A Phase III, Randomized, Double Blind, Placebo Controlled, Parallel Group, Comparative, Multi-Centre Clinical Study to Evaluate the Efficacy and Safety of Ketamine Subcutaneous Injection as an Adjunct Treatment to on-going Antidepressant Therapy in Patients with Treatment Resistant Depression (TRD)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 81
- 试验地点
- 8
- 主要终点
- Percentage of responders in the test group compared to that in placebo group as assessed by MADRS
研究概览
简要总结
Despite availability of many antidepressant medications such as MAO inhibitors, TCA, SSRIs and SNRIs, many patients remain resistant to treatment. Treatment Resistant Depression (TRD), defined as patients who in the current depressive episode, had not responded adequately to at least two different classes of antidepressants of adequate dose and duration, is an unmet medical need. Therefore, there is a need for a more effective and rapid-acting antidepressant for the treatment of such patients.
Ketamine has been approved for general anesthesia either alone or in combination with other anesthetics since 1970 in USA and 1971 in India. Multiple clinical studies published over last 25 years indicate that Ketamine can be an useful option in the treatment of Major Depressive Disorder, especially in treatment-resistant depression. Esketamine (S-enantiomer of ketamine) was approved by US FDA and later in EU as a single-use nasal spray device for the treatment of treatment-resistant-depression (TRD) in adults and Depressive symptoms in adults with major depressive disorder (MDD). Based on published data, subcutaneous ketamine administration is effective in controlling symptoms of MDD and TRD and the risk of adverse events is relatively less in comparison to intravenous injection.
This double blind RCT has been designed to assess the efficacy and safety of Ketamine 50 mg/mL Solution in PFS when administered as subcutaneous injection as an add on treatment to the ongoing antidepressant therapy in patients with treatment resistant depression (TRD).
研究设计
- 研究类型
- Interventional
- 分配方式
- Computer generated randomization
- 盲法
- Participant and Investigator Blinded
入排标准
- 年龄范围
- 18.00 Year(s) 至 55.00 Year(s)（—）
- 性别
- All
入选标准
- •Male and female subjects between 18 to 65 years of age (both inclusive).
- •Subjects of depression who have failed to respond to the treatment with adequate dose and duration (minimum three weeks from initiation of the last antidepressant drug) of at least two different classes of antidepressant medications (TRD), without psychotic features, as assessed by investigator with the Structured Clinical Interview for DSM-5 (Diagnosis of TRD will be made based on patient’s treatment record and clinical interview).
- •Subjects with negative alcohol breath test result and urine screening result for drugs of abuse (including amphetamines, barbiturates, benzodiazepines, marijuana, cocaine and morphine) [Note: If the patient is taking any of these drugs on prescription may be included in the study in spite of a positive screening results for the prescribed drug(s)].
- •Subjects with baseline score of ≥ 22 on the Montgomery and Ã…sberg Depression Rating Scale (MADRS).
- •Subjects with baseline score of ≤ 9 on Bladder Pain/ Interstitial Cystitis Symptom Score (BPIC-SS),
- •For Female Subjects, of childbearing potential practicing an acceptable method of birth control such as sexual abstinence, a double-barrier method, condom plus spermicide, diaphragm plus spermicide, or vaginal spermicidal suppository; for the duration of the study as judged by the investigator(s)/study physician and agree to follow the same should be used during treatment.
- •OR Postmenopausal for at least 1 year.
- •OR Surgically sterile (bilateral tubal ligation/bilateral oophorectomy/ hysterectomy has been performed on the Subject).
- •Subjects who can give voluntary, written informed consent to participate in this clinical investigation and from whom IEC/IRB approved written informed consent has been obtained prior to screening.
- •Subjects shall be willing and able to understand and comply with the requirements of the protocol, administer the medication as instructed, return for the required treatment period visits, comply with therapy prohibitions, and be able to complete the study.
排除标准
- •History of previous non-response to esketamine or ketamine in depressive episode.
- •Subjects having any unstable medical or neurological condition as per principal investigator assessment.
- •Subject has suicidal ideation with intent to act during screening phase or on Day 1 (prior to randomization) based on the Columbia-Suicide Severity Rating Scale (C-SSRS) or per Investigator‟s clinical judgment, or has a history of suicidal behaviour within the past year as assessed on the C SSRS; or subject has homicidal ideation/intent at Screening or on Day
- •Subjects with substance abuse or dependence in the 6 months prior to screening.
- •Subjects with any psychotic disorder, bipolar disorder, obsessive compulsive disorder, intellectual disability, autism, cluster B personality disorder, organic disorder, developmental disorder.
- •Subjects with lifetime abuse or dependence on ketamine.
- •Subjects with previous history of non-response to Ketamine, or to all of the oral antidepressant medications.
- •Subjects with history of Vagus Nerve Stimulation (VNS) or deep brain stimulation in current episode of depression.
- •Subjects with history of homicidal ideation/intent.
- •Subjects with QT prolongation ≥450 msec during screening ECG or other significant arrhythmias.
- •Subjects with Other major medical conditions including coronary artery disease, uncontrolled hypertension, hypertensive crisis.
- •Subjects who have any condition that would compromise compliance with this protocol.
- •Female subjects who are pregnant or lactating or planning to become pregnant during the study period.
- •Female subjects who are not ready to use acceptable contraceptive methods during the study period.
- •Subjects with any other medical condition that might adversely impact the safety of the study participants or confound the study results.
- •Subjects who have been treated with an investigational drug or investigational device within a period of 30 days prior to study entry.
- •Currently taking prohibited concomitant medications(s) listed and inability/unwillingness to discontinue them for the entire study period.
- •Suspected inability or unwillingness to comply with the study procedures.
结局指标
主要结局
Percentage of responders in the test group compared to that in placebo group as assessed by MADRS
时间窗: Subjects in the Test product arm will receive Ketamine Solution 50 mg/mL PFS for Subcutaneous Injection at a dose of 0.5 mg/kg of body weight upto twice a week (on day 1 & day 4) for up to 6 weeks. Subjects in the Reference product arm will receive Matching Placebo of Ketamine solution upto twice a week (on day 1 & day 4) for up to 6 weeks
次要结局
- change in depression severity from baseline to study endpoint using MADRS in test group versus(placebo,)