Menopausal and Female Climacteric States
Conditions
Keywords
menopause, hormone therapy, hot flashes, vasomotor symptoms
Brief summary
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.
Interventions
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
40 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
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 6.3.1. * 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.
Exclusion criteria
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 1. 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 1. 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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Clinical Chemistry Parameters- Calcium, Carbon Dioxide (C02) Content, Chloride, Phosphorous, Inorganic, Potassium, Sodium and Urea at Week 12 | 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 Thyroid Stimulating Hormone (TSH) at Week 12 | 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. |
| Change From Baseline in Thyroxine (T4) and Insulin at Week 12 | 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 | 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) | 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 | 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). |
| Occurrence of Withdrawal Bleeding-duration of Spotting/Bleeding | 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 | 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. |
| Mean Change in Frequency of Vasomotor Symptoms (VMS) From Baseline at Week 12 | 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. |
| Mean Change in Severity of VMS From Baseline at Week 12 | 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. |
| Change From Baseline in Thrombotic Marker- Fibrinogen at Week 12 | 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 in Thrombotic Marker- Tissue Plasminogen Activator (tPA) Antigen at Week 12 | 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 and Week 12 in Inflammatory Marker- High Sensitivity C-reactive Protein (Hs-CRP) at Week 12 | 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 Inflammatory Marker- Endothelin-1 at Week 12 | 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 and Week 12 in Hematology Parameter- Hematocrit at Week 12 | 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 Hematology Parameter- Mean Corpuscle Hemoglobin (MCH) at Week 12 | 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 Hematology Parameter- Mean Corpuscle Volume (MCV) at Week 12 | 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 Hematology Parameter- Red Blood Cell (RBC) Count at Week 12 | 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 Hematology Parameters- Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) at Week 12 | 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 | 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. |
| Change From Baseline in Clinical Chemistry Parameters- Albumin and Total Protein at Week 12 | 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- Creatinine, Direct Bilirubin, Total Bilirubin and Uric Acid at Week 12 | 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 Clinical Chemistry Parameters- Alanine Amino Transferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST) at Week 12 | 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. |
| Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) and Number of Participants With Mild, Moderate and Severe AE | 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. |
| Change From Baseline in Vital Signs of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Week 12 | 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 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change in Severity of VMS From Baseline to Weeks 4 and 8 | Baseline (Week 0) to Week 8 | Individual VMS (hot flash or night sweats) events were recorded by participants in an eDiary using global change questions. The 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 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 | Individual VMS (hot flash or night sweats) events were recorded by participants in an eDiary using global change question. The severity of VMS events were calculated using self-reported participants assessments recorded and transmitted by eDiary. Baseline was Week 0. Change from Baseline was calculated by subtracting Baseline values from post-Baseline values. Percent change was calculated by multiplying the change from baseline value with 100. 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% are presented. |
| 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 | Individual VMS (hot flash or night sweats) events were recorded by participants in an eDiary using global change questions. The VMS severity was as follows: mild (brief wave of heat with minimal discomfort, usually without perspiration; able to continue activity \[or sleep\]), moderate (heat with some discomfort, usually with perspiration; minimal interruption of activity \[or sleep\]), severe (intense heat with considerable discomfort, usually with heavy sweating; may be unable to resume activity \[or sleep\] right away) and extremely severe (unbearable heat with intense discomfort, usually with pouring sweat; may be unable to resume activity \[or sleep\] for quite a while). The severity of VMS events were calculated using self-reported participants assessments recorded and transmitted by eDiary. Baseline was Week 0. Change from Baseline was calculated by subtracting Baseline values from post-Baseline values. Percent change was calculated by multiplying change from Baseline value with 100. |
| 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 | MENQOL instrument is a 32-item, validated questionnaire designed to measure symptoms that participants experience due to menopause and degree to which these symptoms bother them. Each item references a symptom and is composed of two-part question; a yes/no confirmation that the participant has symptom followed by a question asking how bothersome the symptom is, if present. The MENQOL items are designed to be grouped into domains that address vasomotor (items 1-3), psychosocial(items 4-10), physical (items 11-26, 30-32) and sexual symptoms (items 27-29). Each domain is given a separate score; there is no overall score. The domain score is sum of individual item scores divided by number of items in that domain. Since domain subscales are not comprised of an equivalent number of items, mean of subscale is used as overall subscale score. Each domain score ranges from 1 to 8. Baseline was Week 0. Change from Baseline was calculated by subtracting Baseline values from post-Baseline values. |
| 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 | The MOS Sleep Scale is a validated questionnaire designed to measure a participant sleep quality via 12 questions. Items are designed to be grouped into domains that include sleep disturbance (items 1, 3, 7, 8), sleep adequacy (items 4, 12), daytime somnolence (items 6, 9, 11), sleep quantity (2), 6-Item Sleep Scale (items 4, 5, 7, 8, 9, 12) and 9-Item Sleep Scale (items 3, 4, 5, 6, 7, 8, 9, 11, 12). Each domain is given a separate score. The domain score is calculated as the sum of the individual item scores in that domain. Transformed scores were calculated for the domains only. This transformation converts the raw domain score to a 0 to 100 scale following the formula: Transformed score = (\[Raw score - Lowest possible score\]/Possible score range)\*100. Lowest score 0 indicates best sleep quality and higher score 100 indicates worst sleep quality. Baseline was Week 0. Change from Baseline was calculated by subtracting Baseline values from post-Baseline values. |
| Changes in Vulvar Vaginal Atrophy (VVA) Symptom Score From Baseline to Visit 8 (Week 12) | Baseline (Week 0) to Visit 8 (Week 12) | The VVA Symptoms Scale questionnaire is an 18-item instrument that captures symptoms related to VVA, asks participant to identify symptom that bothers them the most and contains items to assess degree of bother participants experience from each symptom and impact that most bothersome symptom has on their daily life. Items 1 to 8 had responses and scores of none=0, mild=1, moderate=2 and severe=3. Items 9 to 18 had responses and scores of not at all=0, a little=1, moderately=2 and a lot=3. Severity item and bothersome item respectively were as follows: vaginal dryness:1 and 9; Vaginal itching:2 and 10; Vaginal irritation:3 and 11; Painful urination:4 and 12; Difficulty urinating:5 and 13; Vaginal pain associated with sexual activity:6 and 14; Vaginal bleeding associated with sexual activity:7 and 15. Total score ranged from 0 to 3; higher score indicated most bothersome. Baseline was Week 0. Change from Baseline was calculated by subtracting Baseline values from post-Baseline values. |
| Change in Brief Fatigue Inventory (BFI) Score From Visit 2 to Visit 7 | Visit 2 (Day -21) to Visit 7 (Week 8) | The BFI is a validated questionnaire designed to measure a participant's fatigue via nine questions that are summated to create a total score. Items 1-3 request a rating on a scale ranging from 0 - 10 with 0 representing 'No Fatigue' and 10 representing 'As bad as you can imagine'. Five items 4A-4F request an interference score on a scale ranging from 0 - 10 with 0 representing 'Does not interfere' and 10 representing 'Completely Interferes'. The values of the scales for all items was used in scoring the response to each item. The following groupings of items was used to create domain scores. The total score is calculated by taking the sum of all 9 rating scales for a minimum score of 0 and a maximum score of 90. Higher score indicates more severe fatigue. Visit 2 was Day -21. Change from Visit 2 was calculated by subtracting Visit 2 values from post-Visit 2 values. |
| 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) | The CES-D is a questionnaire designed to measure depressive symptoms via 20 items that are summed to create a total score. Depressive symptoms are fairly common in postmenopausal women, and it's possible that stimulation of estrogen receptors via a selective estrogen receptor modulator may improve depressive symptoms. Questions 4, 8, 12 and 16 are weighted negatively (the scores are flipped prior to creating total score). If 3 or more items are missing then total score is missing. If fewer than 3 items are missing then missing item is set to group mean of that item for appropriate randomized treatment group. These means are only calculated if more than half of the participants used for calculation have responded to item. The items are summed to give total score ranging from 0 to 60. Lower score 0=no depression, higher score 60=higher degree of depression severity. Visit 2 was Day -21. Change from Visit 2 was calculated by subtracting Visit 2 values from post-Visit 2 values. |
| Change in Work Productivity and Activity Impairment (WPAI) Score From Visit 2 to Visit 7 | Visit 2 (Day -21) to Visit 7 (Week 8) | The WPAI is a questionnaire that measured workplace productivity and absenteeism via 6 items/questions, adapted to participants experiencing menopausal symptoms. Item 1 asks about current employment with a yes/no response. Items 2- 4 ask for continuous response in hours. Item 5 asks for response on rating scale related to WP ranging from 0:Menopausal symptoms had no effect on work to 10:Couldn't work at all. Item 6 asks for response on rating scale related to daily activities ranging from 0:no effect on daily activities to 10:Couldn't perform any daily activities. The score calculation- Effect on work: (Item 5 score÷10); Absenteeism: (Item 2÷Item 2+Item 4); Overall work impairment (\[Item 2÷Item 2+Item 4\]+ \[1- {Item 2÷Item 2+Item 4}\]\*\[ Item 5 score÷10\]); Activity impairment: (Item 6 score÷10). Total score range from 0 to 10 where higher score indicates worst condition. Visit 2 was Day -21. Change from Visit 2 was calculated by subtracting Visit 2 values from post-Visit 2 values. |
| Change From Visit 2 to Visit 8 in Vaginal pH | Visit 2 (Day -21) to Visit 8 (Week 12) | Vaginal pH was measured at Visit 2 and Visit 8 using standard pH indicator strips available at the participating site clinic. The pH indicator strip was inserted to the upper portion of the proximal one third of the vaginal vault, placed in contact with the lateral vaginal mucosal wall for approximately 1 minute, and evaluated according to the instructions provided in the package labeling. pH is calculated on a scale of 0 to 14, such that, the lower the number, more acidic the vagina and higher the number, more alkaline the vagina with 7 being neutral. Change from Visit 2 to Visit 8 was calculated by subtracting Visit 2 values from Visit 8 values. |
| 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) | A lateral vaginal wall specimen was collected at Visit 2 (Day -21) and Visit 8 (Week 12) and was sent to Central Pathology for analysis. Parabasal, intermediate, and superficial squamous cells were counted and percentages calculated. The VMI (also referred to as Maturation Value \[MV\]) of the vaginal mucosa was calculated according to the following equation: VMI (MV)= (% Intermediate Cells x 0.5) + (% Superficial cells). Visit 2 was Day -21 and Visit 8 was Week 12. Change from Visit 2 to Visit 8 was calculated by subtracting Visit 2 values from Visit 8 values. |
| Change From Baseline in Glucose at Week 12 | Baseline (Week 0) and Week 12 | Pharmacodynamic marker included glucose. Baseline was Week 0. Change from Baseline was calculated by subtracting Baseline values from post-Baseline values. |
| Change From Baseline at Week 12 in Serum Hormone Levels- Estradiol | Baseline (Week 0) and Week 12 | Serum hormone included Estradiol. Baseline was Week 0. Change from Baseline was calculated by subtracting Baseline values from post-Baseline values. Mean change from Baseline at Week 12 in estradiol are presented. |
| Change From Baseline at Week 12 in Serum Hormone Levels- Follicle Stimulating Hormone (FSH) and Luteinizing Hormone (LH) | Baseline (Week 0) and Week 12 | Serum hormones included FSH and LH. Baseline was Week 0. Change from Baseline was calculated by subtracting Baseline values from post-Baseline values. |
| Change From Baseline at Week 12 in Serum Hormone Levels- Testosterone | Baseline (Week 0) and Week 12 | Serum hormones included testosterone. Baseline was Week 0. Change from Baseline was calculated by subtracting Baseline values from post-Baseline values. Mean change from Baseline at Week 12 in testosterone are presented. |
| Change From Baseline at Week 12 in Waist Circumference | Baseline (Week 0) and Week 12 | To measure waist circumference, clothing was lifted from around the waist to ensure correct positioning of the measuring tape. Participants were instructed to stand erect with abdomen relaxed, arms at side, feet together, and weight equally divided over both legs. The non-stretchable tape was placed at the waist midway between the palpated iliac crest and the palpated lowest rib margin in the left and right mid-axillary lines. The tape was even, parallel to the floor not twisted with the measurement scale facing outward. The assessor was instructed to ensure that the tape was just touching the skin but not compressing the soft tissue. The measurement was made at the end of a normal expiration. The waist was measured at least twice or more if necessary, until two measurements were within 1 centimeter and the confirmatory reading recorded to one decimal place. Baseline was Week 0. Change from Baseline was calculated by subtracting Baseline values from post-Baseline values. |
| Change From Baseline at Week 12 in Hip Circumference | Baseline (Week 0) and Week 12 | For hip circumference, the participant was instructed to stand erect with arms at sides and feet together. The measurement was taken at the point yielding the maximum circumference over the buttocks (widest part of the greater trochanters) with nonstretchable tape. The tape was even, not twisted with the measurement scale facing outward. The assessor was instructed to ensure that the tape was just touching the skin but not compressing the soft tissue. The hip should be measured at least twice until two measurements are within 1 centimeter and the last reading recorded. Baseline was Week 0. Change from Baseline was calculated by subtracting Baseline values from post-Baseline values. |
| Change From Baseline at Week 12 in Weight | Baseline (Week 0) and Week 12 | Participants were weighed on a calibrated balance beam or digital scale. Participants were instructed to be dressed in light indoor clothing without shoes and also to have empty pockets and to void before weighing. It was strongly recommended that participants were weighed in the morning at the beginning of the clinic visit. Weight was measured at least twice or more if necessary, until two measurements were within 0.5 kilograms. The last (confirmed) reading was recorded in the electronic case report form. Weight was recorded in kilograms to the nearest tenth. When the weight was measured in pounds, it was converted into kilograms using the conversion factor: pounds/ 2.2 = kilograms. Baseline was Week 0. Change from Baseline was calculated by subtracting Baseline values from post-Baseline values. |
| Change From Baseline at Week 12 in Body Mass Index (BMI) | Baseline (Week 0) and Week 12 | BMI was calculated from height (taken at Screening Visit 1 \[Day -35\]) and weight at Week 12 using the formula: BMI = \[weight in kilograms divided by (height in meters)\^2\]. Baseline was Week 0. Change from Baseline was calculated by subtracting Baseline values from post-Baseline values. |
| Change From Baseline at Week 12 in Abdomen Body Circumference, Abdomen Saggital Diameter and Thigh Circumference | Baseline (Week 0) and Week 12 | Thigh circumference was measured on the left leg directly below the gluteal fold; with the participant standing with both arms at the side, feet together, and with equal weight on both feet when this measurement was taken. The thigh was measured at least twice until two measurements were within 1 centimeter, and the last reading recorded. Abdomen body circumference and abdomen saggital diameter was measured in centimeter to once decimal place by Computerized tomography (CT) scan with the participant in supine position. CT scan of the abdomen was conducted at the Lumbar 4 vertebrae level. Scans were performed with 120 kilovolts, 5 millimeter slice thickness and 48 centimeter scan field of view. Baseline was Week 0. Change from Baseline was calculated by subtracting Baseline values from post-Baseline values. |
| 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 | AVAT, ASAT, TSAT and TIAT was measured in centimeter to once decimal place by CT scan. A CT scan of the abdomen was conducted at the Lumbar 4 vertebrae level. A CT scan of the right thigh was performed at half the distance between the knee joint and greater trochanter femoralis. Scans were performed with 120 kilovolts, 5 millimeter slice thickness (thigh scan 3 millimeter slice thickness) and 48 centimeter scan field of view. Baseline was Week 0. Change from Baseline was calculated by subtracting Baseline values from post-Baseline values. |
| Mean Change in Frequency of VMS From Baseline to Weeks 4 and 8 | Baseline (Week 0) to Week 8 | Individual VMS (hot flash or night sweats) events were recorded by participants in an 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. |
Countries
Argentina, Australia, Germany, Italy, New Zealand, Spain, Sweden, United Kingdom, United States
Participant flow
Recruitment details
The study was conducted from at 75 centers (2 in Spain, 3 each in Argentina, New Zealand and the United Kingdom, 4 in Italy, 5 in Australia, 6 in Sweden, 12 in Germany, and 37 in the United States) from 17-July-2007 to 23-July-2008.
Pre-assignment details
A total of 982 healthy postmenopausal participants with moderate to extremely severe vasomotor symptoms were screened (626 screen failures) and 356 were randomized.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Eligible participants received placebo tablets/capsules to match GSK232802 tablets and Premarin capsules, one tablet or capsule via oral route at approximately the same time each morning for a total period of 12 weeks. | 90 |
| GSK232802 25 mg Eligible participants received GSK232802 25 mg tablets, one tablet via oral route at approximately the same time each morning for a total period of 12 weeks. | 87 |
| GSK232802 75 mg Eligible participants received GSK232802 75 mg tablets, one tablet via oral route at approximately the same time each morning for a total period of 12 weeks. | 89 |
| Premarin 0.3 mg Eligible participants received Premarin 0.3 mg capsules, one capsule via oral route at approximately the same time each morning for a total period of 12 weeks. | 90 |
| Total | 356 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 2 | 6 | 7 | 4 |
| Overall Study | Did not meet eligibility criteria | 0 | 0 | 2 | 0 |
| Overall Study | Exclusion criterion met | 0 | 0 | 0 | 1 |
| Overall Study | Lack of Efficacy | 3 | 2 | 1 | 0 |
| Overall Study | Lost to Follow-up | 0 | 3 | 1 | 0 |
| Overall Study | Physician Decision | 0 | 0 | 0 | 1 |
| Overall Study | Protocol Violation | 0 | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 4 | 3 | 5 | 5 |
Baseline characteristics
| Characteristic | Placebo | Total | Premarin 0.3 mg | GSK232802 75 mg | GSK232802 25 mg |
|---|---|---|---|---|---|
| Age, Continuous | 55.2 Years STANDARD_DEVIATION 4.17 | 54.6 Years STANDARD_DEVIATION 4.73 | 54.0 Years STANDARD_DEVIATION 5.18 | 54.2 Years STANDARD_DEVIATION 4.78 | 54.9 Years STANDARD_DEVIATION 4.72 |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 2 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 2 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 31 Participants | 9 Participants | 9 Participants | 9 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 84 Participants | 320 Participants | 79 Participants | 79 Participants | 78 Participants |
| Sex: Female, Male Female | 90 Participants | 356 Participants | 90 Participants | 89 Participants | 87 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 90 | 0 / 87 | 0 / 88 | 0 / 90 |
| other Total, other adverse events | 30 / 90 | 24 / 87 | 21 / 88 | 17 / 90 |
| serious Total, serious adverse events | 2 / 90 | 0 / 878 | 1 / 88 | 1 / 90 |
Outcome results
Primary
Change From Baseline and Week 12 in Hematology Parameter- Hematocrit at Week 12
Hematology parameter included hematocrit. Baseline was Week 0. Change from Baseline was calculated by subtracting Baseline values from post-Baseline values.
