Back to resultsTrial to Investigate the Effect of ESN364 in Early Postmenopausal Women Suffering From Hot Flashes
Primary Purpose
Hot Flashes
Status
Completed
Phase
Phase 2
Locations
Belgium
Study Type
Interventional
Intervention
Fezolinetant
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Hot Flashes focused on measuring Hot flashes, ESN364, ASP2693, fezolinetant, menopause, postmenopausal
Eligibility Criteria
Inclusion Criteria:
- Spontaneous amenorrhea for at least 12 consecutive months; or spontaneous amenorrhea for at least 6 months with biochemical criteria of menopause (FSH >40 IU/L); or spontaneous amenorrhea for at least 3 months with biochemical/physical criteria of menopause (FSH >40 IU/L and E2 <0.21 nmol/); or having had bilateral oophorectomy at least 6 weeks prior to screening (with or without hysterectomy);
- At least 49 moderate or severe hot flashes or night sweats over a period of 7 consecutive days, as recorded in the daily diary during the screening period, with at least 4 of those days with 7 or more moderate or severe hot flashes per day;
- In good general health as determined on the basis of medical history and general physical examination performed at screening; hematology and chemistry parameters, pulse rate and/or blood pressure, and ECG within the reference range for the population studied, or showing no clinically relevant deviations;
- Negative urine test for selected drugs of abuse (amphetamines, tricyclic antidepressants, cannabinoids, cocaine, tetrahydrocannabinol, or opiates) at screening;
- Negative serology panel (including hepatitis B surface antigen [HBsAg], antihepatitis C virus [HCV] and human immunodeficiency virus (HIV) antibody screens);
- Negative urine pregnancy test at screening;
Exclusion Criteria:
- Use of a prohibited therapy or not willing to wash-out drugs considered prohibited therapies;
- History (in the past year) or presence of drug or alcohol abuse;
- Suicide attempt in the past 3 years;
- Previous or current history of a malignant tumor (except basal cell carcinoma);
- Active liver disease or jaundice, or out-of-range values of alanine aminotransferase (ALT) and aspartate aminotransferase (AST); or total bilirubin >1.3 times the upper limit of normal (ULN); or creatinine >1.5 times the ULN; or estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease (MDRD) formula <60 mL/min/1.73 m2 at screening;
- Medical condition or chronic disease (including history of neurological [including cognitive], hepatic, renal, cardiovascular, gastrointestinal, pulmonary [e.g., moderate asthma], or endocrine disease) or malignancy that could confound interpretation of the study outcome;
- Any psychological disorder according to the criteria indicated in the Diagnostics and Statistical Manual of Mental Disorders (DSM, 4th edition) within one year prior to screening. Such disorders include but are not limited to current major depression, alcohol (more than 3 glasses of wine, beer, or equivalent/day) or substance abuse/dependence;
- Unsuited to participate in the study, based on findings observed during physical examination, vital sign assessment, or 12-lead ECG;
- History of severe allergy, hypersensitivity, or intolerance to drugs in general, including the study drug and any of its excipients;
- Presence or sequellae of gastrointestinal, liver, kidney or other conditions known to interfere with the absorption, distribution, metabolism, or excretion (ADME) mechanisms of drugs;
- Concurrent participation in another interventional study (or participation within 3 months prior to screening in this study);
- History of poor compliance in clinical studies;
- Unable or unwilling to complete the study procedures;
- Subject is the Investigator or any sub-investigator, research assistant, pharmacist, study coordinator, or other staff or relative thereof who is directly involved in the conduct of the study.
Sites / Locations
- Site BE32004
- Site BE32003
- Site BE32001
- Site BE32006
- Site BE32005
- Site BE32007
- Site BE32008
- Site BE32009
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Fezolinetant
Placebo
Arm Description
Participants received 90 milligrams (mg) fezolinetant capsules orally, twice daily (BID) for a period of 12 weeks
Participants received fezolinetant matching placebo capsules orally, BID for a period of 12 weeks.
Outcomes
Primary Outcome Measures
Change From Baseline to Week 12 in The Weekly General Hot Flash Score
The HF score (based on severity and frequency) was calculated as:
(number of mild HF/day × 1) + (number of moderate HF/day × 2) + (number of severe HF/day × 3)
The severity of HFs is clinically defined as follows:
Mild: sensation of heat without sweating/dampness. If at night, participant didn't wake up but later notices damp sheets or clothing.
Moderate: Sensation of heat with sweating/dampness, but was able to continue activity. If at night, participant woke up because she was feeling hot and/or was sweating, but no action was necessary other than rearranging the bed sheets.
Severe: Sensation of intense heat with sweating, causing disruption of activity. If at night, participant woke up hot and was sweating and needed to take action (e.g., removing layers of clothes, open the window, or get out of bed).
Higher scores indicate worse symptoms. There is no maximum score since the score was participant dependent for both number and severity.
