ODEN: OSU6162 as add-on in SSRI/SNRI-resistant Depression

Sponsor

Göteborg University (Other)

Overall Status

Recruiting

CT.gov ID

NCT05641623

Collaborator

Arvid Carlsson Research AB (Industry)

Enrollment

Location

Arms

52.3

Anticipated Duration (Months)

1.4

Patients Per Site Per Month

Study Details

Study Description

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.

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.

Condition or Disease	Intervention/Treatment	Phase
Depression Depressive Disorder, Treatment-Resistant Depressive Disorder Depressive Episode Recurrent Depressive Disorder Recurrent Depression	Drug: OSU6162 Drug: Placebo	Phase 2

Detailed Description

The treatment period will be 6 weeks during which all patients 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.

Those responding to treatment will be offered to participate in the extension phase of the study for an additional 4 weeks during which the patients will make 3 study visits and take 3 telephone interviews.

Before inclusion in the study, all patients 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.

For participation in the extension phase, four factors must be fulfilled: 1. The patient must regard himself/herself as clearly improved and be willing to continue. 2. The investigator must assess the patient as clearly improved. 3. The patient must display at least 50% reduction on HDRS6 as compared to baseline. 4. The patient must have signed a new informed consent.

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

72 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Double-blindDouble-blind

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Masking Description:

Monitor

Primary Purpose:

Treatment

Official Title:

OSU6162 as add-on in SSRI/SNRI-resistant Depression (ODEN): a Double-blind, Placebo-controlled Evaluation of Efficacy and Safety

Actual Study Start Date :

Apr 21, 2022

Anticipated Primary Completion Date :

May 31, 2026

Anticipated Study Completion Date :

Aug 31, 2026

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: OSU6162 White, circular, coated tablets. Flexible dosage: the starting dose will be 15 mg TID and the maximal dose 45 mg TID.	Drug: OSU6162 OSU6162 Other Names: OSU-6162 PNU-96391
Placebo Comparator: Placebo Coated tablets, flexible dosage, TID	Drug: Placebo Placebo

Arm

Intervention/Treatment

Active Comparator: OSU6162

White, circular, coated tablets. Flexible dosage: the starting dose will be 15 mg TID and the maximal dose 45 mg TID.

Drug: OSU6162

OSU6162

Other Names:

OSU-6162

PNU-96391

Placebo Comparator: Placebo

Coated tablets, flexible dosage, TID

Drug: Placebo

Placebo

Outcome Measures

Primary Outcome Measures

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

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 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.
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.
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.
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.
Global Rating of Change Scale (GRC) [Endpoint at 42 days treatment]
Patient rating. Lower scores mean a better outcome.
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.
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.
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

25 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Signed informed consent.
Age: 25-65 on the day of screening.
Meeting DSM-5 criteria for major depressive disorder as confirmed by the Mini International Neuropsychiatric Interview (MINI).
A symptom-free period preceding the current episode within the past year confirmed at interview.
Not significantly improved, as judged by both doctor and patient, after having been treated with one of the following SSRIs/SNRIs: citalopram, escitalopram, paroxetine, sertraline, fluoxetine, duloxetine, or venlafaxine for at least 6 weeks.
Displaying a sum score of MADRS ≥22.
In women of childbearing potential (WOCBP): negative result of a pregnancy test and a method of contraception with a failure rate of less than 1 %. Contraception must be used during the treatment and follow-up period. Acceptable forms of contraception are:
Use of combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation

oral
intravaginal
transdermal

progestogen-only hormonal contraception associated with inhibition of ovulation:

oral
injectable
implantable

Placement of intrauterine device (IUD) or intrauterine hormone releasing system (IUS)
Bilateral tubal occlusion or ligation
Vasectomised partner (with appropriate post-vasectomy documentation of the absence of sperm in the ejaculate and provided that male partner is the sole sexual partner of the WOCBP trial participant).
Male patients must agree to use condoms during the study and for 2 weeks after the end of the study/last dose of IMP, unless their partner is using a highly efficient method of contraception, as described above.

Exclusion Criteria:

Meeting MINI criteria at interview for suicidality, manic episode, hypomanic episode, bipolar I, bipolar II, bipolar unspecified, bipolar I with psychotic symptoms, panic disorder, agoraphobia, social anxiety (social phobia), obsessive compulsive disorder, posttraumatic stress disorder, alcohol dependency, alcohol abuse, substance dependency (non-alcoholic), substance abuse (non-alcoholic), psychotic disorders, mood disorders with psychotic features, anorexia nervosa, bulimia nervosa, anorexia nervosa binge eating / purging type, generalised anxiety disorder, or antisocial personality disorder.
A history of substance/alcohol abuse within 2 years prior to screening.
A previous diagnosis of a personality disorder, autism spectrum disorder, attention-deficit/hyperactivity disorder, or intellectual disability.
Any other previously diagnosed or suspected CNS disorder that according to the investigator renders the patient unsuitable for participation in the trial.
Any factor that according to the investigator renders it unlikely that the patient will comply with the instructions regarding treatment, visits etc.
Any somatic illness that according to the investigator renders the patient unsuitable for participation in the trial.
Any signs or symptoms of somatic illness resulting from assessment of vital signs, physical examination, clinical laboratory tests, and 12-lead ECG that according to the investigator renders the patient unsuitable for participation for safety reasons, including a QTc-time on ECG exceeding 450 ms in men and 460 ms in women.
Any change in dosage of said SSRI/SNRI within 4 weeks prior to screening or at any time during the course of the trial.
Treatment with any other psychoactive drug than said SSRI/SNRI with the exception of occasional use of benzodiazepines and benzodiazepine-like anxiolytics or hypnotics and occasional use of antihistaminergic sedatives (without anti-dopaminergic effects) within 4 weeks prior to screening and at any time during the course of the trial.
Patients who are receiving concomitant therapy with potent cytochrome P450 enzyme inhibitors (e.g., bupropion, fluvoxamin, ketoconazol, itraconazole, telitromycin, clarithromycin, protease inhibitors, quinidine, and terbinafine).
Ongoing treatment with drugs with a narrow therapeutic window where either lower or higher serum levels are potentially harmful (including but not limited to warfarin along with other anticoagulants, digoxin along with other antiarrythmics, anticonvulsants prescribed for treatment of epilepsy, cyclosporine, immunosuppressants, and lithium).
Current treatment with any prescribed or OTC drug that according to the investigator renders the subject unsuitable for participation in the trial.
Previous intake of OSU6162.
Current participation in another clinical trial.
Nursing women.