Time frame: Baseline (Week 0) and Week 12
Population: Safety Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline and Week 12 in Hematology Parameter- Hematocrit at Week 12 | -0.003 Fraction | Standard Deviation 0.0303 |
| GSK232802 25 mg | Change From Baseline and Week 12 in Hematology Parameter- Hematocrit at Week 12 | -0.006 Fraction | Standard Deviation 0.0192 |
| GSK232802 75 mg | Change From Baseline and Week 12 in Hematology Parameter- Hematocrit at Week 12 | -0.019 Fraction | Standard Deviation 0.0313 |
| Premarin 0.3 mg | Change From Baseline and Week 12 in Hematology Parameter- Hematocrit at Week 12 | -0.002 Fraction | Standard Deviation 0.0198 |
Primary
Change From Baseline and Week 12 in Inflammatory Marker- Endothelin-1 at Week 12
Inflammatory marker included Endothelin-1. Baseline was Week 0. Change from Baseline was calculated by subtracting Baseline values from post-Baseline values.
Time frame: Baseline (Week 0) and Week 12
Population: Safety Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline and Week 12 in Inflammatory Marker- Endothelin-1 at Week 12 | -1.204 Nanogram per Liter | Standard Deviation 1.4544 |
| GSK232802 25 mg | Change From Baseline and Week 12 in Inflammatory Marker- Endothelin-1 at Week 12 | -0.897 Nanogram per Liter | Standard Deviation 1.3425 |
| GSK232802 75 mg | Change From Baseline and Week 12 in Inflammatory Marker- Endothelin-1 at Week 12 | -1.087 Nanogram per Liter | Standard Deviation 1.572 |
| Premarin 0.3 mg | Change From Baseline and Week 12 in Inflammatory Marker- Endothelin-1 at Week 12 | -0.945 Nanogram per Liter | Standard Deviation 1.6884 |
Primary
Change From Baseline and Week 12 in Inflammatory Marker- High Sensitivity C-reactive Protein (Hs-CRP) at Week 12
Inflammatory marker included hs-CRP. Baseline was Week 0. Change from Baseline was calculated by subtracting Baseline values from post-Baseline values.
Time frame: Baseline (Week 0) and Week 12
Population: Safety Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline and Week 12 in Inflammatory Marker- High Sensitivity C-reactive Protein (Hs-CRP) at Week 12 | 0.008 Milligram per Liter | Standard Deviation 1.578 |
| GSK232802 25 mg | Change From Baseline and Week 12 in Inflammatory Marker- High Sensitivity C-reactive Protein (Hs-CRP) at Week 12 | 2.181 Milligram per Liter | Standard Deviation 9.4203 |
| GSK232802 75 mg | Change From Baseline and Week 12 in Inflammatory Marker- High Sensitivity C-reactive Protein (Hs-CRP) at Week 12 | 0.833 Milligram per Liter | Standard Deviation 2.3385 |
| Premarin 0.3 mg | Change From Baseline and Week 12 in Inflammatory Marker- High Sensitivity C-reactive Protein (Hs-CRP) at Week 12 | 0.557 Milligram per Liter | Standard Deviation 3.6617 |
Primary
Change From Baseline in Bi-layer Endometrial Thickness Measured by Transvaginal Ultrasound (TVUS) or Saline Infusion Sonohysterography (SIS)
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.
Time frame: Baseline (Week 0) to Week 12
Population: Uterine Safety Population which comprised of all randomized participants who had a uterus and also received at least one dose of investigational product. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Bi-layer Endometrial Thickness Measured by Transvaginal Ultrasound (TVUS) or Saline Infusion Sonohysterography (SIS) | SIS Anterior Endometrial Thickness | -1.20 Millimeter | — |
| Placebo | Change From Baseline in Bi-layer Endometrial Thickness Measured by Transvaginal Ultrasound (TVUS) or Saline Infusion Sonohysterography (SIS) | SIS Total Endometrial Thickness | 7.20 Millimeter | — |
| Placebo | Change From Baseline in Bi-layer Endometrial Thickness Measured by Transvaginal Ultrasound (TVUS) or Saline Infusion Sonohysterography (SIS) | SIS Posterior Endometrial Thickness | 8.40 Millimeter | — |
| Placebo | Change From Baseline in Bi-layer Endometrial Thickness Measured by Transvaginal Ultrasound (TVUS) or Saline Infusion Sonohysterography (SIS) | TVUS Bi-layer Endometrial Thickness | -0.07 Millimeter | Standard Deviation 1.255 |
| GSK232802 25 mg | Change From Baseline in Bi-layer Endometrial Thickness Measured by Transvaginal Ultrasound (TVUS) or Saline Infusion Sonohysterography (SIS) | SIS Total Endometrial Thickness | 2.60 Millimeter | — |
| GSK232802 25 mg | Change From Baseline in Bi-layer Endometrial Thickness Measured by Transvaginal Ultrasound (TVUS) or Saline Infusion Sonohysterography (SIS) | SIS Anterior Endometrial Thickness | 1.70 Millimeter | — |
| GSK232802 25 mg | Change From Baseline in Bi-layer Endometrial Thickness Measured by Transvaginal Ultrasound (TVUS) or Saline Infusion Sonohysterography (SIS) | TVUS Bi-layer Endometrial Thickness | 0.13 Millimeter | Standard Deviation 1.383 |
| GSK232802 25 mg | Change From Baseline in Bi-layer Endometrial Thickness Measured by Transvaginal Ultrasound (TVUS) or Saline Infusion Sonohysterography (SIS) | SIS Posterior Endometrial Thickness | 0.90 Millimeter | — |
| GSK232802 75 mg | Change From Baseline in Bi-layer Endometrial Thickness Measured by Transvaginal Ultrasound (TVUS) or Saline Infusion Sonohysterography (SIS) | TVUS Bi-layer Endometrial Thickness | 0.79 Millimeter | Standard Deviation 1.895 |
| Premarin 0.3 mg | Change From Baseline in Bi-layer Endometrial Thickness Measured by Transvaginal Ultrasound (TVUS) or Saline Infusion Sonohysterography (SIS) | TVUS Bi-layer Endometrial Thickness | 1.12 Millimeter | Standard Deviation 2.051 |
Primary
Change From Baseline in Clinical Chemistry Parameters- Alanine Amino Transferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST) at 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.
Time frame: Baseline (Week 0) and Week 12
Population: Safety Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Clinical Chemistry Parameters- Alanine Amino Transferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST) at Week 12 | AST | -0.247 Units per Liter | Standard Deviation 5.219 |
| Placebo | Change From Baseline in Clinical Chemistry Parameters- Alanine Amino Transferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST) at Week 12 | ALP | -0.037 Units per Liter | Standard Deviation 10.0629 |
| Placebo | Change From Baseline in Clinical Chemistry Parameters- Alanine Amino Transferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST) at Week 12 | ALT | 0.160 Units per Liter | Standard Deviation 6.8838 |
| GSK232802 25 mg | Change From Baseline in Clinical Chemistry Parameters- Alanine Amino Transferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST) at Week 12 | AST | -1.139 Units per Liter | Standard Deviation 7.3356 |
| GSK232802 25 mg | Change From Baseline in Clinical Chemistry Parameters- Alanine Amino Transferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST) at Week 12 | ALT | -2.681 Units per Liter | Standard Deviation 10.32 |
| GSK232802 25 mg | Change From Baseline in Clinical Chemistry Parameters- Alanine Amino Transferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST) at Week 12 | ALP | -6.403 Units per Liter | Standard Deviation 9.8577 |
| GSK232802 75 mg | Change From Baseline in Clinical Chemistry Parameters- Alanine Amino Transferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST) at Week 12 | AST | -0.743 Units per Liter | Standard Deviation 6.7643 |
| GSK232802 75 mg | Change From Baseline in Clinical Chemistry Parameters- Alanine Amino Transferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST) at Week 12 | ALT | -1.986 Units per Liter | Standard Deviation 8.8943 |
| GSK232802 75 mg | Change From Baseline in Clinical Chemistry Parameters- Alanine Amino Transferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST) at Week 12 | ALP | -8.878 Units per Liter | Standard Deviation 13.252 |
| Premarin 0.3 mg | Change From Baseline in Clinical Chemistry Parameters- Alanine Amino Transferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST) at Week 12 | ALT | -2.291 Units per Liter | Standard Deviation 6.9746 |
| Premarin 0.3 mg | Change From Baseline in Clinical Chemistry Parameters- Alanine Amino Transferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST) at Week 12 | ALP | -1.962 Units per Liter | Standard Deviation 11.0598 |
| Premarin 0.3 mg | Change From Baseline in Clinical Chemistry Parameters- Alanine Amino Transferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST) at Week 12 | AST | -1.228 Units per Liter | Standard Deviation 4.8831 |
Primary
Change From Baseline in Clinical Chemistry Parameters- Albumin and Total Protein at 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.
Time frame: Baseline (Week 0) and Week 12
Population: Safety Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Clinical Chemistry Parameters- Albumin and Total Protein at Week 12 | Albumin | -0.333 Gram per Liter | Standard Deviation 2.3979 |
| Placebo | Change From Baseline in Clinical Chemistry Parameters- Albumin and Total Protein at Week 12 | Total Protein | -0.519 Gram per Liter | Standard Deviation 3.6301 |
| GSK232802 25 mg | Change From Baseline in Clinical Chemistry Parameters- Albumin and Total Protein at Week 12 | Total Protein | -0.306 Gram per Liter | Standard Deviation 3.1248 |
| GSK232802 25 mg | Change From Baseline in Clinical Chemistry Parameters- Albumin and Total Protein at Week 12 | Albumin | -1.194 Gram per Liter | Standard Deviation 1.9183 |
| GSK232802 75 mg | Change From Baseline in Clinical Chemistry Parameters- Albumin and Total Protein at Week 12 | Total Protein | -0.892 Gram per Liter | Standard Deviation 3.5791 |
| GSK232802 75 mg | Change From Baseline in Clinical Chemistry Parameters- Albumin and Total Protein at Week 12 | Albumin | -1.743 Gram per Liter | Standard Deviation 2.1775 |
| Premarin 0.3 mg | Change From Baseline in Clinical Chemistry Parameters- Albumin and Total Protein at Week 12 | Albumin | -0.810 Gram per Liter | Standard Deviation 2.3484 |
| Premarin 0.3 mg | Change From Baseline in Clinical Chemistry Parameters- Albumin and Total Protein at Week 12 | Total Protein | -0.506 Gram per Liter | Standard Deviation 3.6755 |
Primary
Change From Baseline in Clinical Chemistry Parameters- Calcium, Carbon Dioxide (C02) Content, Chloride, Phosphorous, Inorganic, Potassium, Sodium and Urea at 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.
Time frame: Baseline (Week 0) and Week 12
Population: Safety Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Clinical Chemistry Parameters- Calcium, Carbon Dioxide (C02) Content, Chloride, Phosphorous, Inorganic, Potassium, Sodium and Urea at Week 12 | C02 content/bicarbonate | 0.728 Millimol per Liter | Standard Deviation 2.9284 |
| Placebo | Change From Baseline in Clinical Chemistry Parameters- Calcium, Carbon Dioxide (C02) Content, Chloride, Phosphorous, Inorganic, Potassium, Sodium and Urea at Week 12 | Phosphorous-inorganic | 0.007 Millimol per Liter | Standard Deviation 0.2167 |
| Placebo | Change From Baseline in Clinical Chemistry Parameters- Calcium, Carbon Dioxide (C02) Content, Chloride, Phosphorous, Inorganic, Potassium, Sodium and Urea at Week 12 | Sodium | -0.420 Millimol per Liter | Standard Deviation 1.8899 |
| Placebo | Change From Baseline in Clinical Chemistry Parameters- Calcium, Carbon Dioxide (C02) Content, Chloride, Phosphorous, Inorganic, Potassium, Sodium and Urea at Week 12 | Calcium | -0.009 Millimol per Liter | Standard Deviation 0.073 |
| Placebo | Change From Baseline in Clinical Chemistry Parameters- Calcium, Carbon Dioxide (C02) Content, Chloride, Phosphorous, Inorganic, Potassium, Sodium and Urea at Week 12 | Chloride | 0.012 Millimol per Liter | Standard Deviation 2.0946 |
| Placebo | Change From Baseline in Clinical Chemistry Parameters- Calcium, Carbon Dioxide (C02) Content, Chloride, Phosphorous, Inorganic, Potassium, Sodium and Urea at Week 12 | Urea | 0.102 Millimol per Liter | Standard Deviation 1.235 |
| Placebo | Change From Baseline in Clinical Chemistry Parameters- Calcium, Carbon Dioxide (C02) Content, Chloride, Phosphorous, Inorganic, Potassium, Sodium and Urea at Week 12 | Potassium | -0.049 Millimol per Liter | Standard Deviation 0.2916 |
| GSK232802 25 mg | Change From Baseline in Clinical Chemistry Parameters- Calcium, Carbon Dioxide (C02) Content, Chloride, Phosphorous, Inorganic, Potassium, Sodium and Urea at Week 12 | Urea | 0.160 Millimol per Liter | Standard Deviation 1.3445 |
| GSK232802 25 mg | Change From Baseline in Clinical Chemistry Parameters- Calcium, Carbon Dioxide (C02) Content, Chloride, Phosphorous, Inorganic, Potassium, Sodium and Urea at Week 12 | Calcium | -0.039 Millimol per Liter | Standard Deviation 0.0987 |
| GSK232802 25 mg | Change From Baseline in Clinical Chemistry Parameters- Calcium, Carbon Dioxide (C02) Content, Chloride, Phosphorous, Inorganic, Potassium, Sodium and Urea at Week 12 | Chloride | 0.389 Millimol per Liter | Standard Deviation 2.3887 |
| GSK232802 25 mg | Change From Baseline in Clinical Chemistry Parameters- Calcium, Carbon Dioxide (C02) Content, Chloride, Phosphorous, Inorganic, Potassium, Sodium and Urea at Week 12 | Potassium | -0.038 Millimol per Liter | Standard Deviation 0.4061 |
| GSK232802 25 mg | Change From Baseline in Clinical Chemistry Parameters- Calcium, Carbon Dioxide (C02) Content, Chloride, Phosphorous, Inorganic, Potassium, Sodium and Urea at Week 12 | Sodium | 0.139 Millimol per Liter | Standard Deviation 2.0849 |
| GSK232802 25 mg | Change From Baseline in Clinical Chemistry Parameters- Calcium, Carbon Dioxide (C02) Content, Chloride, Phosphorous, Inorganic, Potassium, Sodium and Urea at Week 12 | C02 content/bicarbonate | 0.014 Millimol per Liter | Standard Deviation 2.2611 |
| GSK232802 25 mg | Change From Baseline in Clinical Chemistry Parameters- Calcium, Carbon Dioxide (C02) Content, Chloride, Phosphorous, Inorganic, Potassium, Sodium and Urea at Week 12 | Phosphorous-inorganic | -0.046 Millimol per Liter | Standard Deviation 0.1525 |
| GSK232802 75 mg | Change From Baseline in Clinical Chemistry Parameters- Calcium, Carbon Dioxide (C02) Content, Chloride, Phosphorous, Inorganic, Potassium, Sodium and Urea at Week 12 | Calcium | -0.050 Millimol per Liter | Standard Deviation 0.0815 |
| GSK232802 75 mg | Change From Baseline in Clinical Chemistry Parameters- Calcium, Carbon Dioxide (C02) Content, Chloride, Phosphorous, Inorganic, Potassium, Sodium and Urea at Week 12 | Phosphorous-inorganic | -0.029 Millimol per Liter | Standard Deviation 0.3494 |
| GSK232802 75 mg | Change From Baseline in Clinical Chemistry Parameters- Calcium, Carbon Dioxide (C02) Content, Chloride, Phosphorous, Inorganic, Potassium, Sodium and Urea at Week 12 | Potassium | 0.004 Millimol per Liter | Standard Deviation 0.3134 |
| GSK232802 75 mg | Change From Baseline in Clinical Chemistry Parameters- Calcium, Carbon Dioxide (C02) Content, Chloride, Phosphorous, Inorganic, Potassium, Sodium and Urea at Week 12 | Urea | 0.385 Millimol per Liter | Standard Deviation 1.1448 |
| GSK232802 75 mg | Change From Baseline in Clinical Chemistry Parameters- Calcium, Carbon Dioxide (C02) Content, Chloride, Phosphorous, Inorganic, Potassium, Sodium and Urea at Week 12 | C02 content/bicarbonate | -0.486 Millimol per Liter | Standard Deviation 2.6651 |
| GSK232802 75 mg | Change From Baseline in Clinical Chemistry Parameters- Calcium, Carbon Dioxide (C02) Content, Chloride, Phosphorous, Inorganic, Potassium, Sodium and Urea at Week 12 | Chloride | 0.189 Millimol per Liter | Standard Deviation 2.1433 |
| GSK232802 75 mg | Change From Baseline in Clinical Chemistry Parameters- Calcium, Carbon Dioxide (C02) Content, Chloride, Phosphorous, Inorganic, Potassium, Sodium and Urea at Week 12 | Sodium | -0.608 Millimol per Liter | Standard Deviation 1.7736 |
| Premarin 0.3 mg | Change From Baseline in Clinical Chemistry Parameters- Calcium, Carbon Dioxide (C02) Content, Chloride, Phosphorous, Inorganic, Potassium, Sodium and Urea at Week 12 | Phosphorous-inorganic | -0.060 Millimol per Liter | Standard Deviation 0.1538 |
| Premarin 0.3 mg | Change From Baseline in Clinical Chemistry Parameters- Calcium, Carbon Dioxide (C02) Content, Chloride, Phosphorous, Inorganic, Potassium, Sodium and Urea at Week 12 | Calcium | -0.051 Millimol per Liter | Standard Deviation 0.0813 |
| Premarin 0.3 mg | Change From Baseline in Clinical Chemistry Parameters- Calcium, Carbon Dioxide (C02) Content, Chloride, Phosphorous, Inorganic, Potassium, Sodium and Urea at Week 12 | Urea | -0.097 Millimol per Liter | Standard Deviation 1.3095 |
| Premarin 0.3 mg | Change From Baseline in Clinical Chemistry Parameters- Calcium, Carbon Dioxide (C02) Content, Chloride, Phosphorous, Inorganic, Potassium, Sodium and Urea at Week 12 | Chloride | 0.304 Millimol per Liter | Standard Deviation 2.1204 |
| Premarin 0.3 mg | Change From Baseline in Clinical Chemistry Parameters- Calcium, Carbon Dioxide (C02) Content, Chloride, Phosphorous, Inorganic, Potassium, Sodium and Urea at Week 12 | Sodium | -0.076 Millimol per Liter | Standard Deviation 1.7743 |
| Premarin 0.3 mg | Change From Baseline in Clinical Chemistry Parameters- Calcium, Carbon Dioxide (C02) Content, Chloride, Phosphorous, Inorganic, Potassium, Sodium and Urea at Week 12 | Potassium | -0.035 Millimol per Liter | Standard Deviation 0.3955 |
| Premarin 0.3 mg | Change From Baseline in Clinical Chemistry Parameters- Calcium, Carbon Dioxide (C02) Content, Chloride, Phosphorous, Inorganic, Potassium, Sodium and Urea at Week 12 | C02 content/bicarbonate | -0.506 Millimol per Liter | Standard Deviation 2.9651 |
Primary
Change From Baseline in Clinical Chemistry Parameters- Creatinine, Direct Bilirubin, Total Bilirubin and Uric Acid at 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.
