Efficacy and Safety of 2 Doses of Tiotropium Respimat® Compared to Placebo in Children With Moderate Persistent Asthma

Phase 3

Completed

• Conditions: Asthma
• Interventions: Drug: Tiotropium high dose QD; Drug: Tiotropium low dose QD; Drug: Placebo

• Registration Number: NCT01634139
• Lead Sponsor: Boehringer Ingelheim

Brief Summary

The overall purpose of the trial is to evaluate efficacy and safety of tiotropium inhalation solution delivered via Respimat® inhaler (2.5 mcg and 5 mcg once daily in the evening) over 48 weeks, compared to placebo, in children (6 to 11 years old) with moderate persistent asthma.

Detailed Description

Not available

Study Timeline

• Study Start: 2012-07
• Study First Submitted: 2012-07-03
• Study First Submitted QC: 2012-07-03
• Study First Posted: 2012-07-06
• Primary Completion: 2015-06
• Study Completion: 2015-12
• Status Verified: 2016-06
• Results First Submitted: 2016-06-02
• Results First Submitted QC: 2016-06-02
• Last Update Submitted: 2016-06-02
• Results First Posted: 2016-07-12
• Last Update Posted: 2016-07-12

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 403

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Tiotropium high dose QD	Tiotropium high dose QD	-
Tiotropium low dose QD	Tiotropium low dose QD	-
Placebo QD	Placebo	-

Primary Outcome Measures

Name	Time	Method
FEV1 Peak (0-3h) Change From Baseline	Baseline and 24 Weeks.	Change from baseline in peak forced expiratory volume (FEV) in 1 second within the first 3 hours (h) post dosing (FEV1 peak(0-3h)) measured at week 24.; Measured values presented are actually adjusted means.; The number of participants analysed displays the number of participants with available data at the timepoint of interest.

