Trial Outcomes & Findings for Venlafaxine ER Phase 3 Study for Major Depressive Disorder (MDD) (NCT NCT01441440)
NCT ID: NCT01441440
Last Updated: 2021-01-28
Results Overview
HAM-D17 is a standardized, clinician-administered rating scale that assesses 17 items characteristically associated with major depression (symptoms such as depressed mood, work and activities, sleep, suicide, psychomotor agitation/retardation, appetite, sexual interest, anxiety, and somatic symptoms). The items of the HAM-D17 are rated on a scale of 0 to 2 or 0 to 4, and the total score ranges from 0 to 52. Higher scores indicate more severe symptoms. Change from baseline: mean score at Week 8 or early termination minus mean score at baseline.
COMPLETED
PHASE3
538 participants
Baseline, Week 8 or Early termination
2021-01-28
Participant Flow
Subjects were confirmed to meet entry criteria at the screening visit, followed by a 2-week screening period. Subjects who continued to meet all study entry criteria at baseline were randomized to 10 weeks of treatment with placebo, venlafaxine ER 75 mg/day Fixed, or venlafaxine ER 75-225 mg/day Flexible in the ratio of 1:1:1.
Participant milestones
| Measure |
Placebo
Participants received placebo capsule orally once daily after meal for 8 weeks.
|
Venlafaxine 75 mg/Day Fixed
Participants received venlafaxine ER capsule orally once daily after meal for 8 weeks. Starting dose was 37.5 mg/day followed by 75 mg/day at Week 1. If there was no tolerability concern at Week 2, the dose was continued 75 mg/day until Week 8.
|
Venlafaxine 75-225 mg/Day Flexible
Participants received venlafaxine ER capsule orally once daily after meal for 8 weeks. Starting dose was 37.5 mg/day followed by 75 mg/day at Week 1. If there was no tolerability concern at Week 2, the dose was increased to 150 mg/day. If there was no tolerability concern at Week 3, the dose was increased to 225 mg/day. Dose was reduced in the case of intolerability and if the participants could not take venlafaxine 75 mg/day or higher doses at Week 1 and the following weeks, the treatment were discontinued. No dose adjustment was allowed from Week 4 to Week 8.
|
|---|---|---|---|
|
Overall Study
STARTED
|
183
|
174
|
180
|
|
Overall Study
COMPLETED
|
166
|
151
|
158
|
|
Overall Study
NOT COMPLETED
|
17
|
23
|
22
|
Reasons for withdrawal
| Measure |
Placebo
Participants received placebo capsule orally once daily after meal for 8 weeks.
|
Venlafaxine 75 mg/Day Fixed
Participants received venlafaxine ER capsule orally once daily after meal for 8 weeks. Starting dose was 37.5 mg/day followed by 75 mg/day at Week 1. If there was no tolerability concern at Week 2, the dose was continued 75 mg/day until Week 8.
|
Venlafaxine 75-225 mg/Day Flexible
Participants received venlafaxine ER capsule orally once daily after meal for 8 weeks. Starting dose was 37.5 mg/day followed by 75 mg/day at Week 1. If there was no tolerability concern at Week 2, the dose was increased to 150 mg/day. If there was no tolerability concern at Week 3, the dose was increased to 225 mg/day. Dose was reduced in the case of intolerability and if the participants could not take venlafaxine 75 mg/day or higher doses at Week 1 and the following weeks, the treatment were discontinued. No dose adjustment was allowed from Week 4 to Week 8.
|
|---|---|---|---|
|
Overall Study
Death
|
1
|
0
|
1
|
|
Overall Study
Adverse Event
|
2
|
9
|
9
|
|
Overall Study
Lost to Follow-up
|
0
|
2
|
1
|
|
Overall Study
Withdrawal by Subject
|
11
|
9
|
9
|
|
Overall Study
Pregnancy
|
1
|
0
|
0
|
|
Overall Study
Lack of Efficacy
|
1
|
0
|
1
|
|
Overall Study
Moving
|
0
|
1
|
1
|
|
Overall Study
Work-related matter
|
0
|
1
|
0
|
|
Overall Study
Difficllty in keeping the schedule
|
1
|
1
|
0
|
Baseline Characteristics
Venlafaxine ER Phase 3 Study for Major Depressive Disorder (MDD)
Baseline characteristics by cohort
| Measure |
Placebo
n=184 Participants
Participants received placebo capsule orally once daily after meal for 8 weeks.