Time frame: Baseline (Week 0) and Week 12
Population: Safety Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Clinical Chemistry Parameters- Creatinine, Direct Bilirubin, Total Bilirubin and Uric Acid at Week 12 | Total bilirubin | -0.556 Micromoles per Liter | Standard Deviation 3.0083 |
| Placebo | Change From Baseline in Clinical Chemistry Parameters- Creatinine, Direct Bilirubin, Total Bilirubin and Uric Acid at Week 12 | Direct bilirubin | -0.037 Micromoles per Liter | Standard Deviation 0.7817 |
| Placebo | Change From Baseline in Clinical Chemistry Parameters- Creatinine, Direct Bilirubin, Total Bilirubin and Uric Acid at Week 12 | Creatinine | -1.765 Micromoles per Liter | Standard Deviation 5.5052 |
| Placebo | Change From Baseline in Clinical Chemistry Parameters- Creatinine, Direct Bilirubin, Total Bilirubin and Uric Acid at Week 12 | Uric acid | 1.395 Micromoles per Liter | Standard Deviation 41.3998 |
| GSK232802 25 mg | Change From Baseline in Clinical Chemistry Parameters- Creatinine, Direct Bilirubin, Total Bilirubin and Uric Acid at Week 12 | Creatinine | 0.847 Micromoles per Liter | Standard Deviation 8.3795 |
| GSK232802 25 mg | Change From Baseline in Clinical Chemistry Parameters- Creatinine, Direct Bilirubin, Total Bilirubin and Uric Acid at Week 12 | Total bilirubin | -0.667 Micromoles per Liter | Standard Deviation 3.9611 |
| GSK232802 25 mg | Change From Baseline in Clinical Chemistry Parameters- Creatinine, Direct Bilirubin, Total Bilirubin and Uric Acid at Week 12 | Uric acid | 0.278 Micromoles per Liter | Standard Deviation 42.8302 |
| GSK232802 25 mg | Change From Baseline in Clinical Chemistry Parameters- Creatinine, Direct Bilirubin, Total Bilirubin and Uric Acid at Week 12 | Direct bilirubin | -0.097 Micromoles per Liter | Standard Deviation 0.7152 |
| GSK232802 75 mg | Change From Baseline in Clinical Chemistry Parameters- Creatinine, Direct Bilirubin, Total Bilirubin and Uric Acid at Week 12 | Creatinine | 0.811 Micromoles per Liter | Standard Deviation 6.6676 |
| GSK232802 75 mg | Change From Baseline in Clinical Chemistry Parameters- Creatinine, Direct Bilirubin, Total Bilirubin and Uric Acid at Week 12 | Uric acid | 11.324 Micromoles per Liter | Standard Deviation 40.0196 |
| GSK232802 75 mg | Change From Baseline in Clinical Chemistry Parameters- Creatinine, Direct Bilirubin, Total Bilirubin and Uric Acid at Week 12 | Direct bilirubin | -0.122 Micromoles per Liter | Standard Deviation 0.8432 |
| GSK232802 75 mg | Change From Baseline in Clinical Chemistry Parameters- Creatinine, Direct Bilirubin, Total Bilirubin and Uric Acid at Week 12 | Total bilirubin | -1.324 Micromoles per Liter | Standard Deviation 2.8579 |
| Premarin 0.3 mg | Change From Baseline in Clinical Chemistry Parameters- Creatinine, Direct Bilirubin, Total Bilirubin and Uric Acid at Week 12 | Total bilirubin | -0.646 Micromoles per Liter | Standard Deviation 3.0215 |
| Premarin 0.3 mg | Change From Baseline in Clinical Chemistry Parameters- Creatinine, Direct Bilirubin, Total Bilirubin and Uric Acid at Week 12 | Uric acid | 1.532 Micromoles per Liter | Standard Deviation 37.4983 |
| Premarin 0.3 mg | Change From Baseline in Clinical Chemistry Parameters- Creatinine, Direct Bilirubin, Total Bilirubin and Uric Acid at Week 12 | Creatinine | -0.506 Micromoles per Liter | Standard Deviation 7.1052 |
| Premarin 0.3 mg | Change From Baseline in Clinical Chemistry Parameters- Creatinine, Direct Bilirubin, Total Bilirubin and Uric Acid at Week 12 | Direct bilirubin | -0.076 Micromoles per Liter | Standard Deviation 0.8129 |
Primary
Change From Baseline in Fasting Lipid Profile at 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.
Time frame: Baseline (Week 0) and Week 12
Population: Safety Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Fasting Lipid Profile at Week 12 | Triglycerides | -0.060 Millimole per Liter | Standard Deviation 0.748 |
| Placebo | Change From Baseline in Fasting Lipid Profile at Week 12 | Cholesterol | 0.055 Millimole per Liter | Standard Deviation 0.7977 |
| Placebo | Change From Baseline in Fasting Lipid Profile at Week 12 | HDL cholestereol, direct | 0.047 Millimole per Liter | Standard Deviation 0.1851 |
| Placebo | Change From Baseline in Fasting Lipid Profile at Week 12 | LDL cholesterol | 0.030 Millimole per Liter | Standard Deviation 0.6987 |
| GSK232802 25 mg | Change From Baseline in Fasting Lipid Profile at Week 12 | HDL cholestereol, direct | 0.093 Millimole per Liter | Standard Deviation 0.2296 |
| GSK232802 25 mg | Change From Baseline in Fasting Lipid Profile at Week 12 | Triglycerides | 0.309 Millimole per Liter | Standard Deviation 0.4718 |
| GSK232802 25 mg | Change From Baseline in Fasting Lipid Profile at Week 12 | Cholesterol | 0.019 Millimole per Liter | Standard Deviation 0.56 |
| GSK232802 25 mg | Change From Baseline in Fasting Lipid Profile at Week 12 | LDL cholesterol | -0.221 Millimole per Liter | Standard Deviation 0.4564 |
| GSK232802 75 mg | Change From Baseline in Fasting Lipid Profile at Week 12 | HDL cholestereol, direct | 0.070 Millimole per Liter | Standard Deviation 0.2184 |
| GSK232802 75 mg | Change From Baseline in Fasting Lipid Profile at Week 12 | LDL cholesterol | -0.430 Millimole per Liter | Standard Deviation 0.529 |
| GSK232802 75 mg | Change From Baseline in Fasting Lipid Profile at Week 12 | Triglycerides | 0.370 Millimole per Liter | Standard Deviation 0.6892 |
| GSK232802 75 mg | Change From Baseline in Fasting Lipid Profile at Week 12 | Cholesterol | -0.203 Millimole per Liter | Standard Deviation 0.5985 |
| Premarin 0.3 mg | Change From Baseline in Fasting Lipid Profile at Week 12 | Cholesterol | -0.062 Millimole per Liter | Standard Deviation 0.73 |
| Premarin 0.3 mg | Change From Baseline in Fasting Lipid Profile at Week 12 | HDL cholestereol, direct | 0.069 Millimole per Liter | Standard Deviation 0.2357 |
| Premarin 0.3 mg | Change From Baseline in Fasting Lipid Profile at Week 12 | LDL cholesterol | 0.208 Millimole per Liter | Standard Deviation 0.6744 |
| Premarin 0.3 mg | Change From Baseline in Fasting Lipid Profile at Week 12 | Triglycerides | 0.166 Millimole per Liter | Standard Deviation 0.4941 |
Primary
Change From Baseline in Hematology Parameter- Mean Corpuscle Hemoglobin (MCH) at Week 12
Hematology parameter included MCH. Baseline was Week 0. Change from Baseline was calculated by subtracting Baseline values from post-Baseline values.
Time frame: Baseline (Week 0) and Week 12
Population: Safety Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Hematology Parameter- Mean Corpuscle Hemoglobin (MCH) at Week 12 | -0.260 Picograms | Standard Deviation 0.6118 |
| GSK232802 25 mg | Change From Baseline in Hematology Parameter- Mean Corpuscle Hemoglobin (MCH) at Week 12 | -0.221 Picograms | Standard Deviation 0.6094 |
| GSK232802 75 mg | Change From Baseline in Hematology Parameter- Mean Corpuscle Hemoglobin (MCH) at Week 12 | -0.207 Picograms | Standard Deviation 0.6878 |
| Premarin 0.3 mg | Change From Baseline in Hematology Parameter- Mean Corpuscle Hemoglobin (MCH) at Week 12 | -0.326 Picograms | Standard Deviation 0.6005 |
Primary
Change From Baseline in Hematology Parameter- Mean Corpuscle Volume (MCV) at Week 12
Hematology parameter included MCV. Baseline was Week 0. Change from Baseline was calculated by subtracting Baseline values from post-Baseline values.
Time frame: Baseline (Week 0) and Week 12
Population: Safety Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Hematology Parameter- Mean Corpuscle Volume (MCV) at Week 12 | -0.813 Femtoliters | Standard Deviation 1.8356 |
| GSK232802 25 mg | Change From Baseline in Hematology Parameter- Mean Corpuscle Volume (MCV) at Week 12 | -0.169 Femtoliters | Standard Deviation 2.1179 |
| GSK232802 75 mg | Change From Baseline in Hematology Parameter- Mean Corpuscle Volume (MCV) at Week 12 | -0.694 Femtoliters | Standard Deviation 2.2558 |
| Premarin 0.3 mg | Change From Baseline in Hematology Parameter- Mean Corpuscle Volume (MCV) at Week 12 | -0.368 Femtoliters | Standard Deviation 1.7802 |
Primary
Change From Baseline in Hematology Parameter- Red Blood Cell (RBC) Count at Week 12
Hematology parameter included RBC count. Baseline was Week 0. Change from Baseline was calculated by subtracting Baseline values from post-Baseline values.
Time frame: Baseline (Week 0) and Week 12
Population: Safety Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Hematology Parameter- Red Blood Cell (RBC) Count at Week 12 | 0.005 Trillion cells per Liter | Standard Deviation 0.3073 |
| GSK232802 25 mg | Change From Baseline in Hematology Parameter- Red Blood Cell (RBC) Count at Week 12 | -0.059 Trillion cells per Liter | Standard Deviation 0.1833 |
| GSK232802 75 mg | Change From Baseline in Hematology Parameter- Red Blood Cell (RBC) Count at Week 12 | -0.179 Trillion cells per Liter | Standard Deviation 0.3053 |
| Premarin 0.3 mg | Change From Baseline in Hematology Parameter- Red Blood Cell (RBC) Count at Week 12 | -0.005 Trillion cells per Liter | Standard Deviation 0.2103 |
Primary
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
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.
Time frame: Baseline (Week 0) and Week 12
Population: Safety Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | 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 | Basophils | -0.000 Gigacells per Liter | Standard Deviation 0.0186 |
| Placebo | 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 | Lymphocytes | 0.025 Gigacells per Liter | Standard Deviation 0.4305 |
| Placebo | 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 | Eosinophils | -0.000 Gigacells per Liter | Standard Deviation 0.0686 |
| Placebo | 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 | Monocytes | 0.021 Gigacells per Liter | Standard Deviation 0.0903 |
| Placebo | 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 | Platelet count | -4.463 Gigacells per Liter | Standard Deviation 28.6153 |
| Placebo | 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 | Segmented neutrophils | -0.126 Gigacells per Liter | Standard Deviation 0.8908 |
| Placebo | 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 | Total neutrophils | -0.127 Gigacells per Liter | Standard Deviation 0.8909 |
| Placebo | 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 | WBC count | -0.078 Gigacells per Liter | Standard Deviation 1.1316 |
| GSK232802 25 mg | 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 | Total neutrophils | 0.160 Gigacells per Liter | Standard Deviation 0.9377 |
| GSK232802 25 mg | 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 | Monocytes | -0.008 Gigacells per Liter | Standard Deviation 0.1224 |
| GSK232802 25 mg | 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 | WBC count | 0.265 Gigacells per Liter | Standard Deviation 1.078 |
| GSK232802 25 mg | 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 | Lymphocytes | 0.121 Gigacells per Liter | Standard Deviation 0.3786 |
| GSK232802 25 mg | 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 | Basophils | 0.000 Gigacells per Liter | Standard Deviation 0.0186 |
| GSK232802 25 mg | 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 | Segmented neutrophils | 0.160 Gigacells per Liter | Standard Deviation 0.9377 |
| GSK232802 25 mg | 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 | Eosinophils | -0.008 Gigacells per Liter | Standard Deviation 0.0789 |
| GSK232802 25 mg | 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 | Platelet count | -8.507 Gigacells per Liter | Standard Deviation 28.6061 |
| GSK232802 75 mg | 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 | Total neutrophils | -0.076 Gigacells per Liter | Standard Deviation 1.0209 |
| GSK232802 75 mg | 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 | Basophils | 0.002 Gigacells per Liter | Standard Deviation 0.0185 |
| GSK232802 75 mg | 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 | WBC count | -0.043 Gigacells per Liter | Standard Deviation 1.1956 |
| GSK232802 75 mg | 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 | Eosinophils | 0.004 Gigacells per Liter | Standard Deviation 0.107 |
| GSK232802 75 mg | 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 | Lymphocytes | 0.020 Gigacells per Liter | Standard Deviation 0.3901 |
| GSK232802 75 mg | 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 | Monocytes | 0.007 Gigacells per Liter | Standard Deviation 0.1033 |
| GSK232802 75 mg | 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 | Segmented neutrophils | -0.076 Gigacells per Liter | Standard Deviation 1.0209 |
| GSK232802 75 mg | 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 | Platelet count | -7.127 Gigacells per Liter | Standard Deviation 33.4873 |
| Premarin 0.3 mg | 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 | Basophils | -0.002 Gigacells per Liter | Standard Deviation 0.0192 |
| Premarin 0.3 mg | 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 | WBC count | 0.042 Gigacells per Liter | Standard Deviation 0.938 |
| Premarin 0.3 mg | 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 | Eosinophils | -0.005 Gigacells per Liter | Standard Deviation 0.0788 |
| Premarin 0.3 mg | 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 | Segmented neutrophils | 0.044 Gigacells per Liter | Standard Deviation 0.8687 |
| Premarin 0.3 mg | 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 | Monocytes | -0.007 Gigacells per Liter | Standard Deviation 0.134 |
| Premarin 0.3 mg | 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 | Lymphocytes | 0.013 Gigacells per Liter | Standard Deviation 0.3742 |
| Premarin 0.3 mg | 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 | Total neutrophils | 0.043 Gigacells per Liter | Standard Deviation 0.8686 |
| Premarin 0.3 mg | 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 | Platelet count | -1.316 Gigacells per Liter | Standard Deviation 53.4174 |
Primary
Change From Baseline in Hematology Parameters- Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) at 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.
Time frame: Baseline (Week 0) and Week 12
Population: Safety Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Hematology Parameters- Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) at Week 12 | Hemoglobin | -1.275 Gram per Liter | Standard Deviation 8.9216 |
| Placebo | Change From Baseline in Hematology Parameters- Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) at Week 12 | MCHC | -0.275 Gram per Liter | Standard Deviation 8.2768 |
| GSK232802 25 mg | Change From Baseline in Hematology Parameters- Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) at Week 12 | MCHC | -2.000 Gram per Liter | Standard Deviation 9.0885 |
| GSK232802 25 mg | Change From Baseline in Hematology Parameters- Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) at Week 12 | Hemoglobin | -2.887 Gram per Liter | Standard Deviation 5.605 |
| GSK232802 75 mg | Change From Baseline in Hematology Parameters- Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) at Week 12 | Hemoglobin | -5.944 Gram per Liter | Standard Deviation 8.3293 |
| GSK232802 75 mg | Change From Baseline in Hematology Parameters- Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) at Week 12 | MCHC | 0.500 Gram per Liter | Standard Deviation 11.1381 |
| Premarin 0.3 mg | Change From Baseline in Hematology Parameters- Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) at Week 12 | Hemoglobin | -1.382 Gram per Liter | Standard Deviation 6.3476 |
| Premarin 0.3 mg | Change From Baseline in Hematology Parameters- Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) at Week 12 | MCHC | -2.079 Gram per Liter | Standard Deviation 8.0957 |
Primary
Change From Baseline in Thrombotic Marker- Fibrinogen at Week 12
Thrombotic marker included fibrinogen. Baseline was Week 0. Change from Baseline was calculated by subtracting Baseline values from post-Baseline values.
Time frame: Baseline (Week 0) and Week 12
Population: Safety Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Thrombotic Marker- Fibrinogen at Week 12 | -0.081 Gram per LIter | Standard Deviation 0.5889 |
| GSK232802 25 mg | Change From Baseline in Thrombotic Marker- Fibrinogen at Week 12 | -0.246 Gram per LIter | Standard Deviation 0.8377 |
| GSK232802 75 mg | Change From Baseline in Thrombotic Marker- Fibrinogen at Week 12 | -0.293 Gram per LIter | Standard Deviation 0.6487 |
| Premarin 0.3 mg | Change From Baseline in Thrombotic Marker- Fibrinogen at Week 12 | -0.198 Gram per LIter | Standard Deviation 0.5291 |
Primary
Change From Baseline in Thrombotic Marker- Tissue Plasminogen Activator (tPA) Antigen at Week 12
Thrombotic marker included tPA antigen. Baseline was Week 0. Change from Baseline was calculated by subtracting Baseline values from post-Baseline values.
Time frame: Baseline (Week 0) and Week 12
Population: Safety Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Thrombotic Marker- Tissue Plasminogen Activator (tPA) Antigen at Week 12 | 0.200 Microgram per Liter | Standard Deviation 3.0996 |
| GSK232802 25 mg | Change From Baseline in Thrombotic Marker- Tissue Plasminogen Activator (tPA) Antigen at Week 12 | -0.139 Microgram per Liter | Standard Deviation 2.2818 |
| GSK232802 75 mg | Change From Baseline in Thrombotic Marker- Tissue Plasminogen Activator (tPA) Antigen at Week 12 | -1.224 Microgram per Liter | Standard Deviation 2.8039 |
| Premarin 0.3 mg | Change From Baseline in Thrombotic Marker- Tissue Plasminogen Activator (tPA) Antigen at Week 12 | 0.115 Microgram per Liter | Standard Deviation 2.4548 |
Primary
Change From Baseline in Thyroid Stimulating Hormone (TSH) at 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.
Time frame: Baseline (Week 0) and Week 12
Population: Safety Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Thyroid Stimulating Hormone (TSH) at Week 12 | 0.236 Milliunits/Liter | Standard Deviation 0.8942 |
| GSK232802 25 mg | Change From Baseline in Thyroid Stimulating Hormone (TSH) at Week 12 | 0.034 Milliunits/Liter | Standard Deviation 0.9951 |
| GSK232802 75 mg | Change From Baseline in Thyroid Stimulating Hormone (TSH) at Week 12 | 0.397 Milliunits/Liter | Standard Deviation 1.3453 |
| Premarin 0.3 mg | Change From Baseline in Thyroid Stimulating Hormone (TSH) at Week 12 | 0.238 Milliunits/Liter | Standard Deviation 0.928 |
Primary
Change From Baseline in Thyroxine (T4) and Insulin at 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.
