Multiple Ascending Dose and Electroencephalography Trial of GATE-202 in Healthy Volunteers

NCT05597241 | Completed Phase 1 FDA Drug

• 1 other identifier: GATE-202-C-101
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

To evaluate the safety, tolerability, pharmacokinetics and EEG pharmacodynamics of single and multiple ascending doses of apimostinel in normal human volunteers

Conditions

Major Depressive Disorder

Keywords

major depressive disorder; single ascending dose; multiple ascending dose; pharmacokinetics; EEG

Outcome Measures

Primary Outcomes (1)

• Treatment Emergent Adverse Events

  Number of Participants with Treatment-Emergent Adverse Events Through Study Completion

  36 days

Secondary Outcomes (1)

• Pharmacokinetics - Maximum Plasma Concentration

  72 hours

Other Outcomes (2)

• EEG - Power

  6 hours

• Event related potential (ERP)

  6 hours

Study Arms (10)

Cohort 1, Apimostinel

EXPERIMENTAL

Apimostinel, 25 mg IV single dose

Drug: apimostinel

Cohort 1, Placebo

PLACEBO COMPARATOR

Placebo, IV single Dose

Drug: Placebo

Cohort 2, Apimostinel, 1 mg IV 8 consecutive daily doses

EXPERIMENTAL

Apimostinel, 1 mg IV 8 consecutive daily doses

Drug: apimostinel

Cohort 2, Placebo IV 8 consecutive daily doses

PLACEBO COMPARATOR

Placebo IV 8 consecutive daily doses

Drug: Placebo

Cohort 3, Apimostinel, 5 mg IV 8 consecutive daily doses

EXPERIMENTAL

Apimostinel, 5 mg IV 8 consecutive daily doses

Drug: apimostinel

Cohort 3, Placebo 8 consecutive daily doses

PLACEBO COMPARATOR

Placebo IV 8 consecutive daily doses

Drug: Placebo

Cohort 4, Apimostinel, 10 mg IV 8 consecutive daily doses

EXPERIMENTAL

Apimostinel, 10 mg IV 8 consecutive daily doses

Drug: apimostinel

Cohort 4, Placebo 8 consecutive daily doses

PLACEBO COMPARATOR

Placebo IV 8 consecutive daily doses

Drug: Placebo

Cohort 5, Apimostinel, 25 mg IV, 8 consecutive daily doses

EXPERIMENTAL

Apimostinel, 25 mg IV 8 consecutive daily doses

Drug: apimostinel

Cohort 5, Placebo IV 8 consecutive daily doses

PLACEBO COMPARATOR

Placebo IV 8 consecutive daily doses

Drug: Placebo

Interventions

apimostinel DRUG

N-methyl-D-aspartate (NMDA) receptor modulator

Also known as: GATE-202

Cohort 1, Apimostinel; Cohort 2, Apimostinel, 1 mg IV 8 consecutive daily doses; Cohort 3, Apimostinel, 5 mg IV 8 consecutive daily doses; Cohort 4, Apimostinel, 10 mg IV 8 consecutive daily doses; Cohort 5, Apimostinel, 25 mg IV, 8 consecutive daily doses

Placebo DRUG

Placebo

Cohort 1, Placebo; Cohort 2, Placebo IV 8 consecutive daily doses; Cohort 3, Placebo 8 consecutive daily doses; Cohort 4, Placebo 8 consecutive daily doses; Cohort 5, Placebo IV 8 consecutive daily doses

Eligibility Criteria

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

You may qualify if:

• Subject is a healthy volunteer who is able 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 must be 18 to 55 (inclusive) years of age, at the time of signing the informed consent.
• Subject has a BMI between 18.5 kg/m2 and 30 kg/m2 (inclusive), with a minimum body weight of 50 kg.
• Subject is male or female.
• Females are eligible to participate if not pregnant, not breastfeeding, and at least one of the following conditions applies:
• Surgically sterile or at least 2 years menopausal, confirmed by follicle-stimulating hormone (FSH) at Screening, or,
• If women of childbearing potential (WOCBP), subject must use an acceptable method of birth control from date of Screening to at least 30 days after the last dose of study intervention and must have a documented negative blood or urine pregnancy test within 24 hours prior to dosing (SAD cohort) or within 48 hours prior to dosing (MAD cohorts). If reported sterile or postmenopausal, will be confirmed by FSH.
• Male subject must meet one of the following:
• Surgically sterile
• If not surgically sterile, then use of an acceptable form of contraception as detailed in Appendix 4 from the time of randomization through 28 days following the last dose of study intervention. Male subjects or male partners of female subjects are recommended to not donate sperm from Screening (Visit 1) until 28 calendar days after the last dose of study intervention. Male subjects are strongly advised to inform female partners of the need for them to use acceptable birth control methods during this time period.
• Clinical laboratory values \<2 times the upper limit of normal or deemed not clinically significant by the Investigator at Screening and Admission Day.

