Hot Flashes
Conditions
Brief summary
This study evaluates the efficacy, safety, tolerability, and pharmacokinetics of once daily SJX-653 in postmenopausal women with moderate to severe VMS.
Interventions
DRUGSJX-653
administered orally once daily
DRUGPlacebo
administered orally once daily
Sponsors
Sojournix, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
40 Years to 65 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change in Average Daily Frequency of Moderate to Severe Vasomotor Symptoms (VMS) From Baseline to Week 4 | Baseline to Week 4 | Moderate to severe vasomotor symptoms collected daily by e-diary |
Secondary
| Measure | Time frame |
|---|---|
| Mean Change in the Severity of Moderate to Severe VMS From Baseline to Week 4 | Baseline to Week 4 |
| Mean Change and Percent Change of Parameters of VMS Frequency and Severity by Study Week | Baseline up to Week 6 |
Other
| Measure | Time frame |
|---|---|
| Change From Baseline in Insomnia Severity Index (ISI) | Baseline up to Week 4 |
| Change From Baseline in Hot Flash Related Daily Interference Scale (HFRDIS) | Baseline up to Week 4 |
Countries
Belgium, Germany, Poland, United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| SJX-653 Participants will receive SJX-653
SJX-653: administered orally once daily | 7 |
| Placebo Participants will receive placebo
Placebo: administered orally once daily | 6 |
| Total | 13 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Protocol Violation | 0 | 1 |
| Overall Study | Study Termination | 2 | 0 |
Baseline characteristics
| Characteristic | SJX-653 | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 7 Participants | 6 Participants | 13 Participants |
| Age, Continuous | 56.1 years STANDARD_DEVIATION 3.29 | 58.3 years STANDARD_DEVIATION 4.03 | 57.2 years STANDARD_DEVIATION 3.67 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 7 Participants | 6 Participants | 13 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 7 Participants | 5 Participants | 12 Participants |
| Sex: Female, Male Female | 7 Participants | 6 Participants | 13 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 7 | 0 / 6 |
| other Total, other adverse events | 6 / 7 | 2 / 6 |
| serious Total, serious adverse events | 0 / 7 | 0 / 6 |
Outcome results
Primary
Mean Change in Average Daily Frequency of Moderate to Severe Vasomotor Symptoms (VMS) From Baseline to Week 4
Moderate to severe vasomotor symptoms collected daily by e-diary
Time frame: Baseline to Week 4
Population: Study was terminated early and program discontinued. Raw data (patient-reported outcomes/diary entries) were not processed to obtain primary outcome measures, therefore primary outcome measures could not be analyzed.
Secondary
Mean Change and Percent Change of Parameters of VMS Frequency and Severity by Study Week
Time frame: Baseline up to Week 6
Secondary
Mean Change in the Severity of Moderate to Severe VMS From Baseline to Week 4
Time frame: Baseline to Week 4
Other Pre-specified
Change From Baseline in Hot Flash Related Daily Interference Scale (HFRDIS)
Time frame: Baseline up to Week 4
Other Pre-specified
Change From Baseline in Insomnia Severity Index (ISI)
Time frame: Baseline up to Week 4