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Effect of High Dose Ciclesonide on Asthma Control (CONTRAST)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Takeda
ClinicalTrials.gov Identifier:
NCT01455194
First received: October 17, 2011
Last updated: August 29, 2016
Last verified: August 2016
  Purpose
The aim of the trial is to investigate asthma control with 160 to 640 mcg ciclesonide/day. Asthma control will be assessed by the Asthma Control Questionnaire (ACQ).

Condition Intervention Phase
Bronchial Asthma
Drug: Ciclesonide
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Control of Moderate or Severe Asthma With 160, 320 and 640 mcg Ciclesonide/Day. A One-year Randomised, Double-blind, Multicenter Trial.

Resource links provided by NLM:


Further study details as provided by Takeda:

Primary Outcome Measures:
  • Asthma Control Questionnaire (ACQ) Score at Baseline [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    The ACQ was developed to measure the adequacy of asthma control in clinical research and in clinical practice. It includes 5 questions about symptoms, 1 question about beta 2 -agonist use and 1 about lung function (FEV1% predicted). Participants recall their experiences during the previous 7 days and respond to each question using a 7-point scale. The items are equally weighted and the ACQ score is the mean of 7 items and ranges between 0 (well controlled) and 6 (extremely poorly controlled). Mean scores of =<0.75 indicate well-controlled asthma, scores between 0.76 and < 1.5 indicate partly controlled asthma, and a score >= 1.5 indicates uncontrolled asthma.

  • Change From Baseline in ACQ Score to Tlast [ Time Frame: Week 52 ] [ Designated as safety issue: No ]
    The ACQ was developed to measure the adequacy of asthma control in clinical research and in clinical practice. It includes 5 questions about symptoms, 1 question about beta 2 -agonist use and 1 about lung function (FEV1% predicted). Participants recall their experiences during the previous 7 days and respond to each question using a 7-point scale. The items are equally weighted and the ACQ score is the mean of 7 items and ranges between 0 (well controlled) and 6 (extremely poorly controlled). Mean scores of =<0.75 indicate well-controlled asthma, scores between 0.76 and < 1.5 indicate partly controlled asthma, and a score >= 1.5 indicates uncontrolled asthma.


Secondary Outcome Measures:
  • Time Course of ACQ [ Time Frame: Baseline, Week 52 (Treatment period) ] [ Designated as safety issue: No ]
    The time course of the incidence of a 0.5 points improvement of ACQ score was evaluated. Mean ACQ values over time by treatment group for on-treatment site measurements was assessed. The time course of asthma control (ACQ) was done on a weekly base using home-based and site-based ACQ measurements. The ACQ was developed to measure the adequacy of asthma control in clinical research and in clinical practice. It includes 5 questions about symptoms, 1 question about beta 2 -agonist use and 1 about lung function (FEV1% predicted). Participants recall their experiences during the previous 7 days and respond to each question using a 7-point scale. The items are equally weighted and the ACQ score is the mean of 7 items and ranges between 0 (well controlled) and 6 (extremely poorly controlled). Mean scores of =<0.75 indicate well-controlled asthma, scores between 0.76 and < 1.5 indicate partly controlled asthma, and a score >= 1.5 indicates uncontrolled asthma.

  • Number of Weeks With Well-controlled Asthma Over the Course of the Study [ Time Frame: Baseline up to Week 52 (treatment period) ] [ Designated as safety issue: No ]
    The number of weeks with well-controlled asthma is defined as the number of weeks that the participant had an ACQ score of 0.75 or lower over the course of the study. The ACQ was developed to measure the adequacy of asthma control in clinical research and in clinical practice. It includes 5 questions about symptoms, 1 question about beta 2 -agonist use and 1 about lung function (FEV1% predicted). Participants recall their experiences during the previous 7 days and respond to each question using a 7-point scale. The items are equally weighted and the ACQ score is the mean of 7 items and ranges between 0 (well controlled) and 6 (extremely poorly controlled). Mean scores of =<0.75 indicate well-controlled asthma, scores between 0.76 and < 1.5 indicate partly controlled asthma, and a score >= 1.5 indicates uncontrolled asthma.