Secondary Outcome Measures
Change From Baseline in The Weekly Hot Flash Severity Score at Weeks 4, 8 and 12 (Method 1)
The HF Severity Score by method 1 takes into account the number and severity of moderate and severe HF occurred during a given time period and was calculated as follows HF Severity score = [(number of moderate HF/day × 2) + (number of severe HF/day × 3)]/(number of moderate HF + number of severe HF)
The severity of HFs was clinically defined as follows:
Moderate: Sensation of heat with sweating/dampness, but was able to continue activity. If at night, participant woke up because she was feeling hot and/or was sweating, but no action was necessary other than rearranging the bed sheets.
Severe: Sensation of intense heat with sweating, causing disruption of activity. If at night, participant woke up hot and was sweating and needed to take action (e.g., removing layers of clothes, open the window, or get out of bed).
Higher scores indicate worse symptoms. There is no maximum score since the score was participant-dependent for both number and severity.
Change From Baseline in The Weekly Hot Flash Severity Score at Weeks 4, 8 and 12 (Method 2)
The HF Severity Score by method 2 takes into account moderate and severe HF during a given time period and was calculated as follows HF Severity score = [(number of moderate HF/day × 2) + (number of severe HF/day × 3)]
The severity of HFs was clinically defined as follows:
Moderate: Sensation of heat with sweating/dampness, but was able to continue activity. If at night, participant woke up because she was feeling hot and/or was sweating, but no action was necessary other than rearranging the bed sheets.
Severe: Sensation of intense heat with sweating, causing disruption of activity. If at night, participant woke up hot and was sweating and needed to take action (e.g., removing layers of clothes, open the window, or get out of bed).
Higher scores indicate worse symptoms. There is no maximum score since the score was participant-dependent for both number and severity.
Change From Baseline in The Weekly Mild, Moderate and Severe Hot Flash Frequency at Weeks 4, 8 and 12
The weekly HF frequency was calculated as number of mild, moderate and severe hot flashes over the week.
Mild: sensation of heat without sweating/dampness. If at night, participant didn't wake up but later notices damp sheets or clothing.
Moderate: Sensation of heat with sweating/dampness, but was able to continue activity. If at night, participant woke up because she was feeling hot and/or was sweating, but no action was necessary other than rearranging the bed sheets.
Severe: Sensation of intense heat with sweating, causing disruption of activity. If at night, participant woke up hot and was sweating and needed to take action (e.g., removing layers of clothes, open the window, or get out of bed).
Higher number of hot flashes is worse.
Percentage of Participants With >=70% Reduction in the Weekly Hot Flash Score From Baseline to Weeks 4, 8 and 12
The HF score (based on severity and frequency) was calculated as:
(number of mild HF/day × 1) + (number of moderate HF/day × 2) + (number of severe HF/day × 3)
The severity of HFs is clinically defined as follows:
Mild: sensation of heat without sweating/dampness. If at night, participant didn't wake up but later notices damp sheets or clothing.
Moderate: Sensation of heat with sweating/dampness, but was able to continue activity. If at night, participant woke up because she was feeling hot and/or was sweating, but no action was necessary other than rearranging the bed sheets.
Severe: Sensation of intense heat with sweating, causing disruption of activity. If at night, participant woke up hot and was sweating and needed to take action (e.g., removing layers of clothes, open the window, or get out of bed).
Higher scores indicate worse symptoms. There is no maximum score since the score was participant-dependent for both number and severity.
Percentage of Participants With >=80% Reduction in the Weekly Hot Flash Score From Baseline to Weeks 4, 8 and 12
The HF score (based on severity and frequency) was calculated as:
(number of mild HF/day × 1) + (number of moderate HF/day × 2) + (number of severe HF/day × 3)
The severity of HFs is clinically defined as follows:
Mild: sensation of heat without sweating/dampness. If at night, participant didn't wake up but later notices damp sheets or clothing.
Moderate: Sensation of heat with sweating/dampness, but was able to continue activity. If at night, participant woke up because she was feeling hot and/or was sweating, but no action was necessary other than rearranging the bed sheets.
Severe: Sensation of intense heat with sweating, causing disruption of activity. If at night, participant woke up hot and was sweating and needed to take action (e.g., removing layers of clothes, open the window, or get out of bed).
Higher scores indicate worse symptoms. There is no maximum score since the score was participant-dependent for both number and severity.
Percentage of Participants With >=90% Reduction in the Weekly Hot Flash Score From Baseline to Weeks 4, 8 and 12
The HF score (based on severity and frequency) was calculated as:
(number of mild HF/day × 1) + (number of moderate HF/day × 2) + (number of severe HF/day × 3)
The severity of HF is clinically defined as follows:
Mild: sensation of heat without sweating/dampness. If at night, participant didn't wake up but later notices damp sheets or clothing.
Moderate: Sensation of heat with sweating/dampness, but was able to continue activity. If at night, participant woke up because she was feeling hot and/or was sweating, but no action was necessary other than rearranging the bed sheets.
Severe: Sensation of intense heat with sweating, causing disruption of activity. If at night, participant woke up hot and was sweating and needed to take action (e.g., removing layers of clothes, open the window, or get out of bed).
Higher scores indicate worse symptoms. There is no maximum score since the score was participant-dependent for both number and severity.
Percentage of Participants With >=50% Reduction in the Weekly Frequency of Moderate and Severe HF From Baseline to Weeks 4, 8 and 12
The weekly HF frequency of moderate and severe HF was calculated as number of moderate and severe HF over the week.
