Clinical trial NCT03596762: A Study of BAY3427080 (NT-814) in the Treatment of Moderate to Severe Post-menopausal Vasomotor Symptoms
Official title: A Double-Blind, Randomised, Placebo Controlled, Adaptive Design Study of the Efficacy, Safety and Pharmacokinetics of NT-814 in Female Subjects With Moderate to Severe Vasomotor Symptoms Associated With the Menopause
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Menopause
Hot Flashes
Night Waking
Lead sponsor: Bayer
Sponsor class: INDUSTRY
Collaborators: name: Nerre Therapeutics Ltd.
First posted: 2018-07-24
Enrollment: 199
Sex: FEMALE
Minimum age (years): 40
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine the effectiveness of BAY3427080 (NT-814), taken once a day, in the treatment of troublesome post-menopausal symptoms.

Detailed description: This is a multi-centre, multi-country, double-blind, randomised, placebo-controlled Phase 2b study. The study will have a single-blind run-in period and will be adaptive with respect to the number of subjects recruited into each dose group. Four doses of BAY3427080 (40 mg once a day, 80 mg once a day, 120 mg once a day and 160 mg once a day) will be investigated and compared to placebo, in five parallel groups. Subjects will participate in the study for a total of approximately 19 weeks, comprising a screening period of 1 week, a 14 week treatment period, and then a final follow up visit 4 weeks after the end of the treatment period. There will be a total of 8 visits whilst participating in the study. Subjects will record their hot flashes in an electronic diary during the screening period to establish eligibility and throughout the study after randomisation.

Eligibility criteria: Key Inclusion Criteria:

* Postmenopausal
* Body mass index between 18 and 38 kg/m2, inclusive
* Subject experiences moderate or severe hot flashes

Key Exclusion Criteria:

* Inability to comply with the use of prohibited and allowed medications as described in the protocol.
* Any prior or ongoing history of clinically relevant drug or alcohol abuse within 12 months of Screening.
* Any clinically significant prior or ongoing history of arrhythmias, either determined through clinical history or on ECG evaluation.
* Any clinically significant abnormal laboratory test result(s) measured at Screening.
* Any active ongoing condition that could have caused difficulty in interpreting vasomotor symptoms.
* Uncontrolled hypertension.
* A history or hyperthyroidism, hypothyroidism or abnormal thyroid function tests at Screening. Treated hypothyroidism with normal thyroid function test results at Screening is acceptable.

Primary outcomes:
measure: Mean Change From Baseline in Mean Daily Frequency of Moderate and Severe Hot Flushes From Baseline to Week 4
timeFrame: From baseline to Week 4
measure: Mean Change From Baseline in Mean Daily Frequency of Moderate and Severe Hot Flushes From Baseline to Week 12
timeFrame: From baseline to Week 12
measure: Mean Change From Baseline in Mean Severity of Moderate and Severe Hot Flushes From Baseline to Week 4
timeFrame: From baseline to Week 4
measure: Mean Change From Baseline in Mean Severity of Moderate and Severe Hot Flushes From Baseline to Week 12
timeFrame: From baseline to Week 12
Secondary outcomes:
measure: Mean Change From Baseline in Frequency of Mean Daily Moderate and Severe Hot Flushes From Baseline to Weeks 1, 2, 8 and 16
timeFrame: From baseline to Weeks 1, 2, 8 and 16
