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Study to Evaluate the Effect and Safety of Quetiapine Extended Release (XR) (FK949E) in Major Depressive Disorder

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ClinicalTrials.gov Identifier: NCT01725282
Recruitment Status : Completed
First Posted : November 12, 2012
Results First Posted : August 28, 2014
Last Update Posted : March 21, 2017
Sponsor:
Information provided by (Responsible Party):
Astellas Pharma Inc

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Major Depressive Disorder
Interventions Drug: quetiapine extended release (XR)
Drug: Placebo
Enrollment 172

Recruitment Details  
Pre-assignment Details  
Arm/Group Title Placebo Quetiapine 50 mg Quetiapine 150 mg Quetiapine 300 mg
Hide Arm/Group Description Participants received matching placebo tablets once daily before bedtime for 7 weeks. Participants received quetiapine extended release (XR) 50 mg tablets once daily before bedtime for 7 weeks. After 2 days of up-titration, participants received quetiapine XR 150 mg tablets once daily before bedtime for 6 weeks followed by quetiapine XR 50 mg tablets once daily for 1 week. After 4 days of up-titration, participants received quetiapine XR 300 mg tablets once daily before bedtime for 6 weeks followed by quetiapine XR 150 mg tablets once daily for 1 week.
Period Title: Overall Study
Started 44 44 41 43
Completed 42 39 33 36
Not Completed 2 5 8 7
Reason Not Completed
Adverse Event             1             3             6             4
Exacerbation of Target Disease             1             0             0             1
Met Exclusion Criteria             0             0             1             0
Study Site Withdrawal             0             1             0             0
Withdrawal by Subject             0             0             1             1
Lack of Efficacy             0             1             0             1
Arm/Group Title Placebo Quetiapine 50 mg Quetiapine 150 mg Quetiapine 300 mg Total
Hide Arm/Group Description Participants received matching placebo tablets once daily before bedtime for 7 weeks. Participants received quetiapine extended release (XR) 50 mg tablets once daily before bedtime for 7 weeks. After 2 days of up-titration, participants received quetiapine XR 150 mg tablets once daily before bedtime for 6 weeks followed by quetiapine XR 50 mg tablets once daily for 1 week. After 4 days of up-titration, participants received quetiapine XR 300 mg tablets once daily before bedtime for 6 weeks followed by quetiapine XR 150 mg tablets once daily for 1 week. Total of all reporting groups
Overall Number of Baseline Participants 44 44 41 43 172
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 44 participants 44 participants 41 participants 43 participants 172 participants
39.8  (11.2) 39.0  (9.5) 35.2  (8.6) 37.3  (9.7) 37.9  (9.9)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 44 participants 44 participants 41 participants 43 participants 172 participants
Female
19
  43.2%
15
  34.1%
17
  41.5%
17
  39.5%
68
  39.5%
Male
25
  56.8%
29
  65.9%
24
  58.5%
26
  60.5%
104
  60.5%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Japan Number Analyzed 44 participants 44 participants 41 participants 43 participants 172 participants
44 44 41 43 172
Montgomery Åsberg Depression Rating Scale (MADRS)   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 44 participants 44 participants 41 participants 43 participants 172 participants
28.5  (5.1) 28.7  (5.9) 29.0  (5.4) 29.3  (5.4) 28.9  (5.4)
[1]
Measure Description: MADRS is a10-item scale to measure the severity of depressive episodes, where each item is rated on a scale from 0 to 6. The MADRS total score ranges from 0 to 60 with lower scores indicating less depressive symptoms.
Hamilton Depression Scale 17-Item (HAM D17)   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 44 participants 44 participants 41 participants 43 participants 172 participants
22.6  (2.3) 22.6  (2.4) 23.3  (3.0) 22.9  (2.5) 22.8  (2.6)
[1]
Measure Description: HAM-D17 is a clinician-rated 17-item scale for assessing the severity of depression symptoms. The scores for each item range from 0 to 4 or 0 to 2, where 0 represents no symptoms. The rating is based on the past 7 days prior to the time of assessment. The total score ranges from 0 to 52, where a higher score indicates a greater depressive state.
1.Primary Outcome
Title Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score
Hide Description The Montgomery Åsberg Depression Rating Scale (MADRS) is a depression rating scale consisting of 10 items, each rated 0 to 6. The 10 items represent the core symptoms of depressive illness. The overall score ranges from 0 (symptoms absent) to 60 (severe depression). Decrease in the total score or on individual items indicates improvement.
Time Frame Baseline and Week 6
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: Participants who met the following requirements: major depressive disorder confirmed at registration; at least one dose of the study drug for the treatment period was administered; and at least one efficacy variable was assessed after the start of treatment. Last observation carried forward (LOCF) imputation was used.
Arm/Group Title Placebo Quetiapine 50 mg Quetiapine 150 mg Quetiapine 300 mg
Hide Arm/Group Description:
Participants received matching placebo tablets once daily before bedtime for 7 weeks.
Participants received quetiapine extended release (XR) 50 mg tablets once daily before bedtime for 7 weeks.
After 2 days of up-titration, participants received quetiapine XR 150 mg tablets once daily before bedtime for 6 weeks followed by quetiapine XR 50 mg tablets once daily for 1 week.
After 4 days of up-titration, participants received quetiapine XR 300 mg tablets once daily before bedtime for 6 weeks followed by quetiapine XR 150 mg tablets once daily for 1 week.
Overall Number of Participants Analyzed 44 44 41 43
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-11.5  (1.2) -11.3  (1.2) -12.1  (1.2) -10.3  (1.2)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Quetiapine 50 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted mean difference
Estimated Value 0.2
Confidence Interval (2-Sided) 95%
-3.1 to 3.6
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.7
Estimation Comments An analysis of covariance model with the baseline as a covariate and treatment group as a fixed effect.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Quetiapine 150 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted mean difference
Estimated Value -0.6
Confidence Interval (2-Sided) 95%
-4.0 to 2.8
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.7
Estimation Comments An analysis of covariance model with the baseline as a covariate and treatment group as a fixed effect.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Quetiapine 300 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted mean difference
Estimated Value 1.3
Confidence Interval (2-Sided) 95%
-2.1 to 4.6
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.7
Estimation Comments An analysis of covariance model with the baseline as a covariate and treatment group as a fixed effect.
2.Secondary Outcome
Title Change From Baseline in Hamilton Rating Score for Depression (HAM-D17)
Hide Description The 17-item Hamilton Depression Scale (HAM-D17) is a clinician-rated 17-item scale for assessing the severity of depression symptoms. The scores for each item range from 0 to 4 or 0 to 2, where 0 represents no symptoms. The rating is based on the past 7 days prior to the time of assessment. The total score range is from 0 to 52 where a higher score indicates a greater depressive state.
Time Frame Baseline and Week 6
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full analysis set; Last observation carried forward (LOCF) imputation was used.
Arm/Group Title Placebo Quetiapine 50 mg Quetiapine 150 mg Quetiapine 300 mg
Hide Arm/Group Description:
Participants received matching placebo tablets once daily before bedtime for 7 weeks.
Participants received quetiapine extended release (XR) 50 mg tablets once daily before bedtime for 7 weeks.
After 2 days of up-titration, participants received quetiapine XR 150 mg tablets once daily before bedtime for 6 weeks followed by quetiapine XR 50 mg tablets once daily for 1 week.
After 4 days of up-titration, participants received quetiapine XR 300 mg tablets once daily before bedtime for 6 weeks followed by quetiapine XR 150 mg tablets once daily for 1 week.
Overall Number of Participants Analyzed 44 44 41 43
Mean (Standard Deviation)
Unit of Measure: units on a scale
-10.1  (6.0) -9.3  (5.9) -10.2  (5.7) -8.7  (6.1)
3.Secondary Outcome
Title Percentage of Participants With Improvement in Clinical Global Impressions-Improvement (CGI-I)
Hide Description