Moderate: Sensation of heat with sweating/dampness, but was able to continue activity. If at night, participant woke up because she was feeling hot and/or was sweating, but no action was necessary other than rearranging the bed sheets.
Severe: Sensation of intense heat with sweating, causing disruption of activity. If at night, participant woke up hot and was sweating and needed to take action (e.g., removing layers of clothes, open the window, or get out of bed).
Higher number of HF indicates worse symptoms.
Percentage of Participants With >=70% Reduction in the Weekly Frequency of Moderate and Severe HF From Baseline to Weeks 4, 8 and 12
The weekly HF frequency of moderate and severe HF was calculated as number of moderate and severe HF over the week.
Moderate: Sensation of heat with sweating/dampness, but was able to continue activity. If at night, participant woke up because she was feeling hot and/or was sweating, but no action was necessary other than rearranging the bed sheets.
Severe: Sensation of intense heat with sweating, causing disruption of activity. If at night, participant woke up hot and was sweating and needed to take action (e.g., removing layers of clothes, open the window, or get out of bed).
Higher number of HF indicates worse symptoms.
Percentage of Participants With >=90% Reduction in the Weekly Frequency of Moderate and Severe HF From Baseline to Weeks 4, 8 and 12
The weekly HF frequency of moderate and severe HF was calculated as number of moderate and severe HF over the week.
Moderate: Sensation of heat with sweating/dampness, but was able to continue activity. If at night, participant woke up because she was feeling hot and/or was sweating, but no action was necessary other than rearranging the bed sheets.
Severe: Sensation of intense heat with sweating, causing disruption of activity. If at night, participant woke up hot and was sweating and needed to take action (e.g., removing layers of clothes, open the window, or get out of bed).
Higher number of HF indicates worse symptoms.
Change From Baseline in Hot Flash Related Daily Interference Scale (HFRDIS) Score at Weeks 4, 8 and 12
The HFRDIS was a 10-item scale which measured a woman's perceptions of the degree to which HF interfere with 9 daily life activities (work, social activities, leisure, sleep, mood, concentration, relations with others, sexuality, enjoying life); the 10th item measures interference with overall quality of life. This scale was modeled after items on the Brief Pain Inventory and Brief Fatigue Inventory both of which assessed the extent to which pain or fatigue interfere with daily life. Participants were asked to rate the extent to which HF had interfered with each item during the previous 4-week time interval using a 0 (do not interfere) to 10 (completely interfere) scale. Overall mean score was calculated as sum of items/number of available items. Higher score indicate a higher interference.
Change From Baseline in Leeds Sleep Evaluation Questionnaire (LSEQ) at Weeks 4, 8 and 12
The LSEQ was a 10-item self-rated questionnaire which assessed participants aspects of sleep and early morning behavior. The questions were grouped into 4 chronological areas: the ease of getting to sleep, the perceived quality of sleep, the ease of awaking from sleep, and the integrity of early morning behavior following wakefulness. The LSEQ was a visual analogue scale which requires respondents to place marks on a group of 10 cm lines. representing the changes they have experienced in a variety of symptoms since the beginning of treatment. Lines extends between extremes like "more difficult than usual" and "easier than usual". Responses are measured using a 100-mm scale and are averaged to provide a score for each domain.
Change From Baseline in Greene Climacteric Scale (GCS) at Weeks 4, 8 and 12
The GCS was a 21-item scale which provides a brief but comprehensive and valid measure of climacteric symptomatology. Each item was rated by the participant according to its severity using a four-point rating scale from 0 (none) to 3 (severe). The first 20 items of the scale combine into three main independent symptom measures: psychological symptoms (items 1 to 11; score 0 to 33), physical symptoms (items 12 to 18; score 0 to 21), and vasomotor symptoms (items 19 to 20; score 0 to 6), by summing up the individual item scores. Item 21 is a probe for sexual dysfunction (Loss of interest in sex). The total score ranges from 0 to 63. Higher scores indicate worse symptoms.
Change From Baseline in Sheehan Disability Scale (SDS) at Weeks 4, 8 and 12
The SDS was a composite of 3 self-rated items designed to measure the extent to which 3 major sectors in a participant's life are impaired by panic, anxiety, phobic, or depressive symptoms. The participant rates the extent to which his/her 1- work/school, 2- social life, and 3- family life are impaired by his/her symptoms on a 10-point visual analog scale. The 3 items could be summed into a single dimensional measure of global functional impairment that ranges from 0 (unimpaired) to 30 (highly impaired).Higher scores indicate significant functional impairment.
Change From Baseline in Sheehan Disability Scale (SDS) at Weeks 4, 8 and 12 (Days Lost and Days Unproductive)
The SDS was a composite of 3 self-rated items designed to measure the extent to which 3 major sectors in a participant's life are impaired by panic, anxiety, phobic, or depressive symptoms. The participant rates the extent to which his/her 1- work/school, 2- social life, and 3- family life are impaired by his/her symptoms. In addition to the 3 items, the participants were asked two questions Days Lost: On how many days in the last week did your symptoms cause you to miss school or work or leave you unable to carry out your normal daily responsibilities? Day Unproductive: On how many days in the last week did you feel so impaired by your symptoms, that even though you went to school or work, your productivity was reduced?