measure: Mean Change From Baseline in Mean Severity of Moderate and Severe Hot Flushes From Baseline to Weeks 1, 2, 8 and 16
timeFrame: From baseline to Weeks 1, 2, 8 and 16
measure: Mean Change From Baseline in Mean Daily Frequency of All Hot Flushes From Baseline to Weeks 1, 2, 4, 8, 12 and 16
timeFrame: From baseline to Weeks 1, 2, 4, 8, 12 and 16
measure: Mean Change From Baseline in Mean Severity of All Hot Flushes From Baseline to Weeks 1, 2, 4, 8, 12 and 16
timeFrame: From baseline to Weeks 1, 2, 4, 8, 12 and 16
measure: Mean Change From Baseline in the Mean Daily Hot Flush Score (Frequency x Severity) at Weeks 1, 2, 4, 8, 12 and 16
timeFrame: From baseline to Weeks 1, 2, 4, 8, 12 and 16
measure: Number of Participants With ≥50% and ≥80% Reduction From Baseline in Mean Daily Hot Flushes Frequency at Week 12
timeFrame: Week 12
measure: Mean Change From Baseline in Number of All Night-time Awakenings (NTA) at Weeks 1, 2, 4, 8, 12 and 16
timeFrame: From baseline to Weeks 1, 2, 4, 8, 12 and 16
measure: Mean Change From Baseline in Mean Daily Number of NTAs Secondary to Hot Flushes at Weeks 1, 2, 4, 8, 12 and 16
timeFrame: From baseline to Weeks 1, 2, 4, 8, 12 and 16
measure: Change From Baseline in the Global and Individual Domain Scores of the Pittsburgh Sleep Quality Index (PSQI) at Weeks 4, 8, 12 and 16
timeFrame: From baseline to Weeks 4, 8, 12 and 16
measure: Change From Baseline in the Insomnia Severity Index (ISI) Score at Weeks 4, 8, 12 and 16
timeFrame: From baseline to Weeks 4, 8, 12 and 16
measure: Change From Baseline in the Hot Flush Related Daily Interference Scale (HFRDIS) Scores at Weeks 2, 4, 8, 12 and 16
timeFrame: From baseline to Weeks 2, 4, 8, 12 and 16
measure: Change From Baseline in the Menopause-specific Quality-of-Life Questionnaire Intervention Version (MenQoL-I) Scores at Weeks 4, 8, 12 and 16
timeFrame: From baseline to Weeks 4, 8, 12 and 16;
measure: Change From Baseline in the Beck Depression Inventory II (BDI-II) Scores at Weeks 2, 4, 8, 12 and 16
timeFrame: From baseline to Weeks 2, 4, 8, 12 and 16
measure: Plasma Elinzanetant Concentrations at Weeks 2, 4, 8 ,12
timeFrame: At Weeks 2, 4, 8 ,12
measure: Nature and Severity of Adverse Events
timeFrame: Up to Week 16
measure: Withdrawals Due to an Adverse Event
timeFrame: Up to Week 16
measure: Number of Subjects Used Concomitant Medications
timeFrame: Up to Week 16
measure: Change From Baseline in Vital Signs (Systolic Blood Pressure) at Weeks 2, 4, 8, 12 and 16
timeFrame: From baseline to Weeks 2, 4, 8, 12 and 16
measure: Change From Baseline in Vital Signs (Diastolic Blood Pressure) at Weeks 2, 4, 8, 12 and 16
timeFrame: From baseline to Weeks 2, 4, 8, 12 and 16
measure: Change From Baseline in Vital Signs (Pulse Rate) at Weeks 2, 4, 8, 12 and 16
timeFrame: From baseline to Weeks 2, 4, 8, 12 and 16
measure: Change From Baseline in Vital Signs (Temperature) at Weeks 2, 4, 8, 12 and 16
timeFrame: From baseline to Weeks 2, 4, 8, 12 and 16
measure: Change From Baseline in Vital Signs (Weight) at Weeks 2, 4, 8, 12 and 16
timeFrame: From baseline to Weeks 2, 4, 8, 12 and 16
measure: Change From Baseline in Vital Signs (Body Mass Index ) at Weeks 2, 4, 8, 12 and 16
timeFrame: From baseline to Weeks 2, 4, 8, 12 and 16
measure: Change From Baseline in Vital Signs (Waist Circumference) at Weeks 2, 4, 8, 12 and 16
timeFrame: From baseline to Weeks 2, 4, 8, 12 and 16
measure: Number of Subjects With Normal Electrocardiogram (ECG) Findings at Each Visit
