A Parallel-group, Double-blind, Randomized, Placebo-controlled, Active Comparator, Multicenter Study to Evaluate the Efficacy, Safety, Tolerability and Pharmacokinetics of Two Doses of GSK232802 Administered Orally as Monotherapy for 12 Weeks in Healthy Postmenopausal Women With Moderate to Extremely Severe Vasomotor Symptoms
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 356
- 试验地点
- 1
- 主要终点
- Change From Baseline in Thyroid Stimulating Hormone (TSH) at Week 12
研究概览
简要总结
The purpose of this study is to determine whether GSK232802 is safe and effective in reducing the frequency and severity of hot flashes associated with menopause.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 40 Years 至 65 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •A subject will be eligible for inclusion in this study only if all of the following criteria apply:
- •Postmenopausal women aged 40 to 65 years old; postmenopausal defined as:
- •i.Amenorrheic for at least 12 consecutive months* OR ii.At least 6 weeks post-surgical bilateral oophorectomy† with or without hysterectomy.
- •*Note: Although duration of amenorrhea is initially determined by subject history at the time of the screening visit (Visit 1), menopausal status must be confirmed by demonstrating levels of follicle stimulating hormone (FSH) >40 mIU/mL (SI: >40 IU/L) and estradiol <35pg/mL (SI: <128pmol/L) at entry. Screening reports provided by the Central Laboratory must be carefully reviewed to determine menopause eligibility prior to conducting Visit 2 assessments. In the event a subject's menopause status has been clearly established (for example, the subject indicates she has been amenorrheic for 10 years), but FSH and/or estradiol levels are not consistent with a post-menopausal condition, determination of subject eligibility should be discussed with the study medical monitor.
- •†For women who are surgically menopausal, a copy of the pathology report or a statement on letterhead from the subject's physician documenting both ovaries have been removed or biochemical evidence of post-menopausal status as noted above is required prior to conducting Visit 2 assessments.
- •A minimum average frequency of seven daily moderate to extremely severe hot flashes or episodes of night sweats sufficient to cause the patient to seek treatment (these episodes must be documented during the baseline period and the subject must have recorded frequency and severity of symptoms for a minimum of eight days in order to be eligible for randomization). This average frequency will be calculated by summing the number of moderate, severe, and extremely severe VMS events during the baseline period and dividing by the total number of non-missing days during this period, with details related to the definition of non-missing days described in Section 6.3.
- •BMI within the range 19 to 35 kg/m2, inclusive.
- •Subject has provided signed and dated written informed consent before admission to the study.
- •Subject is able to understand and comply with the protocol requirements, instructions, and protocol-stated restrictions.
排除标准
- •A subject will not be eligible for inclusion in this study if any of the following criteria apply:
- •Investigator considers subject unfit for the study as a result of medical history, physical examination, or screening tests.
- •Use of prescription or non-prescription drugs including:
- •i.Hormone therapy (estrogen or estrogen/progestin combination or related products) within the following time period prior to conduct of Visit 1 assessments:
- •4 weeks for prior vaginal hormonal products (rings, creams, gels) or transdermal estrogen or estrogen/progestin products.
- •4 weeks for oral estradiol (e.g., micronized estradiol) or SERM products (e.g., raloxifene).
- •8 weeks for prior oral conjugated (equine or synthetic) estrogen or estrogen/progestin products or for prior intrauterine progestin therapy.
- •3 months for prior progestin implants or injectable estrogen.
- •6 months for prior estrogen pellet therapy or injectable progestin. ii.Use of putative therapies for VMS relief (e.g., selective serotonin reuptake inhibitors [SSRIs], serotonin-norepinephrine reuptake inhibitors [SNRIs], clonidine, gabapentin, tibolone, methyldopa, and the phytoestrogens black cohosh and red clover) within the past 30 days or 5 half-lives (whichever is longer) prior to conduct of Visit 1 assessments (note: half-lives will be provided in the SPM). Use of non-medication treatments for VMS, such as acupuncture and biofeedback, and other complementary or alternative therapies for VMS relief (with the exception of black cohosh and red clover which require a specified washout previously noted) must be discontinued at Visit
- •iii.Use of weight loss drugs (e.g., phentermine, sibutramine, orlistat, rimonabant) within 3 months of the first dose of investigational product. Other complementary or alternative therapies for weight reduction must be discontinued at Visit
- •See SPM for listing.