Time frame: Baseline (Week 0) and Week 12
Population: Safety Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Thyroxine (T4) and Insulin at Week 12 | T4 | -0.190 Picomole per Liter | Standard Deviation 1.866 |
| Placebo | Change From Baseline in Thyroxine (T4) and Insulin at Week 12 | Insulin | 12.747 Picomole per Liter | Standard Deviation 83.3643 |
| GSK232802 25 mg | Change From Baseline in Thyroxine (T4) and Insulin at Week 12 | Insulin | 4.563 Picomole per Liter | Standard Deviation 49.232 |
| GSK232802 25 mg | Change From Baseline in Thyroxine (T4) and Insulin at Week 12 | T4 | -0.350 Picomole per Liter | Standard Deviation 1.6473 |
| GSK232802 75 mg | Change From Baseline in Thyroxine (T4) and Insulin at Week 12 | Insulin | 3.205 Picomole per Liter | Standard Deviation 44.1258 |
| GSK232802 75 mg | Change From Baseline in Thyroxine (T4) and Insulin at Week 12 | T4 | -0.582 Picomole per Liter | Standard Deviation 1.6272 |
| Premarin 0.3 mg | Change From Baseline in Thyroxine (T4) and Insulin at Week 12 | T4 | -0.425 Picomole per Liter | Standard Deviation 1.8863 |
| Premarin 0.3 mg | Change From Baseline in Thyroxine (T4) and Insulin at Week 12 | Insulin | -19.297 Picomole per Liter | Standard Deviation 137.5697 |
Primary
Change From Baseline in Vital Sign of Heart Rate at 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.
Time frame: Baseline (Week 0) and Week 12
Population: Safety Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Vital Sign of Heart Rate at Week 12 | -0.2 Beats per minute | Standard Deviation 9.84 |
| GSK232802 25 mg | Change From Baseline in Vital Sign of Heart Rate at Week 12 | 0.6 Beats per minute | Standard Deviation 8.27 |
| GSK232802 75 mg | Change From Baseline in Vital Sign of Heart Rate at Week 12 | 2.8 Beats per minute | Standard Deviation 8.09 |
| Premarin 0.3 mg | Change From Baseline in Vital Sign of Heart Rate at Week 12 | 0.3 Beats per minute | Standard Deviation 9.66 |
Primary
Change From Baseline in Vital Signs of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at 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.
Time frame: Baseline (Week 0) and Week 12
Population: Safety Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Vital Signs of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Week 12 | SBP | 2.6 Millimeters of mercury | Standard Deviation 15.26 |
| Placebo | Change From Baseline in Vital Signs of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Week 12 | DBP | 0.1 Millimeters of mercury | Standard Deviation 8.38 |
| GSK232802 25 mg | Change From Baseline in Vital Signs of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Week 12 | DBP | 1.0 Millimeters of mercury | Standard Deviation 9.28 |
| GSK232802 25 mg | Change From Baseline in Vital Signs of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Week 12 | SBP | 1.8 Millimeters of mercury | Standard Deviation 12.19 |
| GSK232802 75 mg | Change From Baseline in Vital Signs of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Week 12 | SBP | -1.6 Millimeters of mercury | Standard Deviation 11.04 |
| GSK232802 75 mg | Change From Baseline in Vital Signs of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Week 12 | DBP | 0.7 Millimeters of mercury | Standard Deviation 7.04 |
| Premarin 0.3 mg | Change From Baseline in Vital Signs of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Week 12 | SBP | -0.4 Millimeters of mercury | Standard Deviation 12.61 |
| Premarin 0.3 mg | Change From Baseline in Vital Signs of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Week 12 | DBP | -0.1 Millimeters of mercury | Standard Deviation 9.06 |
Primary
Endometrial Biopsy Pathology
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).
Time frame: Baseline (Week 0) to Week 12
Population: Uterine safety Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Placebo | Endometrial Biopsy Pathology | End of treatment | Proliferative endometrium | 0 Participants |
| Placebo | Endometrial Biopsy Pathology | End of treatment | Progestational endometrium | 0 Participants |
| Placebo | Endometrial Biopsy Pathology | End of treatment | Polyp | 0 Participants |
| Placebo | Endometrial Biopsy Pathology | Baseline | Normal | 29 Participants |
| Placebo | Endometrial Biopsy Pathology | Baseline | Proliferative endometrium | 1 Participants |
| Placebo | Endometrial Biopsy Pathology | Baseline | No tissue/insufficient tissue | 23 Participants |
| Placebo | Endometrial Biopsy Pathology | End of treatment | Normal | 19 Participants |
| Placebo | Endometrial Biopsy Pathology | Baseline | Progestational endometrium | 0 Participants |
| Placebo | Endometrial Biopsy Pathology | Baseline | Polyp | 0 Participants |
| Placebo | Endometrial Biopsy Pathology | End of treatment | No tissue/insufficient tissue | 23 Participants |
| GSK232802 25 mg | Endometrial Biopsy Pathology | End of treatment | Polyp | 0 Participants |
| GSK232802 25 mg | Endometrial Biopsy Pathology | Baseline | Normal | 33 Participants |
| GSK232802 25 mg | Endometrial Biopsy Pathology | Baseline | No tissue/insufficient tissue | 19 Participants |
| GSK232802 25 mg | Endometrial Biopsy Pathology | Baseline | Proliferative endometrium | 0 Participants |
| GSK232802 25 mg | Endometrial Biopsy Pathology | Baseline | Polyp | 0 Participants |
| GSK232802 25 mg | Endometrial Biopsy Pathology | End of treatment | Proliferative endometrium | 1 Participants |
| GSK232802 25 mg | Endometrial Biopsy Pathology | End of treatment | No tissue/insufficient tissue | 19 Participants |
| GSK232802 25 mg | Endometrial Biopsy Pathology | End of treatment | Normal | 27 Participants |
| GSK232802 25 mg | Endometrial Biopsy Pathology | End of treatment | Progestational endometrium | 0 Participants |
| GSK232802 25 mg | Endometrial Biopsy Pathology | Baseline | Progestational endometrium | 1 Participants |
| GSK232802 75 mg | Endometrial Biopsy Pathology | End of treatment | Polyp | 0 Participants |
| GSK232802 75 mg | Endometrial Biopsy Pathology | Baseline | Progestational endometrium | 0 Participants |
| GSK232802 75 mg | Endometrial Biopsy Pathology | End of treatment | Progestational endometrium | 0 Participants |
| GSK232802 75 mg | Endometrial Biopsy Pathology | Baseline | Normal | 34 Participants |
| GSK232802 75 mg | Endometrial Biopsy Pathology | End of treatment | Normal | 24 Participants |
| GSK232802 75 mg | Endometrial Biopsy Pathology | Baseline | Polyp | 0 Participants |
| GSK232802 75 mg | Endometrial Biopsy Pathology | End of treatment | No tissue/insufficient tissue | 16 Participants |
| GSK232802 75 mg | Endometrial Biopsy Pathology | Baseline | No tissue/insufficient tissue | 17 Participants |
| GSK232802 75 mg | Endometrial Biopsy Pathology | End of treatment | Proliferative endometrium | 0 Participants |
| GSK232802 75 mg | Endometrial Biopsy Pathology | Baseline | Proliferative endometrium | 1 Participants |
| Premarin 0.3 mg | Endometrial Biopsy Pathology | End of treatment | Polyp | 1 Participants |
| Premarin 0.3 mg | Endometrial Biopsy Pathology | Baseline | Polyp | 0 Participants |
| Premarin 0.3 mg | Endometrial Biopsy Pathology | End of treatment | Normal | 31 Participants |
| Premarin 0.3 mg | Endometrial Biopsy Pathology | Baseline | Normal | 31 Participants |
| Premarin 0.3 mg | Endometrial Biopsy Pathology | Baseline | Proliferative endometrium | 0 Participants |
| Premarin 0.3 mg | Endometrial Biopsy Pathology | Baseline | Progestational endometrium | 0 Participants |
| Premarin 0.3 mg | Endometrial Biopsy Pathology | End of treatment | No tissue/insufficient tissue | 9 Participants |
| Premarin 0.3 mg | Endometrial Biopsy Pathology | End of treatment | Proliferative endometrium | 3 Participants |
| Premarin 0.3 mg | Endometrial Biopsy Pathology | End of treatment | Progestational endometrium | 1 Participants |
| Premarin 0.3 mg | Endometrial Biopsy Pathology | Baseline | No tissue/insufficient tissue | 20 Participants |
Primary
Mean Change in Frequency of Vasomotor Symptoms (VMS) From Baseline at 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.
Time frame: Baseline (Week 0) and Week 12
Population: Intent-to-Treat Population (ITT) Population which comprised of all randomized participants. Last Observation Carried Forward (LOCF) was the imputation technique used.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Change in Frequency of Vasomotor Symptoms (VMS) From Baseline at Week 12 | -5.53 Scores on a Scale | Standard Error 0.466 |
| GSK232802 25 mg | Mean Change in Frequency of Vasomotor Symptoms (VMS) From Baseline at Week 12 | -4.78 Scores on a Scale | Standard Error 0.522 |
| GSK232802 75 mg | Mean Change in Frequency of Vasomotor Symptoms (VMS) From Baseline at Week 12 | -4.31 Scores on a Scale | Standard Error 0.5 |
| Premarin 0.3 mg | Mean Change in Frequency of Vasomotor Symptoms (VMS) From Baseline at Week 12 | -7.59 Scores on a Scale | Standard Error 0.479 |
Comparison: Placebo vs. GSK232802 25 mgp-value: 0.21595% CI: [-0.44, 1.93]General linear model
Comparison: Placebo vs. GSK232802 75 mgp-value: 0.04195% CI: [0.05, 2.37]General linear model
Comparison: Placebo vs. Premarin 0.3 mgp-value: <0.00195% CI: [-3.2, -0.92]General linear model
Primary
Mean Change in Severity of VMS From Baseline at 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.
Time frame: Baseline (Week 0) and Week 12
Population: ITT Population with LOCF analysis. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Change in Severity of VMS From Baseline at Week 12 | -0.37 Scores on a Scale | Standard Error 0.093 |
| GSK232802 25 mg | Mean Change in Severity of VMS From Baseline at Week 12 | -0.21 Scores on a Scale | Standard Error 0.104 |
| GSK232802 75 mg | Mean Change in Severity of VMS From Baseline at Week 12 | -0.05 Scores on a Scale | Standard Error 0.099 |
| Premarin 0.3 mg | Mean Change in Severity of VMS From Baseline at Week 12 | -0.89 Scores on a Scale | Standard Error 0.095 |
Comparison: Placebo vs. GSK232802 25 mgp-value: 0.20295% CI: [-0.08, 0.38]General linear model
Comparison: Placebo vs. GSK232802 75 mgp-value: 0.00895% CI: [0.08, 0.54]General linear model
Comparison: Placebo vs. Premarin 0.3 mgp-value: <0.00195% CI: [-0.75, -0.3]General linear model
Primary
Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) and Number of Participants With Mild, Moderate and Severe AE
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.
Time frame: Up to 21 weeks
Population: Safety Population which comprised of all randomized participants who received at least one dose of investigational product.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) and Number of Participants With Mild, Moderate and Severe AE | AE | 54 Participants |
| Placebo | Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) and Number of Participants With Mild, Moderate and Severe AE | SAE | 2 Participants |
| Placebo | Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) and Number of Participants With Mild, Moderate and Severe AE | Severe AE | 5 Participants |
| Placebo | Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) and Number of Participants With Mild, Moderate and Severe AE | Mild AE | 19 Participants |
| Placebo | Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) and Number of Participants With Mild, Moderate and Severe AE | Moderate AE | 30 Participants |
| GSK232802 25 mg | Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) and Number of Participants With Mild, Moderate and Severe AE | Mild AE | 20 Participants |
| GSK232802 25 mg | Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) and Number of Participants With Mild, Moderate and Severe AE | Moderate AE | 25 Participants |
| GSK232802 25 mg | Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) and Number of Participants With Mild, Moderate and Severe AE | Severe AE | 7 Participants |
| GSK232802 25 mg | Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) and Number of Participants With Mild, Moderate and Severe AE | AE | 52 Participants |
| GSK232802 25 mg | Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) and Number of Participants With Mild, Moderate and Severe AE | SAE | 0 Participants |
| GSK232802 75 mg | Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) and Number of Participants With Mild, Moderate and Severe AE | AE | 45 Participants |
| GSK232802 75 mg | Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) and Number of Participants With Mild, Moderate and Severe AE | SAE | 1 Participants |
| GSK232802 75 mg | Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) and Number of Participants With Mild, Moderate and Severe AE | Mild AE | 8 Participants |
| GSK232802 75 mg | Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) and Number of Participants With Mild, Moderate and Severe AE | Moderate AE | 32 Participants |
| GSK232802 75 mg | Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) and Number of Participants With Mild, Moderate and Severe AE | Severe AE | 4 Participants |
| Premarin 0.3 mg | Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) and Number of Participants With Mild, Moderate and Severe AE | Mild AE | 18 Participants |
| Premarin 0.3 mg | Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) and Number of Participants With Mild, Moderate and Severe AE | AE | 51 Participants |
| Premarin 0.3 mg | Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) and Number of Participants With Mild, Moderate and Severe AE | Severe AE | 10 Participants |
| Premarin 0.3 mg | Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) and Number of Participants With Mild, Moderate and Severe AE | Moderate AE | 23 Participants |
| Premarin 0.3 mg | Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) and Number of Participants With Mild, Moderate and Severe AE | SAE | 1 Participants |
Primary
Occurrence of Withdrawal Bleeding-duration of Spotting/Bleeding
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.
Time frame: Up to Follow-up (Day 112)
Population: Uterine Safety Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Occurrence of Withdrawal Bleeding-duration of Spotting/Bleeding | 0.0 Days |
| GSK232802 25 mg | Occurrence of Withdrawal Bleeding-duration of Spotting/Bleeding | 0.0 Days |
| GSK232802 75 mg | Occurrence of Withdrawal Bleeding-duration of Spotting/Bleeding | 0.0 Days |
| Premarin 0.3 mg | Occurrence of Withdrawal Bleeding-duration of Spotting/Bleeding | 1.0 Days |
Primary
Occurrence of Withdrawal Bleeding-number of Days of Spotting, Number of Days of Bleeding, Number of Days of Spotting/Bleeding Combined
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.
Time frame: Up to Follow-up (Day 112)
Population: Uterine Safety Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | Occurrence of Withdrawal Bleeding-number of Days of Spotting, Number of Days of Bleeding, Number of Days of Spotting/Bleeding Combined | Number of days of spotting/bleeding combined | 0.0 Days |
| Placebo | Occurrence of Withdrawal Bleeding-number of Days of Spotting, Number of Days of Bleeding, Number of Days of Spotting/Bleeding Combined | Number of days of bleeding | 0.0 Days |
| Placebo | Occurrence of Withdrawal Bleeding-number of Days of Spotting, Number of Days of Bleeding, Number of Days of Spotting/Bleeding Combined | Number of days of spotting | 0.0 Days |
| GSK232802 25 mg | Occurrence of Withdrawal Bleeding-number of Days of Spotting, Number of Days of Bleeding, Number of Days of Spotting/Bleeding Combined | Number of days of bleeding | 0.0 Days |
| GSK232802 25 mg | Occurrence of Withdrawal Bleeding-number of Days of Spotting, Number of Days of Bleeding, Number of Days of Spotting/Bleeding Combined | Number of days of spotting | 0.0 Days |
| GSK232802 25 mg | Occurrence of Withdrawal Bleeding-number of Days of Spotting, Number of Days of Bleeding, Number of Days of Spotting/Bleeding Combined | Number of days of spotting/bleeding combined | 0.0 Days |
| GSK232802 75 mg | Occurrence of Withdrawal Bleeding-number of Days of Spotting, Number of Days of Bleeding, Number of Days of Spotting/Bleeding Combined | Number of days of spotting | 0.0 Days |
| GSK232802 75 mg | Occurrence of Withdrawal Bleeding-number of Days of Spotting, Number of Days of Bleeding, Number of Days of Spotting/Bleeding Combined | Number of days of bleeding | 0.0 Days |
| GSK232802 75 mg | Occurrence of Withdrawal Bleeding-number of Days of Spotting, Number of Days of Bleeding, Number of Days of Spotting/Bleeding Combined | Number of days of spotting/bleeding combined | 0.0 Days |
| Premarin 0.3 mg | Occurrence of Withdrawal Bleeding-number of Days of Spotting, Number of Days of Bleeding, Number of Days of Spotting/Bleeding Combined | Number of days of bleeding | 0.0 Days |
| Premarin 0.3 mg | Occurrence of Withdrawal Bleeding-number of Days of Spotting, Number of Days of Bleeding, Number of Days of Spotting/Bleeding Combined | Number of days of spotting/bleeding combined | 1.0 Days |
| Premarin 0.3 mg | Occurrence of Withdrawal Bleeding-number of Days of Spotting, Number of Days of Bleeding, Number of Days of Spotting/Bleeding Combined | Number of days of spotting | 0.0 Days |
Secondary
Change From Baseline at Week 12 in Abdomen Body Circumference, Abdomen Saggital Diameter and Thigh Circumference
Thigh circumference was measured on the left leg directly below the gluteal fold; with the participant standing with both arms at the side, feet together, and with equal weight on both feet when this measurement was taken. The thigh was measured at least twice until two measurements were within 1 centimeter, and the last reading recorded. Abdomen body circumference and abdomen saggital diameter was measured in centimeter to once decimal place by Computerized tomography (CT) scan with the participant in supine position. CT scan of the abdomen was conducted at the Lumbar 4 vertebrae level. Scans were performed with 120 kilovolts, 5 millimeter slice thickness and 48 centimeter scan field of view. Baseline was Week 0. Change from Baseline was calculated by subtracting Baseline values from post-Baseline values.
