Trial Outcomes & Findings for Open Label Safety Study of Enteric-Coated Spheroid Suspension in Infants Aged Less Than 12 Months With Presumed Gastroesophageal Reflux Disease (GERD) (NCT NCT00868296)
NCT ID: NCT00868296
Last Updated: 2010-05-04
Results Overview
Pre-defined criteria were established for each laboratory test to define the values that would be identified as of potential clinical importance. Criteria are as follows: Potassium ≤ 3.0 mEq/L or ≥ 6.2 mEq/L; Carbon dioxide \< 12 mEq/L or \> 35 mEq/L; Total bilirubin \> 1.5xULN; CPK \> 3xULN; Gastrin ≥ 600 pg/mL; Neutrophils \< 10% or \> 80%; Platelet count \< 100 x10 to the third power/ul or \> 600 x10 to the third power/ul; Urine protein albumin \> 2+ (dipstick) 100mg/dL or positive; Urine leukocyte esterase \> 2+ (dipstick) moderate or positive.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
58 participants
Primary outcome timeframe
6 weeks
Results posted on
2010-05-04
Participant Flow
Patients were recruited worldwide March 2006 to February 2008.
Patients were eligible for enrollment into the study after completion of either study 3001B3-331 (NCT00362609) or study 3001B3-333 (NCT00259012).
Participant milestones
| Measure |
Low Dose Pantoprazole
Patients who participated previously in study 3001B3-333 (NCT00259012) (infants) and weighed 2.5 to \<7 kg generally received pantoprazole sodium enteric-coated spheroid suspension daily 2.5 mg; those weighing ≥ 7 kg to ≤ 15 kg generally received pantoprazole sodium enteric-coated spheroid suspension daily 5 mg. (A patient's dose may have been increased from the dose used in the previous study at the start of this open label extension study to manage clinical symptoms) No patients who participated previously in study 3001B3-331 (NCT00362609) (pre-term/neonates) were included in the low dose group.
|
High Dose Pantoprazole
Patients who participated previously in study 3001B3-333 (NCT00259012) (infants) and weighed 2.5 to \<7kg generally received pantoprazole sodium enteric-coated spheroid suspension daily 5 mg; those weighing ≥ 7 kg to ≤ 15 kg generally received pantoprazole sodium enteric-coated spheroid suspension daily 10 mg. (A patient's dose may have been increased from the dose used in the previous study at the start of this open label extension study to manage clinical symptoms.) All patients who participated previously in study 3001B3-331 (NCT00362609) (pre-term/neonates) received 2.5 mg (or higher, if the dose was increased at the start of this open label extension study to manage clinical symptoms) and were classified as part of the high dose group for analysis purposes.
|
|---|---|---|
|
Overall Study
STARTED
|
12
|
46
|
|
Overall Study
COMPLETED
|
12
|
43
|
|
Overall Study
NOT COMPLETED
|
0
|
3
|
Reasons for withdrawal
| Measure |
Low Dose Pantoprazole
Patients who participated previously in study 3001B3-333 (NCT00259012) (infants) and weighed 2.5 to \<7 kg generally received pantoprazole sodium enteric-coated spheroid suspension daily 2.5 mg; those weighing ≥ 7 kg to ≤ 15 kg generally received pantoprazole sodium enteric-coated spheroid suspension daily 5 mg. (A patient's dose may have been increased from the dose used in the previous study at the start of this open label extension study to manage clinical symptoms) No patients who participated previously in study 3001B3-331 (NCT00362609) (pre-term/neonates) were included in the low dose group.
|
High Dose Pantoprazole
Patients who participated previously in study 3001B3-333 (NCT00259012) (infants) and weighed 2.5 to \<7kg generally received pantoprazole sodium enteric-coated spheroid suspension daily 5 mg; those weighing ≥ 7 kg to ≤ 15 kg generally received pantoprazole sodium enteric-coated spheroid suspension daily 10 mg. (A patient's dose may have been increased from the dose used in the previous study at the start of this open label extension study to manage clinical symptoms.) All patients who participated previously in study 3001B3-331 (NCT00362609) (pre-term/neonates) received 2.5 mg (or higher, if the dose was increased at the start of this open label extension study to manage clinical symptoms) and were classified as part of the high dose group for analysis purposes.
|
|---|---|---|
|
Overall Study
Adverse Event
|
0
|
2
|
|
Overall Study
Withdrawal by Subject
|
0
|
1
|
Baseline Characteristics
Open Label Safety Study of Enteric-Coated Spheroid Suspension in Infants Aged Less Than 12 Months With Presumed Gastroesophageal Reflux Disease (GERD)
Baseline characteristics by cohort
| Measure |
Low Dose Pantoprazole
n=12 Participants
Patients who participated previously in study 3001B3-333 (NCT00259012) (infants) and weighed 2.5 to \<7 kg generally received pantoprazole sodium enteric-coated spheroid suspension daily 2.5 mg; those weighing ≥ 7 kg to ≤ 15 kg generally received pantoprazole sodium enteric-coated spheroid suspension daily 5 mg. (A patient's dose may have been increased from the dose used in the previous study at the start of this open label extension study to manage clinical symptoms) No patients who participated previously in study 3001B3-331 (NCT00362609) (pre-term/neonates) were included in the low dose group.
|
High Dose Pantoprazole
n=46 Participants
Patients who participated previously in study 3001B3-333 (NCT00259012) (infants) and weighed 2.5 to \<7kg generally received pantoprazole sodium enteric-coated spheroid suspension daily 5 mg; those weighing ≥ 7 kg to ≤ 15 kg generally received pantoprazole sodium enteric-coated spheroid suspension daily 10 mg. (A patient's dose may have been increased from the dose used in the previous study at the start of this open label extension study to manage clinical symptoms.) All patients who participated previously in study 3001B3-331 (NCT00362609) (pre-term/neonates) received 2.5 mg (or higher, if the dose was increased at the start of this open label extension study to manage clinical symptoms) and were classified as part of the high dose group for analysis purposes.
|
Total
n=58 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age Continuous
|
7.34 months
STANDARD_DEVIATION 3.06 • n=5 Participants
|
5.55 months
STANDARD_DEVIATION 3.44 • n=7 Participants
|
5.92 months
STANDARD_DEVIATION 3.42 • n=5 Participants
|
|
Sex: Female, Male
Female
|
5 Participants
n=5 Participants
|
21 Participants
n=7 Participants
|
26 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
7 Participants
n=5 Participants
|
25 Participants
n=7 Participants
|
32 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 6 weeksPopulation: Patients who received ≥1 dose of pantoprazole and had laboratory test results. The number of patients (n) tested varied by test, variations shown (low dose, high dose): Carbon dioxide (n=7,26), CPK (n=12,42), Gastrin (n=9,25), Neutrophils (n=12,44), Platelet count (n=12,41), Urine protein albumin (n=10,38), Urine leukocyte esterase (n=10,38).
Pre-defined criteria were established for each laboratory test to define the values that would be identified as of potential clinical importance. Criteria are as follows: Potassium ≤ 3.0 mEq/L or ≥ 6.2 mEq/L; Carbon dioxide \< 12 mEq/L or \> 35 mEq/L; Total bilirubin \> 1.5xULN; CPK \> 3xULN; Gastrin ≥ 600 pg/mL; Neutrophils \< 10% or \> 80%; Platelet count \< 100 x10 to the third power/ul or \> 600 x10 to the third power/ul; Urine protein albumin \> 2+ (dipstick) 100mg/dL or positive; Urine leukocyte esterase \> 2+ (dipstick) moderate or positive.
Outcome measures
| Measure |
Low Dose Pantoprazole
n=12 Participants
Patients who participated previously in study 3001B3-333 (NCT00259012) (infants) and weighed 2.5 to \<7 kg generally received pantoprazole sodium enteric-coated spheroid suspension daily 2.5 mg; those weighing ≥ 7 kg to ≤ 15 kg generally received pantoprazole sodium enteric-coated spheroid suspension daily 5 mg. (A patient's dose may have been increased from the dose used in the previous study at the start of this open label extension study to manage clinical symptoms) No patients who participated previously in study 3001B3-331 (NCT00362609) (pre-term/neonates) were included in the low dose group.
|
High Dose Pantoprazole
n=45 Participants
Patients who participated previously in study 3001B3-333 (NCT00259012) (infants) and weighed 2.5 to \<7kg generally received pantoprazole sodium enteric-coated spheroid suspension daily 5 mg; those weighing ≥ 7 kg to ≤ 15 kg generally received pantoprazole sodium enteric-coated spheroid suspension daily 10 mg. (A patient's dose may have been increased from the dose used in the previous study at the start of this open label extension study to manage clinical symptoms.) All patients who participated previously in study 3001B3-331 (NCT00362609) (pre-term/neonates) received 2.5 mg (or higher, if the dose was increased at the start of this open label extension study to manage clinical symptoms) and were classified as part of the high dose group for analysis purposes.
|
|---|---|---|
|
Number of Patients With Laboratory Test Values of Potential Clinical Importance During Treatment Period
Potassium (mmol/L)
|
0 patients
|
3 patients
|
|
Number of Patients With Laboratory Test Values of Potential Clinical Importance During Treatment Period
Carbon dioxide (mmol/L)
|
0 patients
|
1 patients
|
|
Number of Patients With Laboratory Test Values of Potential Clinical Importance During Treatment Period
Total bilirubin (µmol/L)
|
0 patients
|
1 patients
|
|
Number of Patients With Laboratory Test Values of Potential Clinical Importance During Treatment Period
CPK (mU/mL)
|
0 patients
|
2 patients
|
|
Number of Patients With Laboratory Test Values of Potential Clinical Importance During Treatment Period
Gastrin (pg/mL)
|
0 patients
|
1 patients
|
|
Number of Patients With Laboratory Test Values of Potential Clinical Importance During Treatment Period
Neutrophils (1,000,000,000/L)
|
1 patients
|
0 patients
|
|
Number of Patients With Laboratory Test Values of Potential Clinical Importance During Treatment Period
Platelet count (1,000,000,000/L)
|
0 patients
|
2 patients
|
|
Number of Patients With Laboratory Test Values of Potential Clinical Importance During Treatment Period
Urine protein albumin
|
0 patients
|
1 patients
|
|
Number of Patients With Laboratory Test Values of Potential Clinical Importance During Treatment Period
Urine leukocyte esterase
|
1 patients
|
3 patients
|
PRIMARY outcome
Timeframe: 6 weeksPopulation: Safety population (all patients with ≥1 dose of study drug) who also had baseline and end of study evaluations. Data point pairs were analyzed. All patients in study 3001B3-335 originated from study 3001B3-331 or -333 and baselines from the original study they were in were used.
Z-Score is a statistical measure to evaluate how a single data point compares to a standard. A Z-Score describes whether a mean is above or below the standard and how unusual the measurement is. Z-scores primarily range from -3 to +3. A Z-score of 0 indicates the same mean, \>0 a greater mean, and \<0 a lesser mean than the standard. In this study, infant growth parameters were compared to a standard defined by Centers for Disease Control's growth charts.
Outcome measures
| Measure |
Low Dose Pantoprazole
n=12 Participants
Patients who participated previously in study 3001B3-333 (NCT00259012) (infants) and weighed 2.5 to \<7 kg generally received pantoprazole sodium enteric-coated spheroid suspension daily 2.5 mg; those weighing ≥ 7 kg to ≤ 15 kg generally received pantoprazole sodium enteric-coated spheroid suspension daily 5 mg. (A patient's dose may have been increased from the dose used in the previous study at the start of this open label extension study to manage clinical symptoms) No patients who participated previously in study 3001B3-331 (NCT00362609) (pre-term/neonates) were included in the low dose group.
|
High Dose Pantoprazole
n=46 Participants
Patients who participated previously in study 3001B3-333 (NCT00259012) (infants) and weighed 2.5 to \<7kg generally received pantoprazole sodium enteric-coated spheroid suspension daily 5 mg; those weighing ≥ 7 kg to ≤ 15 kg generally received pantoprazole sodium enteric-coated spheroid suspension daily 10 mg. (A patient's dose may have been increased from the dose used in the previous study at the start of this open label extension study to manage clinical symptoms.) All patients who participated previously in study 3001B3-331 (NCT00362609) (pre-term/neonates) received 2.5 mg (or higher, if the dose was increased at the start of this open label extension study to manage clinical symptoms) and were classified as part of the high dose group for analysis purposes.
|
|---|---|---|
|
Growth Parameters Z-scores
Length - Baseline (n=12, 45)
|
0.33 units on scale
Standard Deviation 1.11
|
-1.63 units on scale
Standard Deviation 2.99
|
|
Growth Parameters Z-scores
Length - Final evaluation (n=12, 45)
|
0.45 units on scale
Standard Deviation 1.29
|
-1.04 units on scale
Standard Deviation 2.52
|
|
Growth Parameters Z-scores
Weight - Baseline (n=12, 46)
|
-0.16 units on scale
Standard Deviation 1.15
|
-1.26 units on scale
Standard Deviation 1.90
|
|
Growth Parameters Z-scores
Weight - Final evaluation (n=12, 46)
|
-0.05 units on scale
Standard Deviation 1.33
|
-1.00 units on scale
Standard Deviation 1.73
|
|
Growth Parameters Z-scores
Head circumference - Baseline (n=11, 45)
|
0.31 units on scale
Standard Deviation 1.17
|
-1.06 units on scale
Standard Deviation 2.10
|
|
Growth Parameters Z-scores
Head circumference - Final evaluation (n=11, 45)
|
0.25 units on scale
Standard Deviation 1.21
|
-0.62 units on scale
Standard Deviation 1.71
|
Adverse Events
Low Dose Pantoprazole
Serious events: 1 serious events
Other events: 8 other events
Deaths: 0 deaths
High Dose Pantoprazole
Serious events: 2 serious events
Other events: 30 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Low Dose Pantoprazole
Patients who participated previously in study 3001B3-333 (NCT00259012) (infants) and weighed 2.5 to \<7 kg generally received pantoprazole sodium enteric-coated spheroid suspension daily 2.5 mg; those weighing ≥ 7 kg to ≤ 15 kg generally received pantoprazole sodium enteric-coated spheroid suspension daily 5 mg. (A patient's dose may have been increased from the dose used in the previous study at the start of this open label extension study to manage clinical symptoms) No patients who participated previously in study 3001B3-331 (NCT00362609) (pre-term/neonates) were included in the low dose group.
|
High Dose Pantoprazole
Patients who participated previously in study 3001B3-333 (NCT00259012) (infants) and weighed 2.5 to \<7kg generally received pantoprazole sodium enteric-coated spheroid suspension daily 5 mg; those weighing ≥ 7 kg to ≤ 15 kg generally received pantoprazole sodium enteric-coated spheroid suspension daily 10 mg. (A patient's dose may have been increased from the dose used in the previous study at the start of this open label extension study to manage clinical symptoms.) All patients who participated previously in study 3001B3-331 (NCT00362609) (pre-term/neonates) received 2.5 mg (or higher, if the dose was increased at the start of this open label extension study to manage clinical symptoms) and were classified as part of the high dose group for analysis purposes.
|
|---|---|---|
|
Gastrointestinal disorders
Gastroenteritis
|
8.3%
1/12
|
0.00%
0/46
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory disorder
|
0.00%
0/12
|
2.2%
1/46
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
0.00%
0/12
|
2.2%
1/46
|
|
Ear and labyrinth disorders
Otitis media
|
8.3%
1/12
|
0.00%
0/46
|
Other adverse events
| Measure |
Low Dose Pantoprazole
Patients who participated previously in study 3001B3-333 (NCT00259012) (infants) and weighed 2.5 to \<7 kg generally received pantoprazole sodium enteric-coated spheroid suspension daily 2.5 mg; those weighing ≥ 7 kg to ≤ 15 kg generally received pantoprazole sodium enteric-coated spheroid suspension daily 5 mg. (A patient's dose may have been increased from the dose used in the previous study at the start of this open label extension study to manage clinical symptoms) No patients who participated previously in study 3001B3-331 (NCT00362609) (pre-term/neonates) were included in the low dose group.
|
High Dose Pantoprazole
Patients who participated previously in study 3001B3-333 (NCT00259012) (infants) and weighed 2.5 to \<7kg generally received pantoprazole sodium enteric-coated spheroid suspension daily 5 mg; those weighing ≥ 7 kg to ≤ 15 kg generally received pantoprazole sodium enteric-coated spheroid suspension daily 10 mg. (A patient's dose may have been increased from the dose used in the previous study at the start of this open label extension study to manage clinical symptoms.) All patients who participated previously in study 3001B3-331 (NCT00362609) (pre-term/neonates) received 2.5 mg (or higher, if the dose was increased at the start of this open label extension study to manage clinical symptoms) and were classified as part of the high dose group for analysis purposes.
|
|---|---|---|
|
General disorders
Accidental injury
|
0.00%
0/12
|
2.2%
1/46
|
|
General disorders
Fever
|
8.3%
1/12
|
8.7%
4/46
|
|
General disorders
Hernia
|
0.00%
0/12
|
2.2%
1/46
|
|
General disorders
Immune system disorder
|
8.3%
1/12
|
0.00%
0/46
|
|
General disorders
Infection
|
8.3%
1/12
|
0.00%
0/46
|
|
General disorders
Injection site pain
|
0.00%
0/12
|
2.2%
1/46
|
|
Cardiac disorders
Bradycardia
|
0.00%
0/12
|
2.2%
1/46
|
|
Cardiac disorders
Tachycardia
|
0.00%
0/12
|
2.2%
1/46
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/12
|
6.5%
3/46
|
|
Gastrointestinal disorders
Diarrhea
|
0.00%
0/12
|
2.2%
1/46
|
|
Gastrointestinal disorders
Gastroenteritis
|
0.00%
0/12
|
4.3%
2/46
|
|
Gastrointestinal disorders
Gastroesophageal reflux disease
|
16.7%
2/12
|
2.2%
1/46
|
|
Gastrointestinal disorders
Gingivitis
|
0.00%
0/12
|
2.2%
1/46
|
|
Gastrointestinal disorders
Mouth ulceration
|
0.00%
0/12
|
2.2%
1/46
|
|
Gastrointestinal disorders
Oral moniliasis
|
0.00%
0/12
|
2.2%
1/46
|
|
Gastrointestinal disorders
Tooth disorder
|
8.3%
1/12
|
8.7%
4/46
|
|
Gastrointestinal disorders
Vomiting
|
8.3%
1/12
|
6.5%
3/46
|
|
Blood and lymphatic system disorders
Ecchymosis
|
0.00%
0/12
|
2.2%
1/46
|
|
Metabolism and nutrition disorders
Creatine phosphokinase increased
|
0.00%
0/12
|
2.2%
1/46
|
|
Metabolism and nutrition disorders
Healing abnormal
|
0.00%
0/12
|
2.2%
1/46
|
|
Metabolism and nutrition disorders
Hypophosphatemia
|
0.00%
0/12
|
2.2%
1/46
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal anomaly
|
0.00%
0/12
|
2.2%
1/46
|
|
Nervous system disorders
Agitation
|
0.00%
0/12
|
2.2%
1/46
|
|
Nervous system disorders
Hostility
|
0.00%
0/12
|
2.2%
1/46
|
|
Nervous system disorders
Insomnia
|
8.3%
1/12
|
0.00%
0/46
|
|
Respiratory, thoracic and mediastinal disorders
Apnea
|
0.00%
0/12
|
2.2%
1/46
|
|
Respiratory, thoracic and mediastinal disorders
Bronchiolitis
|
0.00%
0/12
|
2.2%
1/46
|
|
Respiratory, thoracic and mediastinal disorders
Cough increased
|
16.7%
2/12
|
6.5%
3/46
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
0.00%
0/12
|
2.2%
1/46
|
|
Respiratory, thoracic and mediastinal disorders
Pharyngitis
|
8.3%
1/12
|
2.2%
1/46
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary physical finding
|
8.3%
1/12
|
0.00%
0/46
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory disorder
|
0.00%
0/12
|
2.2%
1/46
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory distress syndrome
|
0.00%
0/12
|
2.2%
1/46
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
0.00%
0/12
|
2.2%
1/46
|
|
Respiratory, thoracic and mediastinal disorders
Rhinitis
|
33.3%
4/12
|
8.7%
4/46
|
|
Respiratory, thoracic and mediastinal disorders
Tachypnoea
|
0.00%
0/12
|
2.2%
1/46
|
|
Respiratory, thoracic and mediastinal disorders
Upper respiratory infection
|
16.7%
2/12
|
6.5%
3/46
|
|
Skin and subcutaneous tissue disorders
Dermatitis allergic
|
0.00%
0/12
|
2.2%
1/46
|
|
Skin and subcutaneous tissue disorders
Eczema
|
0.00%
0/12
|
6.5%
3/46
|
|
Skin and subcutaneous tissue disorders
Erythema
|
8.3%
1/12
|
0.00%
0/46
|
|
Skin and subcutaneous tissue disorders
Herpes simplex
|
0.00%
0/12
|
2.2%
1/46
|
|
Skin and subcutaneous tissue disorders
Maculopapular rash
|
0.00%
0/12
|
2.2%
1/46
|
|
Skin and subcutaneous tissue disorders
Pustular rash
|
8.3%
1/12
|
0.00%
0/46
|
|
Skin and subcutaneous tissue disorders
Rash
|
8.3%
1/12
|
4.3%
2/46
|
|
Eye disorders
Blepharitis
|
0.00%
0/12
|
2.2%
1/46
|
|
Eye disorders
Conjunctivitis
|
0.00%
0/12
|
4.3%
2/46
|
|
Ear and labyrinth disorders
Ear pain
|
0.00%
0/12
|
2.2%
1/46
|
|
Eye disorders
Eye disorder
|
8.3%
1/12
|
0.00%
0/46
|
|
Ear and labyrinth disorders
Otitis media
|
16.7%
2/12
|
10.9%
5/46
|
|
Reproductive system and breast disorders
Vaginal moniliasis
|
0.00%
0/12
|
2.2%
1/46
|
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