Trial Outcomes & Findings for A Randomized, Double-blind, Two-arm Study Comparing the Efficacy and Safety of Trazodone Contramid® OAD and Placebo in the Treatment of Unipolar Major Depressive Disorder. (NCT NCT00775203)
NCT ID: NCT00775203
Last Updated: 2012-04-27
Results Overview
The Hamilton Depression Rating Scale 17 items \[HAMD-17\] is a 17-item scale that evaluates depressed mood, vegetative and cognitive symptoms of depression, and co-morbid anxiety symptoms. The 17 items are rated on either a 5-point (0-4) or a 3-point (0-2) scale. In general, the 5 point scale items use a rating of 0=absent; 1=doubtful to mild; 2=mild to moderate; 3=moderate to severe; 4=very severe. The 3-point scale items use a rating of 0=absent; 1=probable or mild; 2=definite. The total HAMD-17score ranges from 0 (not ill) to 52 (severely ill).
COMPLETED
PHASE3
412 participants
Baseline to Week 8
2012-04-27
Participant Flow
Participant milestones
| Measure |
Trazodone Contramid OAD
Subjects with Major Depressive Disorder who were randomized to Trazodone Contramid OAD. Dose was titrated to each subject optimal dose every 3 to 4 days by 75 mg increments from a starting dose of 150 mg to a maximum daily dose of 375 mg. At each dosing step, if a dose was not well tolerated after 2 days, subjects had the option to decrease to the previous dose. Patients then continued six weeks of treatment; further dose adjustments were allowed based on efficacy and tolerability.
|
Placebo
Subjects with Major Depressive Disorder who were randomized to Placebo to match Trazodone Contramid OAD.
|
|---|---|---|
|
Overall Study
STARTED
|
206
|
206
|
|
Overall Study
Received Study Medication
|
202
|
204
|
|
Overall Study
COMPLETED
|
144
|
163
|
|
Overall Study
NOT COMPLETED
|
62
|
43
|
Reasons for withdrawal
| Measure |
Trazodone Contramid OAD
Subjects with Major Depressive Disorder who were randomized to Trazodone Contramid OAD. Dose was titrated to each subject optimal dose every 3 to 4 days by 75 mg increments from a starting dose of 150 mg to a maximum daily dose of 375 mg. At each dosing step, if a dose was not well tolerated after 2 days, subjects had the option to decrease to the previous dose. Patients then continued six weeks of treatment; further dose adjustments were allowed based on efficacy and tolerability.
|
Placebo
Subjects with Major Depressive Disorder who were randomized to Placebo to match Trazodone Contramid OAD.
|
|---|---|---|
|
Overall Study
Adverse Event
|
25
|
6
|
|
Overall Study
Lack of Efficacy
|
8
|
9
|
|
Overall Study
Withdrawal by Subject
|
11
|
9
|
|
Overall Study
Lost to Follow-up
|
11
|
15
|
|
Overall Study
Administrative reason
|
2
|
0
|
|
Overall Study
Noncompliance
|
4
|
2
|
|
Overall Study
Protocol Violation
|
0
|
1
|
|
Overall Study
Entered other study
|
1
|
0
|
|
Overall Study
Physician Decision
|
0
|
1
|
Baseline Characteristics
A Randomized, Double-blind, Two-arm Study Comparing the Efficacy and Safety of Trazodone Contramid® OAD and Placebo in the Treatment of Unipolar Major Depressive Disorder.
Baseline characteristics by cohort
| Measure |
Trazodone Contramid OAD
n=202 Participants
Subjects with Major Depressive Disorder who were randomized to Trazodone Contramid OAD. Dose was titrated to each subject optimal dose every 3 to 4 days by 75 mg increments from a starting dose of 150 mg to a maximum daily dose of 375 mg. At each dosing step, if a dose was not well tolerated after 2 days, subjects had the option to decrease to the previous dose. Patients then continued six weeks of treatment; further dose adjustments were allowed based on efficacy and tolerability.
|
Placebo
n=204 Participants
Subjects with Major Depressive Disorder who were randomized to Placebo to match Trazodone Contramid OAD.
|
Total
n=406 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
193 Participants
n=5 Participants
|
186 Participants
n=7 Participants
|
379 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
9 Participants
n=5 Participants
|
16 Participants
n=7 Participants
|
25 Participants
n=5 Participants
|
|
Age Continuous
|
43.8 years
STANDARD_DEVIATION 12.83 • n=5 Participants
|
44.0 years
STANDARD_DEVIATION 13.45 • n=7 Participants
|
43.9 years
STANDARD_DEVIATION 13.12 • n=5 Participants
|
|
Sex: Female, Male
Female
|
129 Participants
n=5 Participants
|
131 Participants
n=7 Participants
|
260 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
73 Participants
n=5 Participants
|
73 Participants
n=7 Participants
|
146 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
169 participants
n=5 Participants
|
166 participants
n=7 Participants
|
335 participants
n=5 Participants
|
|
Region of Enrollment
Canada
|
33 participants
n=5 Participants
|
38 participants
n=7 Participants
|
71 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline to Week 8Population: Full analysis (intent-to-treat \[ITT\]) population is defined as all randomized patients who received any study medication and had a baseline and at least one post-baseline HAMD-17 assessment. Week 8 Last Observation Carried Forward (LOCF): Trazodone = 202, placebo = 204.
The Hamilton Depression Rating Scale 17 items \[HAMD-17\] is a 17-item scale that evaluates depressed mood, vegetative and cognitive symptoms of depression, and co-morbid anxiety symptoms. The 17 items are rated on either a 5-point (0-4) or a 3-point (0-2) scale. In general, the 5 point scale items use a rating of 0=absent; 1=doubtful to mild; 2=mild to moderate; 3=moderate to severe; 4=very severe. The 3-point scale items use a rating of 0=absent; 1=probable or mild; 2=definite. The total HAMD-17score ranges from 0 (not ill) to 52 (severely ill).
Outcome measures
| Measure |
Trazodone Contramid OAD
n=202 Participants
Subjects with Major Depressive Disorder who were randomized to Trazodone Contramid OAD. Dose was titrated to each subject optimal dose every 3 to 4 days by 75 mg increments from a starting dose of 150 mg to a maximum daily dose of 375 mg. At each dosing step, if a dose was not well tolerated after 2 days, subjects had the option to decrease to the previous dose. Patients then continued six weeks of treatment; further dose adjustments were allowed based on efficacy and tolerability.
|
Placebo
n=204 Participants
Subjects with Major Depressive Disorder who were randomized to Placebo to match Trazodone Contramid OAD.
|
|---|---|---|
|
Change in Hamilton Depression Scale (HAMD-17) Total Score From Baseline
Baseline
|
23.2 Points on HAMD-17 scale
Standard Deviation 4.16
|
22.4 Points on HAMD-17 scale
Standard Deviation 4.43
|
|
Change in Hamilton Depression Scale (HAMD-17) Total Score From Baseline
Week 8 or LOCF
|
11.8 Points on HAMD-17 scale
Standard Deviation 7.99
|
13.2 Points on HAMD-17 scale
Standard Deviation 8.06
|
|
Change in Hamilton Depression Scale (HAMD-17) Total Score From Baseline
Change from baseline
|
-11.4 Points on HAMD-17 scale
Standard Deviation 8.20
|
-9.3 Points on HAMD-17 scale
Standard Deviation 7.94
|
SECONDARY outcome
Timeframe: Weeks 1, 2, 3, 4, 6, 8Population: Full analysis (intent-to-treat \[ITT\]) population is defined as all randomized patients who received any study medication and had a baseline and at least one post-baseline HAMD-17 assessment. Last Observation Carried Forward (LOCF).
Number of patients who show a response (defined as at least a 50% reduction from baseline in HAMD-17 score) at each post-baseline visit.
Outcome measures
| Measure |
Trazodone Contramid OAD
n=202 Participants
Subjects with Major Depressive Disorder who were randomized to Trazodone Contramid OAD. Dose was titrated to each subject optimal dose every 3 to 4 days by 75 mg increments from a starting dose of 150 mg to a maximum daily dose of 375 mg. At each dosing step, if a dose was not well tolerated after 2 days, subjects had the option to decrease to the previous dose. Patients then continued six weeks of treatment; further dose adjustments were allowed based on efficacy and tolerability.
|
Placebo
n=204 Participants
Subjects with Major Depressive Disorder who were randomized to Placebo to match Trazodone Contramid OAD.
|
|---|---|---|
|
HAMD-17 Responders at Each Visit
≥50% reduction in HAMD-17 at Week 1 (n=197, n=199)
|
25 Participants
|
19 Participants
|
|
HAMD-17 Responders at Each Visit
≥50% reduction in HAMD-17 at Week 2 (n=201, n=203)
|
63 Participants
|
41 Participants
|
|
HAMD-17 Responders at Each Visit
≥50% reduction in HAMD-17 at Week 3 (n=202, n=204)
|
89 Participants
|
53 Participants
|
|
HAMD-17 Responders at Each Visit
≥50% reduction in HAMD-17 at Week 4 (n=202, n=204)
|
95 Participants
|
74 Participants
|
|
HAMD-17 Responders at Each Visit
≥50% reduction in HAMD-17 at Week 6 (n=202, n=204)
|
100 Participants
|
81 Participants
|
|
HAMD-17 Responders at Each Visit
≥50% reduction in HAMD-17 at Week 8 (n=202, n=204)
|
109 Participants
|
84 Participants
|
SECONDARY outcome
Timeframe: Weeks 1, 2, 3, 4, 6, 8Population: Full analysis (intent-to-treat \[ITT\]) population is defined as all randomized patients who received any study medication and had a baseline and at least one post-baseline HAMD-17 assessment. Last Observation Carried Forward (LOCF).
Number of patients who are remitters (defined as patients who achieved a HAMD-17 total score ≤7) at each post-baseline visit.
