MT-8554 for Reduction of Vasomotor Symptoms in Postmenopausal Women

Phase 2

Completed

Interventions: Drug: MT-8554 5mg
Drug: MT-8554 10mg
Drug: Placebo
Drug: MT-8554 1mg

Brief Summary: 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: 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.

Recruitment & Eligibility

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

Arm && Interventions

Primary Outcome Measures

Name	Time	Method
Change From Baseline in the Average Daily Severity Score of Mild to Severe VMS at Weeks 4 and 12	Baseline, 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.
Change From Baseline in the Average Daily Frequency of Moderate to Severe VMS at Weeks 4 and 12	Baseline, 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.

Secondary Outcome Measures

Name	Time	Method
Percentage of Responders at Weeks 4 and 12	Week 4 and Week 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.
Change From Baseline in the Insomnia Severity Index at Week 4 and Week 12	Baseline, Weeks 4 and 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.