Change From Baseline in Plasma Concentration of Luteinizing Hormone (LH)
Change From baseline in plasma concentration of LH was reported.
Change From Baseline in Plasma Concentration of Follicle-Stimulating Hormone (FSH)
Change From baseline in plasma concentration of FSH was reported.
Change From Baseline in Plasma Concentration of Estradiol (E2)
Change From baseline in plasma concentration of E2 was reported.
Change From Baseline in Plasma Concentration of Sex Hormone-Binding Globulin (SHBG)
Change From baseline in plasma concentration of SHBG was reported.
Change From Baseline in Plasma Concentration of Leptin
Change From baseline in plasma concentration of leptin was reported.
Change From Baseline in Plasma Concentration of Insulin
Change From baseline in plasma concentration of insulin was reported.
Change From Baseline in Plasma Concentration of C-peptide
Change From baseline in plasma concentration of C-peptide was reported.
Change From Baseline in Plasma Concentration of Glycated Hemoglobin (HBA1c)
Change From baseline in plasma concentration of HBA1C was reported.
Number of Participants With Adverse Events (AE's)
An AE is any untoward medical occurrence in a participant administered a study drug, & which does not necessarily have to have a causal relationship with treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom or disease temporally associated with use of a medicinal product (mp) whether or not considered related to the mp. An AE is considered "serious" if 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, results in congenital anomaly or birth defect, requires inparticipant hospitalization or leads to prolongation of hospitalization, hospitalization for treatment/observation/examination caused by AE is to be considered as serious, discontinuation due to increases in liver enzymes, other medically important events. TEAE was defined as an AE observed from first dose date up to end of study.
Change From Baseline in Plasma Concentration of Bone Alkaline Phosphatase (BALP) at Week 12
Change from baseline in plasma concentration of BALP was reported.
Change From Baseline in Plasma Concentration of Carboxy-terminal Telopeptide of Type I Collagen (CTX) at Week 12
Change from baseline in plasma concentration of CTX was reported.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT05419908
Brief Title
Trial to Investigate the Effect of ESN364 in Early Postmenopausal Women Suffering From Hot Flashes
Official Title
Pilot/Phase IIa Trial to Investigate the Effect of ESN364 in Early Postmenopausal Women Suffering From Hot Flashes
Study Type
Interventional
2. Study Status
Record Verification Date
August 2023
Overall Recruitment Status
Completed
Study Start Date
September 21, 2015 (Actual)
Primary Completion Date
September 21, 2016 (Actual)
Study Completion Date
October 6, 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Ogeda S.A.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The primary purpose of this study was to evaluate the effect of ESN364 on the severity and frequency of hot flashes in early postmenopausal women suffering from hot flashes, in terms of changes in weekly Hot Flash Score from baseline to Week 12.
This study also evaluated the effect of ESN364 on the severity and frequency of hot flashes at additional timepoints; hot flash interference on daily life, in terms of changes from baseline over time in Hot Flash Related Daily Interference Scale (HFRDIS); the effect of ESN364 on climacteric symptoms, in terms of changes from baseline over time in Leeds Sleep Evaluation Questionnaire (LSEQ), Greene Climacteric Scale (GCS), and Sheehan Disability Scale (SDS); pharmacodynamic (PD) effect; and safety and tolerability.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hot Flashes
Keywords
Hot flashes, ESN364, ASP2693, fezolinetant, menopause, postmenopausal
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
87 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Fezolinetant
Arm Type
Experimental
Arm Description
Participants received 90 milligrams (mg) fezolinetant capsules orally, twice daily (BID) for a period of 12 weeks
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Participants received fezolinetant matching placebo capsules orally, BID for a period of 12 weeks.
Intervention Type
Drug
Intervention Name(s)
Fezolinetant
Other Intervention Name(s)
ESN364, ASP2693
Intervention Description
Oral Capsule
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Oral Capsule
Primary Outcome Measure Information:
Title
Change From Baseline to Week 12 in The Weekly General Hot Flash Score
Description
The HF score (based on severity and frequency) was calculated as:
(number of mild HF/day × 1) + (number of moderate HF/day × 2) + (number of severe HF/day × 3)
The severity of HFs is clinically defined as follows:
Mild: sensation of heat without sweating/dampness. If at night, participant didn't wake up but later notices damp sheets or clothing.
Moderate: Sensation of heat with sweating/dampness, but was able to continue activity. If at night, participant woke up because she was feeling hot and/or was sweating, but no action was necessary other than rearranging the bed sheets.
Severe: Sensation of intense heat with sweating, causing disruption of activity. If at night, participant woke up hot and was sweating and needed to take action (e.g., removing layers of clothes, open the window, or get out of bed).
Higher scores indicate worse symptoms. There is no maximum score since the score was participant dependent for both number and severity.
