Study to Evaluate the Efficacy and Safety of XC243 in Patients With Exacerbation of Chronic Cystitis

Multicenter, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of XC243 in Patients With Exacerbation of Chronic Cystitis

Multicenter, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of XC243 in patients with exacerbation of chronic cystitis. It is planned to include patients with chronic cystitis in 4 parallel groups, who will receive XC243 at a dose of 25 mg per day, 50 mg per day, 75 mg per day or placebo for 7-10 days. Efficacy will be assessed by time from first study treatment to resolution of the symptom "Pain, discomfort or burning when urination " assessed on a visual-analog scale (VAS).

Study Overview

• Status: Not yet recruiting
• Conditions: Cystitis
• Intervention / Treatment: Drug: XC243 25 mg; Drug: XC243 50 mg; Drug: XC243 75 mg; Drug: Placebo

Detailed Description

The study will be conducted in 8 centers. The study will include the following periods: screening (1 day), treatment period (up to 10 days), follow-up period (7 days).

Upon completion of screening, patients will be randomized to 4 groups in the ratio 1:1:1:1: XC243 at a dose of 25 mg per day, 50 mg per day, 75 mg per day or placebo group.

Also, all patients will be prescribed furasidin daily at the same time, 2 capsules (total dose 100 mg) 3 times a day after meals. On day 8 the investigator will assess the symptoms of cystitis and decide whether to discontinue or prolong a course of therapy with XC243 and furasidin for up to 10 days.

• Study Type: Interventional
• Enrollment (Estimated): 280
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Vladimir Nebolsin; Phone Number: +79175584626; Email: nve1970@mail.ru

Study Locations

• Russian Federation
  • Moscow, Russian Federation, 119571
    • Unimed-S Cjsc
    • Contact: Elena Volnaya, MD; Phone Number: +79165900601; Email: drvolnaya@yandex.ru
  • Saint Petersburg, Russian Federation, 191119
    • LLC "Research Center Eco-Safety"
  • Saint Petersburg, Russian Federation, 196143
    • LLC "Research Center Eco-Safety"
    • Contact: Dmitriy Zlobin, MD; Phone Number: +79523851666; Email: zlobin_ds@ecosafety.ru
  • Saint Petersburg, Russian Federation, 196158
    • LLC "Clinic Zvezdnaya"
    • Contact: Alexander Bulkin, MD; Phone Number: +79533464851; Email: alexander_bulkin@mail.ru
  • Saint Petersburg, Russian Federation, 199178
    • St. Petersburg State Budgetary Healthcare Institution "City Polyclinic No. 4"
    • Contact: Michail Alexeev, MD, PhD; Phone Number: +79219503727; Email: Alexeevmy@mail.ru
  • Saint Petersburg, Russian Federation, 195427
    • St. Petersburg State Budgetary Healthcare Institution "City Polyclinic № 112"
    • Contact: Alexander Merzlyakov, MD; Phone Number: +79818629541; Email: merzel88@mail.ru
  • Saint Petersburg, Russian Federation, 196158
    • North-West Center of Evidence-Based Medicine Jsc
    • Contact: Alexey Schmelev, MD; Phone Number: +79522648249; Email: aludm2@mail.ru
  • Saint Petersburg, Russian Federation, 197374
    • Prime Rose Medical Center LLC
    • Contact: Anton Boriskin, MD, PhD; Phone Number: +79112120980; Email: flounder@yandex.ru

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Availability of the Form signed and dated by the patient the Patient Information Leaflet informed consent (IMP).
2. Women aged 18 to 65 years inclusive at the time of signing the Informed IMP consent.
3. Established diagnosis of chronic bacterial cystitis (at least three relapses chronic cystitis within 12 months prior to screening or two cases within 6 months prior to screening, including relapse at study entry).
4. The presence of symptoms characteristic of exacerbation of chronic cystitis: pain syndrome (pain in lower abdomen, when urinating), dysuric symptoms (increased urination, pain or burning when urinating, urgency to urinate, feeling of incomplete emptying bladder).
5. The appearance of symptoms of exacerbation of chronic cystitis is not > 48 hours prior to screening visit.
6. Severity of the symptom "Pain, discomfort or burning with urination "from 4 to 8 VAS points.
7. No therapy for current cystitis exacerbation (including phosphomycin and/or furasidin for the treatment of current exacerbation).
8. The patient's consent to refrain from drinking alcoholic beverages during the period of participation in study.
9. Patient consent to use reliable methods contraception throughout the study and through 3 weeks after its end.