- •iv.Use of pravastatin [Pravachol/Lipostat], rosuvastatin [Crestor], or pitavastatin [Livalo] within the past 30 days or 5 half-lives (whichever is longer) of the first dose of investigational product (note: half-lives will be provided in the SPM. Uses of other statins, for example simvastatin [Zocor], atorvastatin [Lipitor], fluvastatin [Lescol], lovastatin [Mevacor] is allowed).
- •v.Use of bupropion, orphenadrine [Norflex], cyclophosphamide, efavirenz, ifosfamide, or methadone (because of the potential for GSK232802 to inhibit CYP2B6), or use of paclitaxel, torsemide, amodiaquine, repaglinide, rosiglitazone, or pioglitazone (because of the potential for GSK232802 to inhibit CYP2C8) within the past 30 days or 5 half-lives (whichever is longer) of the first dose of investigational product (note: half-lives will be provided in the SPM).
- •Please note: Regardless of the reason for prescribing, use of the medications and therapies defined within Exclusion 2 above is prohibited. Concurrent administration of anti-depressants, anti-hypertensives, lipid-lowering therapies, etc. not specifically excluded above is allowed. See SPM for detailed listings and relevant half lives.
- •Use of investigational drug within the past 30 days or 5 half-lives (whichever is longer) before the first dose of investigational product.
- •Uterine disease or medical condition including:
- •Bi-layer endometrial thickness greater than 5mm as determined by TVUS, or for women with a non-informative TVUS, a single layer thickness of greater than 3 mm determined by SIS; presence of fibroids that obscure evaluation of endometrium by TVUS;
- •History of uterine cancer; evidence of endometrial hyperplasia or cancer as assessed by a screening endometrial biopsy. (Note: if a subject has insufficient tissue for diagnosis at screening, but bi-layer endometrial thickness by TVUS is ≤5mm or single wall thickness by SIS is ≤3mm, she may still be eligible for study entry if she meets the remaining inclusion/exclusion criteria);
- •Evidence of an endometrial polyp with hyperplastic or malignant epithelium;
- •Unexplained or unusual endometrial bleeding; or uterine surgery (other than hysterectomy*) within the past 6 months; *Note: hysterectomy must have been conducted at least 6 weeks prior to screening Visit
- •See also Inclusion criterion
- •Abnormal cervical Pap smear with evidence of cervical dysplasia greater than or equal to low grade squamous intraepithelial lesion (LSIL) or with a diagnosis of atypical squamous cells of undetermined significance (ASCUS) that is HPV High Risk positive, or glandular lesions including but not limited to atypical glandular cells of undetermined significance (AGUS), adenocarcinoma in situ (AIS) or malignancy
- •History of breast or ovarian cancer. Any clinically significant findings on mammography suspicious of breast malignancy that would require additional clinical testing to rule out breast cancer (note: simple cysts confirmed by ultrasound are allowed).
- •Note: A screening mammogram is required unless the subject has had a mammogram performed within the last 12 months. If local mammography or medical management guidelines restrict the frequency with which mammograms can be performed, or impose age restrictions on the use of mammography, such that a subject may be unable to undergo the study-required screening mammogram, then these subjects must not be enrolled in the study. See Section 6.2.
- •Cardiovascular conditions including: i. Systolic blood pressure (BP) outside the range 80 to 150 mmHg, diastolic BP outside the range 50 to 90 mmHg, and/or heart rate outside the range 40 to 100 bpm. Subjects with mild to moderate hypertension who are controlled on a stable antihypertension regimen may be enrolled if they meet the inclusion/exclusion criteria.
- •ii. Symptomatic or asymptomatic arrhythmia of any clinical significance. iii. Any clinically significant abnormality identified on the screening 12-lead ECG. Subjects with QTc prolongation (QTc interval >450msec) will be excluded.
- •iv. Has a documented history (within the last year) of myocardial infarction, angina, or has undergone coronary artery bypass surgery and/or percutaneous transluminal coronary angioplasty (PTCA).
- •v. History of venous or arterial thromboembolic disease (e.g., deep vein thrombosis, pulmonary embolism, stroke), history of known coagulopathy or abnormal coagulation factors; increased thrombotic risk as evidenced by positive APC resistance (APCR) evaluated at screening.
- •Has a documented history of hepatobiliary disease or hepatic enzyme elevation including any one of the following: i.ALT or direct (conjugated) bilirubin values 1.5-fold higher than the ULN at screening.
