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

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