Trial Outcomes & Findings for A Study of the Safety and Effect of Repeated Administration of G-CSF on Hot Flashes in Postmenopausal Women (NCT NCT03640754)

NCT ID: NCT03640754

Last Updated: 2023-11-28

Results Overview

An adverse event (AE) is any untoward medical occurrence, including the exacerbation of a pre-existing condition, in a subject or clinical investigation subject administered a pharmaceutical product. This does not necessarily have a causal relationship with this treatment. A serious adverse event (SAE) is any experience that suggests a significant hazard, contraindication, side effect, or precaution. This includes any experience that results in death; is acutely life-threatening; requires inpatient hospitalization or prolongs the existing hospitalization; results in persistent or significant incapacity or substantial disruption of ability to conduct normal life functions; is a congenital anomaly/birth defect; or requires medical or surgical intervention to prevent one of the outcomes listed above.

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 61 participants
• Primary outcome timeframe: From first dose date up to 30 days after last dose (up to 16 weeks)
• Results posted on: 2023-11-28

Participant Flow

Postmenopausal women participants 40 to 65 years of age who had moderate to severe vasomotor symptoms (VMS) and seeking treatment or relief for hot flashes associated with menopause, confirmed as menopausal, had to have 7 to 8 moderate to severe hot flashes per day within the 7 days prior to randomization and who met the inclusion criteria and none of the exclusion criteria were enrolled in this study. A total of 61 subjects were randomized to receive G-CSF or saline in this trial.

Prior to randomization, participants had a screening period during which a minimum 7-day collection of baseline hot flash frequency and severity assessments were performed.

Participant milestones

Measure	Experimental: G-CSF (All Subjects) Intervention: G-CSF (300 mcg/injection as filgrastim) given by subcutaneous injection on days 0, 28 and 56. This group is all women in the study that received G-CSF.	Comparator: Placebo/Saline (All Subjects) Intervention: Placebo (as saline) given by subcutaneous injection on days 0, 28 and 56. This group is all women in the study that received placebo.
Overall Study STARTED	31	30
Overall Study COMPLETED	30	29
Overall Study NOT COMPLETED	1	1

Reasons for withdrawal

Measure	Experimental: G-CSF (All Subjects) Intervention: G-CSF (300 mcg/injection as filgrastim) given by subcutaneous injection on days 0, 28 and 56. This group is all women in the study that received G-CSF.	Comparator: Placebo/Saline (All Subjects) Intervention: Placebo (as saline) given by subcutaneous injection on days 0, 28 and 56. This group is all women in the study that received placebo.
Overall Study Withdrawal by Subject	1	0
Overall Study Lost to Follow-up	0	1

Baseline Characteristics

A Study of the Safety and Effect of Repeated Administration of G-CSF on Hot Flashes in Postmenopausal Women

Baseline characteristics by cohort

Measure	Experimental: G-CSF (All Subjects) n=31 Participants Intervention: G-CSF given by subcutaneous injection repeated 3 times (Days 0, 28, 56) Other name: Filgrastim G-CSF: G-CSF injected subcutaneously 3 times (Days 0, 28, 56)	Comparator: Placebo/Saline (All Subjects) n=30 Participants Intervention: Placebo/saline given by subcutaneous injection repeated 3 times (Days 0, 28, 56) Other name: Saline Placebo/Saline: Placebo/saline injected subcutaneously 3 times (Days 0, 28, 56)	Total n=61 Participants Total of all reporting groups
Age, Continuous	55.4 years STANDARD_DEVIATION 4.39 • n=5 Participants	55.6 years STANDARD_DEVIATION 4.58 • n=7 Participants	55.5 years STANDARD_DEVIATION 4.45 • n=5 Participants
Sex: Female, Male Female	31 Participants n=5 Participants	30 Participants n=7 Participants	61 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	6 Participants n=5 Participants	6 Participants n=7 Participants	12 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	25 Participants n=5 Participants	24 Participants n=7 Participants	49 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	6 Participants n=5 Participants	7 Participants n=7 Participants	13 Participants n=5 Participants
Race (NIH/OMB) White	22 Participants n=5 Participants	23 Participants n=7 Participants	45 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Daily Moderate + Severe Hot Flashes (M+S)	12.5 Number of hot flashes per day STANDARD_DEVIATION 5.14 • n=5 Participants	12.3 Number of hot flashes per day STANDARD_DEVIATION 4.73 • n=7 Participants	12.4 Number of hot flashes per day STANDARD_DEVIATION 4.9 • n=5 Participants
Composite Daily Hot Flash Severity (CDS)	33.7 Number of hot flashes per day STANDARD_DEVIATION 12.72 • n=5 Participants	33.7 Number of hot flashes per day STANDARD_DEVIATION 14.44 • n=7 Participants	33.7 Number of hot flashes per day STANDARD_DEVIATION 13.49 • n=5 Participants
Hot Flash Severity Score (HFSS)	2.3 Score on a scale STANDARD_DEVIATION 0.32 • n=5 Participants	2.4 Score on a scale STANDARD_DEVIATION 0.35 • n=7 Participants	2.3 Score on a scale STANDARD_DEVIATION 0.34 • n=5 Participants
White Blood Cell Counts (WBC)	6007 White Blood Cells per mL STANDARD_DEVIATION 1923 • n=5 Participants	6142 White Blood Cells per mL STANDARD_DEVIATION 1296 • n=7 Participants	6088 White Blood Cells per mL STANDARD_DEVIATION 1633 • n=5 Participants
Menopause-specific Quality of Life Questionnaire - Vasomotor symptom (MENQOL VMS) Score	15.5 Score on a scale STANDARD_DEVIATION 2.6 • n=5 Participants	15.6 Score on a scale STANDARD_DEVIATION 2.5 • n=7 Participants	15.6 Score on a scale STANDARD_DEVIATION 2.5 • n=5 Participants
Hot Flash Related Daily Interference Scale (HFRDIS) Score	56.9 Score on a scale STANDARD_DEVIATION 21.5 • n=5 Participants	62.6 Score on a scale STANDARD_DEVIATION 18.7 • n=7 Participants	59.8 Score on a scale STANDARD_DEVIATION 20.2 • n=5 Participants
Insomnia Severity Index (ISI) Score	18.8 Score on a scale STANDARD_DEVIATION 5.1 • n=5 Participants	19.4 Score on a scale STANDARD_DEVIATION 5.4 • n=7 Participants	19.1 Score on a scale STANDARD_DEVIATION 5.2 • n=5 Participants
Fatigue Severity Scale (FSS) Score	33.8 Score on a scale STANDARD_DEVIATION 15.6 • n=5 Participants	34.0 Score on a scale STANDARD_DEVIATION 15.8 • n=7 Participants	33.9 Score on a scale STANDARD_DEVIATION 15.5 • n=5 Participants

PRIMARY outcome

Timeframe: From first dose date up to 30 days after last dose (up to 16 weeks)

An adverse event (AE) is any untoward medical occurrence, including the exacerbation of a pre-existing condition, in a subject or clinical investigation subject administered a pharmaceutical product. This does not necessarily have a causal relationship with this treatment. A serious adverse event (SAE) is any experience that suggests a significant hazard, contraindication, side effect, or precaution. This includes any experience that results in death; is acutely life-threatening; requires inpatient hospitalization or prolongs the existing hospitalization; results in persistent or significant incapacity or substantial disruption of ability to conduct normal life functions; is a congenital anomaly/birth defect; or requires medical or surgical intervention to prevent one of the outcomes listed above.