|
Venlafaxine 75 mg/Day Fixed
n=174 Participants
Participants received venlafaxine ER capsule orally once daily after meal for 8 weeks. Starting dose was 37.5 mg/day followed by 75 mg/day at Week 1. If there was no tolerability concern at Week 2, the dose was continued 75 mg/day until Week 8.
|
Venlafaxine 75-225 mg/Day Flexible
n=179 Participants
Participants received venlafaxine ER capsule orally once daily after meal for 8 weeks. Starting dose was 37.5 mg/day followed by 75 mg/day at Week 1. If there was no tolerability concern at Week 2, the dose was increased to 150 mg/day. If there was no tolerability concern at Week 3, the dose was increased to 225 mg/day. Dose was reduced in the case of intolerability and if the participants could not take venlafaxine 75 mg/day or higher doses at Week 1 and the following weeks, the treatment were discontinued. No dose adjustment was allowed from Week 4 to Week 8.
|
Total
n=537 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
38.6 years
STANDARD_DEVIATION 11.1 • n=5 Participants
|
38.4 years
STANDARD_DEVIATION 11.9 • n=7 Participants
|
38.3 years
STANDARD_DEVIATION 10.2 • n=5 Participants
|
38.4 years
STANDARD_DEVIATION 11.1 • n=4 Participants
|
|
Sex: Female, Male
FEMALE
|
93 Participants
n=5 Participants
|
90 Participants
n=7 Participants
|
86 Participants
n=5 Participants
|
269 Participants
n=4 Participants
|
|
Sex: Female, Male
MALE
|
91 Participants
n=5 Participants
|
84 Participants
n=7 Participants
|
93 Participants
n=5 Participants
|
268 Participants
n=4 Participants
|
PRIMARY outcome
Timeframe: Baseline, Week 8 or Early terminationPopulation: Participants randomly assigned to treatment who took at least one dose of the study drug in the double-blind period and who had both baseline and at least one post-baseline measurements of the primary efficacy variable.
HAM-D17 is a standardized, clinician-administered rating scale that assesses 17 items characteristically associated with major depression (symptoms such as depressed mood, work and activities, sleep, suicide, psychomotor agitation/retardation, appetite, sexual interest, anxiety, and somatic symptoms). The items of the HAM-D17 are rated on a scale of 0 to 2 or 0 to 4, and the total score ranges from 0 to 52. Higher scores indicate more severe symptoms. Change from baseline: mean score at Week 8 or early termination minus mean score at baseline.
Outcome measures
| Measure |
Placebo
n=184 Participants
Participants received placebo capsule orally once daily after meal for 8 weeks.
|
Venlafaxine 75 mg/Day Fixed
n=174 Participants
Participants received venlafaxine ER capsule orally once daily after meal for 8 weeks. Starting dose was 37.5 mg/day followed by 75 mg/day at Week 1. If there was no tolerability concern at Week 2, the dose was continued 75 mg/day until Week 8.
|
Venlafaxine 75-225 mg/Day Flexible
n=177 Participants
Participants received venlafaxine ER capsule orally once daily after meal for 8 weeks. Starting dose was 37.5 mg/day followed by 75 mg/day at Week 1. If there was no tolerability concern at Week 2, the dose was increased to 150 mg/day. If there was no tolerability concern at Week 3, the dose was increased to 225 mg/day. Dose was reduced in the case of intolerability and if the participants could not take venlafaxine 75 mg/day or higher doses at Week 1 and the following weeks, the treatment were discontinued. No dose adjustment was allowed from Week 4 to Week 8.
|
|---|---|---|---|
|
Change From Baseline in 17-item Hamilton Raing Scale for Depression (HAM-D17) Total Score at Week 8 or Early Termination
|
-9.25 Units on a scale
Standard Error 0.48
|
-10.76 Units on a scale
Standard Error 0.50
|
-10.37 Units on a scale
Standard Error 0.49
|
SECONDARY outcome
Timeframe: Baseline, Week 8 or Early terminationPopulation: Participants randomly assigned to treatment who took at least one dose of the study drug in the double-blind period and who had both baseline and at least one post-baseline measurements of the primary efficacy variable.
MADRS is a scale used in subjects with major depressive disorder to measure the overall severity of depressive symptoms. It is a 10 item, clinician-rated scale that assesses treatment-sensitive change by evaluating ten areas of depressive symptomatology: apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, suicidal thoughts. The items are rated on a 7 point Likert scale (0 - 6) with anchors at 2 point intervals. The total score ranges from 0 to 60, and higher scores indicate more severe symptoms. Change from baseline: mean score at Week 8 or early termination minus mean score at baseline.
Outcome measures
| Measure |
Placebo
n=182 Participants
Participants received placebo capsule orally once daily after meal for 8 weeks.
|
Venlafaxine 75 mg/Day Fixed
n=172 Participants
Participants received venlafaxine ER capsule orally once daily after meal for 8 weeks. Starting dose was 37.5 mg/day followed by 75 mg/day at Week 1. If there was no tolerability concern at Week 2, the dose was continued 75 mg/day until Week 8.
|
Venlafaxine 75-225 mg/Day Flexible
n=176 Participants
Participants received venlafaxine ER capsule orally once daily after meal for 8 weeks. Starting dose was 37.5 mg/day followed by 75 mg/day at Week 1. If there was no tolerability concern at Week 2, the dose was increased to 150 mg/day. If there was no tolerability concern at Week 3, the dose was increased to 225 mg/day. Dose was reduced in the case of intolerability and if the participants could not take venlafaxine 75 mg/day or higher doses at Week 1 and the following weeks, the treatment were discontinued. No dose adjustment was allowed from Week 4 to Week 8.
|
|---|---|---|---|
|
Changes From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score at Week 8 or Early Termination
|
-12.41 Units on a scale
Standard Error 0.75
|
-15.30 Units on a scale
Standard Error 0.77
|
-15.05 Units on a scale
Standard Error 0.76
|
SECONDARY outcome
Timeframe: Baseline, Week 8 or Early terminationPopulation: Participants randomly assigned to treatment who took at least one dose of the study drug in the double-blind period and who had both baseline and at least one post-baseline measurements of the primary efficacy variable.
CGI-S is a 7-point clinician rated scale to assess severity of participant's current illness state; range: 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. Higher scores reflect higher severity of current illness states. Change from baseline: mean score at Week 8 or early termination minus mean score at baseline.
Outcome measures
| Measure |
Placebo
n=184 Participants
Participants received placebo capsule orally once daily after meal for 8 weeks.
|
Venlafaxine 75 mg/Day Fixed
n=174 Participants
Participants received venlafaxine ER capsule orally once daily after meal for 8 weeks. Starting dose was 37.5 mg/day followed by 75 mg/day at Week 1. If there was no tolerability concern at Week 2, the dose was continued 75 mg/day until Week 8.
|
Venlafaxine 75-225 mg/Day Flexible
n=177 Participants
Participants received venlafaxine ER capsule orally once daily after meal for 8 weeks. Starting dose was 37.5 mg/day followed by 75 mg/day at Week 1. If there was no tolerability concern at Week 2, the dose was increased to 150 mg/day. If there was no tolerability concern at Week 3, the dose was increased to 225 mg/day. Dose was reduced in the case of intolerability and if the participants could not take venlafaxine 75 mg/day or higher doses at Week 1 and the following weeks, the treatment were discontinued. No dose adjustment was allowed from Week 4 to Week 8.
|
|---|---|---|---|
|
Changes From Baseline in Clinical Global Impression-Severity (CGI-S) at Week 8 or Early Termination
|
-1.31 Units on a scale
Standard Error 0.08
|
-1.57 Units on a scale
Standard Error 0.08
|
-1.56 Units on a scale
Standard Error 0.08
|
SECONDARY outcome
Timeframe: Baseline, Week 8 or Early terminationPopulation: Participants randomly assigned to treatment who took at least one dose of the study drug in the double-blind period and who had both baseline and at least one post-baseline measurements of the primary efficacy variable.
