Trial Outcomes & Findings for Study to Evaluate the Effect and Safety of Quetiapine Extended Release (XR) (FK949E) in Major Depressive Disorder (NCT NCT01725282)

NCT ID: NCT01725282

Last Updated: 2024-11-15

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

172 participants

Primary outcome timeframe

Baseline and Week 6

Results posted on

2024-11-15

Participant Flow

Participant milestones

Participant milestones
Measure
Placebo
Participants received matching placebo tablets once daily before bedtime for 7 weeks.
Quetiapine 50 mg
Participants received quetiapine extended release (XR) 50 mg tablets once daily before bedtime for 7 weeks.
Quetiapine 150 mg
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.
Quetiapine 300 mg
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 Study
STARTED
44
44
41
43
Overall Study
COMPLETED
42
39
33
36
Overall Study
NOT COMPLETED
2
5
8
7

Reasons for withdrawal

Reasons for withdrawal
Measure
Placebo
Participants received matching placebo tablets once daily before bedtime for 7 weeks.
Quetiapine 50 mg
Participants received quetiapine extended release (XR) 50 mg tablets once daily before bedtime for 7 weeks.
Quetiapine 150 mg
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.
Quetiapine 300 mg
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 Study
Adverse Event
1
3
6
4
Overall Study
Exacerbation of Target Disease
1
0
0
1
Overall Study
Met Exclusion Criteria
0
0
1
0
Overall Study
Study Site Withdrawal
0
1
0
0
Overall Study
Withdrawal by Subject
0
0
1
1
Overall Study
Lack of Efficacy
0
1
0
1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Placebo
n=44 Participants
Participants received matching placebo tablets once daily before bedtime for 7 weeks.
Quetiapine 50 mg
n=44 Participants
Participants received quetiapine extended release (XR) 50 mg tablets once daily before bedtime for 7 weeks.
Quetiapine 150 mg
n=41 Participants
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.
Quetiapine 300 mg
n=43 Participants
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
n=172 Participants
Total of all reporting groups
Age, Continuous
39.8 years
STANDARD_DEVIATION 11.2 • n=5 Participants
39.0 years
STANDARD_DEVIATION 9.5 • n=7 Participants
35.2 years
STANDARD_DEVIATION 8.6 • n=5 Participants
37.3 years
STANDARD_DEVIATION 9.7 • n=4 Participants
37.9 years
STANDARD_DEVIATION 9.9 • n=21 Participants
Sex: Female, Male
Female
19 Participants
n=5 Participants
15 Participants
n=7 Participants
17 Participants
n=5 Participants
17 Participants
n=4 Participants
68 Participants
n=21 Participants
Sex: Female, Male
Male
25 Participants
n=5 Participants
29 Participants
n=7 Participants
24 Participants
n=5 Participants
26 Participants
n=4 Participants
104 Participants
n=21 Participants
Region of Enrollment
Japan
44 participants
n=5 Participants
44 participants
n=7 Participants
41 participants
n=5 Participants
43 participants
n=4 Participants
172 participants
n=21 Participants
Montgomery Åsberg Depression Rating Scale (MADRS)
28.5 units on a scale
STANDARD_DEVIATION 5.1 • n=5 Participants
28.7 units on a scale
STANDARD_DEVIATION 5.9 • n=7 Participants
29.0 units on a scale
STANDARD_DEVIATION 5.4 • n=5 Participants
29.3 units on a scale
STANDARD_DEVIATION 5.4 • n=4 Participants
28.9 units on a scale
STANDARD_DEVIATION 5.4 • n=21 Participants
Hamilton Depression Scale 17-Item (HAM D17)
22.6 units on a scale
STANDARD_DEVIATION 2.3 • n=5 Participants
22.6 units on a scale
STANDARD_DEVIATION 2.4 • n=7 Participants
23.3 units on a scale
STANDARD_DEVIATION 3.0 • n=5 Participants
22.9 units on a scale
STANDARD_DEVIATION 2.5 • n=4 Participants
22.8 units on a scale
STANDARD_DEVIATION 2.6 • n=21 Participants

PRIMARY outcome

Timeframe: Baseline and Week 6

Population: 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.

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.