Outcome measures
| Measure |
Trazodone Contramid OAD
n=202 Participants
Subjects with Major Depressive Disorder who were randomized to Trazodone Contramid OAD. Dose was titrated to each subject optimal dose every 3 to 4 days by 75 mg increments from a starting dose of 150 mg to a maximum daily dose of 375 mg. At each dosing step, if a dose was not well tolerated after 2 days, subjects had the option to decrease to the previous dose. Patients then continued six weeks of treatment; further dose adjustments were allowed based on efficacy and tolerability.
|
Placebo
n=204 Participants
Subjects with Major Depressive Disorder who were randomized to Placebo to match Trazodone Contramid OAD.
|
|---|---|---|
|
HAMD-17 Remitters at Each Visit
Number of remitters at Week 1 (n=197, n=199)
|
10 Participants
|
9 Participants
|
|
HAMD-17 Remitters at Each Visit
Number of remitters at Week 2 (n=201, n=203)
|
29 Participants
|
24 Participants
|
|
HAMD-17 Remitters at Each Visit
Number of remitters at Week 3 (n=202, n=204)
|
51 Participants
|
32 Participants
|
|
HAMD-17 Remitters at Each Visit
Number of remitters at Week 4 (n=202, n=204)
|
61 Participants
|
43 Participants
|
|
HAMD-17 Remitters at Each Visit
Number of remitters at Week 6 (n=202, n=204)
|
66 Participants
|
47 Participants
|
|
HAMD-17 Remitters at Each Visit
Number of remitters at Week 8 (n=202, n=204)
|
72 Participants
|
65 Participants
|
SECONDARY outcome
Timeframe: Baseline to Weeks 1, 2, 3, 4, 6, 8Population: Full analysis (intent-to-treat \[ITT\]) population is defined as all randomized patients who received any study medication and had a baseline and at least one post-baseline HAMD-17 assessment. Last Observation Carried Forward (LOCF).
Change from baseline in the HAMD-17, item 1: Depressed Mood item, at each post-baseline visit. The Depressed Mood item is rated on a 5-point scale ranging from rating of 0=absent; to 4=very severe.
Outcome measures
| Measure |
Trazodone Contramid OAD
n=202 Participants
Subjects with Major Depressive Disorder who were randomized to Trazodone Contramid OAD. Dose was titrated to each subject optimal dose every 3 to 4 days by 75 mg increments from a starting dose of 150 mg to a maximum daily dose of 375 mg. At each dosing step, if a dose was not well tolerated after 2 days, subjects had the option to decrease to the previous dose. Patients then continued six weeks of treatment; further dose adjustments were allowed based on efficacy and tolerability.
|
Placebo
n=204 Participants
Subjects with Major Depressive Disorder who were randomized to Placebo to match Trazodone Contramid OAD.
|
|---|---|---|
|
Change in HAMD-17 Depressed Mood Item (Item 1) Score From Baseline to Each Visit
Change in score at Week 1 (n=197, n=199)
|
-0.7 Points on the HAMD scale
Standard Deviation 0.89
|
-0.5 Points on the HAMD scale
Standard Deviation 0.74
|
|
Change in HAMD-17 Depressed Mood Item (Item 1) Score From Baseline to Each Visit
Change in score at Week 2 (n=201, n=203)
|
-1.1 Points on the HAMD scale
Standard Deviation 1.13
|
-0.8 Points on the HAMD scale
Standard Deviation 0.95
|
|
Change in HAMD-17 Depressed Mood Item (Item 1) Score From Baseline to Each Visit
Change in score at Week 3 (n=202, n=204)
|
-1.4 Points on the HAMD scale
Standard Deviation 1.18
|
-1.0 Points on the HAMD scale
Standard Deviation 1.08
|
|
Change in HAMD-17 Depressed Mood Item (Item 1) Score From Baseline to Each Visit
Change in score at Week 4 (n=202, n=204)
|
-1.5 Points on the HAMD scale
Standard Deviation 1.21
|
-1.2 Points on the HAMD scale
Standard Deviation 1.12
|
|
Change in HAMD-17 Depressed Mood Item (Item 1) Score From Baseline to Each Visit
Change in score at Week 6 (n=202, n=204)
|
-1.5 Points on the HAMD scale
Standard Deviation 1.18
|
-1.3 Points on the HAMD scale
Standard Deviation 1.15
|
|
Change in HAMD-17 Depressed Mood Item (Item 1) Score From Baseline to Each Visit
Change in score at Week 8 (n=202, n=204)
|
-1.6 Points on the HAMD scale
Standard Deviation 1.29
|
-1.3 Points on the HAMD scale
Standard Deviation 1.22
|
SECONDARY outcome
Timeframe: Baseline to Week 8Population: Full analysis (intent-to-treat \[ITT\]) population is defined as all randomized patients who received any study medication and had a baseline and at least one post-baseline HAMD-17 assessment. MADRS Week 8 Observed Cases: Trazodone = 178, placebo = 182.
The Montgomery-Åsberg Depression Rating Scale (MADRS) is a 10 item clinician-administered depression rating scale. The 10 items (apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts) are rated on a scale ranging from 0 (low severity/difficulty) to 6 (high severity/difficulty) with anchors at 2-point intervals. The overall total score range is from 0 (low severity of depressive symptoms) to 60 (high severity of depressive symptoms).