Time Frame
Baseline and week 12
Secondary Outcome Measure Information:
Title
Change From Baseline in The Weekly Hot Flash Severity Score at Weeks 4, 8 and 12 (Method 1)
Description
The HF Severity Score by method 1 takes into account the number and severity of moderate and severe HF occurred during a given time period and was calculated as follows HF Severity score = [(number of moderate HF/day × 2) + (number of severe HF/day × 3)]/(number of moderate HF + number of severe HF)
The severity of HFs was clinically defined as follows:
Moderate: Sensation of heat with sweating/dampness, but was able to continue activity. If at night, participant woke up because she was feeling hot and/or was sweating, but no action was necessary other than rearranging the bed sheets.
Severe: Sensation of intense heat with sweating, causing disruption of activity. If at night, participant woke up hot and was sweating and needed to take action (e.g., removing layers of clothes, open the window, or get out of bed).
Higher scores indicate worse symptoms. There is no maximum score since the score was participant-dependent for both number and severity.
Time Frame
Baseline and weeks 4, 8 and 12
Title
Change From Baseline in The Weekly Hot Flash Severity Score at Weeks 4, 8 and 12 (Method 2)
Description
The HF Severity Score by method 2 takes into account moderate and severe HF during a given time period and was calculated as follows HF Severity score = [(number of moderate HF/day × 2) + (number of severe HF/day × 3)]
The severity of HFs was clinically defined as follows:
Moderate: Sensation of heat with sweating/dampness, but was able to continue activity. If at night, participant woke up because she was feeling hot and/or was sweating, but no action was necessary other than rearranging the bed sheets.
Severe: Sensation of intense heat with sweating, causing disruption of activity. If at night, participant woke up hot and was sweating and needed to take action (e.g., removing layers of clothes, open the window, or get out of bed).
Higher scores indicate worse symptoms. There is no maximum score since the score was participant-dependent for both number and severity.
Time Frame
Baseline and weeks 4, 8 and 12
Title
Change From Baseline in The Weekly Mild, Moderate and Severe Hot Flash Frequency at Weeks 4, 8 and 12
Description
The weekly HF frequency was calculated as number of mild, moderate and severe hot flashes over the week.
Mild: sensation of heat without sweating/dampness. If at night, participant didn't wake up but later notices damp sheets or clothing.
Moderate: Sensation of heat with sweating/dampness, but was able to continue activity. If at night, participant woke up because she was feeling hot and/or was sweating, but no action was necessary other than rearranging the bed sheets.
Severe: Sensation of intense heat with sweating, causing disruption of activity. If at night, participant woke up hot and was sweating and needed to take action (e.g., removing layers of clothes, open the window, or get out of bed).
Higher number of hot flashes is worse.
Time Frame
Baseline and weeks 4, 8 and 12
Title
Percentage of Participants With >=70% Reduction in the Weekly Hot Flash Score From Baseline to Weeks 4, 8 and 12
Description
The HF score (based on severity and frequency) was calculated as:
(number of mild HF/day × 1) + (number of moderate HF/day × 2) + (number of severe HF/day × 3)
The severity of HFs is clinically defined as follows:
Mild: sensation of heat without sweating/dampness. If at night, participant didn't wake up but later notices damp sheets or clothing.
Moderate: Sensation of heat with sweating/dampness, but was able to continue activity. If at night, participant woke up because she was feeling hot and/or was sweating, but no action was necessary other than rearranging the bed sheets.
Severe: Sensation of intense heat with sweating, causing disruption of activity. If at night, participant woke up hot and was sweating and needed to take action (e.g., removing layers of clothes, open the window, or get out of bed).
Higher scores indicate worse symptoms. There is no maximum score since the score was participant-dependent for both number and severity.
Time Frame
Baseline and weeks 4, 8 and 12
Title
Percentage of Participants With >=80% Reduction in the Weekly Hot Flash Score From Baseline to Weeks 4, 8 and 12
Description
The HF score (based on severity and frequency) was calculated as:
(number of mild HF/day × 1) + (number of moderate HF/day × 2) + (number of severe HF/day × 3)
The severity of HFs is clinically defined as follows:
Mild: sensation of heat without sweating/dampness. If at night, participant didn't wake up but later notices damp sheets or clothing.
Moderate: Sensation of heat with sweating/dampness, but was able to continue activity. If at night, participant woke up because she was feeling hot and/or was sweating, but no action was necessary other than rearranging the bed sheets.
Severe: Sensation of intense heat with sweating, causing disruption of activity. If at night, participant woke up hot and was sweating and needed to take action (e.g., removing layers of clothes, open the window, or get out of bed).
Higher scores indicate worse symptoms. There is no maximum score since the score was participant-dependent for both number and severity.
Time Frame
Baseline and weeks 4, 8 and 12
Title
Percentage of Participants With >=90% Reduction in the Weekly Hot Flash Score From Baseline to Weeks 4, 8 and 12
Description
The HF score (based on severity and frequency) was calculated as:
(number of mild HF/day × 1) + (number of moderate HF/day × 2) + (number of severe HF/day × 3)
The severity of HF is clinically defined as follows:
Mild: sensation of heat without sweating/dampness. If at night, participant didn't wake up but later notices damp sheets or clothing.
Moderate: Sensation of heat with sweating/dampness, but was able to continue activity. If at night, participant woke up because she was feeling hot and/or was sweating, but no action was necessary other than rearranging the bed sheets.
