Trial to Investigate the Effect of ESN364 in Early Postmenopausal Women Suffering From Hot Flashes
Study Details
Study Description
Brief Summary
The primary purpose of this study is 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 will also evaluate 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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Fezolinetant Twice daily (b.i.d) for 12 weeks |
Drug: Fezolinetant
oral
Other Names:
|
| Placebo Comparator: Placebo Twice daily (b.i.d) for 12 weeks |
Drug: Placebo
oral
|
Outcome Measures
Primary Outcome Measures
- Change from baseline to Week 12 in weekly Hot Flash Score [Baseline and Week 12]
Hot flash (HF) severity will be assessed via ePRO diary. The severity of HFs is clinically defined as follows: Mild: Sensation of heat without sweating/dampness. If at night, participant doesn't wake up but later notices damp sheets or clothing; Moderate: Sensation of heat with sweating/dampness, but able to continue activity. If at night, participant wakes up because she is feeling hot and/or is sweating, but no action is necessary other than rearranging the bed sheets; Severe: Sensation of intense heat with sweating, causing disruption of activity. If at night, participant wakes up hot and is sweating and needs to take action (e.g., removing layers of clothes, open the window, or get out of bed). The HF daily score (based on severity and frequency) is calculated as follows: (number of mild HFs/day × 1) + (number of moderate HFs/day × 2) + (number of severe HFs/day × 3). Weekly HF score is calculated as mean HF daily score over the week. Higher scores indicate worse symptoms.
Secondary Outcome Measures
- Change from baseline in weekly Hot Flash Score [Baseline and Weeks 4, 8 and Follow-up (up to 15 Weeks)]
Hot flash (HF) severity will be assessed via ePRO diary. The severity of HFs is defined clinically as follows: Mild: Sensation of heat without sweating/dampness. If at night, participant doesn't wake up but later notices damp sheets or clothing; Moderate: Sensation of heat with sweating/dampness, but able to continue activity. If at night, participant wakes up because she is feeling hot and/or is sweating, but no action is necessary other than rearranging the bed sheets; Severe: Sensation of intense heat with sweating, causing disruption of activity. If at night, participant wakes up hot and is sweating and needs to take action (e.g., removing layers of clothes, open the window, or get out of bed). The HF daily score (based on severity and frequency) is calculated as follows: (number of mild HFs/day × 1) + (number of moderate HFs/day × 2) + (number of severe HFs/day × 3). Weekly HF score is calculated as mean HF daily score over the week. Higher scores indicate worse symptoms.
- Change from baseline in weekly Hot Flash Frequency [Baseline and Weeks 4, 8, 12 and Follow-up (up to 15 Weeks)]
Hot flash frequency will be assessed via Electronic Patient Reported Outcome (ePRO) diary. Weekly hot flash frequency is calculated as number of mild, moderate and severe hot flashes over the week. Higher number of hot flashes is worse.
- Change from baseline in Hot Flash Related Daily Interference Scale (HFRDIS) score [Baseline and Weeks 4, 8, 12 and Follow-up (up to 15 Weeks)]
Perceived hot flash interference on daily activities will be evaluated using the HFRDIS. The HFRDIS will be completed at the clinical site in the ePRO diary, at any time during the visit. The HFRDIS is a 10-item scale which measures a woman's perceptions of the degree to which hot flashes 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. Participants will be asked to rate the extent to which hot flashes have interfered with each item during the previous 4-week time interval using a 0 (do not interfere) to 10 (completely interfere) scale. Score is calculated as follows: sum of items/number of available items. Higher scores indicate a higher interference.
- Change from baseline in Leeds Sleep Evaluation Questionnaire (LSEQ) [Baseline and Weeks 4, 8, 12 and Follow-up (up to 15 Weeks)]
Participants' sleep quality will be evaluated using the LSEQ. The questionnaire will be paper-based, administered at the clinical site at any time during the visit. The LSEQ is a 10-item self-rated questionnaire which assesses participants' aspects of sleep and early morning behavior. The questions are 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 is 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 extend 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) [Baseline and Weeks 4, 8, 12 and Follow-up (up to 15 Weeks)]
Changes in climacteric symptoms will be evaluated using the GCS. The questionnaire will be paper-based, administered at the clinical site at any time during the visit. The GCS is a 21-item scale which provides a brief but comprehensive and valid measure of climacteric symptomatology. Each item is 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. The total score can range from 0 to 63. Higher scores indicate worse symptoms.
- Change from baseline in Sheehan Disability Scale (SDS) [Baseline and Weeks 4, 8, 12 and Follow-up (up to 15 Weeks)]
Participants' functional impairment of life will be evaluated using the SDS. The questionnaire will be paper-based, administered at the clinical site at any time during the visit. The SDS is 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 may be summed into a single dimensional measure of global functional impairment that ranges from 0 (unimpaired) to 30 (highly impaired). A higher score indicates a higher impairment.
- Pharmacodynamics (PD) of fezolinetant in plasma: Luteinizing hormone (LH) [Baseline and Weeks 4, 8, 12 and Follow-up (up to 15 Weeks)]
LH will be measured from the PD blood samples collected.
- Pharmacodynamics (PD) of fezolinetant in plasma: Follicle-stimulating hormone (FSH) [Baseline and Weeks 4, 8, 12 and Follow-up (up to 15 Weeks)]
FSH will be measured from the PD blood samples collected.
- Pharmacodynamics (PD) of fezolinetant in plasma: Estradiol (E2) [Baseline and Weeks 4, 8, 12 and Follow-up (up to 15 Weeks)]
E2 will be measured from the PD blood samples collected.
- Pharmacodynamics (PD) of fezolinetant in plasma: Sex hormone-binding globulin (SHBG) [Baseline and Weeks 4, 8, 12 and Follow-up (up to 15 Weeks)]
SHBG will be measured from the PD blood samples collected.
- Pharmacodynamics (PD) of fezolinetant in plasma: leptin [Baseline and Weeks 4, 8, 12 and Follow-up (up to 15 Weeks)]
Leptin will be measured from the PD blood samples collected.
- Pharmacodynamics (PD) of fezolinetant in plasma: insulin [Baseline and Weeks 4, 8, 12 and Follow-up (up to 15 Weeks)]
Insulin will be measured from the PD blood samples collected.
- Pharmacodynamics (PD) of fezolinetant in plasma: C-peptide [Baseline and Weeks 4, 8, 12 and Follow-up (up to 15 Weeks)]
C-peptide will be measured from the PD blood samples collected.
- Pharmacodynamics (PD) of fezolinetant in plasma: Glycated hemoglobin (HBA1c) [Baseline and Week 12]
HBA1c will be measured from the PD blood samples collected.
- Number of participants with Adverse Events (AEs) [Up to 15 Weeks]
An Adverse event (AE) is any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the study drug. An AE can therefore be any unfavorable and unintended sign (including an abnormal finding), symptom, or disease temporally associated with the use of a medicinal (investigational or non-investigational) product, whether or not related to that medicinal (investigational or non-investigational) product.
- Number of participants with laboratory value abnormalities and/or adverse events (AEs) [Up to 15 Weeks]
Number of participants with potentially clinically significant laboratory values.
- Number of participants with vital sign abnormalities and/or adverse events (AEs) [Up to 15 Weeks]
Number of participants with potentially clinically significant vital sign values.
- Number of participants with electrocardiogram (ECG) abnormalities and/or Adverse Events (AEs) [Up to 15 Weeks]
Number of participants with potentially clinically significant ECG values.
- Change from baseline in plasma bone density marker concentrations [Baseline and Week 12]
Plasma concentrations of bone density markers will be assessed.
Eligibility Criteria
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);
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History of poor compliance in clinical studies;
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Unable or unwilling to complete the study procedures;
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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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Site BE32004 | Brussels | Belgium | 1000 | |
| 2 | Site BE32003 | Genk | Belgium | 3600 | |
| 3 | Site BE32001 | Gent | Belgium | 9000 | |
| 4 | Site BE32006 | Jette | Belgium | 1090 | |
| 5 | Site BE32005 | Kraainem | Belgium | 1950 | |
| 6 | Site BE32007 | Leuven | Belgium | ||
| 7 | Site BE32008 | Mons | Belgium | 7000 | |
| 8 | Site BE32009 | Tienen | Belgium | 3300 |
Sponsors and Collaborators
- Ogeda S.A.
Investigators
- Study Director: Medical Expert, Ogeda S.A.
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- ESN364_HF_204
- 2015-002578-20