- •ii.Fasting triglycerides >400mg/dL (SI: >4.52mmol/L) at screening. If a subject is receiving a lipid-lowering therapy, then she must be on a stable dose for at least 1 month before screening.
- •Has an abnormal thyroid function test assessed by TSH at screening (TSH <0.1uU/mL or >10uU/mL [SI: <0.1mU/L or >10mU/L] ).
- •Note: If the TSH is mildly out of range at screening (TSH < 15U/mL), the subject may have her dose adjusted (if already on exogenous therapy) or have therapy initiated as deemed appropriate by the subject's physician, followed by a 3-4 week period to allow adequate equilibration. The TSH may then be re-assayed for eligibility purposes after this stabilization period has been completed. The subject should not progress through subsequent V2 assessments until re-assay demonstrates the TSH is within acceptable protocol-defined limits. Subjects with suppressed levels of TSH, <0.1U/mL, may have dose adjustment if free T4 is in normal range, and they are on exogenous thyroxine therapy.
- •Has either a previous disease or current medical condition, which as judged by the investigator, may affect the interpretation of efficacy or safety data or which otherwise contraindicates participation in a clinical study with a new chemical entity. These diseases include, but are not limited to, cardiovascular disease, malignancy*, complex ovarian pathology, hepatic disease, renal disease, hematological disease, neurological disease, or endocrine disease. A subject with diabetes may be included if her diabetes is well controlled (i.e., HbA1c level is less than 8% at screening).
- •*Note: Any history of malignancy within the past 5 years is exclusionary with the exception of basal cell (excluded if within the prior 2 years) or squamous cell (excluded if within the prior one year) carcinoma of the skin. Subjects with a prior malignancy who have had no evidence of disease for at least the past 5 years are eligible. Note that this timeframe does not apply to uterine, breast, and ovarian cancers which are defined in Exclusions 4 and 5 above.
- •History of alcohol or substance abuse or dependence in the 12 months before screening as determined by the investigator.
- •Positive results for hepatitis B surface antigen or hepatitis C antibodies as evaluated at screening Visit
- •Known history of HIV.
- •Donation of blood in excess of 500mL within a 56-day period before screening.
- •History or presence of allergy to the investigational product or drugs of this class (e.g., raloxifene), or history of drug or other allergy that, in the opinion of the physician responsible, contraindicates their participation.
研究组 & 干预措施
GSK232802
GSK232802
干预措施: GSK232802 (Drug)
PREMARIN
PREMARIN
干预措施: PREMARIN (Drug)
结局指标
主要结局
Change From Baseline in Thyroid Stimulating Hormone (TSH) at Week 12
时间窗: Baseline (Week 0) and Week 12
Serum hormone markers included TSH. Baseline was Week 0. Change from Baseline was calculated by subtracting Baseline values from post-Baseline values. Mean change from Baseline in TSH at Week 12 are presented.
Mean Change in Severity of VMS From Baseline at Week 12
时间窗: Baseline (Week 0) and Week 12
Individual VMS (hot flash or night sweats) events were recorded by participants in an eDiary using global change questions. VMS severity was as follows: mild=score of 1 (brief wave of heat with minimal discomfort, usually without perspiration; able to continue activity \[or sleep\]), moderate=score of 2(heat with some discomfort, usually with perspiration; minimal interruption of activity \[or sleep\]), severe=score of 3(intense heat with considerable discomfort, usually with heavy sweating; may be unable to resume activity \[or sleep\] right away) and extremely severe=score of 4 (unbearable heat with intense discomfort, usually with pouring sweat; may be unable to resume activity \[or sleep\] for quite a while). Total score ranged from 1 to 4 and is the sum of severity scores divided by total number of VMS events. Higher score indicates worst condition. Baseline was Week 0. Change from Baseline was calculated by subtracting Baseline values from post-Baseline values.
Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) and Number of Participants With Mild, Moderate and Severe AE
时间窗: Up to 21 weeks
AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. For marketed medicinal products, this also includes failure to produce expected benefits (i.e., lack of efficacy), abuse or misuse. SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect or is medically significant. The severity of AEs was assessed by the investigator as mild, moderate or severe.
