Adjunctive Oral KET-AD Capsules in Treatment Resistant Bipolar Depression

NCT07644767 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: KETI-CAPS-201
• Study Type: interventional
• Target: 160
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study is testing a new oral ketamine treatment called KET-AD in adults with treatment-resistant bipolar depression (TRBD). The study will look at how safe and tolerable the treatment is, and whether it may help improve symptoms of depression when used together with a participant's usual treatment. About 160 people will take part in the study. Participants will be randomly assigned (like flipping a coin) to receive either KET-AD or a placebo (a treatment with no active medicine). Neither the participant nor the study team will know which treatment the participant is receiving during the study. The study treatment will be taken by mouth 3 times a week for up to 7 weeks. Participants will continue taking their usual standard treatment throughout the study. The study has several parts: Screening Period (up to 28 days) Before joining the study, participants will complete tests and assessments to confirm whether they are eligible to take part. Titration Phase (Weeks 1-3) The first 3 weeks are used to find the highest dose of study treatment that each participant can comfortably tolerate. All doses during this phase are given at the study clinic. Participants will start on a lower dose. Depending on how well the treatment is tolerated, the dose may be increased, kept the same, or reduced. The study doctor will carefully monitor participants for side effects after each dose. Participants who cannot tolerate the treatment, or who cannot reach the required dose level by the end of Week 3, will stop study treatment and complete an early finish visit. Maintenance Phase (Weeks 4-7) Participants who tolerate the treatment during the Titration Phase may continue into the 4-week Maintenance Phase. Participants will stay on the same dose throughout this phase. Some doses will still be given at the study clinic. Other doses may be taken at home if approved by the study doctor. Home doses will be supervised remotely by a mental health professional using a secure telehealth app. Participants will use an electronic app during the study. The app will be used to complete questionnaires and other study assessments both at the clinic and at home. Participants may use their own device or be provided with one by the study team. Training will be provided before participants begin using the app independently. Safety Monitoring Participant safety will be closely monitored throughout the study by the study doctors and by an independent safety committee called a Data Safety Monitoring Board (DSMB). Follow-up Visits After treatment ends, participants will attend: a follow-up clinic visit on Day 50, and an end-of-study visit on Day 64, which may be completed remotely. Participants can leave the study at any time if they choose.

Conditions

Treatment Resistant Bipolar Depression

Keywords

Treatment Resistant Bipolar Depression; Ketamine

Outcome Measures

Primary Outcomes (1)

• Incidence of Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

  Safety and tolerability of oral ketamine (KET-AD) 140 mg to 280 mg compared with placebo will be assessed by the incidence, frequency, severity, and relationship to study treatment of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs).

  Baseline through Day 64 (End of Study)

Secondary Outcomes (14)

• Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score

  Baseline through Week 7 (Day 43)

• Proportion of Participants Achieving Response Based on MADRS

  Week 7 (Day 43)

• Proportion of Participants Achieving Remission Based on MADRS

  Week 7 (Day 43)

• Change From Baseline in Clinical Global Impression-Severity (CGI-S) Score

  Baseline through Week 7 (Day 43)

• Change From Baseline in Clinical Global Impression-Improvement (CGI-I) Score

  Baseline through Week 7 (Day 43)

Other Outcomes (6)

• Change From Baseline in Modified Observer's Assessment of Alertness/Sedation (MOAA/S)

  Baseline through Week 7 (Day 43)

• Change From Baseline in Quick Inventory of Depressive Symptomatology-Self Report (QIDS-SR) Total Score

  Baseline through Week 7 (Day 43)

• Change From Baseline in Snaith-Hamilton Pleasure Scale (SHAPS) Total Score

  Baseline through Week 7 (Day 43)

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Placebo administered orally 3 times a week, over a period of 7 weeks, as adjunctive to standard of care (SOC).

Other: Placebo

KET-AD

EXPERIMENTAL

KET-AD (140 mg to 280 mg) administered orally 3 times a week, over a period of 7 weeks, as adjunctive to standard of care (SOC).

Drug: KET-AD

Interventions

KET-AD DRUG

KET-AD is provided as a 70mg capsule.

KET-AD

Placebo OTHER

Matching placebo

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female aged 18 to 65 years (inclusive) at the time of informed consent, with first major depressive episode (MDE) before the age of 50 years.
• Body mass index (BMI) between 18 and 40 kg/m2, inclusive.
• Meet the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) diagnostic criteria for BD (any type) currently experiencing a depressive episode, without psychotic features, based upon clinical assessment and confirmed by the Mini International Neuropsychiatric Interview (MINI).
• Current MDE must be moderate to severe, as determined by the Hamilton Depression Rating Scale (HDRS-17) score \> 20 with inadequate response (lack of clinically meaningful improvement of clinical symptoms) to 2 or more adequate evidence based treatment trials for bipolar depression, as per the 2018 Canadian Network for Mood and Anxiety Treatments (CANMAT) Bipolar Disorder Guidelines (25) as assessed using the Massachusetts General Hospital - Antidepressant Treatment Response Questionnaire (MGH-ATRQ) and documented by records (eg, medical/pharmacy/prescription records or a letter from treating physician etc.), for the current episode of depression.
• Participant is taking a stable dose of a guideline concordant treatment for the bipolar depression on the MGH-ATRQ for at least 6 weeks at or above the minimum therapeutic dose.
• Any psychotherapeutic treatment has been stable for at least 6 weeks prior to Screening, with no anticipated changes in frequency or therapist anticipated until after the EOS visit.
• Willing to abstain from recreational/illicit drugs from Screening until the end of the study.
• Willing to allow their own GP and/or other mental health professional, to be informed of study participation and agree to the participant withdrawing from their current medication as required.
• Participant has stable, euthyroid thyroid function at Screening, as confirmed by laboratory results. Participants with a history of thyroid disease may be included if they are clinically euthyroid and have been on a stable thyroid treatment regimen for at least 2 months prior to the Screening visit.
• Woman of childbearing potential (WOCBP) or fertile man agrees to use an acceptable method of contraception from at least 1 month prior to the Screening visit (WOCBP) or the start of Screening (fertile man) until 90 days after the last dose of IP. WOCBP must agree to not donate eggs and males must agree to not donate sperm from the first dose of IP until at least 90 days after the last dose of IP.
• Not pregnant or breastfeeding, or willing to cease breastfeeding.
• Any form of exercise, including but not limited to, sporting activities, gym, yoga or Pilates attendance, has been stable for at least 6 weeks prior to Screening, with the participant agreeable to not making changes to their type or frequency of exercise/s until after the EOS visit.
• Able and willing to attend the necessary visits to the study site.
• Able and willing to provide written informed consent after the nature of the study has been explained and prior to the commencement of any study procedures.

You may not qualify if:

• In the Investigator's opinion, participant has chronic, refractory treatment resistant depression characterised by a lifetime history of \> 4 adequate therapeutic trials of guideline concordant medications for bipolar depression (with or without adjuvants and/or electroconvulsive therapy \[ECT\]) without response, as confirmed by the MGH-ATRQ.
• Current MDE for longer than 12 months prior to the Screening visit.
• Current symptoms of mania, hypomania, or mixed features, as determined by the YMRS score \> 12.
• Has a history or current diagnosis of rapid cycling BD.
• History of mania or hypomania in the past 6 months as determined by psychiatric history.
• Has a current substance use disorder or history of any substance use disorder per DSM-5 criteria within 6 months prior to Screening, except for tobacco use disorder.
• Has a history or current diagnosis of schizophrenia, schizoaffective disorders, or any psychotic disorder. Has posttraumatic stress disorder, obsessive compulsive disorder, autism spectrum disorder, borderline personality disorder, antisocial personality disorder, narcissistic personality disorder or histrionic personality disorder, or any other mental disorder with psychotic features.
• Has past suicidal behaviour and/or suicidal thoughts with an intention defined by:
• suicidal ideation as endorsed on items 4 or 5 on the C-SSRS within the past year, during the Screening period, or at Baseline; or
• suicidal behaviours within the past year; or
• clinical assessment of significant suicidal risk during clinical interview; or
• non-suicidal self-injury within the past year.
• Has dementia, delirium, amnesia, or any other significant cognitive disorder.
• Has any known aneurysmal disease, recent myocardial infarction (MI) (within past 12 months), or medical condition for which an increase in blood pressure or intracranial pressure poses a serious risk. Has clinically significant cardiovascular disorders such as uncontrolled atrial fibrillation, heart failure, or ischaemic heart disease.
• Recent hospitalisation (within 6 months of Screening) for procedures, such as percutaneous coronary intervention or coronary artery bypass surgery.

Sponsors & Collaborators

• Neurocentrx Pharma Pty Ltd: lead

Related Links

• Related Info

Study Officials

• Ishrat Husain, MBBS, MD, FRCPsych(UK) FRCP(C)

  University Health Network (UHN); Department of Psychiatry, Temerty Faculty of Medicine, University of Toronto

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 27, 2026
• First Posted: June 12, 2026
• Study Start (Estimated): October 30, 2026
• Primary Completion (Estimated): January 30, 2028
• Study Completion (Estimated): June 1, 2028
• Last Updated: June 12, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share