A Comparative Study of Inhaled Ciclesonide Versus Placebo in Children (6-11 Years) With Asthma (RAINBOW)

This study has been completed.
Sponsor:
Collaborator:
Nycomed GmbH
Information provided by (Responsible Party):
Takeda
ClinicalTrials.gov Identifier:
NCT00384189
First received: October 4, 2006
Last updated: July 6, 2016
Last verified: July 2016
  Purpose
The purpose of this study is to investigate the efficacy of inhaled ciclesonide at three different dose levels compared with placebo with respect to pulmonary function, asthma symptoms, and use of rescue medication in children aged 6-11 years with asthma. Treatment medication will be administered as follows: ciclesonide or placebo will be inhaled once daily in the evening. The study consists of a baseline period (2 to 4 weeks) and a treatment period (12 weeks). The study provides further data on safety and tolerability of ciclesonide.

Condition Intervention Phase
Asthma
Drug: Ciclesonide
Drug: Placebo
Drug: Salbutamol
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: A Comparative Study of Inhaled Ciclesonide Versus Placebo in Children With Asthma

Resource links provided by NLM:


Further study details as provided by Takeda:

Primary Outcome Measures:
  • Change From Baseline in Morning Peak Expiratory Flow (PEF) [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
    PEF is the maximum speed of expiration. A portable electronic PEF meter was used for the home PEF readings. The patients recorded PEF daily, in the morning immediately after getting up. Readings were done preferably at least 4 hours after use of rescue medication and before inhalation of the study medication. At each measurement, three readings were obtained in the standing position. All three values were recorded in the diary; the highest value was used for evaluation. The higher change from Baseline values are the best. Analysis of covariance (ANCOVA) model with the baseline value and age as covariates was used for analysis. Last observation carried forward.


Secondary Outcome Measures:
  • Time to First Event of Lack of Efficacy (LOE) by Week 12 [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    Kaplan Meier Estimates of the probability of not experiencing LOE by Week 12 was measured. LOE was reached if any of the following criteria occurred during the treatment period: • asthma exacerbation (a worsening of asthma symptoms requiring a change in medication; • nocturnal awakenings due to asthma on any 4 or more nights during any 7-consecutive-day period; • use of more than 8 puffs/day of salbutamol on any 4 or more days during any 7-consecutive-day period; • decrease in morning PEF to <80% of randomization value on any 4 consecutive days during the treatment period.

  • Percentage of Days With Asthma Control Based on Symptoms, Use of Rescue Medication, Morning PEF and PEF Fluctuation [ Time Frame: 28 days prior to last visit (Up to 12 Weeks) ] [ Designated as safety issue: No ]
    Control of asthma was evaluated on a daily basis (24 hours) using the following variables: asthma symptoms, use of rescue medication, morning (am) PEF and PEF fluctuation. The median percentage of days with asthma control is presented.

  • Change From Baseline in Lung Function Variable Forced Expiratory Volume in One Second (FEV1) [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
    Spirometry was performed according to local standards. FEV1 is the maximal amount of air forcefully exhaled from the lungs in one second. Higher change numbers indicate better lung function.

  • Change From Baseline in Lung Function Variable PEF by Spirometry [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
    Spirometry was performed according to local standards. PEF is the maximum speed of expiration. Analysis was ANCOVA with factors value at Baseline, treatment, age, sex, center pool, ICS pretreatment, spacer use and asthma severity. Higher change numbers indicate better lung function.

  • Change From Baseline in Morning PEF From Diary [ Time Frame: Baseline and Weeks 1 thru 12 ] [ Designated as safety issue: No ]
    PEF is the maximum speed of expiration. A portable electronic PEF meter was used for the home PEF readings. The patients recorded PEF daily, in the morning immediately after getting up. Readings were done preferably at least 4 hours after use of rescue medication and before inhalation of the study medication. At each measurement, three readings were obtained in the standing position. All three values were recorded in the diary; the highest value was used for evaluation. The higher change from Baseline values are the best. Analysis of covariance (ANCOVA) model with the Baseline value and age as covariates was used for analysis.