Exclusion Criteria:

1. Hypersensitivity to the active and/or any of excipients of the test drug.
2. Hypersensitivity to furasidine and/or any of the excipients concomitant medication.
3. Chronic recurrent cystitis due to infections, sexually transmitted diseases (STIs): gonorrhea, chlamydia, ureaplasmosis, mycoplasmosis, herpes, candidiasis, gardnerellosis, history of trichomoniasis.
4. Chronic recurrent cystitis of viral etiology (caused by adenovirus, cytomegalovirus, virus human papillomavirus herpes).
5. Axillary body temperature ≥ 38 ° C at the screening visit.
6. Presence of menstruation at randomization or estimated onset of menstruation during the period therapy.
7. Pain in the lumbar region.
8. Itching and abundant vaginal discharge and/or purulent discharge from the genitourinary tract.
9. History and/or findings of genitourinary anatomical disorders ultrasound examination (hydronephrosis, sclerosis of the bladder neck, cystocele, descent uterus, paraurethral cyst).
10. Presence of inflammatory diseases of the sexual system (vaginitis, colpitis, cervicitis).
11. Kidney and urinary tract diseases (including urolithiasis), with the exception of chronic cystitis, with a history that, in the opinion of study doctor, may affect the course and results of the clinical study.
12. Chronic renal failure.
13. Type 1 diabetes mellitus or uncontrolled type 2 diabetes mellitus.
14. History of pseudomembranous colitis.
15. Signs of macrohematuria (admixture of blood in the urine, discoloration of the urine).
16. Previous urinary tract surgery or radiation therapy.
17. History of malignancy, per excluding patients who have not had disease within the last 5 years, patients with completely cured basal cell carcinoma or completely cured carcinoma in situ.
18. Patients with HIV, syphilis, hepatitis B and C diseases, including a history.
19. Liver disease that the study doctor believes may affect course and outcomes clinical trial, history of hepatic failure.
20. Severe, decompensated or unstable somatic diseases (any diseases or conditions that threaten the patient's life or worsen the patient's prognosis, and also make it impossible to conduct clinical trial with this patient).
21. Use of analgesic drugs activity, including systemic NSAIDs, as well as antispasmodic drugs less than 24 hours before taking study drug/placebo.
22. No history of efficacy of furasidine and/or no data furasidin sensitivity based on a history of urine microbiology.
23. The need for the use of drugs from the list of prohibited therapy.
24. Use of systemic antibacterial drugs actions within 7 days prior to screening.
25. Administration of other medicinal products which, in the opinion of the study doctor, may affect progress and results clinical trial.
26. Participation in another clinical trial within 3 months prior to screening.
27. Pregnancy or breastfeeding.
28. Alcohol or drug dependence, history of mental illness.
29. Patient unwillingness or inability to comply with procedures protocol (in the opinion of the study physician).
30. Other conditions that prevent the patient from being included in the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Patients will receive the IP once in the morning at least 30 minutes before eating for 7-10 days
Experimental: XC243 25 mg; XC243 25 mg single	Drug: XC243 25 mg; Patients will receive the Investigated Product (IP) once in the morning at least 30 minutes before eating for 7-10 days
Experimental: XC243 50 mg; XC243 50 mg single	Drug: XC243 50 mg; Patients will receive the IP once in the morning at least 30 minutes before eating for 7-10 days
Experimental: XC243 75 mg; XC243 75 mg single	Drug: XC243 75 mg; Patients will receive the IP once in the morning at least 30 minutes before eating for 7-10 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time from the first dose of IP treatment until the symptom "Pain, discomfort or burning when urination " disappears (decreases).	Symptom disappears (decreases) criterion "Pain, discomfort or burning during urination "is considered to be the simultaneous fulfillment of the following conditions: Improvement to 1 point or less in VAS and Maintain VAS score of 1 point or less for 24 hours. Within 96 hours (4 days) after the first dose of the IP assessment of the symptom "Pain, discomfort or burning when urinating" will be conducted by the patient after each urination. After 96 hours (from day 5) evaluation this symptom will be carried out 2 times a day (8-00 to 10-00 hours and from 20-00 to 22-00 hours over time). Superiority over placebo will be considered established if difference in mean between groups (XC243 - placebo) by symptom reduction time would be greater than 11 hours at the time of treatment evaluation.	Day 1 - Day 10