Secondary Outcome Measures

Name	Time	Method
Trough FEV1 Change From Baseline	Baseline and Week 24, Baseline and Week 48.	Change from Baseline in Trough (pre-dose) Forced Expiratory Volume (FEV) in 1 second (FEV1) measured at week 24 and 48.; Measured values presented are actually adjusted means.; The number of participants analysed displays the number of participants included in the statistical model whereas the N's for each timepoint display the number of participants with available data at that timepoint.
FEV1 Peak (0-3h) at Week 48 Change From Baseline	Baseline and Week 48.	Change from baseline in peak forced expiratory volume (FEV) in 1 second within the first 3 hours (h) post dosing (FEV1 peak(0-3h)) measured at week 48.; Measured values presented are actually adjusted means.; The number of participants analysed displays the number of participants with available data at the timepoint of interest.
FEV1 AUC (0-3h) Change From Baseline	Baseline and 10 mins before drug administration and 30 mins, 1 hour (h), 2h, 3h after drug administration at week 24	Change from baseline of area under the curve (AUC) from 0 to 3 hours for FEV1 (FEV1 AUC (0-3h)) after 24 weeks of treatment. The AUC was calculated by using the trapezoidal rule divided by the observation time (3h).; Measured values presented are actually adjusted means.; The number of participants analysed displays the number of participants with available data at the timepoint of interest.
FEV1 Change From Baseline at Each Individual Timepoint	Baseline and 10 mins before drug administration and 30 mins, 1 hour (h), 2h, 3h after drug administration at 24 weeks	FEV1 change from baseline to week 24 at each individual timepoint.; The measured values presented are actually adjusted means.; The number of participants analysed displays the number of participants included in the statistical model whereas the N's for each timepoint display the number of participants with available data at that timepoint.
FVC Peak(0-3h) Change From Baseline	Baseline and Week 24, Baseline and Week 48.	Change from baseline in Maximum forced vital capacity (FVC) measured within the first 3 hours after administration of trial medication (FVC peak(0-3h)) after 24 and 48 Weeks of treatment.; Measured values presented are actually adjusted means.; The number of participants analysed displays the number of participants included in the statistical model whereas the N's for each timepoint display the number of participants with available data at that timepoint.
Trough FVC Change From Baseline	Baseline and Week 24, Baseline and Week 48	Change from baseline in Trough (pre-dose) FVC measured at week 24 and 48.; Measured values presented are actually adjusted means.; The number of participants analysed displays the number of participants included in the statistical model whereas the N's for each timepoint display the number of participants with available data at that timepoint.
FVC AUC (0-3h) Change From Baseline	Baseline and 10 mins before drug administration and 30 mins, 1 hour (h), 2h, 3h after drug administration at 24 weeks	Change from baseline of area under the curve (AUC) from 0 to 3 hours for FVC (Forced vital capacity) (FVC AUC (0-3h)) after 24 weeks of treatment. The AUC was calculated by using the trapezoidal rule divided by the observation time (3h).; Measured values presented are actually adjusted means.; The number of participants analysed displays the number of participants with available data at the timepoint of interest.
FVC Change From Baseline at Each Individual Timepoint	Baseline and 10 mins before drug administration and 30 mins, 1 hour (h), 2h, 3h after drug administration at Week 24	FVC change from baseline to week 24 at each individual timepoint.; The measured values presented are actually adjusted means; The number of participants analysed displays the number of participants included in the statistical model whereas the N's for each timepoint display the number of participants with available data at that timepoint.
Use of PRN (Pro re Nata) Rescue Medication Per Day	Baseline and Week 24, Baseline and Week 48.	Change from baseline in the number of puffs of rescue medication (salbutamol/albuterol) used per day (24 hour period) based on the weekly mean at weeks 24 and 48.; The measured values presented are actually adjusted means.; The number of participants analysed displays the number of participants included in the statistical model whereas the N's for each timepoint display the number of participants with available data at that timepoint.
Use of PRN Rescue Medication During Daytime	Baseline and Week 24, Baseline and Week 48.	Change from baseline in the number of puffs of rescue medication (salbutamol/albuterol) used during daytime based on the weekly mean at weeks 24 and 48.; Measured values presented are actually adjusted means; The number of participants analysed displays the number of participants included in the statistical model whereas the N's for each timepoint display the number of participants with available data at that timepoint.
Use of PRN Rescue Medication During Nighttime	Baseline and Week 24, Baseline and Week 48.	Change from baseline in the number of puffs of rescue medication (salbutamol/albuterol) used during nighttime based on the weekly mean at weeks 24 and 48.; Measured values presented are actually adjusted means.; The number of participants analysed displays the number of participants included in the statistical model whereas the N's for each timepoint display the number of participants with available data at that timepoint.
Peak Expiratory Flow (PEF) a.m. Change From Baseline	Baseline and Week 24, Baseline and Week 48.	Change from baseline in the morning (a.m.) peak expiratory flow based on the weekly mean at weeks 24 and 48.; Measured values presented are actually adjusted means.; The number of participants analysed displays the number of participants included in the statistical model whereas the N's for each timepoint display the number of participants with available data at that timepoint.
PEF p.m. Change From Baseline	Baseline and Week 24, Baseline and Week 48.	Change from baseline in the evening (p.m.) peak expiratory flow based on the weekly mean at weeks 24 and 48.; Measured values presented are actually adjusted means.; The number of participants analysed displays the number of participants included in the statistical model whereas the N's for each timepoint display the number of participants with available data at that timepoint.
PEF Variability Change From Baseline	Baseline and Week 24, Baseline and Week 48.	Change from baseline in the peak expiratory flow variability based on the weekly mean at week 24 and 48.; Measured values presented are actually adjusted means.; The number of participants analysed displays the number of participants included in the statistical model whereas the N's for each timepoint display the number of participants with available data at that timepoint.
FEV1 a.m Change From Baseline	Baseline and Week 24, Baseline and Week 48.	Change from baseline in morning (a.m.) FEV1 based on the weekly mean at week 24 and 48.; The measured values presented are actually adjusted means.; The number of participants analysed displays the number of participants included in the statistical model whereas the N's for each timepoint display the number of participants with available data at that timepoint.
FEV1 p.m. Change From Baseline	Baseline and Week 24, Baseline and Week 48.	Change from baseline in evening (p.m.) FEV1 based on the weekly mean at week 24 and 48.; Measured values presented are actually adjusted means.; The number of participants analysed displays the number of participants included in the statistical model whereas the N's for each timepoint display the number of participants with available data at that timepoint.
ACQ-IA Total Score	Weeks 24 and 48.	Interviewer Administered Asthma Control Questionnaire (ACQ-IA) total score after 24 and 48 weeks of treatment.; The ACQ-IA is a scale containing 7 questions. Each question has a 7 point scale which ranges from 0 to 6. A score of 0 corresponds to no impairment and a score of 6 corresponds to maximum impairment. ACQ-IA total score is calculated as the mean of the responses to all 7 questions.; The measured values presented are actually adjusted means.; The number of participants analysed displays the number of participants included in the statistical model whereas the N's for each timepoint display the number of participants with available data at that timepoint.
ACQ-IA Responder Analysis	Weeks 24 and 48	Responder categories based on the ACQ-IA total score after 24 and 48 weeks of treatment. Analysis was performed using the following categories and definitions: responder (change from trial baseline ≤-0.5), no change (-0.5 \<change from trial baseline \<0.5) and worsening (change from trial baseline ≥0.5). No statistical testing was performed for ACQ-IA total score responders.; The ACQ-IA is a scale containing 7 questions, each question has a 7-point scale which ranges from 0 to 6; a score of 0 corresponds to no impairment and a score of 6 corresponds to maximum impairment.
PAQLQ(S) Total Score	Weeks 24 and 48.	Standardised Paediatric Asthma Quality of Life Questionnaire (PAQLQ(S)) total score at weeks 24 and 48.; The PAQLQ(S) is 23 questions on a 7-point scale, ranging from 1 (worst control) to 7 (best control). Total Score is calculated as mean of all 23 questions.; The measured values presented are actually adjusted means.; The number of participants analysed displays the number of participants included in the statistical model whereas the N's for each timepoint display the number of participants with available data at that timepoint.
PAQLQ(S) Symptom Domain Score	Weeks 24 and 48.	PAQLQ(S) symptom domain score at weeks 24 and 48. The PAQLQ(S) is 23 questions on a 7-point scale, ranging from 1 (worst control) to 7 (best control). The individual domain score was calculated as the mean of the items in the domain.; The measured values presented are actually adjusted means.; The number of participants analysed displays the number of participants included in the statistical model whereas the N's for each timepoint display the number of participants with available data at that timepoint.
PAQLQ(S) Activity Limitation Domain Score	Weeks 24 and 48.	PAQLQ(S) activity limitation domain score at weeks 24 and 48. The PAQLQ(S) is 23 questions on a 7-point scale, ranging from 1 (worst control) to 7 (best control). The individual domain score is calculated as the mean of the items in this domain.; The measured values presented are actually adjusted means.; The number of participants analysed displays the number of participants included in the statistical model whereas the N's for each timepoint display the number of participants with available data at that timepoint.
PAQLQ(S) Emotional Function Domain Score	Weeks 24 and 48.	PAQLQ(S) emotional function domain score at weeks 24 and 48. The PAQLQ(S) is 23 questions on a 7-point scale, ranging from 1 (worst control) to 7 (best control). The individual domain score is calculated as the mean of the items in this domain.; The measured values presented are actually adjusted means.; The number of participants analysed displays the number of participants included in the statistical model whereas the N's for each timepoint display the number of participants with available data at that timepoint.
Responders in PAQLQ(S) at Weeks 24 and 48	Weeks 24 and 48.	Responders in PAQLQ(S) at weeks 24 and 48. Analysis was performed using the following categories and definitions: responder (change from trial baseline ≥0.5), no change (-0.5 \<change from trial baseline \<0.5) and worsening (change from trial baseline ≤-0.5). No statistical testing was performed for PAQLQ(S) total score responders.; The PAQLQ(S) is 23 questions on a 7-point scale, ranging from 1 (worst control) to 7 (best control).
Change From Baseline in Nighttime Awakenings	Baseline and Week 24, Baseline and Week 48.	Change from baseline in nighttime awakenings based on the weekly mean at weeks 24 and 48.; Nighttime awakenings was assessed by the question "Did you wake up during the night due to your asthma?" from the e-diary. Scores range from 1 (did not wake up) to 5 (was awake all night).; Measured values presented are actually adjusted means.; The number of participants analysed displays the number of participants included in the statistical model whereas the N's for each timepoint display the number of participants with available data at that timepoint.
Change From Baseline in Morning Asthma Symptoms	Baseline and Week 24, Baseline and Week 48.	Change from baseline in morning asthma symptoms based on the weekly mean at weeks 24 and 48.; Morning asthma symptoms was assessed by the question "how were your asthma symptoms this morning?" from the e-diary. Scores range from 1 (no asthma symptoms) to 5 (very severe asthma symptoms).; Measured values presented are actually adjusted means.; The number of participants analysed displays the number of participants included in the statistical model whereas the N's for each timepoint display the number of participants with available data at that timepoint.
Change From Baseline in Daytime Asthma Symptoms	Baseline and Week 24, Baseline and Week 48.	Change from baseline in daytime asthma symptoms based on the weekly mean at weeks 24 and 48.; Daytime asthma symptoms was assessed by the question "how were your asthma symptoms during the day?" from the e-diary. Scores range from 1 (no asthma symptoms) to 5 (very severe asthma symptoms).; Measured values presented are actually adjusted means.; The number of participants analysed displays the number of participants included in the statistical model whereas the N's for each timepoint display the number of participants with available data at that timepoint.
Change From Baseline in Daytime Activity Limitations	Baseline and Week 24, Baseline and Week 48.	Change from baseline in daytime activity limitations based on the weekly mean at weeks 24 and 48.; Daytime activity limitations was assessed by the question "how limited were you in your activities today because of your asthma?" from the e-diary. Scores range from 1 (not limited) to 5 (totally limited).; Measured values presented are actually adjusted means.; The number of participants analysed displays the number of participants included in the statistical model whereas the N's for each timepoint display the number of participants with available data at that timepoint.
Change From Baseline in Daytime Experiences of Shortness of Breath	Baseline and Week 24, Baseline and Week 48.	Change from baseline in daytime experiences of shortness of breath based on the weekly mean at weeks 24 and 48.; Daytime experiences of shortness of breath was assessed by the question "how much shortness of breath did you experience during the day" from the e-diary. Scores range from 1 (none) to 5 (a very great deal).; Measured values presented are actually adjusted means.; The number of participants analysed displays the number of participants included in the statistical model whereas the N's for each timepoint display the number of participants with available data at that timepoint.
Change From Baseline in Daytime Experiences of Wheeze or Cough	Baseline and Week 24, Baseline and Week 48.	Change from baseline in daytime experiences of wheeze or cough based on the weekly mean at weeks 24 and 48.; Daytime experiences of wheeze or cough was assessed by the question "did you experience wheeze or cough during the day?" from the e-diary. Scores range from 1 (not at all) to 5 (all the time).; Measured values presented are actually adjusted means.; The number of participants analysed displays the number of participants included in the statistical model whereas the N's for each timepoint display the number of participants with available data at that timepoint.
Change From Baseline in Asthma Symptom-free Days	Baseline and Week 24, Baseline and Week 48.	Change from baseline in asthma symptom-free days based on the weekly mean at weeks 24 and 48.; A day was considered as an asthma symptom-free day if there were no symptoms reported via the e-Diary (electronic diary) and no use of rescue medication reported via the eDiary during that day.; Measured values presented are actually adjusted means.; The number of participants analysed displays the number of participants included in the statistical model whereas the N's for each timepoint display the number of participants with available data at that timepoint.

