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

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 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 10uU/mL [SI: 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.