The Clinical Global Impression - global improvement assesses the participant's improvement (or worsening) as assessed by the clinician relative to Baseline on a 7-point scale: 1, markedly improved; 2, moderately improved; 3, minimally improved; 4, no change; 5, minimally worsened; 6, moderately worsened; or 7, markedly worsened.

Improvement is defined as a score of 1 or 2.

Time Frame Baseline and Week 6
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full analysis set; Last observation carried forward (LOCF) imputation was used.
Arm/Group Title Placebo Quetiapine 50 mg Quetiapine 150 mg Quetiapine 300 mg
Hide Arm/Group Description:
Participants received matching placebo tablets once daily before bedtime for 7 weeks.
Participants received quetiapine extended release (XR) 50 mg tablets once daily before bedtime for 7 weeks.
After 2 days of up-titration, participants received quetiapine XR 150 mg tablets once daily before bedtime for 6 weeks followed by quetiapine XR 50 mg tablets once daily for 1 week.
After 4 days of up-titration, participants received quetiapine XR 300 mg tablets once daily before bedtime for 6 weeks followed by quetiapine XR 150 mg tablets once daily for 1 week.
Overall Number of Participants Analyzed 44 44 41 43
Measure Type: Number
Unit of Measure: percentage of participants
54.5 50.0 53.7 27.2
4.Secondary Outcome
Title Change From Baseline in Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36)
Hide Description

The Medical Outcomes Study SF-36 is a participant self-rated questionnaire that is a general measure of perceived health status comprising 36 questions, which yields an 8-scale health profile. The 8 health concepts are:

  1. Limitation in physical activities because of health problems.
  2. Limitations in usual role activities because of physical health problems.
  3. Bodily pain.
  4. Limitations in social activities because of physical or emotional problems.
  5. General mental health (psychological distress and well-being).
  6. Limitations in usual role activities because of emotional problems.
  7. Vitality (energy and fatigue).
  8. General health perception.