Severe: Sensation of intense heat with sweating, causing disruption of activity. If at night, participant woke up hot and was sweating and needed to take action (e.g., removing layers of clothes, open the window, or get out of bed).
Higher scores indicate worse symptoms. There is no maximum score since the score was participant-dependent for both number and severity.
Time Frame
Baseline and weeks 4, 8 and 12
Title
Percentage of Participants With >=50% Reduction in the Weekly Frequency of Moderate and Severe HF From Baseline to Weeks 4, 8 and 12
Description
The weekly HF frequency of moderate and severe HF was calculated as number of moderate and severe HF over the week.
Moderate: Sensation of heat with sweating/dampness, but was able to continue activity. If at night, participant woke up because she was feeling hot and/or was sweating, but no action was necessary other than rearranging the bed sheets.
Severe: Sensation of intense heat with sweating, causing disruption of activity. If at night, participant woke up hot and was sweating and needed to take action (e.g., removing layers of clothes, open the window, or get out of bed).
Higher number of HF indicates worse symptoms.
Time Frame
Baseline and weeks 4, 8 and 12
Title
Percentage of Participants With >=70% Reduction in the Weekly Frequency of Moderate and Severe HF From Baseline to Weeks 4, 8 and 12
Description
The weekly HF frequency of moderate and severe HF was calculated as number of moderate and severe HF over the week.
Moderate: Sensation of heat with sweating/dampness, but was able to continue activity. If at night, participant woke up because she was feeling hot and/or was sweating, but no action was necessary other than rearranging the bed sheets.
Severe: Sensation of intense heat with sweating, causing disruption of activity. If at night, participant woke up hot and was sweating and needed to take action (e.g., removing layers of clothes, open the window, or get out of bed).
Higher number of HF indicates worse symptoms.
Time Frame
Baseline and weeks 4, 8 and 12
Title
Percentage of Participants With >=90% Reduction in the Weekly Frequency of Moderate and Severe HF From Baseline to Weeks 4, 8 and 12
Description
The weekly HF frequency of moderate and severe HF was calculated as number of moderate and severe HF over the week.
Moderate: Sensation of heat with sweating/dampness, but was able to continue activity. If at night, participant woke up because she was feeling hot and/or was sweating, but no action was necessary other than rearranging the bed sheets.
Severe: Sensation of intense heat with sweating, causing disruption of activity. If at night, participant woke up hot and was sweating and needed to take action (e.g., removing layers of clothes, open the window, or get out of bed).
Higher number of HF indicates worse symptoms.
Time Frame
Baseline and weeks 4, 8 and 12
Title
Change From Baseline in Hot Flash Related Daily Interference Scale (HFRDIS) Score at Weeks 4, 8 and 12
Description
The HFRDIS was a 10-item scale which measured a woman's perceptions of the degree to which HF interfere with 9 daily life activities (work, social activities, leisure, sleep, mood, concentration, relations with others, sexuality, enjoying life); the 10th item measures interference with overall quality of life. This scale was modeled after items on the Brief Pain Inventory and Brief Fatigue Inventory both of which assessed the extent to which pain or fatigue interfere with daily life. Participants were asked to rate the extent to which HF had interfered with each item during the previous 4-week time interval using a 0 (do not interfere) to 10 (completely interfere) scale. Overall mean score was calculated as sum of items/number of available items. Higher score indicate a higher interference.
Time Frame
Baseline and weeks 4, 8 and 12
Title
Change From Baseline in Leeds Sleep Evaluation Questionnaire (LSEQ) at Weeks 4, 8 and 12
Description
The LSEQ was a 10-item self-rated questionnaire which assessed participants aspects of sleep and early morning behavior. The questions were grouped into 4 chronological areas: the ease of getting to sleep, the perceived quality of sleep, the ease of awaking from sleep, and the integrity of early morning behavior following wakefulness. The LSEQ was a visual analogue scale which requires respondents to place marks on a group of 10 cm lines. representing the changes they have experienced in a variety of symptoms since the beginning of treatment. Lines extends between extremes like "more difficult than usual" and "easier than usual". Responses are measured using a 100-mm scale and are averaged to provide a score for each domain.
Time Frame
Baseline and weeks 4, 8 and 12
Title
Change From Baseline in Greene Climacteric Scale (GCS) at Weeks 4, 8 and 12
Description
The GCS was a 21-item scale which provides a brief but comprehensive and valid measure of climacteric symptomatology. Each item was rated by the participant according to its severity using a four-point rating scale from 0 (none) to 3 (severe). The first 20 items of the scale combine into three main independent symptom measures: psychological symptoms (items 1 to 11; score 0 to 33), physical symptoms (items 12 to 18; score 0 to 21), and vasomotor symptoms (items 19 to 20; score 0 to 6), by summing up the individual item scores. Item 21 is a probe for sexual dysfunction (Loss of interest in sex). The total score ranges from 0 to 63. Higher scores indicate worse symptoms.
Time Frame
Baseline and weeks 4, 8 and 12
Title
Change From Baseline in Sheehan Disability Scale (SDS) at Weeks 4, 8 and 12
Description
The SDS was a composite of 3 self-rated items designed to measure the extent to which 3 major sectors in a participant's life are impaired by panic, anxiety, phobic, or depressive symptoms. The participant rates the extent to which his/her 1- work/school, 2- social life, and 3- family life are impaired by his/her symptoms on a 10-point visual analog scale. The 3 items could be summed into a single dimensional measure of global functional impairment that ranges from 0 (unimpaired) to 30 (highly impaired).Higher scores indicate significant functional impairment.