You may not qualify if:

• Type I or Type II diabetes mellitus.
• Malignancy in the last 5 years, with the exception of nonmetastatic basal cell or squamous cell carcinoma of the skin or localized carcinoma in situ of the cervix.
• History of allergy or sensitivity, or intolerance to N-methyl-D-aspartate (NMDA) receptor ligands including ketamine, dextromethorphan, memantine, methadone, dextropropoxyphene, or ketobemidone.
• Psychiatric disease including major depressive disorder, bipolar disorder, anxiety, or schizophrenia, or other medical condition that, in the opinion of the Investigator, would interfere with the evaluation of study intervention safety.
• Any personal or family history of seizure (including febrile seizures) or diagnosis of epilepsy or episode of unexplained loss of consciousness.
• Any history of neurological or other medical conditions which in the opinion of the Investigator has the potential to reduce seizure threshold, e.g., history of head concussion, traumatic brain injury, taking any medications that may reduce seizure threshold, developmental abnormalities in the brain, or metabolic causes, including electrolyte abnormalities such as hyponatremia.
• Subject has a history of excessive bleeding after invasive procedures or surgery or known coagulation or platelet abnormality or has been on any blood thinner or medication affecting platelet function, such as aspirin, nonsteroidal antiinflammatory medications, corticosteroids (except topical) or warfarin within the 7 days prior to enrollment or has known allergy to any anesthetic agent that may be used for the lumbar catheterization.
• Subject has a history of infection that required IV antibiotics within the 45 days or oral antibiotics within 30 days prior to enrollment, and, at the time of clinic admission, be febrile or have signs/symptoms consistent with an infection.
• Subject has a history of or physical examination evidence of a lumbar spine abnormality that may preclude placement of a spinal catheter, presence of intraspinal shunt devices (e.g., ventriculoperitoneal shunt), or history of elevated intracranial pressure, normal pressure hydrocephalus, or other neurological condition that in the opinion of the Investigator precludes safe study participation. A lumbar X-ray that excludes spine abnormalities must have been taken within the past 12 months and made available or the subject must agree to have one taken as part of the qualification.
• In the opinion of the Investigator, the Safety Monitor, or the Sponsor Study Monitor, has a history of severe renal or hepatic impairment, severe active hepatic disease, or other clinically significant medical condition that may preclude safe study participation.
• Subject who has clinical signs and symptoms consistent with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); e.g., fever, dry cough, dyspnea, sore throat, fatigue, or positive SARS-CoV-2 test result within 14 days prior to the Screening Visit or at admission.
• Subject who had a severe course of SARS-CoV-2 (extracorporeal membrane oxygenation, mechanically ventilated).
• Currently taking prescription or over-the-counter medications including herbal therapies, within 14 days of enrollment into the study.
• Received another investigational drug or device within 30 days or 5 half-lives, whichever is longer prior to enrollment in this study (defined as the time of admission; Day -2 for MAD and Day -1 for SAD).
• Previously randomized in this study.

Sponsors & Collaborators

• Syndeio Biosciences, Inc: lead

Study Sites (1)

Woodland Research Northwest

Rogers, Arkansas, 72758, United States

Location

MeSH Terms

Conditions

Depressive Disorder, Major

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Study Officials

• Ronald M Burch, MD PhD

  Syndeio Biosciences, 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

Study Record Dates

• First Submitted: October 21, 2022
• First Posted: October 28, 2022
• Study Start: October 15, 2022
• Primary Completion: April 4, 2023
• Study Completion: April 4, 2023
• Last Updated: April 11, 2023

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)