Outcome measures

Measure	Experimental: G-CSF (All Subjects) n=30 Participants Intervention: G-CSF (300 mcg/injection as filgrastim) given by subcutaneous injection on days 0, 28 and 56. This group is all women in the study that received G-CSF.	Comparator: Placebo/Saline (All Subjects) n=30 Participants Intervention: Placebo (as saline) given by subcutaneous injection on days 0, 28 and 56. This group is all women in the study that received placebo.	Experimental: G-CSF (White, NH Subgroup) n=18 Participants Intervention: G-CSF (300 mcg/injection as filgrastim) given by subcutaneous injection on days 0, 28 and 56. This is a subgroup of the women in the study that received G-CSF and that self-identified as white, non-Hispanic.	Comparator: Placebo/Saline (White, NH Subgroup) n=18 Participants Intervention: Placebo (as saline) given by subcutaneous injection on days 0, 28 and 56. This is a subgroup of the women in the study that received placebo and that self-identified as white, non-Hispanic.	Experimental: G-CSF (Black Subjects) Intervention: G-CSF (300 mcg/injection as filgrastim) given by subcutaneous injection on days 0, 28 and 56. This is a subgroup of the women in the study that received G-CSF and that self-identified as Black.	Comparator: Placebo (Black Subjects) Intervention: Placebo (as saline) given by subcutaneous injection on days 0, 28 and 56. This is a subgroup of the women in the study that received placebo and that self-identified as Black.
Number of Participants With Adverse Events Treatment Emergent Adverse Events (TEAE)	24 Participants	20 Participants	12 Participants	10 Participants	—	—
Number of Participants With Adverse Events Drug-related TEAE	12 Participants	3 Participants	5 Participants	3 Participants	—	—
Number of Participants With Adverse Events Serious TEAE	0 Participants	0 Participants	0 Participants	0 Participants	—	—
Number of Participants With Adverse Events Drug-related serious TEAE	0 Participants	0 Participants	0 Participants	0 Participants	—	—
Number of Participants With Adverse Events TEAE leading to death	0 Participants	0 Participants	0 Participants	0 Participants	—	—
Number of Participants With Adverse Events TEAE leading to withdrawal of treatment	0 Participants	0 Participants	0 Participants	0 Participants	—	—

PRIMARY outcome

Timeframe: Baseline and day 1

Change from baseline in white blood cell counts 24 hours after administration of G-CSF or placebo on day 0. Blood samples were collected 24 hours after adminstration of G-CSF on day 0.

Outcome measures

Measure	Experimental: G-CSF (All Subjects) n=30 Participants Intervention: G-CSF (300 mcg/injection as filgrastim) given by subcutaneous injection on days 0, 28 and 56. This group is all women in the study that received G-CSF.	Comparator: Placebo/Saline (All Subjects) n=30 Participants Intervention: Placebo (as saline) given by subcutaneous injection on days 0, 28 and 56. This group is all women in the study that received placebo.	Experimental: G-CSF (White, NH Subgroup) n=18 Participants Intervention: G-CSF (300 mcg/injection as filgrastim) given by subcutaneous injection on days 0, 28 and 56. This is a subgroup of the women in the study that received G-CSF and that self-identified as white, non-Hispanic.	Comparator: Placebo/Saline (White, NH Subgroup) n=18 Participants Intervention: Placebo (as saline) given by subcutaneous injection on days 0, 28 and 56. This is a subgroup of the women in the study that received placebo and that self-identified as white, non-Hispanic.	Experimental: G-CSF (Black Subjects) Intervention: G-CSF (300 mcg/injection as filgrastim) given by subcutaneous injection on days 0, 28 and 56. This is a subgroup of the women in the study that received G-CSF and that self-identified as Black.	Comparator: Placebo (Black Subjects) Intervention: Placebo (as saline) given by subcutaneous injection on days 0, 28 and 56. This is a subgroup of the women in the study that received placebo and that self-identified as Black.
Change From Baseline in White Blood Cell Counts 24 Hours After Administration of G-CSF or Placebo on Day 0	17493 Number of white blood cells per mL Standard Error 822	103 Number of white blood cells per mL Standard Error 144	17394 Number of white blood cells per mL Standard Error 1095	144 Number of white blood cells per mL Standard Error 210	—	—

PRIMARY outcome

Timeframe: Baseline and day 29

Change from baseline in white blood cell counts 24 hours after administration of G-CSF or placebo on day 28. Blood samples were collected 24 hours after adminstration of G-CSF on day 28.

Outcome measures

Measure	Experimental: G-CSF (All Subjects) n=30 Participants Intervention: G-CSF (300 mcg/injection as filgrastim) given by subcutaneous injection on days 0, 28 and 56. This group is all women in the study that received G-CSF.	Comparator: Placebo/Saline (All Subjects) n=30 Participants Intervention: Placebo (as saline) given by subcutaneous injection on days 0, 28 and 56. This group is all women in the study that received placebo.	Experimental: G-CSF (White, NH Subgroup) n=18 Participants Intervention: G-CSF (300 mcg/injection as filgrastim) given by subcutaneous injection on days 0, 28 and 56. This is a subgroup of the women in the study that received G-CSF and that self-identified as white, non-Hispanic.	Comparator: Placebo/Saline (White, NH Subgroup) n=18 Participants Intervention: Placebo (as saline) given by subcutaneous injection on days 0, 28 and 56. This is a subgroup of the women in the study that received placebo and that self-identified as white, non-Hispanic.	Experimental: G-CSF (Black Subjects) Intervention: G-CSF (300 mcg/injection as filgrastim) given by subcutaneous injection on days 0, 28 and 56. This is a subgroup of the women in the study that received G-CSF and that self-identified as Black.	Comparator: Placebo (Black Subjects) Intervention: Placebo (as saline) given by subcutaneous injection on days 0, 28 and 56. This is a subgroup of the women in the study that received placebo and that self-identified as Black.
Change From Baseline in White Blood Cell Counts 24 Hours After Administration of G-CSF or Placebo on Day 28	18273 Number of white blood cells per mL Standard Error 988	13 Number of white blood cells per mL Standard Error 182	18378 Number of white blood cells per mL Standard Error 1147	67 Number of white blood cells per mL Standard Error 230	—	—

PRIMARY outcome

Timeframe: Baseline and day 57

Change from baseline in white blood cell counts 24 hours after administration of G-CSF or placebo on day 56. Blood samples were collected 24 hours after adminstration of G-CSF on day 56.

Outcome measures

Measure	Experimental: G-CSF (All Subjects) n=30 Participants Intervention: G-CSF (300 mcg/injection as filgrastim) given by subcutaneous injection on days 0, 28 and 56. This group is all women in the study that received G-CSF.	Comparator: Placebo/Saline (All Subjects) n=30 Participants Intervention: Placebo (as saline) given by subcutaneous injection on days 0, 28 and 56. This group is all women in the study that received placebo.	Experimental: G-CSF (White, NH Subgroup) n=18 Participants Intervention: G-CSF (300 mcg/injection as filgrastim) given by subcutaneous injection on days 0, 28 and 56. This is a subgroup of the women in the study that received G-CSF and that self-identified as white, non-Hispanic.	Comparator: Placebo/Saline (White, NH Subgroup) n=18 Participants Intervention: Placebo (as saline) given by subcutaneous injection on days 0, 28 and 56. This is a subgroup of the women in the study that received placebo and that self-identified as white, non-Hispanic.	Experimental: G-CSF (Black Subjects) Intervention: G-CSF (300 mcg/injection as filgrastim) given by subcutaneous injection on days 0, 28 and 56. This is a subgroup of the women in the study that received G-CSF and that self-identified as Black.	Comparator: Placebo (Black Subjects) Intervention: Placebo (as saline) given by subcutaneous injection on days 0, 28 and 56. This is a subgroup of the women in the study that received placebo and that self-identified as Black.
Change From Baseline in White Blood Cell Counts 24 Hours After Administration of G-CSF or Placebo on Day 56.	16403 Number of white blood cells per mL Standard Error 1445	37 Number of white blood cells per mL Standard Error 208	15128 Number of white blood cells per mL Standard Error 2112	150 Number of white blood cells per mL Standard Error 340	—	—

PRIMARY outcome

Timeframe: Baseline and day 84

Change from baseline in white blood cell counts on day 84. Blood samples were collected 24 hours after adminstration of G-CSF on day 84.

Outcome measures

Measure	Experimental: G-CSF (All Subjects) n=30 Participants Intervention: G-CSF (300 mcg/injection as filgrastim) given by subcutaneous injection on days 0, 28 and 56. This group is all women in the study that received G-CSF.	Comparator: Placebo/Saline (All Subjects) n=30 Participants Intervention: Placebo (as saline) given by subcutaneous injection on days 0, 28 and 56. This group is all women in the study that received placebo.	Experimental: G-CSF (White, NH Subgroup) n=18 Participants Intervention: G-CSF (300 mcg/injection as filgrastim) given by subcutaneous injection on days 0, 28 and 56. This is a subgroup of the women in the study that received G-CSF and that self-identified as white, non-Hispanic.	Comparator: Placebo/Saline (White, NH Subgroup) n=18 Participants Intervention: Placebo (as saline) given by subcutaneous injection on days 0, 28 and 56. This is a subgroup of the women in the study that received placebo and that self-identified as white, non-Hispanic.	Experimental: G-CSF (Black Subjects) Intervention: G-CSF (300 mcg/injection as filgrastim) given by subcutaneous injection on days 0, 28 and 56. This is a subgroup of the women in the study that received G-CSF and that self-identified as Black.	Comparator: Placebo (Black Subjects) Intervention: Placebo (as saline) given by subcutaneous injection on days 0, 28 and 56. This is a subgroup of the women in the study that received placebo and that self-identified as Black.
Change From Baseline in White Blood Cell Counts on Day 84 (28 Days After Last Administration of G-CSF or Palcebo)	-107 Number of white blood cells per mL Standard Error 311	-420 Number of white blood cells per mL Standard Error 311	-611 Number of white blood cells per mL Standard Error 297	-256 Number of white blood cells per mL Standard Error 265	—	—

PRIMARY outcome

Timeframe: Baseline and week 4

Population: Full analysis set (FAS) (consisted of all randomized participants who took at least 1 dose of study intervention) with available data at specified time point.

The frequency of moderate to severe hot flashes was the number of moderate to severe hot flashes per 24 hours. A daily frequency per week was derived by taking the mean of the data over 7 days. All subjects who were randomized and received at least one dose of study drug are included in this subset. Subjects are analysed according to the randomized treatment group regardless of treatment received.

Outcome measures

Measure	Experimental: G-CSF (All Subjects) n=30 Participants Intervention: G-CSF (300 mcg/injection as filgrastim) given by subcutaneous injection on days 0, 28 and 56. This group is all women in the study that received G-CSF.	Comparator: Placebo/Saline (All Subjects) n=30 Participants Intervention: Placebo (as saline) given by subcutaneous injection on days 0, 28 and 56. This group is all women in the study that received placebo.	Experimental: G-CSF (White, NH Subgroup) n=18 Participants Intervention: G-CSF (300 mcg/injection as filgrastim) given by subcutaneous injection on days 0, 28 and 56. This is a subgroup of the women in the study that received G-CSF and that self-identified as white, non-Hispanic.	Comparator: Placebo/Saline (White, NH Subgroup) n=18 Participants Intervention: Placebo (as saline) given by subcutaneous injection on days 0, 28 and 56. This is a subgroup of the women in the study that received placebo and that self-identified as white, non-Hispanic.	Experimental: G-CSF (Black Subjects) Intervention: G-CSF (300 mcg/injection as filgrastim) given by subcutaneous injection on days 0, 28 and 56. This is a subgroup of the women in the study that received G-CSF and that self-identified as Black.	Comparator: Placebo (Black Subjects) Intervention: Placebo (as saline) given by subcutaneous injection on days 0, 28 and 56. This is a subgroup of the women in the study that received placebo and that self-identified as Black.
Change From Baseline in the Mean Frequency of Moderate and Severe (M+S) Hot Flashes at Week 4	-3.9 Number of hot flashes per day Interval -5.7 to -2.2	-4.0 Number of hot flashes per day Interval -5.7 to -2.3	-4.1 Number of hot flashes per day Interval -6.4 to -1.8	-4.0 Number of hot flashes per day Interval -6.2 to -1.7	—	—

PRIMARY outcome

Timeframe: Baseline and week 12

The frequency of moderate to severe hot flashes was the number of moderate to severe hot flashes per 24 hours. A daily frequency per week was derived by taking the mean of the data over 7 days. All subjects who were randomized and received at least one dose of study drug are included in this subset. Subjects are analysed according to the randomized treatment group regardless of treatment received.

Outcome measures

Measure	Experimental: G-CSF (All Subjects) n=30 Participants Intervention: G-CSF (300 mcg/injection as filgrastim) given by subcutaneous injection on days 0, 28 and 56. This group is all women in the study that received G-CSF.	Comparator: Placebo/Saline (All Subjects) n=30 Participants Intervention: Placebo (as saline) given by subcutaneous injection on days 0, 28 and 56. This group is all women in the study that received placebo.	Experimental: G-CSF (White, NH Subgroup) n=18 Participants Intervention: G-CSF (300 mcg/injection as filgrastim) given by subcutaneous injection on days 0, 28 and 56. This is a subgroup of the women in the study that received G-CSF and that self-identified as white, non-Hispanic.	Comparator: Placebo/Saline (White, NH Subgroup) n=18 Participants Intervention: Placebo (as saline) given by subcutaneous injection on days 0, 28 and 56. This is a subgroup of the women in the study that received placebo and that self-identified as white, non-Hispanic.	Experimental: G-CSF (Black Subjects) Intervention: G-CSF (300 mcg/injection as filgrastim) given by subcutaneous injection on days 0, 28 and 56. This is a subgroup of the women in the study that received G-CSF and that self-identified as Black.	Comparator: Placebo (Black Subjects) Intervention: Placebo (as saline) given by subcutaneous injection on days 0, 28 and 56. This is a subgroup of the women in the study that received placebo and that self-identified as Black.
Change From Baseline in the Mean Frequency of Moderate and Severe (M+S) Hot Flashes at Week 12	-6.4 Number of hot flashes per day Interval -8.2 to -4.7	-6.0 Number of hot flashes per day Interval -7.7 to -4.3	-7.5 Number of hot flashes per day Interval -9.9 to -4.3	-4.5 Number of hot flashes per day Interval -6.8 to -2.2	—	—

PRIMARY outcome

Timeframe: Baseline and week 4

Population: Full analysis set (FAS) (consisted of all randomized participants who took at least 1 dose of study intervention) with available data at specified time point.

CDS (Composite Daily Hot Flash Severity) was calculated as follows:

[(number of mild hot flashes per day x 1) + (number of moderate hot flashes per day x 2) + (number of severe hot flashes per day x 3)]. A daily frequency per week was derived by taking the mean of the data over 7 days. All subjects who were randomized and received at least one dose of study drug are included in this subset. Subjects are analysed according to the randomized treatment group regardless of treatment received.

Outcome measures

Measure	Experimental: G-CSF (All Subjects) n=30 Participants Intervention: G-CSF (300 mcg/injection as filgrastim) given by subcutaneous injection on days 0, 28 and 56. This group is all women in the study that received G-CSF.	Comparator: Placebo/Saline (All Subjects) n=30 Participants Intervention: Placebo (as saline) given by subcutaneous injection on days 0, 28 and 56. This group is all women in the study that received placebo.	Experimental: G-CSF (White, NH Subgroup) n=18 Participants Intervention: G-CSF (300 mcg/injection as filgrastim) given by subcutaneous injection on days 0, 28 and 56. This is a subgroup of the women in the study that received G-CSF and that self-identified as white, non-Hispanic.	Comparator: Placebo/Saline (White, NH Subgroup) n=18 Participants Intervention: Placebo (as saline) given by subcutaneous injection on days 0, 28 and 56. This is a subgroup of the women in the study that received placebo and that self-identified as white, non-Hispanic.	Experimental: G-CSF (Black Subjects) Intervention: G-CSF (300 mcg/injection as filgrastim) given by subcutaneous injection on days 0, 28 and 56. This is a subgroup of the women in the study that received G-CSF and that self-identified as Black.	Comparator: Placebo (Black Subjects) Intervention: Placebo (as saline) given by subcutaneous injection on days 0, 28 and 56. This is a subgroup of the women in the study that received placebo and that self-identified as Black.
Change From Baseline in the Mean Composite Daily Severity of Hot Flashes (CDS) at Week 4	-10 Number of hot flashes per day Interval -15.0 to -5.5	-11 Number of hot flashes per day Interval -15.0 to -6.2	-11 Number of hot flashes per day Interval -17.0 to -4.3	-10 Number of hot flashes per day Interval -17.0 to -4.3	—	—

PRIMARY outcome

Timeframe: Baseline and week 12

Population: Full analysis set (FAS) (consisted of all randomized participants who took at least 1 dose of study intervention) with available data at specified time point.

