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Treatment Of Hot Flashes/Flushes In Postmenopausal Women (WARM Study)

This study has been completed.
Information provided by (Responsible Party):
GlaxoSmithKline Identifier:
First received: January 17, 2008
Last updated: August 27, 2015
Last verified: August 2015
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.

Condition Intervention Phase
Menopausal and Female Climacteric States Hot Flashes Drug: Other: Placebo Drug: GSK232802 Drug: PREMARIN Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Parallel-group, Double-blind, Randomized, Placebo-controlled, Active Comparator, Multicenter Study to Evaluate the Efficacy, Safety, Tolerability and Pharmacokinetics of Two Doses of GSK232802 Administered Orally as Monotherapy for 12 Weeks in Healthy Postmenopausal Women With Moderate to Extremely Severe Vasomotor Symptoms

Resource links provided by NLM:

Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Change from baseline to 12 weeks in frequency and severity of hot flashes recorded using a daily electronic diary [ Time Frame: 12 Weeks ]

Secondary Outcome Measures:
  • Frequency and severity of hot flashes at 4 and 8 wks; self administered health outcomes questionnaires; vaginal cytology; changes in uterine endometrial lining by ultrasound and biopsy; clinical labs; body weight, BMI by standard measurements [ Time Frame: 12 Weeks ]
  • The secondary efficacy endpoints include the following measures of VMS (see Section 6.3.2): [ Time Frame: 12 Weeks ]
  • Mean change in frequency of VMS from baseline to Weeks 4 and 8 [ Time Frame: 12 Weeks ]
  • Mean change in severity of VMS from baseline to Weeks 4 and 8 [ Time Frame: 12 Weeks ]
  • Proportion of subjects with a reduction in frequency of VMS at Week 12 of at least 50%, at least 75%, and 100% [ Time Frame: 12 Weeks ]
  • Proportion of subjects with a reduction in severity of VMS at Week 12 of at least 50%, at least 75%, and 100% [ Time Frame: 12 Weeks ]
  • Effects on patient-reported outcomes as assessed via the following questionnaires: [ Time Frame: 12 Weeks ]
  • Change in Menopause Quality of Life (MENQOL) score from Visit 4 (Day 0) to Visits 6 and 8 [ Time Frame: 12 Weeks ]
  • Change in Medical Outcomes Study (MOS) Sleep score from Visit 4 (Day 0) to Visits 6 and 8 [ Time Frame: 12 Weeks ]
  • Changes in VVA symptom score from Visit 4 to Visit 8 [ Time Frame: 12 Weeks ]
  • Change in Brief Fatigue Inventory (BFI) score from Visit 2 to Visit 7 [ Time Frame: 12 Weeks ]
  • Change in the Centers for Epidemiologic Studies in Depression (CES-D) score from Visit 2 to Visit 7 [ Time Frame: 12 Weeks ]
  • Change in Work Productivity and Activity Impairment (WPAI) score from Visit 2 to Visit 7 [ Time Frame: 12 Weeks ]
  • Change from Visit 2 to Visit 8 in vaginal pH and percentage of superficial cells to determine the Vaginal Maturation Index (VMI). [ Time Frame: 12 Weeks ]
  • Change in serum hormone levels from Visit 4 to each of the following: [ Time Frame: 12 Weeks ]
  • Visits 6, 7, 8, and 9 and change in additional PD markers including fasting insulin, glucose, leptin, and adiponectin levels, and markers of bone turnover from Visit 4 to Visit 8 (see Section 6.5). [ Time Frame: 12 Weeks ]
  • Absolute change in body weight, body mass index (BMI), waist and hip circumference from Visit 4 to each of the following: Visits 6, 7, 8, and 9. [ Time Frame: 12 Weeks ]
  • In a subset of subjects, absolute change in neck and thigh circumference, and percent change in total body fat, visceral fat, [ Time Frame: 12 Weeks ]
  • and subcutaneous fat from screening (assessed between Visits 2 and 4, before treatment) to follow-up (assessed between Visits 8 and 9). [ Time Frame: 12 Weeks ]