  • Change From Baseline in Evening PEF From Diary [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
    PEF is the maximum speed of expiration. A portable electronic PEF meter was used for the home PEF readings. The patients recorded PEF daily, in the morning immediately after getting up. Readings were done preferably at least 4 hours after use of rescue medication and before inhalation of the study medication. At each measurement, three readings were obtained in the standing position. All three values were recorded in the diary; the highest value was used for evaluation. The higher change from Baseline values are the best. Analysis of covariance (ANCOVA) model with the Baseline value and age as covariates was used for analysis.

  • Change From Baseline in Diurnal PEF Fluctuations [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
    PEF is the maximum speed of expiration. A portable electronic PEF meter was used for the home PEF readings. The patients recorded PEF daily, in the morning immediately after getting up. Readings were done preferably at least 4 hours after use of rescue medication and before inhalation of the study medication. At each measurement, three readings were obtained in the standing position. All three values were recorded in the diary; the highest value was used for evaluation. A negative change from Baseline indicates improvement. Analysis of covariance (ANCOVA) model with the Baseline value and age as covariates was used for analysis.

  • Change in Asthma Symptom Total Score [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
    Measurements of both nighttime and daytime asthma symptoms were assessed on a daily basis by the patient in the electronic diary, according to the following scales: Nighttime Asthma Score using a 5 point scale: 0=no asthma symptoms, slept through the night to 4=bad night, awake most of the night because of asthma. Daytime Asthma Score using a 5 point scale: 0=very well, no asthma symptoms to 4=asthma very bad, unable to carry out daily activities as usual. Total possible overall daily score range from 0(best) to 4 (worst). A negative change from Baseline indicated improvement.

  • Change in Use of Rescue Medications [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
    The daily use of rescue medication (salbutamol) was recorded in the electronic diary in the morning and the evening. A negative change from Baseline indicates improvement.

  • Percentage of Days With Asthma Control Based on Symptoms, Use of Rescue Medication and Morning PEF [ Time Frame: 28 days prior to last visit (Up to 12 Weeks) ] [ Designated as safety issue: No ]
    Control of asthma was evaluated on a daily basis (24 hours) using the following variables: asthma symptoms, use of rescue medication, and morning (am) PEF. The median percentage of days with asthma control is presented.

  • Change From Baseline in Pediatric Asthma Quality of Life Questionnaire Standard [PAQLQ(S)] Overall Score [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
    PAQLQS is a disease specific instrument to assess the impact of asthma on the patient's quality of life. The PAQLQS consists of 23 items in 3 domains evaluating activity limitations, symptoms and emotional function. Patients answered each question using a 7-point scale from 1= maximum impairment to 7=no impairment) about their experience during the previous week. Total possible score ranging from 23 (worst) to 161(best). Higher change from Baseline scores are the best. Analysis of covariance (ANCOVA) model with the baseline value and age as covariates was used for analysis.

  • Change From Baseline in Pediatric Asthma Caregiver's Quality of Life Questionnaire (PACQLQ) Overall [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
    PACQLQ assesses the impact of the child's asthma on the quality of life of the caregiver. The PACQLQ consists of 13 items in 2 domains evaluating activity limitations and emotional function. Caregivers answered each question using a 7-point scale from 1= maximum impairment to 7=no impairment about their experience during the previous week. Total possible score ranging from 13 (worst) to 91(best). Higher change from Baseline scores are the best. Analysis of covariance (ANCOVA) model with the baseline value and age as covariates was used for analysis.


