Trial Outcomes & Findings for A Study of 2 Doses of MAP0010 and Placebo in Asthmatic Children (NCT NCT00569192)

Results Overview

The individual symptoms at each time point to be monitored are: cough, wheeze, and shortness of breath. The individual symptoms were scored using a four point scale: 0=no symptoms; 1=mild symptoms; 2=moderate symptoms; 3=severe symptoms Daily composite symptom score is based on the average of the individual symptom scores for a day. Daytime composite symptom score is defined as average of the last 5 days' daily composite symptom scores within the last 7 days immediately preceding the end day of that week. The range for the daytime composite symptom score is 0 (no symptoms) to 3 (severe symptoms). A negative change indicates an improvement of symptoms and a positive change indicates a worsening of symptoms.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

360 participants

Primary outcome timeframe

baseline, week 12

Results posted on

2014-01-09

Participant Flow

Participant milestones

Participant milestones
Measure	Placebo Placebo delivered by nebulization twice daily for 12 weeks	0.135 mg MAP0010 0.135mg MAP0010 (unit dose budesonide) delivered by nebulization twice daily for 12 weeks	0.25 mg MAP0010 0.125mg MAP0010 (unit dose budesonide) delivered by nebulization twice daily for 12 weeks
Overall Study STARTED	111	125	124
Overall Study COMPLETED	88	105	99
Overall Study NOT COMPLETED	23	20	25

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Study of 2 Doses of MAP0010 and Placebo in Asthmatic Children

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=111 Participants Placebo delivered by nebulization twice daily for 12 weeks	0.135 mg MAP0010 n=125 Participants 0.135mg MAP0010 (unit dose budesonide) delivered by nebulization twice daily for 12 weeks	0.25 mg MAP0010 n=124 Participants 0.25mg MAP0010 (unit dose budesonide) delivered by nebulization twice daily for 12 weeks	Total n=360 Participants Total of all reporting groups
Age, Continuous	4.0 years n=5 Participants	4.4 years STANDARD_DEVIATION 2.33 • n=7 Participants	4.2 years STANDARD_DEVIATION 2.27 • n=5 Participants	4.4 years STANDARD_DEVIATION 2.26 • n=4 Participants
Sex: Female, Male Female	45 Participants n=5 Participants	50 Participants n=7 Participants	49 Participants n=5 Participants	144 Participants n=4 Participants
Sex: Female, Male Male	66 Participants n=5 Participants	75 Participants n=7 Participants	75 Participants n=5 Participants	216 Participants n=4 Participants

PRIMARY outcome

Timeframe: baseline, week 12

Population: Intent-to-treat includes all randomized patients who have received at least one dose of study drug and have baseline and at least one post treatment efficacy assessment available.

The individual symptoms at each time point to be monitored are: cough, wheeze, and shortness of breath. The individual symptoms were scored using a four point scale: 0=no symptoms; 1=mild symptoms; 2=moderate symptoms; 3=severe symptoms Daily composite symptom score is based on the average of the individual symptom scores for a day. Daytime composite symptom score is defined as average of the last 5 days' daily composite symptom scores within the last 7 days immediately preceding the end day of that week. The range for the daytime composite symptom score is 0 (no symptoms) to 3 (severe symptoms). A negative change indicates an improvement of symptoms and a positive change indicates a worsening of symptoms.

Outcome measures

Outcome measures
Measure	Placebo n=110 Participants Placebo delivered by nebulization twice daily for 12 weeks	0.135 mg MAP0010 n=122 Participants 0.135mg MAP0010 (unit dose budesonide) delivered by nebulization twice daily for 12 weeks	0.25 mg MAP0010 n=117 Participants 0.25mg MAP0010 (unit dose budesonide) delivered by nebulization twice daily for 12 weeks
Change From Baseline in Daytime Composite Symptom Score Baseline	2.73 units on a scale Standard Deviation 1.406	2.96 units on a scale Standard Deviation 1.329	2.87 units on a scale Standard Deviation 1.383
Change From Baseline in Daytime Composite Symptom Score Change from Baseline at week 12	-1.38 units on a scale Standard Deviation 1.722	-1.77 units on a scale Standard Deviation 1.618	-1.56 units on a scale Standard Deviation 1.591

PRIMARY outcome

Timeframe: baseline, week 12

Population: Intent-to-treat includes all randomized patients who have received at least one dose of study drug and have baseline and at least one post treatment efficacy assessment available.

The individual symptoms at each time point to be monitored are: cough, wheeze, and shortness of breath. The individual symptoms were scored using a four point scale: 0=no symptoms; 1=mild symptoms; 2=moderate symptoms; 3=severe symptoms Nightly composite symptom score is based on the average of the individual symptom scores for the night. Nightime composite symptom score is defined as average of the last 5 days' nightly composite symptom scores within the last 7 nights immediately preceding the end day of that week. The range for the nighttime composite symptom score is 0 (no symptoms) to 3 (severe symptoms). A negative change indicates an improvement of symptoms and a positive change indicates a worsening of symptoms.

Outcome measures

Outcome measures
Measure	Placebo n=110 Participants Placebo delivered by nebulization twice daily for 12 weeks	0.135 mg MAP0010 n=122 Participants 0.135mg MAP0010 (unit dose budesonide) delivered by nebulization twice daily for 12 weeks	0.25 mg MAP0010 n=117 Participants 0.25mg MAP0010 (unit dose budesonide) delivered by nebulization twice daily for 12 weeks
Change From Baseline in Nighttime Composite Symptom Score Baseline	2.71 units on a scale Standard Deviation 1.393	2.97 units on a scale Standard Deviation 1.466	2.82 units on a scale Standard Deviation 1.349
Change From Baseline in Nighttime Composite Symptom Score Change from Baseline at week 12	-1.47 units on a scale Standard Deviation 1.572	-1.82 units on a scale Standard Deviation 1.907	-1.59 units on a scale Standard Deviation 1.516

SECONDARY outcome

Timeframe: baseline, week 12

Population: The modified-intent-to-treat population includes all randomized patients who were deemed capable of spirometry measurements at baseline and at least at one of the post treatment visits.

The forced expiratory volume in 1 second (FEV1) is the amount forced of air exhaled in 1 second. The percent predicted is calculated for age, gender, and height. Subjects had to perform at least 3 acceptable maneuvers into a spirometer and the largest volume from the 3 maneuvers was selected. An increase indicates an improvement (a greater volume of air expired).

Outcome measures

Outcome measures
Measure	Placebo n=38 Participants Placebo delivered by nebulization twice daily for 12 weeks	0.135 mg MAP0010 n=37 Participants 0.135mg MAP0010 (unit dose budesonide) delivered by nebulization twice daily for 12 weeks	0.25 mg MAP0010 n=40 Participants 0.25mg MAP0010 (unit dose budesonide) delivered by nebulization twice daily for 12 weeks
Change From Baseline in FEV1% Predicted Baseline	96.96 percentage of predicted FEV1 Standard Deviation 18.646	91.20 percentage of predicted FEV1 Standard Deviation 17.713	93.00 percentage of predicted FEV1 Standard Deviation 17.305
Change From Baseline in FEV1% Predicted Change from Baseline at Week 12	1.51 percentage of predicted FEV1 Standard Deviation 13.068	4.14 percentage of predicted FEV1 Standard Deviation 12.845	0.36 percentage of predicted FEV1 Standard Deviation 16.657

SECONDARY outcome

Timeframe: baseline, week 12

Population: The modified-intent-to-treat population includes all randomized patients who were deemed capable of spirometry measurements at baseline and at least at one of the post treatment visits.

The peak expiratory flow (PEF) is the highest air flow achieved from a maximum forced expiratory maneuver measured in liters of air per minute (L/min). Subjects had to perform at least 3 acceptable maneuvers into a PEF meter. An increase indicates an improvement (a greater volume of air expired).

Outcome measures

Outcome measures
Measure	Placebo n=38 Participants Placebo delivered by nebulization twice daily for 12 weeks	0.135 mg MAP0010 n=37 Participants 0.135mg MAP0010 (unit dose budesonide) delivered by nebulization twice daily for 12 weeks	0.25 mg MAP0010 n=40 Participants 0.25mg MAP0010 (unit dose budesonide) delivered by nebulization twice daily for 12 weeks
Change From Baseline in PEF Baseline	170.94 L/min Standard Deviation 49.343	163.39 L/min Standard Deviation 52.881	165.34 L/min Standard Deviation 49.133
Change From Baseline in PEF Change from Baseline at Week 12	0.71 L/min Standard Deviation 44.544	20.10 L/min Standard Deviation 45.444	15.02 L/min Standard Deviation 45.306

SECONDARY outcome

Timeframe: baseline, week 12

Population: Intent-to-treat includes all randomized patients who have received at least one dose of study drug and have baseline and at least one post treatment efficacy assessment available.

The individual symptoms at each time point to be monitored are: cough, wheeze, and shortness of breath. The individual symptoms were scored using a four point scale: 0=no symptoms; 1=mild symptoms; 2=moderate symptoms; 3=severe symptoms Individual Daytime symptom score is defined as an average of the last 5 days' individual symptom scores within the last 7 days immediately preceding the end day of that week. A negative change indicates an improvement of symptoms and a positive change indicates a worsening of symptoms.

Outcome measures

Outcome measures
Measure	Placebo n=110 Participants Placebo delivered by nebulization twice daily for 12 weeks	0.135 mg MAP0010 n=122 Participants 0.135mg MAP0010 (unit dose budesonide) delivered by nebulization twice daily for 12 weeks	0.25 mg MAP0010 n=117 Participants 0.25mg MAP0010 (unit dose budesonide) delivered by nebulization twice daily for 12 weeks
Change From Baseline in Daytime Individual Symptom Scores Cough: Baseline	1.16 units on a scale Standard Deviation 0.544	1.21 units on a scale Standard Deviation 0.490	1.18 units on a scale Standard Deviation 0.582
Change From Baseline in Daytime Individual Symptom Scores Cough: Change from Baseline at week 12	-0.55 units on a scale Standard Deviation 0.734	-0.68 units on a scale Standard Deviation 0.705	-0.58 units on a scale Standard Deviation 0.664
Change From Baseline in Daytime Individual Symptom Scores Wheeze: Baseline	0.84 units on a scale Standard Deviation 0.591	0.91 units on a scale Standard Deviation 0.546	0.88 units on a scale Standard Deviation 0.550
Change From Baseline in Daytime Individual Symptom Scores Wheeze: Change from Baseline at week 12	-0.45 units on a scale Standard Deviation 0.615	-0.58 units on a scale Standard Deviation 0.563	-0.49 units on a scale Standard Deviation 0.589
Change From Baseline in Daytime Individual Symptom Scores Shortness of Breath: Baseline	0.73 units on a scale Standard Deviation 0.557	0.84 units on a scale Standard Deviation 0.612	0.81 units on a scale Standard Deviation 0.602
Change From Baseline in Daytime Individual Symptom Scores Shortness of Breath: Change from Baseline at Wk 12	-0.37 units on a scale Standard Deviation 0.635	-0.51 units on a scale Standard Deviation 0.632	-0.49 units on a scale Standard Deviation 0.626

SECONDARY outcome

Timeframe: baseline, week 12

Population: Intent-to-treat includes all randomized patients who have received at least one dose of study drug and have baseline and at least one post treatment efficacy assessment available.

The individual symptoms at each time point to be monitored are: cough, wheeze, and shortness of breath. The individual symptoms were scored using a four point scale: 0=no symptoms; 1=mild symptoms; 2=moderate symptoms; 3=severe symptoms Individual nighttime symptom score is defined as an average of the last 5 nights' individual symptom scores within the last 7 nights immediately preceding the end day of that week. A negative change indicates an improvement of symptoms and a positive change indicates a worsening of symptoms.

Outcome measures

Outcome measures
Measure	Placebo n=110 Participants Placebo delivered by nebulization twice daily for 12 weeks	0.135 mg MAP0010 n=122 Participants 0.135mg MAP0010 (unit dose budesonide) delivered by nebulization twice daily for 12 weeks	0.25 mg MAP0010 n=117 Participants 0.25mg MAP0010 (unit dose budesonide) delivered by nebulization twice daily for 12 weeks
Change From Baseline in Nighttime Individual Symptom Scores Cough: Baseline	1.16 units on a scale Standard Deviation 0.528	1.20 units on a scale Standard Deviation 0.495	1.17 units on a scale Standard Deviation 0.565
Change From Baseline in Nighttime Individual Symptom Scores Cough: Change from Baseline at week 12	-0.59 units on a scale Standard Deviation 0.663	-0.69 units on a scale Standard Deviation 0.720	-0.61 units on a scale Standard Deviation 0.638
Change From Baseline in Nighttime Individual Symptom Scores Wheeze: Baseline	0.83 units on a scale Standard Deviation 0.563	0.94 units on a scale Standard Deviation 0.592	0.90 units on a scale Standard Deviation 0.548
Change From Baseline in Nighttime Individual Symptom Scores Wheeze: Change from Baseline at week 12	-0.48 units on a scale Standard Deviation 0.594	-0.57 units on a scale Standard Deviation 0.704	-0.51 units on a scale Standard Deviation 0.603
Change From Baseline in Nighttime Individual Symptom Scores Shortness of Breath: Baseline	0.72 units on a scale Standard Deviation 0.543	0.83 units on a scale Standard Deviation 0.622	0.75 units on a scale Standard Deviation 0.569
Change From Baseline in Nighttime Individual Symptom Scores Shortness of Breath: Change from Baseline at Wk 12	-0.39 units on a scale Standard Deviation 0.549	-0.56 units on a scale Standard Deviation 0.690	-0.47 units on a scale Standard Deviation 0.566

Adverse Events

Placebo

Serious events: 1 serious events

Other events: 33 other events

Deaths: 0 deaths

0.135 mg MAP0010

Serious events: 2 serious events

Other events: 31 other events

Deaths: 0 deaths

0.25 mg MAP0010

Serious events: 0 serious events

Other events: 42 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo n=110 participants at risk Placebo delivered by nebulization twice daily for 12 weeks	0.135 mg MAP0010 n=123 participants at risk 0.135mg MAP0010 (unit dose budesonide) delivered by nebulization twice daily for 12 weeks	0.25 mg MAP0010 n=123 participants at risk 0.25mg MAP0010 (unit dose budesonide) delivered by nebulization twice daily for 12 weeks
Infections and infestations Pneumonia Necrotising	0.00% 0/110 All randomized patients who received at least one dose of study drug and who have at least one post dosing safety evaluation were included in the adverse event analysis.	0.81% 1/123 All randomized patients who received at least one dose of study drug and who have at least one post dosing safety evaluation were included in the adverse event analysis.	0.00% 0/123 All randomized patients who received at least one dose of study drug and who have at least one post dosing safety evaluation were included in the adverse event analysis.
Respiratory, thoracic and mediastinal disorders Asthma	0.91% 1/110 All randomized patients who received at least one dose of study drug and who have at least one post dosing safety evaluation were included in the adverse event analysis.	0.81% 1/123 All randomized patients who received at least one dose of study drug and who have at least one post dosing safety evaluation were included in the adverse event analysis.	0.00% 0/123 All randomized patients who received at least one dose of study drug and who have at least one post dosing safety evaluation were included in the adverse event analysis.

Other adverse events

Other adverse events
Measure	Placebo n=110 participants at risk Placebo delivered by nebulization twice daily for 12 weeks	0.135 mg MAP0010 n=123 participants at risk 0.135mg MAP0010 (unit dose budesonide) delivered by nebulization twice daily for 12 weeks	0.25 mg MAP0010 n=123 participants at risk 0.25mg MAP0010 (unit dose budesonide) delivered by nebulization twice daily for 12 weeks
General disorders Pyrexia	8.2% 9/110 All randomized patients who received at least one dose of study drug and who have at least one post dosing safety evaluation were included in the adverse event analysis.	4.1% 5/123 All randomized patients who received at least one dose of study drug and who have at least one post dosing safety evaluation were included in the adverse event analysis.	6.5% 8/123 All randomized patients who received at least one dose of study drug and who have at least one post dosing safety evaluation were included in the adverse event analysis.
Infections and infestations Upper Respiratory Tract Infections	11.8% 13/110 All randomized patients who received at least one dose of study drug and who have at least one post dosing safety evaluation were included in the adverse event analysis.	13.8% 17/123 All randomized patients who received at least one dose of study drug and who have at least one post dosing safety evaluation were included in the adverse event analysis.	15.4% 19/123 All randomized patients who received at least one dose of study drug and who have at least one post dosing safety evaluation were included in the adverse event analysis.
Respiratory, thoracic and mediastinal disorders Asthma	10.0% 11/110 All randomized patients who received at least one dose of study drug and who have at least one post dosing safety evaluation were included in the adverse event analysis.	7.3% 9/123 All randomized patients who received at least one dose of study drug and who have at least one post dosing safety evaluation were included in the adverse event analysis.	12.2% 15/123 All randomized patients who received at least one dose of study drug and who have at least one post dosing safety evaluation were included in the adverse event analysis.
Infections and infestations Nasopharyngitis	4.5% 5/110 All randomized patients who received at least one dose of study drug and who have at least one post dosing safety evaluation were included in the adverse event analysis.	1.6% 2/123 All randomized patients who received at least one dose of study drug and who have at least one post dosing safety evaluation were included in the adverse event analysis.	5.7% 7/123 All randomized patients who received at least one dose of study drug and who have at least one post dosing safety evaluation were included in the adverse event analysis.

Additional Information

VP, Scientific Affairs

MAP Pharmaceuticals Inc., a wholly owned subsidiary of Allergan

Phone: 650-386-3100

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee A disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 90 days from the time submitted to the sponsor for review. The sponsor cannot require changes to the communication and cannot extend the embargo.
Publication restrictions are in place

Restriction type: OTHER