A Study Following Women in Menopause Treated With a Non-hormonal Therapy for Hot Flashes and Night Sweats

Study Overview
=================
Brief Summary
-----------------
Hot flashes and night sweats (also known as vasomotor symptoms or VMS) are the most common symptoms which bother women in menopause. This study will follow women going through menopause who have hot flashes and night sweats that cause them bother. They will be starting a non-hormonal therapy prescribed by their healthcare provider (HCP) to treat these symptoms. The women will receive prescriptions for the non-hormonal therapy from their HCP for up to 1 year. This real-world study will provide information on outcomes from various non-hormonal therapies. The study sponsor (Astellas) will not decide which therapy the women receive. However, the sponsor will provide instructions on when the women visit their HCP's office and what is recorded during the study. Throughout the study, the women will visit their HCP's office. Some of the visits will be in-person, but most will be virtual. The virtual visits can be carried out at home using a smartphone, tablet or computer. The main aim of the study is to check if the hot flashes and night sweats that bother women change after 12 weeks (3 months) of treatment. The study will also check the women's sleep patterns, their productivity at work, and their general well-being before and after starting treatment. The overall safety of the non-hormonal therapies will also be examined.

Official Title
-----------------
A Phase IV, Longitudinal, Observational Study Examining Real-World Outcomes of Non-Hormonal Pharmacotherapies Among Individuals Treated for Bothersome Vasomotor Symptoms

Conditions
-----------------
Hot Flashes

Intervention / Treatment
-----------------
* Drug: Fezolinetant
* Drug: Paroxetine
* Drug: Citalopram
* Drug: Escitalopram
* Drug: Desvenlafaxine
* Drug: Venlafaxine
* Drug: Gabapentin
* Drug: Clonidine
* Drug: Pregabalin
* Drug: Oxybutynin
* Drug: Any other SSRI/SNRI not already specified
* Drug: Any other non-hormonal pharmacologic therapy prescribed for the treatment of VMS not included in a category above


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Participant is diagnosed with bothersome VMS due to/associated with menopause for at least 3 months based on a standard of care assessment captured in consultation with an HCP including the participant's history, routine physical examination, and routine laboratory assessments. HCP has made the clinical decision to begin pharmacologic treatment with a non-HT including, a selective neurokinin 3 receptor (NK3-R) antagonist, an SSRI, SNRI, gabapentin, clonidine, pregabalin, oxybutynin or other non-HT, as part of the standard treatment for VMS. This may be the first course of treatment, a restart or a switch from one drug to another. A restart or switch of a previous therapy requires a minimum of a 10-day period not on therapy/washout period. Participant's health status is stable based on their medical history and general physical exam and determined to be a candidate for treatment with non-HTs. If participant has been prescribed an SSRI or SNRI for the treatment of depression or anxiety, they must be on a stable or consistent dose for a minimum of 3 months. Participant has a negative urine pregnancy test at screening if not post-menopausal. Only for participants utilizing complementary and alternative therapies, mind-body techniques, or supplements for the treatment of VMS: participant has been on such therapies for ≥ 3 months and intends to continue through duration of study. Exclusion Criteria: Participant is currently enrolled in any interventional or non-interventional wearable device study. Participant has any condition which makes the participant unsuitable for the study. Participant has a contraindication to the non-HT they are being prescribed for the treatment of VMS. Participant is currently taking hormonal contraceptives or other hormonal therapies (vaginal/local estrogen preparations and levonorgestrel-releasing intrauterine system are not prohibited). Participant has presence of moderately severe or severe depression per standard of care assessment utilizing a standardized depression screening tool. Participant is currently pregnant or planning to become pregnant. Participant is post-menopausal and has a history of unexplained uterine bleeding within the last 6 months. Participant has pre-existing uncontrolled thyroid disease. Participant has unstable angina or participant has uncontrolled hypertension based on a standard of care assessment. Participants who do not meet these criteria may be re-assessed after initiation or review of antihypertensive measures. Participants with a medical history of hypertension can be enrolled once they are medically clear (stable and compliant). Participant has had insomnia unrelated to either menopause or bothersome VMS due to/associated with menopause. Participant has known substance abuse or alcohol addiction within 6 months of screening. Participant has been on intramuscular estradiol within 8 weeks of screening. Participant has a current diagnosis of a malignancy or history of a malignancy within the past 2 years (This does not include basal cell carcinoma or breast cancer.) Participants with metastatic (Stage 4) breast cancer. Participants with non-metastatic (stage 0 to 3) breast cancer who have not been on stable adjuvant endocrine therapy (tamoxifen or aromatase inhibitors with or without gonadotropin-releasing hormone analogues) for a minimum of 3 months.

