A Randomized Double-Blind, Placebo-Controlled, Parallel Multicenter Phase III Study To Evaluate The Effectiveness And Safety Of VHAKM Akkermansia Muciniphila On The Clinical And Biological Parameters Of Women With Urinary Tract Infection

Study Title- A Randomized double-blind, placebo-controlled, parallel multicentre phase III study to evaluate the effectiveness and safety of VHAKM- Akkermansia muciniphila on the clinical and biological parameters of women with urinary tract infection.

Study Population- 60 Patients with Irritable Bowel Syndrome

Study Duration- 2 Months

Study Design- A randomized double-blind, placebo-controlled, parallel,multi-center, phase 3 clinical trial.

Inclusion Criteria-

1. Women aged between 18 and 70.

2. Post-menopausal women are defined as greater than 12 months since their last menstrual period Menopause may be natural or induced due to surgical or medical intervention.

3. Have a history of recurrent UTIs, defined as greater than or equal 3 episodes in the past year, of which two were approximately in the past 6 months immediately prior to their screening visit at the discretion of the investigator. At least one episode must be diagnosed medically and treated by a health care professional, the remaining two may be self-reported.

4. Voluntarily participating in the clinical study, fully understanding, and being fully informed of the study, and having signed the Informed Consent Form (ICF).

5. Willingness and capability to complete all the study procedures.

Exclusion Criteria –

1. Immunosuppressants

2. Known allergies to investigational product or its excipients.

3. Known vaginal infection other than bacterial vaginosis (BV) or yeast infection at the time of screening.

4. Women who have needed changes to medical intervention or in-office procedures in the last 3 months.

5. Women who wear a pessary.

6. Women who use catheters regularly.

7. Women with an obstruction or neurogenic bladder causing incomplete bladder emptying. Individuals who have taken oral antibiotics (or topical antibiotics in their urogenital area) within the previous 30 days.

8. Individuals that have a significant acute or chronic co-existing illness such as renal diseases (renal failure, nephrolithiasis), anatomical urinary tract abnormalities, intestinal disease, severe uncontrolled metabolic or cardiovascular disease (such as diabetes or hypertension), anticoagulant therapy, cancer.

9. Medical conditions or diseases that may affect subject safety or confound study results in the investigator’s opinion.

Dose & Mode of Administration-

Take one capsule or as directed, best taken prior to a meal. Frequency: One Capsule or as directed Route of Administration: Oral

Primary Outcome Measure-

• Incidence rate of symptomatic UTI

Secondary Outcome Measures-

• Change in the vaginal pH from baseline to Day 60 (end of study)

• The mean number of UTIs experienced per from baseline to Day 60 (end of study)

• Change in the FSH from baseline to Day 60 (end of study)

• Change in the LH from baseline to Day 60 (end of study)

• Change in the Serum estradiol levels from baseline to Day 60 (end of study)

• Change in the Serum testosterone levels from baseline to Day 60 (end of study)

• Change in the antral follicle count from baseline to Day 60 (end of study)

• Change in the ovarian volume from baseline to Day 60 (end of study)

Clinical evaluation-

• Haematological and hepatic biomarkers were analyzed following the standard medical test protocols at screening (baseline) and end of treatment (Day 60)
• Vital signs measurement and physical examination will be carried out at Screening, day 1, day 14, day 28, day 45 and day 60.

Evaluation Schedule-

Visit 01(Day 01) Baseline-

• Informed consent

• Demographic data

• Medical and surgical history

• Medication history

• Physical examination

• Vital signs

• Checking of eligibility criteria (Inclusion/exclusion criteria)

• Randomization

• Dispensing of study medication

• Vaginal pH

• Fasting Blood sugar level

• Subject treatment and diary filling instruction

• Providing patient diary

Visit 05 (Day 60 ± 3 days) End of Treatment Visit

• Vital signs

• Physical examination

• Collection of patient diary and checking treatment compliance

• Fasting Blood sugar level

• Vaginal Ph

• All adverse events will be reported throughout the study duration

Safety Endpoints-

• Number of participants who experienced at least one Adverse Event during the study duration.

• Number of participants who discontinued study drug due to an Adverse Event during the study

Ethical Considerations-

The study will be conducted as per the National Ethical Guidelines for Biomedical and Health Research involving Human participants ICMR (2017), ICH (Step 5) ’Guidance on Good Clinical Practice’, New Drugs and Clinical Trials Rules 2019 G.S.R. 227(E) dated 19 Mar 2019, ’Good Laboratory Practice’, ‘Good Clinical Practices for Clinical Research in India’ Guidelines, Good Clinical Laboratory Practice (GCLP) and Declaration of Helsinki (Fortaleza, October 2013).