Phase 2 Study of SJX-653 in Postmenopausal Women With Moderate to Severe Vasomotor Symptoms
Condition: Hot Flashes
MeSH terms: Hot Flashes
Intervention: SJX-653; Placebo
Intervention description: administered orally once daily; administered orally once daily
Intervention MeSH terms: SJX-653
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 13.0
Sex: Female
Minimum age: 40 Years
Maximum age: 65 Years
Healthy volunteers: No

Summary:

      This study evaluates the efficacy, safety, tolerability, and pharmacokinetics of once daily
      SJX-653 in postmenopausal women with moderate to severe VMS.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Signed a consent form before Screening procedures begin.

          2. Be a postmenopausal female, 40 to 65 years of age (inclusive) at the Screening Visit,
             defined as:

               1. Spontaneous amenorrhea for at least 12 months, OR

               2. 6 months of spontaneous amenorrhea with serum FSH levels >40 milli-International
                  unit (mIU/mL), OR

               3. 6 weeks past a postsurgical bilateral oophorectomy with or without hysterectomy.

             All postmenopausal woman (PMW) must have a serum follicle stimulating hormone (FSH)
             >40 mIU/mL at Screening.

          3. Have an average of at least 7 moderate to severe VMS per day at Baseline. The
             following definitions for severity are used:

               1. Mild: Sensation of heat without sweating/damping; if at night, do not wake up but
                  later notice damp sheets or clothing.

               2. Moderate: Sensation of heat with sweating/dampness, but able to continue
                  activity; if at night, wake up because hot and/or sweating, but no action is
                  necessary other than rearranging the bed sheets.

               3. Severe: Sensation of heat with sweating causing disruption of current activity;
                  if at night, wake up hot and sweating and need to take action (eg, removing layer
                  of clothes, open the window, or get out of bed).

          4. Have a body mass index between 18 and 35 kg/m2, inclusive.

          5. For subjects 50-65 years old, have documentation (written or electronic report) of a
             satisfactory mammogram result at Screening within applicable intervals stated in local
             breast cancer screening guidelines. Subjects 40-49 years old require a mammogram
             within the same intervals.

          6. Have documentation (written or electronic report) of a normal Pap smear (or equivalent
             cervical cytology) ) in combination with Human Papilloma virus (HPV) testing, or a Pap
             smear of no clinical significance in the opinion of the Investigator, at Screening
             within applicable intervals stated in local cervical cancer prevention guidelines.

          7. Have an endometrial thickness ≤4 mm by transvaginal ultrasound at Screening.

          8. Be willing to undergo an endometrial biopsy if they have unexplained bleeding during
             the study or endometrial thickness >4 mm at the EOT visit. An endometrial biopsy is
             not required for subjects who have had a partial (supracervical) or full hysterectomy.

        Exclusion Criteria:

          1. Have clinically significant history or evidence of poorly controlled cardiovascular,
             respiratory, hepatic, renal, gastrointestinal, endocrine, neurological, immunological,
             or psychiatric disorder(s) as determined by the Investigator or have any medical
             condition that requires chronic medication and that in the Investigator's opinion,
             would make subjects unsuitable for participation in the study.

          2. Have manifest or suspected active COVID-19 infection. Have tested positive for
             presence of SARS-CoV-2 based on a RT-PCR or other validated test; or have clinical
             symptoms suggestive of COVID-19 infection; or have to comply with quarantine
             requirements per local Public Health directive.

          3. Have a history of diagnosis of major depressive disorder in the 3 years prior to
             Screening, or are on any antidepressant, anxiolytic or antipsychotic treatment.
             Selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine
             reuptake inhibitors (SNRIs) treatment for mild depression and/or mild anxiety is
             allowed provided medication is stable and well-tolerated in the 3 months prior to the
             Screening Visit and does not change during study participation.

          4. Have a history of suicide ideation or attempt in the past 3 years.

          5. Have a history of a sleep disorder other than insomnia due to VMS (eg, narcolepsy,
             sleep apnea, restless leg syndrome).

          6. Have clinical or biochemical evidence of active hepatitis or other significant hepatic
             or biliary disease (eg, chronic hepatitis, cirrhosis, autoimmune hepatitis, primary
             biliary cholangitis, primary sclerosing cholangitis, nonalcoholic steatohepatitis,
             nonalcoholic fatty liver disease, or hereditary liver disease).

          7. Have any abnormal liver function tests at Screening or an estimated glomerular
             filtration rate (eGFR) <60 mL/min/1.73 m2 (CKD-EPI 2009 calculation; Levey et al
             2009).

          8. Have tested positive for human immunodeficiency virus, hepatitis B, C or E at
             Screening.

          9. Have any gastrointestinal, liver, kidney or other disorder that would significantly
             interfere with the absorption, distribution, metabolism, or excretion (ADME) of drugs
             in the opinion of the Investigator.

         10. Have a history of alcohol abuse or a history of substance abuse.

         11. Smoking >10 cigarettes per day.

         12. Regularly working night shifts.

         13. Systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg, based on
             the median of a total of 4 to 6 readings, from 2 to 3 readings taken on 2 diﬀerent
             occasions.

         14. Have clinically significant abnormal ECG or QT interval prolongation (corrected for
             heart rate using Fridericia formula [QTcF] prolongation >470 ms) at Screening.

         15. Have a history of endometrial hyperplasia or uterine/endometrial cancer.

         16. Have current unexplained uterine bleeding.

         17. Have a history of cancer prior to Screening (other than local, treated basal cell or
             squamous cell carcinoma).

         18. Have any significant illness requiring hospitalization or emergency treatment within 4
             weeks prior to the Screening Visit or during the Screening or Run-in Periods, and as
             determined by the Investigator.

         19. Are pregnant or lactating.

         20. Have used hormonal treatments within defined periods of time prior to the start of the
             Run-in Period. Washout times dependent on treatment.

         21. Are taking any nonhormonal medication for treatment of VMS in the 8-week period prior
             to the start of the Run-in Period.

         22. Have used herbal supplements or over-the-counter (OTC) medications for treatment of
             VMS 8 weeks prior to the start of the Run in Period. Any other herbal supplements or
             OTC supplements that could interfere with the study objectives require a 28-day
             wash-out period prior to the start of the Run-in Period.

         23. Are taking any antiestrogens, selective estrogen receptor modulators, or aromatase
             inhibitors.

         24. Are taking any antigonadotropin medication.