Ages Eligible for Study
-----------------
Minimum Age: 40 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Neurokinin 3 Receptor (NK3-R) Antagonist<br>Participants prescribed NK3-R Antagonist for the treatment of VMS. | Drug: Fezolinetant<br>* Oral<br>* Other names: VEOZAH;|
| Selective serotonin reuptake inhibitor (SSRI)/Serotonin and norepinephrine reuptake inhibitor (SNRI)<br>Participants prescribed SSRI/SNRI for the treatment of VMS. | Drug: Paroxetine<br>* Oral<br>Drug: Citalopram<br>* Oral<br>Drug: Escitalopram<br>* Oral<br>Drug: Desvenlafaxine<br>* Oral<br>Drug: Venlafaxine<br>* Oral<br>Drug: Any other SSRI/SNRI not already specified<br>* Oral<br>|
| Other<br>Participants prescribed something other than NK3-R Antagonist or SSRI/SNRI for the treatment of VMS. | Drug: Gabapentin<br>* Oral<br>Drug: Clonidine<br>* Oral<br>Drug: Pregabalin<br>* Oral<br>Drug: Oxybutynin<br>* Oral<br>Drug: Any other non-hormonal pharmacologic therapy prescribed for the treatment of VMS not included in a category above<br>* Oral<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean change from baseline to week 12 in symptom bother measured by the Menopause-Specific Quality of Life Domain (MENQoL) 1-week recall VMS domain score | The MENQoL is a 29-item patient reported outcome (PRO) measure that assesses the impact of 4 domains of menopausal symptoms: vasomotor, psychosocial, physical, and sexual. Each item score ranges from 1 to 8, and each domain is scored separately; each domain mean ranges from 1 to 8. Higher scores represent more bothersome menopausal symptoms. A reduction (improvement) of 1 is the minimum clinically important difference for the MENQoL. | Baseline and week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of participants classified as 1-point responders as measured by the MENQol 1-week recall VMS domain | Participants with a reduction (improvement) in symptom bother score ≥ 1 unit will be classified as 1-point responders. | Up to week 52 | 
| Percentage of participants classified as 2-point responders as measured by the MENQol 1-week recall VMS domain | Participants with a reduction (improvement) in symptom bother score ≥ 2 unit will be classified as 2-point responders. | Up to week 52 | 
| Mean change from baseline in total score of Patient-Reported Outcomes Measurement Information System Sleep Disturbance Sexual Function (PROMIS SD SF) 8b | The PROMIS SD SF 8b assesses self-reported sleep disturbance over the past 7 days and includes perceptions of restless sleep; satisfaction with sleep; refreshing sleep; difficulties sleeping, getting to sleep or staying asleep; amount of sleep; and sleep quality. Responses to each of the 8 items range from 1 to 5, and the range of possible summed raw scores is 8 to 40. Higher scores on the PROMIS SD SF 8b indicate more of the concept measured (disturbed sleep). | Baseline and weeks 4, 8, 12, 24 and 52 | 
| Total score from Patient Global Impression of Severity (PGI-S) of SD | The PGI-S SD evaluates patient perceived severity of sleep disturbance. Ratings range from (1) no problems to (4) severe problems. | Up to week 52 | 
| Total score from Patient Global Impression of Change (PGI-C) of SD | PGI-C SD evaluates patient perceived change in sleep disturbance from the initiation of treatment. Ratings range from (1) much better to (7) much worse. | Up to week 52 | 
| Change from baseline in average daily total sleep time, as recorded by wearable device | The wearable device will capture movement and physiological signals to derive measures related to sleep. | Baseline to weeks 4, 8 and 12 | 
| Change from baseline in average daily sleep efficiency, as recorded by wearable device | The wearable device will capture movement and physiological signals to derive measures related to sleep. | Baseline to weeks 4, 8 and 12 | 
| Change from baseline in average daily wake after sleep onset (WASO), as recorded by wearable device | The wearable device will capture movement and physiological signals to derive measures related to sleep. | Baseline to weeks 4, 8 and 12 | 
| Change from baseline in average daily number of nighttime awakenings, as recorded by wearable device | The wearable device will capture movement and physiological signals to derive measures related to sleep. | Baseline to weeks 4, 8 and 12 | 
| Change from baseline in average daily sleep latency, as recorded by wearable device | The wearable device will capture movement and physiological signals to derive measures related to sleep. | Baseline to weeks 4, 8 and 12 | 
| Mean change from baseline in the MENQoL total score | The MENQoL is a 29-item patient reported outcome (PRO) measure that assesses the impact of 4 domains of menopausal symptoms: vasomotor, psychosocial, physical, and sexual. Each item score ranges from 1 to 8, and each domain is scored separately; each domain mean ranges from 1 to 8. The total score is the mean of the domain means. Higher scores represent more bothersome menopausal symptoms. A reduction (improvement) of 1 is the minimum clinically important difference for the MENQoL. | Baseline to weeks 4, 8, 12, 24 and 52 | 