Trial Locations

Locations (79)

205.445.50205 Boehringer Ingelheim Investigational Site; 🇬🇹 Guatemala, Guatemala

205.445.37103 Boehringer Ingelheim Investigational Site; 🇱🇻 Riga, Latvia

205.445.37003 Boehringer Ingelheim Investigational Site; 🇱🇹 Vilnius, Lithuania

205.445.47002 Boehringer Ingelheim Investigational Site; 🇳🇴 Oslo, Norway

205.445.35102 Boehringer Ingelheim Investigational Site; 🇵🇹 Lisboa, Portugal

205.445.35105 Boehringer Ingelheim Investigational Site; 🇵🇹 Porto, Portugal

205.445.35101 Boehringer Ingelheim Investigational Site; 🇵🇹 Lisboa, Portugal

205.445.70008 Boehringer Ingelheim Investigational Site; 🇷🇺 Moscow, Russian Federation

205.445.70011 Boehringer Ingelheim Investigational Site; 🇷🇺 Moscow, Russian Federation

205.445.38008 Boehringer Ingelheim Investigational Site; 🇺🇦 Kharkiv, Ukraine

205.445.38017 Boehringer Ingelheim Investigational Site; 🇺🇦 Chernivtsi, Ukraine

205.445.38003 Boehringer Ingelheim Investigational Site; 🇺🇦 Dnipropetrovsk, Ukraine

205.445.38004 Boehringer Ingelheim Investigational Site; 🇺🇦 Kiev, Ukraine

205.445.01002 Boehringer Ingelheim Investigational Site; 🇺🇸 Columbia, Missouri, United States

205.445.02001 Boehringer Ingelheim Investigational Site; 🇨🇦 Sherbrooke, Quebec, Canada

205.445.49001 Boehringer Ingelheim Investigational Site; 🇩🇪 Bochum, Germany

205.445.02003 Boehringer Ingelheim Investigational Site; 🇨🇦 London, Ontario, Canada

205.445.50201 Boehringer Ingelheim Investigational Site; 🇬🇹 Guatemala, Guatemala

205.445.50202 Boehringer Ingelheim Investigational Site; 🇬🇹 Guatemala, Guatemala

205.445.37101 Boehringer Ingelheim Investigational Site; 🇱🇻 Baldone, Latvia

205.445.37002 Boehringer Ingelheim Investigational Site; 🇱🇹 Siauliai, Lithuania

205.445.35108 Boehringer Ingelheim Investigational Site; 🇵🇹 Amadora, Portugal

205.445.49007 Boehringer Ingelheim Investigational Site; 🇩🇪 Dresden, Germany

205.445.82006 Boehringer Ingelheim Investigational Site; 🇰🇷 Sungnam, Korea, Republic of

205.445.35904 Boehringer Ingelheim Investigational Site; 🇧🇬 Sofia, Bulgaria

205.445.37104 Boehringer Ingelheim Investigational Site; 🇱🇻 Adazi, Latvia

205.445.37105 Boehringer Ingelheim Investigational Site; 🇱🇻 Riga, Latvia

205.445.37106 Boehringer Ingelheim Investigational Site; 🇱🇻 Balvi, Latvia

205.445.37005 Boehringer Ingelheim Investigational Site; 🇱🇹 Utena, Lithuania

205.445.35106 Boehringer Ingelheim Investigational Site; 🇵🇹 Aveiro, Portugal

205.445.49015 Boehringer Ingelheim Investigational Site; 🇩🇪 Berlin, Germany

205.445.35107 Boehringer Ingelheim Investigational Site; 🇵🇹 Lisboa, Portugal

205.445.49009 Boehringer Ingelheim Investigational Site; 🇩🇪 Koblenz, Germany

205.445.36003 Boehringer Ingelheim Investigational Site; 🇭🇺 Ajka, Hungary

205.445.35902 Boehringer Ingelheim Investigational Site; 🇧🇬 Sofia, Bulgaria

205.445.35903 Boehringer Ingelheim Investigational Site; 🇧🇬 Sofia, Bulgaria

205.445.35905 Boehringer Ingelheim Investigational Site; 🇧🇬 Sofia, Bulgaria

205.445.37108 Boehringer Ingelheim Investigational Site; 🇱🇻 Daugavpils, Latvia

205.445.37107 Boehringer Ingelheim Investigational Site; 🇱🇻 Rezekne, Latvia

205.445.70003 Boehringer Ingelheim Investigational Site; 🇷🇺 St. Petersburg, Russian Federation

