Major Depressive Disorder
Conditions
Keywords
Open-label Long-term extension study
Brief summary
The primary objective of this study is to evaluate the long-term safety of desvenlafaxine succinate sustained release tablets during 10-month open-label treatment of Japanese subjects with major depressive disorder (MDD). The secondary objective is to evaluate the long-term response of subjects receiving desvenlafaxine succinate sustained release tablets by clinical global evaluation, general well-being and absence of symptoms.
Interventions
DRUGdesvenlafaxine succinate sustained release tablets
25-mg or 50-mg DVS SR tablets taken orally, once daily, at the same time each day. 100 mg dose will be supplied as 2 tablets of 50-mg tablet.
Sponsors
Pfizer
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Outpatients who have completed double-blind therapy in short-term study for the indication of major depressive disorder (MDD), including scheduled evaluations, with no major protocol violations and no study events that, in the opinion of the investigator, would preclude the subject's entry into the long-term, open-label study.
Exclusion criteria
* Clinically important abnormalities on baseline (day 56 of the short-term study) physical examination, or any unresolved clinically significant abnormalities on electrocardiogram (ECG), laboratory test results, or vital signs recorded before day 56 in the previous short-term study for the indication of MDD.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Hamilton Psychiatric Scale for Depression-17 Item (HAM-D17) Score | Baseline (Extension Study) up to Day 308 or Final On-Therapy (FOT) Evaluation | HAM-D17 is a standardized, clinician-administered rating scale that assesses 17 items characteristically associated with major depression. Items are scored on either a 3-point (0 to 2) or a 5-point scale (0 to 4) with 0=none/absent and 4=most severe, for a maximum total score of 50. Higher scores indicate greater severity. FOT evaluation is defined as the last on-therapy evaluation, regardless of the number of days on therapy. Analysis on Observed cases (non-missing data) and Last observation carried forward (LOCF); LOCF method of imputation for any missing value at any visit. |
| Percentage of Participants With Adverse Events (AEs) or Serious Adverse Events (SAEs) | Baseline (Extension Study) up to Day 329 or 15 days after last dose of study treatment | Any untoward medical occurrence in a participant who received study treatment was considered an AE without regard to possibility of causal relationship. An AE resulting in any of the following outcomes, or deemed to be significant for any other reason, was considered to be an SAE: death; initial or prolonged inpatient hospitalization; a life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; or congenital anomaly. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Categorical Scores on Clinical Global Impression-Improvement (CGI-I) | Day 308 or FOT Evaluation | CGI-I is a 7-point clinician rated scale ranging from 1 (very much improved) to 7 (very much worse). Improvement is defined as a score of 1 (very much improved), 2 (much improved), or 3 (minimally improved) on the scale. Higher score = more affected. |
| Change From Baseline in Clinical Global Impression-Severity of Illness [CGI-S] Score | Baseline (Extension Study) up to Day 308 or FOT Evaluation | CGI-S is a 7-point clinician rated scale to assess severity of current illness state. Range is 1 (normal - not ill at all) to 7 (among the most extremely ill). Higher score = more affected. |
Countries
Japan
Participant flow
Recruitment details
This was a 10-month, open-label, multicenter study of Japanese participants with Major Depressive Disorder (MDD) conducted from March 2009 to March 2011 at 61 sites in Japan.
Pre-assignment details
A total of 304 participants who completed the short-term Core Study (NCT00798707 \[3151A1-3359 / B2061003\]) consented to enroll in this long-term, open-label, flexible dosing Extension study (NCT00831415 \[3151A1-3350 / B2061002\]). Baseline in this Extension study = Day 56 of the Core study.
Participants by arm
| Arm | Count |
|---|---|
| DVS SR DVS SR flexible dose 25 mg/day up to 100 mg/day. | 304 |
| Total | 304 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 14 |
| Overall Study | Death | 1 |
| Overall Study | Failed to return | 3 |
| Overall Study | Lost to Follow-up | 9 |
| Overall Study | Physician Decision | 6 |
| Overall Study | Protocol Violation | 3 |
| Overall Study | Unsatisfactory response - Efficacy | 4 |
| Overall Study | Withdrawal by Subject | 35 |
Baseline characteristics
| Characteristic | DVS SR |
|---|---|
| Age, Continuous | 38.45 years STANDARD_DEVIATION 10.81 |
| Categorical scores on Clinical Global Impression-Improvement [CGI-I] 1=Very much improved | 75 participants |
| Categorical scores on Clinical Global Impression-Improvement [CGI-I] 2=Much improved | 81 participants |
| Categorical scores on Clinical Global Impression-Improvement [CGI-I] 3=Minimally improved | 94 participants |
| Categorical scores on Clinical Global Impression-Improvement [CGI-I] 4=No change | 51 participants |
| Categorical scores on Clinical Global Impression-Improvement [CGI-I] 5=Minimally worse | 3 participants |
| Clinical Global Impression-Severity of Illness [CGI-S] score | 3.25 scores on a scale STANDARD_DEVIATION 1.11 |
| Hamilton Psychiatric Scale for Depression-17 Item (HAM-D17) score | 12.86 scores on a scale STANDARD_DEVIATION 6.3 |
| Sex: Female, Male Female | 149 Participants |
| Sex: Female, Male Male | 155 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 247 / 304 |
| serious Total, serious adverse events | 8 / 304 |
Outcome results
Primary
Change From Baseline in Hamilton Psychiatric Scale for Depression-17 Item (HAM-D17) Score
HAM-D17 is a standardized, clinician-administered rating scale that assesses 17 items characteristically associated with major depression. Items are scored on either a 3-point (0 to 2) or a 5-point scale (0 to 4) with 0=none/absent and 4=most severe, for a maximum total score of 50. Higher scores indicate greater severity. FOT evaluation is defined as the last on-therapy evaluation, regardless of the number of days on therapy. Analysis on Observed cases (non-missing data) and Last observation carried forward (LOCF); LOCF method of imputation for any missing value at any visit.
