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 (OASIS-2) (NCT NCT05099159)

Study was conducted at 95 study centers in 10 countries worldwide, between 29-Oct-2021 (first participant first visit) and 10-Oct-2023 (last participant last visit).

A total of 1483 participants were screened, of whom 1083 participants were screen failures. Most common reason for screen failure was not meeting the eligibility criteria (1044 participants). 400 of the screened participants were randomized to treatment and 324 participants completed the study.

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 (OASIS-2)

Participants' assessments of HF were recorded electronically twice daily using the sponsor developed Hot Flash Daily Diary (HFDD). The HFDD was completed in the morning after waking up (morning diary) and each evening at bedtime (evening diary) on the hand-held device. The HFDD items assessed the number of mild, moderate, and severe HF experienced during the day and during the night. Mild HF was defined as a "sensation of heat without sweating", moderate HF was defined as a "sensation of heat with sweating, but able to continue activity", and severe HF was defined as a "sensation of heat with sweating, causing cessation (stopping) of activity". 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, Day 22-28 were used (Day 1 corresponds to start of treatment).

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, Day 78-84 were used (Day 1 corresponds to start of treatment).

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.

Participants' assessments of HF were recorded electronically twice daily using the sponsor developed HFDD. The HFDD was completed in the morning after waking up (morning diary) and each evening at bedtime (evening diary) on the hand-held device.

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 is not available for more than 2 days within a week, the value for that particular week was be 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 participants 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. The four domain scores were calculated as a mean of converted single item scores (range 1-8), and the mean of the four domain scores yielded the MENQOL total score. Higher scores indicated greater bother.

The BDI-II consisted of 21 items to assess the severity of depression 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 indicating mild depression, 20 - 28 indicating moderate and 29 - 63 indicating severe depression (higher score = greater depression).

The BDI-II consisted of 21 items to assess the severity of depression 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 indicating mild depression, 20 - 28 indicating moderate and 29 - 63 indicating severe depression (higher score = greater depression).