Outcome measures
| Measure |
Trazodone Contramid OAD
n=178 Participants
Subjects with Major Depressive Disorder who were randomized to Trazodone Contramid OAD. Dose was titrated to each subject optimal dose every 3 to 4 days by 75 mg increments from a starting dose of 150 mg to a maximum daily dose of 375 mg. At each dosing step, if a dose was not well tolerated after 2 days, subjects had the option to decrease to the previous dose. Patients then continued six weeks of treatment; further dose adjustments were allowed based on efficacy and tolerability.
|
Placebo
n=182 Participants
Subjects with Major Depressive Disorder who were randomized to Placebo to match Trazodone Contramid OAD.
|
|---|---|---|
|
Change in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score From Baseline
Baseline (n=202, n=204)
|
32.6 Units on MADRS scale
Standard Deviation 4.07
|
31.9 Units on MADRS scale
Standard Deviation 4.33
|
|
Change in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score From Baseline
Week 8 (n=178, n=182)
|
16.0 Units on MADRS scale
Standard Deviation 11.24
|
17.7 Units on MADRS scale
Standard Deviation 11.62
|
|
Change in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score From Baseline
Change from baseline (n=178, n=182)
|
-16.6 Units on MADRS scale
Standard Deviation 11.27
|
-14.1 Units on MADRS scale
Standard Deviation 11.27
|
SECONDARY outcome
Timeframe: Baseline to Weeks 1, 2, 3, 4, 6, 8Population: Full analysis (intent-to-treat \[ITT\]) population is defined as all randomized patients who received any study medication and had a baseline and at least one post-baseline HAMD-17 assessment. Last Observation Carried Forward (LOCF).
The CGI-Severity (CGI-S) consists of one question for the investigator: "Considering your total clinical experience with this particular population, how mentally ill is the patient at this time?" which is rated on the following seven-point scale: 1=normal, not ill at all; 2=borderline mentally ill; 3=mildly ill; 4=moderately ill; 5=markedly ill; 6=severely ill; 7=among the most extremely ill patients.
Outcome measures
| Measure |
Trazodone Contramid OAD
n=202 Participants
Subjects with Major Depressive Disorder who were randomized to Trazodone Contramid OAD. Dose was titrated to each subject optimal dose every 3 to 4 days by 75 mg increments from a starting dose of 150 mg to a maximum daily dose of 375 mg. At each dosing step, if a dose was not well tolerated after 2 days, subjects had the option to decrease to the previous dose. Patients then continued six weeks of treatment; further dose adjustments were allowed based on efficacy and tolerability.
|
Placebo
n=204 Participants
Subjects with Major Depressive Disorder who were randomized to Placebo to match Trazodone Contramid OAD.
|
|---|---|---|
|
Change From Baseline in Clinical Global Impression of Severity (CGI-S) to Each Visit
Change in CGI-S score at Week 1 (n=197, n=199)
|
-0.6 Units on CGI-S scale
Standard Deviation 0.72
|
-0.5 Units on CGI-S scale
Standard Deviation 0.75
|
|
Change From Baseline in Clinical Global Impression of Severity (CGI-S) to Each Visit
Change in CGI-S score at Week 2 (n=201, n=203)
|
-1.0 Units on CGI-S scale
Standard Deviation 1.02
|
-0.8 Units on CGI-S scale
Standard Deviation 0.98
|
|
Change From Baseline in Clinical Global Impression of Severity (CGI-S) to Each Visit
Change in CGI-S score at Week 3 (n=202, n=204)
|
-1.4 Units on CGI-S scale
Standard Deviation 1.16
|
-1.1 Units on CGI-S scale
Standard Deviation 1.12
|
|
Change From Baseline in Clinical Global Impression of Severity (CGI-S) to Each Visit
Change in CGI-S score at Week 4 (n=202, n=204)
|
-1.6 Units on CGI-S scale
Standard Deviation 1.22
|
-1.3 Units on CGI-S scale
Standard Deviation 1.17
|
|
Change From Baseline in Clinical Global Impression of Severity (CGI-S) to Each Visit
Change in CGI-S score at Week 6 (n=202, n=204)
|
-1.7 Units on CGI-S scale
Standard Deviation 1.24
|
-1.4 Units on CGI-S scale
Standard Deviation 1.24
|
|
Change From Baseline in Clinical Global Impression of Severity (CGI-S) to Each Visit
Change in CGI-S score at Week 8 (n=202, n=204)
|
-1.7 Units on CGI-S scale
Standard Deviation 1.36
|
-1.4 Units on CGI-S scale
Standard Deviation 1.37
|
SECONDARY outcome
Timeframe: Week 8Population: Full analysis (intent-to-treat \[ITT\]) population is defined as all randomized patients who received any study medication and had a baseline and at least one post-baseline HAMD-17 assessment. CGI-I Week 8 Observed Cases: Trazodone = 178, placebo = 182.
The CGI-Improvement of Illness (CGI-I) consists of one question for the investigator: "Compared to his condition at the start of the study, how much has this patient changed?" which is rated on the following seven-point scale 1=very much improved; 2=much improved; 3=minimally improved; 4=no change from baseline; 5=minimally worse; 6= much worse; 7=very much worse.