CDS (Composite Daily Hot Flash Severity) was calculated as follows:

[(number of mild hot flashes per day x 1) + (number of moderate hot flashes per day x 2) + (number of severe hot flashes per day x 3)]. A daily frequency per week was derived by taking the mean of the data over 7 days. All subjects who were randomized and received at least one dose of study drug are included in this subset. Subjects are analysed according to the randomized treatment group regardless of treatment received.

Outcome measures

Measure	Experimental: G-CSF (All Subjects) n=30 Participants Intervention: G-CSF (300 mcg/injection as filgrastim) given by subcutaneous injection on days 0, 28 and 56. This group is all women in the study that received G-CSF.	Comparator: Placebo/Saline (All Subjects) n=30 Participants Intervention: Placebo (as saline) given by subcutaneous injection on days 0, 28 and 56. This group is all women in the study that received placebo.	Experimental: G-CSF (White, NH Subgroup) n=18 Participants Intervention: G-CSF (300 mcg/injection as filgrastim) given by subcutaneous injection on days 0, 28 and 56. This is a subgroup of the women in the study that received G-CSF and that self-identified as white, non-Hispanic.	Comparator: Placebo/Saline (White, NH Subgroup) n=18 Participants Intervention: Placebo (as saline) given by subcutaneous injection on days 0, 28 and 56. This is a subgroup of the women in the study that received placebo and that self-identified as white, non-Hispanic.	Experimental: G-CSF (Black Subjects) Intervention: G-CSF (300 mcg/injection as filgrastim) given by subcutaneous injection on days 0, 28 and 56. This is a subgroup of the women in the study that received G-CSF and that self-identified as Black.	Comparator: Placebo (Black Subjects) Intervention: Placebo (as saline) given by subcutaneous injection on days 0, 28 and 56. This is a subgroup of the women in the study that received placebo and that self-identified as Black.
Change From Baseline in the Mean Composite Daily Severity of Hot Flashes (CDS) at Week 12	-17 Number of hot flashes per day Interval -22.0 to -12.0	-16 Number of hot flashes per day Interval -21.0 to -12.0	-19 Number of hot flashes per day Interval -25.0 to -13.0	-12 Number of hot flashes per day Interval -18.0 to -5.4	—	—

PRIMARY outcome

Timeframe: Baseline and week 4

Population: Full analysis set (FAS) (consisted of all randomized participants who took at least 1 dose of study intervention) with available data at specified time point.

HFSS (Daily Hot Flash Severity Score) was calculated as follows:

[(number of mild hot flashes per day x 1) + (number of moderate hot flashes per day x 2) + (number of severe hot flashes per day x 3)]/daily total hot flashes), where total hot flashes (THF) = number of daily mild, moderate, and severe hot flashes. A daily severity score per week was derived by taking the mean of the data over 7 days. All subjects who were randomized and received at least one dose of study drug are included in this subset. Subjects are analysed according to the randomized treatment group regardless of treatment received.

Outcome measures

Measure	Experimental: G-CSF (All Subjects) n=30 Participants Intervention: G-CSF (300 mcg/injection as filgrastim) given by subcutaneous injection on days 0, 28 and 56. This group is all women in the study that received G-CSF.	Comparator: Placebo/Saline (All Subjects) n=30 Participants Intervention: Placebo (as saline) given by subcutaneous injection on days 0, 28 and 56. This group is all women in the study that received placebo.	Experimental: G-CSF (White, NH Subgroup) n=18 Participants Intervention: G-CSF (300 mcg/injection as filgrastim) given by subcutaneous injection on days 0, 28 and 56. This is a subgroup of the women in the study that received G-CSF and that self-identified as white, non-Hispanic.	Comparator: Placebo/Saline (White, NH Subgroup) n=18 Participants Intervention: Placebo (as saline) given by subcutaneous injection on days 0, 28 and 56. This is a subgroup of the women in the study that received placebo and that self-identified as white, non-Hispanic.	Experimental: G-CSF (Black Subjects) Intervention: G-CSF (300 mcg/injection as filgrastim) given by subcutaneous injection on days 0, 28 and 56. This is a subgroup of the women in the study that received G-CSF and that self-identified as Black.	Comparator: Placebo (Black Subjects) Intervention: Placebo (as saline) given by subcutaneous injection on days 0, 28 and 56. This is a subgroup of the women in the study that received placebo and that self-identified as Black.
Change From Baseline in the Mean Daily Severity of Hot Flashes (HFSS) at Week 4	-0.09 Hot flash severity score Interval -0.31 to 0.13	-0.08 Hot flash severity score Interval -0.31 to 0.13	-0.11 Hot flash severity score Interval -0.47 to 0.24	-0.07 Hot flash severity score Interval -0.42 to 0.28	—	—

PRIMARY outcome

Timeframe: Baseline and week 12

Population: Full analysis set (FAS) (consisted of all randomized participants who took at least 1 dose of study intervention) with available data at specified time point.

HFSS (Daily Hot Flash Severity Score) was calculated as follows:

[(number of mild hot flashes per day x 1) + (number of moderate hot flashes per day x 2) + (number of severe hot flashes per day x 3)]/daily total hot flashes), where total hot flashes (THF) = number of daily mild, moderate, and severe hot flashes. A daily severity score per week was derived by taking the mean of the data over 7 days. All subjects who were randomized and received at least one dose of study drug are included in this subset. Subjects are analysed according to the randomized treatment group regardless of treatment received.

Outcome measures

Measure	Experimental: G-CSF (All Subjects) n=30 Participants Intervention: G-CSF (300 mcg/injection as filgrastim) given by subcutaneous injection on days 0, 28 and 56. This group is all women in the study that received G-CSF.	Comparator: Placebo/Saline (All Subjects) n=30 Participants Intervention: Placebo (as saline) given by subcutaneous injection on days 0, 28 and 56. This group is all women in the study that received placebo.	Experimental: G-CSF (White, NH Subgroup) n=18 Participants Intervention: G-CSF (300 mcg/injection as filgrastim) given by subcutaneous injection on days 0, 28 and 56. This is a subgroup of the women in the study that received G-CSF and that self-identified as white, non-Hispanic.	Comparator: Placebo/Saline (White, NH Subgroup) n=18 Participants Intervention: Placebo (as saline) given by subcutaneous injection on days 0, 28 and 56. This is a subgroup of the women in the study that received placebo and that self-identified as white, non-Hispanic.	Experimental: G-CSF (Black Subjects) Intervention: G-CSF (300 mcg/injection as filgrastim) given by subcutaneous injection on days 0, 28 and 56. This is a subgroup of the women in the study that received G-CSF and that self-identified as Black.	Comparator: Placebo (Black Subjects) Intervention: Placebo (as saline) given by subcutaneous injection on days 0, 28 and 56. This is a subgroup of the women in the study that received placebo and that self-identified as Black.
Change From Baseline in the Mean Daily Severity of Hot Flashes (HFSS) at Week 12	-0.31 Hot flash severity score Interval -0.53 to -0.09	-0.13 Hot flash severity score Interval -0.34 to 0.09	-0.43 Hot flash severity score Interval -0.79 to -0.08	-0.19 Hot flash severity score Interval -0.55 to 0.17	—	—

SECONDARY outcome

Timeframe: Weeks 1-12

Population: Full analysis set (FAS) (consisted of all randomized participants who took at least 1 dose of study intervention) with available data at specified time point. Outcome Measure Data Table \* Measure Type: Least Squares Mean \* Measure ofDispersion

The frequency of moderate to severe hot flashes was the number of moderate to severe hot flashes per 24 hours. A daily frequency per week was derived by taking the mean of the data over 7 days. All subjects who were randomized and received at least one dose of study drug are included in this subset. Subjects are analysed according to the randomized treatment group regardless of treatment received.

