Efficacy and Safety of Indacaterol Acetate Delivered Via the Concept1 Inhalation Device in Children Greater or Equal to 6 and Less Than 12 Years of Age With Asthma

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02892019
• Collaborator: (none)
• Enrollment: 79
• Locations: 29
• Arms: 2
• Actual Duration (Months): 26.9
• Patients Per Site: 2.7
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This study is designed to explore lung function effects of two doses of indacaterol acetate, 75 μg and 150 μg, in pediatric asthma patients 6-11 years old, and to compare the systemic exposure to indacaterol in plasma with historical data in adults, to identify an appropriate dose to Phase III evaluation.

Condition or Disease	Intervention/Treatment	Phase
Asthma	Drug: Indacaterol acetate 75 μg; Drug: Indacaterol acetate 150 μg	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 79 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Multicenter, Randomized, Double-blind, Active-controlled, 2 Week Treatment, Parallel-group Study to Assess the Efficacy and Safety of Indacaterol Acetate Delivered Via the Concept1 Inhalation Device in Children Greater or Equal to 6 and Less Than 12 Years of Age With Asthma
• Actual Study Start Date: Apr 18, 2017
• Actual Primary Completion Date: Jun 19, 2019
• Actual Study Completion Date: Jul 17, 2019

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Indacaterol acetate 75 μg o.d. Indacaterol acetate 75 μg o.d. delivered via Concept1 inhaler	Drug: Indacaterol acetate 75 μg; Indacaterol acetate 75 μg o.d. delivered via Concept1 inhaler; Other Names: QAB149
Active Comparator: Indacaterol acetate 150 μg o.d. Indacaterol acetate 150 μg o.d. delivered via Concept1 inhaler	Drug: Indacaterol acetate 150 μg; Indacaterol acetate 150 μg o.d. delivered via Concept1 inhaler; Other Names: QAB149

Outcome Measures

Primary Outcome Measures

1. Trough Forced Expiratoty Volume in 1 Second (FEV1) [2 weeks]

   Change from baseline in pre-dose trough FEV1 after 2 weeks of treatment with indacaterol acetate 75 μg o.d and 150 μg o.d. The primary endpoint is change from baseline in pre-dose trough FEV1 (mL) after 2 weeks of treatment. The pre-dose trough FEV1 (mL) is defined as the mean of the two FEV1 (mL), values measured at -45 min and -15 min pre-dose.

Secondary Outcome Measures

1. Systemic Exposure to Indacaterol in Plasma [day 1, day 14]

   Systemic exposure to indacaterol in plasma following sparse pharmacokinetic (PK) sampling on Day 1 and Day 14 after inhalation of indacaterol acetate 75 μg and 150 μg.

2. Asthma Control as Assessed by Pediatric Interviewer-administered Asthma Control Questionnaire [2 weeks]

   Asthma Control as assessed by pediatric interviewer-administered Asthma Control Questionnaire (ACQ-IA) score at week 2 (mean change). A decrease in the score shows an improvement. The scale ranges from 0 (no symptoms) to 6 (severe symptoms every day). Results are given as a change as compared from baseline

3. Pre-dose Morning and Evening Peak Expiratoty Flow (PEF) [2 weeks]

   Pre-dose morning and evening PEF over 2 weeks of treatment as determined by electronic peak flow meter data (mean change)

4. Rescue Medication Usage (Mean Daiily Number of Puffs) [2 weeks]

   Rescue medication usage over 2 weeks of treatment as determined by patient diary data for indacaterol acetate 75 μg and 150 μg o.d.Results given as mean change of puffs of rescue medication.

5. Rescue Medication Usage (Percentage of Rescue Medication Free Days) [2 weeks]

   Rescue medication usage over 2 weeks of treatment as determined by patient diary data for indacaterol acetate 75 μg and 150 μg o.d.

6. Forced Expiratoty Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) [2 weeks]

   FEV1 and FVC at 30 minutes and 1-hour post dose at week 2 for indacaterol acetate 75 μg and 150 μg o.d.

7. Symptoms as Recorded by Patient E-diary (Mean Total Daily Symptom Score) [2 weeks]

   Symptoms as recorded by patient e-diary for indacaterol acetate 75 μg and 150 μg o.d. (mean change) The scale rages from 0 (no problem) - 4 (very severe problems).

8. Symptoms as Recorded by Patient E-diary (Percentage of Asthma Symptoms Free Days) [2 weeks]

   Symptoms as recorded by patient e-diary for indacaterol acetate 75 μg and 150 μg o.d. (mean change)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 6 Years to 11 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Male and female children ≥ 6 years and < 12 years with confirmed diagnosis of asthma for at least 1 year prior to study enrollment.

• Written informed consent by parent(s)/legal guardian(s) and depending upon their age and local requirements a consent or assent for the patient.

• Patients receiving daily treatment with a stable low dose Inhaled Corticosteroid (ICS) (with or without additional controller), or patients receiving daily treatment with a stable mid-dose ICS (monotherapy or together with LTRA) for at least 4 weeks prior to Screening, and able to tolerate fluticasone propionate 100 μg b.i.d. inhaler starting at Visit 1 (or soon after).

• Patients with a pre-bronchodilator FEV1 ≥ 50% and ≤ 90% of the predicted normal value for the patient at the start and end of Run-in (Visits 101 and 199).

• Patients who demonstrate an increase in FEV1 of 12% within 30 minutes after administration of 400 μg salbutamol/360 μg albuterol (or equivalent dose) at Visit

1. All patients must perform a reversibility test at Visit 101.

Exclusion Criteria:

• Patients taking a mid-dose ICS (per GINA guidelines) in combination with LABA or any patient taking high-dose ICS.

• Evidence of unstable disease within 4 weeks prior to Screening (Visit 1).

• Patients who have had an asthma attack/exacerbation requiring systemic steroids (SCS) or hospitalization or emergency room visit within 3 months prior to Visit 1 (Screening) or more than 3 separate exacerbations in the 12 months preceding Visit 1.

• Suspected or documented bacterial or viral infection of the upper or lower respiratory tract, sinus or middle ear that is not resolved within 4 weeks of Screening (Visit 1).

• Prior intubation for asthma.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Brugge		Belgium	8000
2	Novartis Investigative Site	Brussel		Belgium	1020
3	Novartis Investigative Site	Bogota		Colombia
4	Novartis Investigative Site	Bucaramanga		Colombia
5	Novartis Investigative Site	Slavonski Brod		Croatia	35000
6	Novartis Investigative Site	Zagreb		Croatia	10000
7	Novartis Investigative Site	Hamm		Germany	D 59063
8	Novartis Investigative Site	Mannheim		Germany	68161
9	Novartis Investigative Site	Rosenheim		Germany	83026
10	Novartis Investigative Site	Guatemala City	GTM	Guatemala	01010
11	Novartis Investigative Site	Guatemala City		Guatemala	01011
12	Novartis Investigative Site	Guatemala City		Guatemala	01015
13	Novartis Investigative Site	Torokbalint	Pest	Hungary	2045
14	Novartis Investigative Site	Budapest		Hungary	1083
15	Novartis Investigative Site	Szeged		Hungary	6720
16	Novartis Investigative Site	Szigetvar		Hungary	7900
17	Novartis Investigative Site	Manila	Metro Manila	Philippines	1000
18	Novartis Investigative Site	Manila		Philippines	1008
19	Novartis Investigative Site	Quezon City		Philippines	1113
20	Novartis Investigative Site	Saint Petersburg		Russian Federation	199106
21	Novartis Investigative Site	St.Petersburg		Russian Federation	196240
22	Novartis Investigative Site	Nitra	Slovak Republic	Slovakia	949 01
23	Novartis Investigative Site	Nove Zamky	SVK	Slovakia	94001
24	Novartis Investigative Site	Middelburg	Mpumalanga	South Africa	1050
25	Novartis Investigative Site	Panorama	Western Cape	South Africa	7500
26	Novartis Investigative Site	Cape Town		South Africa	7531
27	Novartis Investigative Site	Cape Town		South Africa	7700
28	Novartis Investigative Site	Adana		Turkey	01330
29	Novartis Investigative Site	Ankara		Turkey	06100

Sponsors and Collaborators

• Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study Documents (Full-Text)

• Statistical Analysis Plan - Aug 27, 2019
• Study Protocol - Jun 28, 2016

More Information

Publications

None provided.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT02892019
• Other Study ID Numbers: CQMF149G2202; 2016-002113-21
• First Posted: Sep 8, 2016
• Last Update Posted: Jan 27, 2020
• Last Verified: Jan 1, 2020

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Novartis Pharmaceuticals: indacaterol acetate, asthma, GINA 2015, pediatrics
• Additional relevant MeSH terms: Asthma

Study Results

Participant Flow

Pre-assignment Detail	randomized set : 80 participants (41 and 39) Full analysis set : 79 participants (41 and 38) safety set : 79 participants (41 and 38) per protocol set : 35 participants (35 and 34)

Arm/Group Title	Indacaterol Acetate 150 μg o.d.	Indacaterol Acetate 75 μg o.d.
Arm/Group Description	Indacaterol acetate 150 μg o.d. delivered via Concept1 inhaler	Indacaterol acetate 75 μg o.d. delivered via Concept1 inhaler
Period Title: Overall Study
STARTED	41	39
COMPLETED	40	36
NOT COMPLETED	1	3

Baseline Characteristics

Arm/Group Title	Indacaterol Acetate 150 μg o.d.	Indacaterol Acetate 75 μg o.d.	Total
Arm/Group Description	Indacaterol acetate 150 μg o.d. delivered via Concept1 inhaler	Indacaterol acetate 75 μg o.d. delivered via Concept1 inhaler	Total of all reporting groups
Overall Participants	41	39	80
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	9.3 (1.47)	9.1 (1.58)	9.2 (1.51)
Sex: Female, Male (Count of Participants)
Female	13 31.7%	15 38.5%	28 35%
Male	28 68.3%	24 61.5%	52 65%
Race/Ethnicity, Customized (Count of Participants)
Caucasian	17 41.5%	17 43.6%	34 42.5%
Black	3 7.3%	3 7.7%	6 7.5%
Asian	1 2.4%	3 7.7%	4 5%
Native American	3 7.3%	3 7.7%	6 7.5%
Unknown	1 2.4%	0 0%	1 1.3%
Other	16 39%	13 33.3%	29 36.3%

Outcome Measures

1. Primary Outcome

Title	Trough Forced Expiratoty Volume in 1 Second (FEV1)
Description	Change from baseline in pre-dose trough FEV1 after 2 weeks of treatment with indacaterol acetate 75 μg o.d and 150 μg o.d. The primary endpoint is change from baseline in pre-dose trough FEV1 (mL) after 2 weeks of treatment. The pre-dose trough FEV1 (mL) is defined as the mean of the two FEV1 (mL), values measured at -45 min and -15 min pre-dose.
Time Frame	2 weeks

Outcome Measure Data

Analysis Population Description

full analysis set

Arm/Group Title	Indacaterol Acetate 150 μg o.d.	Indacaterol Acetate 75 μg o.d.
Arm/Group Description	Indacaterol acetate 150 μg o.d. delivered via Concept1 inhaler	Indacaterol acetate 75 μg o.d. delivered via Concept1 inhaler
Measure Participants	41	38
Mean (Standard Deviation) [L]	0.171 (0.1664)	0.212 (0.2521)

2. Secondary Outcome

Title	Systemic Exposure to Indacaterol in Plasma
Description	Systemic exposure to indacaterol in plasma following sparse pharmacokinetic (PK) sampling on Day 1 and Day 14 after inhalation of indacaterol acetate 75 μg and 150 μg.
Time Frame	day 1, day 14

Outcome Measure Data

Analysis Population Description

safety set

Arm/Group Title	Indacaterol Acetate 150 μg o.d.	Indacaterol Acetate 75 μg o.d.
Arm/Group Description	Indacaterol acetate 150 μg o.d. delivered via Concept1 inhaler	Indacaterol acetate 75 μg o.d. delivered via Concept1 inhaler
Measure Participants	41	38
Day 1 <=-2 hours	0.0 (0.0)	0.0 (0.0)
Day 1, 15 minutes	204.1 (98.27)	73.7 (39.55)
Day 1, 1 hour	125.8 (63.13)	43.9 (20.84)
Day 14 <=-2 hours	80.9 (32.51)	46.7 (29.61)
Day 14, 15 minutes	393.1 (182.11)	137.3 (47.43)
Day 14, 1 hour	255.5 (117.67)	103.0 (37.88)

3. Secondary Outcome

Title	Asthma Control as Assessed by Pediatric Interviewer-administered Asthma Control Questionnaire
Description	Asthma Control as assessed by pediatric interviewer-administered Asthma Control Questionnaire (ACQ-IA) score at week 2 (mean change). A decrease in the score shows an improvement. The scale ranges from 0 (no symptoms) to 6 (severe symptoms every day). Results are given as a change as compared from baseline
Time Frame	2 weeks

Outcome Measure Data

Analysis Population Description

full analysis set

Arm/Group Title	Indacaterol Acetate 150 μg o.d.	Indacaterol Acetate 75 μg o.d.
Arm/Group Description	Indacaterol acetate 150 μg o.d. delivered via Concept1 inhaler	Indacaterol acetate 75 μg o.d. delivered via Concept1 inhaler
Measure Participants	41	38
Mean (Standard Deviation) [score on a scale]	-0.375 (0.3796)	-0.270 (0.6341)

4. Secondary Outcome

Title	Pre-dose Morning and Evening Peak Expiratoty Flow (PEF)
Description	Pre-dose morning and evening PEF over 2 weeks of treatment as determined by electronic peak flow meter data (mean change)
Time Frame	2 weeks

Outcome Measure Data

Analysis Population Description

full analysis set

Arm/Group Title	Indacaterol Acetate 150 μg o.d.	Indacaterol Acetate 75 μg o.d.
Arm/Group Description	Indacaterol acetate 150 μg o.d. delivered via Concept1 inhaler	Indacaterol acetate 75 μg o.d. delivered via Concept1 inhaler
Measure Participants	41	38
Morning PEF	29.6 (26.41)	14.7 (29.38)
Evening PEF	29.7 (25.57)	15.2 (28.58)

5. Secondary Outcome

Title	Rescue Medication Usage (Mean Daiily Number of Puffs)
Description	Rescue medication usage over 2 weeks of treatment as determined by patient diary data for indacaterol acetate 75 μg and 150 μg o.d.Results given as mean change of puffs of rescue medication.
Time Frame	2 weeks

Outcome Measure Data

Analysis Population Description

full analysis set

Arm/Group Title	Indacaterol Acetate 150 μg o.d.	Indacaterol Acetate 75 μg o.d.
Arm/Group Description	Indacaterol acetate 150 μg o.d. delivered via Concept1 inhaler	Indacaterol acetate 75 μg o.d. delivered via Concept1 inhaler
Measure Participants	41	38
Mean (Standard Deviation) [number of puffs]	-0.19 (1.479)	-0.22 (0.930)

6. Secondary Outcome

Title	Rescue Medication Usage (Percentage of Rescue Medication Free Days)
Description	Rescue medication usage over 2 weeks of treatment as determined by patient diary data for indacaterol acetate 75 μg and 150 μg o.d.
Time Frame	2 weeks

Outcome Measure Data

Analysis Population Description

full analysis set

Arm/Group Title	Indacaterol Acetate 150 μg o.d.	Indacaterol Acetate 75 μg o.d.
Arm/Group Description	Indacaterol acetate 150 μg o.d. delivered via Concept1 inhaler	Indacaterol acetate 75 μg o.d. delivered via Concept1 inhaler
Measure Participants	41	38
Mean (Standard Deviation) [percentage]	7.4 (22.37)	3.1 (19.42)

7. Secondary Outcome

Title	Forced Expiratoty Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC)
Description	FEV1 and FVC at 30 minutes and 1-hour post dose at week 2 for indacaterol acetate 75 μg and 150 μg o.d.
Time Frame	2 weeks

Outcome Measure Data

Analysis Population Description

full analysis set

Arm/Group Title	Indacaterol Acetate 150 μg o.d.	Indacaterol Acetate 75 μg o.d.
Arm/Group Description	Indacaterol acetate 150 μg o.d. delivered via Concept1 inhaler	Indacaterol acetate 75 μg o.d. delivered via Concept1 inhaler
Measure Participants	41	38
30 minutes	0.234 (0.1786)	0.224 (0.2459)
1 hour	0.224 (0.1725)	0.258 (0.2451)

8. Secondary Outcome

Title	Symptoms as Recorded by Patient E-diary (Mean Total Daily Symptom Score)
Description	Symptoms as recorded by patient e-diary for indacaterol acetate 75 μg and 150 μg o.d. (mean change) The scale rages from 0 (no problem) - 4 (very severe problems).
Time Frame	2 weeks

Outcome Measure Data

Analysis Population Description

full analysis set

Arm/Group Title	Indacaterol Acetate 150 μg o.d.	Indacaterol Acetate 75 μg o.d.
Arm/Group Description	Indacaterol acetate 150 μg o.d. delivered via Concept1 inhaler	Indacaterol acetate 75 μg o.d. delivered via Concept1 inhaler
Measure Participants	41	38
Mean (Standard Deviation) [score on a scale]	-0.18 (0.695)	0.08 (0.365)

9. Secondary Outcome

Title	Symptoms as Recorded by Patient E-diary (Percentage of Asthma Symptoms Free Days)
Description	Symptoms as recorded by patient e-diary for indacaterol acetate 75 μg and 150 μg o.d. (mean change)
Time Frame	2 weeks

Outcome Measure Data

Analysis Population Description

full analysis set

Arm/Group Title	Indacaterol Acetate 150 μg o.d.	Indacaterol Acetate 75 μg o.d.
Arm/Group Description	Indacaterol acetate 150 μg o.d. delivered via Concept1 inhaler	Indacaterol acetate 75 μg o.d. delivered via Concept1 inhaler
Measure Participants	41	38
Mean (Standard Deviation) [percentage]	12.3 (21.25)	4.4 (26.60)

Adverse Events

Time Frame	2 years
Adverse Event Reporting Description	AE additional description
Arm/Group Title	QAB149 150 ug OD		QAB149 75 ug OD
Arm/Group Description	QAB149 150 ug OD		QAB149 75 ug OD
All Cause Mortality
	QAB149 150 ug OD		QAB149 75 ug OD
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/41 (0%)		0/38 (0%)
Serious Adverse Events
	QAB149 150 ug OD		QAB149 75 ug OD
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/41 (0%)		0/38 (0%)
Other (Not Including Serious) Adverse Events
	QAB149 150 ug OD		QAB149 75 ug OD
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/41 (7.3%)		13/38 (34.2%)
Cardiac disorders
Defect conduction intraventricular	0/41 (0%)		1/38 (2.6%)
Gastrointestinal disorders
Nausea	1/41 (2.4%)		1/38 (2.6%)
Vomiting	0/41 (0%)		1/38 (2.6%)
Infections and infestations
Conjunctivitis	0/41 (0%)		1/38 (2.6%)
Influenza	0/41 (0%)		2/38 (5.3%)
Rhinitis	0/41 (0%)		1/38 (2.6%)
Upper respiratory tract infection	0/41 (0%)		3/38 (7.9%)
Injury, poisoning and procedural complications
Limb injury	0/41 (0%)		1/38 (2.6%)
Investigations
Blood glucose increased	0/41 (0%)		1/38 (2.6%)
Peak expiratory flow rate decreased	0/41 (0%)		1/38 (2.6%)
Nervous system disorders
Dizziness	1/41 (2.4%)		0/38 (0%)
Respiratory, thoracic and mediastinal disorders
Asthma	1/41 (2.4%)		2/38 (5.3%)
Dysphonia	0/41 (0%)		1/38 (2.6%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (ie, data from all sites) in the clinical trial.