Outcome measures
| Measure |
Trazodone Contramid OAD
n=178 Participants
Subjects with Major Depressive Disorder who were randomized to Trazodone Contramid OAD. Dose was titrated to each subject optimal dose every 3 to 4 days by 75 mg increments from a starting dose of 150 mg to a maximum daily dose of 375 mg. At each dosing step, if a dose was not well tolerated after 2 days, subjects had the option to decrease to the previous dose. Patients then continued six weeks of treatment; further dose adjustments were allowed based on efficacy and tolerability.
|
Placebo
n=182 Participants
Subjects with Major Depressive Disorder who were randomized to Placebo to match Trazodone Contramid OAD.
|
|---|---|---|
|
Clinical Global Impression - Improvement of Illness (CGI-I) Score at Last Study Visit
|
2.4 Units on the CGI-I scale
Standard Deviation 1.23
|
2.5 Units on the CGI-I scale
Standard Deviation 1.32
|
SECONDARY outcome
Timeframe: Week 8Population: Full analysis (intent-to-treat \[ITT\]) population is defined as all randomized patients who received any study medication and had a baseline and at least one post-baseline HAMD-17 assessment. PGI-I Week 8 Observed Cases: Trazodone = 176, placebo = 183.
The PGI-Improvement of Illness (PGI-I) consists of one question for the patient: "Since the start of the study, my overall status with regard to depression is?" which is rated on the following seven-point scale 1=very much improved; 2=much improved; 3=minimally improved; 4=no change; 5=minimally worse; 6= much worse; 7=very much worse.
Outcome measures
| Measure |
Trazodone Contramid OAD
n=176 Participants
Subjects with Major Depressive Disorder who were randomized to Trazodone Contramid OAD. Dose was titrated to each subject optimal dose every 3 to 4 days by 75 mg increments from a starting dose of 150 mg to a maximum daily dose of 375 mg. At each dosing step, if a dose was not well tolerated after 2 days, subjects had the option to decrease to the previous dose. Patients then continued six weeks of treatment; further dose adjustments were allowed based on efficacy and tolerability.
|
Placebo
n=183 Participants
Subjects with Major Depressive Disorder who were randomized to Placebo to match Trazodone Contramid OAD.
|
|---|---|---|
|
Patient Global Impression - Improvement of Illness (PGI-I) Score at Last Study Visit
|
2.6 Units on PGI-I scale
Standard Deviation 1.19
|
2.8 Units on PGI-I scale
Standard Deviation 1.35
|
SECONDARY outcome
Timeframe: Week 8Population: Full analysis (intent-to-treat \[ITT\]) population is defined as all randomized patients who received any study medication and had a baseline and at least one post-baseline HAMD-17 assessment. CGI-I Responders Week 8 Observed Cases: Trazodone = 180, placebo = 183.
Patients were responders if the CGI-I rating was "Much Improved" or "Very Much Improved". The CGI-Improvement of Illness (CGI-I) consists of one question for the investigator: "Compared to his condition at the start of the study, how much has this patient changed?" which is rated on the following seven-point scale 1=very much improved; 2=much improved; 3=minimally improved; 4=no change from baseline; 5=minimally worse; 6= much worse; 7=very much worse. Results are expressed in number of patients.
Outcome measures
| Measure |
Trazodone Contramid OAD
n=180 Participants
Subjects with Major Depressive Disorder who were randomized to Trazodone Contramid OAD. Dose was titrated to each subject optimal dose every 3 to 4 days by 75 mg increments from a starting dose of 150 mg to a maximum daily dose of 375 mg. At each dosing step, if a dose was not well tolerated after 2 days, subjects had the option to decrease to the previous dose. Patients then continued six weeks of treatment; further dose adjustments were allowed based on efficacy and tolerability.
|
Placebo
n=183 Participants
Subjects with Major Depressive Disorder who were randomized to Placebo to match Trazodone Contramid OAD.
|
|---|---|---|
|
Clinical Global Impression - Improvement of Illness (CGI-I) Responders at Last Study Visit
|
96 participants
|
89 participants
|
SECONDARY outcome
Timeframe: Week 8Population: Full analysis (intent-to-treat \[ITT\]) population is defined as all randomized patients who received any study medication and had a baseline and at least one post-baseline HAMD-17 assessment. PGI-I Responders Week 8 Observed Cases: Trazodone = 176, placebo = 183.
Patients were responders if the PGI-I rating was "Much Improved" or "Very Much Improved". The PGI-Improvement of Illness (PGI-I) consists of one question for the patient: "Since the start of the study, my overall status with regard to depression is?" which is rated on the following seven-point scale 1=very much improved; 2=much improved; 3=minimally improved; 4=no change; 5=minimally worse; 6= much worse; 7=very much worse. Results are expressed in number of patients.
Outcome measures
| Measure |
Trazodone Contramid OAD
n=176 Participants
Subjects with Major Depressive Disorder who were randomized to Trazodone Contramid OAD. Dose was titrated to each subject optimal dose every 3 to 4 days by 75 mg increments from a starting dose of 150 mg to a maximum daily dose of 375 mg. At each dosing step, if a dose was not well tolerated after 2 days, subjects had the option to decrease to the previous dose. Patients then continued six weeks of treatment; further dose adjustments were allowed based on efficacy and tolerability.
|
Placebo
n=183 Participants
Subjects with Major Depressive Disorder who were randomized to Placebo to match Trazodone Contramid OAD.
|
|---|---|---|
|
Patient Global Impression - Improvement of Illness (PGI-I) Responders at Last Study Visit
|
90 participants
|
80 participants
|
SECONDARY outcome
Timeframe: Weeks 1, 2, 3, 4, 6, 8Population: Full analysis (intent-to-treat \[ITT\]) population is defined as all randomized patients who received any study medication and had a baseline and at least one post-baseline HAMD-17 assessment. Last Observation Carried Forward (LOCF).