Outcome measures

Measure	Experimental: G-CSF (All Subjects) n=30 Participants Intervention: G-CSF (300 mcg/injection as filgrastim) given by subcutaneous injection on days 0, 28 and 56. This group is all women in the study that received G-CSF.	Comparator: Placebo/Saline (All Subjects) n=30 Participants Intervention: Placebo (as saline) given by subcutaneous injection on days 0, 28 and 56. This group is all women in the study that received placebo.	Experimental: G-CSF (White, NH Subgroup) n=18 Participants Intervention: G-CSF (300 mcg/injection as filgrastim) given by subcutaneous injection on days 0, 28 and 56. This is a subgroup of the women in the study that received G-CSF and that self-identified as white, non-Hispanic.	Comparator: Placebo/Saline (White, NH Subgroup) n=18 Participants Intervention: Placebo (as saline) given by subcutaneous injection on days 0, 28 and 56. This is a subgroup of the women in the study that received placebo and that self-identified as white, non-Hispanic.	Experimental: G-CSF (Black Subjects) Intervention: G-CSF (300 mcg/injection as filgrastim) given by subcutaneous injection on days 0, 28 and 56. This is a subgroup of the women in the study that received G-CSF and that self-identified as Black.	Comparator: Placebo (Black Subjects) Intervention: Placebo (as saline) given by subcutaneous injection on days 0, 28 and 56. This is a subgroup of the women in the study that received placebo and that self-identified as Black.
Number of Subjects Achieving >50% Reduction in the Mean Frequency of Moderate and Severe (M+S) Hot Flashes up to Week 12 Week 1	5 Number of subjects	4 Number of subjects	2 Number of subjects	3 Number of subjects	—	—
Number of Subjects Achieving >50% Reduction in the Mean Frequency of Moderate and Severe (M+S) Hot Flashes up to Week 12 Week 2	8 Number of subjects	7 Number of subjects	5 Number of subjects	3 Number of subjects	—	—
Number of Subjects Achieving >50% Reduction in the Mean Frequency of Moderate and Severe (M+S) Hot Flashes up to Week 12 Week 3	7 Number of subjects	9 Number of subjects	5 Number of subjects	4 Number of subjects	—	—
Number of Subjects Achieving >50% Reduction in the Mean Frequency of Moderate and Severe (M+S) Hot Flashes up to Week 12 Week 4	8 Number of subjects	8 Number of subjects	5 Number of subjects	4 Number of subjects	—	—
Number of Subjects Achieving >50% Reduction in the Mean Frequency of Moderate and Severe (M+S) Hot Flashes up to Week 12 Week 5	15 Number of subjects	9 Number of subjects	10 Number of subjects	3 Number of subjects	—	—
Number of Subjects Achieving >50% Reduction in the Mean Frequency of Moderate and Severe (M+S) Hot Flashes up to Week 12 Week 6	15 Number of subjects	12 Number of subjects	10 Number of subjects	5 Number of subjects	—	—
Number of Subjects Achieving >50% Reduction in the Mean Frequency of Moderate and Severe (M+S) Hot Flashes up to Week 12 Week 7	15 Number of subjects	12 Number of subjects	10 Number of subjects	5 Number of subjects	—	—
Number of Subjects Achieving >50% Reduction in the Mean Frequency of Moderate and Severe (M+S) Hot Flashes up to Week 12 Week 8	12 Number of subjects	13 Number of subjects	7 Number of subjects	5 Number of subjects	—	—
Number of Subjects Achieving >50% Reduction in the Mean Frequency of Moderate and Severe (M+S) Hot Flashes up to Week 12 Week 9	15 Number of subjects	10 Number of subjects	9 Number of subjects	4 Number of subjects	—	—
Number of Subjects Achieving >50% Reduction in the Mean Frequency of Moderate and Severe (M+S) Hot Flashes up to Week 12 Week 10	14 Number of subjects	12 Number of subjects	9 Number of subjects	5 Number of subjects	—	—
Number of Subjects Achieving >50% Reduction in the Mean Frequency of Moderate and Severe (M+S) Hot Flashes up to Week 12 Week 11	15 Number of subjects	13 Number of subjects	9 Number of subjects	6 Number of subjects	—	—
Number of Subjects Achieving >50% Reduction in the Mean Frequency of Moderate and Severe (M+S) Hot Flashes up to Week 12 Week 12	15 Number of subjects	14 Number of subjects	9 Number of subjects	6 Number of subjects	—	—

SECONDARY outcome

Timeframe: Weeks 1-12

Population: Full analysis set (FAS) (consisted of all randomized participants who took at least 1 dose of study intervention) with available data at specified time point.

CDS was calculated as follows:

[(number of mild hot flashes per day x 1) + (number of moderate hot flashes per day x 2) + (number of severe hot flashes per day x 3)]. A daily frequency per week was derived by taking the mean of the data over 7 days. All subjects who were randomized and received at least one dose of study drug are included in this subset. Subjects are analysed according to the randomized treatment group regardless of treatment received.

Outcome measures

Measure	Experimental: G-CSF (All Subjects) n=30 Participants Intervention: G-CSF (300 mcg/injection as filgrastim) given by subcutaneous injection on days 0, 28 and 56. This group is all women in the study that received G-CSF.	Comparator: Placebo/Saline (All Subjects) n=30 Participants Intervention: Placebo (as saline) given by subcutaneous injection on days 0, 28 and 56. This group is all women in the study that received placebo.	Experimental: G-CSF (White, NH Subgroup) n=18 Participants Intervention: G-CSF (300 mcg/injection as filgrastim) given by subcutaneous injection on days 0, 28 and 56. This is a subgroup of the women in the study that received G-CSF and that self-identified as white, non-Hispanic.	Comparator: Placebo/Saline (White, NH Subgroup) n=18 Participants Intervention: Placebo (as saline) given by subcutaneous injection on days 0, 28 and 56. This is a subgroup of the women in the study that received placebo and that self-identified as white, non-Hispanic.	Experimental: G-CSF (Black Subjects) Intervention: G-CSF (300 mcg/injection as filgrastim) given by subcutaneous injection on days 0, 28 and 56. This is a subgroup of the women in the study that received G-CSF and that self-identified as Black.	Comparator: Placebo (Black Subjects) Intervention: Placebo (as saline) given by subcutaneous injection on days 0, 28 and 56. This is a subgroup of the women in the study that received placebo and that self-identified as Black.
Number of Subjects Acheiving >50% Reduction in the Mean Composite Daily Hot Flash Severity (CDS) up to Week 12 Week 1	5 Number of subjects	4 Number of subjects	2 Number of subjects	3 Number of subjects	—	—
Number of Subjects Acheiving >50% Reduction in the Mean Composite Daily Hot Flash Severity (CDS) up to Week 12 Week 2	8 Number of subjects	7 Number of subjects	5 Number of subjects	3 Number of subjects	—	—
Number of Subjects Acheiving >50% Reduction in the Mean Composite Daily Hot Flash Severity (CDS) up to Week 12 Week 3	7 Number of subjects	8 Number of subjects	5 Number of subjects	4 Number of subjects	—	—
Number of Subjects Acheiving >50% Reduction in the Mean Composite Daily Hot Flash Severity (CDS) up to Week 12 Week 4	7 Number of subjects	7 Number of subjects	4 Number of subjects	4 Number of subjects	—	—
Number of Subjects Acheiving >50% Reduction in the Mean Composite Daily Hot Flash Severity (CDS) up to Week 12 Week 5	15 Number of subjects	9 Number of subjects	10 Number of subjects	3 Number of subjects	—	—
Number of Subjects Acheiving >50% Reduction in the Mean Composite Daily Hot Flash Severity (CDS) up to Week 12 Week 6	14 Number of subjects	13 Number of subjects	10 Number of subjects	6 Number of subjects	—	—
Number of Subjects Acheiving >50% Reduction in the Mean Composite Daily Hot Flash Severity (CDS) up to Week 12 Week 7	15 Number of subjects	11 Number of subjects	10 Number of subjects	5 Number of subjects	—	—
Number of Subjects Acheiving >50% Reduction in the Mean Composite Daily Hot Flash Severity (CDS) up to Week 12 Week 8	12 Number of subjects	11 Number of subjects	7 Number of subjects	4 Number of subjects	—	—
Number of Subjects Acheiving >50% Reduction in the Mean Composite Daily Hot Flash Severity (CDS) up to Week 12 Week 9	14 Number of subjects	11 Number of subjects	8 Number of subjects	5 Number of subjects	—	—
Number of Subjects Acheiving >50% Reduction in the Mean Composite Daily Hot Flash Severity (CDS) up to Week 12 Week 10	13 Number of subjects	12 Number of subjects	8 Number of subjects	5 Number of subjects	—	—
Number of Subjects Acheiving >50% Reduction in the Mean Composite Daily Hot Flash Severity (CDS) up to Week 12 Week 11	15 Number of subjects	13 Number of subjects	9 Number of subjects	6 Number of subjects	—	—
Number of Subjects Acheiving >50% Reduction in the Mean Composite Daily Hot Flash Severity (CDS) up to Week 12 Week 12	15 Number of subjects	13 Number of subjects	9 Number of subjects	5 Number of subjects	—	—

SECONDARY outcome

Timeframe: Weeks 1-12

Population: Full analysis set (FAS) (consisted of all randomized participants who took at least 1 dose of study intervention) with available data at specified time point.