Enrollment: 1080
Study Start Date: September 2006
Study Completion Date: August 2008
Primary Completion Date: August 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Ciclesonide 40 µg
Placebo-matching ciclesonide, inhaled via a metered-dose inhaler (MDI) with 1,1,1,2-hydrofluoroalkane (HFA)-134a as propellant, once daily, in the evening for 2 to 4 weeks in the Baseline period followed by ciclesonide 40 µg, inhaled via a MDI with HFA-134a as propellant, once daily in the evening for 12 weeks. Salbutamol 100 μg/puff was available to be used as rescue medication if needed.
Drug: Ciclesonide
inhaled Ciclesonide
Drug: Placebo
Ciclesonide placebo-matching inhaler
Drug: Salbutamol
Salbutamol inhalation powder
Active Comparator: Ciclesonide 80 µg
Placebo-matching ciclesonide, inhaled via a MDI with HFA-134a as propellant, once daily, in the evening for 2 to 4 weeks in the Baseline period followed by ciclesonide 80 µg, inhaled via a MDI with HFA-134a as propellant, once daily in the evening for 12 weeks. Salbutamol 100 μg/puff was available to be used as rescue medication if needed.
Drug: Ciclesonide
inhaled Ciclesonide
Drug: Placebo
Ciclesonide placebo-matching inhaler
Drug: Salbutamol
Salbutamol inhalation powder
Active Comparator: Ciclesonide 160 µg
Placebo-matching ciclesonide, inhaled via a MDI with HFA-134a as propellant, once daily, in the evening for 2 to 4 weeks in the Baseline period followed by ciclesonide 160 µg, inhaled via a MDI with HFA-134a as propellant, once daily in the evening for 12 weeks. Salbutamol 100 μg/puff was available to be used as rescue medication if needed.
Drug: Ciclesonide
inhaled Ciclesonide
Drug: Placebo
Ciclesonide placebo-matching inhaler
Drug: Salbutamol
Salbutamol inhalation powder
Placebo Comparator: Placebo
Placebo-matching Ciclesonide, inhaled via a MDI with HFA-134a as propellant, once daily in the evening for 2 to 4 week in the Baseline period followed by placebo-matching ciclesonide, inhaled via a MDI with HFA-134a as propellant, once daily in the evening for 12 weeks. Salbutamol 100 μg/puff was available to be used as rescue medication if needed.
Drug: Placebo
Ciclesonide placebo-matching inhaler
Drug: Salbutamol
Salbutamol inhalation powder

Detailed Description:

The drug being tested is called ciclesonide. This study looked at the safety and efficacy of inhaled ciclesonide in children with asthma. The study enrolled 1080 patients.

Participants were randomly assigned to 1 of 4 treatment groups which were undisclosed to the patient and study doctor during the study:• Ciclesonide 40 µg, 80 µg or 160 µg • Placebo- this is similar to study drug but has no active ingredient. Ciclesonide was inhaled via a metered-dose inhaler (MDI with HFA-134a propellant), with or without spacer, once daily in the evening throughout the study. All participants were asked to document daily AM and PM peak expiratory flow (PEF), daytime and nighttime asthma symptom scores and number of puffs of rescue medicine in an electronic diary. This multi-centre trial was conducted worldwide. The overall time to participate in this study was 20 weeks. Participants made multiple visits to the clinic plus a final visit 30 days after the last dose of study drug for a follow-up assessment.

  Eligibility

Ages Eligible for Study:   6 Years to 11 Years   (Child)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Main Inclusion Criteria:

  • History of asthma for at least 6 months
  • Ability to show optimal use of MDI, including inhalation technique
  • Lung function and reversibility within specified limits

Main Exclusion Criteria:

  • Concomitant severe diseases
  • Diseases which are contraindications for the use of inhaled steroids
  • Two or more inpatient hospitalizations for asthma within the last year
  • Respiratory tract infection or asthma exacerbation within the last 30 days prior to entry into the study
  • Use of systemic steroids within the last 30 days prior to inclusion (depot steroids 6 weeks)
  • Beginning of or change in immunotherapy within the last 6 months prior to inclusion
  • Inability to follow the procedures of the study
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00384189

  Show 123 Study Locations
Sponsors and Collaborators
Takeda
Nycomed GmbH
Investigators
Principal Investigator: Søren Pedersen, Prof. Odense University Hospital, Kolding, Denmark
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Takeda
ClinicalTrials.gov Identifier: NCT00384189     History of Changes
Other Study ID Numbers: BY9010/M1-209  U1111-1172-2297 
Study First Received: October 4, 2006
Results First Received: July 6, 2016
Last Updated: July 6, 2016
Health Authority: South Africa: Medicines Control Council
Bulgaria: Bulgarian Drug Agency
Germany: Federal Institute for Drugs and Medical Devices
Hungary: National Institute of Pharmacy
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Romania: National Medicines Agency
Spain: Spanish Agency for Medicines and Health Products

Keywords provided by Takeda:
Asthma
Ciclesonide
children

Additional relevant MeSH terms:
Asthma
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Albuterol
Ciclesonide
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Asthmatic Agents
Respiratory System Agents
Tocolytic Agents
Reproductive Control Agents
Adrenergic beta-2 Receptor Agonists
Adrenergic beta-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Anti-Allergic Agents

ClinicalTrials.gov processed this record on August 23, 2016