Overall Quality of Sleep was measured on a 4-point rating scale ranging from 1 = very poor to 4 = excellent in response to the question: "Since the last study visit, how would you rate the overall quality of your sleep?".
Outcome measures
| Measure |
Trazodone Contramid OAD
n=202 Participants
Subjects with Major Depressive Disorder who were randomized to Trazodone Contramid OAD. Dose was titrated to each subject optimal dose every 3 to 4 days by 75 mg increments from a starting dose of 150 mg to a maximum daily dose of 375 mg. At each dosing step, if a dose was not well tolerated after 2 days, subjects had the option to decrease to the previous dose. Patients then continued six weeks of treatment; further dose adjustments were allowed based on efficacy and tolerability.
|
Placebo
n=204 Participants
Subjects with Major Depressive Disorder who were randomized to Placebo to match Trazodone Contramid OAD.
|
|---|---|---|
|
Overall Quality of Sleep at Each Visit
Score at Baseline (n=202, n=204)
|
1.6 Points on a scale
Standard Deviation 0.65
|
1.6 Points on a scale
Standard Deviation 0.70
|
|
Overall Quality of Sleep at Each Visit
Score at Week 1 (n=196, n=199)
|
0.7 Points on a scale
Standard Deviation 0.90
|
0.4 Points on a scale
Standard Deviation 0.83
|
|
Overall Quality of Sleep at Each Visit
Score at Week 2 (n=200, n=203)
|
0.8 Points on a scale
Standard Deviation 0.97
|
0.7 Points on a scale
Standard Deviation 0.99
|
|
Overall Quality of Sleep at Each Visit
Score at Week 3 (n=201, n=204)
|
0.9 Points on a scale
Standard Deviation 1.00
|
0.7 Points on a scale
Standard Deviation 1.00
|
|
Overall Quality of Sleep at Each Visit
Score at Week 4 (n=201, n=204)
|
1.0 Points on a scale
Standard Deviation 1.02
|
0.7 Points on a scale
Standard Deviation 1.02
|
|
Overall Quality of Sleep at Each Visit
Score at Week 6 (n=201, n=204)
|
1.0 Points on a scale
Standard Deviation 1.01
|
0.9 Points on a scale
Standard Deviation 1.04
|
|
Overall Quality of Sleep at Each Visit
Score at Week 8 (n=201, n=204)
|
1.0 Points on a scale
Standard Deviation 1.05
|
0.8 Points on a scale
Standard Deviation 1.10
|
SECONDARY outcome
Timeframe: Weeks 1, 2, 3, 4, 6, 8Population: Full Analysis set (intent-to-treat \[ITT\]) population is defined as all randomized patients who received any study medication and had a baseline and at least one post-baseline HAMD-17 assessment. Last Observation Carried Forward (LOCF).
Trouble Falling Asleep was measured on a 4-point rating scale ranging from 1 = never to 4 = always in response to the question: "Since the last study visit, how often did you experience trouble falling asleep?".
Outcome measures
| Measure |
Trazodone Contramid OAD
n=202 Participants
Subjects with Major Depressive Disorder who were randomized to Trazodone Contramid OAD. Dose was titrated to each subject optimal dose every 3 to 4 days by 75 mg increments from a starting dose of 150 mg to a maximum daily dose of 375 mg. At each dosing step, if a dose was not well tolerated after 2 days, subjects had the option to decrease to the previous dose. Patients then continued six weeks of treatment; further dose adjustments were allowed based on efficacy and tolerability.
|
Placebo
n=204 Participants
Subjects with Major Depressive Disorder who were randomized to Placebo to match Trazodone Contramid OAD.
|
|---|---|---|
|
Trouble Falling Asleep at Each Visit
Score at Week 8 (n=201, n=204)
|
2.1 Units on a scale
Standard Deviation 0.85
|
2.3 Units on a scale
Standard Deviation 0.95
|
|
Trouble Falling Asleep at Each Visit
Score at Baseline (n=202, n=204)
|
3.0 Units on a scale
Standard Deviation 0.86
|
2.9 Units on a scale
Standard Deviation 0.91
|
|
Trouble Falling Asleep at Each Visit
Score at Week 1 (n=196, n=199)
|
2.5 Units on a scale
Standard Deviation 1.02
|
2.6 Units on a scale
Standard Deviation 0.98
|
|
Trouble Falling Asleep at Each Visit
Score at Week 2 (n=200, n=203)
|
2.3 Units on a scale
Standard Deviation 0.93
|
2.5 Units on a scale
Standard Deviation 0.96
|
|
Trouble Falling Asleep at Each Visit
Score at Week 3 (n=201, n=204)
|
2.2 Units on a scale
Standard Deviation 0.90
|
2.3 Units on a scale
Standard Deviation 0.99
|
|
Trouble Falling Asleep at Each Visit
Score at Week 4 (n=201, n=204)
|
2.1 Units on a scale
Standard Deviation 0.89
|
2.3 Units on a scale
Standard Deviation 0.95
|
|
Trouble Falling Asleep at Each Visit
Score at Week 6 (n=201, n=204)
|
2.1 Units on a scale
Standard Deviation 0.89
|
2.3 Units on a scale
Standard Deviation 0.95
|
SECONDARY outcome
Timeframe: Weeks 1, 2, 3, 4, 6, 8Population: Full analysis (intent-to-treat \[ITT\]) population is defined as all randomized patients who received any study medication and had a baseline and at least one post-baseline HAMD-17 assessment. Last Observation Carried Forward (LOCF).
