Safety, Tolerability, PK of Oral NYX-2925 in Healthy Volunteers

NCT02834741 | Completed Phase 1

• 1 other identifier: NYX-2925-1001
• Study Type: interventional
• Target: 84
• Locations: 1 country
• Sites: 1

Brief Summary

This is a first in human study of NYX-2925. It will evaluate single and multiple ascending doses of NYX-2925 in healthy volunteers.

Conditions

Healthy Volunteers

Outcome Measures

Primary Outcomes (1)

• Number of subjects with adverse events

  Subjects will be followed for up to 30 days post-dose

Secondary Outcomes (9)

• Cmax of NYX-2925

  Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post-dose

• Tmax of NYX-2925

  Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post-dose

• AUC of NYX-2925

  Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post-dose

• Half-life of NYX-2925

  Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post-dose

• Clearance of NYX-2925

  Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post-dose

Study Arms (2)

SAD Phase

PLACEBO COMPARATOR

Up to 36 subjects: 50 - 1200 mg NYX-2925, Up to 12 subjects: placebo 6 additional subjects will receive a fed dose of NYX-2925, 2 additional subjects will receive a fed dose of placebo (Food Effect Cohort) 6 additional subjects will receive 1 dose of 50 mg NYX-2925 followed by a lumbar puncture at 1 and 4 (3 subjects) or 2 and 8 (3 subjects) hours post dose

Drug: NYX-2925

MAD Phase

PLACEBO COMPARATOR

Up to 24 subjects : 150 - 600 mg NYX-2925 daily for 7 days, up to 6 subjects : placebo daily for 7 days 6 additional subjects will receive 300 mg NYX-2925 daily for 7 days and undergo lumbar puncture on Day 6 in order to have two CSF samples taken (CSF Cohort).

Drug: NYX-2925

Interventions

NYX-2925 DRUG

NYX-2925 is a small molecule that acts as an N-methyl-D-aspartate receptor (NMDAR) functional glycine-site partial agonist.

MAD Phase; SAD Phase

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Male and female subjects.
• to 55 years of age, inclusive, at the time of signing the informed consent form (ICF). 55 to 80 years of age for elderly cohort.
• Female subjects with a negative serum pregnancy test prior to entry into the study and who are practicing an adequate method of birth control (e.g., oral or parenteral contraceptives, intrauterine device, barrier, abstinence) and who do not plan to become pregnant during the course of the study.
• Male subjects and their female sexual partner should use an acceptable method of birth control during the study. Male subjects must agree to use barrier contraception (condom with spermicide), and refrain from sperm donation, from the first dose of study drug until 90 days after the last dose of study drug.
• Clinical laboratory values within normal limits or deemed not clinically significant by the investigator and/or the sponsor.
• Ability to understand the requirements of the study, provide written informed consent, abide by the study restrictions, and agree to return for the required assessments.
• Subject is judged to be in good health as determined by the investigator based on the results of a medical history, physical examination (PE), clinical laboratory profile, and electrocardiogram (ECG) performed during the screening period and confirmed prior to dosing.
• Body mass index (BMI) between 18 and 30 kg/m2 (inclusive).
• Normal renal and hepatic function, with calculated creatinine clearance ≥ 90 mL/minute (Cockcroft-Gault Formula) at Screening or ≥ 60 mL/minute only in the case of the elderly cohort.

You may not qualify if:

• Clinically significant alcohol or other substance abuse within the last 24 months, in the opinion of the investigator; or, unable to abstain from alcoholic beverages during the course of the study.
• Positive screen for alcohol or drugs of abuse (with the exception of a positive result considered by the investigator to be directly attributable to prescription medication approved for subject use): including benzodiazepines, opiates, cocaine, cannabinoids, and amphetamines.
• History of smoking or tobacco use within 30 days of Screening.
• Women who are pregnant, breast feeding, or planning to become pregnant during the course of the study.
• History of allergy, sensitivity, or intolerance to NMDAR ligands including ketamine, dextromethorphan, memantine, methadone, dextropropoxyphene, or ketobemidone, as well as current use of such agents.
• Received an investigational drug or device within 30 days (or 5 half-lives, whichever is longer) of dosing.
• Previously assigned to treatment during this study (except those who did not take study medication).
• Screening QT interval corrected for heart rate by Fridericia's formula (QTcF) \> 450 (males) or 470 (females) millisecond (msec) or an ECG that is not suitable for QT measurements (e.g., poorly defined termination of T-wave in the investigator's opinion).
• Type I or Type II diabetes.
• History of severe renal or hepatic impairment, in the opinion of the investigator or the sponsor-designated medical monitor.
• History of excessive bleeding, blood thinners within 6 months, antibiotics or infection within 3 months (CSF cohort only), lumbar spine abnormality, history of elevated intracranial pressure, normal pressure hydrocephalus or other neurological conditions considered clinically significant by the investigator.
• Human immunodeficiency virus infection, hepatitis, or other ongoing infectious disease that the investigator considers clinically significant.
• Current evidence of dysplasia or history of malignancy (including lymphoma and leukemia) in the last 5 years, with the exception of successfully treated non-metastatic basal cell or squamous cell carcinoma of the skin or localized carcinoma in situ of the cervix.
• History of seizures.
• History of gastrointestinal disease or surgery (except simple appendectomy or hernia repair), which can influence the absorption of the study drug.

Sponsors & Collaborators

• Aptinyx: lead
• Spaulding Clinical Research LLC: collaborator

Study Sites (1)

Spaulding Clinical

West Bend, Wisconsin, 53095, United States

Location

MeSH Terms

Interventions

NYX-2925

Study Officials

• Carlos Sanabria, MD

  Spaulding Clinical Research LLC

  PRINCIPAL INVESTIGATOR

• Laurel Sindelar

  Aptinyx Inc.

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: July 13, 2016
• First Posted: July 15, 2016
• Study Start: July 1, 2016
• Primary Completion: March 1, 2017
• Study Completion: March 1, 2017
• Last Updated: April 5, 2017

Record last verified: 2017-04

Data Sharing

• IPD Sharing: Will share

Locations

US (1)