Clinical trial NCT02229825: Study to Assess Clinical Response of Duloxetine in Patients Hospitalized for Severe Depression
Official title: An Eight-week, Randomized, Double-blind, Two Parallel Groups, Study to Assess Clinical Response of Duloxetine 60 mg and 120 mg Per Day in Patients Hospitalized for Severe Depression
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Depressive Disorder, Major
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2014-09-01
Enrollment: 339
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Study to assess efficacy of Duloxetine 120 mg and Duloxetine 60 mg in patients hospitalized for severe depression after 4 weeks of treatment. To evaluate the rescue option in non-responding patients. Safety of Duloxetine will also be assessed.


Eligibility criteria: Inclusion Criteria:

1. Male or female patients of 18 years of age at the screening visit or older
2. Meet criteria for severe Major Depressive Disorder (MDD)
3. Montgomery-Asberg-depression rating scale (MADRS) total score ≥ 30 and the 6-item Hamilton Depression scale (HAMD-6) score ≥12 at both screening (V1) visit and baseline (V2) visits
4. Clinical Global Impression of Severity (CGI-Severity) score ≥4 at both screening visit and baseline visit.
5. Requirement of hospitalization (not for social or other non-medical reasons) at screening visit and at least up to Visit 4
6. Patient willing and able to comply with the requirement for hospitalization and with all scheduled visits, tests and procedures required by the protocol
7. Have a level of understanding sufficient to provide informed consent and to communicate with the investigators and site personnel. Informed consent document must be signed at screening visit, in accordance with Good Clinical Practice (GCP) and local regulatory requirements, prior to any study procedure

Exclusion Criteria:

1. More than two previous episodes of major depression that did not respond to adequate doses and duration (minimum of 6 weeks) of two different antidepressant therapies
2. Lack of response to at least two antidepressant therapies given at adequate doses for at least 6 weeks for the current depressive episode
3. Concurrent presence of symptoms fulfilling criteria for any Axis I disorder other than anxiety disorders (with exception of the Obsessive-Compulsive Disorder (OCD)) or Major Depressive Disorder, in the investigator's judgment
4. Any previous diagnosis of a bipolar disorder, schizophrenia or OCD
5. Depression with catatonic features, depression with post-partum onset, or organic mental disorders
6. The presence of an Axis II disorder
7. MDD with psychotic features requiring neuroleptic treatment and/or interfering with patient's ability to provide informed consent, at investigator's discretion
8. History of substance abuse or dependence within the past year, excluding nicotine and caffeine, but including alcohol or benzodiazepines
9. Positive urine screen for drug abuse (cannabinoids, cocaine, opiates including methadone, or amphetamines) at screening
10. Epilepsy or a history of seizure disorder or of a treatment with anticonvulsant medication for epilepsy or seizures
11. Patients with acute liver injury (such as hepatitis) or severe cirrhosis (such as Child-Pugh Class C)
12. Known diagnosis of congenital galactosaemia, glucose or galactose malabsorption syndrome, or lactose deficiency
13. Patient with a known diagnosis of raised intraocular pressure, or at known risk of acute narrow-angle glaucoma
14. Serious medical illness or clinically significant laboratory abnormalities that, in the judgment of the investigator, are likely to require intervention/exclusion of study medication during the course of the study: cardiovascular (e.g. uncontrolled hypertension, abnormal initial ECG findings according to investigator judgement), respiratory, haematological, hepatic or gastrointestinal
15. End stage renal disease (estimated creatinine clearance ≤30 mL/min) and undergoing dialysis
16. Abnormal thyroid-stimulating hormone (TSH) concentrations, based on the performing laboratory's reference ranges. Patients must be clinically and chemically euthyroid at the time of randomization. Patients may be taking thyroid replacement therapy provided their dose is stable and their compliance is good for at least three months before the screening visit
17. Pregnancy (to be excluded by urine pregnancy test at screening visit) or breast-feeding
18. Sexually active woman of childbearing potential (i.e. not 6 months post-menopausal, or not surgically sterilized) not using a medically approved method of birth control (i.e. oral contraceptives, intrauterine device, or double-barrier) for at least one month prior to the screening visit and throughout the study
19. Participation in another clinical trial within 30 days prior to screening visit
20. Current treatment with Duloxetine for any indication and previous treatment with Duloxetine for psychiatric indications
21. Known hypersensitivity to Duloxetine or any of the inactive ingredients
22. History of oversensitivity to psychotropic drugs, in the investigator's judgment
23. Electro-convulsive Therapy (ECT) or Transcranial Magnetic Stimulation (TMS) within one year prior to screening visit and during the study
24. Initiation or discontinuation of depression-oriented psychotherapeutic treatment (e.g. behaviour therapy, psychoanalytic therapy, cognitive therapy, etc) within 6 weeks prior to screening visit, or planned use of such treatment at any time during the study
25. Treatment with a Monoamine Oxidase Inhibitor (MAOI) within 14 days prior to baseline visit or the potential need to use an MAOI during the study or within 5 days after discontinuation of duloxetine
26. Treatment with Fluoxetine within 30 days prior to baseline visit
27. Treatment with any excluded medication listed in the protocol

