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NCT05419908

Trial to Investigate the Effect of ESN364 in Early Postmenopausal Women Suffering From Hot Flashes

Completed Phase 2 Results posted Last updated 27 November 2024
What this trial tests

Phase 2 trial testing Fezolinetant in Hot Flashes in 87 participants. Completed in 6 October 2016.

Timeline
21 September 2015
Primary endpoint
21 September 2016
6 October 2016

Quick facts

Lead sponsorOgeda S.A.
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingdouble
Primary purposetreatment
Enrollment87
Start date21 September 2015
Primary completion21 September 2016
Estimated completion6 October 2016
Sites8 locations across Belgium

Drugs / interventions tested

Conditions studied

Sponsor

Ogeda S.A.

Who can join

Adults 40 to 65, female only, with Hot Flashes. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Change From Baseline to Week 12 in The Weekly General Hot Flash Score Primary · Baseline and week 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:

GroupValue95% CI
Placebo-12.19-16.55 – -7.83
Fezolinetant-26.51-30.83 – -22.18
Change From Baseline in The Weekly Hot Flash Severity Score at Weeks 4, 8 and 12 (Method 1) Secondary · Baseline and weeks 4, 8 and 12

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. *

Week 4
GroupValue95% CI
Placebo-0.294-0.473 – -0.116
Fezolinetant-1.428-1.718 – -1.138
Week 8
GroupValue95% CI
Placebo-0.608-0.899 – -0.318
Fezolinetant-1.557-1.858 – -1.257
Week 12
GroupValue95% CI
Placebo-0.534-0.798 – -0.270
Fezolinetant-1.656-1.937 – -1.376
Change From Baseline in The Weekly Hot Flash Severity Score at Weeks 4, 8 and 12 (Method 2) Secondary · Baseline and weeks 4, 8 and 12

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. I

Week 4
GroupValue95% CI
Placebo-9.55-12.73 – -6.36
Fezolinetant-25.26-29.64 – -20.89
Week 8
GroupValue95% CI
Placebo-11.91-15.72 – -8.10
Fezolinetant-25.71-30.15 – -21.27
Week 12
GroupValue95% CI
Placebo-12.14-16.62 – -7.65
Fezolinetant-26.61-31.06 – -22.17
Change From Baseline in The Weekly Mild, Moderate and Severe Hot Flash Frequency at Weeks 4, 8 and 12 Secondary · Baseline and 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

Week 4
GroupValue95% CI
Placebo-26.4-35.2 – -17.5
Fezolinetant-72.3-82.7 – -61.8
Week 8
GroupValue95% CI
Placebo-32.9-43.2 – -22.7
Fezolinetant-73.3-83.8 – -62.8
Week 12
GroupValue95% CI
Placebo-35.6-46.7 – -24.5
Fezolinetant-75.3-86.4 – -64.3
Percentage of Participants With >=70% Reduction in the Weekly Hot Flash Score From Baseline to Weeks 4, 8 and 12 Secondary · Baseline and 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:

Week 4
GroupValue95% CI
Placebo22.710.34 – 35.11
Fezolinetant87.877.79 – 97.82
Week 8
GroupValue95% CI
Placebo39.024.09 – 53.96
Fezolinetant87.577.25 – 97.75
Week 12
GroupValue95% CI
Placebo42.527.18 – 57.82
Fezolinetant95.088.25 – 100.00
Percentage of Participants With >=80% Reduction in the Weekly Hot Flash Score From Baseline to Weeks 4, 8 and 12 Secondary · Baseline and 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:

Week 4
GroupValue95% CI
Placebo9.10.60 – 17.59
Fezolinetant78.065.38 – 90.72
Week 8
GroupValue95% CI
Placebo26.813.27 – 40.39
Fezolinetant77.564.56 – 90.44
Week 12
GroupValue95% CI
Placebo30.015.80 – 44.20
Fezolinetant87.577.25 – 97.75
Percentage of Participants With >=90% Reduction in the Weekly Hot Flash Score From Baseline to Weeks 4, 8 and 12 Secondary · Baseline and 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:

Week 4
GroupValue95% CI
Placebo6.80.00 – 14.27
Fezolinetant61.046.04 – 75.91
Week 8
GroupValue95% CI
Placebo12.22.18 – 22.21
Fezolinetant60.044.82 – 75.18
Week 12
GroupValue95% CI
Placebo15.03.93 – 26.07
Fezolinetant62.547.50 – 77.50
Percentage of Participants With >=50% Reduction in the Weekly Frequency of Moderate and Severe HF From Baseline to Weeks 4, 8 and 12 Secondary · Baseline and 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 nu

