Long-Term Safety of 30 mg and 60 mg Oral Daily Dose of Ospemifene in the Treatment of Vulvar and Vaginal Atrophy (VVA) in Postmenopausal Women With Intact Uterus

Long-Term Safety of 30 mg and 60 mg Oral Daily Dose of Ospemifene in the Treatment of Vulvar and Vaginal Atrophy (VVA) in Postmenopausal Women With Intact Uterus: A 40 Week Randomized, Double Blind, Placebo Controlled, Follow-Up to Protocol 15-50310.

The primary objective of the study was to assess the long-term safety of 30- and 60-mg daily doses of ospemifene in the treatment of Vulvar and Vaginal Atrophy (VVA) in postmenopausal women with an intact uterus.

Study Overview

• Status: Completed
• Conditions: Atrophy; Vaginal Diseases
• Intervention / Treatment: Drug: Placebo; Drug: Ospemifene (Dose 1); Drug: Ospemifene (Dose 2)

• Study Type: Interventional
• Enrollment (Actual): 180
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Postmenopausal women aged 40 to 80 years with a diagnosis of vulvar and vaginal atrophy (VVA) as assessed by vaginal pH, maturation index of vaginal smear, and self-reported symptoms at Baseline for Protocol 15-50310
• Had an intact uterus
• Met the inclusion and exclusion criteria for Protocol 15-50310
• Had completed Protocol 15-50310

Exclusion Criteria:

• Had clinically significant abnormal findings at the Week 12 End of Study visit for Protocol 15-50310
• Had any physical or mental condition which, in the opinion of the investigator, may have interfered with the subject's ability to comply with the study procedures