Enrollment: 359
Study Start Date: July 2007
Study Completion Date: July 2008
Primary Completion Date: July 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo
Drug: Other: Placebo
Active Comparator: GSK232802
Drug: GSK232802
Experimental: PREMARIN
Other Names:
  • GSK232802
  • Other: Placebo


Ages Eligible for Study:   40 Years to 65 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts 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/exclusion criteria);
  • Evidence of an endometrial polyp with hyperplastic or malignant epithelium;
  • Unexplained or unusual endometrial bleeding; or uterine surgery (other than hysterectomy*) within the past 6 months; *Note: hysterectomy must have been conducted at least 6 weeks prior to screening Visit 1. See also Inclusion criterion 1.
  • Abnormal cervical Pap smear with evidence of cervical dysplasia greater than or equal to low grade squamous intraepithelial lesion (LSIL) or with a diagnosis of atypical squamous cells of undetermined significance (ASCUS) that is HPV High Risk positive, or glandular lesions including but not limited to atypical glandular cells of undetermined significance (AGUS), adenocarcinoma in situ (AIS) or malignancy
  • History of breast or ovarian cancer. Any clinically significant findings on mammography suspicious of breast malignancy that would require additional clinical testing to rule out breast cancer (note: simple cysts confirmed by ultrasound are allowed).

Note: A screening mammogram is required unless the subject has had a mammogram performed within the last 12 months. If local mammography or medical management guidelines restrict the frequency with which mammograms can be performed, or impose age restrictions on the use of mammography, such that a subject may be unable to undergo the study-required screening mammogram, then these subjects must not be enrolled in the study. See Section 6.2.7.

- Cardiovascular conditions including: i. Systolic blood pressure (BP) outside the range 80 to 150 mmHg, diastolic BP outside the range 50 to 90 mmHg, and/or heart rate outside the range 40 to 100 bpm. Subjects with mild to moderate hypertension who are controlled on a stable antihypertension regimen may be enrolled if they meet the inclusion/exclusion criteria.

ii. Symptomatic or asymptomatic arrhythmia of any clinical significance. iii. Any clinically significant abnormality identified on the screening 12-lead ECG. Subjects with QTc prolongation (QTc interval >450msec) will be excluded.

iv. Has a documented history (within the last year) of myocardial infarction, angina, or has undergone coronary artery bypass surgery and/or percutaneous transluminal coronary angioplasty (PTCA).

v. History of venous or arterial thromboembolic disease (e.g., deep vein thrombosis, pulmonary embolism, stroke), history of known coagulopathy or abnormal coagulation factors; increased thrombotic risk as evidenced by positive APC resistance (APCR) evaluated at screening.

- Has a documented history of hepatobiliary disease or hepatic enzyme elevation including any one of the following: i.ALT or direct (conjugated) bilirubin values 1.5-fold higher than the ULN at screening.

ii.Fasting triglycerides >400mg/dL (SI: >4.52mmol/L) at screening. If a subject is receiving a lipid-lowering therapy, then she must be on a stable dose for at least 1 month before screening.

  • Has an abnormal thyroid function test assessed by TSH at screening (TSH <0.1uU/mL or >10uU/mL [SI: <0.1mU/L or >10mU/L] ).

Note: If the TSH is mildly out of range at screening (TSH < 15U/mL), the subject may have her dose adjusted (if already on exogenous therapy) or have therapy initiated as deemed appropriate by the subject's physician, followed by a 3-4 week period to allow adequate equilibration. The TSH may then be re-assayed for eligibility purposes after this stabilization period has been completed. The subject should not progress through subsequent V2 assessments until re-assay demonstrates the TSH is within acceptable protocol-defined limits. Subjects with suppressed levels of TSH, <0.1U/mL, may have dose adjustment if free T4 is in normal range, and they are on exogenous thyroxine therapy.

  • Has either a previous disease or current medical condition, which as judged by the investigator, may affect the interpretation of efficacy or safety data or which otherwise contraindicates participation in a clinical study with a new chemical entity. These diseases include, but are not limited to, cardiovascular disease, malignancy*, complex ovarian pathology, hepatic disease, renal disease, hematological disease, neurological disease, or endocrine disease. A subject with diabetes may be included if her diabetes is well controlled (i.e., HbA1c level is less than 8% at screening).

