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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Alzheimer Disease

Intervention / Treatment
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* Drug: NNI-362
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 72 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Placebo versus NNI-362 at 10 mg, 20 mg, 60 and 120 mg liquid suspension
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo liquid suspension. | Drug: Placebo<br>* Placebo liquid suspension<br>|
| Active Comparator: NNI-362, 10 mg<br>NNI-362 at 10 mg in liquid suspension | Drug: NNI-362<br>* NNI-362 small molecule in liquid suspension.<br>|
| Active Comparator: NNI-362, 20 mg<br>NNI-362 at 20 mg in liquid suspension | Drug: NNI-362<br>* NNI-362 small molecule in liquid suspension.<br>|
| Active Comparator: NNI-362, 60 mg<br>NNI-362 at 60 mg in liquid suspension | Drug: NNI-362<br>* NNI-362 small molecule in liquid suspension.<br>|
| Active Comparator: NNI-362, 120 mg<br>NNI-362 at 120 mg in liquid suspension | Drug: NNI-362<br>* NNI-362 small molecule in liquid suspension.<br>|
| Active Comparator: NNI-362, 240 mg<br>NNI-362 at 240 mg in liquid suspension | Drug: NNI-362<br>* NNI-362 small molecule in liquid suspension.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measure number of treatment related adverse events following single and multiple dosing of NNI-362. | To examine the number of participants with treatment-related adverse events according to criteria of CTCAE v4.0 | 5 to 15 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measure Maximum Plasma Concentration with single or multiple dosing of NNI-362. | Following single and multiple dosing of oral NNI-362 assess the maximum plasma concentration [Cmax]. | 48 hours | 
| Measure Area Under the Curve with single and multiple dosing of NNI-362 | Following single and multiple dosing of oral NNI-362 assess the area under the curve [AUC]. | 48 hours |