CTRI/2012/07/002773 [Registered on: 06/07/2012] Trial Registered Prospectively
Last Modified On:
16/07/2014
Post Graduate Thesis
No
Type of Trial
Interventional
Type of Study
Drug
Study Design
Randomized, Parallel Group, Multiple Arm Trial
Public Title of Study
A Multicenter, Double-Blind, 58 week Rollover Study to assess the Safety and Tolerability of
BMS-820836 in Patients with Treatment Resistant Major Depression
Scientific Title of Study
A Multicenter, Double-Blind, 58 week Rollover Study to assess the Safety and Tolerability of
BMS-820836 in Patients with Treatment Resistant Major Depression
Trial Acronym
Secondary IDs if Any
Secondary ID
Identifier
CN162-010 dated 21-Apr-2011
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study) Modification(s)
Department of Psychiatry , ground floor , Erandwane , Pune - 411004 Pune MAHARASHTRA
9823262786 02040151000 sanjay_phadke@hotmail.com
Dr Venu Gopal Jhanwar
Deva Institute of Healthcare and Research Centre
Deva Institute of Health Care & Research Pvt. Ltd.,
Dept of Psychiatry clinics,
27/70,MN Badhal Koti,
Durgakund,
Varanasi-211 005 Varanasi UTTAR PRADESH
9936611111
vgjhanwar@devainstitute.com
Dr NN Raju
Maharshi Institute of Neuro-Psychological Disorders (M.I.N.D)
1) Signed Written Informed Consent a) Subjects, 18 - 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/CN162007. 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.
ExclusionCriteria
Details
Exclusion Criteria
1) Target Disease Exceptions
a) Subjects must have met all Target Disease criteria for protocol CN162006 or
CN162007.
2) 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.
3) 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.
4) 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.
5) 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.
6) 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.
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
Centralized
Blinding/Masking
Double Blind Double Dummy
Primary Outcome
Outcome
TimePoints
The primary objective of this study is to compare the long term effect of 3 target doses of
BMS-820836 (0.5, 1, and 2 mg/day) through 54 weeks of follow-up in the change from
randomization baseline in mean seated blood pressure in subjects with Treatment
Resistant Depression.
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
54 weeks of the Rollover study as measured by the frequency and severity of AEs,
frequency of SAEs and discontinuations due to AEs.
Total Sample Size="500" Sample Size from India="60" Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials" Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials"
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).