Time frame: Baseline (Week 0) and Week 12
Population: Body Composition Population which comprised of any ITT participants who provided consent for the body composition sub-study and received additional body composition assessments. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline at Week 12 in Abdomen Body Circumference, Abdomen Saggital Diameter and Thigh Circumference | Thigh circumference | 0.13 Centimeters | Standard Deviation 0.15 |
| Placebo | Change From Baseline at Week 12 in Abdomen Body Circumference, Abdomen Saggital Diameter and Thigh Circumference | Abdomen body circumference | -1.20 Centimeters | Standard Deviation 2.963 |
| Placebo | Change From Baseline at Week 12 in Abdomen Body Circumference, Abdomen Saggital Diameter and Thigh Circumference | Abdomen saggital circumference | -0.50 Centimeters | Standard Deviation 1.236 |
| GSK232802 25 mg | Change From Baseline at Week 12 in Abdomen Body Circumference, Abdomen Saggital Diameter and Thigh Circumference | Abdomen saggital circumference | -0.04 Centimeters | Standard Deviation 0.841 |
| GSK232802 25 mg | Change From Baseline at Week 12 in Abdomen Body Circumference, Abdomen Saggital Diameter and Thigh Circumference | Abdomen body circumference | -0.30 Centimeters | Standard Deviation 1.739 |
| GSK232802 25 mg | Change From Baseline at Week 12 in Abdomen Body Circumference, Abdomen Saggital Diameter and Thigh Circumference | Thigh circumference | 0.00 Centimeters | Standard Deviation 0.797 |
| GSK232802 75 mg | Change From Baseline at Week 12 in Abdomen Body Circumference, Abdomen Saggital Diameter and Thigh Circumference | Abdomen saggital circumference | 0.17 Centimeters | Standard Deviation 0.379 |
| GSK232802 75 mg | Change From Baseline at Week 12 in Abdomen Body Circumference, Abdomen Saggital Diameter and Thigh Circumference | Abdomen body circumference | 2.07 Centimeters | Standard Deviation 3.066 |
| GSK232802 75 mg | Change From Baseline at Week 12 in Abdomen Body Circumference, Abdomen Saggital Diameter and Thigh Circumference | Thigh circumference | 0.23 Centimeters | Standard Deviation 0.961 |
| Premarin 0.3 mg | Change From Baseline at Week 12 in Abdomen Body Circumference, Abdomen Saggital Diameter and Thigh Circumference | Abdomen body circumference | -1.90 Centimeters | Standard Deviation 2.884 |
| Premarin 0.3 mg | Change From Baseline at Week 12 in Abdomen Body Circumference, Abdomen Saggital Diameter and Thigh Circumference | Thigh circumference | -0.07 Centimeters | Standard Deviation 2.25 |
| Premarin 0.3 mg | Change From Baseline at Week 12 in Abdomen Body Circumference, Abdomen Saggital Diameter and Thigh Circumference | Abdomen saggital circumference | -0.77 Centimeters | Standard Deviation 1.002 |
Secondary
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)
AVAT, ASAT, TSAT and TIAT was measured in centimeter to once decimal place by CT scan. A CT scan of the abdomen was conducted at the Lumbar 4 vertebrae level. A CT scan of the right thigh was performed at half the distance between the knee joint and greater trochanter femoralis. Scans were performed with 120 kilovolts, 5 millimeter slice thickness (thigh scan 3 millimeter slice thickness) and 48 centimeter scan field of view. Baseline was Week 0. Change from Baseline was calculated by subtracting Baseline values from post-Baseline values.
Time frame: Baseline (Week 0) and Week 12
Population: Body Composition Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | 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) | AVAT | 0.50 Square centimeters | Standard Deviation 23.779 |
| Placebo | 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) | ASAT | -3.12 Square centimeters | Standard Deviation 6.544 |
| Placebo | 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) | TSAT | 0.73 Square centimeters | Standard Deviation 4.366 |
| Placebo | 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) | TIAT | 0.05 Square centimeters | Standard Deviation 0.131 |
| GSK232802 25 mg | 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) | ASAT | -2.10 Square centimeters | Standard Deviation 18.822 |
| GSK232802 25 mg | 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) | TSAT | 1.59 Square centimeters | Standard Deviation 7.763 |
| GSK232802 25 mg | 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) | TIAT | 0.12 Square centimeters | Standard Deviation 0.399 |
| GSK232802 25 mg | 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) | AVAT | 7.66 Square centimeters | Standard Deviation 11.251 |
| GSK232802 75 mg | 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) | TSAT | 6.12 Square centimeters | Standard Deviation 7.869 |
| GSK232802 75 mg | 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) | ASAT | 22.37 Square centimeters | Standard Deviation 43.273 |
| GSK232802 75 mg | 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) | TIAT | 0.18 Square centimeters | Standard Deviation 0.32 |
| GSK232802 75 mg | 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) | AVAT | -5.50 Square centimeters | Standard Deviation 12.418 |
| Premarin 0.3 mg | 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) | TIAT | 0.17 Square centimeters | Standard Deviation 0.322 |
| Premarin 0.3 mg | 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) | ASAT | -13.42 Square centimeters | Standard Deviation 17.175 |
| Premarin 0.3 mg | 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) | AVAT | 2.98 Square centimeters | Standard Deviation 5.047 |
| Premarin 0.3 mg | 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) | TSAT | 2.90 Square centimeters | Standard Deviation 13.194 |
Secondary
Change From Baseline at Week 12 in Body Mass Index (BMI)
BMI was calculated from height (taken at Screening Visit 1 \[Day -35\]) and weight at Week 12 using the formula: BMI = \[weight in kilograms divided by (height in meters)\^2\]. Baseline was Week 0. Change from Baseline was calculated by subtracting Baseline values from post-Baseline values.
Time frame: Baseline (Week 0) and Week 12
Population: ITT Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline at Week 12 in Body Mass Index (BMI) | 0.05 Kilogram per square meters | Standard Error 0.085 |
| GSK232802 25 mg | Change From Baseline at Week 12 in Body Mass Index (BMI) | 0.15 Kilogram per square meters | Standard Error 0.095 |
| GSK232802 75 mg | Change From Baseline at Week 12 in Body Mass Index (BMI) | 0.12 Kilogram per square meters | Standard Error 0.092 |
| Premarin 0.3 mg | Change From Baseline at Week 12 in Body Mass Index (BMI) | 0.25 Kilogram per square meters | Standard Error 0.088 |
Secondary
Change From Baseline at Week 12 in Hip Circumference
For hip circumference, the participant was instructed to stand erect with arms at sides and feet together. The measurement was taken at the point yielding the maximum circumference over the buttocks (widest part of the greater trochanters) with nonstretchable tape. The tape was even, not twisted with the measurement scale facing outward. The assessor was instructed to ensure that the tape was just touching the skin but not compressing the soft tissue. The hip should be measured at least twice until two measurements are within 1 centimeter and the last reading recorded. Baseline was Week 0. Change from Baseline was calculated by subtracting Baseline values from post-Baseline values.
Time frame: Baseline (Week 0) and Week 12
Population: ITT Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline at Week 12 in Hip Circumference | -0.72 Centimeters | Standard Error 0.596 |
| GSK232802 25 mg | Change From Baseline at Week 12 in Hip Circumference | 0.13 Centimeters | Standard Error 0.666 |
| GSK232802 75 mg | Change From Baseline at Week 12 in Hip Circumference | 0.89 Centimeters | Standard Error 0.65 |
| Premarin 0.3 mg | Change From Baseline at Week 12 in Hip Circumference | 0.14 Centimeters | Standard Error 0.621 |
Secondary
Change From Baseline at Week 12 in Serum Hormone Levels- Estradiol
Serum hormone included Estradiol. Baseline was Week 0. Change from Baseline was calculated by subtracting Baseline values from post-Baseline values. Mean change from Baseline at Week 12 in estradiol are presented.
Time frame: Baseline (Week 0) and Week 12
Population: Safety Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline at Week 12 in Serum Hormone Levels- Estradiol | -1.775 Picomoles per Liter | Standard Deviation 88.9767 |
| GSK232802 25 mg | Change From Baseline at Week 12 in Serum Hormone Levels- Estradiol | 2.324 Picomoles per Liter | Standard Deviation 71.597 |
| GSK232802 75 mg | Change From Baseline at Week 12 in Serum Hormone Levels- Estradiol | -8.403 Picomoles per Liter | Standard Deviation 120.9173 |
| Premarin 0.3 mg | Change From Baseline at Week 12 in Serum Hormone Levels- Estradiol | 178.312 Picomoles per Liter | Standard Deviation 618.0547 |
Secondary
Change From Baseline at Week 12 in Serum Hormone Levels- Follicle Stimulating Hormone (FSH) and Luteinizing Hormone (LH)
Serum hormones included FSH and LH. Baseline was Week 0. Change from Baseline was calculated by subtracting Baseline values from post-Baseline values.
Time frame: Baseline (Week 0) and Week 12
Population: Safety Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline at Week 12 in Serum Hormone Levels- Follicle Stimulating Hormone (FSH) and Luteinizing Hormone (LH) | FSH | 0.359 International units per Liter | Standard Deviation 12.405 |
| Placebo | Change From Baseline at Week 12 in Serum Hormone Levels- Follicle Stimulating Hormone (FSH) and Luteinizing Hormone (LH) | LH | -1.454 International units per Liter | Standard Deviation 9.7558 |
| GSK232802 25 mg | Change From Baseline at Week 12 in Serum Hormone Levels- Follicle Stimulating Hormone (FSH) and Luteinizing Hormone (LH) | FSH | -5.322 International units per Liter | Standard Deviation 15.3625 |
| GSK232802 25 mg | Change From Baseline at Week 12 in Serum Hormone Levels- Follicle Stimulating Hormone (FSH) and Luteinizing Hormone (LH) | LH | -1.571 International units per Liter | Standard Deviation 8.6063 |
| GSK232802 75 mg | Change From Baseline at Week 12 in Serum Hormone Levels- Follicle Stimulating Hormone (FSH) and Luteinizing Hormone (LH) | FSH | -7.999 International units per Liter | Standard Deviation 17.5791 |
| GSK232802 75 mg | Change From Baseline at Week 12 in Serum Hormone Levels- Follicle Stimulating Hormone (FSH) and Luteinizing Hormone (LH) | LH | -3.362 International units per Liter | Standard Deviation 9.4806 |
| Premarin 0.3 mg | Change From Baseline at Week 12 in Serum Hormone Levels- Follicle Stimulating Hormone (FSH) and Luteinizing Hormone (LH) | LH | -1.732 International units per Liter | Standard Deviation 13.2826 |
| Premarin 0.3 mg | Change From Baseline at Week 12 in Serum Hormone Levels- Follicle Stimulating Hormone (FSH) and Luteinizing Hormone (LH) | FSH | -18.401 International units per Liter | Standard Deviation 18.6976 |
Secondary
Change From Baseline at Week 12 in Serum Hormone Levels- Testosterone
Serum hormones included testosterone. Baseline was Week 0. Change from Baseline was calculated by subtracting Baseline values from post-Baseline values. Mean change from Baseline at Week 12 in testosterone are presented.
Time frame: Baseline (Week 0) and Week 12
Population: Safety Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline at Week 12 in Serum Hormone Levels- Testosterone | -0.086 Nanomol per Liter | Standard Deviation 0.5454 |
| GSK232802 25 mg | Change From Baseline at Week 12 in Serum Hormone Levels- Testosterone | 0.115 Nanomol per Liter | Standard Deviation 0.5598 |
| GSK232802 75 mg | Change From Baseline at Week 12 in Serum Hormone Levels- Testosterone | 0.105 Nanomol per Liter | Standard Deviation 0.4587 |
| Premarin 0.3 mg | Change From Baseline at Week 12 in Serum Hormone Levels- Testosterone | -0.009 Nanomol per Liter | Standard Deviation 0.4252 |
Secondary
Change From Baseline at Week 12 in Waist Circumference
To measure waist circumference, clothing was lifted from around the waist to ensure correct positioning of the measuring tape. Participants were instructed to stand erect with abdomen relaxed, arms at side, feet together, and weight equally divided over both legs. The non-stretchable tape was placed at the waist midway between the palpated iliac crest and the palpated lowest rib margin in the left and right mid-axillary lines. The tape was even, parallel to the floor not twisted with the measurement scale facing outward. The assessor was instructed to ensure that the tape was just touching the skin but not compressing the soft tissue. The measurement was made at the end of a normal expiration. The waist was measured at least twice or more if necessary, until two measurements were within 1 centimeter and the confirmatory reading recorded to one decimal place. Baseline was Week 0. Change from Baseline was calculated by subtracting Baseline values from post-Baseline values.
Time frame: Baseline (Week 0) and Week 12
Population: ITT Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline at Week 12 in Waist Circumference | -0.83 Centimeters | Standard Error 0.651 |
| GSK232802 25 mg | Change From Baseline at Week 12 in Waist Circumference | -1.29 Centimeters | Standard Error 0.728 |
| GSK232802 75 mg | Change From Baseline at Week 12 in Waist Circumference | 1.03 Centimeters | Standard Error 0.709 |
| Premarin 0.3 mg | Change From Baseline at Week 12 in Waist Circumference | 0.12 Centimeters | Standard Error 0.68 |
Secondary
Change From Baseline at Week 12 in Weight
Participants were weighed on a calibrated balance beam or digital scale. Participants were instructed to be dressed in light indoor clothing without shoes and also to have empty pockets and to void before weighing. It was strongly recommended that participants were weighed in the morning at the beginning of the clinic visit. Weight was measured at least twice or more if necessary, until two measurements were within 0.5 kilograms. The last (confirmed) reading was recorded in the electronic case report form. Weight was recorded in kilograms to the nearest tenth. When the weight was measured in pounds, it was converted into kilograms using the conversion factor: pounds/ 2.2 = kilograms. Baseline was Week 0. Change from Baseline was calculated by subtracting Baseline values from post-Baseline values.
Time frame: Baseline (Week 0) and Week 12
Population: ITT Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline at Week 12 in Weight | 0.13 Kilograms | Standard Error 0.224 |
| GSK232802 25 mg | Change From Baseline at Week 12 in Weight | 0.38 Kilograms | Standard Error 0.25 |
| GSK232802 75 mg | Change From Baseline at Week 12 in Weight | 0.36 Kilograms | Standard Error 0.243 |
| Premarin 0.3 mg | Change From Baseline at Week 12 in Weight | 0.64 Kilograms | Standard Error 0.234 |
Secondary
Change From Baseline in Glucose at Week 12
Pharmacodynamic marker included glucose. Baseline was Week 0. Change from Baseline was calculated by subtracting Baseline values from post-Baseline values.
Time frame: Baseline (Week 0) and Week 12
Population: ITT Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Glucose at Week 12 | 0.119 Millimoles per Liter | Standard Deviation 0.7004 |
| GSK232802 25 mg | Change From Baseline in Glucose at Week 12 | 0.078 Millimoles per Liter | Standard Deviation 0.601 |
| GSK232802 75 mg | Change From Baseline in Glucose at Week 12 | -0.072 Millimoles per Liter | Standard Deviation 0.7097 |
| Premarin 0.3 mg | Change From Baseline in Glucose at Week 12 | -0.110 Millimoles per Liter | Standard Deviation 0.6488 |
Secondary
Change From Visit 2 to Visit 8 in Percentage of Superficial Cells to Determine the Vaginal Maturation Index (VMI)
A lateral vaginal wall specimen was collected at Visit 2 (Day -21) and Visit 8 (Week 12) and was sent to Central Pathology for analysis. Parabasal, intermediate, and superficial squamous cells were counted and percentages calculated. The VMI (also referred to as Maturation Value \[MV\]) of the vaginal mucosa was calculated according to the following equation: VMI (MV)= (% Intermediate Cells x 0.5) + (% Superficial cells). Visit 2 was Day -21 and Visit 8 was Week 12. Change from Visit 2 to Visit 8 was calculated by subtracting Visit 2 values from Visit 8 values.
Time frame: Visit 2 (Day -21) to Visit 8 (Week 12)
Population: ITT Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Visit 2 to Visit 8 in Percentage of Superficial Cells to Determine the Vaginal Maturation Index (VMI) | -1.0 Percentage of cells | Standard Error 1.99 |
| GSK232802 25 mg | Change From Visit 2 to Visit 8 in Percentage of Superficial Cells to Determine the Vaginal Maturation Index (VMI) | -0.3 Percentage of cells | Standard Error 2.16 |
| GSK232802 75 mg | Change From Visit 2 to Visit 8 in Percentage of Superficial Cells to Determine the Vaginal Maturation Index (VMI) | 9.2 Percentage of cells | Standard Error 2.11 |
| Premarin 0.3 mg | Change From Visit 2 to Visit 8 in Percentage of Superficial Cells to Determine the Vaginal Maturation Index (VMI) | 13.5 Percentage of cells | Standard Error 2.05 |
Secondary
Change From Visit 2 to Visit 8 in Vaginal pH
Vaginal pH was measured at Visit 2 and Visit 8 using standard pH indicator strips available at the participating site clinic. The pH indicator strip was inserted to the upper portion of the proximal one third of the vaginal vault, placed in contact with the lateral vaginal mucosal wall for approximately 1 minute, and evaluated according to the instructions provided in the package labeling. pH is calculated on a scale of 0 to 14, such that, the lower the number, more acidic the vagina and higher the number, more alkaline the vagina with 7 being neutral. Change from Visit 2 to Visit 8 was calculated by subtracting Visit 2 values from Visit 8 values.
Time frame: Visit 2 (Day -21) to Visit 8 (Week 12)
Population: ITT Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Visit 2 to Visit 8 in Vaginal pH | -0.13 Points on a scale | Standard Error 0.137 |
| GSK232802 25 mg | Change From Visit 2 to Visit 8 in Vaginal pH | -0.03 Points on a scale | Standard Error 0.151 |
| GSK232802 75 mg | Change From Visit 2 to Visit 8 in Vaginal pH | -0.09 Points on a scale | Standard Error 0.146 |
| Premarin 0.3 mg | Change From Visit 2 to Visit 8 in Vaginal pH | -0.59 Points on a scale | Standard Error 0.138 |
Secondary
Change in Brief Fatigue Inventory (BFI) Score From Visit 2 to Visit 7
The BFI is a validated questionnaire designed to measure a participant's fatigue via nine questions that are summated to create a total score. Items 1-3 request a rating on a scale ranging from 0 - 10 with 0 representing 'No Fatigue' and 10 representing 'As bad as you can imagine'. Five items 4A-4F request an interference score on a scale ranging from 0 - 10 with 0 representing 'Does not interfere' and 10 representing 'Completely Interferes'. The values of the scales for all items was used in scoring the response to each item. The following groupings of items was used to create domain scores. The total score is calculated by taking the sum of all 9 rating scales for a minimum score of 0 and a maximum score of 90. Higher score indicates more severe fatigue. Visit 2 was Day -21. Change from Visit 2 was calculated by subtracting Visit 2 values from post-Visit 2 values.