Occurrence of Withdrawal Bleeding-duration of Spotting/Bleeding
时间窗: Up to Follow-up (Day 112)
After completion of the 12-week treatment period, participants with an intact uterus received a 14-day cycle of progestogen (10 mg medroxyprogesterone acetate \[MPA\]) to induce withdrawal bleeding. All participants were required to return to clinic for Follow-Up Visit. Participants were asked to record occurrence of bleeding/spotting each day, from the day MPA dosing began until Follow-up using the following criteria: None (no bleeding or spotting), Spotting: any vaginal flow requiring not more than one sanitary napkin or tampon per day (lightly stained and not soaked through) and Bleeding: any vaginal flow requiring more than one sanitary napkin or tampon per day. The following information was recorded in electronic case report form: start and stop date of MPA administration as well as dates of any spotting/bleeding. Duration of spotting or bleeding is presented.
Occurrence of Withdrawal Bleeding-number of Days of Spotting, Number of Days of Bleeding, Number of Days of Spotting/Bleeding Combined
时间窗: Up to Follow-up (Day 112)
After completion of the 12-week treatment period, participants with an intact uterus received a 14-day cycle of progestogen (10 mg MPA) to induce withdrawal bleeding. All participants were required to return to clinic for Follow-Up Visit. Participants were asked to record occurrence of bleeding/spotting each day, from the day MPA dosing began until Follow-up using the following criteria: None (no bleeding or spotting), Spotting: any vaginal flow requiring not more than one sanitary napkin or tampon per day (lightly stained and not soaked through) and Bleeding: any vaginal flow requiring more than one sanitary napkin or tampon per day. The following information was recorded in electronic case report form: start and stop date of MPA administration as well as dates of any spotting/bleeding. Duration of spotting, bleeding and also spotting/bleeding combined is presented.
Change From Baseline in Thyroxine (T4) and Insulin at Week 12
时间窗: Baseline (Week 0) and Week 12
Serum hormone markers included T4 and additional pharmacodynamics marker included insulin. Baseline was Week 0. Change from Baseline was calculated by subtracting Baseline values from post-Baseline values. Mean change from Baseline in T4 and insulin at Week 12 are presented.
Change From Baseline in Fasting Lipid Profile at Week 12
时间窗: Baseline (Week 0) and Week 12
Fasting lipids included total cholesterol, low density lipoprotein (LDL) cholesterol, high density lipoprotein (HDL) cholestereol direct and triglycerides. Baseline was Week 0. Change from Baseline was calculated by subtracting Baseline values from post-Baseline values. Mean change from Baseline in fasting lipid profile at Week 12 are presented.
Change From Baseline in Bi-layer Endometrial Thickness Measured by Transvaginal Ultrasound (TVUS) or Saline Infusion Sonohysterography (SIS)
时间窗: Baseline (Week 0) to Week 12
All participants with an intact uterus participating in this study underwent a TVUS at Baseline and at Week 12, to investigate the cause of any abnormal uterine bleeding during the study. In the event the TVUS was not well visualized or there were abnormal findings at either visit, or the bi-layer thickness exceeded 5 millimeter at Week 12, a SIS was conducted to visualize the anterior and posterior walls. Baseline was Week 0. Change from Baseline was calculated by subtracting Baseline values from post-Baseline values. Mean change from Baseline and Week 12 in heart rate are presented.
Endometrial Biopsy Pathology
时间窗: Baseline (Week 0) to Week 12
Endometrial biopsies were conducted at Baseline and end-of-treatment (end-of-treatment values were defined as the last available post-Baseline values before treatment was stopped) for all study participants with an intact uterus. These procedures were performed by an experienced physician. Each biopsy was obtained after the TVUS was performed. Proliferative endometrium also meant hyperplasia without atypia (normal).
Change From Baseline in Hematology Parameter- Red Blood Cell (RBC) Count at Week 12
时间窗: Baseline (Week 0) and Week 12
Hematology parameter included RBC count. Baseline was Week 0. Change from Baseline was calculated by subtracting Baseline values from post-Baseline values.
Change From Baseline in Vital Signs of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Week 12
时间窗: Baseline (Week 0) and Week 12
SBP and DBP were measured after the participant had rested for at least 5 minutes in a sitting or supine position. Baseline was Week 0. Change from Baseline was calculated by subtracting Baseline values from post-Baseline values. Mean change from Baseline in SBP and DBP at Week 12 are presented.
