Major Depressive DisorderPhase 1NCT05666687
An Open-label, Adaptive Design, Positron Emission Tomography Study in Healthy Male Participants to Characterize Receptor Occupancy by MIJ821 in the Brain
A Phase 1 study testing MIJ821 in people with Major Depressive Disorder, run by Novartis Pharmaceuticals at 1 site in United Kingdom.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 45 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Major Depressive Disorder
- What is being tested?
- MIJ821
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 11 Jan 2023to 7 Nov 2023
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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.
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- 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
Who cannot join
- 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
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- 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.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Novartis Investigative Site
Watford Road Harrow, HA1 3UJ
About this study
Official title: An Open-label, Adaptive Design Study in Healthy Male Participants to Characterize the Occupancy of NR2B Subunit Containing NMDA Receptors in the Brain Following a Single Intravenous Dose of MIJ821 Using Positron Emission Tomography (PET) With the Radioligand [11C]Me-NB1
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).
Read the 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
- Being tested
- MIJ821
- Keywords
- NR2B receptor modulator, Healthy subject, safety, pharmacokinetics receptor occupancy, PET scan, Major Depressive Disorder, adult
- Medical subject headings
- Depressive Disorder, Major
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MIJ821Drug
MIJ821 will be administered as an i.v. infusion
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 | Experimental | MIJ821, starting dose Receives: Drug: MIJ821 |
| Cohort 2 | Experimental | MIJ821, dose will be defined based on the results of the previous cohort(s). Receives: Drug: MIJ821 |
| Cohort 3 | Experimental | MIJ821, dose will be defined based on the results of the previous cohort(s). Receives: Drug: MIJ821 |
| Cohort 4 | Experimental | MIJ821, dose will be defined based on the results of the previous cohort(s). Receives: Drug: MIJ821 |
| Cohort 5 | Experimental | MIJ821, dose will be defined based on the results of the previous cohort(s). Receives: Drug: MIJ821 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Baseline PET Scan up to 15 days post dose
Secondary outcomes (6)
Binding parameters of [11C]-MeNB1
To characterize the binding properties of [11C]-Me-NB1 in the human brain
Measured: 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
To evaluate the relationship between displacement of central (brain) radioligand binding and systemic (plasma) concentration of MIJ821
Measured: Baseline PET scan up to 36 hours post dose
Tmax will be calculated as a PK parameter of MIJ821 in plasma.
To assess the systemic pharmacokinetics (PK) of MIJ821 after a single intravenous (i.v.) dose in healthy participants
Measured: 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
To assess the systemic pharmacokinetics (PK) of MIJ821 after a single intravenous (i.v.) dose in healthy participants
Measured: 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
To assess the systemic pharmacokinetics (PK) of MIJ821 after a single intravenous (i.v.) dose in healthy participants
Measured: 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.
Number of adverse events and serious adverse events.
The occurrence of adverse events must be sought by non-directive questioning of the participant at each visit during the study. Adverse events also may be detected when they are volunteered by the participant during or between visits or through physical examination findings, laboratory test findings, or other assessments (e.g., CADSS and C-SSRS).
Measured: Baseline up to Day 15, plus 30 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Dec 2022
- Study start11 Jan 2023
- Primary completion7 Nov 2023
- Study completion7 Nov 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Major Depressive DisorderStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Model description
- There will be 5 Cohorts
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- David Steel, MD, Principal investigator, Parexel Early Phase Clinical Unit (LONDON),
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05666687
- Sponsor's protocol ID
- CMIJ821A02111
- Other IDs
- 2022-002317-42
- Status last verified
- Mar 2024
- First submitted
- 18 Dec 2022
- Last updated
- 1 Apr 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label, Adaptive Design Study in Healthy Male Participants to Characterize the Occupancy of NR2B Subunit Containing NMDA Receptors in the Brain Following a Single Intravenous Dose of MIJ821 Using Positron Emission Tomography (PET) With the Radioligand [11C]Me-NB1
- ClinicalTrials.gov ID
- NCT05666687
- Acronym / sponsor ID
- CMIJ821A02111
- Conditions
- Major Depressive Disorder
- Keywords
- NR2B receptor modulator, Healthy subject, safety, pharmacokinetics receptor occupancy, PET scan, Major Depressive Disorder, adult
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 11 Jan 2023 (actual)
- Primary completion
- 7 Nov 2023 (actual)
- Study completion
- 7 Nov 2023 (actual)
- First posted
- 28 Dec 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 5
- Model description
- There will be 5 Cohorts
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 | Experimental | Drug: MIJ821MIJ821, starting dose |
| Cohort 2 | Experimental | Drug: MIJ821MIJ821, dose will be defined based on the results of the previous cohort(s). |
| Cohort 3 | Experimental | Drug: MIJ821MIJ821, dose will be defined based on the results of the previous cohort(s). |
| Cohort 4 | Experimental | Drug: MIJ821MIJ821, dose will be defined based on the results of the previous cohort(s). |
| Cohort 5 | Experimental | Drug: MIJ821MIJ821, dose will be defined based on the results of the previous cohort(s). |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (9 listed)
- 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
Key exclusion criteria (14 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MIJ821MIJ821 will be administered as an i.v. infusion | Drug | Cohort 1, Cohort 2, Cohort 3, Cohort 4, Cohort 5 |
Primary outcome
Human Brain Receptor Occupancy and Plasma Concentration of MIJ821
Time frame: Baseline PET Scan up to 15 days post dose
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
6 secondary outcomes
Binding parameters of [11C]-MeNB1
Time frame: 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
Time frame: Baseline PET scan up to 36 hours post dose
Tmax will be calculated as a PK parameter of MIJ821 in plasma.
Time frame: 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
Time frame: 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
Time frame: 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.
Number of adverse events and serious adverse events.
Time frame: Baseline up to Day 15, plus 30 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Apr 2024.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
David Steel, MD principal investigator
Parexel Early Phase Clinical Unit (LONDON),
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing MIJ821 in people with Major Depressive Disorder, run by Novartis Pharmaceuticals at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Human Brain Receptor Occupancy and Plasma Concentration of MIJ821 (time frame: Baseline PET Scan up to 15 days post dose). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Apr 2024.