We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05641623
Recruitment Status : Recruiting
First Posted : December 7, 2022
Last Update Posted : December 7, 2022
Sponsor:
Collaborator:
Arvid Carlsson Research AB
Information provided by (Responsible Party):
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.

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.

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 72 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Double-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 : April 21, 2022
Estimated Primary Completion Date : May 31, 2026
Estimated Study Completion Date : August 31, 2026

Resource links provided by the National Library of Medicine


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




Primary Outcome Measures :
  1. Bech 6-item subscale of the Hamilton Depression Rating Scale (HDRS) [ Time Frame: 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 :
  1. Hamilton Depression Rating Scale (HDRS) [ Time Frame: 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.


  2. Investigator-rated Montgomery Åsberg Depression Rating Scale (MADRS) [ Time Frame: Endpoint at 42 days treatment ]
    Change from baseline with respect to the total score. Lower scores mean a better outcome.

  3. investigator-rated Clinical Global Impression - Severity scale (CGI-S) [ Time Frame: Endpoint at 42 days treatment ]
    Change from baseline with respect to the total score. Lower scores mean a better outcome.

  4. Clinical Global Impression - Change scale (CGI-C) [ Time Frame: Endpoint at 42 days treatment ]
    Investigator rating. Lower scores mean a better outcome.

  5. Patient-rated Fatigue Severity Scale (FSS) [ Time Frame: Endpoint at 42 days treatment ]
    Change from baseline with respect to the total score. Lower scores mean a better outcome.

  6. Patient-rated MADRS-S (self) [ Time Frame: Endpoint at 42 days treatment ]
    Change from baseline with respect to the total score. Lower scores mean a better outcome.

  7. Patient-rated Snaith-Hamilton Pleasure Scale (SHAPS) [ Time Frame: Endpoint at 42 days treatment ]
    Change from baseline with respect to the total score. Lower scores mean a better outcome.

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

  9. Bech 6-item subscale of the HDRS [ Time Frame: 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.


  10. Patient Global Rating of Change Scale (GRC) [ Time Frame: 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.


  11. Possible markers of depression [ Time Frame: 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).

  12. AE/SAE [ Time Frame: Through study completion ]
    Number of participants with individual AEs and individual SAEs throughout the trial.

  13. Serum levels of medications [ Time Frame: Endpoint at 42 days treatment ]
    Serum levels of OSU6162 at endpoint and of the prescribed SSRI/SNRI at screening and endpoint.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   25 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Signed informed consent.
  2. Age: 25-65 on the day of screening.
  3. Meeting DSM-5 criteria for major depressive disorder as confirmed by the Mini International Neuropsychiatric Interview (MINI).
  4. A symptom-free period preceding the current episode within the past year confirmed at interview.
  5. 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.
  6. Displaying a sum score of MADRS ≥22.
  7. 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:

    1. Use of combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation

      • oral
      • intravaginal
      • transdermal
    2. progestogen-only hormonal contraception associated with inhibition of ovulation:

      • oral
      • injectable
      • implantable
    3. Placement of intrauterine device (IUD) or intrauterine hormone releasing system (IUS)
    4. Bilateral tubal occlusion or ligation
    5. 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).
  8. 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:

  1. 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.
  2. A history of substance/alcohol abuse within 2 years prior to screening.
  3. A previous diagnosis of a personality disorder, autism spectrum disorder, attention-deficit/hyperactivity disorder, or intellectual disability.
  4. Any other previously diagnosed or suspected CNS disorder that according to the investigator renders the patient unsuitable for participation in the trial.
  5. Any factor that according to the investigator renders it unlikely that the patient will comply with the instructions regarding treatment, visits etc.
  6. Any somatic illness that according to the investigator renders the patient unsuitable for participation in the trial.
  7. 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.
  8. Any change in dosage of said SSRI/SNRI within 4 weeks prior to screening or at any time during the course of the trial.
  9. 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.
  10. 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).
  11. 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).
  12. Current treatment with any prescribed or OTC drug that according to the investigator renders the subject unsuitable for participation in the trial.
  13. Previous intake of OSU6162.
  14. Current participation in another clinical trial.
  15. Nursing women.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05641623


Contacts
Layout table for location contacts
Contact: Elias Eriksson, Professor +46 709 555055 elias.eriksson@neuro.gu.se
Contact: Jakob Näslund, MD, PhD +46 702 947960 jakob.naslund@vgregion.se

Locations
Layout table for location information
Sweden
Sahlgrenska Universitetssjukhuset Recruiting
Göteborg, Västra Götaland, Sweden
Contact: Jakob Näslund, MD, PhD    +46702947960    jakob.naslund@pharm.gu.se   
Contact: Christin Englund, MD    +46313421000    christin.englund@vgregion.se   
Sponsors and Collaborators
Göteborg University
Arvid Carlsson Research AB
Investigators
Layout table for investigator information
Study Director: Elias Eriksson, Professor Göteborg University
Layout table for additonal information
Responsible Party: Göteborg University
ClinicalTrials.gov Identifier: NCT05641623    
Other Study ID Numbers: EudraCT number: 2020-005860-69
2020-005860-69 ( EudraCT Number )
First Posted: December 7, 2022    Key Record Dates
Last Update Posted: December 7, 2022
Last Verified: December 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Göteborg University:
Antidepressant
drug therapy, combination
Dopamine Drugs
Dopamine
Selective Serotonin Reuptake Inhibitor
SNRI
SSRI
Serotonin and Norepinephrine Reuptake Inhibitors
Additional relevant MeSH terms:
Layout table for MeSH terms
Disease
Recurrence
Depression
Depressive Disorder
Depressive Disorder, Treatment-Resistant
Pathologic Processes
Disease Attributes
Behavioral Symptoms
Mood Disorders
Mental Disorders
3-(3-(methylsulfonyl)phenyl)-1-propylpiperidine
Dopamine D2 Receptor Antagonists
Dopamine Antagonists
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs