A Multiple Dose Study of the Safety and Pharmacokinetics of NTRX-07

NCT06194552 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: NTRX-C102
• Study Type: interventional
• Target: 32
• Locations: 2 countries
• Sites: 2

Brief Summary

This is a Phase 1, Randomized, Placebo-Controlled, Modified Parallel Design Multiple Ascending Dose Study of NTRX 07 to Assess Safety and Tolerability and Pharmacokinetics in Adult Healthy Volunteers and Subjects with MCI or Early AD. In addition, an exploratory study of the effect of a high fat meal was conducted.

Conditions

Alzheimer Disease

Keywords

CB2

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Treatment-Related Adverse Events

  AEs observed and recorded according to MEDRA

  From admission to discharge, up to 2 weeks

Secondary Outcomes (3)

• Time to Maximum Concentration of NTRX-07 NTRX-07

  Day 1 and Day 7

• Maximum Concentration of NTRX-07 NTRX-07

  Day 1 and Day 7

• Area Under the Plasma Concentration Versus Time Curve (AUC) NTRX-07

  Day 1 and Day 7

Other Outcomes (5)

• Plasma levels of neuro-inflammatory biomarkers

  Day 1 and Day 7

• Plasma levels of high-sensitivity C-reactive protein (CRP)

  Day 1 and Day 7

• MOCA Montreal Cognitive Assessment

  Day 1 and Day 7

Study Arms (6)

NTRX-07 Low Dose Normal Volunteers

EXPERIMENTAL

NTRX-07 administered orally once per day for 7 days

Drug: NTRX-07

NTRX-07 Mid Dose Normal Volunteers

EXPERIMENTAL

NTRX-07 administered orally once per day for 7 days

Drug: NTRX-07

NTRX-07 High Dose Normal Volunteers

EXPERIMENTAL

NTRX-07 administered orally once per day for 7 days

Drug: NTRX-07

NTRX-07 High Dose Alzheimer's Participants

EXPERIMENTAL

NTRX-07 administered orally once per day for 7 days

Drug: NTRX-07

Placebo Control

PLACEBO COMPARATOR

Placebo administered orally once per day for 7 days

Drug: Placebo

Mid Dose Fed

EXPERIMENTAL

NTRX-07 administered orally once with high fat meal

Drug: NTRX-07

Interventions

NTRX-07 DRUG

Investigational orally administered CB2 agonist

Also known as: MDA7

Mid Dose Fed; NTRX-07 High Dose Alzheimer's Participants; NTRX-07 High Dose Normal Volunteers; NTRX-07 Low Dose Normal Volunteers; NTRX-07 Mid Dose Normal Volunteers

Placebo DRUG

Matched placebo administered orally

Placebo Control

Eligibility Criteria

• Age: 45 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participant must be 45 80 years of age inclusive, at the time of signing the informed consent
• Cohorts A-C participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring.
• Cohort D - AD as characterized by the following clinical, cognitive, and functional criteria.
• Diagnosis of a clinical syndrome of cognitive impairment consistent with prodromal AD per International Working Group (IWG) diagnostic criteria or mild AD per National Institute on Aging - Alzheimer's Association (NIAA-AA) diagnostic criteria
• Self or informant report of memory decline
• Mini-Mental State Examination (MMSE) scores between 18-27 inclusive within the last 4 months
• Objective memory loss by education-adjusted Wechsler Memory Scale Logical Memory II consistent with mild cognitive impairment with Alzheimer's disease (MCI AD) or mild AD
• Absence of significant levels of impairment in other cognitive assessments
• Cohort D - Previous brain imaging study, such as magnetic resonance imaging (MRI) and/or computed tomography (CT), consistent with a diagnosis of probably AD without any other clinically significant co-morbid pathologies within 12 months prior to the Screening Visit. If there has been a significant change in clinical status suggestive of stroke or other possible central neurological disease with onset between the time of the last MRI or CT and the Screening evaluation, the scan should be repeated during Screening procedures if considered appropriate by the Investigator OR Screening cerebrospinal fluid (CSF) results consistent with the presence of amyloid pathology.
• Cohort D - No active depression and a Geriatric Depression Score of \<6.
• Cohort D - Absence of other (non-AD) types of dementia.
• Cohort D - Participants previously enrolled in an AD clinical trial involving a disease modifying or symptomatic therapeutic agent may enroll in this study if treatment with the symptomatic therapeutic agent ended more than 6 months before the first dose of NTRX 07-SDD in this study.
• Body weight within 55 110 kg and body mass index (BMI) within the range 18 35 kg/m2 (inclusive)
• Male or Female
• The effects of NTRX 07 on pregnancy, fetal development, and excretion in breast milk is currently unknown. Contraceptive use should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.

