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

NCT ID: NCT05666687

Last Updated: 2024-04-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-01-11
• Study Completion Date: 2023-11-07

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).

Detailed Description

This is a Phase I, open-label, adaptive design study in healthy male participants using PET imaging with the radioligand [11C]Me-NB1 to measure occupancy of the NR2B-containing NMDA receptors by MIJ821. This exploratory study will be performed at a single clinical site and a separate PET imaging site.

Up to 10 participants will be enrolled into 5 sequential cohorts. Each participant will receive a single dose of MIJ821 as an i.v. infusion. As part of the adaptive design, the dose of MIJ821 will be changed across cohorts to achieve the primary study objective in the smallest possible number of participants.

After confirming eligibility during screening, each participant will undergo a baseline PET scan. Each participant will receive a single dose of i.v. MIJ821 during the treatment period, followed by up to two post dose PET scans. Post dose safety assessments will be performed up to End of Study visit which will happen once between Day 9 and Day 15.

Conditions

Major Depressive Disorder

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Cohort 1

MIJ821, starting dose

Group Type: EXPERIMENTAL

MIJ821

Intervention Type: DRUG

MIJ821 will be administered as an i.v. infusion

Cohort 2

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

Group Type: EXPERIMENTAL

MIJ821

Intervention Type: DRUG

MIJ821 will be administered as an i.v. infusion

Cohort 3

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

Group Type: EXPERIMENTAL

MIJ821

Intervention Type: DRUG

MIJ821 will be administered as an i.v. infusion

Cohort 4

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

Group Type: EXPERIMENTAL

MIJ821

Intervention Type: DRUG

MIJ821 will be administered as an i.v. infusion

Cohort 5

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

Group Type: EXPERIMENTAL

MIJ821

Intervention Type: DRUG

MIJ821 will be administered as an i.v. infusion

Interventions

MIJ821

MIJ821 will be administered as an i.v. infusion

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

• 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

David Steel, MD

Role: PRINCIPAL_INVESTIGATOR

Parexel Early Phase Clinical Unit (LONDON),

Locations

Novartis Investigative Site

Watford Road Harrow, , United Kingdom

Countries

United Kingdom

Other Identifiers

2022-002317-42

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CMIJ821A02111

Identifier Type: -

Identifier Source: org_study_id