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

Neuronascent

Status and phase: Completed; Phase 1

Conditions: Alzheimer Disease

Treatments: Drug: Placebo; Drug: NNI-362

Study type: Interventional

Funder types: Industry; NIH

Identifiers

NCT04074837

1R01AG056561-01A1 (U.S. NIH Grant/Contract)

NNI-001

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 56 patients

Sex: All

Ages: 50 to 72 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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56 participants in 6 patient groups, including a placebo group

Placebo

Placebo Comparator group

Description:

Placebo liquid suspension.

Treatment:

Drug: Placebo

NNI-362, 10 mg

Active Comparator group

Description:

NNI-362 at 10 mg in liquid suspension

Treatment:

Drug: NNI-362

NNI-362, 20 mg

Active Comparator group

Description:

NNI-362 at 20 mg in liquid suspension

Treatment:

Drug: NNI-362

NNI-362, 60 mg

Active Comparator group

Description:

NNI-362 at 60 mg in liquid suspension

Treatment:

Drug: NNI-362

NNI-362, 120 mg

Active Comparator group

Description:

NNI-362 at 120 mg in liquid suspension

Treatment:

Drug: NNI-362

NNI-362, 240 mg

Active Comparator group

Description:

NNI-362 at 240 mg in liquid suspension

Treatment:

Drug: NNI-362