You may not qualify if:

• Reported history or presence of clinically significant history of or current cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrinological, hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study intervention; or interfering with the interpretation of data. Participants with stable well controlled conditions may be accepted on review with the Investigator and sponsor.
• Reported current or chronic history of clinically significant liver disease. This includes but is not limited to hepatitis virus infections, drug- or alcohol-related liver disease, nonalcoholic steatohepatitis, autoimmune hepatitis, hemochromatosis, Wilson's disease, α-1 antitrypsin deficiency, primary biliary cholangitis, primary sclerosing cholangitis, or any other liver disease considered clinically significant by the investigator.
• Reported hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
• Cohort D - Reside in a nursing home or assisted care facility with need for direct continuous medical care and nursing supervision. Participant may reside in such facilities provided continuous direct medical care is not required.
• Cohort D - Unable to provide for self for basic activities of daily living.
• Cohort D - Major structural brain disease by reported history or chart review (eg, ischemic infarcts, subdural hematoma, hemorrhage, hydrocephalus, brain tumors, multiple subcortical ischemic lesions, or a single lesion in a critical region eg, thalamus, hippocampus).
• Any other reported history of central nervous system (CNS) trauma (eg, contusion), or infections that affect brain function (eg, human immunodeficiency virus \[HIV\], syphilis), history of seizures
• Diagnosis of schizophrenia
• Any reported history from patient, family, or on supplied chart review or current suicide risk
• Cohort D - Diagnosis of a dementia-related CNS disease other than AD (eg, Parkinson's Disease, Huntington's Disease, frontotemporal dementia, multi-infarct dementia, dementia with Lewy bodies, normal pressure hydrocephalus)
• Reported past or intended use of over-the-counter or prescription medication including herbal medications within 7 days prior to dosing. Specific medications listed in Section Concomittant Therapy may be allowed.
• Reported treatment with biologic agents (such as monoclonal antibodies including marketed drugs) within 3 months or 5 half-lives (whichever is longer) prior to dosing.
• Current enrollment or past participation within the last 30 days before signing of consent in any other clinical study involving an investigational study intervention or any other type of medical research.
• Alanine transaminase (ALT) or aspartate transaminase (AST) \>1.5 x upper limit of normal (ULN)
• Total bilirubin \>1.5 x ULN (isolated bilirubin \>1.5 x ULN is acceptable if total bilirubin is fractionated and direct bilirubin \<35%)

Sponsors & Collaborators

• NeuroTherapia, Inc.: lead
• CRU Early Phase Unit Kistarcsa: collaborator

Study Sites (2)

NeuroTherapia

Gates Mills, Ohio, 44040, United States

Location

CRU Early Phase Unit Kistarcsa

Kistarcsa, Hungary

Location

MeSH Terms

Conditions

Alzheimer Disease

Condition Hierarchy (Ancestors)

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

Study Design

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

Study Record Dates

• First Submitted: October 23, 2023
• First Posted: January 8, 2024
• Study Start: September 6, 2022
• Primary Completion: May 31, 2023
• Study Completion: June 30, 2023
• Last Updated: January 8, 2024

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will not share

Locations

HU (1); US (1)