OSU6162 as add-on in SSRI/SNRI-resistant Depression (ODEN): a Double-blind, Placebo-controlled Evaluation of Efficacy and Safety
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 180
- 试验地点
- 7
- 主要终点
- Bech 6-item subscale of the Hamilton Depression Rating Scale (HDRS)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Monitor
入排标准
- 年龄范围
- 25 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •In order to be included in the study, subjects must meet the following criteria:
- •Signed informed consent.
- •Age: 25-75 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 two years 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 ≥
- •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
- •intravaginal
- •transdermal
- •progestogen-only hormonal contraception associated with inhibition of ovulation:
- •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).
- •Sexual abstinence.
- •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.
排除标准
- •Subjects must not be included in the study if any of the following criteria are met:
- •Meeting MINI criteria at interview for suicidality, manic episode, hypomanic episode, bipolar I, bipolar II, bipolar unspecified, bipolar I with psychotic symptoms, panic disorder (current), agoraphobia, 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, or antisocial personality disorder.
- •Meeting MINI criteria at interview for generalised anxiety disorder, obsessive compulsive disorder or social anxiety (social phobia), unless the present symptoms can predominantly be attributed to a diagnosis of major depressive 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, refraining from use of central stimulants 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 using mirtazapine up to 15 mg for sleep, 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, ketoconazole, itraconazole, telithromycin, 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 OSU
- •Current participation in another clinical trial.
- •Nursing women.
- •Substudy only: Relative and/or absolute contraindications to lumbar puncture and functional Magnetic Resonance Imaging (fMRI), as per clinical practice. This includes ongoing treatment with anticoagulants such as NOAC or warfarin.
研究组 & 干预措施
OSU6162
White, circular, coated tablets. Flexible dosage: the starting dose will be 15 mg TID and the maximal dose 45 mg TID.
干预措施: OSU6162 (Drug)
Placebo
Coated tablets, flexible dosage, TID
干预措施: Placebo (Drug)
结局指标
主要结局
Bech 6-item subscale of the Hamilton Depression Rating Scale (HDRS)
时间窗: 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.
次要结局
- Global Rating of Change Scale (GRC)(Endpoint at 42 days treatment)
- Serum levels of medications(Endpoint at 42 days treatment)
- Investigator-rated Montgomery Åsberg Depression Rating Scale (MADRS)(Endpoint at 42 days treatment)
- Clinical Global Impression - Change scale (CGI-C)(Endpoint at 42 days treatment)
- Patient-rated Fatigue Severity Scale (FSS)(Endpoint at 42 days treatment)
- Hamilton Depression Rating Scale (HDRS)(Endpoint at 42 days treatment)
- investigator-rated Clinical Global Impression - Severity scale (CGI-S)(Endpoint at 42 days treatment)
- Patient-rated MADRS-S (self)(Endpoint at 42 days treatment)
- Patient-rated Snaith-Hamilton Pleasure Scale (SHAPS)(Endpoint at 42 days treatment)
- Patient Global Rating of Change Scale (GRC)(Endpoint at 42 days treatment)
- Possible markers of depression(Endpoint at 42 days treatment)
- AE/SAE(Through study completion)
- Bech 6-item subscale of the HDRS(Endpoint at 42 days treatment)