Safety and Efficacy of Asimadoline (TP0052) in Patients With Vasomotor Symptoms (VMS).

Safety as Assessed by Adverse Events, Clinical Laboratory Parameters, and Vital Signs

Safety will be evaluated based on the incidence and severity of adverse events and changes from baseline in laboratory values and vital signs. Adverse events will be graded using the Common Terminology Criteria for Adverse Events, Version 5.0 (grade 1 = mild; grade 5 = death; higher scores indicate worse outcomes). Liver function tests include alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase, alkaline phosphatase, and total bilirubin. Higher values indicate worse liver function. Kidney function will be assessed by estimated glomerular filtration rate (scale: 0 to ≥90 mL/min/1.73 m²; \<60 considered abnormal; higher is better). Hematocrit will be monitored (percent; \<30% is abnormal; higher is better within normal range). Vital signs include blood pressure, heart rate, respiratory rate, and oral temperature; higher blood pressure and heart rate indicate worse outcomes. A urine pregnancy test (positive or negative) will also be performed.

Change in Frequency of Moderate to Severe Vasomotor Symptoms (VMS)

The frequency of moderate and severe vasomotor symptoms (VMS) will be measured using participant-completed diaries (paper or electronic) recorded twice daily (morning and evening) from Baseline to Week 8. VMS frequency is defined as the number of moderate or severe hot flashes or night sweats reported per day. Moderate VMS: sensation of heat with sweating, without disruption of activity. Severe VMS: sensation of heat with sweating that causes cessation of activity or awakening at night. The outcome is calculated as the average number of moderate/severe VMS episodes per day, averaged over the 8-week treatment period. Due to protocol-defined eligibility criteria, all participants will report at least 40 moderate/severe VMS episodes per week at baseline. During treatment, the minimum possible observed value is 0 episodes/day. There is no fixed upper limit; values of 20-30 episodes/day may occur. Higher values indicate worse symptom frequency.

Change in Severity-Weighted Vasomotor Symptom (VMS) Score (Composite Severity Index).

VMS severity will be assessed using a composite score derived from participant diaries recorded twice daily from Baseline to Week 8. Each VMS episode is assigned a severity score: Mild = 1 Moderate = 2 Severe = 3 Daily VMS severity scores are calculated as: (# Mild × 1) + (# Moderate × 2) + (# Severe × 3) Weekly averages of daily severity scores are computed for each participant. The average across the 8-week treatment period will serve as the outcome measure. Due to protocol-defined eligibility criteria, all participants will report ≥40 moderate/severe VMS episodes per week at baseline. During treatment, the minimum possible observed value is 0. There is no fixed upper limit; for example, 10 severe episodes per day would result in a score of 30. Higher scores indicate worse symptom severity.

Exploratory Outcome Measure - Change in VMS (vasomotor symptoms) Bothersomeness Score

Participant-reported bothersomeness of vasomotor symptoms (VMS) will be assessed using a numeric rating scale completed twice daily (morning and evening) via VMS diaries from Baseline to Week 8. Scale: 0 (not bothersome at all) to 10 (extremely bothersome) Minimum = 0 Maximum = 10 Higher scores indicate greater VMS-related bother.

Exploratory Outcome Measure - Change in Sleep Quality Rating

Sleep quality will be assessed via participant-reported ratings recorded in daily VMS diaries twice daily (morning and evening) from Baseline to Week 8. Participants will indicate the degree to which VMS disrupted their sleep using a 0-10 numeric scale. Minimum score: 0 (no disruption to sleep) Maximum score: 10 (extreme disruption to sleep) Higher scores indicate worse sleep quality.

Exploratory Outcome Measure - Change in Menopause-Specific Quality of Life (MENQOL) Score.

Quality of life will be measured using the MENQOL questionnaire, a validated 29-item scale assessing four domains: vasomotor, psychosocial, physical, and sexual. Participants will complete the MENQOL at baseline and at Week 8. Scale range per item: 1 (not at all bothered) to 8 (extremely bothered) Overall score = mean of all item responses Minimum = 1 Maximum = 8 Higher scores indicate worse menopause-related quality of life.

Exploratory Outcome Measure - Change in Female Sexual Function Index (FSFI) Score.

Sexual functioning will be assessed using the FSFI questionnaire, a validated 19-item instrument covering desire, arousal, lubrication, orgasm, satisfaction, and pain. FSFI will be administered at Baseline and Week 8. Scale total range: 2 to 36 Minimum = 2 Maximum = 36 Higher scores indicate better sexual functioning.