timeFrame: At Weeks 2, 4, 8, 12 and 16
measure: Number of Subjects With Abnormal Not Clinically Significant ECG Findings at Each Visit
timeFrame: At Weeks 2, 4, 8, 12 and 16
measure: Number of Subjects With Abnormal Clinically Significant ECG Findings at Each Visit
timeFrame: At Weeks 2, 4, 8, 12 and 16
measure: Change From Baseline at Weeks 2, 4, 8, 12 and 16 in ECG Intervals (RR)
timeFrame: At Weeks 2, 4, 8, 12 and 16
measure: Change From Baseline at Weeks 2, 4, 8, 12 and 16 in ECG Intervals (PR)
timeFrame: At Weeks 2, 4, 8, 12 and 16
measure: Change From Baseline at Weeks 2, 4, 8, 12 and 16 in ECG Intervals (QT)
timeFrame: At Weeks 2, 4, 8, 12 and 16
measure: Change From Baseline at Weeks 2, 4, 8, 12 and 16 in ECG Intervals (QTc)
timeFrame: At Weeks 2, 4, 8, 12 and 16
measure: Change From Baseline at Weeks 2, 4, 8, 12 and 16 in ECG Intervals (QTcF)
timeFrame: At Weeks 2, 4, 8, 12 and 16
measure: Number of Subjects With Absolute QTcF Values by Category at Each Visit: ≤450, >450 to ≤480, >480 to ≤500, >500 Msec
timeFrame: From baseline to Weeks 2, 4, 8, 12 and 16
measure: Number of Subjects With Change From Baseline in ECG QTcF Values by Category at Weeks 2, 4, 8, 12 and 16: ≤0, >0 to ≤30, >30 to ≤60, >60 Msec
timeFrame: From baseline to Weeks 2, 4, 8, 12 and 16
measure: Change From Baseline in the Electronic Columbia Suicide Severity Rating Scale (eC-SSRS) at Weeks 4, 12 and 16
timeFrame: Baseline to Weeks 4, 12 and 16
measure: Change From Baseline at Weeks 2, 4, 12 and 16 for Clinical Laboratory Parameters Hematology: Erythrocytes
timeFrame: From baseline to Weeks 2, 4, 12 and 16
measure: Change From Baseline at Weeks 2, 4, 12 and 16 for Clinical Laboratory Parameters Hematology: Hematocrit
timeFrame: From baseline to Weeks 2, 4, 12 and 16
measure: Change From Baseline at Weeks 2, 4, 12 and 16 in Clinical Laboratory Parameters Hematology: Hemoglobin
timeFrame: From baseline to Weeks 2, 4, 12 and 16
measure: Change From Baseline at Weeks 2, 4, 12 and 16 in Clinical Laboratory Parameters Hematology: Erythrocytes Mean Corpuscular Volume
timeFrame: From baseline to Weeks 2, 4, 12 and 16
measure: Change From Baseline at Weeks 2, 4, 12 and 16 in Clinical Laboratory Parameters Hematology: Leukocytes, Platelets, Basophils, Eosinophils, Lymphocytes, Monocytes and Neutrophils
timeFrame: From baseline to Weeks 2, 4, 12 and 16
measure: Change From Baseline at Weeks 2, 4, 12 and 16 in Clinical Laboratory Parameters Hematology: Leukocytes, Basophils, Eosinophils, Lymphocytes, Monocytes and Neutrophils
timeFrame: From baseline to Weeks 2, 4, 12 and 16
measure: Change From Baseline at Weeks 2, 4, 8, 12 and 16 in Clinical Laboratory Parameters Biochemistry: Sodium, Potassium, Glucose, Urea Nitrogen, Calcium, Phosphate, Bicarbonate, Magnesium and Chloride
timeFrame: From baseline to Weeks 2, 4, 8, 12 and 16
measure: Change From Baseline at Weeks 2, 4, 8, 12 and 16 in Clinical Laboratory Parameters Biochemistry: Creatinine and Bilirubin
timeFrame: From baseline to Weeks 2, 4, 8, 12 and 16
measure: Change From Baseline at Weeks 2, 4, 8, 12 and 16 in Clinical Laboratory Parameters Biochemistry: Creatinine Kinase, Alkaline Phosphatase, Aspartate Aminotransferase, Alanine Aminotransferase and Gamma Glutamyl Transferase
timeFrame: From baseline to Weeks 2, 4, 8, 12 and 16
measure: Change From Baseline at Weeks 2, 4, 8, 12 and 16 in Clinical Laboratory Parameters Biochemistry: Protein and Albumin