Outcome measures

Outcome measures
Measure
Placebo
n=44 Participants
Participants received matching placebo tablets once daily before bedtime for 7 weeks.
Quetiapine 50 mg
n=44 Participants
Participants received quetiapine extended release (XR) 50 mg tablets once daily before bedtime for 7 weeks.
Quetiapine 150 mg
n=41 Participants
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.
Quetiapine 300 mg
n=43 Participants
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.
Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score
-11.5 units on a scale
Standard Error 1.2
-11.3 units on a scale
Standard Error 1.2
-12.1 units on a scale
Standard Error 1.2
-10.3 units on a scale
Standard Error 1.2

SECONDARY outcome

Timeframe: Baseline and Week 6

Population: Full analysis set; Last observation carried forward (LOCF) imputation was used.

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.

Outcome measures

Outcome measures
Measure
Placebo
n=44 Participants
Participants received matching placebo tablets once daily before bedtime for 7 weeks.
Quetiapine 50 mg
n=44 Participants
Participants received quetiapine extended release (XR) 50 mg tablets once daily before bedtime for 7 weeks.
Quetiapine 150 mg
n=41 Participants
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.
Quetiapine 300 mg
n=43 Participants
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.
Change From Baseline in Hamilton Rating Score for Depression (HAM-D17)
-10.1 units on a scale
Standard Deviation 6.0
-9.3 units on a scale
Standard Deviation 5.9
-10.2 units on a scale
Standard Deviation 5.7
-8.7 units on a scale
Standard Deviation 6.1

SECONDARY outcome

Timeframe: Baseline and Week 6

Population: Full analysis set; Last observation carried forward (LOCF) imputation was used.

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.

Outcome measures

Outcome measures
Measure
Placebo
n=44 Participants
Participants received matching placebo tablets once daily before bedtime for 7 weeks.
Quetiapine 50 mg
n=44 Participants
Participants received quetiapine extended release (XR) 50 mg tablets once daily before bedtime for 7 weeks.
Quetiapine 150 mg
n=41 Participants
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.
Quetiapine 300 mg
n=43 Participants
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.
Percentage of Participants With Improvement in Clinical Global Impressions-Improvement (CGI-I)
54.5 percentage of participants
50.0 percentage of participants
53.7 percentage of participants
27.2 percentage of participants

SECONDARY outcome

Timeframe: Baseline and Week 6

Population: Full analysis set with available SF-36 data; LOCF was used.

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.

Outcome measures

Outcome measures
Measure
Placebo
n=44 Participants
Participants received matching placebo tablets once daily before bedtime for 7 weeks.
Quetiapine 50 mg
n=44 Participants
Participants received quetiapine extended release (XR) 50 mg tablets once daily before bedtime for 7 weeks.
Quetiapine 150 mg
n=39 Participants
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.
Quetiapine 300 mg
n=42 Participants
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.
Change From Baseline in Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36)
Vitality
7.5 units on a scale
Standard Deviation 15.8
8.1 units on a scale
Standard Deviation 21.3
6.7 units on a scale
Standard Deviation 15.8
9.2 units on a scale
Standard Deviation 18.6
Change From Baseline in Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36)
Physical Functioning
2.8 units on a scale
Standard Deviation 13.3
1.4 units on a scale
Standard Deviation 14.3
0.4 units on a scale
Standard Deviation 14.9
1.4 units on a scale
Standard Deviation 12.5
Change From Baseline in Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36)
Role Limitations - Physical
8.8 units on a scale
Standard Deviation 24.8
1.1 units on a scale
Standard Deviation 28.0
7.4 units on a scale
Standard Deviation 31.1
6.1 units on a scale
Standard Deviation 26.2
Change From Baseline in Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36)
Bodily pain
4.4 units on a scale
Standard Deviation 21.4
11.2 units on a scale
Standard Deviation 23.9
2.5 units on a scale
Standard Deviation 25.2
-0.5 units on a scale
Standard Deviation 26.9
Change From Baseline in Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36)
General Health Perception
6.3 units on a scale
Standard Deviation 12.3
6.0 units on a scale
Standard Deviation 14.8
4.7 units on a scale
Standard Deviation 16.8
8.7 units on a scale
Standard Deviation 13.5
Change From Baseline in Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36)
Social Functioning
7.1 units on a scale
Standard Deviation 21.3
6.5 units on a scale
Standard Deviation 27.3
7.4 units on a scale
Standard Deviation 25.9
6.0 units on a scale
Standard Deviation 20.3
Change From Baseline in Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36)
Role Limitations - Emotional
9.8 units on a scale
Standard Deviation 29.5
13.8 units on a scale
Standard Deviation 24.0
11.8 units on a scale
Standard Deviation 27.7
9.7 units on a scale
Standard Deviation 27.3
Change From Baseline in Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36)
Mental Health
2.5 units on a scale
Standard Deviation 18.9
9.7 units on a scale
Standard Deviation 22.0
8.1 units on a scale
Standard Deviation 16.7
7.5 units on a scale
Standard Deviation 19.4

SECONDARY outcome

Timeframe: Baseline and Week 6

Population: Full analysis set with available PSQI data; LOCF was used.

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.

Outcome measures

Outcome measures
Measure
Placebo
n=44 Participants
Participants received matching placebo tablets once daily before bedtime for 7 weeks.
Quetiapine 50 mg
n=44 Participants
Participants received quetiapine extended release (XR) 50 mg tablets once daily before bedtime for 7 weeks.
Quetiapine 150 mg
n=39 Participants
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.
Quetiapine 300 mg
n=42 Participants
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.
Change From Baseline in Pittsburgh Sleep Quality Index (PSQI)
-1.1 units on a scale
Standard Deviation 2.9
-1.8 units on a scale
Standard Deviation 2.7
-1.5 units on a scale
Standard Deviation 2.7
-1.8 units on a scale
Standard Deviation 3.0

SECONDARY outcome

Timeframe: Up to 8 weeks

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.

Outcome measures

Outcome measures
Measure
Placebo
n=44 Participants
Participants received matching placebo tablets once daily before bedtime for 7 weeks.
Quetiapine 50 mg
n=44 Participants
Participants received quetiapine extended release (XR) 50 mg tablets once daily before bedtime for 7 weeks.
Quetiapine 150 mg
n=41 Participants
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.
Quetiapine 300 mg
n=43 Participants
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.
Safety Assessed by the Incidence of Adverse Events (AE), Vital Signs, Electrocardiogram (ECG) and Laboratory Tests
Any adverse event
25 participants
33 participants
35 participants
35 participants
Safety Assessed by the Incidence of Adverse Events (AE), Vital Signs, Electrocardiogram (ECG) and Laboratory Tests
Drug-related adverse event
21 participants
24 participants
29 participants
31 participants
Safety Assessed by the Incidence of Adverse Events (AE), Vital Signs, Electrocardiogram (ECG) and Laboratory Tests
Deaths
0 participants
0 participants
0 participants
0 participants
Safety Assessed by the Incidence of Adverse Events (AE), Vital Signs, Electrocardiogram (ECG) and Laboratory Tests
Serious adverse event
0 participants
1 participants
0 participants
1 participants
Safety Assessed by the Incidence of Adverse Events (AE), Vital Signs, Electrocardiogram (ECG) and Laboratory Tests
Drug-related serious adverse event
0 participants
1 participants
0 participants
1 participants
Safety Assessed by the Incidence of Adverse Events (AE), Vital Signs, Electrocardiogram (ECG) and Laboratory Tests
AE leading to discontinuation
2 participants
2 participants
6 participants
4 participants
Safety Assessed by the Incidence of Adverse Events (AE), Vital Signs, Electrocardiogram (ECG) and Laboratory Tests
Drug-related AE leading to discontinuation
1 participants
2 participants
6 participants
2 participants

