Overview

The goal of this clinical trial is to learn if drug U101 works to prevent recurrent urinary tract infection (rUTI) in women (≥ 20 and < 76 years old) with a medical history. It will also investigate the safety and the impact on the Quality of Life improvement of drug U101. The main questions it aims to answer are:

• Does the drug prevent or decrease the recurrence of urinary tract infection (UTI) during the 24-week treatment?
• Will the Quality of Life be improved during the 24-week treatment?
• What medical problems do participants have when taking drug U101?

Researchers will compare drug U101 to a placebo (a look-alike substance that contains no drug) to see if drug U101 works to prevent rUTI.

Participants will:

• Orally take drug U101 or placebo every day for 24 weeks in the main study, three times per day (TID) for 8 weeks and twice per day (BID) for 16 weeks.
• Visit the site once every 4 weeks for checkups and tests during the main study.
• be asked to enroll in extensional study (the open-label extension (OLE) with drug U101 treatment or the Safety Follow-Up Visits with no investigational product treatment) for 24 weeks after they complete the 24-week main study.
• Visit the site when the suspected UTI occurred during the main study or the extension study.

Eligibility

Inclusion Criteria:

1. Provide a signed informed consent form.
2. Non-pregnant, non-nursing females ≥ 20 and < 76 years old.
3. Having a history of ≥ 2 UTI events during the preceding 6 months or ≥ 3 UTI events during the preceding 12 months (including any UTI event that occurs on the date of ICF signing). At least one of the previous UTI events must have microbiologic evidence (e.g., per the investigator's judgment based on urine culture results).
4. The last urine culture (including those conducted for suspected UTI event or retest) before the randomization has to be negative.
5. Having a negative urinalysis result and no symptoms suggestive of a UTI on the day of randomization.

Exclusion Criteria:

1. Females who are pregnant, nursing, have a desire for pregnancy or have a positive pregnancy test at screening.
2. Women of childbearing potential who are unwilling or unable to use an acceptable contraceptive method to avoid pregnancy for the entire study period (use of spermicide is prohibited). Women of childbearing potential are defined as premenopausal females capable of becoming pregnant.
3. Serum aspartate transaminase (AST), serum alanine transaminase (ALT) and serum total bilirubin > 1.5 x upper limit of normal (ULN).
4. Serum creatinine > 1.5 x ULN.
5. Prothrombin time (PT) or INR > 1.2 x ULN.
6. Platelet counts < 100,000/μL.
7. Serum vitamin D level < 11 ng/mL.
8. HbA1c > 8.0%.
9. Positive test for hepatitis B (both HBsAg and HBeAg), hepatitis C (anti-HCV antibody) or HIV (anti-HIV antibody).
10. Symptoms suggestive of a systemic inflammatory response (fever > 38℃ or WBC count > 12,000) at the screening.
11. A major functional or anatomical abnormality of the urogenital tract (e.g., renal cell carcinoma, outlet obstruction, etc.).
12. Diagnosis of pelvic organ prolapse ≥ grade 2 (according to pelvic organ prolapse quantification POP-Q classification) without any treatment within 6 months of the screening visit.
13. Diagnosis of complicated UTIs within 6 months of the screening visit.
14. Residual urine volume > 100 mL within a month of the screening visit.
15. History of interstitial cystitis, pelvic inflammatory disease, or chronic pelvic pain syndrome.
16. Having any of the following procedures within a week of the screening: urinary catheterization (e.g., Foley catheter), ureteral stent, percutaneous nephrostomy, or cystostomy.
17. Intravesical instillation of hyaluronic acid within 6 months of the screening visit.
18. Treatment with pentosan polysulfate sodium (PPS) within 6 months of the screening visit.
19. Use of antibiotic prophylaxis for rUTI within a month of the screening visit.
20. Use of local hormone therapy (cream, gel, insert, ring, or tablets) in urogenital areas within a month of the screening.
21. Any history of thrombocytopenia, hemophilia, or bladder cancer; history of endoscopy-confirmed gastrointestinal ulcers within 3 years prior to randomization.
22. Active malignancy (under intensive cancer treatment or considered in progression) or a history of any malignancy involving the pelvic cavity within 5 years prior to randomization, with the exception of adequately treated basal cell carcinoma and cervical cancer in-situ. Subjects in stable condition will be evaluated and discussed individually with the investigator.
23. Immunocompromised or history of organ transplant.
24. History of allergies to pentosan polysulfate sodium.
25. Having planned major surgery within 24 weeks after the study.
26. Participation in any interventional clinical trial within 30 days of the screening visit.
27. Other significant medical problem(s) or intercurrent acute illness(es) that in the opinion of the Investigators, would make participation in the study unsafe, complicate the interpretation of study outcome data, or otherwise interfere with achieving the study objective.
28. Subjects who are illiterate.
29. Subjects having a family history of macular degeneration or having been diagnosed with macular degeneration (except for those with asymptomatic age-related macular degeneration) .