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment Group 1	Drug: Ospemifene (Dose 1)
Experimental: Treatment Group 2	Drug: Ospemifene (Dose 2)
Placebo Comparator: Treatment Group 3	Drug: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Adverse Events (AEs)		Week 20 (Phone Contact) to Week 56 (Visit 7)
Assessment of Cervical Pap Smear Samples	Cervical Pap smear samples were used to evaluate: atypical squamous cells of undetermined significance (ASC-US), squamous intraepithelial lesions (SILs), intraepithelial lesions or malignancy, and reactive endocervical cells and/or metaplastic cells.	Week 52 (Visit 6)
Assessment of Endometrial Biopsy	Assessments were based on Blaustein's classification.	Week 52 (Visit 6)
Mean Percent Change From Baseline in Serum Lipids		Baseline to Week 26 (Visit 5)
Mean Percent Change From Baseline in Serum Lipids		Baseline to Week 52 (Visit 6)
Mean Change in Blood Chemistry Parameters		Baseline to Week 26 (Visit 5)
Mean Change in Blood Chemistry Parameters		Baseline to Week 52 (Visit 6)
Assessment of Endometrial Safety With a Transvaginal Ultrasound (TVU)	Mean change in endometrial thickness from baseline	Baseline to Week 26 (Visit 5)
Assessment of Endometrial Safety With a TVU	Mean change in endometrial thickness from baseline	Baseline to Week 52 (Visit 6)
Change From Baseline in Visual Evaluation of the Vagina	Petechiae, pallor, friability, dryness in the mucosa, and redness in the mucosa were assessed on a 4-point scale (0=None, 1=Mild, 2=Moderate, 3=Severe).	Baseline to Week 26 (Visit 5)
Change From Baseline in Visual Evaluation of the Vagina	Petechiae, pallor, friability, dryness in the mucosa, and redness in the mucosa were assessed on a 4-point scale (0=None, 1=Mild, 2=Moderate, 3=Severe).	Baseline to Week 52 (Visit 6)
Change From Baseline in Estradiol (E2) Levels		Baseline to Week 26 (Visit 5)
Change From Baseline in Luteinizing Hormone (LH) Levels		Baseline to Week 26 (Visit 5)
Change From Baseline in Follicle Stimulating Hormone (FSH) Levels		Baseline to Week 26 (Visit 5)
Change From Baseline in Sex Hormone Binding Globulin (SHBG) Levels		Baseline to Week 26 (Visit 5)
Change From Baseline in Testosterone (Total) Levels		Baseline to Week 26 (Visit 5)
Change From Baseline in Testosterone (Free) Levels		Baseline to Week 26 (Visit 5)
Change From Baseline in E2 Levels		Baseline to Week 52 (Visit 6)
Change From Baseline in LH Levels		Baseline to Week 52 (Visit 6)
Change From Baseline in FSH Levels		Baseline to Week 52 (Visit 6)
Change From Baseline in SHBG Levels		Baseline to Week 52 (Visit 6)
Assessment of Mammography	Mammography was done for the detection of characteristic masses and microcalcifications in the breast.	Week 52 (Visit 6)
Change From Baseline in Testosterone (Total) Levels		Baseline to Week 52 (Visit 6)
Change From Baseline in Testosterone (Free) Levels		Baseline to Week 52 (Visit 6)
Change From Baseline in Antithrombin Antigen, P Levels		Baseline to Week 26 (Visit 5)
Change From Baseline in Fibrinogen Levels		Baseline to Week 26 (Visit 5)
Change From Baseline in Protein C Ag, P Levels		Baseline to Week 26 (Visit 5)
Change From Baseline in Protein S Ag (Free), P Levels		Baseline to Week 26 (Visit 5)
Change From Baseline in Thromboplastin Time		Baseline to Week 26 (Visit 5)
Change From Baseline in Antithrombin Antigen, P Levels		Baseline to Week 52 (Visit 6)
Change From Baseline in Fibrinogen Levels		Baseline to Week 52 (Visit 6)
Change From Baseline in Protein C Ag, P Levels		Baseline to Week 52 (Visit 6)
Change From Baseline in Protein S Ag (Free), P Levels		Baseline to Week 52 (Visit 6)
Change From Baseline in Thromboplastin Time		Baseline to Week 52 (Visit 6)
Assessment of Breast Palpation	Breast palpation was done by the investigator to assess abnormalities in the breast.	Week 26 (Visit 5)
Assessment of Breast Palpation	Breast palpation was done by the investigator to assess abnormalities in the breast.	Week 52 (Visit 6)
Assessment of Hematology Tests	Change from baseline	Baseline to Week 26 (Visit 5)
Change From Baseline in Erythrocyte (RBC) Levels		Baseline to Week 26 (Visit 5)
Change From Baseline in Hemogobin Levels		Baseline to Week 26 (Visit 5)
Change From Baseline in Hematocrit Levels		Baseline to Week 26 (Visit 5)
Assessment of Hematology Test Values	Change from baseline	Baseline to Week 52 (Visit 6)
Change From Baseline in Erythrocyte (RBC) Levels		Baseline to Week 52 (Visit 6)
Change From Baseline in Hemoglobin Levels		Baseine to Week 52 (Visit 6)
Change From Baseline in Hematocrit Levels		Baseline to Week 52 (Visit 6)
Change From Baseline in pH of Urine		Baseline to Week 26 (Visit 5)
Change From Baseline in Specific Gravtiy of Urine		Baseline to Week 26 (Visit 5)
Change From Baseline in pH of Urine		Baseline to Week 52 (Visit 6)
Change From Baseline in Specific Gravity of Urine		Baseline to Week 52 (Visit 6)
Change From Baseline in Systolic Blood Pressure (SBP)		Baseline to Week 26 (Visit 5)
Change From Baseline in Diastolic Blood Pressure (DBP)		Baseline to Week 26 (Visit 5)
Change From Baseline in Pulse Rate		Baseline to Week 26 (Visit 5)
Change From Baseline in Weight		Baseline to Week 26 (Visit 5)
Change From Baseline in BMI		Baseline to Week 26
Change From Baseline in SBP		Baseline to Week 52 (Visit 6)
Change From Baseline in DBP		Baseline to Week 52 (Visit 6)
Change From Baseline in Pulse Rate		Baseline to Week 52 (Visit 6)
Change From Baseline in Weight		Baseline to Week 52 (Visit 6)
Change From Baseline in BMI		Baseline to Week 52 (Visit 6)

Collaborators and Investigators

• Sponsor: Shionogi
• Collaborators: QuatRx Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): May 16, 2006
• Primary Completion (Actual): August 19, 2008
• Study Completion (Actual): September 18, 2008

Study Registration Dates

• First Submitted: April 18, 2012
• First Submitted That Met QC Criteria: April 23, 2012
• First Posted (Estimate): April 26, 2012

Study Record Updates

• Last Update Posted (Actual): May 21, 2018
• Last Update Submitted That Met QC Criteria: April 19, 2018
• Last Verified: April 1, 2018

More Information

Terms related to this study

• Keywords: Menopausal symptoms; Urogenital atrophy; Vaginal atrophy; Vulvar and vaginal atrophy in menopausal women
• Additional Relevant MeSH Terms: Pathological Conditions, Anatomical; Vaginal Diseases; Atrophy; Physiological Effects of Drugs; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Hormone Antagonists; Bone Density Conservation Agents; Estrogen Antagonists; Selective Estrogen Receptor Modulators; Estrogen Receptor Modulators; Tamoxifen
• Other Study ID Numbers: 15-50310X