Time Frame
Baseline and weeks 4, 8 and 12
Title
Change From Baseline in Sheehan Disability Scale (SDS) at Weeks 4, 8 and 12 (Days Lost and Days Unproductive)
Description
The SDS was a composite of 3 self-rated items designed to measure the extent to which 3 major sectors in a participant's life are impaired by panic, anxiety, phobic, or depressive symptoms. The participant rates the extent to which his/her 1- work/school, 2- social life, and 3- family life are impaired by his/her symptoms. In addition to the 3 items, the participants were asked two questions Days Lost: On how many days in the last week did your symptoms cause you to miss school or work or leave you unable to carry out your normal daily responsibilities? Day Unproductive: On how many days in the last week did you feel so impaired by your symptoms, that even though you went to school or work, your productivity was reduced?
Time Frame
Baseline and weeks 4, 8 and 12
Title
Change From Baseline in Plasma Concentration of Luteinizing Hormone (LH)
Description
Change From baseline in plasma concentration of LH was reported.
Time Frame
Baseline and week 4: pre-dose, week 8:pre-dose, week 12:pre-dose, week 12: 3h, follow-up (week 15)
Title
Change From Baseline in Plasma Concentration of Follicle-Stimulating Hormone (FSH)
Description
Change From baseline in plasma concentration of FSH was reported.
Time Frame
Baseline and week 4: pre-dose, week 8:pre-dose, week 12:pre-dose, week 12:3h, follow-up (week 15)
Title
Change From Baseline in Plasma Concentration of Estradiol (E2)
Description
Change From baseline in plasma concentration of E2 was reported.
Time Frame
Baseline and week 4: pre-dose, week 8:pre-dose, week 12:pre-dose, week 12:3h, follow-up (week 15)
Title
Change From Baseline in Plasma Concentration of Sex Hormone-Binding Globulin (SHBG)
Description
Change From baseline in plasma concentration of SHBG was reported.
Time Frame
Baseline and week 4: pre-dose, week 8:pre-dose, week 12:pre-dose, week 12:3h, follow-up (week 15)
Title
Change From Baseline in Plasma Concentration of Leptin
Description
Change From baseline in plasma concentration of leptin was reported.
Time Frame
Baseline and week 4: pre-dose, week 8:pre-dose, week 12:pre-dose, week 12:3h, follow-up (week 15)
Title
Change From Baseline in Plasma Concentration of Insulin
Description
Change From baseline in plasma concentration of insulin was reported.
Time Frame
Baseline and week 4: pre-dose, week 8:pre-dose, week 12:pre-dose, week 12:3h, follow-up (week 15)
Title
Change From Baseline in Plasma Concentration of C-peptide
Description
Change From baseline in plasma concentration of C-peptide was reported.
Time Frame
Baseline and week 4: pre-dose, week 8:pre-dose, week 12:pre-dose, week 12:3h, follow-up (week 15)
Title
Change From Baseline in Plasma Concentration of Glycated Hemoglobin (HBA1c)
Description
Change From baseline in plasma concentration of HBA1C was reported.
Time Frame
Baseline and week 12
Title
Number of Participants With Adverse Events (AE's)
Description
An AE is any untoward medical occurrence in a participant administered a study drug, & which does not necessarily have to have a causal relationship with treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom or disease temporally associated with use of a medicinal product (mp) whether or not considered related to the mp. An AE is considered "serious" if 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, results in congenital anomaly or birth defect, requires inparticipant hospitalization or leads to prolongation of hospitalization, hospitalization for treatment/observation/examination caused by AE is to be considered as serious, discontinuation due to increases in liver enzymes, other medically important events. TEAE was defined as an AE observed from first dose date up to end of study.
Time Frame
From first dose of study drug until end of the study (Up to week 15)
Title
Change From Baseline in Plasma Concentration of Bone Alkaline Phosphatase (BALP) at Week 12
Description
Change from baseline in plasma concentration of BALP was reported.
Time Frame
Baseline and week 12
Title
Change From Baseline in Plasma Concentration of Carboxy-terminal Telopeptide of Type I Collagen (CTX) at Week 12
Description
Change from baseline in plasma concentration of CTX was reported.
