Trial Outcomes & Findings for A 6-week Study in Asthmatic Children Aged 6 to <12 Yrs Comparing Budesonide pMDI 160ug Twice Daily With Placebo (NCT NCT01136382)

NCT ID: NCT01136382

Last Updated: 2014-08-01

Results Overview

The peak expiratory flow rate is the maximal rate that a person can exhale during a short maximal expiratory effort after a full inspiration. Baseline was calculated using the mean of the data recorded during the last 7 days of the run-in period, and the treatment period average was calculated as the mean of all available data recorded during the entire treatment period.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 304 participants
• Primary outcome timeframe: Baseline to 6 weeks
• Results posted on: 2014-08-01

Participant Flow

This multicenter study was conducted in Bulgaria, Hungary, Latvia, Poland, Slovakia, South Africa, and the United States between 07 August 2011 and 05 April 2013.

The study consisted of a screening visit (Visit 1), an enrollment visit (Visit 2), a 7- to 21-day run-in/qualification period, a randomization visit (Visit 3), and 6 further weekly visits during a treatment period of 6 weeks. A telephone follow-up was conducted approximately 2 weeks after the final study visit.

Participant milestones

Measure	Placebo Placebo pMDI bid	Budesonide Budesonide pMDI 160 mcg bid
Overall Study STARTED	152	152
Overall Study COMPLETED	92	121
Overall Study NOT COMPLETED	60	31

Reasons for withdrawal

Measure	Placebo Placebo pMDI bid	Budesonide Budesonide pMDI 160 mcg bid
Overall Study Other	8	3
Overall Study Study-Specific Withdrawal Criteria	48	25
Overall Study Severe Non-Compliance to Protocol	0	2
Overall Study Withdrawal by Subject	4	1

Baseline Characteristics

A 6-week Study in Asthmatic Children Aged 6 to <12 Yrs Comparing Budesonide pMDI 160ug Twice Daily With Placebo

Baseline characteristics by cohort

Measure	Placebo n=152 Participants Placebo pMDI bid	Budesonide n=152 Participants Budesonide pMDI 160 mcg bid	Total n=304 Participants Total of all reporting groups
Age, Continuous	9.0 years STANDARD_DEVIATION 1.62 • n=5 Participants	9.0 years STANDARD_DEVIATION 1.63 • n=7 Participants	9.0 years STANDARD_DEVIATION 1.62 • n=5 Participants
Age, Customized 6 to <8 years	33 participants n=5 Participants	33 participants n=7 Participants	66 participants n=5 Participants
Age, Customized 8 to- <12 years	119 participants n=5 Participants	119 participants n=7 Participants	238 participants n=5 Participants
Sex: Female, Male Female	58 Participants n=5 Participants	54 Participants n=7 Participants	112 Participants n=5 Participants
Sex: Female, Male Male	94 Participants n=5 Participants	98 Participants n=7 Participants	192 Participants n=5 Participants
Race/Ethnicity, Customized Hispanic or Latino	10 participants n=5 Participants	11 participants n=7 Participants	21 participants n=5 Participants
Race/Ethnicity, Customized Native Hawaiian/Pacific Islander	1 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants
Race/Ethnicity, Customized African American	7 participants n=5 Participants	9 participants n=7 Participants	16 participants n=5 Participants
Race/Ethnicity, Customized Asian (other than Chinese and Japanese)	0 participants n=5 Participants	2 participants n=7 Participants	2 participants n=5 Participants
Race/Ethnicity, Customized Not Applicable	128 participants n=5 Participants	126 participants n=7 Participants	254 participants n=5 Participants
Race/Ethnicity, Customized Other	6 participants n=5 Participants	4 participants n=7 Participants	10 participants n=5 Participants
Forced expiratory volume in 1 second (FEV1)	1.70 liters STANDARD_DEVIATION 0.416 • n=5 Participants	1.69 liters STANDARD_DEVIATION 0.388 • n=7 Participants	1.70 liters STANDARD_DEVIATION 0.401 • n=5 Participants

PRIMARY outcome

Timeframe: Baseline to 6 weeks

Population: The efficacy analysis set consisted of all patients who were randomized, received at least 1 dose of study medication, and contributed data for at least 1 efficacy endpoint.

The peak expiratory flow rate is the maximal rate that a person can exhale during a short maximal expiratory effort after a full inspiration. Baseline was calculated using the mean of the data recorded during the last 7 days of the run-in period, and the treatment period average was calculated as the mean of all available data recorded during the entire treatment period.

Outcome measures

Measure	Placebo n=151 Participants Placebo pMDI bid	Budesonide n=151 Participants Budesonide pMDI 160 mcg bid
Change in Morning Peak Expiratory Flow (PEF) From Baseline to the Treatment Period Average	4.1 liters/minute Standard Error 3.19	17.8 liters/minute Standard Error 3.24

SECONDARY outcome

Timeframe: Baseline to 6 weeks

Population: The efficacy analysis set consisted of all patients who were randomized, received at least 1 dose of study medication, and contributed data for at least 1 efficacy endpoint.

FEV1 is the volume exhaled during the first second of a forced expiratory maneuver started from the level of total lung capacity. Baseline was defined as the pre-dose assessment value measured at randomization (Visit 3), and the treatment period average was calculated as the mean of all available data recorded during the entire treatment period.

Outcome measures

Measure	Placebo n=149 Participants Placebo pMDI bid	Budesonide n=152 Participants Budesonide pMDI 160 mcg bid
Change in Forced Expiratory Volume in 1 Second (FEV1) From Baseline to Treatment Period Average	0.00 liters Standard Error 0.023	0.06 liters Standard Error 0.023

SECONDARY outcome

Timeframe: Baseline to 6 weeks

Population: The efficacy analysis set consisted of all patients who were randomized, received at least 1 dose of study medication, and contributed data for at least 1 efficacy endpoint.

The peak expiratory flow rate is the maximal rate that a person can exhale during a short maximal expiratory effort after a full inspiration. Baseline was calculated using the mean of the data recorded during the last 7 days of the run-in period, and the treatment period average was calculated as the mean of all available data recorded during the entire treatment period.

Outcome measures

Measure	Placebo n=150 Participants Placebo pMDI bid	Budesonide n=151 Participants Budesonide pMDI 160 mcg bid
Change in Evening PEF From Baseline to the Treatment Period Average	4.0 liters/minute Standard Error 3.08	14.7 liters/minute Standard Error 3.13

SECONDARY outcome

Timeframe: Baseline to 6 weeks

Population: The efficacy analysis set consisted of all patients who were randomized, received at least 1 dose of study medication, and contributed data for at least 1 efficacy endpoint.

FVC is the total volume of air expired after a full inspiration. Baseline was defined as the pre-dose assessment value measured at randomization (Visit 3), and the treatment period average was calculated as the mean of all available data recorded during the entire treatment period.

Outcome measures

Measure	Placebo n=149 Participants Placebo pMDI bid	Budesonide n=152 Participants Budesonide pMDI 160 mcg bid
Change in Forced Vital Capacity (FVC) From Baseline to Treatment Period Average	0.00 liters Standard Error 0.021	0.04 liters Standard Error 0.021

SECONDARY outcome

Timeframe: Baseline to 6 weeks

Population: The efficacy analysis set consisted of all patients who were randomized, received at least 1 dose of study medication, and contributed data for at least 1 efficacy endpoint.

FEF25-75 is the average rate of airflow during the midportion of the forced vital capacity. Baseline was defined as the pre-dose assessment value measured at randomization (Visit 3), and the treatment period average was calculated as the mean of all available data recorded during the entire treatment period.

Outcome measures

Measure	Placebo n=149 Participants Placebo pMDI bid	Budesonide n=152 Participants Budesonide pMDI 160 mcg bid
Change in Forced Mid-expiratory Flow Between 25% and 75% of the FVC (FEF25-75) From Baseline to Treatment Period Average	0.01 liters/second Standard Error 0.045	0.11 liters/second Standard Error 0.045

SECONDARY outcome

Timeframe: Baseline to 6 weeks

Population: The efficacy analysis set consisted of all patients who were randomized, received at least 1 dose of study medication, and contributed data for at least 1 efficacy endpoint.

Patients, with the help of their caregiver, were required to rate and document their asthma symptoms twice daily as an overall symptom score for the time period since their previous recording. The following rating scales were used: 0 = None; no symptoms of asthma; 1 = Mild symptoms; awareness of asthma symptoms and/or signs that are easily tolerated; 2 = Moderate symptoms, asthma symptoms with some discomfort, causing some interference with daily activities or sleep; 3 = Severe symptoms; incapacitating asthma symptoms and/or signs, with inability to perform daily activities or to sleep.

Outcome measures

Measure	Placebo n=151 Participants Placebo pMDI bid	Budesonide n=152 Participants Budesonide pMDI 160 mcg bid
Change in Total Daily and Daytime Asthma Symptom Scores From Baseline to Treatment Period Average Daytime asthma symptom score	-0.2 units on a scale Standard Error 0.06	-0.4 units on a scale Standard Error 0.06
Change in Total Daily and Daytime Asthma Symptom Scores From Baseline to Treatment Period Average Total asthma symptom score	-0.5 units on a scale Standard Error 0.11	-0.8 units on a scale Standard Error 0.11

SECONDARY outcome

Timeframe: Baseline to 6 weeks

Population: The efficacy analysis set consisted of all patients who were randomized, received at least 1 dose of study medication, and contributed data for at least 1 efficacy endpoint.

Patients, with the help of their caregiver, were required to rate and document their asthma symptoms twice daily as an overall symptom score for the time period since their previous recording. The following rating scales were used: 0 = None; no symptoms of asthma; 1 = Mild symptoms; awareness of asthma symptoms and/or signs that are easily tolerated; 2 = Moderate symptoms, asthma symptoms with some discomfort, causing some interference with daily activities or sleep; 3 = Severe symptoms; incapacitating asthma symptoms and/or signs, with inability to perform daily activities or to sleep.

Outcome measures

Measure	Placebo n=152 Participants Placebo pMDI bid	Budesonide n=152 Participants Budesonide pMDI 160 mcg bid
Change in Nighttime Asthma Symptom Score From Baseline to Treatment Period Average	-0.3 units on a scale Standard Error 0.06	-0.4 units on a scale Standard Error 0.06

SECONDARY outcome

Timeframe: Baseline to 6 weeks

Population: The efficacy analysis set consisted of all patients who were randomized, received at least 1 dose of study medication, and contributed data for at least 1 efficacy endpoint.

Patients, with the help of their caregiver, were asked to respond to a standard question each morning as they completed their eDiary. The question to be answered was, "Did your asthma cause you to wake-up last night?" If yes, patients were asked, "Did you need to use your reliever medication (albuterol/salbutamol inhaler) before you went back to sleep?" Baseline is defined as the percentage of days where patient experienced nighttime awakenings out of all available days where data was collected during the last 7 days of the run-in period.

Outcome measures

Measure	Placebo n=152 Participants Placebo pMDI bid	Budesonide n=152 Participants Budesonide pMDI 160 mcg bid
Change in Nighttime Awakenings and Nighttime Awakenings With Reliever Medication Use From Baseline to Treatment Period Average Nighttime awakenings	-9.8 percentage of days with awakenings Standard Error 1.81	-14.5 percentage of days with awakenings Standard Error 1.84
Change in Nighttime Awakenings and Nighttime Awakenings With Reliever Medication Use From Baseline to Treatment Period Average Nighttime awakenings with reliever use	-6.1 percentage of days with awakenings Standard Error 1.17	-10.0 percentage of days with awakenings Standard Error 1.18

SECONDARY outcome

Timeframe: Baseline to 6 weeks

Population: The efficacy analysis set consisted of all patients who were randomized, received at least 1 dose of study medication, and contributed data for at least 1 efficacy endpoint.

The patient, with the help of their caregiver, recorded the number of inhalations of reliever medication used, for relief of asthma symptoms, twice daily in the eDiary. Patients were asked to respond to a standard question twice daily (morning and evening). The question to be answered was, "How many albuterol/salbutamol inhalations since last diary entry?"

Outcome measures

Measure	Placebo n=151 Participants Placebo pMDI bid	Budesonide n=152 Participants Budesonide pMDI 160 mcg bid
Change in Total Daily and Daytime Reliever Medication Use From Baseline to Treatment Period Average Daytime reliever medication use	-0.1 inhalations per day Standard Error 0.07	-0.4 inhalations per day Standard Error 0.07
Change in Total Daily and Daytime Reliever Medication Use From Baseline to Treatment Period Average Total reliever medication use	-0.3 inhalations per day Standard Error 0.11	-0.7 inhalations per day Standard Error 0.11

SECONDARY outcome

Timeframe: Baseline to 6 weeks

Population: The efficacy analysis set consisted of all patients who were randomized, received at least 1 dose of study medication, and contributed data for at least 1 efficacy endpoint.

The patient, with the help of their caregiver, recorded the number of inhalations of reliever medication used, for relief of asthma symptoms, twice daily in the eDiary. Patients were asked to respond to a standard question twice daily (morning and evening). The question to be answered was, "How many albuterol/salbutamol inhalations since last diary entry?"

Outcome measures

Measure	Placebo n=152 Participants Placebo pMDI bid	Budesonide n=152 Participants Budesonide pMDI 160 mcg bid
Change in Nighttime Reliever Medication Use From Baseline to Treatment Period Average	-0.1 inhalations per day Standard Error 0.06	-0.4 inhalations per day Standard Error 0.06

SECONDARY outcome

Timeframe: Baseline to 6 weeks

Population: The efficacy analysis set consisted of all patients who were randomized, received at least 1 dose of study medication, and contributed data for at least 1 efficacy endpoint.

Patients were considered to have experienced a "pre-defined asthma event" if any of the following conditions were met during the study: 1. At each visit or follow-up visit, a decrease in morning pre-dose FEV1 >=20% from the Visit 3 (randomization visit) morning pre-dose FEV1 or a decrease to <65% of predicted normal value; 2. The use of >=8 actuations of albuterol/salbutamol per day on 3 or more days within any period of 7 consecutive days following randomization; 3. A decrease in morning PEF >=20% from baseline on 3 or more days within any period of 7 consecutive days after randomization; 4. Two or more nights with an awakening due to asthma, which required the use of reliever medication within any period of 7 consecutive days after randomization; 5. A clinical exacerbation requiring emergency treatment, hospitalization, or use of an asthma medication not allowed by the study protocol.

Outcome measures

Measure	Placebo n=152 Participants Placebo pMDI bid	Budesonide n=152 Participants Budesonide pMDI 160 mcg bid
Number of Withdrawals Due to Pre-defined Asthma Events	50 participants	25 participants

Adverse Events

Budesonide pMDI 160mcg b.i.d.

Serious events: 0 serious events

Other events: 27 other events

Deaths: 0 deaths

Placebo pMDI b.i.d.

Serious events: 0 serious events

Other events: 40 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Budesonide pMDI 160mcg b.i.d. n=152 participants at risk	Placebo pMDI b.i.d. n=152 participants at risk
Infections and infestations INFLUENZA	2.6% 4/152 • Number of events 5	2.6% 4/152 • Number of events 5
Infections and infestations NASOPHARYNGITIS	7.9% 12/152 • Number of events 12	5.9% 9/152 • Number of events 11
Infections and infestations PHARYNGITIS	3.3% 5/152 • Number of events 5	5.3% 8/152 • Number of events 8
Infections and infestations VIRAL UPPER RESPIRATORY TRACT INFECTION	2.0% 3/152 • Number of events 3	5.3% 8/152 • Number of events 9
Respiratory, thoracic and mediastinal disorders ASTHMA	0.66% 1/152 • Number of events 1	7.2% 11/152 • Number of events 11
Respiratory, thoracic and mediastinal disorders OROPHARYNGEAL PAIN	2.0% 3/152 • Number of events 3	2.6% 4/152 • Number of events 4

Additional Information

Geoff Gilmartin

AstraZeneca

Email: ClinicalTrialTransparency@astrazeneca.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: GT60