Safety, tolerability, pharmacokinetics,... — Clinical Trial Details

Phase Ib open-label study of a single 27.5 mg IV SPL026 (DMT fumarate) infusion administered as a 10-minute continuous infusion in adults with major depressive disorder; two cohorts enrolled: patients on a stable SSRI and patients not receiving pharmacological treatment who receive concurrent therapy.

Primary assessments include adverse events, vital signs, ECG and laboratory safety to Day 29 and C-SSRS for suicidal ideation/behaviour; secondary measures cover PK sampling and multiple PD/psychometric scales (DAS, RRS, SCS-R, WEMWBS, PIS, PTCS, MEQ, EDI, EBI, CEQ, VAS).

Sentinel dosing of two patients in the Test Cohort occurred with a minimum 48-hour safety review before continuation of dosing in the remaining cohort participants.

Participants

Ages

18 – 99

Sexes

Male & Female

BMI

18 - 33.9

Psychosis History

Excluded

Inclusion Criteria

1. Patients with MDD, as defined in 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 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 GP in the UK.
9. Under the care of a healthcare professional who can confirm the diagnosis and previous treatment received.
10. Sufficient intelligence to understand the nature of the trial and communicate satisfactorily.
11. Healthy as determined by physician based on medical evaluation including ECG and labs at Screening.
12. Agree to follow contraception requirements.
13. Willing to be contacted by email/telephone/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 written informed consent.

Exclusion Criteria

1. Meets DSM-5 criteria for substance abuse disorder or positive urine drug screen at Screening or Day -1 (excluding cannabis up to 24 h).
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.
3. In first-degree relatives, a clinically relevant history of a psychotic disorder (see full protocol).
4. Significant history of mania.
5. Psychiatric condition judged incompatible with rapport/safe exposure to DMT.
6. Significant suicide risk, defined by C-SSRS items 4 or 5 within 1 year, suicidal behaviours within 1 year, history of serious suicide attempts requiring hospitalisation, or clinical assessment of significant suicide risk.
7. Control Cohort Only: received any pharmacological treatment for MDD within 6 months of dosing (except MAO-inhibitors exception noted above).
8. Test Cohort Only: ongoing use of antidepressant augmentation or combination therapies other than a single SSRI.
9. Clinically relevant abnormal physical/mental health interfering with study.
10. Clinically relevant abnormal labs, ECG or vital signs at Screening/Day -1 as judged by Investigator.
11. Any acute condition or infection or chronic illness posing unacceptable risk.
12. Current or previous significant cardiovascular conditions or family history of long QT/sudden death.
13. AST/ALT/GGT/total bilirubin ≥1.5×ULN at Screening or Day -1 (with Gilbert's allowance per protocol).
14. Psychological or neurological conditions associated with seizures or convulsions.
15. BP or HR outside specified ranges at Screening.
16. QTcF ≥450 ms (males) or ≥470 ms (females) at Screening or predose on Day 1.
17. Presence of clinically significant ECG abnormalities at Screening.
18. Positive HBsAg, anti-HCV or anti-HIV I/II at Screening.
19. Use of serotonergic psychedelics within 6 months prior to dosing.
20. Intake of >21 units alcohol weekly or inability to refrain from alcohol from 24 h prior to visits.
21. Unable to refrain from smoking from 4 h prior to dosing until 4 h after dosing (low-dose nicotine patch permitted).
22. Receipt of an investigational product in another trial within 3 months prior to Day -1 or during Follow-up.

Company

Product

Legal

Detailed Description

Study Protocol

Preparation

Locations

Dosing

Integration

Therapeutic Protocol

Study Arms & Interventions

Test cohort (SSRI)

Interventions

Control cohort (no SSRI + therapy)

Interventions

Participants

Inclusion Criteria

Exclusion Criteria

Study Details