Safety, tolerability, pharmacokinetics, pharmacodynamics and exploratory efficacy of intravenous dosing of SPL026 drug product (N, N-dimethyltryptamine fumarate; DMT Fumarate [A Serotonergic Psychedelic]) alone or in combination with selective serotonin reuptake inhibitors in patients with major depressive disorder
- Conditions
- Major Depressive Disorder (MDD)Mental and Behavioural Disorders
- Registration Number
- ISRCTN10974027
- Lead Sponsor
- Cybin UK Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- All
- Target Recruitment
- 18
1. Patients with MDD, as defined in the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) of a mild to severe degree (scoring =14 on the 17-item HAM-D).
2. Patient is aged =18 years.
3. Patient has a body mass index (BMI) of 18 to 33.9 kg/m2, inclusive.
4. Test Cohort Only: Patient is currently on a stable dose of an unspecified single SSRI alone and not in combination with any other psychiatric medications, for at least 6 weeks prior to Screening with no intention of making any changes.
5. Patient has tried at least one approved method of treatment for their depression.
6. Patient has not been administered any Monoamine Oxidase-Inhibitor (MAO-inhibitor) class antidepressants for at least 3 months prior to Screening.
7. No psychedelic drug use 6 months prior to dosing (excluding the study drug) until the end of the study.
8. Registered with a General Practitioner (GP) in the UK.
9. Under the care of a healthcare professional who can confirm the diagnosis and previous treatment received by the patient.
10. Sufficient intelligence to understand the nature of the trial and any hazards of participation in it. Ability to communicate satisfactorily with the Investigator and therapist team to participate in, and comply with the requirements of, the entire trial.
11. Healthy as determined by a responsible physician, based on no clinically significant findings from medical evaluation including medical history, a physical examination, concomitant medication, vital signs, 12-lead Electrocardiogram (ECG) and clinical laboratory evaluations (including haematology, coagulation, biochemistry and urinalysis) at the Screening visit and admission.
12. Agree to follow the contraception requirements of the trial.
13. Willing to be contacted by email and telephone and video call.
14. Proficient in reading and writing English sufficient to complete questionnaires.
15. Willing to give written consent to have data entered into The Over-volunteering Prevention System.
16. Provision of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form, and after the having the opportunity to discuss the trial with the Investigator or their delegate.
1. Patient meets the DSM-5 criteria for substance abuse disorder, as assessed the Mini International Neuropsychiatric Interview (MINI) Version 7.0.2 at Screening, or a positive urine drugs of abuse result at Screening or Day -1 (excluding cannabis which is permitted to be taken up to 24 hours before each trial visit, but which may be detected in urine). Repeat tests may be considered by the Investigator with justification.
2. Current or clinically relevant history of a psychotic disorder, including schizophrenia, psychosis, bipolar disorder, delusional disorder, paranoid personality disorder, schizoaffective disorder, borderline personality disorder, emotionally unstable personality disorder or panic disorder, as assessed by a structured clinical interview (MINI, Version 7.0.2) at Screening. 3. In first-degree relatives, a clinically relevant history of a psychotic disorder, including schizophrenia, psychosis, bipolar disorder, delusional disorder, paranoid personality disorder or schizoaffective disorder.
4. Significant history of mania (as determined by the Investigator and medical records, in agreement with the Sponsor’s Medical Monitor).
5. Psychiatric condition judged to be incompatible with establishment of rapport with the therapy team and/or safe exposure to DMT, based on the Investigator’s clinical evaluation (e.g., borderline personality disorder).
6. Significant suicide risk, as defined by: · Suicidal ideation as endorsed on items 4 or 5 on the C-SSRS within 1 year prior to Screening or on Day -1, or Suicidal behaviours within 1 year prior to Screening, or History of serious suicide attempts in lifetime (i.e., those that require hospitalisation), or Clinical assessment of significant suicide risk during Patient interview.
General Medical Exclusion Criteria
Patients with any of the following will be excluded from study participation:
1. Control Cohort Only: Patient has received any pharmacological treatment for MDD within 6 months of dosing, with the exception of MAO-inhibitors which they cannot have received within 3 months of Screening.
2. Test Cohort Only: Ongoing use of antidepressant augmentation or combination therapies, other than a single SSRI.
3. Clinically relevant history of abnormal physical or mental health interfering with the study as determined by medical history and physical examinations obtained during Screening, as judged by the Investigator (including [but not limited to]: neurological, psychiatric, endocrine, thyroid, cardiovascular, respiratory, GI, hepatic, haematological, musculoskeletal, immunological, renal, connective tissue diseases or disorders or any other medically relevant condition as judged by the Investigator).
4. Clinically relevant abnormal laboratory results (including hepatic and renal panels, complete blood count, chemistry panel and urinalysis), 12-lead ECG and vital signs, or physical findings at Screening and/or Day -1 as judged by the Investigator, that in the Investigator’s opinion may constitute a risk for an individual who is exposed to DMT. In case of uncertain or questionable results, tests performed during Screening may be repeated to confirm eligibility or judged to be clinically irrelevant for otherwise healthy MDD patients.
5. Any other acute condition or infection, or history of chronic illness or condition, that could interfere with, or for which the treatment might interfere with, the conduct of the study as outlined in this Protocol, or that would, in the opinion of the
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method 1.Safety will be evaluated by the monitoring of adverse events (AEs), vital signs (blood pressure, heart rate and temperature), 12-lead electrocardiogram (ECG) evaluations, clinical laboratory assessments (haematology, clinical chemistry, coagulation and urinalysis), cannulation site reactions and physical examination findings. To Day 29.<br>2.Suicidal ideation and behaviour will be evaluated using the Columbia Suicide Severity Rating Scale (C-SSRS). To Day 29.<br>3.Tolerability will be evaluated by reviewing the therapists’ notes that document the subjective psychedelic effects and a tolerability assessment. To Day 2.<br>
- Secondary Outcome Measures
Name Time Method