MT-8554 for Reduction of Vasomotor Symptoms in Postmenopausal Women

Study Overview
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Brief Summary
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The purpose of this study is to assess the efficacy and safety of MT-8554 for treatment of vasomotor symptoms (VMS) associated with menopause.

Detailed Description
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This is a Phase II randomized, double-blind, placebo-controlled study for dose selection in postmenopausal women with moderate to severe VMS, defined as follows: Moderate: sensation of heat with sweating, able to continue activity Severe: sensation of heat with sweating, causing cessation of activity This study is comprised of a screening period, a run-in period and a 12-week double-blind treatment period.

Official Title
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A Randomized, Double Blind, Placebo Controlled Study to Assess the Effect of MT-8554 on the Frequency and Severity of Vasomotor Symptoms in Postmenopausal Women

Conditions
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Menopause Hot Flashes

Intervention / Treatment
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* Drug: MT-8554 1mg
* Drug: MT-8554 5mg
* Drug: MT-8554 10mg
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Additional screening criteria check may apply for qualification: Provide written informed consent to participate in this study Spontaneous amenorrhea for ≥12 months; or spontaneous amenorrhea for at least 6 months and with follicle stimulating hormone (FSH) levels >40 mIU/mL; or documented bilateral salpingo oophorectomy ≥6 weeks, with or without hysterectomy 7 or more moderate to severe VMS per day, or 50 or more moderate to severe VMS per week Have a consistent bedtime on at least 5 nights per week Mean VMS frequency during the Placebo Run in period does not drop by more than 50% from the mean level reported for 2 weeks during the Screening period VMS diary compliance >50% In the Investigator's opinion, subject is able to understand the nature of the study and any risk involved in participation, and is willing to cooperate and comply with the protocol restrictions and requirements Exclusion Criteria: Additional screening criteria check may apply for qualification: History of any cancer within 5 years except for basal cell carcinoma History of undiagnosed abnormal vaginal bleeding History of Hepatitis B, Hepatitis C or HIV History of psychiatric illness, excessive alcohol intake or use of recreational drugs who are unsuitable for study enrollment and compliance Presence or history of severe adverse reaction or allergy to any drug Peripheral vascular disease or disorders with associated vasculopathies Clinically significant conditions which could interfere with the objectives of the study or the safety of the subject, as judged by the Investigator Endometrial thickness of >=5 mm as measured by transvaginal ultrasound Abnormal result from baseline endometrial biopsy (i.e., endometrial hyperplasia or endometrial cancer) Aspartate aminotransferase (AST), alanine aminotransferase (ALT), or total bilirubin ≥2.0 × upper limit of normal (ULN) above the reference range Subjects of childbearing potential

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MT-8554 1mg<br> | Drug: MT-8554 1mg<br>* MT-8554 1mg QD, oral, 12 weeks<br>|
| Experimental: MT-8554 5mg<br> | Drug: MT-8554 5mg<br>* MT-8554 5mg QD, oral, 12 weeks<br>|
| Experimental: MT-8554 10mg<br> | Drug: MT-8554 10mg<br>* MT-8554 10mg QD, oral, 12 weeks<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Placebo QD, oral, 12 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in the Average Daily Frequency of Moderate to Severe VMS at Weeks 4 and 12 | The average daily frequency of moderate to severe VMS at a time point (Baseline, Weeks 4 and 12) was the average of the frequency of moderate to severe VMS of available diary days in a 7-day window. Changes in the average daily frequency of moderate to severe VMS at Week 4 and Week 12 compared to baseline were evaluated. | Baseline, Weeks 4 and 12 | 
| Change From Baseline in the Average Daily Severity Score of Mild to Severe VMS at Weeks 4 and 12 | The daily severity score of VMS was defined as (2xFmo + 3xFse)/(Fmo + Fse) for baseline, and (1xFmi + 2xFmo + 3xFse)/(Fmi + Fmo + Fse) for Weeks 4 and 12, where Fmi, Fmo, and Fse were the daily frequencies of mild, moderate, and severe VMS, respectively. The average daily severity score of mild to severe VMS at a time point (Baseline, Week 4 and Week 12) was the average of the daily severity of available diary days in the corresponding 7-day window. The severity score of VMS ranged from 0 (lowest severity) to 3 (highest severity). Change in the average daily severity score of mild to severe VMS at Week 4 and Week 12 compared to baseline were evaluated. | Baseline, Weeks 4 and 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Responders at Weeks 4 and 12 | Subjects with cutoff number or greater reduction in the average daily frequency of moderate and severe VMS compared to baseline. The cutoff number was calculated using anchor-based method. The cutoff number was defined as numerical value to maximize the sensitivity and the specificity, using Patient Global Impression of Change (PGIC) as the anchor. | Week 4 and Week 12 | 
| Change From Baseline in the Insomnia Severity Index at Week 4 and Week 12 | The Insomnia Severity Index was a self-rated, 7-item validated sleep scale that measured clinical insomnia severity. The total score ranged from 0-28 where higher values indicated increased severity of insomnia. | Baseline, Weeks 4 and 12 |