A Multicenter, Double-Blind, 58 week Rollover Study to assess the Safety and Tolerability ofBMS-820836 in Patients with Treatment Resistant Major Depression
试验速览
- 阶段
- 2 期
- 状态
- Other
- 入组人数
- 500
- 试验地点
- 7
- 主要终点
- The primary objective of this study is to compare the long term effect of 3 target doses of
研究概览
简要总结
A Multicenter, Double-Blind, 58 Week Rollover Study to assess the Safety and Tolerability of BMS-820836 in Patients with Treatment Resistant Major Depression.
Investigational Product(s), Dose and Mode of Administration, Duration of Treatment with Investigational Product(s): This is a multicenter, double-blind, parallel group, study designed to assess the safety and tolerability of 3 doses of BMS-820836 (0.5, 1, and 2 mg/day) in subjects with TRD. The study population will include male and female outpatients between the ages of 18 - 65 years of age with a DSM-IV-TR diagnosis of non-psychotic Major Depressive Disorder (MDD) who have completed participation in CN162006 or CN162007 (the “parent studiesâ€).The study will be organized into 3 phases: Baseline Visit: Subjects who complete CN162006 or CN162007 will have the option to enter the rollover study. For subjects who consent to enter the study, the last visit of the parent study will be the Baseline visit of the rollover study. Therefore the Week 14 visit CN162006 and Week 13 visit in CN162007 will also be the Baseline visit for the current study. Additional assessments, which were not completed in the parent study visit schedule, may be required for the Baseline visit of the current study.
Treatment Phase: Subjects meeting entry criteria for this study and who consent to enter the study will be enrolled into a 54-week Treatment Phase on the day of the last visit in the parent study. All subjects treated with BMS-820836 in the parent studies will be assigned to a target BMS-820836 dose group (0.5, 1, and 2 mg) in the current study in accordance with the last dose of BMS-820836 received in the parent study.Subjects randomized in Phase C of the respective parent study to duloxetine (CN162006) or duloxetine and escitalopram (CN162007) will be re-randomized in the current study to one of the three target dose arms of BMS-820836 (0.5, 1, and 2 mg).
The study will be organized into 3 phases:Baseline Visit: Subjects who complete CN162006 or CN162007 will have the option to enter the rollover study. For subjects who consent to enter the study, the last visit of the parent study will be the Baseline visit of the rollover study. Therefore the Week 14 visit CN162006 and Week 13 visit in CN162007 will also be the Baseline visit for the current study. Additional assessments, which were not completed in the parent study visit schedule, may be required for the Baseline visit of the current study. Treatment Phase: Subjects meeting entry criteria for this study and who consent to enter the study will be enrolled into a 54-week Treatment Phase on the day of the last visit in the parent study. All subjects treated with BMS-820836 in the parent studies will be assigned to a target BMS-820836 dose group (0.5, 1, and 2 mg) in the current study in accordance with the last dose of BMS-820836 received in the parent study. Subjects randomized in Phase C of the respective parent study to duloxetine (CN162006) or duloxetine and escitalopram (CN162007) will be re-ran domized in the current study to one of the three target dose arms of BMS-820836 (0.5, 1, and 2 mg).
研究设计
- 研究类型
- Interventional
- 分配方式
- Computer generated randomization
- 盲法
- Double Blind Double Dummy
入排标准
- 年龄范围
- 18.00 Year(s) 至 65.00 Year(s)（—）
- 性别
- All
入选标准
- •Signed Written Informed Consent a) Subjects,
- •65 years (at entry of the parent study: CN162006 or CN162007), able to give informed consent, and/or consent obtained from a legally acceptable representative (as required by IRB/IEC), prior to the initiation of any protocol required procedures. 2) Target Population b) Subjects must be able to understand the nature of the study, agree to comply with the prescribed dosage regimens, report for regularly scheduled office visits, and communicate to study personnel about adverse events and concomitant medication use. c) Subjects must meet 1 of the following criteria: i) Subjects must have been randomized in and completed the parent study protocol CN162006 (Week 14 Visit) or CN162007 (Week 13 Visit) or ii) Subjects must have been parent study Phase B responders in CN162006 or CN162007 (ie, were not randomized in parent study and have completed the parent study and met the following criteria for inadequate response at the parent study Final Visit of Phase C). Non-response is defined as either: (1) At the completion of Phase C of the parent study the subject meets all 3 criteria below: (a) < 50% decrease in HAMD-17 total score from the parent study Phase B Baseline Visit to the final visit of CN162006/CN162007 and (b) HAMD-17 total score ≥ 16 at the Final Visit of CN162006/CN162007 and (c) A CGI improvement score ≥ 3 at the last 2 scheduled visits of CN162006/CN
- •OR (2) At the Final Visit of Phase C of CN162006 or CN162007 the subject has a HAMD-17 total score ≥ 14, and demonstrates ≥ 25% worsening of their HAMD-17 score compared with the score at the end of the Phase B in the parent study. 3) Age and Reproductive Status a) Women of childbearing potential (WOCBP) and men must be using an acceptable method of contraception to avoid pregnancy throughout the study and for up to 30 days after the last dose of investigational product in such a manner that the risk of pregnancy is minimized. See Section 3.3.3 for the definition of WOCBP. The requisite drug interaction studies to determine the interaction of BMS-820836 with oral contraceptives have not been performed to date. It is therefore not possible to determine the efficacy of oral contraceptives as an effective method of contraception for WOCBP who participate in this study. Oral estrogen and progestin hormonal contraceptives as a sole method of contraception are therefore prohibited. It is recommended that all WOCBP use 2 methods of contraception for the duration of the study ie, from the start of treatment phase to 30 days after the last dose of study drug. The 2 methods should include 1 barrier method (for eg, condom with spermicidal gel, intrauterine devices, cervical cap, etc) and 1 other method which could include oral contraceptives. b) WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 72 hours prior to the start of investigational product. c) Women must not be breastfeeding. d) Sexually active fertile men must use effective birth control if their partners are WOCBP.