    *Note: Any history of malignancy within the past 5 years is exclusionary with the exception of basal cell (excluded if within the prior 2 years) or squamous cell (excluded if within the prior one year) carcinoma of the skin. Subjects with a prior malignancy who have had no evidence of disease for at least the past 5 years are eligible. Note that this timeframe does not apply to uterine, breast, and ovarian cancers which are defined in Exclusions 4 and 5 above.

  • History of alcohol or substance abuse or dependence in the 12 months before screening as determined by the investigator.
  • Positive results for hepatitis B surface antigen or hepatitis C antibodies as evaluated at screening Visit 1. Known history of HIV.
  • Donation of blood in excess of 500mL within a 56-day period before screening.
  • History or presence of allergy to the investigational product or drugs of this class (e.g., raloxifene), or history of drug or other allergy that, in the opinion of the physician responsible, contraindicates their participation.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT00604825

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United States, Arizona
GSK Investigational Site
Chandler, Arizona, United States, 85225
GSK Investigational Site
Glendale, Arizona, United States, 85308
GSK Investigational Site
Scottsdale, Arizona, United States, 85251
GSK Investigational Site
Tucson, Arizona, United States, 85710
United States, California
GSK Investigational Site
Poway, California, United States, 92064
GSK Investigational Site
San Diego, California, United States, 92103
GSK Investigational Site
San Diego, California, United States, 92108
United States, Colorado
GSK Investigational Site
Aurora, Colorado, United States, 80012
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Boulder, Colorado, United States, 80301
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Denver, Colorado, United States, 80202
GSK Investigational Site
Wheat Ridge, Colorado, United States, 80043
United States, District of Columbia
GSK Investigational Site
Washington, District of Columbia, United States, 20036
United States, Florida
GSK Investigational Site
Crystal River, Florida, United States, 34429
GSK Investigational Site
Fort Myers, Florida, United States, 33916
GSK Investigational Site
Jacksonville, Florida, United States, 32259
GSK Investigational Site
Miami, Florida, United States, 33143
GSK Investigational Site
Pinellas Park, Florida, United States, 33781
United States, Georgia
GSK Investigational Site
Atlanta, Georgia, United States, 30328
GSK Investigational Site
Savannah, Georgia, United States, 31405
United States, Kansas
GSK Investigational Site
Overland Park, Kansas, United States, 66202
United States, Kentucky
GSK Investigational Site
Louisville, Kentucky, United States, 40291
United States, Louisiana
GSK Investigational Site
Sunset, Louisiana, United States, 70584
United States, Michigan
GSK Investigational Site
St Clair Shores, Michigan, United States, 48081
United States, Montana
GSK Investigational Site
Billings, Montana, United States, 59102
United States, Nevada
GSK Investigational Site
Las Vegas, Nevada, United States, 89119
GSK Investigational Site
Las Vegas, Nevada, United States, 89146
United States, New Jersey
GSK Investigational Site
New Brunswick, New Jersey, United States, 08901
United States, New Mexico
GSK Investigational Site
Albuquerque, New Mexico, United States, 87102
GSK Investigational Site
Albuquerque, New Mexico, United States, 87106
United States, North Carolina
GSK Investigational Site
Chapel Hill, North Carolina, United States, 27599-7570
United States, Ohio
GSK Investigational Site
Cincinnati, Ohio, United States, 45249
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Cleveland, Ohio, United States, 44122
United States, Oregon
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Eugene, Oregon, United States, 97401
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Portland, Oregon, United States, 97205
United States, Pennsylvania
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Philadelphia, Pennsylvania, United States, 19114
United States, South Carolina
