A Randomized Controlled Phase 2 Study to Determine Lowest Efficacious Dose of Ovestin in Vulvar and Vaginal Atrophy

NCT04159493 | Withdrawn Phase 2 FDA Drug

• 1 other identifier: CLINTECUS-19-OVDFP2
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a prospective, multicenter, randomized, double-blind, placebo-controlled, dose-de-escalation study whose purpose is to establish the lowest efficacious dose. The first 40 subjects will be randomized 1:1:1:1 to either 500 mcg, 50 mcg, 10 mcg, or placebo. After four weeks of dosing with 500 mcg, vaginal pH, vaginal maturation index, and subject's most bothersome moderate to severe symptom will be assessed; the changes observed will be used as the benchmark for efficacy throughout the remainder of the study and select the next dose-level to be investigated. Subjects will be enrolled in small cohorts at various doses until the lowest effective dose is identified. Then, 1 to 2 doses and a placebo group will be expanded to enroll 70 subjects per treatment group.

Conditions

Vaginal Atrophy

Outcome Measures

Primary Outcomes (3)

• Vaginal Maturation Index

  Mean change from baseline at Week 12 in vaginal maturation index (percentage of superficial and parabasal cells)

  12 weeks

• Vaginal pH

  Mean change from baseline at Week 12 in vaginal pH

  12 Weeks

• Most Bothersome Symptom

  Mean change from baseline at Week 12 in the moderate to severe symptom that has been identified by the subject as being the most bothersome to her

  12 weeks

Secondary Outcomes (1)

• Incidence of adverse events

  12 weeks

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Subjects will be randomized to placebo. Placebo, Vaginal Application 0.5 to 2 g administered daily for the 1st 14 days, then twice weekly for following 10 weeks

Drug: Placebo

Ovestin

ACTIVE COMPARATOR

Subjects will be randomized or assigned to varying doses of Ovestin (500, 50, 25, 12.5, 10, 5, 2.5, 0.5, 0.25 mcg) as determined by the dose de-escalation constraints specified in the protocol. Active, Vaginal Application 0.5 to 2 g administered daily for the 1st 14 days, then twice weekly for following 10 weeks

Drug: Estriol

Interventions

Estriol DRUG

Vaginal Application

Also known as: Ovestin

Ovestin

Placebo DRUG

Vaginal Application

Placebo

Eligibility Criteria

• Age: 45 Years - 85 Years
• Gender Eligibility Details: Post-menopausal women aged 45 to 85 years at randomization will be enrolled to the study.
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may not qualify if:

• Subjects will be excluded from the study for:
• History of endometrial hyperplasia or cervical cancer for participants who have a uterus.
• Known, previous or suspected breast cancer.
• Known, previous or suspected estrogen-dependent malignant tumors (e.g. endometrial cancer). In participants with a uterus, the histological diagnosis of disordered proliferative endometrium, endometrial hyperplasia or cancer based on endometrial biopsy.
• Any malignancy unless free of disease for at least 5 years.
• Know hypersensitivity to the active substance or any of the excipients.
• Undiagnosed uterine bleeding.
• Known pelvic organ prolapse past the level of the hymen.
• Evidence of vaginal infection on physical examination.
• Previous or current venous thromboembolism (deep venous thrombosis, pulmonary embolism).
• Active or recent arterial thromboembolic disease (e.g. angina or myocardial infarction)
• Known thrombophilic disorders or conditions that may adversely affect coagulation, including:
• Protein C, Protein S, or antithrombin III deficiency
• Factor XIII mutation, dysfibrinogenemia, antiphospholipid syndrome, heparin-induced thrombocytopenia, paroxysmal nocturnal hemoglobinuria, sickle-cell disease, polycythemia vera, essential thrombocytosis, nephrotic syndrome
• History of elevated levels of factor VIII, factor IX, factor XI, fibrinogen and thrombin-activatable fibrinolysis inhibitor, or decreased levels of tissue factor pathway inhibitor

Sponsors & Collaborators

• Aspen USA Inc: lead

MeSH Terms

Interventions

Estriol

Intervention Hierarchy (Ancestors)

Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This is a prospective, multicenter, randomized, double-blind, placebo-controlled, dose de-escalation study whose purpose is to establish the lowest efficacious dose of Ovestin

Study Record Dates

• First Submitted: October 22, 2019
• First Posted: November 12, 2019
• Study Start: June 5, 2021
• Primary Completion: February 28, 2023
• Study Completion: May 15, 2023
• Last Updated: July 23, 2021

Record last verified: 2021-07

Data Sharing

• IPD Sharing: Will not share