Primary outcomes:
measure: Change in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score From Baseline to Week 4
timeFrame: At baseline and at Week 4.
Secondary outcomes:
measure: Change in Hamilton Depression 6-item Scale (HAMD-6) Total Score From Baseline to Week 1, 2, 3 and Week 4
timeFrame: At baseline and at Week 1, 2, 3 and Week 4.
measure: Change in Hamilton Depression 6-item Scale (HAMD-6) Total Score From Baseline to Week 6 and Week 8 - by Post-week 4 Treatment Groups
timeFrame: At baseline and at Week 6 and Week 8.
measure: Change in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score From Baseline to Week 1, 2 and Week 3
timeFrame: At baseline and at Week 1, 2 and Week 3.
measure: Change in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score From Baseline to Week 6 and Week 8 - by Post-week 4 Treatment Groups
timeFrame: At baseline and at Week 6 and Week 8.
measure: Percentage of Responders at Week 1, 2, 3 and Week 4 According to Montgomery-Asberg Depression Rating Scale (MADRS) Scale
timeFrame: At week 1, 2, 3 and week 4.
measure: Percentage of Responders at Week 6 and Week 8 According to Montgomery-Asberg Depression Rating Scale (MADRS) Scale - by Post-week 4 Treatment Groups
timeFrame: At week 6 and week 8.
measure: Percentage of Responders at Week 1, 2, 3 and Week 4 According to Hamilton Depression 6-item Scale (HAMD-6)
timeFrame: At week 1, 2, 3 and week 4.
measure: Percentage of Responders at Week 6 and Week 8 According to Hamilton Depression 6-item Scale (HAMD-6) - by Post-week 4 Treatment Group
timeFrame: At week 6 and week 8.
measure: Percentage of Patients Reaching Remission at Week 8
timeFrame: At week 8.
measure: Clinical Global Impressions Scales of Severity of Illness (CGI-SI): Number of Patients Per Score at Baseline, Week 1, 2, 3 and Week 4
timeFrame: At baseline and at week 1, 2, 3 and week 4.
measure: Clinical Global Impressions Scales of Severity of Illness (CGI-SI): Number of Patients Per Score at Week 6 and Week 8 - by Post-week 4 Treatment Groups
timeFrame: At week 6 and week 8.
measure: Clinical Global Impression of Improvement (CGI-I) Scale: Number of Patients Per Score at Week 1, 2, 3 and Week 4
timeFrame: At week 1, 2, 3 and week 4.
measure: Clinical Global Impression of Improvement (CGI-I) Scale: Number of Patients Per Score at Week 6 and Week 8 - by Post-week 4 Treatment Groups
timeFrame: At week 6 and week 8.
measure: Patient Global Impressions of Improvement (PGI-I) Score: Number of Patients Per Score at Week 1, 2, 3 and Week 4
timeFrame: At week 1, 2, 3 and week 4.
measure: Patient Global Impressions of Improvement (PGI-I) Score: Number of Patients Per Score at Week 6 and Week 8 - by Post-week 4 Treatment Groups
timeFrame: At week 6 and week 8.
measure: Change in Hamilton Scale of Anxiety (HAMA) Score From Baseline to Week 4
timeFrame: At baseline and at week 4.
measure: Change in Hamilton Scale of Anxiety (HAMA) Score From Baseline to Week 8 - by Post-week 4 Treatment Groups
timeFrame: At baseline and at week 8.
measure: Reason for Living (RFL) Questionaire at Baseline
timeFrame: At baseline.
measure: Change From Baseline to Week 8 in Reason for Living (RFL) Questionnaire - by Post-week 4 Treatment Groups
timeFrame: At baseline and at week 8.
measure: Number of Patients With Intake of Concomitant Medication for Anxiety and Sleep
timeFrame: 1 week prior to baseline and at baseline, week 1, 2, 3, 4, 5, 6, 7, 8 and week 10.
measure: Number of Patients With Treatment Emergent Adverse Event
timeFrame: From start of treatment until 3 days after end of treatment, up to 120 days.
measure: Change From Baseline in Blood Pressure to Week 4 and Week 8
timeFrame: At baseline, at week 4 and week 8.
measure: Change From Baseline in Weight to Week 4 and Week 8
timeFrame: At baseline, at week 4 and week 8.
measure: Number of Patients With Potentially Clinically Significant Laboratory Findings
timeFrame: Up to week 8.
measure: Number of Patients Withdrawn Due to Adverse Events
timeFrame: From start of treatment until 3 days after end of treatment, up to 120 days.
Other outcomes:
Locations:
Study officials:
References: