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

Study to Assess the Safety and Effect of Repeated Administration of Granulocyte Colony-Stimulating Factor (G-CSF; Filgrastim) on Hot Flashes and Other Vasomotor Symptoms of Menopause in Postmenopausal Women

The purpose of this study is to assess the efficacy and safety of repeated administration of G-CSF for the treatment of hot flashes and vasomotor symptoms in women with naturally-occurring or surgically induced menopause. G-CSF will be administered three times at 28 day intervals to postmenopausal women, ages 40 to 65, suffering at least 49 moderate to severe hot flashes per week.

This is a 12-week, multicenter, randomized, double-blind, placebo-controlled study. Eligible subjects will be stratified by natural or surgical menopause and randomized (1:1) to receive 3 single injections, 28-days apart, of either G-CSF or placebo.

This study will consist of a 14-21 day screening period. Subjects enrolled will be given three single 1.0 mL subcutaneous (SC) injections (repeated 28-days apart), in the outer area of either upper arm, of either G-CSF or placebo (sterile physiological saline) at Baseline, Day 28 and Day 56. Subjects will be followed for 12 weeks and will complete hot flash diary entries every day for the duration of treatment. Safety will be assessed by adverse events, clinical laboratory tests (clinical chemistry and complete blood count with differential) and vital signs. A follow-up phone call will occur 60 days after the last dose of study drug.

Eligibility will be assessed via physical examination, clinical laboratory testing, vital signs.

Subjects will receive a diary in which to record daily hot flashes symptoms during the duration of the screening period. Subjects must have at least 14 days of hot flash recordings to participate in the study. The diary will be reviewed by study site staff on Baseline (Day 0) to confirm study eligibility.

During the treatment period, subjects will return to the study site at Days 1, 21, 28, 29, 49, 56, 57, and 84 for assessments.

The follow-up phone call will occur approximately 60 days following the last dose of study drug.

Inclusion Criteria:

• Female, aged 49 to 65 for natural postmenopausal or aged 40 to 65 for surgical postmenopausal
• Body Mass Index (BMI) 18 to 35
• At least 7 moderate to severe hot flashes per day on average (or at least 49 moderate to severe hot flashes per week)
• Naturally postmenopausal or surgically postmenopausal women:
• Naturally postmenopausal is defined as having no menstrual periods for at least 12 months prior to study entry; with a biochemical criteria of menopause (FSH >40 IU/L)
• Surgically postmenopausal is defined as at least 3 months after documented bilateral salpingo oophorectomy
• Normal pelvic exam and pap smear within 2 years
• Signed informed consent

Exclusion Criteria:

• Radiation or chemotherapy-induced (including gonadotropin-releasing hormone (GnRH) agonist) menopause
• Prior chemotherapy or radiation therapy for cancer
• Prior diagnosis of hematologic malignancy
• Type 1 diabetics or Type 2 diabetics with HbA1c > 7.0%
• Use of hormone replacement therapy or oral contraceptives within the past three months
• Use of alternative or complementary medicines or herbs for menopausal symptoms within 30 days (refer to Appendix 2)
• Use of any selective serotonin reuptake inhibitor (SSRI) or serotonin norepinephrine reuptake inhibitor (SNRI) within 30 days
• Use of selective estrogen receptor modulators within 30 days
• Use of gabapentin within 30 days
• Use of clonidine within 30 days
• Use of megestrol acetate (Megace) within 30 days
• Use of, prescription corticosteroids within 30 days (nasal or other inhaled corticosteroids and over-the-counter (OTC) hydrocortisone ointment or cream excepted)
• Current use of lithium therapy (related to possible risk of G-CSF)
• History (in the past year) or presence of drug or alcohol use which, in the opinion of the Investigator, might compromise the study or confound the study results
• History of use of any anti-inflammatory biologics
• History of or current splenomegaly (related to possible risk of G-CSF)
• History of sickle cell disease (related to possible risk of G-CSF)
• High risk for medical complications that might affect the subject's ability to complete the trial without a serious co-morbid event, based on medical history, physical examination and laboratory screening evaluation in the opinion of the Investigator
• Presence of an acute or chronic condition (such as a hematological, rheumatologic auto-immune disease, chronic inflammatory disorder or osteoporosis) based on history, clinical, or laboratory evaluation, which, in the opinion of the Investigator, might compromise the study, confound the study results or place the subject at risk
• Follicle stimulating hormone (FSH) < 40 IU/L or below the reference range for menopause for the local laboratory used for screening
• Thyroid stimulating hormone (TSH) outside normal limits at study entry
• Absolute neutrophil count (ANC) ≤ 1.0 x 109/L
• Total white blood cell count (WBC) ≤ 3.0 x 109/L
• Platelet count (PLT) ≤ 150 x 109/L
• Hemoglobin count (HGB) consistent with anemia
• Positive urine pregnancy test at Baseline visit
• Allergy or hypersensitivity to E coli-derived proteins' G-CSF' or any component of the product
• Mentally or legally incapacitated such that informed consent cannot be obtained
• Inability or unwillingness to complete daily hot flash diary and study questionnaires appropriately
• Participation in another investigational trial within the past 30 days