OSU6162 as add-on in SSRI/SNRI-resistant Depression
- Conditions
- DepressionDepressive DisorderRecurrent Depressive DisorderRecurrent DepressionDepressive EpisodeDepressive Disorder, Treatment-Resistant
- Interventions
- Drug: Placebo
- Registration Number
- NCT05641623
- Lead Sponsor
- Göteborg University
- Brief Summary
This is a randomised, placebo-controlled, parallel-group trial comparing OSU6162 at flexible dosage with placebo as add-on to treatment with an SSRI/SNRI in patients with depression that have not responded to treatment with an SSRI/SNRI per se for at least 6 weeks. The study will last for 6 weeks, after which those not having responded will leave the trial and those having responded will be offered to continue treatment without unblinding for another 4 weeks. Optional Substudy 1 and 2: Baseline and treatment-associated change in reward-related striatal activity per fMRI-assessment. (Substudy 1).
Brain signal variability per fMRI-assessment. (Substudy 1). Probabilistic Reward Task (PRT). (Substudy 2).
While assessment of the efficacy and safety of OSU6162 is the main objective of this study, possible differences between the two treatment groups with respect to a number of biomarkers in serum will also be explored.
Multicenter trial: Multiple sites four Gothenburg, Lund, Stockholm and Uppsala.
- Detailed Description
The treatment period will be 6 weeks during which all subjects will make 7 study visits and be in contact with study nurse or physician by phone at 4 occasions. The first visit is a screening visit followed by a baseline visit for inclusion and start of treatment with OSU6162 or placebo.
Optional for the subjects Substudy 1 and 2: Baseline and treatment-associated change in reward-related striatal activity per fMRI-assessment. (Substudy 1).
Brain signal variability per fMRI-assessment. (Substudy 1). Probabilistic Reward Task (PRT). (Substudy 2).
Those responding to treatment will be offered to participate in the extension phase of the study for an additional 4 weeks during which the subjects will make 3 study visits and take 3 telephone interviews.
Before inclusion in the study, all subjects will be informed both verbally and in writing about its purpose, its procedures, and possible risks associated with participation. Before any study-specific procedures take place, written informed consent will be obtained.
Multicenter trial. Multiple sites 4: Sahlgrenska University Hospital Gothenburg, Skåne University Hospital Psychiatry Lund, North Stockholm psychiatry Stockholm region and Uppsala University Hospital Department of neuroscience Uppsala.
For participation in the extension phase, four factors must be fulfilled: 1. The subject must regard himself/herself as clearly improved and be willing to continue. 2. The investigator must assess the subject as clearly improved. 3. The subject must display at least 50% reduction on HDRS6 as compared to baseline. 4. The subject must have signed a new informed consent.
While assessment of the efficacy and safety of OSU6162 is the main objective of this study, possible differences between the two treatment groups with respect to a number of biomarkers in serum will also be explored.
The primary evaluation of efficacy will be undertaken at the endpoint of the 6-week trial. All analyses will however be repeated also at the endpoint of the 4-week extension phase for subjects participating in this part of the study.
Data will be analysed using mixed models for repeated measurement which means that the model includes data from all depression ratings from baseline to endpoint; this method, which is usually recommended to be used in depression trials by the authorities, is considered to handle data loss due to patients leaving a study prematurely in a better way than imputation methods such as the last observation carried forward (LOCF) technique.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 180
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo Coated tablets, flexible dosage, TID OSU6162 OSU6162 White, circular, coated tablets. Flexible dosage: the starting dose will be 15 mg TID and the maximal dose 45 mg TID.
- Primary Outcome Measures
Name Time Method Bech 6-item subscale of the Hamilton Depression Rating Scale (HDRS) Endpoint at 42 days treatment Change from baseline with respect to the total score of the investigator-rated Bech 6-item subscale of the Hamilton Depression Rating Scale (HDRS) at endpoint.
Lower scores mean a better outcome.
- Secondary Outcome Measures
Name Time Method Global Rating of Change Scale (GRC) Endpoint at 42 days treatment Patient rating. Lower scores mean a better outcome.
Serum levels of medications Endpoint at 42 days treatment Serum levels of OSU6162 at endpoint and of the prescribed SSRI/SNRI at screening and endpoint.
Investigator-rated Montgomery Åsberg Depression Rating Scale (MADRS) Endpoint at 42 days treatment Change from baseline with respect to the total score. Lower scores mean a better outcome.
Clinical Global Impression - Change scale (CGI-C) Endpoint at 42 days treatment Investigator rating. Lower scores mean a better outcome.
Patient-rated Fatigue Severity Scale (FSS) Endpoint at 42 days treatment Change from baseline with respect to the total score. Lower scores mean a better outcome.
Hamilton Depression Rating Scale (HDRS) Endpoint at 42 days treatment Number of participants displaying clinical response defined as ≥50% reduction in the total score of the investigator-rated Bech 6-item subscale of the HDRS.
Number of participants displaying clinical remission defined as a sum rating of ≤4 in the total score of the investigator-rated Bech 6-item subscale of the HDRS.
Change from baseline with respect to investigator-rated item 1 (depressed mood) of the HDRS.
Change from baseline with respect to the total score of the investigator-rated HDRS.
Lower scores mean a better outcome.investigator-rated Clinical Global Impression - Severity scale (CGI-S) Endpoint at 42 days treatment Change from baseline with respect to the total score. Lower scores mean a better outcome.
Patient-rated MADRS-S (self) Endpoint at 42 days treatment Change from baseline with respect to the total score. Lower scores mean a better outcome.
Patient-rated Snaith-Hamilton Pleasure Scale (SHAPS) Endpoint at 42 days treatment Change from baseline with respect to the total score. Lower scores mean a better outcome.
Patient Global Rating of Change Scale (GRC) Endpoint at 42 days treatment Patient rating of the Global Rating of Change Scale (GRC) at endpoint in patients displaying a sum rating of ≥36 at the Fatigue Severity Scale at baseline.
Lower scores mean a better outcome.Possible markers of depression Endpoint at 42 days treatment Change from baseline to endpoint with respect to serum levels of a number of possible markers of depression: C-reactive protein (CRP), tumor necrosis factor alpha (TNFα), brain-derived neurotrophic factor (BDNF) and interleukin-6 (IL-6).
AE/SAE Through study completion Number of participants with individual AEs and individual SAEs throughout the trial.
Bech 6-item subscale of the HDRS Endpoint at 42 days treatment Change from baseline with respect to the total score of the investigator-rated Bech 6-item subscale of the HDRS at endpoint in patients displaying a sum rating of ≥36 at the Fatigue Severity Scale at baseline.
Lower scores mean a better outcome.
Trial Locations
- Locations (4)
North Stockholm psychiatry Stockholm region
🇸🇪Stockholm, Sweden
Skåne University Hospital Psychiatry Lund
🇸🇪Lund, Skåne, Sweden
Sahlgrenska University Hospital
🇸🇪Gothenburg, Västra Götaland, Sweden
Uppsala University Hospital Department of neuroscience
🇸🇪Uppsala, Sweden