HFSS was calculated as follows:

[(number of mild hot flashes per day x 1) + (number of moderate hot flashes per day x 2) + (number of severe hot flashes per day x 3)]. HFSS = ((number of daily mild hot flashes x1) + (number of daily moderate hot flashes x2) + (number of severe hot flashes x3))/daily total hot flashes), where total hot flashes (THF) = number of daily mild, moderate, and severe (S) hot flashes. A daily severity score per week was derived by taking the mean of the data over 7 days. All subjects who were randomized and received at least one dose of study drug are included in this subset. Subjects are analysed according to the randomized treatment group regardless of treatment received.

Severity was zero for participants that had no mild or moderate or severe VMS. Higher scores indicates greater severity.

Outcome measures

Measure	Experimental: G-CSF (All Subjects) n=30 Participants Intervention: G-CSF (300 mcg/injection as filgrastim) given by subcutaneous injection on days 0, 28 and 56. This group is all women in the study that received G-CSF.	Comparator: Placebo/Saline (All Subjects) n=30 Participants Intervention: Placebo (as saline) given by subcutaneous injection on days 0, 28 and 56. This group is all women in the study that received placebo.	Experimental: G-CSF (White, NH Subgroup) n=18 Participants Intervention: G-CSF (300 mcg/injection as filgrastim) given by subcutaneous injection on days 0, 28 and 56. This is a subgroup of the women in the study that received G-CSF and that self-identified as white, non-Hispanic.	Comparator: Placebo/Saline (White, NH Subgroup) n=18 Participants Intervention: Placebo (as saline) given by subcutaneous injection on days 0, 28 and 56. This is a subgroup of the women in the study that received placebo and that self-identified as white, non-Hispanic.	Experimental: G-CSF (Black Subjects) Intervention: G-CSF (300 mcg/injection as filgrastim) given by subcutaneous injection on days 0, 28 and 56. This is a subgroup of the women in the study that received G-CSF and that self-identified as Black.	Comparator: Placebo (Black Subjects) Intervention: Placebo (as saline) given by subcutaneous injection on days 0, 28 and 56. This is a subgroup of the women in the study that received placebo and that self-identified as Black.
Number of Subjects Acheiving >0.30 Reduction in the Mean Daily Hot Flash Severity Score (HFSS) up to Week 12 Week 9	9 Number of subjects	5 Number of subjects	7 Number of subjects	3 Number of subjects	—	—
Number of Subjects Acheiving >0.30 Reduction in the Mean Daily Hot Flash Severity Score (HFSS) up to Week 12 Week 10	8 Number of subjects	4 Number of subjects	6 Number of subjects	2 Number of subjects	—	—
Number of Subjects Acheiving >0.30 Reduction in the Mean Daily Hot Flash Severity Score (HFSS) up to Week 12 Week 11	9 Number of subjects	5 Number of subjects	6 Number of subjects	3 Number of subjects	—	—
Number of Subjects Acheiving >0.30 Reduction in the Mean Daily Hot Flash Severity Score (HFSS) up to Week 12 Week 12	7 Number of subjects	6 Number of subjects	6 Number of subjects	3 Number of subjects	—	—
Number of Subjects Acheiving >0.30 Reduction in the Mean Daily Hot Flash Severity Score (HFSS) up to Week 12 Week 1	4 Number of subjects	4 Number of subjects	2 Number of subjects	3 Number of subjects	—	—
Number of Subjects Acheiving >0.30 Reduction in the Mean Daily Hot Flash Severity Score (HFSS) up to Week 12 Week 2	4 Number of subjects	5 Number of subjects	3 Number of subjects	2 Number of subjects	—	—
Number of Subjects Acheiving >0.30 Reduction in the Mean Daily Hot Flash Severity Score (HFSS) up to Week 12 Week 3	7 Number of subjects	6 Number of subjects	4 Number of subjects	4 Number of subjects	—	—
Number of Subjects Acheiving >0.30 Reduction in the Mean Daily Hot Flash Severity Score (HFSS) up to Week 12 Week 4	5 Number of subjects	6 Number of subjects	3 Number of subjects	4 Number of subjects	—	—
Number of Subjects Acheiving >0.30 Reduction in the Mean Daily Hot Flash Severity Score (HFSS) up to Week 12 Week 5	6 Number of subjects	6 Number of subjects	3 Number of subjects	4 Number of subjects	—	—
Number of Subjects Acheiving >0.30 Reduction in the Mean Daily Hot Flash Severity Score (HFSS) up to Week 12 Week 6	8 Number of subjects	5 Number of subjects	6 Number of subjects	3 Number of subjects	—	—
Number of Subjects Acheiving >0.30 Reduction in the Mean Daily Hot Flash Severity Score (HFSS) up to Week 12 Week 7	7 Number of subjects	6 Number of subjects	5 Number of subjects	4 Number of subjects	—	—
Number of Subjects Acheiving >0.30 Reduction in the Mean Daily Hot Flash Severity Score (HFSS) up to Week 12 Week 8	7 Number of subjects	6 Number of subjects	5 Number of subjects	4 Number of subjects	—	—

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: Full analysis set (FAS) (consisted of all randomized participants who took at least 1 dose of study intervention) with available data at specified time point.

The frequency of moderate to severe hot flashes was the number of moderate to severe hot flashes per 24 hours. A daily frequency per week was derived by taking the mean of the data over 7 days. All subjects who were randomized and received at least one dose of study drug are included in this subset. Subjects are analysed according to the randomized treatment group regardless of treatment received.

Outcome measures

Measure	Experimental: G-CSF (All Subjects) n=18 Participants Intervention: G-CSF (300 mcg/injection as filgrastim) given by subcutaneous injection on days 0, 28 and 56. This group is all women in the study that received G-CSF.	Comparator: Placebo/Saline (All Subjects) n=18 Participants Intervention: Placebo (as saline) given by subcutaneous injection on days 0, 28 and 56. This group is all women in the study that received placebo.	Experimental: G-CSF (White, NH Subgroup) n=6 Participants Intervention: G-CSF (300 mcg/injection as filgrastim) given by subcutaneous injection on days 0, 28 and 56. This is a subgroup of the women in the study that received G-CSF and that self-identified as white, non-Hispanic.	Comparator: Placebo/Saline (White, NH Subgroup) n=5 Participants Intervention: Placebo (as saline) given by subcutaneous injection on days 0, 28 and 56. This is a subgroup of the women in the study that received placebo and that self-identified as white, non-Hispanic.	Experimental: G-CSF (Black Subjects) n=6 Participants Intervention: G-CSF (300 mcg/injection as filgrastim) given by subcutaneous injection on days 0, 28 and 56. This is a subgroup of the women in the study that received G-CSF and that self-identified as Black.	Comparator: Placebo (Black Subjects) n=6 Participants Intervention: Placebo (as saline) given by subcutaneous injection on days 0, 28 and 56. This is a subgroup of the women in the study that received placebo and that self-identified as Black.
Percent Change in M+S at 12 Weeks in Demographic Subgroups	-51 Percent change in hot flashes Standard Error 8	-33 Percent change in hot flashes Standard Error 8	-32 Percent change in hot flashes Standard Error 18	-62 Percent change in hot flashes Standard Error 15	-46 Percent change in hot flashes Standard Error 18	-55 Percent change in hot flashes Standard Error 14

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: Full analysis set (FAS) (consisted of all randomized participants who took at least 1 dose of study intervention) with available data at specified time point.