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Hilton Head Island, South Carolina, United States, 29926
United States, Texas
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Dallas, Texas, United States, 75234
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Midland, Texas, United States, 79707
United States, Virginia
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Norfolk, Virginia, United States, 23507
United States, Washington
GSK Investigational Site
Seattle, Washington, United States, 98105
GSK Investigational Site
Tacoma, Washington, United States, 98405
GSK Investigational Site
Buenos Aries, Buenos Aires, Argentina, C1425AWC
GSK Investigational Site
Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina, C1117ABH
GSK Investigational Site
Buenos Aires, Argentina, 1425
GSK Investigational Site
Ciudad Autonoma de Buenos Aires, Argentina, 1012
GSK Investigational Site
Ciudad Autónoma de Buenos Aires, Argentina, C1128AAF
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Mendoza, Argentina, 5500
Australia, Queensland
GSK Investigational Site
Auchenflower, Queensland, Australia, 4066
GSK Investigational Site
Kippa Ring, Queensland, Australia, 4021
Australia, South Australia
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Dulwich, South Australia, Australia, 5065
Australia, Western Australia
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Nedlands, Western Australia, Australia, 6009
GSK Investigational Site
Subiaco, Western Australia, Australia, 6008
GSK Investigational Site
Frankfurt, Hessen, Germany, 60322
GSK Investigational Site
Frankfurt, Hessen, Germany, 60439
GSK Investigational Site
Muehlheim, Hessen, Germany, 63165
GSK Investigational Site
Hannover, Niedersachsen, Germany, 30159
GSK Investigational Site
Muenster, Nordrhein-Westfalen, Germany, 48149
GSK Investigational Site
Magdeburg, Sachsen-Anhalt, Germany, 39112
GSK Investigational Site
Magdeburg, Sachsen-Anhalt, Germany, 39122
GSK Investigational Site
Dresden, Sachsen, Germany, 01307
GSK Investigational Site
Leipzg, Sachsen, Germany, 04109
GSK Investigational Site
Leipzig, Sachsen, Germany, 04103
GSK Investigational Site
Nordhausen, Thueringen, Germany, 99734
GSK Investigational Site
Berlin, Germany, 12163
GSK Investigational Site
Hamburg, Germany, 22159
GSK Investigational Site
Napoli, Campania, Italy, 80131
GSK Investigational Site
Bologna, Emilia-Romagna, Italy, 40138
GSK Investigational Site
Modena, Emilia-Romagna, Italy, 41100
GSK Investigational Site
Firenze, Toscana, Italy, 50134
New Zealand
GSK Investigational Site
Auckland, New Zealand, 0622
GSK Investigational Site
Christchurch, New Zealand
GSK Investigational Site
Wellington, New Zealand
GSK Investigational Site
Lugo, Spain, 27002
GSK Investigational Site
Oviedo, Spain, 33006
GSK Investigational Site
Santiago de Compostela, Spain, 15706
GSK Investigational Site
Göteborg, Sweden, SE-411 15
GSK Investigational Site
Göteborg, Sweden, SE-411 17
GSK Investigational Site
Göteborg, Sweden, SE-411 37
GSK Investigational Site
Göteborg, Sweden, SE-416 85
GSK Investigational Site
Kungsbacka, Sweden, SE-434 30
GSK Investigational Site
Uddevalla, Sweden, SE-451 30
United Kingdom
GSK Investigational Site
Cambridge, Cambridgeshire, United Kingdom, CB2 2GG
GSK Investigational Site
Buckshaw Village, Chorley, Lancashire, United Kingdom, PR7 7NA
GSK Investigational Site
Manchester, Lancashire, United Kingdom, M15 6SX
GSK Investigational Site
Harrow, Middlesex, United Kingdom, HA1 3UJ
GSK Investigational Site
Oxford, Oxfordshire, United Kingdom, OX3 9DU
GSK Investigational Site
Waterloo, Liverpool, United Kingdom, L22 0LG
Sponsors and Collaborators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

Responsible Party: GlaxoSmithKline Identifier: NCT00604825     History of Changes
Other Study ID Numbers: 105106
Study First Received: January 17, 2008
Last Updated: August 27, 2015

Keywords provided by GlaxoSmithKline:
vasomotor symptoms
hormone therapy
hot flashes

Additional relevant MeSH terms:
Hot Flashes
Signs and Symptoms
Estrogens, Conjugated (USP)
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs processed this record on August 22, 2017