Adverse Events

Placebo

Serious events: 0 serious events
Other events: 18 other events
Deaths: 0 deaths

Quetiapine 50 mg

Serious events: 1 serious events
Other events: 23 other events
Deaths: 0 deaths

Quetiapine 150 mg

Serious events: 0 serious events
Other events: 26 other events
Deaths: 0 deaths

Quetiapine 300 mg

Serious events: 1 serious events
Other events: 28 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
Placebo
n=44 participants at risk
Participants received matching placebo tablets once daily before bedtime for 7 weeks.
Quetiapine 50 mg
n=44 participants at risk
Participants received quetiapine extended release (XR) 50 mg tablets once daily before bedtime for 7 weeks.
Quetiapine 150 mg
n=41 participants at risk
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.
Quetiapine 300 mg
n=43 participants at risk
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.
Hepatobiliary disorders
Hepatitis acute
0.00%
0/44 • 8 weeks
0.00%
0/44 • 8 weeks
0.00%
0/41 • 8 weeks
2.3%
1/43 • 8 weeks
Nervous system disorders
Partial seizures
0.00%
0/44 • 8 weeks
2.3%
1/44 • 8 weeks
0.00%
0/41 • 8 weeks
0.00%
0/43 • 8 weeks

Other adverse events

Other adverse events
Measure
Placebo
n=44 participants at risk
Participants received matching placebo tablets once daily before bedtime for 7 weeks.
Quetiapine 50 mg
n=44 participants at risk
Participants received quetiapine extended release (XR) 50 mg tablets once daily before bedtime for 7 weeks.
Quetiapine 150 mg
n=41 participants at risk
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.
Quetiapine 300 mg
n=43 participants at risk
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.
General disorders
Malaise
0.00%
0/44 • 8 weeks
2.3%
1/44 • 8 weeks
2.4%
1/41 • 8 weeks
7.0%
3/43 • 8 weeks
General disorders
Thirst
4.5%
2/44 • 8 weeks
11.4%
5/44 • 8 weeks
12.2%
5/41 • 8 weeks
20.9%
9/43 • 8 weeks
Infections and infestations
Nasopharyngitis
6.8%
3/44 • 8 weeks
6.8%
3/44 • 8 weeks
14.6%
6/41 • 8 weeks
14.0%
6/43 • 8 weeks
Infections and infestations
Pharyngitis
6.8%
3/44 • 8 weeks
2.3%
1/44 • 8 weeks
0.00%
0/41 • 8 weeks
0.00%
0/43 • 8 weeks
Investigations
Blood cholesterol increased
0.00%
0/44 • 8 weeks
0.00%
0/44 • 8 weeks
7.3%
3/41 • 8 weeks
4.7%
2/43 • 8 weeks
Investigations
Blood prolactin increased
6.8%
3/44 • 8 weeks
2.3%
1/44 • 8 weeks
9.8%
4/41 • 8 weeks
4.7%
2/43 • 8 weeks
Investigations
Blood triglycerides increased
4.5%
2/44 • 8 weeks
13.6%
6/44 • 8 weeks
9.8%
4/41 • 8 weeks
11.6%
5/43 • 8 weeks
Investigations
Weight increased
0.00%
0/44 • 8 weeks
4.5%
2/44 • 8 weeks
7.3%
3/41 • 8 weeks
4.7%
2/43 • 8 weeks
Metabolism and nutrition disorders
Increased appetite
0.00%
0/44 • 8 weeks
2.3%
1/44 • 8 weeks
7.3%
3/41 • 8 weeks
0.00%
0/43 • 8 weeks
Nervous system disorders
Dizziness
0.00%
0/44 • 8 weeks
0.00%
0/44 • 8 weeks
7.3%
3/41 • 8 weeks
14.0%
6/43 • 8 weeks
Nervous system disorders
Dizziness postural
2.3%
1/44 • 8 weeks
2.3%
1/44 • 8 weeks
4.9%
2/41 • 8 weeks
9.3%
4/43 • 8 weeks
Nervous system disorders
Headache
6.8%
3/44 • 8 weeks
11.4%
5/44 • 8 weeks
2.4%
1/41 • 8 weeks
2.3%
1/43 • 8 weeks
Nervous system disorders
Somnolence
13.6%
6/44 • 8 weeks
20.5%
9/44 • 8 weeks
31.7%
13/41 • 8 weeks
39.5%
17/43 • 8 weeks

Additional Information

Vice President, Clinical Development Administration

Astellas Pharma Inc.

Results disclosure agreements

  • Principal investigator is a sponsor employee PI needs to get prior approval from Sponsor in writing for publication of trial data.
  • Publication restrictions are in place

Restriction type: OTHER