An Open-label, Adaptive Design, Positron Emission Tomography Study in Healthy Male Participants to Characterize Receptor Occupancy by MIJ821 in the Brain

NCT05666687 | Completed Phase 1

• 2 other identifiers: CMIJ821A021112022-002317-42
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to confirm binding of MIJ821 to the NR2B-containing NMDA receptors in the human brain and assess the PC-RO relationship over time using positron emission tomography (PET).

Conditions

Major Depressive Disorder

Keywords

NR2B receptor modulator; Healthy subject; safety; pharmacokinetics receptor occupancy; PET scan; Major Depressive Disorder; adult

Outcome Measures

Primary Outcomes (1)

• Human Brain Receptor Occupancy and Plasma Concentration of MIJ821

  To evaluate the relationship between plasma concentration of MIJ821 and brain receptor occupancy by MIJ821 in healthy participants, by using positron emission tomography (PET) with \[11C\]Me-NB1

  Baseline PET Scan up to 15 days post dose

Secondary Outcomes (6)

• Binding parameters of [11C]-MeNB1

  Baseline PET scan up to 15 days post dose

• Percentage change in PET imaging outcome measures after treatment with MIJ821 compared to baseline and plasma concentration of MIJ821

  Baseline PET scan up to 36 hours post dose

• Tmax will be calculated as a PK parameter of MIJ821 in plasma.

  PK samples are collected at the end of i.v. infusion (Day 1) and at the beginning and end of each PET scan. Each cohort has 5 samples collected at various timepoints (dependent on time of PET scans) from i.v. infusion up to 5 days.

• AUC will be calculated as a PK parameter of MIJ821 in plasma

  PK samples are collected at the end of i.v. infusion (Day 1) and at the beginning and end of each PET scan. Each cohort has 5 samples collected at various timepoints (dependent on time of PET scans) from i.v. infusion up to 5 days.

• Cmax will be calculated as a PK parameter of MIJ821 in plasma

  PK samples are collected at the end of i.v. infusion (Day 1) and at the beginning and end of each PET scan. Each cohort has 5 samples collected at various timepoints (dependent on time of PET scans) from i.v. infusion up to 5 days.

Study Arms (5)

Cohort 1

EXPERIMENTAL

MIJ821, starting dose

Drug: MIJ821

Cohort 2

EXPERIMENTAL

MIJ821, dose will be defined based on the results of the previous cohort(s).

Drug: MIJ821

Cohort 3

EXPERIMENTAL

MIJ821, dose will be defined based on the results of the previous cohort(s).

Drug: MIJ821

Cohort 4

EXPERIMENTAL

MIJ821, dose will be defined based on the results of the previous cohort(s).

Drug: MIJ821

Cohort 5

EXPERIMENTAL

MIJ821, dose will be defined based on the results of the previous cohort(s).

Drug: MIJ821

Interventions

MIJ821 DRUG

MIJ821 will be administered as an i.v. infusion

Cohort 1; Cohort 2; Cohort 3; Cohort 4; Cohort 5

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Signed informed consent must be obtained prior to participation in the study
• Healthy males, aged 23 to 55 years (inclusive), and in good health as determined by past medical history, physical and neurological examination, vital signs, electrocardiogram, and laboratory tests at Screening and Baseline (whenever applicable)
• At screening and at baseline (Day -1), vital signs after 3 minutes resting (in sitting position during screening and supine position during baseline) must be within the following ranges:
• Body temperature (otic) from 35.0 °C to 37.5 °C, inclusive
• Systolic blood pressure (BP) from 90 to 139 mmHg, inclusive
• Diastolic BP from 50 to 89 mmHg, inclusive.
• Pulse rate from 50 to 90 beats per minute, inclusive
• Participants must weigh at least 50 kg to participate in the study and must have a body mass index (BMI) within the range of 18.0 to 29.9 kg/m² at screening. BMI = body weight (kg) / height2 (m2)
• Participants must be able to communicate well with the Investigator and to comply with the requirements of the entire study, including adhering to study restrictions and visit schedule

You may not qualify if:

• Hypersensitivity to NMDA antagonists (MIJ821 or other compounds with similar mechanism of action, like ketamine or compounds with similar chemical structure to ketamine) or to any excipients, local anesthetics, or anticoagulants used in this study.
• Any significant illness, including infectious diseases, which has not resolved within 2 weeks prior to baseline.
• Any of the following ECG abnormalities at Screening or Baseline:
• PR interval outside 110-200 ms
• QRS duration outside 70-120 ms
• Resting heart rate in sinus rhythm outside 50-90 bpm
• QTcF \> 450 ms
• Exposure to ionizing radiation as part of a research study, which, in addition to the exposure from this study, would lead to a total effective dose of more than 10 mSv in a period of one year.
• Any history of neurological disorders, including, but not limited to any of the followings:
• Any history of stroke or known cerebrovascular disorders (e.g. aneurysm or arteriovenous malformation) or known aneurysmal vascular disease in other location (e.g. aorta)
• Any history or presence of epilepsy or of seizures or convulsions of any kind.
• Any history of head trauma leading to permanent sequelae or history of head trauma leading to clinically significant but transient symptoms within 2 years of baseline.
• Score "yes" on item 4 or item 5 of the Suicidal Ideation section of the C-SSRS, if this ideation occurred in the past 6 months from screening, or "yes" on any item of the Suicidal Behavior section, except for the "Non-Suicidal Self-Injurious Behavior" (item also included in the Suicidal Behavior section), if this behavior occurred in the past 2 years.
• Sexually active males unwilling to use a condom during intercourse while taking study treatment and for 90 days following dosing. A condom is required for all sexually active male participants for 90 days following dosing (including vasectomized men) to prevent them from fathering a child AND to prevent delivery of the investigational drug via seminal fluid to their partner.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (1)

Novartis Investigative Site

Watford Road Harrow, HA1 3UJ, United Kingdom

Location

MeSH Terms

Conditions

Depressive Disorder, Major

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Study Officials

• David Steel, MD

  Parexel Early Phase Clinical Unit (LONDON),

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: There will be 5 Cohorts

Study Record Dates

• First Submitted: December 18, 2022
• First Posted: December 28, 2022
• Study Start: January 11, 2023
• Primary Completion: November 7, 2023
• Study Completion: November 7, 2023
• Last Updated: April 1, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)