timeFrame: From baseline to Weeks 2, 4, 8, 12 and 16
measure: Change From Baseline at Weeks 2, 4, 8, 12 and 16 in Clinical Laboratory Parameters Biochemistry: Hemoglobin A1C
timeFrame: From baseline to Weeks 2, 4, 8, 12 and 16
measure: Change From Baseline at Weeks 12 and 16 in Clinical Laboratory Parameters Bone: Bone Specific Alkaline Phosphatase and Procollagen 1 N-Terminal Propeptide
timeFrame: From baseline to Weeks 12 and 16
measure: Change From Baseline at Weeks 2, 4, 12 and 16 in Clinical Laboratory Parameters Urinalysis: pH
timeFrame: From baseline to Weeks 2, 4, 12 and 16
measure: Change From Baseline at Weeks 2, 4, 12 and 16 in Clinical Laboratory Parameters Urinalysis: Specific Gravity
timeFrame: From baseline to Weeks 2, 4, 12 and 16
measure: Change From Baseline at Weeks 2, 4, 12 and 16 in Clinical Laboratory Parameters Urinalysis: Glucose, Bilirubin, Ketones, Occult Blood, Protein, Urobilinogen and Nitrite
timeFrame: From baseline to Weeks 2, 4, 12 and 16
measure: Change From Baseline at Weeks 2, 4, 12 and 16 in Clinical Laboratory Parameters Urinalysis: Erythrocytes and Leukocytes
timeFrame: From baseline to Weeks 2, 4, 12 and 16
measure: Change From Baseline at Weeks 2, 4, 12 and 16 in Clinical Laboratory Parameters Urinalysis: Hyaline Casts
timeFrame: From baseline to Weeks 2, 4, 12 and 16
measure: Change From Baseline at Weeks 2, 4, 12 and 16 in Clinical Laboratory Parameters Urinalysis: Bacteria, Yeast Cells, Granular Casts, RBC Casts, Waxy Casts, WBC Casts, Calcium Oxalate Crystals, Triple Phosphate Crystals and Uric Acid Crystals
timeFrame: From baseline to Weeks 2, 4, 12 and 16
Other outcomes:
Locations:
city: Mesa
country: United States
facility: Study Site 12
state: Arizona
city: San Diego
country: United States
facility: Study Site 19
state: California
city: Aventura
country: United States
facility: Study Site 13
state: Florida
city: Lake Worth
country: United States
facility: Study Site 15
state: Florida
city: Atlanta
country: United States
facility: Study Site 18
state: Georgia
city: New Orleans
country: United States
facility: Study Site 16
state: Louisiana
city: Boston
country: United States
facility: Study Site 10
state: Massachusetts
city: Boston
country: United States
facility: Study Site 11
state: Massachusetts
city: Las Vegas
country: United States
facility: Study Site 17
state: Nevada
city: Houston
country: United States
facility: Study Site 14
state: Texas
city: Red Deer
country: Canada
facility: Study Site 50
state: Alberta
city: Mission
country: Canada
facility: Study Site 51
state: British Columbia
city: Guelph
country: Canada
facility: Study Site 54
state: Ontario
city: Scarborough
country: Canada
facility: Study Site 52
state: Ontario
city: Toronto
country: Canada
facility: Study Site 53
state: Ontario
city: Blackpool
country: United Kingdom
facility: Study Site 37
city: Cannock
country: United Kingdom
facility: Study Site 34
city: Glasgow
country: United Kingdom
facility: Study Site 31
city: Leeds
country: United Kingdom
facility: Study Site 39
city: Liverpool
country: United Kingdom
facility: Study Site 38
city: London
country: United Kingdom
facility: Study Site 30
city: Manchester
country: United Kingdom
facility: Study Site 36
city: Poole
country: United Kingdom
facility: Study Site 33
city: Southport
country: United Kingdom
facility: Study Site 32
city: Stockton-on-Tees
country: United Kingdom
facility: Study Site 35
Study officials:
References: