Study to Assess the Safety, Tolerability and Pharmacokinetics of Single Ascending Oral Doses of J147

NCT03838185 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: ABRJ147001
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 1

Brief Summary

This Phase I clinical study is a randomized, double-blind, placebo-controlled, parallel-design study to thoroughly assess the safety profile and PK properties of J147 in healthy subjects. The study will include single ascending dose (SAD) in healthy young and elderly subjects.

Conditions

Alzheimer's Disease

Keywords

Dementia; Neurodegenerative Disease

Outcome Measures

Primary Outcomes (7)

• Incidence of treatment-emergent adverse events

  Nature, frequency and severity of adverse events

  from pre-dose to 7+/-2 days post dose

• Number of subjects with abnormal electrocardiogram

  12-lead electrocardiogram measurement

  from pre-dose to 7+/-2 days post dose

• Incidence of clinically significant changes in serum biomarker levels in a standard serum chemistry panel

  Changes in standard serum chemistry measures will be assessed.

  from pre-dose to 7+/-2 days post dose

• Incidence of clinically significant changes in hematological biomarker levels in a standard hematology panel

  Changes in standard hematology measures will be assessed.

  from pre-dose to 7+/-2 days post dose

• Incidence of clinically significant changes in urine biomarker levels in a standard urinalysis panel

  Changes in standard urinalysis measures will be assessed.

  from pre-dose to 7+/-2 days post dose

• Number of patients exhibiting changes in standard Physical Examination results

  from pre-dose to 7+/-2 days post dose

• Number of patients exhibiting changes in standard Neurological Examination results

  from pre-dose to 7+/-2 days post dose

Secondary Outcomes (7)

• Maximum plasma concentration (Cmax)

  0-48 hours post dose

• Time to Cmax (Tmax)

  0-48 hours post dose

• Area under the plasma concentration vs. time curve (AUC)

  0-48 hours post dose

• Terminal rate constant

  0-48 hours post dose

• Terminal half-life (t1/2)

  0-48 hours post dose

Study Arms (2)

Study Drug

EXPERIMENTAL

Healthy young male subjects will receive a single ascending oral dose of J147 following an overnight fast of at least 8 hours. Healthy elderly subjects will receive doses that have been found to be safe in healthy young subjects.

Drug: J147

Placebo

PLACEBO COMPARATOR

Subjects will receive a single oral dose of placebo with 240 mL non-carbonated water in the morning following an overnight fast of at least 8 hours.

Drug: Placebo

Interventions

J147 DRUG

Single oral dose of J147

Study Drug

Placebo DRUG

Single oral dose of corn oil

Placebo

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provide voluntarily agreement to participate in this study and signs an IRB/IEC-approved informed consent prior to performing any of the screening procedures
• Healthy male subjects, between 18 to 50 years of age, inclusive, at the time of signing the informed consent; OR, Healthy male and female subjects, between 60 to 85 years of age, inclusive, at the time of signing the informed consent
• If male, subjects with partners of child bearing potential must be practicing abstinence, part of an abstinent life style or agree to use a highly effective contraception method during the intervention period and for at least 3 months after the last dose of study medication and refrain from donating sperm during this period. Because of the unacceptable failure rate of barrier (chemical and/or physical) methods, the barrier method of contraception must only be used in combination with a highly effective method. Post coital methods of contraception are not permitted.
• If female, must not be pregnant, must not be lactating, and must be of non-childbearing potential (surgically sterile \[hysterectomy or bilateral tubal ligation\] or postmenopausal ≥ 1 year.
• Body mass index (BMI) between 18.0 and 30.0 kg/m2, inclusive, at screening with a weight of at least 50 kg
• Nonsmokers (or other nicotine use) as determined by history (no nicotine use over the past year) and by urine cotinine concentration (\< 200 ng/mL) at the screening visit and admission

You may not qualify if:

• Has clinically significant history or evidence of cardiovascular, endocrine, hematologic, immune, gastrointestinal, genitourinary or other body system disease as determined by an Investigator
• Has clinically significant history or evidence of disease or dysfunction in neurological or psychiatric system that is likely to affect the results of the study in the opinion of an Investigator
• Has any disorder that would interfere with the absorption, distribution, metabolism or excretion of drugs
• Subject has any concurrent disease or condition that, in the opinion of the Principal Investigator, would make the subject unsuitable for participation in the clinical study
• Has positive test for hepatitis B surface antigen (HBsAg), hepatitis C antibody (HCV) or human immunodeficiency virus (HIV) antibodies
• Has a urine blood test for ethanol or cotinine at the screening visit or admission
• Has a positive urine drug test (e.g., cocaine, amphetamines, barbiturates, opiates, benzodiazepines, cannabinoids) at the screening visit or admission
• Females who are breastfeeding
• Is unwilling to or has not avoided consumption of grapefruit, grapefruit juice, Seville oranges, Seville orange marmalade or other products containing grapefruit or Seville oranges within 14 days of dosing with study medication
• Has history of alcohol and/or illicit drug abuse within 1 year of entry or is unwilling to avoid use of alcohol or alcohol-containing foods, medications or beverages, within 48 hours prior to admission until discharge from the clinical unit
• Has donated blood (\> 500 mL) or blood products within 30 days prior to first day of dosing
• Requires treatment with any medication, prescription or over-the-counter (OTC) medications (including vitamins \[mega doses\], dietary supplements or herbal medications), prescription medications within 14 days prior to administration of study medication. By exception, acetaminophen ≤ 1000 mg per day and vitamin products at recommended daily doses are permitted
• Has received any known hepatic or renal clearance altering agents (e.g., erythromycin, cimetidine, barbiturates, phenothiazines or herbal/plant-derived preparations such as St. John's wort) for a period of 30 days prior to dosing
• Has used an investigational drug within 30 days prior to screening
• Has a history of hypersensitivity or allergies to J147, any components of formulated J147, or any drug within the same class; minor drug allergies to a drug in another drug class may be approved by an Investigator if not considered of clinical relevance

Sponsors & Collaborators

• Abrexa Pharmaceuticals, Inc.: lead
• Iqvia Pty Ltd: collaborator

Study Sites (1)

Vince & Associates Clinical Research, Inc.

Overland Park, Kansas, 66206, United States

Location

Related Publications (5)

• Chen Q, Prior M, Dargusch R, Roberts A, Riek R, Eichmann C, Chiruta C, Akaishi T, Abe K, Maher P, Schubert D. A novel neurotrophic drug for cognitive enhancement and Alzheimer's disease. PLoS One. 2011;6(12):e27865. doi: 10.1371/journal.pone.0027865. Epub 2011 Dec 14.

  PMID: 22194796 BACKGROUND

• Prior M, Dargusch R, Ehren JL, Chiruta C, Schubert D. The neurotrophic compound J147 reverses cognitive impairment in aged Alzheimer's disease mice. Alzheimers Res Ther. 2013 May 14;5(3):25. doi: 10.1186/alzrt179. eCollection 2013.

  PMID: 23673233 BACKGROUND

• Currais A, Goldberg J, Farrokhi C, Chang M, Prior M, Dargusch R, Daugherty D, Armando A, Quehenberger O, Maher P, Schubert D. A comprehensive multiomics approach toward understanding the relationship between aging and dementia. Aging (Albany NY). 2015 Nov;7(11):937-55. doi: 10.18632/aging.100838.

  PMID: 26564964 BACKGROUND

• Prior M, Goldberg J, Chiruta C, Farrokhi C, Kopynets M, Roberts AJ, Schubert D. Selecting for neurogenic potential as an alternative for Alzheimer's disease drug discovery. Alzheimers Dement. 2016 Jun;12(6):678-86. doi: 10.1016/j.jalz.2016.03.016. Epub 2016 May 2.

  PMID: 27149904 BACKGROUND

• Goldberg J, Currais A, Prior M, Fischer W, Chiruta C, Ratliff E, Daugherty D, Dargusch R, Finley K, Esparza-Molto PB, Cuezva JM, Maher P, Petrascheck M, Schubert D. The mitochondrial ATP synthase is a shared drug target for aging and dementia. Aging Cell. 2018 Apr;17(2):e12715. doi: 10.1111/acel.12715. Epub 2018 Jan 7.

  PMID: 29316249 BACKGROUND

MeSH Terms

Conditions

Alzheimer Disease; Dementia; Neurodegenerative Diseases

Interventions

J147

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurocognitive Disorders; Mental Disorders

Study Officials

• Martin Kankam, MD, PhD, MPH

  Vince & Associates Clinical Research, Inc.

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Subjects will receive a single dose of J147 or placebo in a fasted state. The dose levels are planned to be administered in ascending order. Progression to the next dose level, and dose selection, will be based on all available safety and tolerability data up to at least 48 hours post-dose and available PK data (up to at least 24 hours post-dose) from a minimum of 6 subjects (J147 n ≥4) in the preceding dose cohort. Healthy elderly subjects will receive doses that have been found to be safe in healthy young subjects.

Study Record Dates

• First Submitted: February 7, 2019
• First Posted: February 12, 2019
• Study Start: January 22, 2019
• Primary Completion: February 1, 2020
• Study Completion: February 1, 2020
• Last Updated: September 3, 2020

Record last verified: 2020-09

Locations

US (1)