Time frame: Visit 2 (Day -21) to Visit 7 (Week 8)
Population: ITT Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change in Brief Fatigue Inventory (BFI) Score From Visit 2 to Visit 7 | Total Score | -0.84 Scores on a Scale | Standard Error 0.251 |
| Placebo | Change in Brief Fatigue Inventory (BFI) Score From Visit 2 to Visit 7 | Interference domain | -0.82 Scores on a Scale | Standard Error 0.261 |
| Placebo | Change in Brief Fatigue Inventory (BFI) Score From Visit 2 to Visit 7 | Severity domain | -0.87 Scores on a Scale | Standard Error 0.289 |
| GSK232802 25 mg | Change in Brief Fatigue Inventory (BFI) Score From Visit 2 to Visit 7 | Total Score | -0.43 Scores on a Scale | Standard Error 0.279 |
| GSK232802 25 mg | Change in Brief Fatigue Inventory (BFI) Score From Visit 2 to Visit 7 | Interference domain | -0.33 Scores on a Scale | Standard Error 0.29 |
| GSK232802 25 mg | Change in Brief Fatigue Inventory (BFI) Score From Visit 2 to Visit 7 | Severity domain | -0.58 Scores on a Scale | Standard Error 0.323 |
| GSK232802 75 mg | Change in Brief Fatigue Inventory (BFI) Score From Visit 2 to Visit 7 | Severity domain | -0.53 Scores on a Scale | Standard Error 0.314 |
| GSK232802 75 mg | Change in Brief Fatigue Inventory (BFI) Score From Visit 2 to Visit 7 | Total Score | -0.33 Scores on a Scale | Standard Error 0.27 |
| GSK232802 75 mg | Change in Brief Fatigue Inventory (BFI) Score From Visit 2 to Visit 7 | Interference domain | -0.25 Scores on a Scale | Standard Error 0.281 |
| Premarin 0.3 mg | Change in Brief Fatigue Inventory (BFI) Score From Visit 2 to Visit 7 | Total Score | -0.40 Scores on a Scale | Standard Error 0.26 |
| Premarin 0.3 mg | Change in Brief Fatigue Inventory (BFI) Score From Visit 2 to Visit 7 | Interference domain | -0.38 Scores on a Scale | Standard Error 0.271 |
| Premarin 0.3 mg | Change in Brief Fatigue Inventory (BFI) Score From Visit 2 to Visit 7 | Severity domain | -0.43 Scores on a Scale | Standard Error 0.301 |
Secondary
Change in Medical Outcomes Study (MOS) Sleep Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12)
The MOS Sleep Scale is a validated questionnaire designed to measure a participant sleep quality via 12 questions. Items are designed to be grouped into domains that include sleep disturbance (items 1, 3, 7, 8), sleep adequacy (items 4, 12), daytime somnolence (items 6, 9, 11), sleep quantity (2), 6-Item Sleep Scale (items 4, 5, 7, 8, 9, 12) and 9-Item Sleep Scale (items 3, 4, 5, 6, 7, 8, 9, 11, 12). Each domain is given a separate score. The domain score is calculated as the sum of the individual item scores in that domain. Transformed scores were calculated for the domains only. This transformation converts the raw domain score to a 0 to 100 scale following the formula: Transformed score = (\[Raw score - Lowest possible score\]/Possible score range)\*100. Lowest score 0 indicates best sleep quality and higher score 100 indicates worst sleep quality. Baseline was Week 0. Change from Baseline was calculated by subtracting Baseline values from post-Baseline values.
Time frame: Baseline (Week 0) to Week 12
Population: ITT Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change in Medical Outcomes Study (MOS) Sleep Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) | 6-Item Sleep Scale domain; Week 4 | 2.19 Scores on a Scale | Standard Error 0.56 |
| Placebo | Change in Medical Outcomes Study (MOS) Sleep Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) | Transformed Sleep Adequacy domain; Week 4 | 4.75 Scores on a Scale | Standard Error 2.45 |
| Placebo | Change in Medical Outcomes Study (MOS) Sleep Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) | Transformed 9-Item Sleep Scale domain; Week 4 | 5.57 Scores on a Scale | Standard Error 1.434 |
| Placebo | Change in Medical Outcomes Study (MOS) Sleep Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) | 9-Item Sleep Scale domain; Week 4 | 3.01 Scores on a Scale | Standard Error 0.774 |
| Placebo | Change in Medical Outcomes Study (MOS) Sleep Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) | Transformed Sleep Disturbance domain; Week 12 | 5.57 Scores on a Scale | Standard Error 1.525 |
| Placebo | Change in Medical Outcomes Study (MOS) Sleep Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) | Transformed Sleep Somnolence domain; Week 12 | 0.41 Scores on a Scale | Standard Error 1.639 |
| Placebo | Change in Medical Outcomes Study (MOS) Sleep Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) | Transformed Sleep Adequacy domain; Week 12 | 11.35 Scores on a Scale | Standard Error 2.514 |
| Placebo | Change in Medical Outcomes Study (MOS) Sleep Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) | Transformed Sleep Disturbance domain; Week 4 | 6.76 Scores on a Scale | Standard Error 1.577 |
| Placebo | Change in Medical Outcomes Study (MOS) Sleep Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) | Transformed 6-Item Sleep Scale domain; Week 4 | 6.08 Scores on a Scale | Standard Error 1.556 |
| Placebo | Change in Medical Outcomes Study (MOS) Sleep Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) | Sleep Quantity domain; Week 12 | 0.22 Scores on a Scale | Standard Error 0.131 |
| Placebo | Change in Medical Outcomes Study (MOS) Sleep Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) | Sleep Somnolence domain; Week 12 | 0.07 Scores on a Scale | Standard Error 0.295 |
| Placebo | Change in Medical Outcomes Study (MOS) Sleep Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) | Sleep Adequacy domain; Week 4 | 0.57 Scores on a Scale | Standard Error 0.294 |
| Placebo | Change in Medical Outcomes Study (MOS) Sleep Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) | 9-Item Sleep Scale domain; Week 12 | 2.87 Scores on a Scale | Standard Error 0.774 |
| Placebo | Change in Medical Outcomes Study (MOS) Sleep Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) | Sleep Adequacy domain; Week 12 | 1.36 Scores on a Scale | Standard Error 0.302 |
| Placebo | Change in Medical Outcomes Study (MOS) Sleep Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) | Sleep Disturbance domain; Week 12 | 1.34 Scores on a Scale | Standard Error 0.366 |
| Placebo | Change in Medical Outcomes Study (MOS) Sleep Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) | Sleep Somnolence domain; Week 4 | 0.43 Scores on a Scale | Standard Error 0.297 |
| Placebo | Change in Medical Outcomes Study (MOS) Sleep Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) | Transformed Sleep Somnolence domain; Week 4 | 2.38 Scores on a Scale | Standard Error 1.651 |
| Placebo | Change in Medical Outcomes Study (MOS) Sleep Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) | Transformed 9-Item Sleep Scale domain; Week 12 | 5.32 Scores on a Scale | Standard Error 1.433 |
| Placebo | Change in Medical Outcomes Study (MOS) Sleep Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) | Sleep Quantity domain; Week 4 | 0.24 Scores on a Scale | Standard Error 0.121 |
| Placebo | Change in Medical Outcomes Study (MOS) Sleep Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) | 6-Item Sleep Scale domain; Week 12 | 2.62 Scores on a Scale | Standard Error 0.571 |
| Placebo | Change in Medical Outcomes Study (MOS) Sleep Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) | Transformed 6-Item Sleep Scale domain; Week 12 | 7.27 Scores on a Scale | Standard Error 1.586 |
| Placebo | Change in Medical Outcomes Study (MOS) Sleep Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) | Sleep Disturbance domain; Week 4 | 1.62 Scores on a Scale | Standard Error 0.378 |
| GSK232802 25 mg | Change in Medical Outcomes Study (MOS) Sleep Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) | Transformed 9-Item Sleep Scale domain; Week 4 | 4.19 Scores on a Scale | Standard Error 1.588 |
| GSK232802 25 mg | Change in Medical Outcomes Study (MOS) Sleep Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) | Sleep Disturbance domain; Week 4 | 1.29 Scores on a Scale | Standard Error 0.422 |
| GSK232802 25 mg | Change in Medical Outcomes Study (MOS) Sleep Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) | Transformed Sleep Disturbance domain; Week 4 | 5.35 Scores on a Scale | Standard Error 1.758 |
| GSK232802 25 mg | Change in Medical Outcomes Study (MOS) Sleep Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) | Transformed Sleep Adequacy domain; Week 4 | 5.48 Scores on a Scale | Standard Error 2.738 |
| GSK232802 25 mg | Change in Medical Outcomes Study (MOS) Sleep Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) | Sleep Adequacy domain; Week 4 | 0.66 Scores on a Scale | Standard Error 0.329 |
| GSK232802 25 mg | Change in Medical Outcomes Study (MOS) Sleep Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) | Sleep Somnolence domain; Week 4 | -0.19 Scores on a Scale | Standard Error 0.332 |
| GSK232802 25 mg | Change in Medical Outcomes Study (MOS) Sleep Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) | Sleep Quantity domain; Week 4 | 0.21 Scores on a Scale | Standard Error 0.134 |
| GSK232802 25 mg | Change in Medical Outcomes Study (MOS) Sleep Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) | 6-Item Sleep Scale domain; Week 4 | 1.85 Scores on a Scale | Standard Error 0.621 |
| GSK232802 25 mg | Change in Medical Outcomes Study (MOS) Sleep Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) | 9-Item Sleep Scale domain; Week 4 | 2.26 Scores on a Scale | Standard Error 0.858 |
| GSK232802 25 mg | Change in Medical Outcomes Study (MOS) Sleep Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) | Transformed 6-Item Sleep Scale domain; Week 4 | 5.15 Scores on a Scale | Standard Error 1.724 |
| GSK232802 25 mg | Change in Medical Outcomes Study (MOS) Sleep Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) | Transformed Sleep Adequacy domain; Week 12 | 6.62 Scores on a Scale | Standard Error 2.734 |
| GSK232802 25 mg | Change in Medical Outcomes Study (MOS) Sleep Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) | Transformed Sleep Somnolence domain; Week 12 | 2.30 Scores on a Scale | Standard Error 1.781 |
| GSK232802 25 mg | Change in Medical Outcomes Study (MOS) Sleep Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) | Transformed 6-Item Sleep Scale domain; Week 12 | 6.08 Scores on a Scale | Standard Error 1.711 |
| GSK232802 25 mg | Change in Medical Outcomes Study (MOS) Sleep Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) | Transformed 9-Item Sleep Scale domain; Week 12 | 5.88 Scores on a Scale | Standard Error 1.544 |
| GSK232802 25 mg | Change in Medical Outcomes Study (MOS) Sleep Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) | Sleep Disturbance domain; Week 12 | 1.37 Scores on a Scale | Standard Error 0.397 |
| GSK232802 25 mg | Change in Medical Outcomes Study (MOS) Sleep Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) | Sleep Adequacy domain; Week 12 | 0.79 Scores on a Scale | Standard Error 0.328 |
| GSK232802 25 mg | Change in Medical Outcomes Study (MOS) Sleep Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) | Sleep Somnolence domain; Week 12 | 0.41 Scores on a Scale | Standard Error 0.321 |
| GSK232802 25 mg | Change in Medical Outcomes Study (MOS) Sleep Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) | Sleep Quantity domain; Week 12 | 0.23 Scores on a Scale | Standard Error 0.142 |
| GSK232802 25 mg | Change in Medical Outcomes Study (MOS) Sleep Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) | 6-Item Sleep Scale domain; Week 12 | 2.19 Scores on a Scale | Standard Error 0.616 |
| GSK232802 25 mg | Change in Medical Outcomes Study (MOS) Sleep Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) | 9-Item Sleep Scale domain; Week 12 | 3.17 Scores on a Scale | Standard Error 0.834 |
| GSK232802 25 mg | Change in Medical Outcomes Study (MOS) Sleep Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) | Transformed Sleep Disturbance domain; Week 12 | 5.70 Scores on a Scale | Standard Error 1.654 |
| GSK232802 25 mg | Change in Medical Outcomes Study (MOS) Sleep Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) | Transformed Sleep Somnolence domain; Week 4 | -1.03 Scores on a Scale | Standard Error 1.842 |
| GSK232802 75 mg | Change in Medical Outcomes Study (MOS) Sleep Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) | 6-Item Sleep Scale domain; Week 4 | 1.53 Scores on a Scale | Standard Error 0.588 |
| GSK232802 75 mg | Change in Medical Outcomes Study (MOS) Sleep Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) | Sleep Somnolence domain; Week 4 | 0.00 Scores on a Scale | Standard Error 0.314 |
| GSK232802 75 mg | Change in Medical Outcomes Study (MOS) Sleep Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) | Sleep Somnolence domain; Week 12 | 0.13 Scores on a Scale | Standard Error 0.315 |
| GSK232802 75 mg | Change in Medical Outcomes Study (MOS) Sleep Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) | Transformed 6-Item Sleep Scale domain; Week 12 | 1.57 Scores on a Scale | Standard Error 1.678 |
| GSK232802 75 mg | Change in Medical Outcomes Study (MOS) Sleep Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) | Transformed Sleep Adequacy domain; Week 4 | 3.10 Scores on a Scale | Standard Error 2.594 |
| GSK232802 75 mg | Change in Medical Outcomes Study (MOS) Sleep Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) | Sleep Disturbance domain; Week 4 | 1.05 Scores on a Scale | Standard Error 0.4 |
| GSK232802 75 mg | Change in Medical Outcomes Study (MOS) Sleep Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) | Sleep Quantity domain; Week 12 | -0.08 Scores on a Scale | Standard Error 0.142 |
| GSK232802 75 mg | Change in Medical Outcomes Study (MOS) Sleep Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) | Transformed Sleep Somnolence domain; Week 12 | 0.72 Scores on a Scale | Standard Error 1.749 |
| GSK232802 75 mg | Change in Medical Outcomes Study (MOS) Sleep Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) | Transformed Sleep Disturbance domain; Week 4 | 4.37 Scores on a Scale | Standard Error 1.667 |
| GSK232802 75 mg | Change in Medical Outcomes Study (MOS) Sleep Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) | 9-Item Sleep Scale domain; Week 12 | 1.36 Scores on a Scale | Standard Error 0.818 |
| GSK232802 75 mg | Change in Medical Outcomes Study (MOS) Sleep Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) | Sleep Disturbance domain; Week 12 | 0.82 Scores on a Scale | Standard Error 0.39 |
| GSK232802 75 mg | Change in Medical Outcomes Study (MOS) Sleep Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) | Transformed Sleep Somnolence domain; Week 4 | 0.02 Scores on a Scale | Standard Error 1.747 |
| GSK232802 75 mg | Change in Medical Outcomes Study (MOS) Sleep Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) | Transformed Sleep Disturbance domain; Week 12 | 3.41 Scores on a Scale | Standard Error 1.627 |
| GSK232802 75 mg | Change in Medical Outcomes Study (MOS) Sleep Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) | Transformed 6-Item Sleep Scale domain; Week 4 | 4.25 Scores on a Scale | Standard Error 1.634 |
| GSK232802 75 mg | Change in Medical Outcomes Study (MOS) Sleep Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) | Transformed 9-Item Sleep Scale domain; Week 4 | 3.73 Scores on a Scale | Standard Error 1.506 |
| GSK232802 75 mg | Change in Medical Outcomes Study (MOS) Sleep Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) | Sleep Adequacy domain; Week 4 | 0.37 Scores on a Scale | Standard Error 0.311 |
| GSK232802 75 mg | Change in Medical Outcomes Study (MOS) Sleep Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) | Sleep Quantity domain; Week 4 | 0.13 Scores on a Scale | Standard Error 0.127 |
| GSK232802 75 mg | Change in Medical Outcomes Study (MOS) Sleep Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) | 6-Item Sleep Scale domain; Week 12 | 0.57 Scores on a Scale | Standard Error 0.604 |
| GSK232802 75 mg | Change in Medical Outcomes Study (MOS) Sleep Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) | Transformed Sleep Adequacy domain; Week 12 | 0.19 Scores on a Scale | Standard Error 2.682 |
| GSK232802 75 mg | Change in Medical Outcomes Study (MOS) Sleep Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) | Sleep Adequacy domain; Week 12 | 0.02 Scores on a Scale | Standard Error 0.322 |
| GSK232802 75 mg | Change in Medical Outcomes Study (MOS) Sleep Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) | 9-Item Sleep Scale domain; Week 4 | 2.01 Scores on a Scale | Standard Error 0.813 |
| GSK232802 75 mg | Change in Medical Outcomes Study (MOS) Sleep Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) | Transformed 9-Item Sleep Scale domain; Week 12 | 2.51 Scores on a Scale | Standard Error 1.515 |
| Premarin 0.3 mg | Change in Medical Outcomes Study (MOS) Sleep Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) | 6-Item Sleep Scale domain; Week 4 | 2.87 Scores on a Scale | Standard Error 0.568 |
| Premarin 0.3 mg | Change in Medical Outcomes Study (MOS) Sleep Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) | 6-Item Sleep Scale domain; Week 12 | 3.68 Scores on a Scale | Standard Error 0.565 |
| Premarin 0.3 mg | Change in Medical Outcomes Study (MOS) Sleep Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) | Transformed Sleep Somnolence domain; Week 12 | 6.48 Scores on a Scale | Standard Error 1.635 |
| Premarin 0.3 mg | Change in Medical Outcomes Study (MOS) Sleep Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) | Transformed 6-Item Sleep Scale domain; Week 12 | 10.23 Scores on a Scale | Standard Error 1.57 |
| Premarin 0.3 mg | Change in Medical Outcomes Study (MOS) Sleep Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) | Sleep Somnolence domain; Week 4 | 0.65 Scores on a Scale | Standard Error 0.303 |
| Premarin 0.3 mg | Change in Medical Outcomes Study (MOS) Sleep Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) | Transformed Sleep Adequacy domain; Week 4 | 8.35 Scores on a Scale | Standard Error 2.501 |
| Premarin 0.3 mg | Change in Medical Outcomes Study (MOS) Sleep Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) | Transformed 9-Item Sleep Scale domain; Week 12 | 9.85 Scores on a Scale | Standard Error 1.417 |
| Premarin 0.3 mg | Change in Medical Outcomes Study (MOS) Sleep Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) | Transformed 9-Item Sleep Scale domain; Week 4 | 7.50 Scores on a Scale | Standard Error 1.453 |
| Premarin 0.3 mg | Change in Medical Outcomes Study (MOS) Sleep Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) | Sleep Adequacy domain; Week 4 | 1.00 Scores on a Scale | Standard Error 0.3 |
| Premarin 0.3 mg | Change in Medical Outcomes Study (MOS) Sleep Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) | Sleep Disturbance domain; Week 12 | 2.12 Scores on a Scale | Standard Error 0.364 |
| Premarin 0.3 mg | Change in Medical Outcomes Study (MOS) Sleep Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) | 9-Item Sleep Scale domain; Week 12 | 5.32 Scores on a Scale | Standard Error 0.765 |
| Premarin 0.3 mg | Change in Medical Outcomes Study (MOS) Sleep Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) | Sleep Adequacy domain; Week 12 | 1.36 Scores on a Scale | Standard Error 0.301 |
| Premarin 0.3 mg | Change in Medical Outcomes Study (MOS) Sleep Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) | Sleep Disturbance domain; Week 4 | 1.68 Scores on a Scale | Standard Error 0.386 |
| Premarin 0.3 mg | Change in Medical Outcomes Study (MOS) Sleep Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) | Sleep Somnolence domain; Week 12 | 1.17 Scores on a Scale | Standard Error 0.294 |
| Premarin 0.3 mg | Change in Medical Outcomes Study (MOS) Sleep Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) | Sleep Quantity domain; Week 12 | 0.46 Scores on a Scale | Standard Error 0.133 |
| Premarin 0.3 mg | Change in Medical Outcomes Study (MOS) Sleep Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) | Transformed Sleep Disturbance domain; Week 4 | 7.01 Scores on a Scale | Standard Error 1.607 |
| Premarin 0.3 mg | Change in Medical Outcomes Study (MOS) Sleep Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) | Transformed Sleep Somnolence domain; Week 4 | 3.62 Scores on a Scale | Standard Error 1.685 |
| Premarin 0.3 mg | Change in Medical Outcomes Study (MOS) Sleep Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) | Transformed 6-Item Sleep Scale domain; Week 4 | 7.98 Scores on a Scale | Standard Error 1.577 |
| Premarin 0.3 mg | Change in Medical Outcomes Study (MOS) Sleep Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) | Transformed Sleep Disturbance domain; Week 12 | 8.85 Scores on a Scale | Standard Error 1.518 |
| Premarin 0.3 mg | Change in Medical Outcomes Study (MOS) Sleep Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) | 9-Item Sleep Scale domain; Week 4 | 4.05 Scores on a Scale | Standard Error 0.784 |
| Premarin 0.3 mg | Change in Medical Outcomes Study (MOS) Sleep Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) | Transformed Sleep Adequacy domain; Week 12 | 11.30 Scores on a Scale | Standard Error 2.508 |
| Premarin 0.3 mg | Change in Medical Outcomes Study (MOS) Sleep Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) | Sleep Quantity domain; Week 4 | 0.47 Scores on a Scale | Standard Error 0.124 |
Secondary
Change in Menopause Quality of Life (MENQoL) Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12)
MENQOL instrument is a 32-item, validated questionnaire designed to measure symptoms that participants experience due to menopause and degree to which these symptoms bother them. Each item references a symptom and is composed of two-part question; a yes/no confirmation that the participant has symptom followed by a question asking how bothersome the symptom is, if present. The MENQOL items are designed to be grouped into domains that address vasomotor (items 1-3), psychosocial(items 4-10), physical (items 11-26, 30-32) and sexual symptoms (items 27-29). Each domain is given a separate score; there is no overall score. The domain score is sum of individual item scores divided by number of items in that domain. Since domain subscales are not comprised of an equivalent number of items, mean of subscale is used as overall subscale score. Each domain score ranges from 1 to 8. Baseline was Week 0. Change from Baseline was calculated by subtracting Baseline values from post-Baseline values.
