Trial Outcomes & Findings for To Evaluate Ezetimibe Plus Atorvastatin Versus Atorvastatin in Patients With High Cholesterol Not Controlled on Atorvastatin 20 mg (0653-079)(COMPLETED) (NCT NCT00276458)
NCT ID: NCT00276458
Last Updated: 2024-05-13
Results Overview
\[(6 week value - baseline value)/baseline value\]\*100%.
COMPLETED
PHASE3
196 participants
6 weeks
2024-05-13
Participant Flow
Phase III First Patient In: 4/5/2006; Last Patient Last Visit 1/17/2008 72 centers worldwide (US, Canada, Austria, Costa Rica) Eligible patients include those on a stable dose of atorvastatin 20 mg; or patients with adjusted LDL-C pre-screen ranges who were treated with other lipid modifying therapy, or were statin and/or ezetimibe naïve.
Patients received and were blinded to atorvastatin 20 mg for a 4/5- week run-in period. Patients needed an LDL-C ≥ 100 mg/dL and ≤ 160 mg/dL at Visit 2 (week -1). Eligible patients were randomized at Visit 3 (Week 0) to either atorvastatin 40 mg or addition of ezetimibe 10 mg to their 20 mg dose of atorvastatin for a 6-week treatment period.
Participant milestones
| Measure |
Atorvastatin + Ezetimibe
Atorvastatin 20 mg + Ezetemibe 10 mg daily for 6 weeks
|
Atorvastatin
Atorvastatin 40 mg Daily for 6 weeks
|
|---|---|---|
|
Overall Study
STARTED
|
98
|
98
|
|
Overall Study
COMPLETED
|
92
|
91
|
|
Overall Study
NOT COMPLETED
|
6
|
7
|
Reasons for withdrawal
| Measure |
Atorvastatin + Ezetimibe
Atorvastatin 20 mg + Ezetemibe 10 mg daily for 6 weeks
|
Atorvastatin
Atorvastatin 40 mg Daily for 6 weeks
|
|---|---|---|
|
Overall Study
Adverse Event
|
0
|
2
|
|
Overall Study
Lost to Follow-up
|
2
|
2
|
|
Overall Study
Protocol Violation
|
4
|
3
|
Baseline Characteristics
To Evaluate Ezetimibe Plus Atorvastatin Versus Atorvastatin in Patients With High Cholesterol Not Controlled on Atorvastatin 20 mg (0653-079)(COMPLETED)
Baseline characteristics by cohort
| Measure |
Atorvastatin + Ezetimibe
n=98 Participants
Atorvastatin 20 mg + Ezetemibe 10 mg daily for 6 weeks
|
Atorvastatin
n=98 Participants
Atorvastatin 40 mg Daily for 6 weeks
|
Total
n=196 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
56.4 years
n=39 Participants
|
58.0 years
n=41 Participants
|
57.2 years
n=35 Participants
|
|
Sex: Female, Male
Female
|
40 Participants
n=39 Participants
|
49 Participants
n=41 Participants
|
89 Participants
n=35 Participants
|
|
Sex: Female, Male
Male
|
58 Participants
n=39 Participants
|
49 Participants
n=41 Participants
|
107 Participants
n=35 Participants
|
|
Race/Ethnicity, Customized
White
|
58 participants
n=39 Participants
|
60 participants
n=41 Participants
|
118 participants
n=35 Participants
|
|
Race/Ethnicity, Customized
American Indian or Alaska Native
|
1 participants
n=39 Participants
|
0 participants
n=41 Participants
|
1 participants
n=35 Participants
|
|
Race/Ethnicity, Customized
Asian
|
7 participants
n=39 Participants
|
8 participants
n=41 Participants
|
15 participants
n=35 Participants
|
|
Race/Ethnicity, Customized
Black
|
3 participants
n=39 Participants
|
9 participants
n=41 Participants
|
12 participants
n=35 Participants
|
|
Race/Ethnicity, Customized
