Trial Outcomes & Findings for Study Evaluating the Efficacy and Safety of Pantoprazole in Infants With Symptomatic Gastroesophageal Reflux Disease (GERD) (NCT NCT00365300)
NCT ID: NCT00365300
Last Updated: 2010-05-04
Results Overview
Lack of efficacy defined as 1 or more of the following occurring during the double blind treatment-withdrawal phase: significant worsening of gastroesophageal reflux disease (GERD) symptoms frequency, a diagnostic test (e.g., endoscopy) demonstrating worsening of esophagitis, maximal antacid intake for ≥ 7 continuous days, or severe GERD symptoms based on physician's judgment.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
129 participants
Primary outcome timeframe
4 weeks double-blind
Results posted on
2010-05-04
Participant Flow
Patients were recruited worldwide from September 2006 to August 2007.
Patients were screened for 2 weeks and provided non-pharmacologic conservative therapy including hypoallergenic formula thickened with rice cereal. Patients who improved on this treatment were not eligible for enrollment.
Participant milestones
| Measure |
Pantoprazole Sodium Granules
Double Blind Treatment-withdrawal phase (weeks 5-8) Pantoprazole sodium granules at a dose of approximately 1.2 mg/kg daily (5 mg for weight \< 7 kg or 10 mg for weight ≥ 7 kg) in an oral suspension. An Open Label Treatment run-in phase (weeks 1-4) preceded the Double Blind Treatment-withdrawal phase and patients received: Pantoprazole sodium granules at a dose of approximately 1.2 mg/kg daily (5 mg for weight \< 7 kg or 10 mg for weight ≥7 kg) in an oral suspension.
|
Placebo
Double Blind Treatment-withdrawal phase (weeks 5-8): Matching placebo. An Open Label Treatment run-in phase (weeks 1-4) preceded the Double Blind Treatment-withdrawal phase and patients received Pantoprazole sodium granules at a dose of approximately 1.2 mg/kg daily (5 mg for weight \< 7 kg or 10 mg for weight ≥7 kg) in an oral suspension.
|
|---|---|---|
|
Open-label Phase
STARTED
|
129
|
0
|
|
Open-label Phase
COMPLETED
|
107
|
0
|
|
Open-label Phase
NOT COMPLETED
|
22
|
0
|
|
Double-blind Phase
STARTED
|
54
|
54
|
|
Double-blind Phase
COMPLETED
|
43
|
45
|
|
Double-blind Phase
NOT COMPLETED
|
11
|
9
|
Reasons for withdrawal
| Measure |
Pantoprazole Sodium Granules
Double Blind Treatment-withdrawal phase (weeks 5-8) Pantoprazole sodium granules at a dose of approximately 1.2 mg/kg daily (5 mg for weight \< 7 kg or 10 mg for weight ≥ 7 kg) in an oral suspension. An Open Label Treatment run-in phase (weeks 1-4) preceded the Double Blind Treatment-withdrawal phase and patients received: Pantoprazole sodium granules at a dose of approximately 1.2 mg/kg daily (5 mg for weight \< 7 kg or 10 mg for weight ≥7 kg) in an oral suspension.
|
Placebo
Double Blind Treatment-withdrawal phase (weeks 5-8): Matching placebo. An Open Label Treatment run-in phase (weeks 1-4) preceded the Double Blind Treatment-withdrawal phase and patients received Pantoprazole sodium granules at a dose of approximately 1.2 mg/kg daily (5 mg for weight \< 7 kg or 10 mg for weight ≥7 kg) in an oral suspension.