Time frame: Baseline (Week 0) to Week 12
Population: ITT Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change in Menopause Quality of Life (MENQoL) Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) | Psychosocial Domain Score; Week 4 | -0.51 Scores on a Scale | Standard Error 0.157 |
| Placebo | Change in Menopause Quality of Life (MENQoL) Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) | Physical Domain Score; Week 4 | -0.65 Scores on a Scale | Standard Error 0.122 |
| Placebo | Change in Menopause Quality of Life (MENQoL) Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) | Sexual Domain Score; Week 12 | -0.47 Scores on a Scale | Standard Error 0.194 |
| Placebo | Change in Menopause Quality of Life (MENQoL) Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) | Physical Domain Score; Week 12 | -0.59 Scores on a Scale | Standard Error 0.133 |
| Placebo | Change in Menopause Quality of Life (MENQoL) Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) | Psychosocial Domain Score; Week 12 | -0.46 Scores on a Scale | Standard Error 0.178 |
| Placebo | Change in Menopause Quality of Life (MENQoL) Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) | Vasomotor Domain Score; Week 12 | -1.79 Scores on a Scale | Standard Error 0.241 |
| Placebo | Change in Menopause Quality of Life (MENQoL) Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) | Sexual Domain Score; Week 4 | -0.62 Scores on a Scale | Standard Error 0.187 |
| Placebo | Change in Menopause Quality of Life (MENQoL) Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) | Vasomotor Domain Score; Week 4 | -1.36 Scores on a Scale | Standard Error 0.205 |
| GSK232802 25 mg | Change in Menopause Quality of Life (MENQoL) Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) | Vasomotor Domain Score; Week 4 | -1.26 Scores on a Scale | Standard Error 0.227 |
| GSK232802 25 mg | Change in Menopause Quality of Life (MENQoL) Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) | Psychosocial Domain Score; Week 4 | -0.46 Scores on a Scale | Standard Error 0.173 |
| GSK232802 25 mg | Change in Menopause Quality of Life (MENQoL) Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) | Physical Domain Score; Week 4 | -0.50 Scores on a Scale | Standard Error 0.135 |
| GSK232802 25 mg | Change in Menopause Quality of Life (MENQoL) Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) | Sexual Domain Score; Week 4 | -0.62 Scores on a Scale | Standard Error 0.203 |
| GSK232802 25 mg | Change in Menopause Quality of Life (MENQoL) Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) | Vasomotor Domain Score; Week 12 | -1.21 Scores on a Scale | Standard Error 0.26 |
| GSK232802 25 mg | Change in Menopause Quality of Life (MENQoL) Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) | Psychosocial Domain Score; Week 12 | -0.45 Scores on a Scale | Standard Error 0.193 |
| GSK232802 25 mg | Change in Menopause Quality of Life (MENQoL) Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) | Physical Domain Score; Week 12 | -0.36 Scores on a Scale | Standard Error 0.144 |
| GSK232802 25 mg | Change in Menopause Quality of Life (MENQoL) Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) | Sexual Domain Score; Week 12 | -0.18 Scores on a Scale | Standard Error 0.214 |
| GSK232802 75 mg | Change in Menopause Quality of Life (MENQoL) Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) | Psychosocial Domain Score; Week 12 | -0.33 Scores on a Scale | Standard Error 0.189 |
| GSK232802 75 mg | Change in Menopause Quality of Life (MENQoL) Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) | Physical Domain Score; Week 4 | -0.58 Scores on a Scale | Standard Error 0.127 |
| GSK232802 75 mg | Change in Menopause Quality of Life (MENQoL) Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) | Vasomotor Domain Score; Week 4 | -1.27 Scores on a Scale | Standard Error 0.213 |
| GSK232802 75 mg | Change in Menopause Quality of Life (MENQoL) Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) | Vasomotor Domain Score; Week 12 | -1.09 Scores on a Scale | Standard Error 0.253 |
| GSK232802 75 mg | Change in Menopause Quality of Life (MENQoL) Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) | Psychosocial Domain Score; Week 4 | -0.42 Scores on a Scale | Standard Error 0.165 |
| GSK232802 75 mg | Change in Menopause Quality of Life (MENQoL) Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) | Physical Domain Score; Week 12 | -0.50 Scores on a Scale | Standard Error 0.139 |
| GSK232802 75 mg | Change in Menopause Quality of Life (MENQoL) Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) | Sexual Domain Score; Week 12 | -0.52 Scores on a Scale | Standard Error 0.215 |
| GSK232802 75 mg | Change in Menopause Quality of Life (MENQoL) Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) | Sexual Domain Score; Week 4 | -0.62 Scores on a Scale | Standard Error 0.2 |
| Premarin 0.3 mg | Change in Menopause Quality of Life (MENQoL) Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) | Physical Domain Score; Week 4 | -0.70 Scores on a Scale | Standard Error 0.123 |
| Premarin 0.3 mg | Change in Menopause Quality of Life (MENQoL) Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) | Vasomotor Domain Score; Week 12 | -2.99 Scores on a Scale | Standard Error 0.237 |
| Premarin 0.3 mg | Change in Menopause Quality of Life (MENQoL) Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) | Sexual Domain Score; Week 12 | -1.04 Scores on a Scale | Standard Error 0.194 |
| Premarin 0.3 mg | Change in Menopause Quality of Life (MENQoL) Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) | Psychosocial Domain Score; Week 12 | -0.91 Scores on a Scale | Standard Error 0.174 |
| Premarin 0.3 mg | Change in Menopause Quality of Life (MENQoL) Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) | Vasomotor Domain Score; Week 4 | -2.13 Scores on a Scale | Standard Error 0.207 |
| Premarin 0.3 mg | Change in Menopause Quality of Life (MENQoL) Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) | Sexual Domain Score; Week 4 | -0.85 Scores on a Scale | Standard Error 0.188 |
| Premarin 0.3 mg | Change in Menopause Quality of Life (MENQoL) Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) | Psychosocial Domain Score; Week 4 | -0.63 Scores on a Scale | Standard Error 0.161 |
| Premarin 0.3 mg | Change in Menopause Quality of Life (MENQoL) Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) | Physical Domain Score; Week 12 | -0.87 Scores on a Scale | Standard Error 0.129 |
Secondary
Change in the Centers for Epidemiologic Studies in Depression (CES-D) Score From Visit 2 to Visit 7
The CES-D is a questionnaire designed to measure depressive symptoms via 20 items that are summed to create a total score. Depressive symptoms are fairly common in postmenopausal women, and it's possible that stimulation of estrogen receptors via a selective estrogen receptor modulator may improve depressive symptoms. Questions 4, 8, 12 and 16 are weighted negatively (the scores are flipped prior to creating total score). If 3 or more items are missing then total score is missing. If fewer than 3 items are missing then missing item is set to group mean of that item for appropriate randomized treatment group. These means are only calculated if more than half of the participants used for calculation have responded to item. The items are summed to give total score ranging from 0 to 60. Lower score 0=no depression, higher score 60=higher degree of depression severity. Visit 2 was Day -21. Change from Visit 2 was calculated by subtracting Visit 2 values from post-Visit 2 values.
Time frame: Visit 2 (Day -21) to Visit 7 (Week 8)
Population: ITT Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in the Centers for Epidemiologic Studies in Depression (CES-D) Score From Visit 2 to Visit 7 | -2.55 Scores on a Scale | Standard Error 1.077 |
| GSK232802 25 mg | Change in the Centers for Epidemiologic Studies in Depression (CES-D) Score From Visit 2 to Visit 7 | -1.26 Scores on a Scale | Standard Error 1.172 |
| GSK232802 75 mg | Change in the Centers for Epidemiologic Studies in Depression (CES-D) Score From Visit 2 to Visit 7 | -0.38 Scores on a Scale | Standard Error 1.132 |
| Premarin 0.3 mg | Change in the Centers for Epidemiologic Studies in Depression (CES-D) Score From Visit 2 to Visit 7 | -1.27 Scores on a Scale | Standard Error 1.09 |
Secondary
Change in Work Productivity and Activity Impairment (WPAI) Score From Visit 2 to Visit 7
The WPAI is a questionnaire that measured workplace productivity and absenteeism via 6 items/questions, adapted to participants experiencing menopausal symptoms. Item 1 asks about current employment with a yes/no response. Items 2- 4 ask for continuous response in hours. Item 5 asks for response on rating scale related to WP ranging from 0:Menopausal symptoms had no effect on work to 10:Couldn't work at all. Item 6 asks for response on rating scale related to daily activities ranging from 0:no effect on daily activities to 10:Couldn't perform any daily activities. The score calculation- Effect on work: (Item 5 score÷10); Absenteeism: (Item 2÷Item 2+Item 4); Overall work impairment (\[Item 2÷Item 2+Item 4\]+ \[1- {Item 2÷Item 2+Item 4}\]\*\[ Item 5 score÷10\]); Activity impairment: (Item 6 score÷10). Total score range from 0 to 10 where higher score indicates worst condition. Visit 2 was Day -21. Change from Visit 2 was calculated by subtracting Visit 2 values from post-Visit 2 values.
Time frame: Visit 2 (Day -21) to Visit 7 (Week 8)
Population: ITT Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change in Work Productivity and Activity Impairment (WPAI) Score From Visit 2 to Visit 7 | Effect on work | -16.80 Scores on a Scale | Standard Error 3.319 |
| Placebo | Change in Work Productivity and Activity Impairment (WPAI) Score From Visit 2 to Visit 7 | Absenteeism | -1.10 Scores on a Scale | Standard Error 1.229 |
| Placebo | Change in Work Productivity and Activity Impairment (WPAI) Score From Visit 2 to Visit 7 | Overall work impairment | -19.37 Scores on a Scale | Standard Error 3.761 |
| Placebo | Change in Work Productivity and Activity Impairment (WPAI) Score From Visit 2 to Visit 7 | Activity impairment | -20.21 Scores on a Scale | Standard Error 2.823 |
| GSK232802 25 mg | Change in Work Productivity and Activity Impairment (WPAI) Score From Visit 2 to Visit 7 | Absenteeism | -2.01 Scores on a Scale | Standard Error 1.409 |
| GSK232802 25 mg | Change in Work Productivity and Activity Impairment (WPAI) Score From Visit 2 to Visit 7 | Overall work impairment | -17.82 Scores on a Scale | Standard Error 4.318 |
| GSK232802 25 mg | Change in Work Productivity and Activity Impairment (WPAI) Score From Visit 2 to Visit 7 | Activity impairment | -13.50 Scores on a Scale | Standard Error 3.082 |
| GSK232802 25 mg | Change in Work Productivity and Activity Impairment (WPAI) Score From Visit 2 to Visit 7 | Effect on work | -11.71 Scores on a Scale | Standard Error 3.681 |
| GSK232802 75 mg | Change in Work Productivity and Activity Impairment (WPAI) Score From Visit 2 to Visit 7 | Overall work impairment | -13.30 Scores on a Scale | Standard Error 3.768 |
| GSK232802 75 mg | Change in Work Productivity and Activity Impairment (WPAI) Score From Visit 2 to Visit 7 | Absenteeism | -2.67 Scores on a Scale | Standard Error 1.224 |
| GSK232802 75 mg | Change in Work Productivity and Activity Impairment (WPAI) Score From Visit 2 to Visit 7 | Activity impairment | -7.57 Scores on a Scale | Standard Error 2.972 |
| GSK232802 75 mg | Change in Work Productivity and Activity Impairment (WPAI) Score From Visit 2 to Visit 7 | Effect on work | -6.43 Scores on a Scale | Standard Error 3.199 |
| Premarin 0.3 mg | Change in Work Productivity and Activity Impairment (WPAI) Score From Visit 2 to Visit 7 | Activity impairment | -18.58 Scores on a Scale | Standard Error 2.886 |
| Premarin 0.3 mg | Change in Work Productivity and Activity Impairment (WPAI) Score From Visit 2 to Visit 7 | Absenteeism | -0.51 Scores on a Scale | Standard Error 1.211 |
| Premarin 0.3 mg | Change in Work Productivity and Activity Impairment (WPAI) Score From Visit 2 to Visit 7 | Effect on work | -17.69 Scores on a Scale | Standard Error 3.437 |
| Premarin 0.3 mg | Change in Work Productivity and Activity Impairment (WPAI) Score From Visit 2 to Visit 7 | Overall work impairment | -18.48 Scores on a Scale | Standard Error 3.763 |
Secondary
Changes in Vulvar Vaginal Atrophy (VVA) Symptom Score From Baseline to Visit 8 (Week 12)
The VVA Symptoms Scale questionnaire is an 18-item instrument that captures symptoms related to VVA, asks participant to identify symptom that bothers them the most and contains items to assess degree of bother participants experience from each symptom and impact that most bothersome symptom has on their daily life. Items 1 to 8 had responses and scores of none=0, mild=1, moderate=2 and severe=3. Items 9 to 18 had responses and scores of not at all=0, a little=1, moderately=2 and a lot=3. Severity item and bothersome item respectively were as follows: vaginal dryness:1 and 9; Vaginal itching:2 and 10; Vaginal irritation:3 and 11; Painful urination:4 and 12; Difficulty urinating:5 and 13; Vaginal pain associated with sexual activity:6 and 14; Vaginal bleeding associated with sexual activity:7 and 15. Total score ranged from 0 to 3; higher score indicated most bothersome. Baseline was Week 0. Change from Baseline was calculated by subtracting Baseline values from post-Baseline values.