HAM-D6 is a subset of the HAM-D17 that assesses 6 items associated with major depression. The scale uses HAM-D17 items 1, 2, 7, 8, 10 and 13. Item 13 is scored 0 to 2 and all others are scored 0 to 4. Total score ranges from 0 to 22; higher score indicates more depression. Change from baseline: mean score at Week 8 or early termination minus mean score at baseline.
Outcome measures
| Measure |
Placebo
n=184 Participants
Participants received placebo capsule orally once daily after meal for 8 weeks.
|
Venlafaxine 75 mg/Day Fixed
n=174 Participants
Participants received venlafaxine ER capsule orally once daily after meal for 8 weeks. Starting dose was 37.5 mg/day followed by 75 mg/day at Week 1. If there was no tolerability concern at Week 2, the dose was continued 75 mg/day until Week 8.
|
Venlafaxine 75-225 mg/Day Flexible
n=177 Participants
Participants received venlafaxine ER capsule orally once daily after meal for 8 weeks. Starting dose was 37.5 mg/day followed by 75 mg/day at Week 1. If there was no tolerability concern at Week 2, the dose was increased to 150 mg/day. If there was no tolerability concern at Week 3, the dose was increased to 225 mg/day. Dose was reduced in the case of intolerability and if the participants could not take venlafaxine 75 mg/day or higher doses at Week 1 and the following weeks, the treatment were discontinued. No dose adjustment was allowed from Week 4 to Week 8.
|
|---|---|---|---|
|
Changes From Baseline in 6-item Hamilton Rating Scale for Depression (HAM-D6) Total Score at Week 8 or Early Termination
|
-4.92 Units on a scale
Standard Error 0.28
|
-6.10 Units on a scale
Standard Error 0.29
|
-5.99 Units on a scale
Standard Error 0.29
|
SECONDARY outcome
Timeframe: Baseline, Week 8 or Early terminationPopulation: Participants randomly assigned to treatment who took at least one dose of the study drug in the double-blind period and who had both baseline and at least one post-baseline measurements of the primary efficacy variable.
QIDS16-SR-J is a self-rated scale used in patients with major depressive disorder to measure the overall severity of depressive symptoms: 1) sad mood; 2) concentration; 3) self-criticism; 4) suicidal ideation; 5) interest; 6) energy/fatigue; 7) sleep disturbance (initial, middle, and late insomnia or hypersomnia); 8) decrease/increase in appetite/weight; and 9) psychomotor agitation/retardation. QIDS16-SR-J items are rated on a scale of 0 to 3. The total score ranges from 0 to 27, and higher scores indicate more severe symptoms. Change from baseline: mean score at Week 8 or early termination minus mean score at baseline.
Outcome measures
| Measure |
Placebo
n=182 Participants
Participants received placebo capsule orally once daily after meal for 8 weeks.
|
Venlafaxine 75 mg/Day Fixed
n=172 Participants
Participants received venlafaxine ER capsule orally once daily after meal for 8 weeks. Starting dose was 37.5 mg/day followed by 75 mg/day at Week 1. If there was no tolerability concern at Week 2, the dose was continued 75 mg/day until Week 8.
|
Venlafaxine 75-225 mg/Day Flexible
n=175 Participants
Participants received venlafaxine ER capsule orally once daily after meal for 8 weeks. Starting dose was 37.5 mg/day followed by 75 mg/day at Week 1. If there was no tolerability concern at Week 2, the dose was increased to 150 mg/day. If there was no tolerability concern at Week 3, the dose was increased to 225 mg/day. Dose was reduced in the case of intolerability and if the participants could not take venlafaxine 75 mg/day or higher doses at Week 1 and the following weeks, the treatment were discontinued. No dose adjustment was allowed from Week 4 to Week 8.
|
|---|---|---|---|
|
Changes From Baseline in 16-item Quick Inventory of Depressive Symptomatology Self-Report Japanese Version (QIDS16-SR-J) Total Score at Week 8 or Early Termination
|
-6.50 Units on a scale
Standard Error 0.36
|
-8.00 Units on a scale
Standard Error 0.37
|
-7.27 Units on a scale
Standard Error 0.37
|
SECONDARY outcome
Timeframe: Baseline, Week 8 or Early terminationPopulation: Participants randomly assigned to treatment who took at least one dose of the study drug in the double-blind period and who had both baseline and at least one post-baseline measurements of the primary efficacy variable.