HFSS (Daily Hot Flash Severity Score) was calculated as follows:

[(number of mild hot flashes per day x 1) + (number of moderate hot flashes per day x 2) + (number of severe hot flashes per day x 3)]. HFSS = ((number of daily mild hot flashes x1) + (number of daily moderate hot flashes x2) + (number of severe hot flashes x3))/daily total hot flashes), where total hot flashes (THF) = number of daily mild, moderate, and severe (S) hot flashes. A daily severity score per week was derived by taking the mean of the data over 7 days. All subjects who were randomized and received at least one dose of study drug are included in this subset. Subjects are analysed according to the randomized treatment group regardless of treatment received

Outcome measures

Measure	Experimental: G-CSF (All Subjects) n=19 Participants Intervention: G-CSF (300 mcg/injection as filgrastim) given by subcutaneous injection on days 0, 28 and 56. This group is all women in the study that received G-CSF.	Comparator: Placebo/Saline (All Subjects) n=21 Participants Intervention: Placebo (as saline) given by subcutaneous injection on days 0, 28 and 56. This group is all women in the study that received placebo.	Experimental: G-CSF (White, NH Subgroup) n=5 Participants Intervention: G-CSF (300 mcg/injection as filgrastim) given by subcutaneous injection on days 0, 28 and 56. This is a subgroup of the women in the study that received G-CSF and that self-identified as white, non-Hispanic.	Comparator: Placebo/Saline (White, NH Subgroup) n=5 Participants Intervention: Placebo (as saline) given by subcutaneous injection on days 0, 28 and 56. This is a subgroup of the women in the study that received placebo and that self-identified as white, non-Hispanic.	Experimental: G-CSF (Black Subjects) n=6 Participants Intervention: G-CSF (300 mcg/injection as filgrastim) given by subcutaneous injection on days 0, 28 and 56. This is a subgroup of the women in the study that received G-CSF and that self-identified as Black.	Comparator: Placebo (Black Subjects) n=6 Participants Intervention: Placebo (as saline) given by subcutaneous injection on days 0, 28 and 56. This is a subgroup of the women in the study that received placebo and that self-identified as Black.
Net Change in HFSS at 12 Weeks in Demographic Subgroups	-0.29 Hot flash severity score Standard Error 0.16	-0.09 Hot flash severity score Standard Error 0.11	0.13 Hot flash severity score Standard Error 0.14	-0.13 Hot flash severity score Standard Error 0.2	-0.14 Hot flash severity score Standard Error 0.1	0.13 Hot flash severity score Standard Error 0.21

SECONDARY outcome

Timeframe: Baseline and week 12

Population: Full analysis set (FAS) (consisted of all randomized participants who took at least 1 dose of study intervention) with available data at specified time point.

Menopause-specific Quality of Life (MENQOL) Questionnaire. The MENQOL is self-administered and consists of a total of 29 items in a Likert-scale format. Each item assesses the impact of one of four domains of menopausal symptoms, as experienced over the last month: vasomotor (items 1-3), psychosocial (items 4-10), physical (items 11-26), and sexual (items 27-29). MENQOL VMS refers to the answers to items 1-3 where 6 = most bothersome and 0 = least bothersome). (Maximum bothersomeness = 18; No bothersomeness = 0)

Outcome measures

Measure	Experimental: G-CSF (All Subjects) n=30 Participants Intervention: G-CSF (300 mcg/injection as filgrastim) given by subcutaneous injection on days 0, 28 and 56. This group is all women in the study that received G-CSF.	Comparator: Placebo/Saline (All Subjects) n=29 Participants Intervention: Placebo (as saline) given by subcutaneous injection on days 0, 28 and 56. This group is all women in the study that received placebo.	Experimental: G-CSF (White, NH Subgroup) n=18 Participants Intervention: G-CSF (300 mcg/injection as filgrastim) given by subcutaneous injection on days 0, 28 and 56. This is a subgroup of the women in the study that received G-CSF and that self-identified as white, non-Hispanic.	Comparator: Placebo/Saline (White, NH Subgroup) n=18 Participants Intervention: Placebo (as saline) given by subcutaneous injection on days 0, 28 and 56. This is a subgroup of the women in the study that received placebo and that self-identified as white, non-Hispanic.	Experimental: G-CSF (Black Subjects) Intervention: G-CSF (300 mcg/injection as filgrastim) given by subcutaneous injection on days 0, 28 and 56. This is a subgroup of the women in the study that received G-CSF and that self-identified as Black.	Comparator: Placebo (Black Subjects) Intervention: Placebo (as saline) given by subcutaneous injection on days 0, 28 and 56. This is a subgroup of the women in the study that received placebo and that self-identified as Black.
Net Change in MENQOL VMS Score	-5.7 Score on a scale Standard Error 1.0	-4.8 Score on a scale Standard Error 1.2	-6.0 Score on a scale Standard Error 1.2	-3.6 Score on a scale Standard Error 1.5	—	—

SECONDARY outcome

Timeframe: Baseline and week 12

Population: Full analysis set (FAS) (consisted of all randomized participants who took at least 1 dose of study intervention) with available data at specified time point.

The Hot Flash Related Daily Interference Scale (HFRDIS) measures (as a score of 0 to 10) the effect of hot flashes on overall quality of life and on nine specific activities: work, social activities, leisure activities, sleep, mood, concentration, relations with others, sexuality, and enjoyment of life. The 10 answers are added up to get a total score. HFRDIS Score (Maximum Bothersomness = 100; No Bothersomeness = 0). The higher the score, the more bothersome the symptoms.

Outcome measures

Measure	Experimental: G-CSF (All Subjects) n=28 Participants Intervention: G-CSF (300 mcg/injection as filgrastim) given by subcutaneous injection on days 0, 28 and 56. This group is all women in the study that received G-CSF.	Comparator: Placebo/Saline (All Subjects) n=28 Participants Intervention: Placebo (as saline) given by subcutaneous injection on days 0, 28 and 56. This group is all women in the study that received placebo.	Experimental: G-CSF (White, NH Subgroup) n=17 Participants Intervention: G-CSF (300 mcg/injection as filgrastim) given by subcutaneous injection on days 0, 28 and 56. This is a subgroup of the women in the study that received G-CSF and that self-identified as white, non-Hispanic.	Comparator: Placebo/Saline (White, NH Subgroup) n=18 Participants Intervention: Placebo (as saline) given by subcutaneous injection on days 0, 28 and 56. This is a subgroup of the women in the study that received placebo and that self-identified as white, non-Hispanic.	Experimental: G-CSF (Black Subjects) Intervention: G-CSF (300 mcg/injection as filgrastim) given by subcutaneous injection on days 0, 28 and 56. This is a subgroup of the women in the study that received G-CSF and that self-identified as Black.	Comparator: Placebo (Black Subjects) Intervention: Placebo (as saline) given by subcutaneous injection on days 0, 28 and 56. This is a subgroup of the women in the study that received placebo and that self-identified as Black.
Net Change in HFRDIS Score	-22.5 score on a scale Standard Error 6.1	-26.7 score on a scale Standard Error 4.5	-21.2 score on a scale Standard Error 7.7	-25.1 score on a scale Standard Error 5.0	—	—

SECONDARY outcome

Timeframe: Baseline and week 12

Population: Full analysis set (FAS) (consisted of all randomized participants who took at least 1 dose of study intervention) with available data at specified time point.

