Open Label Dose Escalation Phase I Study to Investigate the Safety and Pharmacokinetics of T121E01F in Healthy Postmenopausal Women

Inclusion Criteria:

• Healthy, postmenopausal women between the ages of 35 and 70 years, inclusive. Postmenopausal females (based on medical history) defined as 12 continuous months of spontaneous amenorrhea or bilateral oopherectomy. Women 60 years of age and older will be considered postmenopausal. Women 35-59 must have a serum follicle-stimulating hormone (FSH) result consistent with postmenopausal state.
• Body Mass Index (BMI) of 17.5 to 32 kg/m2; and a total body weight >50 kg (110 lbs)
• Signed informed consent

Exclusion Criteria:

• Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease
• History of any severe allergic reaction or known allergy to ZA
• Evidence or history of any gastrointestinal disease, such as irritable bowel syndrome, Crohn's Disease, chronic gastritis, peptic ulcer disease, H. pylori infection, or other gastrointestinal condition possibly affecting drug absorption
• History of gastric surgery, including the Roux-en-Y gastric bypass surgery or an antrectomy with vagotomy, or gastrectomy
• Evidence or history of any clinically significant cardiovascular (CV) disease or condition
• History of any autoimmune disease (e.g., systemic lupus erythematosus [SLE], scleroderma, psoriasis, vitiligo, primary biliary cirrhosis, etc.)
• History of any endocrine disorders (e.g., type 1 or 2 diabetes mellitus, adrenal insufficiency, thyroid disease, hypoparathyroidism, etc.)
• Mucolipidosis type IV
• Any clinically significant hematological condition (e.g., pernicious anemia)
• Evidence or history of any other severe acute or chronic medical (including renal, pulmonary, hepatic, neurologic, psychiatric, etc.) disease or condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration, or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study.
• A positive urine drug screen.
• A positive pregnancy test
• History of difficulty swallowing large pills/tablets
• Active dental or oral disease that would increase risk of bisphosphonate use and/or requires dental care

• Prohibited substance use, including:

  • Any documented history of drug or alcohol abuse
  • Chronic consumption over the past 12 months of more than 2 standard units per day of alcohol (a standard unit equals 12 ounces of beer, 1 ½ ounces of 80-proof alcohol or 6 ounces of wine)
  • Subject reported tobacco or nicotine use within previous 30 days

• Prohibited medication use, including:

  • Treatment with an investigational drug within 30 days (or as determined by the local requirement, whichever is longer) or 5 half-lives preceding the first dose of study medication, whichever is longer;
  • Use of nonprescription drugs and dietary and/or vitamin supplements within 7 days prior to the first dose of study medication. Use of acetaminophen is acceptable for management of acute (e.g., pain) condition, as long as the daily dose is < 1500 mg and the duration does not exceed 3 consecutive days. The need for other non-prescription drug(s) during the study should be discussed with the Medical Monitor.
  • Prescription or herbal supplements within 14 days prior to the first dose of study medication.
  • Use of any P450 enzyme inducer or inhibitor within 30 days prior to the first dose of study medication.
  • History of chronic proton pump inhibitor (PPI) use Proton pump inhibitors, H2 blockers, hormone replacement therapy, aminoglycosides, loop diuretics and nephrotoxic drugs within 30 days prior to the first dose of study medication.
  • Bisphosphonate use within 90 days prior to the first dose of study medication.
  • Use of acid reducer medication, both non-prescription and prescription, within 3 days of study medication administration
• A positive serology for Hepatitis B, Hepatitis C, HIV, or H. pylori
• Any invasive dental or oral procedure completed within 30 days prior to the first dose of study medication or anticipated during the study or within 30 days of completion of the study

• Clinically significant abnormal laboratory test values, as determined by the Investigator, or any of the following:

  • alanine aminotransferase (ALT), aspartate aminotransferase (AST), or creatinine 1.5 times above the upper limit of normal (ULN);
  • platelets below the lower limit of normal;
  • hemoglobin 10% below the lower level of normal;
  • any out of normal range values for serum sodium, serum calcium, serum potassium or serum magnesium.
  • Glomerular filtration rate (eGFR) < 60 mL/ minute as calculated by the modified Modification of Diet in Renal Disease (MDRD) formula.