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

NCT ID: NCT00604825

Last Updated: 2017-10-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 356 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-07-17
• Study Completion Date: 2008-07-23

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.

Conditions

Menopausal and Female Climacteric States

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Placebo

Placebo

Group Type: PLACEBO_COMPARATOR

Other: Placebo

Intervention Type: DRUG

GSK232802

GSK232802

Group Type: ACTIVE_COMPARATOR

GSK232802

Intervention Type: DRUG

PREMARIN

PREMARIN

Group Type: EXPERIMENTAL

PREMARIN

Intervention Type: DRUG

Interventions

Other: Placebo

Intervention Type: DRUG

GSK232802

Intervention Type: DRUG

PREMARIN

Intervention Type: DRUG

Other Intervention Names

Other: Placebo; GSK232802

Eligibility Criteria

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;
• 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.

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.

• Minimum Eligible Age: 40 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

GSK Investigational Site

Buenos Aires, , Argentina

GSK Investigational Site

Buenos Aires, , Argentina

GSK Investigational Site

Mendoza, , Argentina

GSK Investigational Site

Chandler, Arizona, United States

GSK Investigational Site

Glendale, Arizona, United States

GSK Investigational Site

Scottsdale, Arizona, United States

GSK Investigational Site

Tucson, Arizona, United States

GSK Investigational Site

Poway, California, United States

GSK Investigational Site

San Diego, California, United States

GSK Investigational Site

San Diego, California, United States

GSK Investigational Site

Aurora, Colorado, United States

GSK Investigational Site

Boulder, Colorado, United States

GSK Investigational Site

Denver, Colorado, United States

GSK Investigational Site

Wheat Ridge, Colorado, United States

GSK Investigational Site

Washington D.C., District of Columbia, United States

GSK Investigational Site

Crystal River, Florida, United States

GSK Investigational Site

Fort Myers, Florida, United States

GSK Investigational Site

Jacksonville, Florida, United States

GSK Investigational Site

Miami, Florida, United States

GSK Investigational Site

Pinellas Park, Florida, United States

GSK Investigational Site

Atlanta, Georgia, United States

GSK Investigational Site

Savannah, Georgia, United States

GSK Investigational Site

Overland Park, Kansas, United States

GSK Investigational Site

Louisville, Kentucky, United States

GSK Investigational Site

Sunset, Louisiana, United States

GSK Investigational Site

Saint Clair Shores, Michigan, United States

GSK Investigational Site

Billings, Montana, United States

GSK Investigational Site

Las Vegas, Nevada, United States

GSK Investigational Site

Las Vegas, Nevada, United States

GSK Investigational Site

New Brunswick, New Jersey, United States

GSK Investigational Site

Albuquerque, New Mexico, United States

GSK Investigational Site

Albuquerque, New Mexico, United States

GSK Investigational Site

Chapel Hill, North Carolina, United States

GSK Investigational Site

Cincinnati, Ohio, United States

GSK Investigational Site

Cleveland, Ohio, United States

GSK Investigational Site

Eugene, Oregon, United States

GSK Investigational Site

Portland, Oregon, United States

GSK Investigational Site

Philadelphia, Pennsylvania, United States

GSK Investigational Site

Hilton Head Island, South Carolina, United States

GSK Investigational Site

Dallas, Texas, United States

GSK Investigational Site

Midland, Texas, United States

GSK Investigational Site

Norfolk, Virginia, United States

GSK Investigational Site

Seattle, Washington, United States

GSK Investigational Site

Tacoma, Washington, United States

GSK Investigational Site

Buenos Aries, Buenos Aires, Argentina

GSK Investigational Site

Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina

GSK Investigational Site

Buenos Aires, , Argentina

GSK Investigational Site

Auchenflower, Queensland, Australia

GSK Investigational Site

Kippa-Ring, Queensland, Australia

GSK Investigational Site

Dulwich, South Australia, Australia

GSK Investigational Site

Nedlands, Western Australia, Australia

GSK Investigational Site

Subiaco, Western Australia, Australia

GSK Investigational Site

Frankfurt am Main, Hesse, Germany

GSK Investigational Site

Frankfurt am Main, Hesse, Germany

GSK Investigational Site

Mühlheim am Main, Hesse, Germany

GSK Investigational Site

Hanover, Lower Saxony, Germany

GSK Investigational Site

Münster, North Rhine-Westphalia, Germany

GSK Investigational Site

Dresden, Saxony, Germany

GSK Investigational Site

Leipzg, Saxony, Germany

GSK Investigational Site

Leipzig, Saxony, Germany

GSK Investigational Site

Magdeburg, Saxony-Anhalt, Germany

GSK Investigational Site

Magdeburg, Saxony-Anhalt, Germany

GSK Investigational Site

Nordhausen, Thuringia, Germany

GSK Investigational Site

Berlin, , Germany

GSK Investigational Site

Hamburg, , Germany

GSK Investigational Site

Napoli, Campania, Italy

GSK Investigational Site

Bologna, Emilia-Romagna, Italy

GSK Investigational Site

Modena, Emilia-Romagna, Italy

GSK Investigational Site

Florence, Tuscany, Italy

GSK Investigational Site

Auckland, , New Zealand

GSK Investigational Site

Christchurch, , New Zealand

GSK Investigational Site

Wellington, , New Zealand

GSK Investigational Site

Lugo, , Spain

GSK Investigational Site

Oviedo, , Spain

GSK Investigational Site

Santiago de Compostela, , Spain

GSK Investigational Site

Gothenburg, , Sweden

GSK Investigational Site

Gothenburg, , Sweden

GSK Investigational Site

Gothenburg, , Sweden

GSK Investigational Site

Gothenburg, , Sweden

GSK Investigational Site

Kungsbacka, , Sweden

GSK Investigational Site

Uddevalla, , Sweden

GSK Investigational Site

Cambridge, Cambridgeshire, United Kingdom

GSK Investigational Site

Buckshaw Village, Chorley, Lancashire, United Kingdom

GSK Investigational Site

Manchester, Lancashire, United Kingdom

GSK Investigational Site

Harrow, Middlesex, United Kingdom

GSK Investigational Site

Oxford, Oxfordshire, United Kingdom

GSK Investigational Site

Waterloo, Liverpool, , United Kingdom

Countries

United States; Argentina; Australia; Germany; Italy; New Zealand; Spain; Sweden; United Kingdom

Other Identifiers

105106

Identifier Type: -

Identifier Source: org_study_id