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Severity of the symptom "Pain, discomfort or burning with urination "as per VAS	Severity of the symptom "Pain, discomfort or burning with urination "as per VAS to Visit 2 (Day 2), Visit 3 (Day 5), Visit 4 (Day 8), End of therapy Visit (Day 11)	Day 1 - Day 11
Dynamics of the symptom "Pain, discomfort or burning when urinating" by VAS.	Dynamics of the symptom "Pain, discomfort or burning when urinating" by VAS to End of therapy Visit	Day 1 - Day 11
Assessment of disease symptoms by Acute Cystitis Symptom Score (ACSS).	ACSS assessment of disease symptoms to Visit 2 (Day 2), Visit 3 (Day 5), Visit 4 (Day 8), End of therapy Visit (Day 11)	Day 1 - Day 11
Dynamics of typical symptoms according to the ACSS scale	Dynamics of typical symptoms of the disease according to the ACSS scale to Visit 2 (Day 2), Visit 3 (Day 5), Visit 4 (Day 8), End of therapy Visit (Day 11)	Day 1 - Day 11
Dynamics of quality of life according to the ACSS scale	Dynamics of quality of life according to the ACSS scale to Visit 2 (Day 2), Visit 3 (Day 5), Visit 4 (Day 8), End of therapy Visit (Day 11)	Day 1 - Day 11
Frequency of patients with disappearance of all typical symptoms diseases	Frequency of patients with disappearance of all typical symptoms diseases (ACSS score 0) to Visit 2 (Day 2), Visit 3 (Day 5), Visit 4 (Day 8), End of therapy Visit (Day 11)	Day 1 - Day 11
Time to disappearance of typical disease symptoms for each symptom by ACSS	Time to disappearance of typical disease symptoms (score 0 on the ACSS scale) for each symptom to Visit 2 (Day 2), Visit 3 (Day 5), Visit 4 (Day 8), End of therapy Visit (Day 11)	Day 1 - Day 11
Frequency of patients with disappearance of the symptom "pain or urinary burning " by ACSS	Frequency of patients with disappearance of the symptom "pain or urinary burning "(ACSS score 0) to Visit 2 (Day 2), Visit 3 (Day 5), Visit 4 (Day 8), End of therapy Visit (Day 11)	Day 1 - Day 11
Frequency of patients with disappearance of the symptom "pain or discomfort in the lower abdomen (suprapubic region) " by ACSS	Frequency of patients with disappearance of the symptom "pain or discomfort in the lower abdomen (suprapubic region) "(score 0 according to ACSS) to Visit 2 (Day 2), Visit 3 (Day 5), Visit 4 (Day 8), End of therapy Visit (Day 11)	Day 1 - Day 11
Scale score by Pelvic Pain and Urgency/Frequency Patient Symptom Scale (PUF Scale)	Scale score by PUF Scale to Visit 2 (Day 2), Visit 3 (Day 5), Visit 4 (Day 8), End of therapy Visit (Day 11)	Day 1 - Day 11
Dynamics of symptoms of the disease according to the Diary patient.	Dynamics of symptoms of the disease according to the Diary patient to Visit 2 (Day 2), Visit 3 (Day 5), Visit 4 (Day 8), End of therapy Visit (Day 11)	Day 1 - Day 11
Dynamics of the symptom "Pain or burning when urinating" according to VAS within first 24 hours post-dose	Dynamics of the symptom "Pain or burning when urinating" according to VAS within first 24 hours post-dose	Day 1 - Day 2
Mean urinary frequency per day by Patient Diary	Mean urinary frequency per day by Patient Diary to Visit 2 (Day 2), Visit 3 (Day 5), Visit 4 (Day 8), End of therapy Visit (Day 11)	Day 1 - Day 11
Assesment by Global Clinical Impression Scale score (CGI-i)	Patient's CGI-i score	Day 1 - Day 11
Evaluation of the efficacy of therapy by 5 rating scale	Evaluation of the efficacy of therapy by 5 rating scale to Visit 2 (Day 2), Visit 3 (Day 5), Visit 4 (Day 8), End of therapy Visit (Day 11). This scale is assessed by the investigator, where 1 point - absence, 2 points - regression, 3 points - decrease in severity, 4 points - lack of positive dynamics, 5 points - increase in the main clinical symptoms	Day 1 - Day 11

Collaborators and Investigators

• Sponsor: PHARMENTERPRISES LLC

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2024
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: April 25, 2024
• First Submitted That Met QC Criteria: April 25, 2024
• First Posted (Actual): April 30, 2024

Study Record Updates

• Last Update Posted (Actual): April 30, 2024
• Last Update Submitted That Met QC Criteria: April 25, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: VAS; Phase II
• Additional Relevant MeSH Terms: Urologic Diseases; Urinary Bladder Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Cystitis
• Other Study ID Numbers: PAIN-XC243-02-01-2023

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No