Change From Baseline in Vital Sign of Heart Rate at Week 12
时间窗: Baseline (Week 0) and Week 12
Heart rate was measured after the participant had rested for at least 5 minutes in a sitting or supine position. Baseline was Week 0. Change from Baseline was calculated by subtracting Baseline values from post-Baseline values. Mean change from Baseline in heart rate at Week 12 are presented.
Mean Change in Frequency of Vasomotor Symptoms (VMS) From Baseline at Week 12
时间窗: Baseline (Week 0) and Week 12
Individual VMS (hot flash or night sweats) events were recorded by participants in an electronic diary (eDiary) using as Global Change Question. The frequency was assessed using the question 1 as "Since you started the study medication, how has the number of your hot flashes (including night sweats) changed?". the response was rated on a 7-point scale from +3 to -3, where +3=A great deal better, +2=Moderately better, +1=A little better, 0=No change, -1=A little worse, -2=Moderately worse and -3=A great deal worse. The score ranged from +3 to -3, where +3 implied absence of symptoms and lower score implied more severe symptoms. Baseline was Week 0. Change from Baseline was calculated by subtracting Baseline values from post-Baseline values. Adjusted mean is presented as least square mean.
Change From Baseline in Thrombotic Marker- Fibrinogen at Week 12
时间窗: Baseline (Week 0) and Week 12
Thrombotic marker included fibrinogen. Baseline was Week 0. Change from Baseline was calculated by subtracting Baseline values from post-Baseline values.
Change From Baseline and Week 12 in Inflammatory Marker- Endothelin-1 at Week 12
时间窗: Baseline (Week 0) and Week 12
Inflammatory marker included Endothelin-1. Baseline was Week 0. Change from Baseline was calculated by subtracting Baseline values from post-Baseline values.
Change From Baseline in Hematology Parameter- Mean Corpuscle Hemoglobin (MCH) at Week 12
时间窗: Baseline (Week 0) and Week 12
Hematology parameter included MCH. Baseline was Week 0. Change from Baseline was calculated by subtracting Baseline values from post-Baseline values.
Change From Baseline in Clinical Chemistry Parameters- Albumin and Total Protein at Week 12
时间窗: Baseline (Week 0) and Week 12
Clinical chemistry parameters included albumin and total protein. Baseline was Week 0. Change from Baseline was calculated by subtracting Baseline values from post-Baseline values.
Change From Baseline in Clinical Chemistry Parameters- Calcium, Carbon Dioxide (C02) Content, Chloride, Phosphorous, Inorganic, Potassium, Sodium and Urea at Week 12
时间窗: Baseline (Week 0) and Week 12
Clinical chemistry parameters included calcium, C02 content, chloride, phosphorous, inorganic, potassium, sodium and urea. Baseline was Week 0. Change from Baseline was calculated by subtracting Baseline values from post-Baseline values.
Change From Baseline in Thrombotic Marker- Tissue Plasminogen Activator (tPA) Antigen at Week 12
时间窗: Baseline (Week 0) and Week 12
Thrombotic marker included tPA antigen. Baseline was Week 0. Change from Baseline was calculated by subtracting Baseline values from post-Baseline values.
Change From Baseline in Hematology Parameter- Mean Corpuscle Volume (MCV) at Week 12
时间窗: Baseline (Week 0) and Week 12
Hematology parameter included MCV. Baseline was Week 0. Change from Baseline was calculated by subtracting Baseline values from post-Baseline values.
Change From Baseline in Clinical Chemistry Parameters- Alanine Amino Transferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST) at Week 12
时间窗: Baseline (Week 0) and Week 12
Clinical chemistry parameters included ALT, ALP and AST. Baseline was Week 0. Change from Baseline was calculated by subtracting Baseline values from post-Baseline values.
Change From Baseline and Week 12 in Inflammatory Marker- High Sensitivity C-reactive Protein (Hs-CRP) at Week 12
时间窗: Baseline (Week 0) and Week 12
Inflammatory marker included hs-CRP. Baseline was Week 0. Change from Baseline was calculated by subtracting Baseline values from post-Baseline values.
Change From Baseline and Week 12 in Hematology Parameter- Hematocrit at Week 12
时间窗: Baseline (Week 0) and Week 12
Hematology parameter included hematocrit. Baseline was Week 0. Change from Baseline was calculated by subtracting Baseline values from post-Baseline values.
Change From Baseline in Clinical Chemistry Parameters- Creatinine, Direct Bilirubin, Total Bilirubin and Uric Acid at Week 12
时间窗: Baseline (Week 0) and Week 12
Clinical chemistry parameters included creatinine, direct bilirubin, total bilirubin and uric acid. Baseline was Week 0. Change from Baseline was calculated by subtracting Baseline values from post-Baseline values.