Awakening during the night was measured on a 4-point rating scale ranging from 1 = never to 4 = always in response to the question: "Since the last study visit did you awaken during the night?".
Outcome measures
| Measure |
Trazodone Contramid OAD
n=202 Participants
Subjects with Major Depressive Disorder who were randomized to Trazodone Contramid OAD. Dose was titrated to each subject optimal dose every 3 to 4 days by 75 mg increments from a starting dose of 150 mg to a maximum daily dose of 375 mg. At each dosing step, if a dose was not well tolerated after 2 days, subjects had the option to decrease to the previous dose. Patients then continued six weeks of treatment; further dose adjustments were allowed based on efficacy and tolerability.
|
Placebo
n=204 Participants
Subjects with Major Depressive Disorder who were randomized to Placebo to match Trazodone Contramid OAD.
|
|---|---|---|
|
Awakening During the Night at Each Visit
Score at Baseline (n=202, n=204)
|
3.2 Units on a scale
Standard Deviation 0.78
|
3.2 Units on a scale
Standard Deviation 0.78
|
|
Awakening During the Night at Each Visit
Score at Week 1 (n=196, n=199)
|
2.4 Units on a scale
Standard Deviation 0.96
|
2.7 Units on a scale
Standard Deviation 0.85
|
|
Awakening During the Night at Each Visit
Score at Week 2 (n=200, n=203)
|
2.4 Units on a scale
Standard Deviation 0.94
|
2.5 Units on a scale
Standard Deviation 0.92
|
|
Awakening During the Night at Each Visit
Score at Week 3 (n=201, n=204)
|
2.2 Units on a scale
Standard Deviation 0.91
|
2.6 Units on a scale
Standard Deviation 0.90
|
|
Awakening During the Night at Each Visit
Score at Week 4 (n=201, n=204)
|
2.2 Units on a scale
Standard Deviation 0.89
|
2.6 Units on a scale
Standard Deviation 0.93
|
|
Awakening During the Night at Each Visit
Score at Week 6 (n=201, n=204)
|
2.2 Units on a scale
Standard Deviation 0.94
|
2.5 Units on a scale
Standard Deviation 0.95
|
|
Awakening During the Night at Each Visit
Score at Week 8 (n=201, n=204)
|
2.2 Units on a scale
Standard Deviation 0.89
|
2.5 Units on a scale
Standard Deviation 0.95
|
SECONDARY outcome
Timeframe: Baseline to Week 8Population: Safety population is defined as all randomized patients who received any study medication.
Number of patients who discontinued due to lack of efficacy during the whole study period (8 weeks).
Outcome measures
| Measure |
Trazodone Contramid OAD
n=202 Participants
Subjects with Major Depressive Disorder who were randomized to Trazodone Contramid OAD. Dose was titrated to each subject optimal dose every 3 to 4 days by 75 mg increments from a starting dose of 150 mg to a maximum daily dose of 375 mg. At each dosing step, if a dose was not well tolerated after 2 days, subjects had the option to decrease to the previous dose. Patients then continued six weeks of treatment; further dose adjustments were allowed based on efficacy and tolerability.
|
Placebo
n=204 Participants
Subjects with Major Depressive Disorder who were randomized to Placebo to match Trazodone Contramid OAD.
|
|---|---|---|
|
Discontinuation Due to Lack of Efficacy
|
8 participants
|
9 participants
|
Adverse Events
Trazodone Contramid OAD
Placebo
Serious adverse events
| Measure |
Trazodone Contramid OAD
n=202 participants at risk
Subjects with Major Depressive Disorder who were randomized to Trazodone Contramid OAD. Dose was titrated to each subject optimal dose every 3 to 4 days by 75 mg increments from a starting dose of 150 mg to a maximum daily dose of 375 mg. At each dosing step, if a dose was not well tolerated after 2 days, subjects had the option to decrease to the previous dose. Patients then continued six weeks of treatment; further dose adjustments were allowed based on efficacy and tolerability.
|
Placebo
n=204 participants at risk
Subjects with Major Depressive Disorder who were randomized to Placebo to match Trazodone Contramid OAD.
