary objective is to assess the overall safety and tolerability of SIR1-365 administered orally at 200 mg, two times per day (BID) for 28 days relative to the placebo group. The secondary objectives are to assess the effects of SIR1-365 on clinical efficacy endpoints, and the biomarkers indicative of inflammation, and target engagement as well as the plasma SIR1-365 levels.
Interventions
RIP1 mediates the downstream effects of multiple biological activities including inflammatory responses. Therefore RIP1 inhibitors may be advantageous over selective inhibitors for a specific cytokine to reduce inflammatory response. SIR1-365 is a Receptor-Interacting Protein1 (RIP1) inhibitor that is under development as a new investigational drug for the treatment of inflammatory diseases.
Type III prostatitis is also known as chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). Curren
RIP1 mediates the downstream effects of multiple biological activities including inflammatory responses. Therefore RIP1 inhibitors may be advantageous over selective inhibitors for a specific cytokine to reduce inflammatory response. SIR1-365 is a Receptor-Interacting Protein1 (RIP1) inhibitor that is under development as a new investigational drug for the treatment of inflammatory diseases. Type III prostatitis is also known as chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). Currently, there is a lack of a clear evidence proved effective treatment. This will be a multicenter, randomized, double-blinded, placebo-controlled study to evaluate safety and preliminary efficacy of SIR1-365 in patients with CP/CPPS. Enrolled patients will take two 100mg tablets of either SIR1-365 or matching placebo orally, two times a day for 28 consecutive days. Patients will return to the clinical site on Days 7 (±1 day), 14 (±1 day), be contacted by telephone on Day 21 (±1 day), 28 (±2 days) end of treatment and 42 (±5 days) follow up visit/end of study to receive all the activities scheduled for the respective visits. The afternoon dose for Day 28 (±2) or last visit day will not be administered. Study staff will instruct enrolled patients to take the study medication exactly as instructed as compliance is necessary for patient safety and for the validity of the study. Excluding the follow-up visit, patients will take their morning dose on the days they attend the clinical site. Study staff will contact patients on a weekly basis to schedule their next clinic visit and to remind them to take their study medication. IP bottles will be returned to the clinical site on Days 7, 14 and 28. Study staff will perform a pill count to determine treatment compliance and record the information in the source.
Sponsors
Sironax Aus Pty Ltd
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver)
Eligibility
Sex/Gender
Male
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
1. Men 18 to 60 years of age at the time of signing the informed consent. 2. Patient has signed and dated the appropriate Informed Consent document. 3. Patient has pain or discomfort in the pelvic region for at least 3 months in the last 6 months, in the absence of a urinary tract infection or other pelvic/urological cause and have a physician diagnosis of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) based on NIH Classification System. If treated with antibiotics, symptoms persist. 4. Patient with NIH-CPSI score of at least 15 at screening, 5. Patient or female partner of patient must agree to use a reliable contraceptive method for sexual intercourse from Screening until at least 90 days after the last dose of study drug, unless they have been surgically sterilized (vasectomy) for a minimum of 6 months. 6. Patient agrees not to participate in another interventional study after signing the informed consent form and until the end of study (EoS) visit has been completed.
Exclusion criteria
1. Patient has experienced 2 or more UTI in the 12 months prior to screening and facultative Gram negative or enterococcus with a value of greater than or equal to 1000 colony forming units (CFU) /ml in mid-stream urine (VB2) in the last 3 months prior to screening. 2. Patient has a history of or currently has prostate, penile, testicular, bladder, or urethral cancer or has undergone pelvic radiation, systemic chemotherapy, or intravesical chemotherapy. 3. For patients with suspected lower urinary tract malignancy, investigator should make clinical determination based on patient’s overall profiles including positive (micro) hematuria in urine sediment or prostate specific antigen (PSA) >4 ng/mL. 4. Patient with currently active sexually transmittable disease. 5. Patient with symptomatic urethral stricture or symptomatic bladder or urethral calculi, severe bladder outlet obstruction, overactive bladder with incontinence or post void residual volume greater than 150 mL. 6. Patient has unilateral orchialgia without pelvic symptoms, or neurological disease or disorder affecting the bladder. 7. Patient has undergone transurethral prostatectomy, transurethral incision of the prostate, transurethral incision or resection of the bladder neck, transurethral microwave thermotherapy, transurethral needle ablation, balloon dilation of the prostate, open prostatectomy or any other prostate surgery or treatment such as cryotherapy or thermal therapy, or any prior prostate and/or bladder intervention within 3 months prior to screening. 8. Patient with clinically relevant abnormal urine or blood safety laboratory values or active hepatic and/or biliary disease (Aspartate aminotransferase (AST) or Alanine aminotransferase (ALT) should be >3 times the upper limit of normal, total bilirubin should be >2 times the upper limit of normal). 9. Patient has a history of moderate or severe hepatic impairment, severe renal sufficiency, severe or unstable cardiovascular (i.e. prolonged QT), respiratory, hematological, endocrinological, neurological or other somatic disorders, which will impact the safety and efficacy evaluation by investigator judgements. 10. Patient with initiation, discontinuation, or variation in the dose of antidepressants, alpha- blockers, 5-alpha reductase inhibitors, antimuscarinics, benzodiazepines, skeletal muscle relaxants, non-steroidal anti-inflammatory drugs, non-opioid analgesics and herbal therapies during the last 4 weeks before screening. Patients should continue these medications at the same stable dose throughout the study. 11. Patient has a neurological impairment or psychiatric disorder preventing his understanding of consent and his ability to comply with the protocol. 12. Patient is taking any medicine that is mainly metabolized by CYP450 2C19. The investigator could provide an alternative medicine that is not mainly metabolized by CYP450 2C19. 13. Patient has a known or suspected hypersensitivity to SIR1-365 or any components of SIR1-365 tablets. 14. Patient has received any investigational drug within 30 days or 5 half-lives, whichever is longer, prior to screening. 15. Patient has any other condition, which makes the patient unsuitable for study participation by investigator’s judgement.
Outcome results
None listed