Time Frame
Baseline and week 12
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
40 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Spontaneous amenorrhea for at least 12 consecutive months; or spontaneous amenorrhea for at least 6 months with biochemical criteria of menopause (FSH >40 IU/L); or spontaneous amenorrhea for at least 3 months with biochemical/physical criteria of menopause (FSH >40 IU/L and E2 <0.21 nmol/); or having had bilateral oophorectomy at least 6 weeks prior to screening (with or without hysterectomy);
At least 49 moderate or severe hot flashes or night sweats over a period of 7 consecutive days, as recorded in the daily diary during the screening period, with at least 4 of those days with 7 or more moderate or severe hot flashes per day;
In good general health as determined on the basis of medical history and general physical examination performed at screening; hematology and chemistry parameters, pulse rate and/or blood pressure, and ECG within the reference range for the population studied, or showing no clinically relevant deviations;
Negative urine test for selected drugs of abuse (amphetamines, tricyclic antidepressants, cannabinoids, cocaine, tetrahydrocannabinol, or opiates) at screening;
Negative serology panel (including hepatitis B surface antigen [HBsAg], antihepatitis C virus [HCV] and human immunodeficiency virus (HIV) antibody screens);
Negative urine pregnancy test at screening;
Exclusion Criteria:
Use of a prohibited therapy or not willing to wash-out drugs considered prohibited therapies;
History (in the past year) or presence of drug or alcohol abuse;
Suicide attempt in the past 3 years;
Previous or current history of a malignant tumor (except basal cell carcinoma);
Active liver disease or jaundice, or out-of-range values of alanine aminotransferase (ALT) and aspartate aminotransferase (AST); or total bilirubin >1.3 times the upper limit of normal (ULN); or creatinine >1.5 times the ULN; or estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease (MDRD) formula <60 mL/min/1.73 m2 at screening;
Medical condition or chronic disease (including history of neurological [including cognitive], hepatic, renal, cardiovascular, gastrointestinal, pulmonary [e.g., moderate asthma], or endocrine disease) or malignancy that could confound interpretation of the study outcome;
Any psychological disorder according to the criteria indicated in the Diagnostics and Statistical Manual of Mental Disorders (DSM, 4th edition) within one year prior to screening. Such disorders include but are not limited to current major depression, alcohol (more than 3 glasses of wine, beer, or equivalent/day) or substance abuse/dependence;
Unsuited to participate in the study, based on findings observed during physical examination, vital sign assessment, or 12-lead ECG;
History of severe allergy, hypersensitivity, or intolerance to drugs in general, including the study drug and any of its excipients;
Presence or sequellae of gastrointestinal, liver, kidney or other conditions known to interfere with the absorption, distribution, metabolism, or excretion (ADME) mechanisms of drugs;
Concurrent participation in another interventional study (or participation within 3 months prior to screening in this study);
History of poor compliance in clinical studies;
Unable or unwilling to complete the study procedures;
Subject is the Investigator or any sub-investigator, research assistant, pharmacist, study coordinator, or other staff or relative thereof who is directly involved in the conduct of the study.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Expert
Organizational Affiliation
Ogeda S.A.
Official's Role
Study Director
Facility Information:
Facility Name
Site BE32004
City
Brussels
ZIP/Postal Code
1000
Country
Belgium
Facility Name
Site BE32003
City
Genk
ZIP/Postal Code
3600
Country
Belgium
Facility Name
Site BE32001
City
Gent
ZIP/Postal Code
9000
Country
Belgium
Facility Name
Site BE32006
City
Jette
ZIP/Postal Code
1090
Country
Belgium
Facility Name
Site BE32005
City
Kraainem
ZIP/Postal Code
1950
Country
Belgium
Facility Name
Site BE32007
City
Leuven
Country
Belgium
Facility Name
Site BE32008
City
Mons
ZIP/Postal Code
7000
Country
Belgium
Facility Name
Site BE32009
City
Tienen
ZIP/Postal Code
3300
Country
Belgium
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Access to anonymized individual participant level data collected during the study, in addition to study-related supporting documentation, is planned for studies conducted with approved product indications and formulations, as well as compounds terminated during development. Studies conducted with product indications or formulations that remain active in development are assessed after study completion to determine if Individual Participant Data can be shared. Conditions and exceptions are described under the Sponsor Specific Details for Astellas on www.clinicalstudydatarequest.com.
IPD Sharing Time Frame
Access to participant level data is offered to researchers after publication of the primary manuscript (if applicable) and is available as long as Astellas has legal authority to provide the data.
IPD Sharing Access Criteria
Researchers must submit a proposal to conduct a scientifically relevant analysis of the study data. The research proposal is reviewed by an Independent Research Panel. If the proposal is approved, access to the study data is provided in a secure data sharing environment after receipt of a signed Data Sharing Agreement.
IPD Sharing URL
https://www.clinicalstudydatarequest.com/
Citations:
PubMed Identifier
31415087
Citation
Depypere H, Timmerman D, Donders G, Sieprath P, Ramael S, Combalbert J, Hoveyda HR, Fraser GL. Treatment of Menopausal Vasomotor Symptoms With Fezolinetant, a Neurokinin 3 Receptor Antagonist: A Phase 2a Trial. J Clin Endocrinol Metab. 2019 Dec 1;104(12):5893-5905. doi: 10.1210/jc.2019-00677.
Results Reference
result
Links:
URL
http://www.trialsummaries.com/Study/StudyDetails?id=25137&tenant=MT_AST_9011
Description
Link to plain language summary of the study on the Trial Results Summaries website.
URL
http://www.clinicaltrials.astellas.com/study/ESN364_HF_204/
Description
Link to results and other applicable study documents on the Astellas Clinical Trials website.
Learn more about this trial
Trial to Investigate the Effect of ESN364 in Early Postmenopausal Women Suffering From Hot Flashes
We'll reach out to this number within 24 hrs