CGI-I is a 7-point clinician rated scale ranging from 1=very much improved, 2=much improved, 3=minimally improved, 4=no change, 5=minimally worse, 6=much worse, 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. Scores above 4 reflect worsening of illness state as compared to baseline.
Outcome measures
| Measure |
Placebo
n=184 Participants
Participants received placebo capsule orally once daily after meal for 8 weeks.
|
Venlafaxine 75 mg/Day Fixed
n=174 Participants
Participants received venlafaxine ER capsule orally once daily after meal for 8 weeks. Starting dose was 37.5 mg/day followed by 75 mg/day at Week 1. If there was no tolerability concern at Week 2, the dose was continued 75 mg/day until Week 8.
|
Venlafaxine 75-225 mg/Day Flexible
n=177 Participants
Participants received venlafaxine ER capsule orally once daily after meal for 8 weeks. Starting dose was 37.5 mg/day followed by 75 mg/day at Week 1. If there was no tolerability concern at Week 2, the dose was increased to 150 mg/day. If there was no tolerability concern at Week 3, the dose was increased to 225 mg/day. Dose was reduced in the case of intolerability and if the participants could not take venlafaxine 75 mg/day or higher doses at Week 1 and the following weeks, the treatment were discontinued. No dose adjustment was allowed from Week 4 to Week 8.
|
|---|---|---|---|
|
Mean Clinical Global Impression - Improvement (CGI-I) Score at Week 8 or Early Termination
|
2.53 Units on a scale
Standard Error 0.08
|
2.32 Units on a scale
Standard Error 0.09
|
2.28 Units on a scale
Standard Error 0.08
|
Adverse Events
Placebo
Venlafaxine 75 mg/Day Fixed
Venlafaxine 75-225 mg/Day Flexible
Serious adverse events
| Measure |
Placebo
n=183 participants at risk
Participants received placebo capsule orally once daily after meal for 8 weeks.
|
Venlafaxine 75 mg/Day Fixed
n=174 participants at risk
Participants received venlafaxine ER capsule orally once daily after meal for 8 weeks. Starting dose was 37.5 mg/day followed by 75 mg/day at Week 1. If there was no tolerability concern at Week 2, the dose was continued 75 mg/day until Week 8.
|
Venlafaxine 75-225 mg/Day Flexible
n=180 participants at risk
Participants received venlafaxine ER capsule orally once daily after meal for 8 weeks. Starting dose was 37.5 mg/day followed by 75 mg/day at Week 1. If there was no tolerability concern at Week 2, the dose was increased to 150 mg/day. If there was no tolerability concern at Week 3, the dose was increased to 225 mg/day. Dose was reduced in the case of intolerability and if the participants could not take venlafaxine 75 mg/day or higher doses at Week 1 and the following weeks, the treatment were discontinued. No dose adjustment was allowed from Week 4 to Week 8.
|
|---|---|---|---|
|
Ear and labyrinth disorders
Meniere's disease
|
0.00%
0/183
|
0.57%
1/174
|
0.00%
0/180
|
|
Psychiatric disorders
Completed suicide
|
0.55%
1/183
|
0.00%
0/174
|
0.56%
1/180
|
|
Blood and lymphatic system disorders
Anaemia
|
0.55%
1/183
|
0.00%
0/174
|
0.00%
0/180
|
Other adverse events
| Measure |
Placebo
n=183 participants at risk
Participants received placebo capsule orally once daily after meal for 8 weeks.
|
Venlafaxine 75 mg/Day Fixed
n=174 participants at risk
Participants received venlafaxine ER capsule orally once daily after meal for 8 weeks. Starting dose was 37.5 mg/day followed by 75 mg/day at Week 1. If there was no tolerability concern at Week 2, the dose was continued 75 mg/day until Week 8.