Change From Baseline in Hematology Parameters- Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) at Week 12
时间窗: Baseline (Week 0) and Week 12
Hematology parameters included Hemoglobin and MCHC. Baseline was Week 0. Change from Baseline was calculated by subtracting Baseline values from post-Baseline values.
Change From Baseline in Hematology Parameters- Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Segmented Neutrophils, Total Neutrophils and White Blood Cell (WBC) Count at Week 12
时间窗: Baseline (Week 0) and Week 12
Hematology parameters included basophils, eosinophils, lymphocytes, monocytes, platelet count, segmented neutrophils, total neutrophils and WBC count. Baseline was Week 0. Change from Baseline was calculated by subtracting Baseline values from post-Baseline values. Mean change from Baseline and Week 12 in basophils, eosinophils, lymphocytes, monocytes, platelet count, segmented neutrophils, total neutrophils and WBC count are presented.
次要结局
- Changes in Vulvar Vaginal Atrophy (VVA) Symptom Score From Baseline to Visit 8 (Week 12)(Baseline (Week 0) to Visit 8 (Week 12))
- Change in Menopause Quality of Life (MENQoL) Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12)(Baseline (Week 0) to Week 12)
- Change in Work Productivity and Activity Impairment (WPAI) Score From Visit 2 to Visit 7(Visit 2 (Day -21) to Visit 7 (Week 8))
- Change From Baseline at Week 12 in Serum Hormone Levels- Follicle Stimulating Hormone (FSH) and Luteinizing Hormone (LH)(Baseline (Week 0) and Week 12)
- Mean Change in Severity of VMS From Baseline to Weeks 4 and 8(Baseline (Week 0) to Week 8)
- Number of Participants With VMS Percent Change From Baseline Responders With a Reduction in Frequency at Week 12 of at Least 50%, at Least 75%, and 100%(Baseline (Week 0) and Week 12)
- Change From Baseline at Week 12 in Serum Hormone Levels- Estradiol(Baseline (Week 0) and Week 12)
- Mean Change in Frequency of VMS From Baseline to Weeks 4 and 8(Baseline (Week 0) to Week 8)
- Number of Participants With VMS Percent Change From Baseline Responders With a Reduction in Severity at Week 12 of at Least 50%, at Least 75%, and 100%(Baseline (Week 0) and Week 12)
- Change in Medical Outcomes Study (MOS) Sleep Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12)(Baseline (Week 0) to Week 12)
- Change in the Centers for Epidemiologic Studies in Depression (CES-D) Score From Visit 2 to Visit 7(Visit 2 (Day -21) to Visit 7 (Week 8))
- Change in Brief Fatigue Inventory (BFI) Score From Visit 2 to Visit 7(Visit 2 (Day -21) to Visit 7 (Week 8))
- Change From Visit 2 to Visit 8 in Vaginal pH(Visit 2 (Day -21) to Visit 8 (Week 12))
- Change From Visit 2 to Visit 8 in Percentage of Superficial Cells to Determine the Vaginal Maturation Index (VMI)(Visit 2 (Day -21) to Visit 8 (Week 12))
- Change From Baseline at Week 12 in Weight(Baseline (Week 0) and Week 12)
- Change From Baseline in Glucose at Week 12(Baseline (Week 0) and Week 12)
- Change From Baseline at Week 12 in Serum Hormone Levels- Testosterone(Baseline (Week 0) and Week 12)
- Change From Baseline at Week 12 in Waist Circumference(Baseline (Week 0) and Week 12)
- Change From Baseline at Week 12 in Body Mass Index (BMI)(Baseline (Week 0) and Week 12)
- Change From Baseline at Week 12 in Hip Circumference(Baseline (Week 0) and Week 12)
- Change From Baseline at Week 12 in Abdomen Body Circumference, Abdomen Saggital Diameter and Thigh Circumference(Baseline (Week 0) and Week 12)
- Change From Baseline at Week 12 in Abdomen Visceral Adipose Tissue (AVAT), Abdomen Subcutaneous Adipose Tissue (ASAT), Thigh Subcutaneous Adipose Tissue (TSAT) and Thigh Intermuscular Adipose Tissue (TIAT)(Baseline (Week 0) and Week 12)