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

Phase1a, Randomized Placebo-controlled, Single and Multiple Dose, Dose-escalation Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Oral NNI-362 in Healthy Aged Volunteers 50 to 72 Years of Age

The purpose of this study is to examine the safety, tolerability and pharmacokinetics of single and multiple doses of NNI-362 in healthy aged population.

The early clinical development strategy consists of the initial evaluation of safety and tolerability of NNI-362. This FIH Phase I includes single and multiple ascending dose studies in healthy aged volunteers. Assessment of suicidal ideation/behavior will be performed at baseline and at all study visits and on days of inpatient confinement in conformance with FDA recommendations.

Inclusion Criteria:

• 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