205.445.46001 Boehringer Ingelheim Investigational Site; 🇸🇪 Stockholm, Sweden

205.445.70005 Boehringer Ingelheim Investigational Site; 🇷🇺 Moscow, Russian Federation

205.445.70009 Boehringer Ingelheim Investigational Site; 🇷🇺 St. Petersburg, Russian Federation

205.445.38011 Boehringer Ingelheim Investigational Site; 🇺🇦 Donetsk, Ukraine

205.445.70002 Boehringer Ingelheim Investigational Site; 🇷🇺 Moscow, Russian Federation

205.445.38005 Boehringer Ingelheim Investigational Site; 🇺🇦 Donetsk, Ukraine

205.445.38001 Boehringer Ingelheim Investigational Site; 🇺🇦 Lviv, Ukraine

205.445.49014 Boehringer Ingelheim Investigational Site; 🇩🇪 Marburg, Germany

205.445.01001 Boehringer Ingelheim Investigational Site; 🇺🇸 Cincinnati, Ohio, United States

205.445.01010 Boehringer Ingelheim Investigational Site; 🇺🇸 Oklahoma City, Oklahoma, United States

205.445.01006 Boehringer Ingelheim Investigational Site; 🇺🇸 Charleston, South Carolina, United States

205.445.01012 Boehringer Ingelheim Investigational Site; 🇺🇸 Arlington, Texas, United States

205.445.01004 Boehringer Ingelheim Investigational Site; 🇺🇸 El Paso, Texas, United States

205.445.35901 Boehringer Ingelheim Investigational Site; 🇧🇬 Sofia, Bulgaria

205.445.49004 Boehringer Ingelheim Investigational Site; 🇩🇪 Ettenheim, Germany

205.445.50204 Boehringer Ingelheim Investigational Site; 🇬🇹 Guatemala, Guatemala

205.445.50203 Boehringer Ingelheim Investigational Site; 🇬🇹 Guatemala, Guatemala

205.445.36002 Boehringer Ingelheim Investigational Site; 🇭🇺 Dombovar, Hungary

205.445.82003 Boehringer Ingelheim Investigational Site; 🇰🇷 Guri, Korea, Republic of

205.445.82002 Boehringer Ingelheim Investigational Site; 🇰🇷 Incheon, Korea, Republic of

205.445.82001 Boehringer Ingelheim Investigational Site; 🇰🇷 Seoul, Korea, Republic of

205.445.36001 Boehringer Ingelheim Investigational Site; 🇭🇺 Budapest, Hungary

205.445.37102 Boehringer Ingelheim Investigational Site; 🇱🇻 Ogre, Latvia

205.445.35103 Boehringer Ingelheim Investigational Site; 🇵🇹 Porto, Portugal

205.445.40003 Boehringer Ingelheim Investigational Site; 🇷🇴 Cluj Napoca, Romania

205.445.40001 Boehringer Ingelheim Investigational Site; 🇷🇴 Bucharest, Romania

205.445.40004 Boehringer Ingelheim Investigational Site; 🇷🇴 Bucharest, Romania

205.445.70001 Boehringer Ingelheim Investigational Site; 🇷🇺 St. Petersburg, Russian Federation

205.445.70004 Boehringer Ingelheim Investigational Site; 🇷🇺 St. Petersburg, Russian Federation

205.445.70010 Boehringer Ingelheim Investigational Site; 🇷🇺 Yaroslavl, Russian Federation

205.445.38012 Boehringer Ingelheim Investigational Site; 🇺🇦 Kriviy Rig, Ukraine

205.445.38009 Boehringer Ingelheim Investigational Site; 🇺🇦 Lviv, Ukraine

205.445.38016 Boehringer Ingelheim Investigational Site; 🇺🇦 Odessa, Ukraine

205.445.38006 Boehringer Ingelheim Investigational Site; 🇺🇦 Vinnytsya, Ukraine

205.445.38002 Boehringer Ingelheim Investigational Site; 🇺🇦 Zaporizhzhya, Ukraine

205.445.38010 Boehringer Ingelheim Investigational Site; 🇺🇦 Zaporizhya, Ukraine

205.445.44001 Boehringer Ingelheim Investigational Site; 🇬🇧 London, United Kingdom

205.445.49012 Boehringer Ingelheim Investigational Site; 🇩🇪 Berlin, Germany

205.445.82005 Boehringer Ingelheim Investigational Site; 🇰🇷 Seoul, Korea, Republic of