Clinical trial NCT04074837: Phase1a, Dose-escalation Study of NNI-362 in Healthy Aged Volunteers
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Alzheimer Disease
Lead sponsor: Neuronascent, Inc.
Sponsor class: INDUSTRY
Collaborators: name: National Institute on Aging (NIA)
First posted: 2019-08-30
Enrollment: 56
Sex: ALL
Minimum age (years): 50
Maximum age (years): 72
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Placebo versus NNI-362 at 10 mg, 20 mg, 60 and 120 mg liquid suspension
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Measure number of treatment related adverse events following single and multiple dosing of NNI-362.
timeFrame: 5 to 15 days
Secondary outcomes:
measure: Measure Maximum Plasma Concentration with single or multiple dosing of NNI-362.
timeFrame: 48 hours
measure: Measure Area Under the Curve with single and multiple dosing of NNI-362
timeFrame: 48 hours
Other outcomes:
Locations:
city: Glendale
country: United States
facility: Parexel, International
state: California
Study officials:
References:
citation: Sumien N, Wells MS, Sidhu A, Wong JM, Forster MJ, Zheng QX, Kelleher-Andersson JA. Novel pharmacotherapy: NNI-362, an allosteric p70S6 kinase stimulator, reverses cognitive and neural regenerative deficits in models of aging and disease. Stem Cell Res Ther. 2021 Jan 13;12(1):59. doi: 10.1186/s13287-020-02126-3.