Dose Escalation Study in Female Subjects With Breast Cancer Receiving Aromatase Inhibitor or Tamoxifen

Vasomotor symptoms are significant in postmenopausal women with the most effective medications for relief being hormonal preparations. Non-hormonal medications have demonstrated efficacy but at a far lower level than estrogen replacement therapy. For women with a history of breast cancer hormone replacement therapy is problematic especially if their therapeutic regime involves an aromatase inhibitor. Therefore, this study will explore the effect of Q-122 in a population of women with a history of breast cancer taking an aromatase inhibitor or tamoxifen.

The study is an open-label, two dose study (Group 1: 100 mg once daily and Group 2: 200 mg once daily) of Q-122, over a 4 week treatment period. As eligible subjects are enrolled, they will be assigned to Group 1 until Group 1 is fully enrolled. Dose escalation to the 200 mg level will only occur following a review of the safety experience of at least 6 subjects treated with 100 mg Q-122 once daily for at least 2 weeks. Once Group 1 is fully enrolled, eligible subjects will be enrolled into Group 2.

A two-week screening phase will be used to establish a stable baseline of vasomotor symptoms and to establish study eligibility. Qualified subjects will be treated with Q-122 for four weeks either at 100 mg/day dose or the 200 mg/day dose, during which time they will be evaluated for safety, tolerability, and pharmacokinetics of Q-122 and tamoxifen levels; subjects will continue to record their hot flashes in identical fashion to the screening period. Following the 28 day treatment, period subjects who complete the study will continue to record their hot flashes for a two week follow up period.

Inclusion criteria

• Be a female of any race between the ages of 30-70 years.
• History of breast cancer and presently taking an aromatase inhibitor or tamoxifen.
• Naturally menopausal: ≥ 12 months spontaneous amenorrhea or > 6 but < 12 months amenorrhea with a serum follicle stimulating hormone (FSH) level of > 40 mIU/mL (Milli-international Units Per Milliliter).
• Surgically menopausal with an FSH level > 40 mIU/mL.
• Have a minimum of 7 moderate to severe hot flushes/day or 50 moderate to severe hot flushes per week, as verified for both weeks during the 14-day Screening Phase, prior to enrollment into the treatment phase of the study.
• Able to read, understand and complete the required subject diary.
• Willing and able to complete the daily subject diary, attend all study visits, and participate in all study procedures, including PK blood draws.

Exclusion criteria

• Childbearing potential, including pregnancy, or lactation.
• Undiagnosed abnormal genital bleeding.
• Significant day-to-day variability in hot flushes.
• Participation in another clinical trial within 30 days prior to screening or during the study.
• Legal incapacity or limited legal capacity.
• Chronic renal (serum creatinine > 2.0 mg/dL) or hepatic disease [SGPT (ALT) or SGOT (AST) > 2X normal limits].
• Gastrointestinal, liver, kidney or other conditions which could interfere with the absorption, distribution, metabolism or excretion of Q-122.
• Untreated overt hyperthyroidism.
• Use of thyroid medication of less than 12 weeks on a stable dose.
• Any clinically important systemic disease in the judgement of the investigator.
• Inability to complete all study visits and study assessments for scheduling or other reasons.
• Any other reason which in the investigator's opinion makes the subject unsuitable for a clinical trial.
• Abnormal laboratory findings including:

• Hematocrit < 30% or hemoglobin < 9.5 gm/dL
• Fasting blood sugar > 140 mg/dL
• Fasting serum triglycerides > 300 mg/dL
• Fasting SGOT, SGPT, GGT, or bilirubin greater than twice the upper limit of normal (a subject will not be excluded if a second measurement is less than twice the upper limit of normal)
• Creatinine > 2.0 mg/dL