Multi-Racial
|
29 participants
n=39 Participants
|
21 participants
n=41 Participants
|
50 participants
n=35 Participants
|
|
Apolipoprotein A-I
|
161.8 mg/dL
STANDARD_DEVIATION 25.2 • n=39 Participants
|
163.4 mg/dL
STANDARD_DEVIATION 24.6 • n=41 Participants
|
162.6 mg/dL
STANDARD_DEVIATION 24.8 • n=35 Participants
|
|
Apolipoprotein A-I:Apolipoprotein B ratio
|
0.8 Ratio
STANDARD_DEVIATION 0.2 • n=39 Participants
|
0.7 Ratio
STANDARD_DEVIATION 0.2 • n=41 Participants
|
0.8 Ratio
STANDARD_DEVIATION 0.2 • n=35 Participants
|
|
Apolipoprotein B
|
122.9 mg/dL
STANDARD_DEVIATION 22.4 • n=39 Participants
|
119.9 mg/dL
STANDARD_DEVIATION 21.0 • n=41 Participants
|
121.4 mg/dL
STANDARD_DEVIATION 21.7 • n=35 Participants
|
|
C Reactive Protein
|
1.6 mg/dL
STANDARD_DEVIATION 2.6 • n=39 Participants
|
1.2 mg/dL
STANDARD_DEVIATION 1.7 • n=41 Participants
|
1.5 mg/dL
STANDARD_DEVIATION 2.1 • n=35 Participants
|
|
High Density Lipoprotein (HDL)
|
51.1 mg/dL
STANDARD_DEVIATION 12.1 • n=39 Participants
|
51.7 mg/dL
STANDARD_DEVIATION 11.5 • n=41 Participants
|
51.4 mg/dL
STANDARD_DEVIATION 11.8 • n=35 Participants
|
|
Low Density Lipoprotein (LDL)
|
119.9 mg/dL
STANDARD_DEVIATION 19.4 • n=39 Participants
|
117.9 mg/dL
STANDARD_DEVIATION 16.8 • n=41 Participants
|
118.9 mg/dL
STANDARD_DEVIATION 18.1 • n=35 Participants
|
|
Low Density Lipoprotein Cholesterol (LDL-C):High Density Lipoprotein Cholesterol (HDL-C) ratio
|
2.4 Ratio
STANDARD_DEVIATION 0.6 • n=39 Participants
|
2.5 Ratio
STANDARD_DEVIATION 0.7 • n=41 Participants
|
2.4 Ratio
STANDARD_DEVIATION 0.7 • n=35 Participants
|
|
Non- High Density Lipoprotein (Non-HDL) Cholesterol
|
151.6 mg/dL
STANDARD_DEVIATION 24.1 • n=39 Participants
|
148.4 mg/dL
STANDARD_DEVIATION 21.1 • n=41 Participants
|
150.0 mg/dL
STANDARD_DEVIATION 22.7 • n=35 Participants
|
|
NonHigh Density Lipoprotein-Cholesterol (NonHDL-C):High Density Lipoprotein-Cholesterol (HDL-C)ratio
|
3.2 Ratio
STANDARD_DEVIATION 1.0 • n=39 Participants
|
3.0 Ratio
STANDARD_DEVIATION 0.9 • n=41 Participants
|
3.1 Ratio
STANDARD_DEVIATION 1.0 • n=35 Participants
|
|
Total Cholesterol
|
202.6 mg/dL
STANDARD_DEVIATION 25.2 • n=39 Participants
|
200.0 mg/dL
STANDARD_DEVIATION 21.5 • n=41 Participants
|
201.3 mg/dL
STANDARD_DEVIATION 23.4 • n=35 Participants
|
|
Total cholesterol:High Density Lipoprotein Cholesterol (HDL-C) ratio
|
4.2 Ratio
STANDARD_DEVIATION 1.0 • n=39 Participants
|
4.0 Ratio
STANDARD_DEVIATION 0.9 • n=41 Participants
|
4.1 Ratio
STANDARD_DEVIATION 1.0 • n=35 Participants
|
|
Triglycerides (TG)
|
152.5 mg/dL
STANDARD_DEVIATION 68.8 • n=39 Participants
|
147.8 mg/dL
STANDARD_DEVIATION 75.3 • n=41 Participants
|
149.0 mg/dL
STANDARD_DEVIATION 75.3 • n=35 Participants
|
PRIMARY outcome
Timeframe: 6 weeksPopulation: Full Analysis Set (FAS): The FAS population includes all randomized patients who took at least 1 dose of study medication and had a baseline (BL) value and at least one post BL value. Post BL measurements up to 3 days following the last dose of double-blind study medication were included in the analysis.
\[(6 week value - baseline value)/baseline value\]\*100%.