|
|---|---|---|
|
Open-label Phase
Adverse Event
|
4
|
0
|
|
Open-label Phase
Failed to Return
|
1
|
0
|
|
Open-label Phase
Physician Decision
|
1
|
0
|
|
Open-label Phase
Noncompliance
|
9
|
0
|
|
Open-label Phase
Parent/Legal Guardian Request
|
4
|
0
|
|
Open-label Phase
Protocol Violation
|
1
|
0
|
|
Open-label Phase
Lack of Efficacy
|
1
|
0
|
|
Open-label Phase
Patient skipped open label phase
|
1
|
0
|
|
Double-blind Phase
Failed to return
|
1
|
0
|
|
Double-blind Phase
Noncompliance
|
1
|
1
|
|
Double-blind Phase
Withdrawal by Subject
|
0
|
1
|
|
Double-blind Phase
Protocol Violation
|
3
|
1
|
|
Double-blind Phase
Lack of Efficacy
|
6
|
6
|
Baseline Characteristics
Study Evaluating the Efficacy and Safety of Pantoprazole in Infants With Symptomatic Gastroesophageal Reflux Disease (GERD)
Baseline characteristics by cohort
| Measure |
Pantoprazole Sodium Granules
n=52 Participants
Double Blind Treatment-withdrawal phase (weeks 5-8) Pantoprazole sodium granules at a dose of approximately 1.2 mg/kg daily (5 mg for weight \< 7 kg or 10 mg for weight ≥ 7 kg) in an oral suspension. An Open Label Treatment run-in phase (weeks 1-4) preceded the Double Blind Treatment-withdrawal phase and patients received: Pantoprazole sodium granules at a dose of approximately 1.2 mg/kg daily (5 mg for weight \< 7 kg or 10 mg for weight ≥7 kg) in an oral suspension.
|
Placebo
n=54 Participants
Double Blind Treatment-withdrawal phase (weeks 5-8): Matching placebo. An Open Label Treatment run-in phase (weeks 1-4) preceded the Double Blind Treatment-withdrawal phase and patients received Pantoprazole sodium granules at a dose of approximately 1.2 mg/kg daily (5 mg for weight \< 7 kg or 10 mg for weight ≥7 kg) in an oral suspension.
|
Total
n=106 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age Continuous
|
5.15 months
STANDARD_DEVIATION 2.81 • n=5 Participants
|
5.04 months
STANDARD_DEVIATION 2.81 • n=7 Participants
|
5.09 months
STANDARD_DEVIATION 2.80 • n=5 Participants
|
|
Sex: Female, Male
Female
|
18 Participants
n=5 Participants
|
20 Participants
n=7 Participants
|
38 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
34 Participants
n=5 Participants
|
34 Participants
n=7 Participants
|
68 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 4 weeks double-blindPopulation: The analysis population was the Modified Intent to Treat, which included all GERD patients who completed the 4 week open-label treatment phase, were randomized into the 4 week double-blind phase, and took at least one dose of double-blind treatment.
Lack of efficacy defined as 1 or more of the following occurring during the double blind treatment-withdrawal phase: significant worsening of gastroesophageal reflux disease (GERD) symptoms frequency, a diagnostic test (e.g., endoscopy) demonstrating worsening of esophagitis, maximal antacid intake for ≥ 7 continuous days, or severe GERD symptoms based on physician's judgment.
Outcome measures
| Measure |
Pantoprazole Sodium Granules
n=52 Participants
Double Blind Treatment-withdrawal phase (weeks 5-8) Pantoprazole sodium granules at a dose of approximately 1.2 mg/kg daily (5 mg for weight \< 7 kg or 10 mg for weight ≥ 7 kg) in an oral suspension. An Open Label Treatment run-in phase (weeks 1-4) preceded the Double Blind Treatment-withdrawal phase and patients received: Pantoprazole sodium granules at a dose of approximately 1.2 mg/kg daily (5 mg for weight \< 7 kg or 10 mg for weight ≥7 kg) in an oral suspension.
|
Placebo
n=54 Participants
Double Blind Treatment-withdrawal phase (weeks 5-8): Matching placebo. An Open Label Treatment run-in phase (weeks 1-4) preceded the Double Blind Treatment-withdrawal phase and patients received Pantoprazole sodium granules at a dose of approximately 1.2 mg/kg daily (5 mg for weight \< 7 kg or 10 mg for weight ≥7 kg) in an oral suspension.
|
|---|---|---|
|
Number of Patients Withdrawn From Study Due to Lack of Efficacy.