|
|---|---|---|
|
Gastrointestinal disorders
Abdominal pain
|
0.50%
1/202 • Number of events 1 • 8 weeks (plus an additional 30 days for SAEs only)
|
0.00%
0/204 • 8 weeks (plus an additional 30 days for SAEs only)
|
|
Gastrointestinal disorders
Duodenal ulcer
|
0.50%
1/202 • Number of events 1 • 8 weeks (plus an additional 30 days for SAEs only)
|
0.00%
0/204 • 8 weeks (plus an additional 30 days for SAEs only)
|
|
Gastrointestinal disorders
Gastritis
|
0.50%
1/202 • Number of events 1 • 8 weeks (plus an additional 30 days for SAEs only)
|
0.00%
0/204 • 8 weeks (plus an additional 30 days for SAEs only)
|
|
General disorders
Death
|
0.00%
0/202 • 8 weeks (plus an additional 30 days for SAEs only)
|
0.49%
1/204 • Number of events 1 • 8 weeks (plus an additional 30 days for SAEs only)
|
|
Infections and infestations
Staphylococcal sepsis
|
0.50%
1/202 • Number of events 1 • 8 weeks (plus an additional 30 days for SAEs only)
|
0.00%
0/204 • 8 weeks (plus an additional 30 days for SAEs only)
|
|
Infections and infestations
Viral pericarditis
|
0.50%
1/202 • Number of events 1 • 8 weeks (plus an additional 30 days for SAEs only)
|
0.00%
0/204 • 8 weeks (plus an additional 30 days for SAEs only)
|
|
Psychiatric disorders
Suicide attempt
|
0.00%
0/202 • 8 weeks (plus an additional 30 days for SAEs only)
|
0.49%
1/204 • Number of events 2 • 8 weeks (plus an additional 30 days for SAEs only)
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
0.50%
1/202 • Number of events 1 • 8 weeks (plus an additional 30 days for SAEs only)
|
0.00%
0/204 • 8 weeks (plus an additional 30 days for SAEs only)
|
Other adverse events
| Measure |
Trazodone Contramid OAD
n=202 participants at risk
Subjects with Major Depressive Disorder who were randomized to Trazodone Contramid OAD. Dose was titrated to each subject optimal dose every 3 to 4 days by 75 mg increments from a starting dose of 150 mg to a maximum daily dose of 375 mg. At each dosing step, if a dose was not well tolerated after 2 days, subjects had the option to decrease to the previous dose. Patients then continued six weeks of treatment; further dose adjustments were allowed based on efficacy and tolerability.
|
Placebo
n=204 participants at risk
Subjects with Major Depressive Disorder who were randomized to Placebo to match Trazodone Contramid OAD.
|
|---|---|---|
|
Eye disorders
Vision blurred
|
5.4%
11/202 • Number of events 12 • 8 weeks (plus an additional 30 days for SAEs only)
|
0.00%
0/204 • 8 weeks (plus an additional 30 days for SAEs only)
|
|
Gastrointestinal disorders
Constipation
|
7.9%
16/202 • Number of events 17 • 8 weeks (plus an additional 30 days for SAEs only)
|
2.0%
4/204 • Number of events 7 • 8 weeks (plus an additional 30 days for SAEs only)
|
|
Gastrointestinal disorders
Diarrhea
|
9.4%
19/202 • Number of events 23 • 8 weeks (plus an additional 30 days for SAEs only)
|
11.3%
23/204 • Number of events 29 • 8 weeks (plus an additional 30 days for SAEs only)
|
|
Gastrointestinal disorders
Dry mouth
|
25.2%
51/202 • Number of events 58 • 8 weeks (plus an additional 30 days for SAEs only)
|
12.7%
26/204 • Number of events 26 • 8 weeks (plus an additional 30 days for SAEs only)
|
|
Gastrointestinal disorders
Nausea
|
20.8%
42/202 • Number of events 51 • 8 weeks (plus an additional 30 days for SAEs only)
|
12.7%
26/204 • Number of events 30 • 8 weeks (plus an additional 30 days for SAEs only)
|
|
General disorders
Fatigue
|
14.9%
30/202 • Number of events 34 • 8 weeks (plus an additional 30 days for SAEs only)
|
8.3%
17/204 • Number of events 17 • 8 weeks (plus an additional 30 days for SAEs only)
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
5.4%
11/202 • Number of events 15 • 8 weeks (plus an additional 30 days for SAEs only)
|
3.4%
7/204 • Number of events 8 • 8 weeks (plus an additional 30 days for SAEs only)
|
|
Nervous system disorders
Dizziness
|
24.8%
50/202 • Number of events 57 • 8 weeks (plus an additional 30 days for SAEs only)
|
12.3%
25/204 • Number of events 25 • 8 weeks (plus an additional 30 days for SAEs only)
|
|
Nervous system disorders
Headache
|
33.2%
67/202 • Number of events 89 • 8 weeks (plus an additional 30 days for SAEs only)
|
27.0%
55/204 • Number of events 98 • 8 weeks (plus an additional 30 days for SAEs only)
|
|
Nervous system disorders
Sedation
|
16.8%
34/202 • Number of events 39 • 8 weeks (plus an additional 30 days for SAEs only)
|
3.4%
7/204 • Number of events 10 • 8 weeks (plus an additional 30 days for SAEs only)
|
|
Nervous system disorders
Somnolence
|
31.2%
63/202 • Number of events 80 • 8 weeks (plus an additional 30 days for SAEs only)
|
15.7%
32/204 • Number of events 36 • 8 weeks (plus an additional 30 days for SAEs only)
|
Additional Information
Director of Regulatory Affairs
Labopharm Inc.
Results disclosure agreements
- Principal investigator is a sponsor employee Prior to submitting results communications, the investigator shall allow Labopharm at least 60 days to review the proposed communication. If the proposed publication/disclosure risks Labopharm's ability to patent any invention related to the study, the publication or disclosure will be modified/delayed to allow Labopharm to seek patent protection. This statement does not give Labopharm any editorial rights other than to restrict the disclosure of Labopharm's confidential information.
- Publication restrictions are in place
Restriction type: OTHER