Clinical trial NCT03192176 (phase 2, status: completed)
Conditions: menopause, hot flashes
ICD codes: E28.310, E28.319
Drugs: fezolinetant, placebo, placebo
SMILES: CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O, CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O
Eligibility criteria:

        Inclusion Criteria:

          -  Women >40 years and ≤65 years of age at the screening visit;

          -  A body mass index between 18 kg/sqm to 38 kg/sqm (extremes included);

          -  Spontaneous amenorrhea for ≥12 consecutive months; or spontaneous amenorrhea for ≥6
             months with biochemical criteria of menopause (follicle-stimulating hormone [FSH] >40
             IU/L); or having had bilateral oophorectomy ≥6 weeks prior to the screening visit
             (with or without hysterectomy);

          -  At least 50 moderate to severe vasomotor symptoms per week (ie, 7 consecutive days),
             as recorded in the daily diary during the screening period;

          -  In good general health as determined on the basis of medical history and general
             physical examination, including a bimanual clinical pelvic examination and clinical
             breast examination devoid of relevant clinical findings, performed at the screening
             visit; hematology and biochemistry parameters, pulse rate and/or blood pressure, and
             ECG within the reference range for the population studied, or showing no clinically
             relevant deviations, as judged by the Investigator;

          -  Women >40 years of age who have documentation of a normal/negative or no clinically
             significant findings mammogram (obtained at Screening or within the prior 9 months of
             trial enrollment.) Appropriate documentation includes a written report or an
             electronic report indicating normal/negative or no clinically significant mammographic
             findings;

          -  Willing to undergo a transvaginal ultrasound to assess endometrial thickness at
             Screening and at Week 12 (end-of-treatment, - and subjects) who are withdrawn from the
             study prior to completion, at the Early Termination (ET) Visit. This is not required
             for subjects who have had a partial (supracervical) or full hysterectomy;

          -  Willing to undergo an endometrial biopsy at Screening (in the event that the subject's
             transvaginal ultrasound shows endometrial thickness ≥4 mm) and at Week 12
             (end--of--treatment) - all subjects), for subjects with uterine bleeding, and for
             subjects who are withdrawn from the study prior to completion, at the ET Visit if
             study drug exposure is ≥10 weeks. This is not required for subjects who have had a
             partial (supracervical) or full hysterectomy;

          -  Negative alcohol breath test and negative urine test for selected drugs of abuse
             (amphetamines, tricyclic antidepressants, cocaine, or opiates) at the screening visit;

          -  Negative urine pregnancy test;

          -  Negative serology panel (including hepatitis B surface antigen, hepatitis C virus
             antibody, and human immunodeficiency virus antibody screens);

          -  Informed Consent Form signed voluntarily before any study-related procedure is
             performed, indicating that the subject understands the purpose of and procedures
             required for the study and is willing to participate in the study; and

          -  Documentation of a normal Pap smear (or equivalent cervical cytology) or of no
             clinical significance in the opinion of the Investigator within the previous 9 months
             or at Screening.

        Exclusion Criteria:

          -  Use of a prohibited therapy (hormone therapy, hormonal contraceptive, or vasomotor
             symptom medication [prescription, over the counter, or herbal]) or not willing to wash
             out drugs

          -  History (in the past year) or presence of drug or alcohol abuse;

          -  Previous or current history of a malignant tumor, except for basal cell carcinoma;

          -  Uncontrolled hypertension and a systolic blood pressure ≥140 mmHg and/or a diastolic
             blood pressure ≥90 mmHg;

          -  Judged by the Investigator to be unsuited to participate in the study based on
             findings observed during physical examination, vital sign assessment, or 12-lead
             electrocardiogram (ECG);

          -  History of severe allergy, hypersensitivity, or intolerance to drugs in general,
             including the study drug and any of its excipients;

          -  Exclusion criterion 7 has been removed in Amendment 1;

          -  An unacceptable result from endometrial biopsy (performed when endometrial thickness
             is ≥ 4mm measured by transvaginal ultrasound) of endometrial hyperplasia, endometrial
             cancer, or inadequate specimen at Screening (1 repeat biopsy permitted if technically
             possible);

          -  History of endometrial hyperplasia or uterine/endometrial cancer;

          -  History of unexplained uterine bleeding;

          -  History of seizures or other convulsive disorders;

          -  Medical condition or chronic disease (including history of neurological [including
             cognitive], hepatic, renal, cardiovascular, gastrointestinal, pulmonary [eg, moderate
             asthma], endocrine, or gynecological disease) or malignancy that could confound
             interpretation of the study outcome;

          -  Presence or sequelae of gastrointestinal, liver, kidney, or other conditions known to
             interfere with the absorption, distribution, metabolism, or excretion (ADME)
             mechanisms of drugs as judged by the Investigator;

          -  Active liver disease or jaundice, or values of alanine aminotransferase (ALT) and
             aspartate aminotransferase (AST) >1.5 x the upper limit of normal (ULN); or total
             bilirubin >1.5 x ULN; or creatinine >1.5 x ULN; or estimated glomerular filtration
             rate (eGFR) using the Modification of Diet in Renal Disease formula ≤59 mL/min/1.73
             sqm at the screening visit;

          -  Concurrent participation in another interventional study (or participation within 3
             months prior to screening in this study);

          -  Suicide attempt in the past 3 years;

          -  Unable or unwilling to complete the study procedures; or

          -  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.