|
6 patients
|
6 patients
|
Adverse Events
Screening
Serious events: 2 serious events
Other events: 52 other events
Deaths: 0 deaths
Pantoprazole Sodium Granules (Open-Label Phase)
Serious events: 4 serious events
Other events: 85 other events
Deaths: 0 deaths
Pantoprazole Sodium Granules (Double-blind Phase)
Serious events: 0 serious events
Other events: 28 other events
Deaths: 0 deaths
Placebo (Double-blind Phase)
Serious events: 1 serious events
Other events: 28 other events
Deaths: 0 deaths
Follow-up
Serious events: 3 serious events
Other events: 25 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Screening
n=129 participants at risk
|
Pantoprazole Sodium Granules (Open-Label Phase)
n=128 participants at risk
|
Pantoprazole Sodium Granules (Double-blind Phase)
n=54 participants at risk
|
Placebo (Double-blind Phase)
n=54 participants at risk
|
Follow-up
n=127 participants at risk
|
|---|---|---|---|---|---|
|
Gastrointestinal disorders
Gastroesophageal reflux disease
|
0.78%
1/129
|
0.78%
1/128
|
0.00%
0/54
|
0.00%
0/54
|
0.00%
0/127
|
|
Respiratory, thoracic and mediastinal disorders
Laryngitis
|
0.78%
1/129
|
0.00%
0/128
|
0.00%
0/54
|
0.00%
0/54
|
0.00%
0/127
|
|
Gastrointestinal disorders
Gastroenteritis
|
0.00%
0/129
|
0.78%
1/128
|
0.00%
0/54
|
0.00%
0/54
|
0.00%
0/127
|
|
Metabolism and nutrition disorders
Failure to thrive
|
0.00%
0/129
|
0.78%
1/128
|
0.00%
0/54
|
0.00%
0/54
|
0.79%
1/127
|
|
Respiratory, thoracic and mediastinal disorders
Bronchiolitis
|
0.00%
0/129
|
0.78%
1/128
|
0.00%
0/54
|
0.00%
0/54
|
0.79%
1/127
|
|
Respiratory, thoracic and mediastinal disorders
Asthma
|
0.00%
0/129
|
0.00%
0/128
|
0.00%
0/54
|
1.9%
1/54
|
0.00%
0/127
|
|
Vascular disorders
Syncope
|
0.00%
0/129
|
0.00%
0/128
|
0.00%
0/54
|
0.00%
0/54
|
0.79%
1/127
|
|
Ear and labyrinth disorders
Otitis media
|
0.00%
0/129
|
0.00%
0/128
|
0.00%
0/54
|
0.00%
0/54
|
0.79%
1/127
|
Other adverse events
| Measure |
Screening
n=129 participants at risk
|
Pantoprazole Sodium Granules (Open-Label Phase)
n=128 participants at risk
|
Pantoprazole Sodium Granules (Double-blind Phase)
n=54 participants at risk
|
Placebo (Double-blind Phase)
n=54 participants at risk
|
Follow-up
n=127 participants at risk
|
|---|---|---|---|---|---|
|
General disorders
Accidental injury
|
0.78%
1/129
|
0.78%
1/128
|
1.9%
1/54
|
3.7%
2/54
|
0.79%
1/127
|
|
General disorders
Fever
|
7.8%
10/129
|
11.7%
15/128
|
5.6%
3/54
|
3.7%
2/54
|
0.00%
0/127
|
|
General disorders
Flu syndrome
|
0.00%
0/129
|
0.78%
1/128
|
1.9%
1/54
|
0.00%
0/54
|
0.00%
0/127
|
|
General disorders
Infection
|
2.3%
3/129
|
3.1%
4/128
|
0.00%
0/54
|
1.9%
1/54
|
0.00%
0/127
|
|
General disorders
Lab test abnormal
|
0.00%
0/129
|
0.78%
1/128
