Trial Outcomes & Findings for A Study to Learn More About How Well Elinzanetant Works and How Safe it is for the Treatment of Vasomotor Symptoms (Hot Flashes) That Are Caused by Hormonal Changes Over 26 Weeks in Women Who Have Been Through the Menopause (NCT NCT05042362)

Study was conducted at 89 study centers in 8 countries, between 27-Aug-2021 (first participant first visit) and 27-Nov-2023 (last participant last visit).

A total of 1535 participants were screened; 1139 participants were not randomized. Most common reason for not being randomized was not meeting the eligibility criteria (1087 participants). 396 participants were randomized to treatment. A total of 197 participants were randomized to placebo - elinzanetant 120 mg arm and 199 participants to elinzanetant 120 mg arm.

A Study to Learn More About How Well Elinzanetant Works and How Safe it is for the Treatment of Vasomotor Symptoms (Hot Flashes) That Are Caused by Hormonal Changes Over 26 Weeks in Women Who Have Been Through the Menopause

The frequency of moderate to severe HF for each week during the treatment period was calculated using the available data during that particular week. Specifically for Week 4, Days 22-28 were used (Day 1 corresponds to start of treatment). Mean daily frequency is calculated as total number of moderate to severe HF during that week divided by the total number of available days with data during that week

The frequency of moderate to severe HF for each week during the treatment period was calculated using the available data during that particular week. Specifically for Week 12, Days 78-84 were used (Day 1 corresponds to start of treatment). Mean daily frequency is calculated as total number of moderate to severe HF during that week divided by the total number of available days with data during that week

In the HFDD, hot flash (HF) severity is scored as 1=mild, 2=moderate, and 3=severe; a decrease indicates improvement. The diary records the number of mild, moderate, and severe HFs during day and night. Mild HFs are a "sensation of heat without sweating"; moderate are "heat with sweating but able to continue activity"; severe are "heat with sweating that stops activity." Baseline mean daily severity is calculated as: (2×moderateHFs+3×severeHFs)÷(totalmoderate+severeHFs).(2 × moderate HFs + 3 × severe HFs) ÷ (total moderate + severe HFs).(2×moderateHFs+3×severeHFs)÷(totalmoderate+severeHFs). If none occur, severity=0. Weekly severity during treatment is based on available days (Week 4: Days 22-28; Week 12: Days 78-84; Day 1=start of treatment), averaging the mean daily severity for that week. If more than 2 days are missing, the weekly value is set to missing.

In the HFDD, hot flash (HF) severity is categorized as 1=mild, 2=moderate, 3=severe; thus, a decrease indicates improvement. The HFDD records the number of mild, moderate, and severe HFs during day and night. Mild HFs are a "sensation of heat without sweating"; moderate involve "heat with sweating but able to continue activity"; severe involve "heat with sweating that stops activity." Mean daily severity at baseline is calculated as: (2 × moderate HFs) + (3 × severe HFs)\\\] ÷ (total moderate + severe HFs). If none occur, severity is set to 0. Weekly severity during treatment is based on available days (Week 4: Days 22-28; Week 12: Days 78-84; Day 1=start of treatment), averaging mean daily severity across that week. If more than 2 days are missing, the week is set to missing.

The frequency of moderate to severe HF for each week during the treatment period was calculated using the available data during that particular week. Specifically for Week 1, Days 2-8 were used (Day 1 corresponds to start of treatment). Mean daily frequency is calculated as total number of moderate to severe HF during that week divided by the total number of available days with data during that week

The frequency of moderate to severe HF for each week during the treatment period was calculated using the available data during that particular week. Specifically, for Week 1 Days 2-8 were used instead of 1-7, because the intake started on Day 1 only before going to bed, for Week 4 Days 22-28 were used and for Week 12 Days 78-84 were used (Day 1 corresponds to start of treatment). These data were aggregated to a mean daily frequency as (total number of moderate to severe HF during that week) / (total number of available days with data during that week). In case data was not available for more than 2 days within a week, the value for that particular week was set to missing.

In controversy of what you have been proposing above here you are just explaining the PROMIS SD SF 8b scores, not the secondary endpoint which is the change in the T-scores from BL to week 12 The PROMIS Sleep Disturbance Short Form 8b (PROMIS SD SF 8b) measures sleep disturbance over the past 7 days using 8 items assessing sleep quality, depth, restorative sleep, difficulty falling or staying asleep, and perceptions of sleep adequacy and satisfaction. Items use 5-point response options that vary by item (e.g., Not at all → Very much; Never → Always; Very poor → Very good). Item scores sum to a raw score of 8-40, which is converted to a T-score (mean 50, SD 10; range 28.9-76.5). Higher scores reflect greater sleep disturbance. PROMIS cut points classify T-scores of 55-59 as mild, 60-69 as moderate, and ≥70 as severe disturbance.

The MENQOL questionnaire was comprised of 29 items assessing the presence of menopausal symptoms and the impact of menopause on health-related quality of life over the past week. The items assessed four domains of symptoms and functioning: VMS, psychosocial functioning, physical functioning, and sexual functioning. For each item, the participant indicated if they had experienced the symptom (yes/no). If participants selected yes, participants rated how bothered they were by the symptom using a six-point verbal descriptor scale, with response options ranging from 0 'not at all bothered' to 6 'extremely bothered'. Based on the individual responses, item scores, domain scores, and a total MENQOL score were calculated. Each score ranged from 1-8, higher scores indicated greater bother.

The BDI-II was a 21-item questionnaire assessed the intensity of depressive symptoms over the past 2 weeks. Each item was a list of four statements arranged in increasing levels of severity about a particular symptom of depression. Items used a 4-point verbal response scale ranging from 0 (not at all) to 3 (extreme form of each symptom); specific response options were tailored to the aspect of depression being measured in each item. A total score ranging from 0 to 63 was calculated with scores of 0-13 indicating mild minimal range, 14 - 19 mild depression, 20 - 28 indicating moderate and 29 - 63 severe depression (higher score = greater depression).

The BDI-II was a 21-item questionnaire assessing the intensity of depressive symptoms over the past 2 weeks. Each item was a list of four statements arranged in increasing levels of severity about a particular symptom of depression. Items used a 4-point verbal response scale ranging from 0 (not at all) to 3 (extreme form of each symptom); specific response options were tailored to the aspect of depression being measured in each item. A total score ranging from 0 to 63 was calculated with scores of 0-13 indicating mild minimal range, 14 - 19 mild depression, 20 - 28 indicating moderate and 29 - 63 severe depression (higher score = greater depression).