| Mean change from baseline in the MENQoL vasomotor 1-week recall VMS domain score | The MENQoL is a 29-item patient reported outcome (PRO) measure that assesses the impact of 4 domains of menopausal symptoms: vasomotor, psychosocial, physical, and sexual. Each item score ranges from 1 to 8, and each domain is scored separately; each domain mean ranges from 1 to 8. Higher scores represent more bothersome menopausal symptoms. A reduction (improvement) of 1 is the minimum clinically important difference for the MENQoL. | Baseline to weeks 4, 8, 24 and 52 | 
| Mean change from baseline in the MENQoL 1-week recall psychosocial domain score | The MENQoL is a 29-item patient reported outcome (PRO) measure that assesses the impact of 4 domains of menopausal symptoms: vasomotor, psychosocial, physical, and sexual. Each item score ranges from 1 to 8, and each domain is scored separately; each domain mean ranges from 1 to 8. Higher scores represent more bothersome menopausal symptoms. A reduction (improvement) of 1 is the minimum clinically important difference for the MENQoL. | Baseline to weeks 4, 8, 12, 24 and 52 | 
| Mean change from baseline in the MENQoL 1-week recall physical domain score | The MENQoL is a 29-item patient reported outcome (PRO) measure that assesses the impact of 4 domains of menopausal symptoms: vasomotor, psychosocial, physical, and sexual. Each item score ranges from 1 to 8, and each domain is scored separately; each domain mean ranges from 1 to 8. Higher scores represent more bothersome menopausal symptoms. A reduction (improvement) of 1 is the minimum clinically important difference for the MENQoL. | Baseline to weeks 4, 8, 12, 24 and 52 | 
| Mean change from baseline in the MENQoL 1-week recall sexual domain score | The MENQoL is a 29-item patient reported outcome (PRO) measure that assesses the impact of 4 domains of menopausal symptoms: vasomotor, psychosocial, physical, and sexual. Each item score ranges from 1 to 8, and each domain is scored separately; each domain mean ranges from 1 to 8. Higher scores represent more bothersome menopausal symptoms. A reduction (improvement) of 1 is the minimum clinically important difference for the MENQoL. | Baseline to weeks 4, 8, 12, 24 and 52 | 
| Total score from PGI-C VMS | PGI-C VMS evaluates participant perceived change in VMS. Ratings range from (1) much better to (7) much worse. | Up to week 52 | 
| Mean change from baseline in the VMS-related work productivity and activity impairment (WPAI-VMS) domain score | The WPAI-VMS is a 6-item PRO measure that examines VMS-related work productivity and activity in the preceding 7 days. It consists of 4 domains: absenteeism, presenteeism, overall work productivity loss, and activity impairment. WPAI-VMS outcomes are expressed as impairment percentages, with higher numbers indicating greater impairment and less productivity (that is, worse outcomes). | Baseline to weeks 4, 8, 12, 24 and 52 | 
| Mean change from baseline in the female sexual function index (FSFI) domain score | The FSFI is comprised of 19 questions with response options varying among items and ranging from 0 to 5 or 1 to 5. The FSFI has 6 domains: desire, arousal, lubrication, orgasm, satisfaction and pain. Within the individual domains, a domain score of zero indicates that the participant-reported having no sexual activity during the past month. The overall score can range from 2 to 36. A higher score overall or for individual domains indicates better sexual function. | Baseline to weeks 4, 8, 12, 24 and 52 | 
| Mean change from baseline in the mean number of VMS episodes per 24 hours self-reported by participants via wearable device event marker | Participant manually records VMS episodes on the wearable device. | Baseline to weeks 4, 8 and 12 | 
| Mean change from baseline in the mean number of daytime VMS episodes per 24 hours self-reported by participants via wearable device event marker | Participant manually records VMS episodes on the wearable device. | Baseline to weeks 4, 8 and 12 | 
| Mean change from baseline in the mean number of nighttime VMS episodes per 24 hours self-reported by participants via wearable device event marker | Participant manually records VMS episodes on the wearable device. | Baseline to weeks 4, 8 and 12 | 
| Number of participants with Adverse Events (AEs) | An AE is defined as any untoward medical occurrence in a participant administered a study drug, and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product whether or not considered related to the medicinal (investigational) product. | Up to 52 weeks | 
| Number of participants with Serious Adverse Events (SAEs) | An AE is considered serious if, in the view of either the investigator or sponsor, it: Results in death, is life-threatening, results in persistent or significant disability/incapacity or substantial disruption of the ability to conduct normal life functions, is a congenital anomaly or birth defect of a child conceived during the exposure of one of the parents to the drug studied, requires inpatient hospitalization or leads to prolongation of hospitalization, is a medically important event or reaction. | Up to 52 weeks | 
| Number of participants with vital sign abnormalities and/or adverse events (AEs) | Number of participants with potentially clinically significant vital sign values. | Up to 52 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
fezolinetant, vasomotor symptoms, menopause, night sweats, non-hormonal treatment