|
Venlafaxine 75-225 mg/Day Flexible
n=180 participants at risk
Participants received venlafaxine ER capsule orally once daily after meal for 8 weeks. Starting dose was 37.5 mg/day followed by 75 mg/day at Week 1. If there was no tolerability concern at Week 2, the dose was increased to 150 mg/day. If there was no tolerability concern at Week 3, the dose was increased to 225 mg/day. Dose was reduced in the case of intolerability and if the participants could not take venlafaxine 75 mg/day or higher doses at Week 1 and the following weeks, the treatment were discontinued. No dose adjustment was allowed from Week 4 to Week 8.
|
|---|---|---|---|
|
Cardiac disorders
Palpitations
|
2.7%
5/183
|
4.6%
8/174
|
3.3%
6/180
|
|
Cardiac disorders
Tachycardia
|
0.00%
0/183
|
2.3%
4/174
|
3.9%
7/180
|
|
Ear and labyrinth disorders
Vertigo
|
1.1%
2/183
|
2.3%
4/174
|
3.3%
6/180
|
|
Gastrointestinal disorders
Abdominal discomfort
|
2.2%
4/183
|
4.0%
7/174
|
6.1%
11/180
|
|
Gastrointestinal disorders
Abdominal pain upper
|
3.8%
7/183
|
2.9%
5/174
|
0.00%
0/180
|
|
Gastrointestinal disorders
Constipation
|
4.4%
8/183
|
9.8%
17/174
|
9.4%
17/180
|
|
Gastrointestinal disorders
Diarrhoea
|
3.8%
7/183
|
3.4%
6/174
|
4.4%
8/180
|
|
Gastrointestinal disorders
Dry mouth
|
0.55%
1/183
|
2.9%
5/174
|
3.9%
7/180
|
|
Gastrointestinal disorders
Nausea
|
13.1%
24/183
|
22.4%
39/174
|
29.4%
53/180
|
|
Gastrointestinal disorders
Vomiting
|
3.8%
7/183
|
2.9%
5/174
|
2.2%
4/180
|
|
General disorders
Feeling abnormal
|
0.00%
0/183
|
1.1%
2/174
|
2.2%
4/180
|
|
General disorders
Malaise
|
2.7%
5/183
|
5.2%
9/174
|
6.1%
11/180
|
|
General disorders
Thirst
|
7.7%
14/183
|
6.3%
11/174
|
10.0%
18/180
|
|
Infections and infestations
Nasopharyngitis
|
22.4%
41/183
|
20.1%
35/174
|
17.8%
32/180
|
|
Investigations
Alanine aminotransferase increased
|
0.00%
0/183
|
2.3%
4/174
|
1.1%
2/180
|
|
Investigations
Blood pressure increased
|
1.1%
2/183
|
2.3%
4/174
|
2.8%
5/180
|
|
Investigations
Heart rate increased
|
2.2%
4/183
|
5.7%
10/174
|
7.2%
13/180
|
|
Metabolism and nutrition disorders
Decreased appetite
|
0.55%
1/183
|
2.3%
4/174
|
2.2%
4/180
|
|
Nervous system disorders
Dizziness
|
2.7%
5/183
|
5.7%
10/174
|
10.0%
18/180
|
|
Nervous system disorders
Dizziness postural
|
0.55%
1/183
|
1.1%
2/174
|
2.8%
5/180
|
|
Nervous system disorders
Headache
|
7.7%
14/183
|
9.2%
16/174
|
10.0%
18/180
|
|
Nervous system disorders
Somnolence
|
8.2%
15/183
|
12.1%
21/174
|
17.2%
31/180
|
|
Psychiatric disorders
Insomnia
|
3.3%
6/183
|
2.3%
4/174
|
4.4%
8/180
|
|
Renal and urinary disorders
Pollakiuria
|
0.00%
0/183
|
1.1%
2/174
|
2.8%
5/180
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
1.1%
2/183
|
1.7%
3/174
|
8.3%
15/180
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
- Publication restrictions are in place
Restriction type: OTHER