Trial Outcomes & Findings for Dose-Ranging Study of Oral Viscous Budesonide in Pediatrics With Eosinophilic Esophagitis (NCT NCT00762073)

NCT ID: NCT00762073

Last Updated: 2021-06-11

Results Overview

Response was defined as a ≥50% reduction from baseline in the eosinophilic esophagitis (EoE) clinical symptom score (CSS) and a reduction in peak eosinophil count to ≤6/high power field (light microscopy) from esophageal biopsies collected at the final evaluation. The EoE CSS, scored from 0 to 18 by a doctor, assessed 6 categories: 1) heartburn, 2) abdominal pain, 3) nocturnal awakening with symptoms, 4) nausea, regurgitation, or vomiting, 5) anorexia or early satiety, and 6) dysphagia, odynophagia, or food impaction (a severe symptom). Each domain was scored as follows, based on symptoms in the 2 weeks prior to the assessment: 0 = No symptoms and no coping behaviors required; 1 = Mild: Symptoms limited to 1-3 days or no symptoms because coping behaviors were required to avoid symptoms; 2 = Moderate: Symptoms on \>3 days, with or without minor coping behaviors; 3 = Severe: Symptoms interfered with activities of daily living or symptoms persisted and required major coping behaviors.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

82 participants

Primary outcome timeframe

12 weeks after the start of treatment

Results posted on

2021-06-11

Participant Flow

Participant milestones

Participant milestones
Measure	Placebo Participants received placebo twice daily at bedtime (hs) and after breakfast (qAM, pc) for 12 weeks with a 3 week taper period.	Low Dose Participants received oral budesonide suspension (OBS) 0.05 mg/mL at bedtime (hs) and placebo after breakfast (qAM, pc) for 12 weeks, with a total daily dose of 0.35 mg (2 to 9 years) or 0.50 mg (10 to 18 years), followed by a 3 week taper period.	Medium Dose Participants received oral budesonide suspension (OBS) 0.2 mg/mL at bedtime (hs) and placebo after breakfast (qAM, pc) for 12 weeks, with a total daily dose of 1.4 mg (2 to 9 years) or 2.0 mg (10 to 18 years), followed by a 3 week taper period.	High Dose Participants received oral budesonide suspension (OBS) 0.2 mg/mL at bedtime (hs) and after breakfast (qAM, pc) for 12 weeks, with a total daily dose of 2.8 mg (2 to 9 years) or 4.0 mg (10 to 18 years), followed by a 3 week taper period.
Overall Study STARTED	21	21	20	20
Overall Study COMPLETED	17	17	18	17
Overall Study NOT COMPLETED	4	4	2	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Participants received placebo twice daily at bedtime (hs) and after breakfast (qAM, pc) for 12 weeks with a 3 week taper period.	Low Dose Participants received oral budesonide suspension (OBS) 0.05 mg/mL at bedtime (hs) and placebo after breakfast (qAM, pc) for 12 weeks, with a total daily dose of 0.35 mg (2 to 9 years) or 0.50 mg (10 to 18 years), followed by a 3 week taper period.	Medium Dose Participants received oral budesonide suspension (OBS) 0.2 mg/mL at bedtime (hs) and placebo after breakfast (qAM, pc) for 12 weeks, with a total daily dose of 1.4 mg (2 to 9 years) or 2.0 mg (10 to 18 years), followed by a 3 week taper period.	High Dose Participants received oral budesonide suspension (OBS) 0.2 mg/mL at bedtime (hs) and after breakfast (qAM, pc) for 12 weeks, with a total daily dose of 2.8 mg (2 to 9 years) or 4.0 mg (10 to 18 years), followed by a 3 week taper period.
Overall Study Lack of Efficacy	1	1	0	0
Overall Study Adverse Event	1	0	1	1
Overall Study Significant Subject Noncompliance	0	1	0	1
Overall Study Withdrawal by Subject	1	2	1	1
Overall Study Not on treatment for >/= 77 days	1	0	0	0

Baseline Characteristics

Dose-Ranging Study of Oral Viscous Budesonide in Pediatrics With Eosinophilic Esophagitis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=21 Participants Participants received placebo twice daily at bedtime (hs) and after breakfast (qAM, pc) for 12 weeks with a 3 week taper period.	Low Dose n=21 Participants Participants received oral budesonide suspension (OBS) 0.05 mg/mL at bedtime (hs) and placebo after breakfast (qAM, pc) for 12 weeks, with a total daily dose of 0.35 mg (2 to 9 years) or 0.50 mg (10 to 18 years), followed by a 3 week taper period.	Medium Dose n=19 Participants Participants received oral budesonide suspension (OBS) 0.2 mg/mL at bedtime (hs) and placebo after breakfast (qAM, pc) for 12 weeks, with a total daily dose of 1.4 mg (2 to 9 years) or 2.0 mg (10 to 18 years), followed by a 3 week taper period.	High Dose n=20 Participants Participants received oral budesonide suspension (OBS) 0.2 mg/mL at bedtime (hs) and after breakfast (qAM, pc) for 12 weeks, with a total daily dose of 2.8 mg (2 to 9 years) or 4.0 mg (10 to 18 years), followed by a 3 week taper period.	Total n=81 Participants Total of all reporting groups
Age, Continuous	9.2 years STANDARD_DEVIATION 4.36 • n=5 Participants	9.0 years STANDARD_DEVIATION 5.88 • n=7 Participants	10.2 years STANDARD_DEVIATION 4.89 • n=5 Participants	8.1 years STANDARD_DEVIATION 4.58 • n=4 Participants	9.1 years STANDARD_DEVIATION 4.93 • n=21 Participants
Age, Customized 2 to 9 years	12 Participants n=5 Participants	12 Participants n=7 Participants	10 Participants n=5 Participants	12 Participants n=4 Participants	46 Participants n=21 Participants
Age, Customized 10 to 18 years	9 Participants n=5 Participants	9 Participants n=7 Participants	9 Participants n=5 Participants	8 Participants n=4 Participants	35 Participants n=21 Participants
Sex: Female, Male Female	5 Participants n=5 Participants	4 Participants n=7 Participants	2 Participants n=5 Participants	4 Participants n=4 Participants	15 Participants n=21 Participants
Sex: Female, Male Male	16 Participants n=5 Participants	17 Participants n=7 Participants	17 Participants n=5 Participants	16 Participants n=4 Participants	66 Participants n=21 Participants

PRIMARY outcome

Timeframe: 12 weeks after the start of treatment

Population: The Full Analysis Set (FAS), defined as participants who received at least one dose of study drug and had evaluable post-baseline esophageal biopsy and clinical symptom data.

Outcome measures

Outcome measures
Measure	Placebo n=18 Participants Participants received placebo twice daily at bedtime (hs) and after breakfast (qAM, pc) for 12 weeks, followed by a 3 week taper period.	Low Dose n=17 Participants Participants received oral budesonide suspension (OBS) 0.05 mg/mL at bedtime (hs) and placebo after breakfast (qAM, pc) for 12 weeks, with a total daily dose of 0.35 mg (2 to 9 years) or 0.50 mg (10 to 18 years), followed by a 3 week taper period.	Medium Dose n=19 Participants Participants received oral budesonide suspension (OBS) 0.2 mg/mL at bedtime (hs) and placebo after breakfast (qAM, pc) for 12 weeks, with a total daily dose of 1.4 mg (2 to 9 years) or 2.0 mg (10 to 18 years), followed by a 3 week taper period.	High Dose n=17 Participants Participants received oral budesonide suspension (OBS) 0.2 mg/mL at bedtime (hs) and after breakfast (qAM, pc) for 12 weeks, with a total daily dose of 2.8 mg (2 to 9 years) or 4.0 mg (10 to 18 years), followed by a 3 week taper period.
Percent of Participants Who Responded to Therapy	5.6 percentage of participants	11.8 percentage of participants	52.6 percentage of participants	47.1 percentage of participants

SECONDARY outcome

Timeframe: 12 weeks after the start of treatment

Population: The FAS, defined as participants who received at least one dose of study drug and had evaluable post-baseline esophageal biopsy and clinical symptom data.

Histologic response was defined as a maximum peak eosinophil count at the final treatment evaluation of ≤6 eosinophils/high power field (light microscopy). The maximum peak was identified by examining the peak eosinophil counts obtained from the proximal, mid, and distal esophageal biopsies and selecting the maximum value.

Outcome measures

Outcome measures
Measure	Placebo n=18 Participants Participants received placebo twice daily at bedtime (hs) and after breakfast (qAM, pc) for 12 weeks, followed by a 3 week taper period.	Low Dose n=17 Participants Participants received oral budesonide suspension (OBS) 0.05 mg/mL at bedtime (hs) and placebo after breakfast (qAM, pc) for 12 weeks, with a total daily dose of 0.35 mg (2 to 9 years) or 0.50 mg (10 to 18 years), followed by a 3 week taper period.	Medium Dose n=19 Participants Participants received oral budesonide suspension (OBS) 0.2 mg/mL at bedtime (hs) and placebo after breakfast (qAM, pc) for 12 weeks, with a total daily dose of 1.4 mg (2 to 9 years) or 2.0 mg (10 to 18 years), followed by a 3 week taper period.	High Dose n=17 Participants Participants received oral budesonide suspension (OBS) 0.2 mg/mL at bedtime (hs) and after breakfast (qAM, pc) for 12 weeks, with a total daily dose of 2.8 mg (2 to 9 years) or 4.0 mg (10 to 18 years), followed by a 3 week taper period.
Percent of Participants With Histologic Response	5.6 percentage of participants	23.5 percentage of participants	52.6 percentage of participants	94.1 percentage of participants

SECONDARY outcome

Timeframe: 12 weeks after the start of treatment

Population: The FAS, defined as participants who received at least one dose of study drug and had evaluable post-baseline esophageal biopsy and clinical symptom data.

Histologic remission was defined as a maximum peak eosinophil count at the final treatment evaluation of ≤1 eosinophils/high power field (light microscopy). The maximum peak was identified by examining the peak eosinophil counts obtained from the proximal, mid, and distal esophageal biopsies and selecting the maximum value.

Outcome measures

Outcome measures
Measure	Placebo n=18 Participants Participants received placebo twice daily at bedtime (hs) and after breakfast (qAM, pc) for 12 weeks, followed by a 3 week taper period.	Low Dose n=17 Participants Participants received oral budesonide suspension (OBS) 0.05 mg/mL at bedtime (hs) and placebo after breakfast (qAM, pc) for 12 weeks, with a total daily dose of 0.35 mg (2 to 9 years) or 0.50 mg (10 to 18 years), followed by a 3 week taper period.	Medium Dose n=19 Participants Participants received oral budesonide suspension (OBS) 0.2 mg/mL at bedtime (hs) and placebo after breakfast (qAM, pc) for 12 weeks, with a total daily dose of 1.4 mg (2 to 9 years) or 2.0 mg (10 to 18 years), followed by a 3 week taper period.	High Dose n=17 Participants Participants received oral budesonide suspension (OBS) 0.2 mg/mL at bedtime (hs) and after breakfast (qAM, pc) for 12 weeks, with a total daily dose of 2.8 mg (2 to 9 years) or 4.0 mg (10 to 18 years), followed by a 3 week taper period.
Percent of Participants With Histologic Remission	0.0 percentage of participants	11.8 percentage of participants	42.1 percentage of participants	76.5 percentage of participants

SECONDARY outcome

Timeframe: Baseline, 12 weeks after the start of treatment

Population: The FAS, defined as all participants who received at least one dose of study drug and had evaluable post-baseline esophageal biopsy and clinical symptom data.

The maximum peak number of eosinophils at baseline and at the final treatment evaluation was identified by examining the peak eosinophil counts obtained from the proximal, mid, and distal esophageal biopsies and selecting the maximum value. A negative change from baseline indicates that eosinophil count has decreased.

Outcome measures

Outcome measures
Measure	Placebo n=18 Participants Participants received placebo twice daily at bedtime (hs) and after breakfast (qAM, pc) for 12 weeks, followed by a 3 week taper period.	Low Dose n=17 Participants Participants received oral budesonide suspension (OBS) 0.05 mg/mL at bedtime (hs) and placebo after breakfast (qAM, pc) for 12 weeks, with a total daily dose of 0.35 mg (2 to 9 years) or 0.50 mg (10 to 18 years), followed by a 3 week taper period.	Medium Dose n=19 Participants Participants received oral budesonide suspension (OBS) 0.2 mg/mL at bedtime (hs) and placebo after breakfast (qAM, pc) for 12 weeks, with a total daily dose of 1.4 mg (2 to 9 years) or 2.0 mg (10 to 18 years), followed by a 3 week taper period.	High Dose n=17 Participants Participants received oral budesonide suspension (OBS) 0.2 mg/mL at bedtime (hs) and after breakfast (qAM, pc) for 12 weeks, with a total daily dose of 2.8 mg (2 to 9 years) or 4.0 mg (10 to 18 years), followed by a 3 week taper period.
Percent Change From Baseline in Peak Eosinophil Count	7.93 percent change Standard Deviation 84.162	-52.62 percent change Standard Deviation 51.22	-44.02 percent change Standard Deviation 89.106	-94.75 percent change Standard Deviation 19.615

SECONDARY outcome

Timeframe: Baseline, 12 weeks after the start of treatment

Population: The FAS, defined as all participants who received at least one dose of study drug and had evaluable post-baseline esophageal biopsy and clinical symptom data.

Esophageal endoscopy was used to assess the level of inflammation and eosinophilia. Four categories of endoscopic findings were evaluated and scored for this study: (1) pallor and diminished vascular markings; (2) furrowing with thickened mucosa; (3) presence of white mucosal plaques; and (4) concentric rings or strictures. For each category, 0 points were allocated if no esophageal sites were involved, 1 point if 1 or 2 esophageal sites were involved, and 2 points for pan-esophageal involvement (see Aceves et al., 2007). The maximum possible endoscopy score was 8 points. A negative change from baseline indicates that esophageal inflammation decreased.

Outcome measures

Outcome measures
Measure	Placebo n=18 Participants Participants received placebo twice daily at bedtime (hs) and after breakfast (qAM, pc) for 12 weeks, followed by a 3 week taper period.	Low Dose n=17 Participants Participants received oral budesonide suspension (OBS) 0.05 mg/mL at bedtime (hs) and placebo after breakfast (qAM, pc) for 12 weeks, with a total daily dose of 0.35 mg (2 to 9 years) or 0.50 mg (10 to 18 years), followed by a 3 week taper period.	Medium Dose n=19 Participants Participants received oral budesonide suspension (OBS) 0.2 mg/mL at bedtime (hs) and placebo after breakfast (qAM, pc) for 12 weeks, with a total daily dose of 1.4 mg (2 to 9 years) or 2.0 mg (10 to 18 years), followed by a 3 week taper period.	High Dose n=17 Participants Participants received oral budesonide suspension (OBS) 0.2 mg/mL at bedtime (hs) and after breakfast (qAM, pc) for 12 weeks, with a total daily dose of 2.8 mg (2 to 9 years) or 4.0 mg (10 to 18 years), followed by a 3 week taper period.
Change From Baseline in Endoscopy Score	-0.6 scores on a scale Standard Deviation 2.28	-0.9 scores on a scale Standard Deviation 1.90	-1.3 scores on a scale Standard Deviation 2.23	-2.2 scores on a scale Standard Deviation 1.81

SECONDARY outcome

Timeframe: 12 weeks after the start of treatment

Population: The FAS, defined as participants who received at least one dose of study drug and had evaluable post-baseline esophageal biopsy and clinical symptom data.

Response was defined as a ≥50% reduction from baseline in the eosinophilic esophagitis (EoE) clinical symptom score (CSS). The EoE CSS, scored from 0 to 18 by a doctor, assessed 6 categories: 1) heartburn, 2) abdominal pain, 3) nocturnal awakening with symptoms, 4) nausea, regurgitation, or vomiting, 5) anorexia or early satiety, and 6) dysphagia, odynophagia, or food impaction (a severe symptom). Each domain was scored as follows, based on symptoms in the 2 weeks prior to the assessment: 0 = No symptoms and no coping behaviors required; 1 = Mild: Symptoms limited to 1-3 days or no symptoms because coping behaviors were required to avoid symptoms; 2 = Moderate: Symptoms on \>3 days, with or without minor coping behaviors; 3 = Severe: Symptoms interfered with activities of daily living or symptoms persisted and required major coping behaviors.

Outcome measures

Outcome measures
Measure	Placebo n=18 Participants Participants received placebo twice daily at bedtime (hs) and after breakfast (qAM, pc) for 12 weeks, followed by a 3 week taper period.	Low Dose n=17 Participants Participants received oral budesonide suspension (OBS) 0.05 mg/mL at bedtime (hs) and placebo after breakfast (qAM, pc) for 12 weeks, with a total daily dose of 0.35 mg (2 to 9 years) or 0.50 mg (10 to 18 years), followed by a 3 week taper period.	Medium Dose n=19 Participants Participants received oral budesonide suspension (OBS) 0.2 mg/mL at bedtime (hs) and placebo after breakfast (qAM, pc) for 12 weeks, with a total daily dose of 1.4 mg (2 to 9 years) or 2.0 mg (10 to 18 years), followed by a 3 week taper period.	High Dose n=17 Participants Participants received oral budesonide suspension (OBS) 0.2 mg/mL at bedtime (hs) and after breakfast (qAM, pc) for 12 weeks, with a total daily dose of 2.8 mg (2 to 9 years) or 4.0 mg (10 to 18 years), followed by a 3 week taper period.
Percent of Participants With Clinical Response	77.8 percentage of participants	64.7 percentage of participants	78.9 percentage of participants	52.9 percentage of participants

SECONDARY outcome

Timeframe: 12 weeks after the start of treatment

Population: The FAS, defined as all participants who received at least one dose of study drug and had evaluable post-baseline esophageal biopsy and clinical symptom data.

Clinical remission was defined as an eosinophilic esophagitis (EoE) clinical symptom score (CSS) of zero. EoE CSS, scored from 0 to 18 by a doctor, assessed 6 categories: 1) heartburn, 2) abdominal pain, 3) nocturnal awakening with symptoms, 4) nausea, regurgitation, or vomiting, 5) anorexia or early satiety, and 6) dysphagia, odynophagia, or food impaction (a severe symptom). Each domain was scored as follows, based on symptoms in the 2 weeks prior to the assessment: 0 = No symptoms and no coping behaviors required; 1 = Mild: Symptoms limited to 1-3 days or no symptoms because coping behaviors were required to avoid symptoms; 2 = Moderate: Symptoms on \>3 days, with or without minor coping behaviors; 3 = Severe: Symptoms interfered with activities of daily living or symptoms persisted and required major coping behaviors.

Outcome measures

Outcome measures
Measure	Placebo n=18 Participants Participants received placebo twice daily at bedtime (hs) and after breakfast (qAM, pc) for 12 weeks, followed by a 3 week taper period.	Low Dose n=17 Participants Participants received oral budesonide suspension (OBS) 0.05 mg/mL at bedtime (hs) and placebo after breakfast (qAM, pc) for 12 weeks, with a total daily dose of 0.35 mg (2 to 9 years) or 0.50 mg (10 to 18 years), followed by a 3 week taper period.	Medium Dose n=19 Participants Participants received oral budesonide suspension (OBS) 0.2 mg/mL at bedtime (hs) and placebo after breakfast (qAM, pc) for 12 weeks, with a total daily dose of 1.4 mg (2 to 9 years) or 2.0 mg (10 to 18 years), followed by a 3 week taper period.	High Dose n=17 Participants Participants received oral budesonide suspension (OBS) 0.2 mg/mL at bedtime (hs) and after breakfast (qAM, pc) for 12 weeks, with a total daily dose of 2.8 mg (2 to 9 years) or 4.0 mg (10 to 18 years), followed by a 3 week taper period.
Percent of Participants With Clinical Remission	33.3 percentage of participants	17.6 percentage of participants	31.6 percentage of participants	17.6 percentage of participants

SECONDARY outcome

Timeframe: Baseline, 12 weeks after the start of treatment

Population: The FAS, defined as all participants who received at least one dose of study drug and had evaluable post-baseline esophageal biopsy and clinical symptom data.

The EoE CSS, scored from 0 to 18 by a doctor, assessed 6 categories: 1) heartburn, 2) abdominal pain, 3) nocturnal awakening with symptoms, 4) nausea, regurgitation, or vomiting, 5) anorexia or early satiety, and 6) dysphagia, odynophagia, or food impaction (a severe symptom). Each domain was scored as follows, based on symptoms in the 2 weeks prior to the assessment: 0 = No symptoms and no coping behaviors required; 1= Mild: Symptoms limited to 1-3 days or no symptoms because coping behaviors were required to avoid symptoms; 2= Moderate: Symptoms on \>3 days, with or without minor coping behaviors; 3= Severe: Symptoms interfered with activities of daily living or symptoms persisted and required major coping behaviors. A negative change from baseline indicates that symptoms decreased.

Outcome measures

Outcome measures
Measure	Placebo n=18 Participants Participants received placebo twice daily at bedtime (hs) and after breakfast (qAM, pc) for 12 weeks, followed by a 3 week taper period.	Low Dose n=17 Participants Participants received oral budesonide suspension (OBS) 0.05 mg/mL at bedtime (hs) and placebo after breakfast (qAM, pc) for 12 weeks, with a total daily dose of 0.35 mg (2 to 9 years) or 0.50 mg (10 to 18 years), followed by a 3 week taper period.	Medium Dose n=19 Participants Participants received oral budesonide suspension (OBS) 0.2 mg/mL at bedtime (hs) and placebo after breakfast (qAM, pc) for 12 weeks, with a total daily dose of 1.4 mg (2 to 9 years) or 2.0 mg (10 to 18 years), followed by a 3 week taper period.	High Dose n=17 Participants Participants received oral budesonide suspension (OBS) 0.2 mg/mL at bedtime (hs) and after breakfast (qAM, pc) for 12 weeks, with a total daily dose of 2.8 mg (2 to 9 years) or 4.0 mg (10 to 18 years), followed by a 3 week taper period.
Percent Change From Baseline in Eosinophilic Esophagitis (EoE) Clinical Symptom Score (CSS)	-64.46 percent change Standard Deviation 45.759	-60.83 percent change Standard Deviation 30.347	-65.89 percent change Standard Deviation 32.382	-47.21 percent change Standard Deviation 40.790

SECONDARY outcome

Timeframe: Baseline, 12 weeks after the start of treatment

Population: The FAS, defined as all participants who received at least one dose of study drug and had evaluable post-baseline esophageal biopsy and clinical symptom data.

Physician investigators were asked to complete a visual analog scale (VAS) to provide a global assessment of eosinophilic esophagitis (EoE) activity in each participant. The VAS was a 100-mm horizontal line on which the right extreme (100) was labeled "worst possible disease activity" and the left (0) was labeled "no disease activity." Investigators were instructed to consider the line for the VAS as a continuum with their own opinion of extremes on either end. Investigators drew a vertical line at a point that best approximated the participant's current level of EoE disease activity. The investigator was to take into consideration how esophageal disease was impacting the participant's daily activities. The following instruction was given to the investigators: "Using the visual analog scale below, please mark a vertical line on the scale to indicate your assessment of EoE activity in this participant at this time." A negative change from baseline indicates that symptoms decreased.

Outcome measures

Outcome measures
Measure	Placebo n=18 Participants Participants received placebo twice daily at bedtime (hs) and after breakfast (qAM, pc) for 12 weeks, followed by a 3 week taper period.	Low Dose n=17 Participants Participants received oral budesonide suspension (OBS) 0.05 mg/mL at bedtime (hs) and placebo after breakfast (qAM, pc) for 12 weeks, with a total daily dose of 0.35 mg (2 to 9 years) or 0.50 mg (10 to 18 years), followed by a 3 week taper period.	Medium Dose n=19 Participants Participants received oral budesonide suspension (OBS) 0.2 mg/mL at bedtime (hs) and placebo after breakfast (qAM, pc) for 12 weeks, with a total daily dose of 1.4 mg (2 to 9 years) or 2.0 mg (10 to 18 years), followed by a 3 week taper period.	High Dose n=16 Participants Participants received oral budesonide suspension (OBS) 0.2 mg/mL at bedtime (hs) and after breakfast (qAM, pc) for 12 weeks, with a total daily dose of 2.8 mg (2 to 9 years) or 4.0 mg (10 to 18 years), followed by a 3 week taper period.
Change From Baseline in Physician's Global Assessment Score of Disease Severity	-38.9 scores on a scale Standard Deviation 28.02	-30.2 scores on a scale Standard Deviation 27.11	-39.3 scores on a scale Standard Deviation 22.89	-35.7 scores on a scale Standard Deviation 28.49

SECONDARY outcome

Timeframe: Week 2, 4, or 8, or at the Final Treatment Evaluation

Population: The Pharmacokinetic (PK) Set, defined as all participants in the safety analysis set who received oral budesonide suspension (OBS) and had sufficient PK samples to calculate PK parameters.

On the day that pharmacokinetic (PK) blood samples were obtained, each participant delayed the morning dose of study medication until instructed to dose in the clinic. The sampling timepoints included pre-dose (0), and 0.5, 1, 2, 3, 4, 6, and 8 hours post-dose. The lower limit of quantitation (LLOQ) for the analytical method was approximately 20 pg/mL in plasma using 0.2 mL of the sample. Because the PK analyses for the medium and high dose oral budesonide suspension (OBS) groups were based on plasma samples collected following administration of identical single doses of OBS, the data for the medium-dose group (OBS once-daily) and high-dose group (OBS twice-daily) were summarized together.

Outcome measures

Outcome measures
Measure	Placebo n=4 Participants Participants received placebo twice daily at bedtime (hs) and after breakfast (qAM, pc) for 12 weeks, followed by a 3 week taper period.	Low Dose n=5 Participants Participants received oral budesonide suspension (OBS) 0.05 mg/mL at bedtime (hs) and placebo after breakfast (qAM, pc) for 12 weeks, with a total daily dose of 0.35 mg (2 to 9 years) or 0.50 mg (10 to 18 years), followed by a 3 week taper period.	Medium Dose n=15 Participants Participants received oral budesonide suspension (OBS) 0.2 mg/mL at bedtime (hs) and placebo after breakfast (qAM, pc) for 12 weeks, with a total daily dose of 1.4 mg (2 to 9 years) or 2.0 mg (10 to 18 years), followed by a 3 week taper period.	High Dose n=13 Participants Participants received oral budesonide suspension (OBS) 0.2 mg/mL at bedtime (hs) and after breakfast (qAM, pc) for 12 weeks, with a total daily dose of 2.8 mg (2 to 9 years) or 4.0 mg (10 to 18 years), followed by a 3 week taper period.
Maximum Plasma Concentration (Cmax) of Budesonide	492.0 pg/mL Standard Deviation 417.81	195.0 pg/mL Standard Deviation 64.37	1019.5 pg/mL Standard Deviation 670.18	958.4 pg/mL Standard Deviation 527.64

SECONDARY outcome

Timeframe: Week 2, 4, or 8, or at the Final Treatment Evaluation

Population: The PK Set, defined as all participants in the safety analysis set who received oral budesonide suspension (OBS) and had sufficient PK samples to calculate PK parameters.

Outcome measures

Outcome measures
Measure	Placebo n=4 Participants Participants received placebo twice daily at bedtime (hs) and after breakfast (qAM, pc) for 12 weeks, followed by a 3 week taper period.	Low Dose n=5 Participants Participants received oral budesonide suspension (OBS) 0.05 mg/mL at bedtime (hs) and placebo after breakfast (qAM, pc) for 12 weeks, with a total daily dose of 0.35 mg (2 to 9 years) or 0.50 mg (10 to 18 years), followed by a 3 week taper period.	Medium Dose n=15 Participants Participants received oral budesonide suspension (OBS) 0.2 mg/mL at bedtime (hs) and placebo after breakfast (qAM, pc) for 12 weeks, with a total daily dose of 1.4 mg (2 to 9 years) or 2.0 mg (10 to 18 years), followed by a 3 week taper period.	High Dose n=13 Participants Participants received oral budesonide suspension (OBS) 0.2 mg/mL at bedtime (hs) and after breakfast (qAM, pc) for 12 weeks, with a total daily dose of 2.8 mg (2 to 9 years) or 4.0 mg (10 to 18 years), followed by a 3 week taper period.
Time to Maximum (Tmax) And Half Maximum (T1/2) Plasma Concentration of Budesonide T1/2	3.288 hours Standard Deviation 0.8265	3.398 hours Standard Deviation 0.7841	3.472 hours Standard Deviation 2.6753	3.528 hours Standard Deviation 1.0223
Time to Maximum (Tmax) And Half Maximum (T1/2) Plasma Concentration of Budesonide Tmax	0.68 hours Standard Deviation 0.360	1.20 hours Standard Deviation 0.447	0.93 hours Standard Deviation 0.372	1.12 hours Standard Deviation 0.546

SECONDARY outcome

Timeframe: Week 2, 4, or 8, or at the Final Treatment Evaluation

Population: The PK Set, defined as all participants in the safety analysis set who received oral budesonide suspension (OBS) and had sufficient PK samples to calculate PK parameters.

Outcome measures

Outcome measures
Measure	Placebo n=4 Participants Participants received placebo twice daily at bedtime (hs) and after breakfast (qAM, pc) for 12 weeks, followed by a 3 week taper period.	Low Dose n=5 Participants Participants received oral budesonide suspension (OBS) 0.05 mg/mL at bedtime (hs) and placebo after breakfast (qAM, pc) for 12 weeks, with a total daily dose of 0.35 mg (2 to 9 years) or 0.50 mg (10 to 18 years), followed by a 3 week taper period.	Medium Dose n=15 Participants Participants received oral budesonide suspension (OBS) 0.2 mg/mL at bedtime (hs) and placebo after breakfast (qAM, pc) for 12 weeks, with a total daily dose of 1.4 mg (2 to 9 years) or 2.0 mg (10 to 18 years), followed by a 3 week taper period.	High Dose n=13 Participants Participants received oral budesonide suspension (OBS) 0.2 mg/mL at bedtime (hs) and after breakfast (qAM, pc) for 12 weeks, with a total daily dose of 2.8 mg (2 to 9 years) or 4.0 mg (10 to 18 years), followed by a 3 week taper period.
Area Under The Plasma Concentration-Time Curve (AUC) of Budesonide From Time Zero to Time of The Last Measurable Concentration (AUC0-last)	1139.5 hr*pg/mL Standard Deviation 800.84	743.8 hr*pg/mL Standard Deviation 425.26	3259.3 hr*pg/mL Standard Deviation 2109.37	3636.9 hr*pg/mL Standard Deviation 1769.88

SECONDARY outcome

Timeframe: 15 weeks after the start of treatment

Population: The Safety Analysis Set, defined as all randomized participants who received at least one dose of double-blind study drug.

Corticosteroid-Related TEAEs included candidiasis, oesophageal candidiasis, crying, psychomotor hyperactivity, aggression, anger, anxiety, conduct disorder, emotional disorder, insomnia, or mood altered mood. Corticosteroid-Related TEAEs were assessed systematically during the treatment and taper periods.

Outcome measures

Outcome measures
Measure	Placebo n=21 Participants Participants received placebo twice daily at bedtime (hs) and after breakfast (qAM, pc) for 12 weeks, followed by a 3 week taper period.	Low Dose n=21 Participants Participants received oral budesonide suspension (OBS) 0.05 mg/mL at bedtime (hs) and placebo after breakfast (qAM, pc) for 12 weeks, with a total daily dose of 0.35 mg (2 to 9 years) or 0.50 mg (10 to 18 years), followed by a 3 week taper period.	Medium Dose n=19 Participants Participants received oral budesonide suspension (OBS) 0.2 mg/mL at bedtime (hs) and placebo after breakfast (qAM, pc) for 12 weeks, with a total daily dose of 1.4 mg (2 to 9 years) or 2.0 mg (10 to 18 years), followed by a 3 week taper period.	High Dose n=20 Participants Participants received oral budesonide suspension (OBS) 0.2 mg/mL at bedtime (hs) and after breakfast (qAM, pc) for 12 weeks, with a total daily dose of 2.8 mg (2 to 9 years) or 4.0 mg (10 to 18 years), followed by a 3 week taper period.
Percent of Participants With Potential Corticosteroid-Related Treatment-Emergent Adverse Events (TEAEs)	9.5 percentage of participants	9.5 percentage of participants	21.0 percentage of participants	15.0 percentage of participants

SECONDARY outcome

Timeframe: Baseline, 12 weeks after the start of treatment

Population: The Safety Analysis Set, defined as all randomized participants who received at least one dose of double-blind study drug.

BP was assessed for each treatment group at baseline and at each post-baseline visit including the final treatment evaluation.

Outcome measures

Outcome measures
Measure	Placebo n=21 Participants Participants received placebo twice daily at bedtime (hs) and after breakfast (qAM, pc) for 12 weeks, followed by a 3 week taper period.	Low Dose n=21 Participants Participants received oral budesonide suspension (OBS) 0.05 mg/mL at bedtime (hs) and placebo after breakfast (qAM, pc) for 12 weeks, with a total daily dose of 0.35 mg (2 to 9 years) or 0.50 mg (10 to 18 years), followed by a 3 week taper period.	Medium Dose n=19 Participants Participants received oral budesonide suspension (OBS) 0.2 mg/mL at bedtime (hs) and placebo after breakfast (qAM, pc) for 12 weeks, with a total daily dose of 1.4 mg (2 to 9 years) or 2.0 mg (10 to 18 years), followed by a 3 week taper period.	High Dose n=20 Participants Participants received oral budesonide suspension (OBS) 0.2 mg/mL at bedtime (hs) and after breakfast (qAM, pc) for 12 weeks, with a total daily dose of 2.8 mg (2 to 9 years) or 4.0 mg (10 to 18 years), followed by a 3 week taper period.
Mean Change in Blood Pressure (BP) at End of Treatment Systolic BP	-1.5 mmHg Standard Deviation 14.74	1.8 mmHg Standard Deviation 11.13	3.5 mmHg Standard Deviation 8.20	8.0 mmHg Standard Deviation 13.58
Mean Change in Blood Pressure (BP) at End of Treatment Diastolic BP	-3.1 mmHg Standard Deviation 10.31	0.5 mmHg Standard Deviation 8.89	3.1 mmHg Standard Deviation 9.18	5.1 mmHg Standard Deviation 8.83

Adverse Events

Placebo

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

Low Dose

Serious events: 0 serious events

Other events: 13 other events

Deaths: 0 deaths

Medium Dose

Serious events: 0 serious events

Other events: 16 other events

Deaths: 0 deaths

High Dose

Serious events: 1 serious events

Other events: 17 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo n=21 participants at risk Participants received placebo twice daily at bedtime (hs) and after breakfast (qAM, pc) for 12 weeks with a 3 week taper period.	Low Dose n=21 participants at risk Participants received oral budesonide suspension (OBS) 0.05 mg/mL at bedtime (hs) and placebo after breakfast (qAM, pc) for 12 weeks with a 3 week taper period.	Medium Dose n=19 participants at risk Participants received oral budesonide suspension (OBS) 0.2 mg/mL at bedtime (hs) and placebo after breakfast (qAM, pc) for 12 weeks with a 3 week taper period.	High Dose n=20 participants at risk Participants received oral budesonide suspension (OBS) 0.2 mg/mL at bedtime (hs) and after breakfast (qAM, pc) for 12 weeks with a 3 week taper period.
Metabolism and nutrition disorders Diet refusal	0.00% 0/21 Adverse events are presented for the Safety Analysis Set, defined as all randomized participants who received at least one dose of double-blind study drug. Treatment group assignment was the treatment actually received. One participant in the medium dose group was enrolled and randomized then withdrew consent and did not receive study drug.	0.00% 0/21 Adverse events are presented for the Safety Analysis Set, defined as all randomized participants who received at least one dose of double-blind study drug. Treatment group assignment was the treatment actually received. One participant in the medium dose group was enrolled and randomized then withdrew consent and did not receive study drug.	0.00% 0/19 Adverse events are presented for the Safety Analysis Set, defined as all randomized participants who received at least one dose of double-blind study drug. Treatment group assignment was the treatment actually received. One participant in the medium dose group was enrolled and randomized then withdrew consent and did not receive study drug.	5.0% 1/20 • Number of events 1 Adverse events are presented for the Safety Analysis Set, defined as all randomized participants who received at least one dose of double-blind study drug. Treatment group assignment was the treatment actually received. One participant in the medium dose group was enrolled and randomized then withdrew consent and did not receive study drug.

Other adverse events

Additional Information

Study Director

Shire

Phone: +1 866 842 5335

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee If a multicenter publication is not submitted within twelve (12) months after conclusion, abandonment or termination of the Study at all sites, or after Sponsor confirms there shall be no multicenter Study publication, the Institution and/or such Principal Investigator may publish the results from the Institution site individually.
Publication restrictions are in place

Restriction type: OTHER