排除标准
- •Exclusion Criteria 1) Target Disease Exceptions a) Subjects must have met all Target Disease criteria for protocol CN162006 or CN
- •Medical History and Concurrent Diseases a) Subjects who represent a significant risk of committing suicide based on the clinical judgment of the investigator, history, or routine psychiatric status exam.
- •Physical and Laboratory Test Findings a) Subjects should be excluded if they have an abnormal laboratory test result, vital sign result, or ECG finding that in the investigators judgment is medically significant, in that it would impact the safety of the subject or the interpretation of the study results.
- •Sex and Reproductive Status a) Women of childbearing potential (WOCBP) and men not using an acceptable method of contraception to avoid pregnancy throughout the study and up to 30 days after the last dose of investigational product.
- •b) Women must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 72 hours prior to the start of investigational product.
- •c) Women must not be breastfeeding.
- •Prohibited and Restricted Medications a) Monoamine oxidase inhibitors (MAOIs) (eg, Nardil [phenelzine], selegeline, rasagiline, etc) treatment; b) Antidepressant agents including SSRIs, SNRIs, tricyclic antidepressants, norepinephrine reuptake inhibitors.
- •c) Stimulants used for the treatment of depression such as Provigil® (modafinil).
- •d) Herbal over-the-counter preparations or supplements such as hypericum perforatum (St. John’s Wort), omega-3 fatty acids, S-adenosyl methionine (SAM e) or kava extracts.
- •e) Any other psychotropic medications such as but not limited to the following: antipsychotics, antiepileptics (including Neurontin® [gabapentin], Lamictal® [lamotrigine], Depakote® [divalproic acid], Depakene® [valproic acid], Tegretol® [carbamazepine]), lithium, anxiolytics (including benzodiazepines, if not on a stable dose, Buspar® [buspirone]) and diphenhydramine.
- •f) Moderate to Potent CYP3A inhibitors (such as but not limited to ketoconazole, itraconazole, fluconazole, nefazodone, HIV protease inhibitors such as atazanavir and ritonavir, clarithromycin, diltiazem, erythromycin amongst others) or inducers (such as but not limited to rifampin, rifabutin, phenytoin, carbamazepine, phenobarbital, modafinil amongst others) during the remainder of the study.
- •g) Potent CYP1A2 inhibitors (such as but not limited to ciprofloxacin, clinafloxacin, enoxacin amongst others) are prohibited during the study.
- •h) Subjects who would be likely to require prohibited concomitant therapy during the trial.
- •Other Exclusion Criteria a) Prisoners or subjects who are involuntarily incarcerated b) Subjects who are compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness c) Subjects who during the course of their participation in either Study CN162006 or CN162007 were treated in violation of the protocol.
- •Eligibility criteria for this study have been carefully considered to ensure the safety of the study subjects and to ensure that the results of the study can be used.
- •It is imperative that subjects fully meet all eligibility criteria.
结局指标
主要结局
The primary objective of this study is to compare the long term effect of 3 target doses of
时间窗: At Weeks 3, 6, 12, 18, 24, 30, 36, 42, 48, 54, | 56,
BMS-820836 (0.5, 1, and 2 mg/day) through 54 weeks of follow-up in the change from
时间窗: At Weeks 3, 6, 12, 18, 24, 30, 36, 42, 48, 54, | 56,
randomization baseline in mean seated blood pressure in subjects with Treatment
时间窗: At Weeks 3, 6, 12, 18, 24, 30, 36, 42, 48, 54, | 56,
Resistant Depression.
时间窗: At Weeks 3, 6, 12, 18, 24, 30, 36, 42, 48, 54, | 56,
次要结局
- To assess the long term safety and tolerability of 3 target doses of BMS-820836 (0.5, 1,(or 2 mg/day) in the treatment of subjects with TRD from randomization baseline through)