Phase1a, Dose-escalation Study of NNI-362 in Healthy Aged Volunteers

• Healthy aged volunteers of either sex between the ages of 50 and 72 inclusive at time of screening.

  • Subjects must be in reasonably good health as determined by investigator based on medical history, vital signs measurements, physical examination, screening laboratory results and ECG.
  • Normal age-related findings as well as well-controlled, chronic and stable medical conditions (e.g., hypertension, osteoarthritis, non-insulin dependent diabetes mellitus, osteoporosis, gout, Paget's disease, hypothyroidism) will not be exclusionary if they are not expected to compromise subject safety, study conduct, or study objectives.
  • Non-interacting medications for stable allowable medical conditions will be allowed following review and approval by the medical monitor.
  • An adequate understanding of the requirements of the study, provision of written informed consent, and agreement to abide by the study restrictions.
  • Negative urine screen for drugs of abuse within 24 h before the administration of the first dose of study drug and in the multiple dose study upon readmission to the clinical unit from outpatient status.
  • Body Mass Index (BMI) of between 18 and 30 kg/m2 inclusive, and a total body weight greater than 48kg at screening.

Exclusion Criteria:

• • Women of child-bearing potential, defined as premenopausal (unless the potential research subject has previously undergone hysterectomy and/or bilateral salpingo-oophorectomy)

    • Pregnant or breastfeeding
    • Any clinically significant hematology, chemistry, coagulation, or urinalysis value at screening and day -1 Abnormal liver enzymes (ALT and/or AST >1.5X ULN) at screening and day -1
    • Serum creatinine > ULN at screening and day -1
    • Hemoglobin \<13 g/dL for males or \<11.5 g/dL for females, leukocytes \<3.0 X 103/uL, absolute neutrophil count \<1000/uL, or platelets \<150 X 103/uL at screening and day -1

    • Any significant medical illness that could compromise the interpretability of study data or affect subject safety including, but not necessarily limited to:

      • Chronic pulmonary disease or sleep apnea
      • Clinically significant cardiac arrhythmia (either at screening or based on history)
      • Congestive heart failure, valvular heart disease or ischemic heart disease
      • Pulmonary hypertension
      • Any disorder of the kidney or urinary tract
      • Active peptic ulcer disease, gastrointestinal bleeding, inflammatory bowel disease, chronic pancreatitis
      • Liver disease (excluding Gilbert's syndrome)
      • Any neurologic disorder other than chronic Bell's Palsy
      • History of malignancy that has not been cured or in complete remission for at least 10 years (excluding resected non-metastatic basal cell carcinoma)
      • History of seizure activity other than early childhood
      • Any traumatic brain injury in adulthood
    • Current smoker or nicotine user (quit less than 2 months)
    • Active substance abuse.
    • Glomerular filtration rate \<50 mL/min based on Cockcroft-Gault calculation using ideal (lean) body weight or present weight.
    • Difficulty swallowing