The Insomnia Severity Index has seven questions. For each question, most bothersome = 4; not bothersome = 0. The seven answers are added up to get a total score. Total score categories: 0-7 = No clinically significant insomnia; 8-14 = Subthreshold insomnia; 15-21 = Clinical insomnia (moderate severity); 22-28 = Clinical insomnia (severe)

Outcome measures

Measure	Experimental: G-CSF (All Subjects) n=29 Participants Intervention: G-CSF (300 mcg/injection as filgrastim) given by subcutaneous injection on days 0, 28 and 56. This group is all women in the study that received G-CSF.	Comparator: Placebo/Saline (All Subjects) n=29 Participants Intervention: Placebo (as saline) given by subcutaneous injection on days 0, 28 and 56. This group is all women in the study that received placebo.	Experimental: G-CSF (White, NH Subgroup) n=17 Participants Intervention: G-CSF (300 mcg/injection as filgrastim) given by subcutaneous injection on days 0, 28 and 56. This is a subgroup of the women in the study that received G-CSF and that self-identified as white, non-Hispanic.	Comparator: Placebo/Saline (White, NH Subgroup) n=18 Participants Intervention: Placebo (as saline) given by subcutaneous injection on days 0, 28 and 56. This is a subgroup of the women in the study that received placebo and that self-identified as white, non-Hispanic.	Experimental: G-CSF (Black Subjects) Intervention: G-CSF (300 mcg/injection as filgrastim) given by subcutaneous injection on days 0, 28 and 56. This is a subgroup of the women in the study that received G-CSF and that self-identified as Black.	Comparator: Placebo (Black Subjects) Intervention: Placebo (as saline) given by subcutaneous injection on days 0, 28 and 56. This is a subgroup of the women in the study that received placebo and that self-identified as Black.
Net Change in ISI Score at 12 Weeks	-5.5 score on a scale Standard Error 1.5	-6.0 score on a scale Standard Error 1.1	-4.6 score on a scale Standard Error 2.0	-3.8 score on a scale Standard Error 1.4	—	—

SECONDARY outcome

Timeframe: Baseline and week 12

Population: Full analysis set (FAS) (consisted of all randomized participants who took at least 1 dose of study intervention) with available data at specified time point.

Fatigue Severity Scale (FSS) of Sleep Disorders. The Fatigue Severity Scale (FSS) is a method of evaluating the impact of fatigue. The FSS is a short questionnaire (10 questions) that requires the subject to rate level of fatigue. The FSS questionnaire contains nine statements that rate the severity of fatigue symptoms. Each statement is read and the corresponding number from 1 to 7 is circled. A low value (e.g., 1) indicates strong disagreement with the statement, whereas a high value (e.g., 7) indicates strong agreement. (Maximum bother = 70; No bother = 0)

Outcome measures

Measure	Experimental: G-CSF (All Subjects) n=28 Participants Intervention: G-CSF (300 mcg/injection as filgrastim) given by subcutaneous injection on days 0, 28 and 56. This group is all women in the study that received G-CSF.	Comparator: Placebo/Saline (All Subjects) n=29 Participants Intervention: Placebo (as saline) given by subcutaneous injection on days 0, 28 and 56. This group is all women in the study that received placebo.	Experimental: G-CSF (White, NH Subgroup) n=17 Participants Intervention: G-CSF (300 mcg/injection as filgrastim) given by subcutaneous injection on days 0, 28 and 56. This is a subgroup of the women in the study that received G-CSF and that self-identified as white, non-Hispanic.	Comparator: Placebo/Saline (White, NH Subgroup) n=18 Participants Intervention: Placebo (as saline) given by subcutaneous injection on days 0, 28 and 56. This is a subgroup of the women in the study that received placebo and that self-identified as white, non-Hispanic.	Experimental: G-CSF (Black Subjects) Intervention: G-CSF (300 mcg/injection as filgrastim) given by subcutaneous injection on days 0, 28 and 56. This is a subgroup of the women in the study that received G-CSF and that self-identified as Black.	Comparator: Placebo (Black Subjects) Intervention: Placebo (as saline) given by subcutaneous injection on days 0, 28 and 56. This is a subgroup of the women in the study that received placebo and that self-identified as Black.
Net Change in FSS Score at 12 Weeks	-5.3 score on a scale Standard Error 3.0	-6.2 score on a scale Standard Error 2.2	-6.9 score on a scale Standard Error 3.7	-7.0 score on a scale Standard Error 2.8	—	—

Adverse Events

Experimental: G-CSF (All Subjects)

Serious events: 0 serious events

Other events: 24 other events

Deaths: 0 deaths

Comparator: Placebo/Saline (All Subjects)

Serious events: 0 serious events

Other events: 20 other events

Deaths: 0 deaths

Experimental: G-CSF (White, NH Subgroup)

Serious events: 0 serious events

Other events: 12 other events

Deaths: 0 deaths

Comparator: Placebo/Saline (White, NH Subgroup)

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Experimental: G-CSF (All Subjects) n=30 participants at risk Intervention: G-CSF (300 mcg/injection as filgrastim) given by subcutaneous injection on days 0, 28 and 56. This group is all women in the study that received G-CSF.	Comparator: Placebo/Saline (All Subjects) n=30 participants at risk Intervention: Placebo (as saline) given by subcutaneous injection on days 0, 28 and 56. This group is all women in the study that received placebo.	Experimental: G-CSF (White, NH Subgroup) n=18 participants at risk Intervention: G-CSF (300 mcg/injection as filgrastim) given by subcutaneous injection on days 0, 28 and 56. This is a subgroup of the women in the study that received G-CSF and that self-identified as white, non-Hispanic.	Comparator: Placebo/Saline (White, NH Subgroup) n=18 participants at risk Intervention: Placebo (as saline) given by subcutaneous injection on days 0, 28 and 56. This is a subgroup of the women in the study that received placebo and that self-identified as white, non-Hispanic.
General disorders General	33.3% 10/30 • Number of events 10 • From first dose date up to 30 days after last dose (up to 16 weeks)	46.7% 14/30 • Number of events 14 • From first dose date up to 30 days after last dose (up to 16 weeks)	33.3% 6/18 • Number of events 6 • From first dose date up to 30 days after last dose (up to 16 weeks)	38.9% 7/18 • Number of events 7 • From first dose date up to 30 days after last dose (up to 16 weeks)
Infections and infestations Cold/Sinus	26.7% 8/30 • Number of events 8 • From first dose date up to 30 days after last dose (up to 16 weeks)	23.3% 7/30 • Number of events 7 • From first dose date up to 30 days after last dose (up to 16 weeks)	22.2% 4/18 • Number of events 4 • From first dose date up to 30 days after last dose (up to 16 weeks)	27.8% 5/18 • Number of events 5 • From first dose date up to 30 days after last dose (up to 16 weeks)
Gastrointestinal disorders Nausea/GI Disorders	13.3% 4/30 • Number of events 4 • From first dose date up to 30 days after last dose (up to 16 weeks)	13.3% 4/30 • Number of events 4 • From first dose date up to 30 days after last dose (up to 16 weeks)	16.7% 3/18 • Number of events 3 • From first dose date up to 30 days after last dose (up to 16 weeks)	0.00% 0/18 • From first dose date up to 30 days after last dose (up to 16 weeks)
General disorders Headache	20.0% 6/30 • Number of events 6 • From first dose date up to 30 days after last dose (up to 16 weeks)	3.3% 1/30 • Number of events 1 • From first dose date up to 30 days after last dose (up to 16 weeks)	22.2% 4/18 • Number of events 4 • From first dose date up to 30 days after last dose (up to 16 weeks)	5.6% 1/18 • Number of events 1 • From first dose date up to 30 days after last dose (up to 16 weeks)
General disorders Fatigue	20.0% 6/30 • Number of events 6 • From first dose date up to 30 days after last dose (up to 16 weeks)	10.0% 3/30 • Number of events 3 • From first dose date up to 30 days after last dose (up to 16 weeks)	11.1% 2/18 • Number of events 2 • From first dose date up to 30 days after last dose (up to 16 weeks)	11.1% 2/18 • Number of events 2 • From first dose date up to 30 days after last dose (up to 16 weeks)
Musculoskeletal and connective tissue disorders Musculo/Skeletal (not incl. bone pain)	30.0% 9/30 • Number of events 9 • From first dose date up to 30 days after last dose (up to 16 weeks)	20.0% 6/30 • Number of events 6 • From first dose date up to 30 days after last dose (up to 16 weeks)	27.8% 5/18 • Number of events 5 • From first dose date up to 30 days after last dose (up to 16 weeks)	11.1% 2/18 • Number of events 2 • From first dose date up to 30 days after last dose (up to 16 weeks)
Musculoskeletal and connective tissue disorders Bone Pain	6.7% 2/30 • Number of events 2 • From first dose date up to 30 days after last dose (up to 16 weeks)	0.00% 0/30 • From first dose date up to 30 days after last dose (up to 16 weeks)	11.1% 2/18 • Number of events 2 • From first dose date up to 30 days after last dose (up to 16 weeks)	0.00% 0/18 • From first dose date up to 30 days after last dose (up to 16 weeks)

Additional Information

Debra Duke

MenoGeniX

Phone: 303-995-7979

Email: debra.duke@menogenix.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place