Time frame: Baseline (Week 0) to Visit 8 (Week 12)
Population: ITT Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Changes in Vulvar Vaginal Atrophy (VVA) Symptom Score From Baseline to Visit 8 (Week 12) | Severity of vaginal irritation | 0.0 Scores on a Scale | Standard Deviation 0.65 |
| Placebo | Changes in Vulvar Vaginal Atrophy (VVA) Symptom Score From Baseline to Visit 8 (Week 12) | Bothered by vaginal irritation | -0.1 Scores on a Scale | Standard Deviation 0.74 |
| Placebo | Changes in Vulvar Vaginal Atrophy (VVA) Symptom Score From Baseline to Visit 8 (Week 12) | Bothered by vaginal pain due to sexual activity | -0.2 Scores on a Scale | Standard Deviation 0.84 |
| Placebo | Changes in Vulvar Vaginal Atrophy (VVA) Symptom Score From Baseline to Visit 8 (Week 12) | Bothered by painful urination | -0.1 Scores on a Scale | Standard Deviation 0.48 |
| Placebo | Changes in Vulvar Vaginal Atrophy (VVA) Symptom Score From Baseline to Visit 8 (Week 12) | Bothered by difficulty in urination | -0.1 Scores on a Scale | Standard Deviation 0.34 |
| Placebo | Changes in Vulvar Vaginal Atrophy (VVA) Symptom Score From Baseline to Visit 8 (Week 12) | Severity of vaginal dryness | -0.2 Scores on a Scale | Standard Deviation 0.79 |
| Placebo | Changes in Vulvar Vaginal Atrophy (VVA) Symptom Score From Baseline to Visit 8 (Week 12) | Vaginal symptoms interference with social activity | 0.0 Scores on a Scale | Standard Deviation 0.69 |
| Placebo | Changes in Vulvar Vaginal Atrophy (VVA) Symptom Score From Baseline to Visit 8 (Week 12) | Severity of painful urination | 0.0 Scores on a Scale | Standard Deviation 0.43 |
| Placebo | Changes in Vulvar Vaginal Atrophy (VVA) Symptom Score From Baseline to Visit 8 (Week 12) | Severity of urinating difficulty | 0.0 Scores on a Scale | Standard Deviation 0.19 |
| Placebo | Changes in Vulvar Vaginal Atrophy (VVA) Symptom Score From Baseline to Visit 8 (Week 12) | Vaginal symptoms interference with sexual activity | -0.1 Scores on a Scale | Standard Deviation 0.85 |
| Placebo | Changes in Vulvar Vaginal Atrophy (VVA) Symptom Score From Baseline to Visit 8 (Week 12) | Severity of vaginal pain due to sexual activity | -0.1 Scores on a Scale | Standard Deviation 0.75 |
| Placebo | Changes in Vulvar Vaginal Atrophy (VVA) Symptom Score From Baseline to Visit 8 (Week 12) | Vaginal symptoms interference with daily activity | -0.1 Scores on a Scale | Standard Deviation 0.8 |
| Placebo | Changes in Vulvar Vaginal Atrophy (VVA) Symptom Score From Baseline to Visit 8 (Week 12) | Vaginal bleeding severity due to sexual activity | 0.0 Scores on a Scale | Standard Deviation 0 |
| Placebo | Changes in Vulvar Vaginal Atrophy (VVA) Symptom Score From Baseline to Visit 8 (Week 12) | Severity of vaginal itching | 0.0 Scores on a Scale | Standard Deviation 0.75 |
| Placebo | Changes in Vulvar Vaginal Atrophy (VVA) Symptom Score From Baseline to Visit 8 (Week 12) | Bothered by vaginal dryness | -0.1 Scores on a Scale | Standard Deviation 0.79 |
| Placebo | Changes in Vulvar Vaginal Atrophy (VVA) Symptom Score From Baseline to Visit 8 (Week 12) | Vaginal bleeding due to sexual activity bothering | 0.0 Scores on a Scale | Standard Deviation 0 |
| Placebo | Changes in Vulvar Vaginal Atrophy (VVA) Symptom Score From Baseline to Visit 8 (Week 12) | Bothered by vaginal itching | -0.1 Scores on a Scale | Standard Deviation 0.69 |
| GSK232802 25 mg | Changes in Vulvar Vaginal Atrophy (VVA) Symptom Score From Baseline to Visit 8 (Week 12) | Bothered by vaginal dryness | -0.1 Scores on a Scale | Standard Deviation 0.83 |
| GSK232802 25 mg | Changes in Vulvar Vaginal Atrophy (VVA) Symptom Score From Baseline to Visit 8 (Week 12) | Bothered by vaginal pain due to sexual activity | -0.1 Scores on a Scale | Standard Deviation 0.7 |
| GSK232802 25 mg | Changes in Vulvar Vaginal Atrophy (VVA) Symptom Score From Baseline to Visit 8 (Week 12) | Severity of urinating difficulty | 0.0 Scores on a Scale | Standard Deviation 0.43 |
| GSK232802 25 mg | Changes in Vulvar Vaginal Atrophy (VVA) Symptom Score From Baseline to Visit 8 (Week 12) | Bothered by vaginal irritation | -0.1 Scores on a Scale | Standard Deviation 0.66 |
| GSK232802 25 mg | Changes in Vulvar Vaginal Atrophy (VVA) Symptom Score From Baseline to Visit 8 (Week 12) | Vaginal symptoms interference with social activity | -0.1 Scores on a Scale | Standard Deviation 0.62 |
| GSK232802 25 mg | Changes in Vulvar Vaginal Atrophy (VVA) Symptom Score From Baseline to Visit 8 (Week 12) | Vaginal symptoms interference with daily activity | 0.0 Scores on a Scale | Standard Deviation 0.5 |
| GSK232802 25 mg | Changes in Vulvar Vaginal Atrophy (VVA) Symptom Score From Baseline to Visit 8 (Week 12) | Vaginal bleeding severity due to sexual activity | 0.0 Scores on a Scale | Standard Deviation 0.35 |
| GSK232802 25 mg | Changes in Vulvar Vaginal Atrophy (VVA) Symptom Score From Baseline to Visit 8 (Week 12) | Bothered by painful urination | 0.1 Scores on a Scale | Standard Deviation 0.46 |
| GSK232802 25 mg | Changes in Vulvar Vaginal Atrophy (VVA) Symptom Score From Baseline to Visit 8 (Week 12) | Severity of vaginal irritation | 0.0 Scores on a Scale | Standard Deviation 0.5 |
| GSK232802 25 mg | Changes in Vulvar Vaginal Atrophy (VVA) Symptom Score From Baseline to Visit 8 (Week 12) | Bothered by difficulty in urination | 0.1 Scores on a Scale | Standard Deviation 0.4 |
| GSK232802 25 mg | Changes in Vulvar Vaginal Atrophy (VVA) Symptom Score From Baseline to Visit 8 (Week 12) | Severity of vaginal itching | 0.1 Scores on a Scale | Standard Deviation 0.65 |
| GSK232802 25 mg | Changes in Vulvar Vaginal Atrophy (VVA) Symptom Score From Baseline to Visit 8 (Week 12) | Severity of vaginal pain due to sexual activity | 0.0 Scores on a Scale | Standard Deviation 0.78 |
| GSK232802 25 mg | Changes in Vulvar Vaginal Atrophy (VVA) Symptom Score From Baseline to Visit 8 (Week 12) | Bothered by vaginal itching | 0.0 Scores on a Scale | Standard Deviation 0.58 |
| GSK232802 25 mg | Changes in Vulvar Vaginal Atrophy (VVA) Symptom Score From Baseline to Visit 8 (Week 12) | Vaginal bleeding due to sexual activity bothering | 0.0 Scores on a Scale | Standard Deviation 0.41 |
| GSK232802 25 mg | Changes in Vulvar Vaginal Atrophy (VVA) Symptom Score From Baseline to Visit 8 (Week 12) | Severity of painful urination | 0.0 Scores on a Scale | Standard Deviation 0.36 |
| GSK232802 25 mg | Changes in Vulvar Vaginal Atrophy (VVA) Symptom Score From Baseline to Visit 8 (Week 12) | Severity of vaginal dryness | -0.1 Scores on a Scale | Standard Deviation 0.81 |
| GSK232802 25 mg | Changes in Vulvar Vaginal Atrophy (VVA) Symptom Score From Baseline to Visit 8 (Week 12) | Vaginal symptoms interference with sexual activity | -0.1 Scores on a Scale | Standard Deviation 0.86 |
| GSK232802 75 mg | Changes in Vulvar Vaginal Atrophy (VVA) Symptom Score From Baseline to Visit 8 (Week 12) | Severity of vaginal itching | -0.2 Scores on a Scale | Standard Deviation 0.74 |
| GSK232802 75 mg | Changes in Vulvar Vaginal Atrophy (VVA) Symptom Score From Baseline to Visit 8 (Week 12) | Severity of vaginal dryness | -0.3 Scores on a Scale | Standard Deviation 0.86 |
| GSK232802 75 mg | Changes in Vulvar Vaginal Atrophy (VVA) Symptom Score From Baseline to Visit 8 (Week 12) | Severity of vaginal irritation | -0.1 Scores on a Scale | Standard Deviation 0.74 |
| GSK232802 75 mg | Changes in Vulvar Vaginal Atrophy (VVA) Symptom Score From Baseline to Visit 8 (Week 12) | Severity of painful urination | 0.0 Scores on a Scale | Standard Deviation 0.48 |
| GSK232802 75 mg | Changes in Vulvar Vaginal Atrophy (VVA) Symptom Score From Baseline to Visit 8 (Week 12) | Severity of urinating difficulty | -0.1 Scores on a Scale | Standard Deviation 0.36 |
| GSK232802 75 mg | Changes in Vulvar Vaginal Atrophy (VVA) Symptom Score From Baseline to Visit 8 (Week 12) | Severity of vaginal pain due to sexual activity | -0.1 Scores on a Scale | Standard Deviation 0.93 |
| GSK232802 75 mg | Changes in Vulvar Vaginal Atrophy (VVA) Symptom Score From Baseline to Visit 8 (Week 12) | Vaginal bleeding severity due to sexual activity | 0.0 Scores on a Scale | Standard Deviation 0.36 |
| GSK232802 75 mg | Changes in Vulvar Vaginal Atrophy (VVA) Symptom Score From Baseline to Visit 8 (Week 12) | Bothered by vaginal dryness | -0.3 Scores on a Scale | Standard Deviation 0.89 |
| GSK232802 75 mg | Changes in Vulvar Vaginal Atrophy (VVA) Symptom Score From Baseline to Visit 8 (Week 12) | Bothered by vaginal itching | -0.3 Scores on a Scale | Standard Deviation 0.72 |
| GSK232802 75 mg | Changes in Vulvar Vaginal Atrophy (VVA) Symptom Score From Baseline to Visit 8 (Week 12) | Bothered by vaginal irritation | -0.2 Scores on a Scale | Standard Deviation 0.77 |
| GSK232802 75 mg | Changes in Vulvar Vaginal Atrophy (VVA) Symptom Score From Baseline to Visit 8 (Week 12) | Bothered by painful urination | -0.1 Scores on a Scale | Standard Deviation 0.69 |
| GSK232802 75 mg | Changes in Vulvar Vaginal Atrophy (VVA) Symptom Score From Baseline to Visit 8 (Week 12) | Bothered by difficulty in urination | -0.1 Scores on a Scale | Standard Deviation 0.51 |
| GSK232802 75 mg | Changes in Vulvar Vaginal Atrophy (VVA) Symptom Score From Baseline to Visit 8 (Week 12) | Bothered by vaginal pain due to sexual activity | 0.0 Scores on a Scale | Standard Deviation 0.96 |
| GSK232802 75 mg | Changes in Vulvar Vaginal Atrophy (VVA) Symptom Score From Baseline to Visit 8 (Week 12) | Vaginal bleeding due to sexual activity bothering | -0.1 Scores on a Scale | Standard Deviation 0.58 |
| GSK232802 75 mg | Changes in Vulvar Vaginal Atrophy (VVA) Symptom Score From Baseline to Visit 8 (Week 12) | Vaginal symptoms interference with sexual activity | -0.2 Scores on a Scale | Standard Deviation 1.1 |
| GSK232802 75 mg | Changes in Vulvar Vaginal Atrophy (VVA) Symptom Score From Baseline to Visit 8 (Week 12) | Vaginal symptoms interference with social activity | -0.1 Scores on a Scale | Standard Deviation 0.88 |
| GSK232802 75 mg | Changes in Vulvar Vaginal Atrophy (VVA) Symptom Score From Baseline to Visit 8 (Week 12) | Vaginal symptoms interference with daily activity | -0.2 Scores on a Scale | Standard Deviation 0.64 |
| Premarin 0.3 mg | Changes in Vulvar Vaginal Atrophy (VVA) Symptom Score From Baseline to Visit 8 (Week 12) | Bothered by vaginal pain due to sexual activity | -0.3 Scores on a Scale | Standard Deviation 0.95 |
| Premarin 0.3 mg | Changes in Vulvar Vaginal Atrophy (VVA) Symptom Score From Baseline to Visit 8 (Week 12) | Bothered by vaginal dryness | -0.3 Scores on a Scale | Standard Deviation 1.04 |
| Premarin 0.3 mg | Changes in Vulvar Vaginal Atrophy (VVA) Symptom Score From Baseline to Visit 8 (Week 12) | Severity of vaginal pain due to sexual activity | -0.4 Scores on a Scale | Standard Deviation 0.98 |
| Premarin 0.3 mg | Changes in Vulvar Vaginal Atrophy (VVA) Symptom Score From Baseline to Visit 8 (Week 12) | Severity of vaginal dryness | -0.4 Scores on a Scale | Standard Deviation 1.03 |
| Premarin 0.3 mg | Changes in Vulvar Vaginal Atrophy (VVA) Symptom Score From Baseline to Visit 8 (Week 12) | Vaginal bleeding due to sexual activity bothering | 0.0 Scores on a Scale | Standard Deviation 0.13 |
| Premarin 0.3 mg | Changes in Vulvar Vaginal Atrophy (VVA) Symptom Score From Baseline to Visit 8 (Week 12) | Severity of urinating difficulty | 0.0 Scores on a Scale | Standard Deviation 0.5 |
| Premarin 0.3 mg | Changes in Vulvar Vaginal Atrophy (VVA) Symptom Score From Baseline to Visit 8 (Week 12) | Severity of painful urination | -0.1 Scores on a Scale | Standard Deviation 0.64 |
| Premarin 0.3 mg | Changes in Vulvar Vaginal Atrophy (VVA) Symptom Score From Baseline to Visit 8 (Week 12) | Vaginal bleeding severity due to sexual activity | 0.0 Scores on a Scale | Standard Deviation 0.15 |
| Premarin 0.3 mg | Changes in Vulvar Vaginal Atrophy (VVA) Symptom Score From Baseline to Visit 8 (Week 12) | Vaginal symptoms interference with sexual activity | -0.6 Scores on a Scale | Standard Deviation 1.15 |
| Premarin 0.3 mg | Changes in Vulvar Vaginal Atrophy (VVA) Symptom Score From Baseline to Visit 8 (Week 12) | Severity of vaginal irritation | 0.0 Scores on a Scale | Standard Deviation 0.67 |
| Premarin 0.3 mg | Changes in Vulvar Vaginal Atrophy (VVA) Symptom Score From Baseline to Visit 8 (Week 12) | Severity of vaginal itching | 0.0 Scores on a Scale | Standard Deviation 0.58 |
| Premarin 0.3 mg | Changes in Vulvar Vaginal Atrophy (VVA) Symptom Score From Baseline to Visit 8 (Week 12) | Bothered by painful urination | -0.1 Scores on a Scale | Standard Deviation 0.52 |
| Premarin 0.3 mg | Changes in Vulvar Vaginal Atrophy (VVA) Symptom Score From Baseline to Visit 8 (Week 12) | Vaginal symptoms interference with daily activity | -0.2 Scores on a Scale | Standard Deviation 0.57 |
| Premarin 0.3 mg | Changes in Vulvar Vaginal Atrophy (VVA) Symptom Score From Baseline to Visit 8 (Week 12) | Bothered by difficulty in urination | 0.0 Scores on a Scale | Standard Deviation 0.46 |
| Premarin 0.3 mg | Changes in Vulvar Vaginal Atrophy (VVA) Symptom Score From Baseline to Visit 8 (Week 12) | Bothered by vaginal irritation | -0.1 Scores on a Scale | Standard Deviation 0.63 |
| Premarin 0.3 mg | Changes in Vulvar Vaginal Atrophy (VVA) Symptom Score From Baseline to Visit 8 (Week 12) | Bothered by vaginal itching | 0.1 Scores on a Scale | Standard Deviation 0.69 |
| Premarin 0.3 mg | Changes in Vulvar Vaginal Atrophy (VVA) Symptom Score From Baseline to Visit 8 (Week 12) | Vaginal symptoms interference with social activity | -0.2 Scores on a Scale | Standard Deviation 0.72 |
Secondary
Mean Change in Frequency of VMS From Baseline to Weeks 4 and 8
Individual VMS (hot flash or night sweats) events were recorded by participants in an 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.
Time frame: Baseline (Week 0) to Week 8
Population: ITT Population with LOCF analysis. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Mean Change in Frequency of VMS From Baseline to Weeks 4 and 8 | Week 4 | -4.20 Scores on a Scale | Standard Error 0.435 |
| Placebo | Mean Change in Frequency of VMS From Baseline to Weeks 4 and 8 | Week 8 | -5.00 Scores on a Scale | Standard Error 0.446 |
| GSK232802 25 mg | Mean Change in Frequency of VMS From Baseline to Weeks 4 and 8 | Week 8 | -4.09 Scores on a Scale | Standard Error 0.5 |
| GSK232802 25 mg | Mean Change in Frequency of VMS From Baseline to Weeks 4 and 8 | Week 4 | -3.95 Scores on a Scale | Standard Error 0.487 |
| GSK232802 75 mg | Mean Change in Frequency of VMS From Baseline to Weeks 4 and 8 | Week 4 | -4.27 Scores on a Scale | Standard Error 0.469 |
| GSK232802 75 mg | Mean Change in Frequency of VMS From Baseline to Weeks 4 and 8 | Week 8 | -4.07 Scores on a Scale | Standard Error 0.479 |
| Premarin 0.3 mg | Mean Change in Frequency of VMS From Baseline to Weeks 4 and 8 | Week 4 | -5.68 Scores on a Scale | Standard Error 0.447 |
| Premarin 0.3 mg | Mean Change in Frequency of VMS From Baseline to Weeks 4 and 8 | Week 8 | -7.24 Scores on a Scale | Standard Error 0.459 |
Secondary
Mean Change in Severity of VMS From Baseline to Weeks 4 and 8
Individual VMS (hot flash or night sweats) events were recorded by participants in an eDiary using global change questions. The 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.
Time frame: Baseline (Week 0) to Week 8
Population: ITT Population with LOCF analysis. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Mean Change in Severity of VMS From Baseline to Weeks 4 and 8 | Week 4 | -0.39 Scores on a Scale | Standard Error 0.072 |
| Placebo | Mean Change in Severity of VMS From Baseline to Weeks 4 and 8 | Week 8 | -0.32 Scores on a Scale | Standard Error 0.081 |
| GSK232802 25 mg | Mean Change in Severity of VMS From Baseline to Weeks 4 and 8 | Week 8 | -0.11 Scores on a Scale | Standard Error 0.091 |
| GSK232802 25 mg | Mean Change in Severity of VMS From Baseline to Weeks 4 and 8 | Week 4 | -0.22 Scores on a Scale | Standard Error 0.079 |
| GSK232802 75 mg | Mean Change in Severity of VMS From Baseline to Weeks 4 and 8 | Week 4 | -0.22 Scores on a Scale | Standard Error 0.076 |
| GSK232802 75 mg | Mean Change in Severity of VMS From Baseline to Weeks 4 and 8 | Week 8 | -0.14 Scores on a Scale | Standard Error 0.086 |
| Premarin 0.3 mg | Mean Change in Severity of VMS From Baseline to Weeks 4 and 8 | Week 4 | -0.62 Scores on a Scale | Standard Error 0.073 |
| Premarin 0.3 mg | Mean Change in Severity of VMS From Baseline to Weeks 4 and 8 | Week 8 | -0.77 Scores on a Scale | Standard Error 0.083 |
Secondary
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%
Individual VMS (hot flash or night sweats) events were recorded by participants in an eDiary using global change question. The severity of VMS events were calculated using self-reported participants assessments recorded and transmitted by eDiary. Baseline was Week 0. Change from Baseline was calculated by subtracting Baseline values from post-Baseline values. Percent change was calculated by multiplying the change from baseline value with 100. 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% are presented.
Time frame: Baseline (Week 0) and Week 12
Population: ITT Population with LOCF analysis. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | 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% | At least 50% reduction in frequency | 43 Participants |
| Placebo | 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% | At least 100% reduction in frequency | 3 Participants |
| Placebo | 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% | At least 75% reduction in frequency | 21 Participants |
| GSK232802 25 mg | 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% | At least 100% reduction in frequency | 1 Participants |
| GSK232802 25 mg | 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% | At least 75% reduction in frequency | 16 Participants |
| GSK232802 25 mg | 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% | At least 50% reduction in frequency | 36 Participants |
| GSK232802 75 mg | 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% | At least 100% reduction in frequency | 0 Participants |
| GSK232802 75 mg | 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% | At least 50% reduction in frequency | 32 Participants |
| GSK232802 75 mg | 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% | At least 75% reduction in frequency | 15 Participants |
| Premarin 0.3 mg | 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% | At least 100% reduction in frequency | 10 Participants |
| Premarin 0.3 mg | 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% | At least 50% reduction in frequency | 61 Participants |
| Premarin 0.3 mg | 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% | At least 75% reduction in frequency | 42 Participants |
Secondary
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%
Individual VMS (hot flash or night sweats) events were recorded by participants in an eDiary using global change questions. The VMS severity was as follows: mild (brief wave of heat with minimal discomfort, usually without perspiration; able to continue activity \[or sleep\]), moderate (heat with some discomfort, usually with perspiration; minimal interruption of activity \[or sleep\]), severe (intense heat with considerable discomfort, usually with heavy sweating; may be unable to resume activity \[or sleep\] right away) and extremely severe (unbearable heat with intense discomfort, usually with pouring sweat; may be unable to resume activity \[or sleep\] for quite a while). The severity of VMS events were calculated using self-reported participants assessments recorded and transmitted by eDiary. Baseline was Week 0. Change from Baseline was calculated by subtracting Baseline values from post-Baseline values. Percent change was calculated by multiplying change from Baseline value with 100.
Time frame: Baseline (Week 0) and Week 12
Population: ITT Population with LOCF analysis. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | 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% | At least 100% reduction in severity | 3 Participants |
| Placebo | 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% | At least 75% reduction in severity | 3 Participants |
| Placebo | 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% | At least 50% reduction in severity | 8 Participants |
| GSK232802 25 mg | 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% | At least 75% reduction in severity | 1 Participants |
| GSK232802 25 mg | 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% | At least 100% reduction in severity | 1 Participants |
| GSK232802 25 mg | 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% | At least 50% reduction in severity | 7 Participants |
| GSK232802 75 mg | 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% | At least 100% reduction in severity | 0 Participants |
| GSK232802 75 mg | 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% | At least 50% reduction in severity | 3 Participants |
| GSK232802 75 mg | 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% | At least 75% reduction in severity | 0 Participants |
| Premarin 0.3 mg | 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% | At least 75% reduction in severity | 10 Participants |
| Premarin 0.3 mg | 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% | At least 50% reduction in severity | 28 Participants |
| Premarin 0.3 mg | 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% | At least 100% reduction in severity | 10 Participants |