Each scale ranges from 0 to 100, with 0 indicating the least favorable status and 100 being the most favorable health status.

Time Frame Baseline and Week 6
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full analysis set with available SF-36 data; LOCF was used.
Arm/Group Title Placebo Quetiapine 50 mg Quetiapine 150 mg Quetiapine 300 mg
Hide Arm/Group Description:
Participants received matching placebo tablets once daily before bedtime for 7 weeks.
Participants received quetiapine extended release (XR) 50 mg tablets once daily before bedtime for 7 weeks.
After 2 days of up-titration, participants received quetiapine XR 150 mg tablets once daily before bedtime for 6 weeks followed by quetiapine XR 50 mg tablets once daily for 1 week.
After 4 days of up-titration, participants received quetiapine XR 300 mg tablets once daily before bedtime for 6 weeks followed by quetiapine XR 150 mg tablets once daily for 1 week.
Overall Number of Participants Analyzed 44 44 39 42
Mean (Standard Deviation)
Unit of Measure: units on a scale
Physical Functioning 2.8  (13.3) 1.4  (14.3) 0.4  (14.9) 1.4  (12.5)
Role Limitations - Physical 8.8  (24.8) 1.1  (28.0) 7.4  (31.1) 6.1  (26.2)
Bodily pain 4.4  (21.4) 11.2  (23.9) 2.5  (25.2) -0.5  (26.9)
General Health Perception 6.3  (12.3) 6.0  (14.8) 4.7  (16.8) 8.7  (13.5)
Vitality 7.5  (15.8) 8.1  (21.3) 6.7  (15.8) 9.2  (18.6)
Social Functioning 7.1  (21.3) 6.5  (27.3) 7.4  (25.9) 6.0  (20.3)
Role Limitations - Emotional 9.8  (29.5) 13.8  (24.0) 11.8  (27.7) 9.7  (27.3)
Mental Health 2.5  (18.9) 9.7  (22.0) 8.1  (16.7) 7.5  (19.4)
5.Secondary Outcome
Title Change From Baseline in Pittsburgh Sleep Quality Index (PSQI)
Hide Description The Pittsburgh Sleep Quality Index (PSQI) is a self-rated questionnaire which assesses sleep quality and disturbances over a 1-month time interval. Nineteen individual items generate seven “component” scores: subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medication, and daytime dysfunction, each on a scale from 0 (best) to 3 (worst). The sum of scores for these seven components yields one global score, ranging from 0 to 21, with higher scores indicative of poor sleep quality.
Time Frame Baseline and Week 6
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full analysis set with available PSQI data; LOCF was used.
Arm/Group Title Placebo Quetiapine 50 mg Quetiapine 150 mg Quetiapine 300 mg
Hide Arm/Group Description:
Participants received matching placebo tablets once daily before bedtime for 7 weeks.
Participants received quetiapine extended release (XR) 50 mg tablets once daily before bedtime for 7 weeks.
After 2 days of up-titration, participants received quetiapine XR 150 mg tablets once daily before bedtime for 6 weeks followed by quetiapine XR 50 mg tablets once daily for 1 week.
After 4 days of up-titration, participants received quetiapine XR 300 mg tablets once daily before bedtime for 6 weeks followed by quetiapine XR 150 mg tablets once daily for 1 week.
Overall Number of Participants Analyzed 44 44 39 42
Mean (Standard Deviation)
Unit of Measure: units on a scale
-1.1  (2.9) -1.8  (2.7) -1.5  (2.7) -1.8  (3.0)
6.Secondary Outcome
Title Safety Assessed by the Incidence of Adverse Events (AE), Vital Signs, Electrocardiogram (ECG) and Laboratory Tests
Hide Description An AE is defined as any untoward medical occurrence in a patient administered a study drug, and which does not necessarily have a causal relationship with this treatment. Abnormal laboratory parameters, vital signs or ECG data were defined as AEs if the abnormality induced clinical signs or symptoms, needed active intervention, interruption or discontinuation of study medication or was clinically significant. A serious AE was an event resulting in death, persistent or significant disability/incapacity or congenital anomaly or birth defect, was life-threatening, required or prolonged hospitalization or was considered medically important. AEs were assessed by the Investigator for intensity as mild, moderate or severe and for causal relationship to study drug.
Time Frame Up to 8 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Placebo Quetiapine 50 mg Quetiapine 150 mg Quetiapine 300 mg
Hide Arm/Group Description:
Participants received matching placebo tablets once daily before bedtime for 7 weeks.
Participants received quetiapine extended release (XR) 50 mg tablets once daily before bedtime for 7 weeks.
After 2 days of up-titration, participants received quetiapine XR 150 mg tablets once daily before bedtime for 6 weeks followed by quetiapine XR 50 mg tablets once daily for 1 week.
After 4 days of up-titration, participants received quetiapine XR 300 mg tablets once daily before bedtime for 6 weeks followed by quetiapine XR 150 mg tablets once daily for 1 week.
Overall Number of Participants Analyzed 44 44 41 43
Measure Type: Number
Unit of Measure: participants
Any adverse event 25 33 35 35
Drug-related adverse event 21 24 29 31
Deaths 0 0 0 0
Serious adverse event 0 1 0 1
Drug-related serious adverse event 0 1 0 1
AE leading to discontinuation 2 2 6 4
Drug-related AE leading to discontinuation 1 2 6 2
Time Frame 8 weeks
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Placebo Quetiapine 50 mg Quetiapine 150 mg Quetiapine 300 mg
Hide Arm/Group Description Participants received matching placebo tablets once daily before bedtime for 7 weeks. Participants received quetiapine extended release (XR) 50 mg tablets once daily before bedtime for 7 weeks. After 2 days of up-titration, participants received quetiapine XR 150 mg tablets once daily before bedtime for 6 weeks followed by quetiapine XR 50 mg tablets once daily for 1 week. After 4 days of up-titration, participants received quetiapine XR 300 mg tablets once daily before bedtime for 6 weeks followed by quetiapine XR 150 mg tablets once daily for 1 week.
All-Cause Mortality
Placebo Quetiapine 50 mg Quetiapine 150 mg Quetiapine 300 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Placebo Quetiapine 50 mg Quetiapine 150 mg Quetiapine 300 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/44 (0.00%)   1/44 (2.27%)   0/41 (0.00%)   1/43 (2.33%) 
Hepatobiliary disorders         
Hepatitis acute  1  0/44 (0.00%)  0/44 (0.00%)  0/41 (0.00%)  1/43 (2.33%) 
Nervous system disorders         
Partial seizures  1  0/44 (0.00%)  1/44 (2.27%)  0/41 (0.00%)  0/43 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA/J 14.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo Quetiapine 50 mg Quetiapine 150 mg Quetiapine 300 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   18/44 (40.91%)   23/44 (52.27%)   26/41 (63.41%)   28/43 (65.12%) 
General disorders         
Malaise  1  0/44 (0.00%)  1/44 (2.27%)  1/41 (2.44%)  3/43 (6.98%) 
Thirst  1  2/44 (4.55%)  5/44 (11.36%)  5/41 (12.20%)  9/43 (20.93%) 
Infections and infestations         
Nasopharyngitis  1  3/44 (6.82%)  3/44 (6.82%)  6/41 (14.63%)  6/43 (13.95%) 
Pharyngitis  1  3/44 (6.82%)  1/44 (2.27%)  0/41 (0.00%)  0/43 (0.00%) 
Investigations         
Blood cholesterol increased  1  0/44 (0.00%)  0/44 (0.00%)  3/41 (7.32%)  2/43 (4.65%) 
Blood prolactin increased  1  3/44 (6.82%)  1/44 (2.27%)  4/41 (9.76%)  2/43 (4.65%) 
Blood triglycerides increased  1  2/44 (4.55%)  6/44 (13.64%)  4/41 (9.76%)  5/43 (11.63%) 
Weight increased  1  0/44 (0.00%)  2/44 (4.55%)  3/41 (7.32%)  2/43 (4.65%) 
Metabolism and nutrition disorders         
Increased appetite  1  0/44 (0.00%)  1/44 (2.27%)  3/41 (7.32%)  0/43 (0.00%) 
Nervous system disorders         
Dizziness  1  0/44 (0.00%)  0/44 (0.00%)  3/41 (7.32%)  6/43 (13.95%) 
Dizziness postural  1  1/44 (2.27%)  1/44 (2.27%)  2/41 (4.88%)  4/43 (9.30%) 
Headache  1  3/44 (6.82%)  5/44 (11.36%)  1/41 (2.44%)  1/43 (2.33%) 
Somnolence  1  6/44 (13.64%)  9/44 (20.45%)  13/41 (31.71%)  17/43 (39.53%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA/J 14.1
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
PI needs to get prior approval from Sponsor in writing for publication of trial data.
Results Point of Contact
Name/Title: Vice President, Clinical Development Administration
Organization: Astellas Pharma Inc.
Responsible Party: Astellas Pharma Inc
ClinicalTrials.gov Identifier: NCT01725282     History of Changes
Other Study ID Numbers: 6949-CL-0005
First Submitted: November 8, 2012
First Posted: November 12, 2012
Results First Submitted: August 14, 2014
Results First Posted: August 28, 2014
Last Update Posted: March 21, 2017