|
0.00%
0/54
|
1.9%
1/54
|
0.00%
0/127
|
|
General disorders
Moniliasis
|
0.78%
1/129
|
0.00%
0/128
|
0.00%
0/54
|
1.9%
1/54
|
0.00%
0/127
|
|
Gastrointestinal disorders
Anorexia
|
0.00%
0/129
|
2.3%
3/128
|
1.9%
1/54
|
1.9%
1/54
|
0.00%
0/127
|
|
Gastrointestinal disorders
Constipation
|
0.78%
1/129
|
3.9%
5/128
|
1.9%
1/54
|
3.7%
2/54
|
0.00%
0/127
|
|
Gastrointestinal disorders
Diarrhea
|
3.9%
5/129
|
10.9%
14/128
|
3.7%
2/54
|
3.7%
2/54
|
0.79%
1/127
|
|
Gastrointestinal disorders
Oral moniliasis
|
1.6%
2/129
|
5.5%
7/128
|
1.9%
1/54
|
0.00%
0/54
|
0.00%
0/127
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/129
|
5.5%
7/128
|
5.6%
3/54
|
3.7%
2/54
|
2.4%
3/127
|
|
Metabolism and nutrition disorders
Creatine phosphokinase increased
|
0.78%
1/129
|
0.78%
1/128
|
5.6%
3/54
|
0.00%
0/54
|
0.00%
0/127
|
|
Metabolism and nutrition disorders
Dehydration
|
0.00%
0/129
|
0.78%
1/128
|
1.9%
1/54
|
0.00%
0/54
|
0.00%
0/127
|
|
Metabolism and nutrition disorders
Hyperlipidemia
|
0.78%
1/129
|
0.00%
0/128
|
1.9%
1/54
|
0.00%
0/54
|
0.00%
0/127
|
|
Musculoskeletal and connective tissue disorders
Muscle cramp
|
0.00%
0/129
|
0.78%
1/128
|
1.9%
1/54
|
0.00%
0/54
|
0.00%
0/127
|
|
Nervous system disorders
Anxiety
|
0.00%
0/129
|
0.78%
1/128
|
0.00%
0/54
|
1.9%
1/54
|
0.00%
0/127
|
|
Nervous system disorders
Emotional lability
|
0.00%
0/129
|
1.6%
2/128
|
1.9%
1/54
|
0.00%
0/54
|
0.00%
0/127
|
|
Nervous system disorders
Sleep disorder
|
0.00%
0/129
|
0.78%
1/128
|
1.9%
1/54
|
0.00%
0/54
|
0.00%
0/127
|
|
Nervous system disorders
Twitching
|
0.00%
0/129
|
0.00%
0/128
|
1.9%
1/54
|
0.00%
0/54
|
0.00%
0/127
|
|
Respiratory, thoracic and mediastinal disorders
Asthma
|
1.6%
2/129
|
0.78%
1/128
|
0.00%
0/54
|
1.9%
1/54
|
0.00%
0/127
|
|
Respiratory, thoracic and mediastinal disorders
Bronchiolitis
|
1.6%
2/129
|
2.3%
3/128
|
3.7%
2/54
|
1.9%
1/54
|
1.6%
2/127
|
|
Respiratory, thoracic and mediastinal disorders
Cough increased
|
3.1%
4/129
|
6.2%
8/128
|
3.7%
2/54
|
7.4%
4/54
|
0.79%
1/127
|
|
Respiratory, thoracic and mediastinal disorders
Laryngitis
|
0.78%
1/129
|
0.78%
1/128
|
3.7%
2/54
|
0.00%
0/54
|
0.00%
0/127
|
|
Respiratory, thoracic and mediastinal disorders
Pharyngitis
|
0.00%
0/128
|
1.6%
2/128
|
1.9%
1/54
|
0.00%
0/54
|
1.6%
2/127
|
|
Respiratory, thoracic and mediastinal disorders
Rhinitis
|
2.3%
3/129
|
9.4%
12/128
|
5.6%
3/54
|
1.9%
1/54
|
0.79%
1/127
|
|
Respiratory, thoracic and mediastinal disorders
Tachypnoea
|
0.00%
0/129
|
0.00%
0/128
|
0.00%
0/54
|
1.9%
1/54
|
0.00%
0/127
|
|
Respiratory, thoracic and mediastinal disorders
Upper respiratory infection
|
10.9%
14/129
|
22.7%
29/128
|
16.7%
9/54
|
14.8%
8/54
|
4.7%
6/127
|
|
Respiratory, thoracic and mediastinal disorders
Wheezing
|
0.00%
0/129
|
0.78%
1/128
|
0.00%
0/54
|
1.9%
1/54
|
0.00%
0/127
|
|
Skin and subcutaneous tissue disorders
Contact dermatitis
|
3.9%
5/129
|
6.2%
8/128
|
3.7%
2/54
|
0.00%
0/54
|
0.00%
0/127
|
|
Skin and subcutaneous tissue disorders
Cutaneous moniliasis
|
0.78%
1/129
|
3.9%
5/128
|
1.9%
1/54
|
1.9%
1/54
|
0.00%
0/127
|
|
Skin and subcutaneous tissue disorders
Eczema
|
1.6%
2/129
|
3.9%
5/128
|
0.00%
0/54
|
1.9%
1/54
|
0.00%
0/127
|
|
Skin and subcutaneous tissue disorders
Erythema
|
0.00%
0/129
|
1.6%
2/128
|
0.00%
0/54
|
1.9%
1/54
|
0.00%
0/127
|
|
Skin and subcutaneous tissue disorders
Furunculosis
|
0.00%
0/129
|
0.00%
0/128
|
0.00%
0/54
|
1.9%
1/54
|
0.00%
0/127
|
|
Skin and subcutaneous tissue disorders
Impetigo
|
0.00%
0/129
|
0.00%
0/128
|
0.00%
0/54
|
1.9%
1/54
|
0.00%
0/127
|
|
Skin and subcutaneous tissue disorders
Miliaria
|
0.00%
0/129
|
0.78%
1/128
|
0.00%
0/54
|
1.9%
1/54
|
0.00%
0/127
|
|
Skin and subcutaneous tissue disorders
Rash
|
2.3%
3/129
|
3.1%
4/128
|
5.6%
3/54
|
3.7%
2/54
|
0.79%
1/127
|
|
Skin and subcutaneous tissue disorders
Seborrhea
|
0.78%
1/129
|
0.78%
1/128
|
1.9%
1/54
|
0.00%
0/54
|
0.00%
0/127
|
|
Eye disorders
Conjunctivitis
|
0.00%
0/129
|
1.6%
2/128
|
0.00%
0/54
|
1.9%
1/54
|
0.79%
1/127
|
|
Ear and labyrinth disorders
Otitis media
|
1.6%
2/129
|
10.2%
13/128
|
5.6%
3/54
|
0.00%
0/54
|
3.1%
4/127
|
|
Renal and urinary disorders
Urinary tract infection
|
3.1%
4/129
|
0.00%
0/128
|
0.00%
0/54
|
3.7%
2/54
|
1.6%
2/127
|
|
Gastrointestinal disorders
Tooth disorder
|
0.00%
0/129
|
3.9%
5/128
|
0.00%
0/54
|
3.7%
2/54
|
0.00%
0/127
|
|
Gastrointestinal disorders
Gastroesophageal reflux disease
|
0.78%
1/129
|
3.1%
4/128
|
0.00%
0/54
|
0.00%
0/54
|
0.00%
0/127
|
|
Gastrointestinal disorders
Hematemesis
|
0.78%
1/129
|
0.00%
0/128
|
0.00%
0/54
|
0.00%
0/54
|
0.00%
0/127
|
|
Respiratory, thoracic and mediastinal disorders
Sinus congestion
|
0.78%
1/129
|
0.78%
1/128
|
0.00%
0/54
|
0.00%
0/54
|
0.00%
0/127
|
|
Respiratory, thoracic and mediastinal disorders
Sinusitis
|
0.78%
1/129
|
2.3%
3/128
|
0.00%
0/54
|
0.00%
0/54
|
0.00%
0/127
|
|
Respiratory, thoracic and mediastinal disorders
Stridor
|
0.78%
1/129
|
0.00%
0/128
|
0.00%
0/54
|
0.00%
0/54
|
0.00%
0/127
|
|
Skin and subcutaneous tissue disorders
Skin disorder
|
0.78%
1/129
|
0.78%
1/128
|
0.00%
0/54
|
0.00%
0/54
|
0.00%
0/127
|
|
General disorders
Abdominal pain
|
0.00%
0/129
|
0.78%
1/128
|
0.00%
0/54
|
0.00%
0/54
|
0.00%
0/127
|
|
General disorders
Hernia
|
0.00%
0/129
|
0.78%
1/128
|
0.00%
0/54
|
0.00%
0/54
|
0.00%
0/127
|
|
General disorders
Injection site reaction
|
0.00%
0/129
|
0.78%
1/128
|
0.00%
0/54
|
0.00%
0/54
|
0.00%
0/127
|
|
Gastrointestinal disorders
Flatulence
|
0.00%
0/129
|
0.78%
1/128
|
0.00%
0/54
|
0.00%
0/54
|
0.00%
0/127
|
|
Gastrointestinal disorders
Gastroenteritis
|
0.00%
0/129
|
1.6%
2/128
|
0.00%
0/54
|
0.00%
0/54
|
0.79%
1/127
|
|
Metabolism and nutrition disorders
Alkaline phosphatase increased
|
0.00%
0/129
|
0.78%
1/128
|
0.00%
0/54
|
0.00%
0/54
|
0.79%
1/127
|
|
Metabolism and nutrition disorders
Failure to thrive
|
0.00%
0/129
|
0.78%
1/128
|
0.00%
0/54
|
0.00%
0/54
|
0.79%
1/127
|
|
Metabolism and nutrition disorders
SGOT increased
|
0.00%
0/129
|
0.78%
1/128
|
0.00%
0/54
|
0.00%
0/54
|
0.79%
1/127
|
|
Metabolism and nutrition disorders
SGPT increased
|
0.00%
0/129
|
0.78%
1/128
|
0.00%
0/54
|
0.00%
0/54
|
0.79%
1/127
|
|
Nervous system disorders
Agitation
|
0.00%
0/129
|
0.78%
1/128
|
0.00%
0/54
|
0.00%
0/54
|
0.00%
0/127
|
|
Nervous system disorders
Nervousness
|
0.00%
0/129
|
0.78%
1/128
|
0.00%
0/54
|
0.00%
0/54
|
0.00%
0/127
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
0.00%
0/129
|
0.78%
1/128
|
0.00%
0/54
|
0.00%
0/54
|
0.00%
0/127
|
|
Respiratory, thoracic and mediastinal disorders
Nasal septum disorder
|
0.00%
0/129
|
0.78%
1/128
|
0.00%
0/54
|
0.00%
0/54
|
0.00%
0/127
|
|
Skin and subcutaneous tissue disorders
Fungal dermatitis
|
0.00%
0/129
|
3.9%
5/128
|
0.00%
0/54
|
0.00%
0/54
|
0.00%
0/127
|
|
Skin and subcutaneous tissue disorders
Maculopapular rash
|
0.00%
0/129
|
0.78%
1/128
|
0.00%
0/54
|
0.00%
0/54
|
0.00%
0/127
|
|
Reproductive system and breast disorders
Testis disorder
|
0.00%
0/129
|
0.78%
1/128
|
0.00%
0/54
|
0.00%
0/54
|
0.00%
0/127
|
|
Vascular disorders
Syncope
|
0.00%
0/129
|
0.00%
0/128
|
0.00%
0/54
|
0.00%
0/54
|
0.79%
1/127
|
|
Gastrointestinal disorders
Dyspepsia
|
0.00%
0/129
|
0.00%
0/128
|
0.00%
0/54
|
0.00%
0/54
|
0.79%
1/127
|
|
Blood and lymphatic system disorders
Anemia
|
0.00%
0/129
|
0.00%
0/128
|
0.00%
0/54
|
0.00%
0/54
|
0.79%
1/127
|
|
Respiratory, thoracic and mediastinal disorders
Rhinitis allergic
|
0.00%
0/129
|
0.00%
0/128
|
0.00%
0/54
|
0.00%
0/54
|
0.79%
1/127
|
|
Ear and labyrinth disorders
Ear pain
|
0.00%
0/129
|
0.00%
0/128
|
0.00%
0/54
|
0.00%
0/54
|
0.79%
1/127
|
|
Reproductive system and breast disorders
Vulvovaginal disorder
|
0.00%
0/129
|
0.00%
0/128
|
0.00%
0/54
|
0.00%
0/54
|
0.79%
1/127
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The PIs agreed to allow the sponsor 60 days to review and require changes to presentations or publications but only to protect confidential information and intellectual property, and for the sponsor to file a patent application, as applicable. The PIs also agreed for data to be presented first as a joint, multi-center publication.
- Publication restrictions are in place
Restriction type: OTHER