Week 4
GroupValue95% CI
Placebo45.530.74 – 60.17
Fezolinetant95.188.53 – 100.00
Week 8
GroupValue95% CI
Placebo53.738.39 – 68.92
Fezolinetant97.592.66 – 100.00
Week 12
GroupValue95% CI
Placebo55.039.58 – 70.42
Fezolinetant97.592.66 – 100.00
Percentage of Participants With >=70% Reduction in the Weekly Frequency of Moderate and Severe HF From Baseline to Weeks 4, 8 and 12 Secondary · Baseline and 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 nu

Week 4
GroupValue95% CI
Placebo25.012.21 – 37.79
Fezolinetant87.877.79 – 97.82
Week 8
GroupValue95% CI
Placebo46.331.08 – 61.61
Fezolinetant92.584.34 – 100.00
Week 12
GroupValue95% CI
Placebo40.024.82 – 55.18
Fezolinetant97.592.66 – 100.00
Percentage of Participants With >=90% Reduction in the Weekly Frequency of Moderate and Severe HF From Baseline to Weeks 4, 8 and 12 Secondary · Baseline and 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 nu

Week 4
GroupValue95% CI
Placebo6.80.00 – 14.27
Fezolinetant68.354.05 – 82.54
Week 8
GroupValue95% CI
Placebo24.411.25 – 37.54
Fezolinetant67.552.99 – 82.01
Week 12
GroupValue95% CI
Placebo20.07.60 – 32.40
Fezolinetant72.558.66 – 86.34
Change From Baseline in Hot Flash Related Daily Interference Scale (HFRDIS) Score at Weeks 4, 8 and 12 Secondary · Baseline and 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

Week 4: Work
GroupValue95% CI
Placebo-1.7± 2.93
Fezolinetant-4.6± 2.65
Week 8: Work
GroupValue95% CI
Placebo-2.4± 2.80
Fezolinetant-5.0± 2.38
Week 12: Work
GroupValue95% CI
Placebo-2.3± 2.58
Fezolinetant-4.6± 2.68
Week 4: Social Activities
GroupValue95% CI
Placebo-1.6± 2.53
Fezolinetant-4.3± 2.48
Week 8: Social Activities
GroupValue95% CI
Placebo-1.9± 2.85
Fezolinetant-4.7± 2.37
Week 12: Social Activities
GroupValue95% CI
Placebo-1.8± 2.51
Fezolinetant-4.3± 2.35
Week 4: Leisure Activities
GroupValue95% CI
Placebo-1.6± 2.63
Fezolinetant-4.0± 2.51
Week 8: Leisure Activities
GroupValue95% CI
Placebo-1.7± 2.72
Fezolinetant-4.2± 2.50
Change From Baseline in Leeds Sleep Evaluation Questionnaire (LSEQ) at Weeks 4, 8 and 12 Secondary · Baseline and 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

Week 4: Getting to Sleep
GroupValue95% CI
Placebo1.017± 1.9195
Fezolinetant2.283± 2.7364
Week 8: Getting to Sleep
GroupValue95% CI
Placebo1.145± 1.7931
Fezolinetant2.248± 2.5233
Week 12: Getting to Sleep
GroupValue95% CI
Placebo1.282± 1.7761
Fezolinetant2.094± 2.4419
Week 4: Quality of Sleep
GroupValue95% CI
Placebo2.145± 2.6443
Fezolinetant4.437± 4.0768
Week 8: Quality of Sleep
GroupValue95% CI
Placebo2.378± 2.8160
Fezolinetant4.703± 3.1971
Week 12: Quality of Sleep
GroupValue95% CI
Placebo1.904± 2.7872
Fezolinetant4.385± 3.4477
Week 4: Awake Following Sleep
GroupValue95% CI
Placebo0.642± 2.0739
Fezolinetant2.180± 3.0579
Week 8: Awake Following Sleep
GroupValue95% CI
Placebo0.653± 2.5019
Fezolinetant2.920± 3.0219

Adverse events — posted to ClinicalTrials.gov

Time frame: From first dose of study drug until end of the study (Up to week 15). Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Placebo
Serious: 1/44 (2%)
Deaths: 0/44
Fezolinetant
Serious: 0/43 (0%)
Deaths: 0/43

Serious adverse events (1 terms)

ReactionSystemPlaceboFezolinetant
Upper limb fractureInjury, poisoning and procedural complications
Other adverse events (8 terms — click to expand)

ReactionSystemPlaceboFezolinetant
HeadacheNervous system disorders
NasopharyngitisInfections and infestations
PalpitationsCardiac disorders
DiarrhoeaGastrointestinal disorders
FatigueGeneral disorders
InfluenzaInfections and infestations
ArthritisMusculoskeletal and connective tissue disorders
Back painMusculoskeletal and connective tissue disorders

Most-reported serious reactions: Upper limb fracture.

Data from ClinicalTrials.gov NCT05419908 adverse events section.

Sponsor's own description

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.

Publications & conference data

No peer-reviewed publications indexed yet for this trial. Completed trials usually publish results within 12-18 months.

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