The Efficacy of Topical Vaginal Oxytocin Gel in Postmenopausal Women With Vulvovaginal Atrophy

The Efficacy of Topical Vaginal Oxytocin Gel in Postmenopausal Women With Vuluvovaginal Atrophy: A Randomized Controlled Trial

A Phase three randomized, double-blinded, study to asses the efficacy and safety of oxytocin gel in postmenopausal women with vaginal atrophy due to Genitourinary Syndrome of Menopause GSM.

Study Overview

• Status: Not yet recruiting
• Conditions: Vaginal Atrophy; Genitourinary Syndrome of Menopause; Vulvar Atrophy
• Intervention / Treatment: Drug: Oxytocin; Other: Hydroxypropyl methylcellulose

Detailed Description

A Phase three randomized, double-blinded, placebo- controlled study to asses the efficacy and safety of oxytocin gel in postmenopausal women with vaginal atrophy due to Genitourinary Syndrome of Menopause GSM. This study shall include 242 subjects. After screening , subject who meet eligibility criterial will be randomized in a 1:1 ratio to receive wither study intervention or placebo to be applied once daily for sixty days and followed up extra fifteen days. objectives is to evaluate the efficacy and effectiveness of topical oxytocin gel compared with placebo in improving postmenopausal vaginal atrophy symptoms in women with GSM , also assessing the safety and tolerability of topical oxytocin gel.

• Study Type: Interventional
• Enrollment (Estimated): 244
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Ibrahim Gado; Phone Number: 00201094742244; Email: ibrahim.gado@oxagon-ab.com

Study Locations

• Egypt
  • Cairo, Egypt
    • Oxagon
    • Contact: Ibrahim Gado; Phone Number: 00201094742244; Email: ibrahim.gado@oxagon-ab.com
    • Contact: Khaled Prince; Email: khaled.prince@clinmax.net
    • Principal Investigator: Asem Anwar

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Postmenopausal, sexually active female subject of age 47 - 65 years, at the time of randomization, willing to provide an informed consent.
2. Physical Assessment showing vaginal atrophy (according to the following criteria: pale, smooth, or shiny vaginal epithelium, friable, epithelium showing no rugae, loss of elasticity or turgor of the skin, dryness of labia, fusion of labia minora, vulvar lesions, or erythema.) 3. Patients with at least one present symptom (ex. vaginal dryness, itching, burning, dysuria, and/or dyspareunia) and able to identify one symptom as the most bothersome symptom, with at least moderate severity.

4. Vaginal smear cytology at screening showing ≤ 5% superficial cells 5. Vaginal pH > 5.0 at screening 6. A level of estradiol ≤ 30 pg/mL and a level of Follicle Stimulating Hormone (FSH) > 40 milli International Units (mIU)/ml at screening 7. Be willing to abstain from sexual activity and the use of vaginal douching within 24 hours prior to vaginal pH measurements at screening and the study follow-up visits

Exclusion Criteria:

1. Previous treatment with other local non-hormonal moisturizers/hormonal products within 1 month or use of lubricants within 1 week prior to inclusion.
2. Women taking systemic hormone replacement or pills within the last 6 months.
3. Current or history of endometrial hyperplasia or uterine/endometrial, breast, or ovarian cancer, or undiagnosed vaginal bleeding
4. Any untreated urogenital infection within 14 days prior to randomization.
5. Ongoing treatment with systemic medications for other non-related health conditions which might impact the study results and have the potential to bring about change in the vaginal environment e.g. glucocorticosteroids, antibiotics, etc.
6. Critically ill patients.
7. Patients with severe renal impairment (GFR < 30 ml/min/1.73 m2 as measured by the Cockcroft-Gault formula).
8. Patients with known severe hepatic impairment (Child-Pugh C; 10 - 15 points), biliary cirrhosis, or cholestasis.
9. Patients with known or suspected allergy or any contraindications to oxytocin.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: MenOxy; The investigational product will contain a Plastic tube containing 36 g of study product (gel) and a Vaginal calibrated plastic applicator for dose (1 ml) administration. The active constituent is oxytocin 600 IU/ml dissolved in a gel based on Hypromellose with a pH of 3.8.	Drug: Oxytocin; Oxytocin gel 600 IU . 1mg/g
Placebo Comparator: Placebo; The placebo gel will match the IP gel (Hypromellose) with a pH of 3.8, without oxytocin.	Other: Hydroxypropyl methylcellulose; Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The mean change from the baseline to Day 60 of the severity of the Most Bothersome Symptom (MBS) self-assessment.	MBS is a moderate to severe symptom identified as the most bothersome by the subject at baseline, recorded as none, mild, moderate, or severe was analyzed using the score values of 0, 1, 2, or 3, respectively. Symptoms include vaginal dryness, vaginal/vulvar irritation/itching, dysuria, vaginal pain (dyspareunia), or bleeding associated with sexual activity.	60 days
The mean change from the baseline to Day 60 of the vaginal pH	Vaginal pH as measured by a pH strip applied directly to the lateral wall of the vagina, recording the pH value (to one decimal) according to the comparison to the color chart.	60 days
The mean change from the baseline to Day 60 of the Vaginal Maturation Index (VMI)	VMI is calculated using the Meisels'(Meisels, 1967) formula: (0 * Parabasal Cells) + (0.5 * Intermediate Cells) + (1 * Superficial Cells).	60 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The mean changes in MBS severity, pH, and VMI from the baseline to Days 30 and 75		Days 30 and 75
The percentage of subjects identified as Responders on days 60 and 75.	A responder is a subject meeting all the following criteria: at least 1 point improvement (decrease) in the severity of the MBS, at least a 0.5-point decrease in the vaginal pH, and at least 20% improvement in the VMI.	Days 60 and 75
The mean change from the baseline to Days 30, 60, and 75 of the physical examination of the vulva and vagina	Assessment of the physical signs of VA (Vaginal secretions, Vaginal Epithelial Integrity, Vaginal Epithelial Surface Thickness, and Vaginal Color) as evaluated by the physician/gynecologist and corresponding to none, mild, moderate, or severe atrophy and analyzed using the score values of 0, 1, 2, and 3, respectively.	Days 30, 60, and 75
The mean changes from the baseline to Days 30, 60, and 75 in Vaginal Wall Thickness as measured by transvaginal ultrasound.		Days 30, 60, and 75
The mean changes from the baseline to Days 30, 60, and 75 in Doppler indices measured by transvaginal ultrasound.		Days 30, 60, and 75
The mean change from the baseline to Days 60 and 75 in selected items from the Female Sexual Function Index (FSFI).		Days 60, and 75
The mean change from the baseline to Days 60 and 75 in patient-reported psychometric outcomes.		Days 60 and 75
The number and percentage of subjects on Days 30, 60, and 75 reporting Treatment-Emergent Adverse Event (TEAE), defined as any AE that occurs on or after the application of the first dose of the study intervention.		Days 30, 60 and 75
The rate of abnormal findings on Days 30, 60, and 75 during the physical, gynecological, and breast examinations.		Days 30, 60 and 75
The rate of abnormal findings on Days 30, 60, and 75 of the transvaginal ultrasound for women with an intact uterus only.		Days 30, 60 and 75
The mean medication incompliance rate (%) will be calculated in Days 30, and 60 for each subject as [(Total number of missed doses) / (Expected number of applications)] *100%.		Days 30,and 60
The incidence of AEs reported by the subjects, summarized by system organ class, severity, and relationship to study intervention, over the course of treatment.		Days 30, 60 and 75

Other Outcome Measures

Outcome Measure	Time Frame
The mean change in weight from baseline to days 60 and 75, and BMI from baseline to day 75.	Days 60 and 75
The number of subjects reporting changes in appetite (satiety/hunger) on days 30, 60, and 75.	Days 30, 60 and 75
The mean change in fasting blood glucose, HbA1C, and insulin levels from baseline to days 60.	Day 60
The mean change in blood pressure from baseline to days 30, 60, and 75.	Days 30, 60 and 75
The mean change in IL-6 from baseline to days 60.	Day 60
The mean changes in metabolic bone marker (Alkaline phosphatase (ALP)) from baseline to day 60	Day 60

Collaborators and Investigators

• Sponsor: Oxagon
• Investigators: Principal Investigator: Assem Anwar, Azhar Univeristy

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2024
• Primary Completion (Estimated): June 1, 2025
• Study Completion (Estimated): August 1, 2025

Study Registration Dates

• First Submitted: April 22, 2024
• First Submitted That Met QC Criteria: July 17, 2024
• First Posted (Actual): July 23, 2024

Study Record Updates

• Last Update Posted (Actual): July 23, 2024
• Last Update Submitted That Met QC Criteria: July 17, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: atrophy; postmenopause; vulvovaginal atrophy; vulvovaginal
• Additional Relevant MeSH Terms: Pathological Conditions, Anatomical; Atrophy; Physiological Effects of Drugs; Reproductive Control Agents; Oxytocics; Oxytocin
• Other Study ID Numbers: Oxagon

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No