Time frame: Baseline (Extension Study) up to Day 308 or Final On-Therapy (FOT) Evaluation
Population: Intent to treat (ITT): all enrolled participants who received at least 1 dose of study treatment in Extension Study and at least 1 available post-baseline evaluation for any endpoint; (n)=number of participants with analyzable data at observation.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| DVS SR | Change From Baseline in Hamilton Psychiatric Scale for Depression-17 Item (HAM-D17) Score | LOCF - change at FOT (n=304) | -4.76 scores on a scale |
| DVS SR | Change From Baseline in Hamilton Psychiatric Scale for Depression-17 Item (HAM-D17) Score | Observed cases - change at Day 308 (n=224) | -5.82 scores on a scale |
Primary
Percentage of Participants With Adverse Events (AEs) or Serious Adverse Events (SAEs)
Any untoward medical occurrence in a participant who received study treatment was considered an AE without regard to possibility of causal relationship. An AE resulting in any of the following outcomes, or deemed to be significant for any other reason, was considered to be an SAE: death; initial or prolonged inpatient hospitalization; a life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; or congenital anomaly.
Time frame: Baseline (Extension Study) up to Day 329 or 15 days after last dose of study treatment
Population: Safety population: all enrolled participants who received at least 1 dose of study treatment in this extension study.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| DVS SR | Percentage of Participants With Adverse Events (AEs) or Serious Adverse Events (SAEs) | Adverse Events | 81.3 percentage of participants |
| DVS SR | Percentage of Participants With Adverse Events (AEs) or Serious Adverse Events (SAEs) | Serious Adverse Events | 2.6 percentage of participants |
Secondary
Change From Baseline in Clinical Global Impression-Severity of Illness [CGI-S] Score
CGI-S is a 7-point clinician rated scale to assess severity of current illness state. Range is 1 (normal - not ill at all) to 7 (among the most extremely ill). Higher score = more affected.
Time frame: Baseline (Extension Study) up to Day 308 or FOT Evaluation
Population: ITT; LOCF and Observed cases (non-missing data); (n)=number of participants with analyzable data at observation.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| DVS SR | Change From Baseline in Clinical Global Impression-Severity of Illness [CGI-S] Score | LOCF - change at FOT (n=304) | -0.82 scores on a scale |
| DVS SR | Change From Baseline in Clinical Global Impression-Severity of Illness [CGI-S] Score | Observed cases - change at Day 308 (n=224) | -0.95 scores on a scale |
Secondary
Number of Participants With Categorical Scores on Clinical Global Impression-Improvement (CGI-I)
CGI-I is a 7-point clinician rated scale ranging from 1 (very much improved) to 7 (very much worse). Improvement is defined as a score of 1 (very much improved), 2 (much improved), or 3 (minimally improved) on the scale. Higher score = more affected.
Time frame: Day 308 or FOT Evaluation
Population: ITT; LOCF. Improvement measured against CGI-I baseline (Day -1) data in Core study (NCT00798707 \[3151A1-3359 / B2061003\]).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| DVS SR | Number of Participants With Categorical Scores on Clinical Global Impression-Improvement (CGI-I) | 4=No change | 15 participants |
| DVS SR | Number of Participants With Categorical Scores on Clinical Global Impression-Improvement (CGI-I) | 7=Very much worse | 0 participants |
| DVS SR | Number of Participants With Categorical Scores on Clinical Global Impression-Improvement (CGI-I) | 1=Very much improved | 164 participants |
| DVS SR | Number of Participants With Categorical Scores on Clinical Global Impression-Improvement (CGI-I) | 2=Much improved | 82 participants |
| DVS SR | Number of Participants With Categorical Scores on Clinical Global Impression-Improvement (CGI-I) | 3=Minimally improved | 36 participants |
| DVS SR | Number of Participants With Categorical Scores on Clinical Global Impression-Improvement (CGI-I) | 5=Minimally worse | 6 participants |
| DVS SR | Number of Participants With Categorical Scores on Clinical Global Impression-Improvement (CGI-I) | 6=Much worse | 1 participants |