Outcome measures
| Measure |
Atorvastatin + Ezetimibe
n=92 Participants
Atorvastatin 20 mg + Ezetemibe 10 mg daily for 6 weeks
|
Atorvastatin
n=92 Participants
Atorvastatin 40 mg Daily for 6 weeks
|
|---|---|---|
|
Percent Change From Baseline in Low Density Lipoprotein-Cholesterol (LDL-C) at Week 6
|
-30.8 Percent
Interval -34.5 to -27.0
|
-10.9 Percent
Interval -14.7 to -7.1
|
SECONDARY outcome
Timeframe: 6 weeksPopulation: Full Analysis Set (FAS): The FAS population includes all randomized patients who took at least 1 dose of study medication and had a baseline (BL) value and at least one post BL value. Post BL measurements up to 3 days following the last dose of double-blind study medication were included in the analysis.
\[(6 week value - baseline value)/baseline value\]\*100%.
Outcome measures
| Measure |
Atorvastatin + Ezetimibe
n=92 Participants
Atorvastatin 20 mg + Ezetemibe 10 mg daily for 6 weeks
|
Atorvastatin
n=92 Participants
Atorvastatin 40 mg Daily for 6 weeks
|
|---|---|---|
|
Percent Change in High Density Lipoprotein -Cholesterol (HDL-C)at Week 6
|
3.2 Percent
Interval 0.2 to 6.2
|
0.8 Percent
Interval -2.2 to 3.8
|
SECONDARY outcome
Timeframe: 6 WeeksPopulation: Full Analysis Set (FAS): The FAS population includes all randomized patients who took at least 1 dose of study medication and had a baseline (BL) value and at least one post BL value. Post BL measurements up to 3 days following the last dose of double-blind study medication were included in the analysis.
\[(6 week value - baseline value)/baseline value\]\*100%.
Outcome measures
| Measure |
Atorvastatin + Ezetimibe
n=92 Participants
Atorvastatin 20 mg + Ezetemibe 10 mg daily for 6 weeks
|
Atorvastatin
n=92 Participants
Atorvastatin 40 mg Daily for 6 weeks
|
|---|---|---|
|
Percent Change in Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 6
|
-26.7 Percent
Interval -30.1 to -23.3
|
-10.2 Percent
Interval -13.6 to -6.9
|
SECONDARY outcome
Timeframe: 6 WeeksPopulation: Full Analysis Set (FAS): The FAS population includes all randomized patients who took at least 1 dose of study medication and had a baseline (BL) value and at least one post BL value. Post BL measurements up to 3 days following the last dose of double-blind study medication were included in the analysis.
(\[6 week value - baseline value)/baseline value\]\*100%.
Outcome measures
| Measure |
Atorvastatin + Ezetimibe
n=92 Participants
Atorvastatin 20 mg + Ezetemibe 10 mg daily for 6 weeks
|
Atorvastatin
n=92 Participants
Atorvastatin 40 mg Daily for 6 weeks
|
|---|---|---|
|
Percent Change From Baseline in Total-Cholesterol at Week 6
|
-19.7 percent
Interval -22.2 to -17.1
|
-7.4 percent
Interval -10.0 to -4.9
|
SECONDARY outcome
Timeframe: 6 weeksPopulation: Full Analysis Set (FAS): The FAS population includes all randomized patients who took at least 1 dose of study medication and had a baseline (BL) value and at least one post BL value. Post BL measurements up to 3 days following the last dose of double-blind study medication were included in the analysis.
\[(6 week value - baseline value)/baseline value\]\*100%.
Outcome measures
| Measure |
Atorvastatin + Ezetimibe
n=92 Participants
Atorvastatin 20 mg + Ezetemibe 10 mg daily for 6 weeks
|
Atorvastatin
n=92 Participants
Atorvastatin 40 mg Daily for 6 weeks
|
|---|---|---|
|
Percent Change From Baseline in Triglycerides (TG) at Week 6
|
-17.8 Percent
Interval -23.7 to -11.4
|
-5.5 Percent
Interval -14.4 to 0.0
|
SECONDARY outcome
Timeframe: 6 WeeksPopulation: Full Analysis Set (FAS): The FAS population includes all randomized patients who took at least 1 dose of study medication and had a baseline (BL) value and at least one post BL value. Post BL measurements up to 3 days following the last dose of double-blind study medication were included in the analysis.
\[(6 week value - baseline value)/baseline value\]\*100%.
Outcome measures
| Measure |
Atorvastatin + Ezetimibe
n=89 Participants
Atorvastatin 20 mg + Ezetemibe 10 mg daily for 6 weeks
|
Atorvastatin
n=90 Participants
Atorvastatin 40 mg Daily for 6 weeks
|
|---|---|---|
|
Percent Change From Baseline in Apolipoprotein B at Week 6
|
-21.4 Percent
Interval -24.3 to -18.5
|
-7.7 Percent
Interval -10.6 to -4.8
|
SECONDARY outcome
Timeframe: 6 WeeksPopulation: Full Analysis Set (FAS): The FAS population includes all randomized patients who took at least 1 dose of study medication and had a baseline (BL) value and at least one post BL value. Post BL measurements up to 3 days following the last dose of double-blind study medication were included in the analysis.
\[(6 week value - baseline value)/baseline value\]\*100%.
Outcome measures
| Measure |
Atorvastatin + Ezetimibe
n=92 Participants
Atorvastatin 20 mg + Ezetemibe 10 mg daily for 6 weeks
|
Atorvastatin
n=92 Participants
Atorvastatin 40 mg Daily for 6 weeks
|
|---|---|---|
|
Percent Change From Baseline in Total-Cholesterol:High Density Lipoprotein Cholesterol (HDL-C) Ratio at Week 6
|
-20.6 Percent
Interval -23.7 to -17.5
|
-7.5 Percent
Interval -10.6 to -4.4
|
SECONDARY outcome
Timeframe: 6 WeeksPopulation: Full Analysis Set (FAS): The FAS population includes all randomized patients who took at least 1 dose of study medication and had a baseline (BL) value and at least one post BL value. Post BL measurements up to 3 days following the last dose of double-blind study medication were included in the analysis.
\[(6 week value - baseline value)/baseline value\]\*100%.
Outcome measures
| Measure |
Atorvastatin + Ezetimibe
n=92 Participants
Atorvastatin 20 mg + Ezetemibe 10 mg daily for 6 weeks
|
Atorvastatin
n=92 Participants
Atorvastatin 40 mg Daily for 6 weeks
|
|---|---|---|
|
Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C):High Density Lipoprotein Cholesterol (HDL-C) Ratio at Week 6
|
-31.9 Percent
Interval -35.8 to -27.9
|
-11.0 Percent
Interval -14.9 to -7.0
|
SECONDARY outcome
Timeframe: 6 WeeksPopulation: Full Analysis Set (FAS): The FAS population includes all randomized patients who took at least 1 dose of study medication and had a baseline (BL) value and at least one post BL value. Post BL measurements up to 3 days following the last dose of double-blind study medication were included in the analysis.
\[(6 week value - baseline value)/baseline value\]\*100%.
Outcome measures
| Measure |
Atorvastatin + Ezetimibe
n=89 Participants
Atorvastatin 20 mg + Ezetemibe 10 mg daily for 6 weeks
|
Atorvastatin
n=90 Participants
Atorvastatin 40 mg Daily for 6 weeks
|
|---|---|---|
|
Percent Change From Baseline in Apolipoprotein B: Apolipoprotein A-I Ratio at Week 6
|
-19.0 Percent
Interval -22.3 to -15.6
|
-5.8 Percent
Interval -9.2 to -2.5
|
SECONDARY outcome
Timeframe: 6 WeeksPopulation: Full Analysis Set (FAS): The FAS population includes all randomized patients who took at least 1 dose of study medication and had a baseline (BL) value and at least one post BL value. Post BL measurements up to 3 days following the last dose of double-blind study medication were included in the analysis.
\[(6 week value - baseline value)/baseline value\]\*100%.
Outcome measures
| Measure |
Atorvastatin + Ezetimibe
n=92 Participants
Atorvastatin 20 mg + Ezetemibe 10 mg daily for 6 weeks
|
Atorvastatin
n=92 Participants
Atorvastatin 40 mg Daily for 6 weeks
|
|---|---|---|
|
Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (HDL-C):High Density Lipoprotein Cholesterol (HDL-C) Ratio at Week 6
|
-27.2 Percent
Interval -31.4 to -23.0
|
-9.9 Percent
Interval -14.1 to -5.7
|
SECONDARY outcome
Timeframe: 6 WeeksPopulation: Full Analysis Set (FAS): The FAS population includes all randomized patients who took at least 1 dose of study medication and had a baseline (BL) value and at least one post BL value. Post BL measurements up to 3 days following the last dose of double-blind study medication were included in the analysis.
\[(6 week value - baseline value)/baseline value\]\*100%.
Outcome measures
| Measure |
Atorvastatin + Ezetimibe
n=89 Participants
Atorvastatin 20 mg + Ezetemibe 10 mg daily for 6 weeks
|
Atorvastatin
n=89 Participants
Atorvastatin 40 mg Daily for 6 weeks
|
|---|---|---|
|
Percent Change From Baseline in C-Reactive Protein (CRP) at Week 6
|
-6.7 percent
Interval -23.7 to 14.2
|
-9.2 percent
Interval -25.8 to 11.1
|
SECONDARY outcome
Timeframe: 6 weeksPopulation: Full Analysis Set (FAS): The FAS population includes all randomized patients who took at least 1 dose of study medication and had a baseline (BL) value and at least one post BL value. Post BL measurements up to 3 days following the last dose of double-blind study medication were included in the analysis.
Outcome measures
| Measure |
Atorvastatin + Ezetimibe
n=92 Participants
Atorvastatin 20 mg + Ezetemibe 10 mg daily for 6 weeks
|
Atorvastatin
n=92 Participants
Atorvastatin 40 mg Daily for 6 weeks
|
|---|---|---|
|
Number of Participants Who Attained Target LDL-C <100 mg/dL at Week 6
<100 mg/dL
|
77 Participants
|
45 Participants
|
|
Number of Participants Who Attained Target LDL-C <100 mg/dL at Week 6
≥100 mg/dL
|
15 Participants
|
47 Participants
|
POST_HOC outcome
Timeframe: 6 WeeksPopulation: Full Analysis Set (FAS): The FAS population includes all randomized patients who took at least 1 dose of study medication and had a baseline (BL) value and at least one post BL value. Post BL measurements up to 3 days following the last dose of double-blind study medication were included in the analysis.
\[(6 week value - baseline value)/baseline value\]\*100%.
Outcome measures
| Measure |
Atorvastatin + Ezetimibe
n=89 Participants
Atorvastatin 20 mg + Ezetemibe 10 mg daily for 6 weeks
|
Atorvastatin
n=90 Participants
Atorvastatin 40 mg Daily for 6 weeks
|
|---|---|---|
|
Percent Change in Apolipoprotein A-I at Week 6
|
-1.9 Percent
Interval -4.2 to 0.4
|
-1.2 Percent
Interval -3.5 to 1.1
|
POST_HOC outcome
Timeframe: 6 weeksPopulation: Full Analysis Set (FAS): The FAS population includes all randomized patients who took at least 1 dose of study medication and had a baseline (BL) value and at least one post BL value. Post BL measurements up to 3 days following the last dose of double-blind study medication were included in the analysis.
\[(6 week value - baseline value)/baseline value\]\*100%.
Outcome measures
| Measure |
Atorvastatin + Ezetimibe
n=89 Participants
Atorvastatin 20 mg + Ezetemibe 10 mg daily for 6 weeks
|
Atorvastatin
n=89 Participants
Atorvastatin 40 mg Daily for 6 weeks
|
|---|---|---|
|
Percent Change in C-Reactive Protein (CRP) at Week 6
|
-19.2 Percent
Interval -25.0 to -4.0
|
-9.1 Percent
Interval -22.2 to 5.3
|
Adverse Events
Atorvastatin + Ezetimibe
Atorvastatin
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Atorvastatin + Ezetimibe
n=96 participants at risk
Atorvastatin 20 mg + Ezetemibe 10 mg daily for 6 weeks
|
Atorvastatin
n=98 participants at risk
Atorvastatin 40 mg Daily for 6 weeks
|
|---|---|---|
|
Ear and labyrinth disorders
Vertigo
|
2.1%
2/96
|
0.00%
0/98
|
|
Gastrointestinal disorders
Abdominal tenderness
|
1.0%
1/96
|
0.00%
0/98
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/96
|
1.0%
1/98
|
|
Gastrointestinal disorders
Gastrointestinal Disorder
|
0.00%
0/96
|
1.0%
1/98
|
|
Gastrointestinal disorders
Irritable bowel syndrome
|
0.00%
0/96
|
2.0%
2/98
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/96
|
1.0%
1/98
|
|
General disorders
Chest Discomfort
|
1.0%
1/96
|
0.00%
0/98
|
|
General disorders
Fatigue
|
2.1%
2/96
|
1.0%
1/98
|
|
General disorders
Edema
|
1.0%
1/96
|
0.00%
0/98
|
|
Infections and infestations
Gastroenteritis
|
1.0%
1/96
|
1.0%
1/98
|
|
Infections and infestations
Influenza
|
0.00%
0/96
|
1.0%
1/98
|
|
Infections and infestations
Nasopharyngitis
|
2.1%
2/96
|
0.00%
0/98
|
|
Infections and infestations
Oral herpes
|
1.0%
1/96
|
0.00%
0/98
|
|
Infections and infestations
Sinusitis
|
0.00%
0/96
|
1.0%
1/98
|
|
Infections and infestations
Upper respiratory tract infection
|
1.0%
1/96
|
0.00%
0/98
|
|
General disorders
Alanine aminotransferase increased
|
1.0%
1/96
|
1.0%
1/98
|
|
General disorders
Aspartate aminotransferase increased
|
1.0%
1/96
|
0.00%
0/98
|
|
General disorders
Blood creatinine phosphokinase increased
|
0.00%
0/96
|
1.0%
1/98
|
|
General disorders
Gamma-glutamyltransferase increased
|
1.0%
1/96
|
0.00%
0/98
|
|
General disorders
Transaminases increased
|
0.00%
0/96
|
1.0%
1/98
|
|
Musculoskeletal and connective tissue disorders
Intervertebral disc disorder
|
0.00%
0/96
|
1.0%
1/98
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
1.0%
1/96
|
0.00%
0/98
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.00%
0/96
|
1.0%
1/98
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Seborrhoeic keratosis
|
0.00%
0/96
|
1.0%
1/98
|
|
Nervous system disorders
Dizziness
|
0.00%
0/96
|
1.0%
1/98
|
|
Nervous system disorders
Headache
|
0.00%
0/96
|
1.0%
1/98
|
|
Psychiatric disorders
Insomnia
|
1.0%
1/96
|
0.00%
0/98
|
|
Renal and urinary disorders
Renal impairment
|
0.00%
0/96
|
1.0%
1/98
|
|
Respiratory, thoracic and mediastinal disorders
Asthma
|
0.00%
0/96
|
1.0%
1/98
|
|
Respiratory, thoracic and mediastinal disorders
Pharyngolaryngeal pain
|
0.00%
0/96
|
1.0%
1/98
|
|
Skin and subcutaneous tissue disorders
Actinic keratosis
|
0.00%
0/96
|
1.0%
1/98
|
|
Vascular disorders
Hypertension
|
0.00%
0/96
|
1.0%
1/98
|
Additional Information
Senior Vice President, Global Clinical Development
Merck Sharp & Dohme Corp.
Results disclosure agreements
- Principal investigator is a sponsor employee Merck agreements may vary with individual investigators, but will not prohibit any investigator from publishing. Merck supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
- Publication restrictions are in place
Restriction type: OTHER