  • Number of Participants With Well-controlled Asthma and ACQ Improvement at the End of the Study [ Time Frame: Week 52 ] [ Designated as safety issue: No ]
    Well-controlled asthma at the end of the study was defined as a participant with an ACQ score of 0.75 or lower. ACQ improvement was defined as a decrease in ACQ score of at least 0.5. The ACQ was developed to measure the adequacy of asthma control in clinical research and in clinical practice. It includes 5 questions about symptoms, 1 question about beta 2 -agonist use and 1 about lung function (FEV1% predicted). Participants recall their experiences during the previous 7 days and respond to each question using a 7-point scale. The items are equally weighted and the ACQ score is the mean of 7 items and ranges between 0 (well controlled) and 6 (extremely poorly controlled). Mean scores of =<0.75 indicate well-controlled asthma, scores between 0.76 and < 1.5 indicate partly controlled asthma, and a score >= 1.5 indicates uncontrolled asthma.

  • Number of Participants Reporting Time to First Well-Controlled Asthma and ACQ Improvement [ Time Frame: Baseline up to Week 52 (treatment period) ] [ Designated as safety issue: No ]
    Well-controlled asthma at the end of the study was defined as a participant with an ACQ score of 0.75 or lower. ACQ improvement was defined as a decrease in ACQ score of at least 0.5. The ACQ was developed to measure the adequacy of asthma control in clinical research and in clinical practice. It includes 5 questions about symptoms, 1 question about beta 2 -agonist use and 1 about lung function (FEV1% predicted). Participants recall their experiences during the previous 7 days and respond to each question using a 7-point scale. The items are equally weighted and the ACQ score is the mean of 7 items and ranges between 0 (well controlled) and 6 (extremely poorly controlled). Mean scores of =<0.75 indicate well-controlled asthma, scores between 0.76 and < 1.5 indicate partly controlled asthma, and a score >= 1.5 indicates uncontrolled asthma.

  • Number of Participants Reporting Time to First Well-Controlled Asthma Measurement by ACQ Cut-Off Point [ Time Frame: Baseline up to Week 52 (treatment period) ] [ Designated as safety issue: No ]
    Well-controlled asthma was defined as an ACQ score of equal to or lower than the ACQ cut-off point.The ACQ was developed to measure the adequacy of asthma control in clinical research and in clinical practice. It includes 5 questions about symptoms, 1 question about beta 2 -agonist use and 1 about lung function (FEV1% predicted). Participants recall their experiences during the previous 7 days and respond to each question using a 7-point scale. The items are equally weighted and the ACQ score is the mean of 7 items and ranges between 0 (well controlled) and 6 (extremely poorly controlled). Mean scores of =<0.75 indicate well-controlled asthma, scores between 0.76 and < 1.5 indicate partly controlled asthma, and a score >= 1.5 indicates uncontrolled asthma.

  • Number of Participants Reporting Time to First Asthma Exacerbation [ Time Frame: Baseline up to Week 52 (treatment period) ] [ Designated as safety issue: No ]
    Asthma exacerbations were defined as a worsening of asthma requiring either treatment with oral (or other systemic) glucocorticosteroids for at least 3 days or hospitalisation or a visit to the emergency room because of asthma. Baseline was defined as the average of the ACQ measurements of the last 2 weeks at site prior to first intake of double-blind study medication

  • Number of Participants Reporting Asthma Exacerbations Rates [ Time Frame: Baseline up to Week 52 (treatment period) ] [ Designated as safety issue: Yes ]
    Participants with at least 1 asthma exacerbation in the double-blind treatment period have been reported. As predefined in the protocol, the results for participants with missing data for any category were not included.

  • Number of Participants With Markedly High Benefits [ Time Frame: Week 1 up to Week 52 ] [ Designated as safety issue: No ]
    The analyses was intended to identify participant's subsets that would benefit from dose escalation. This analysis tested the potential factors, including age, sex, pretrial inhaled corticosteroid (ICS) dose category, history of exacerbations, baseline ACQ score, baseline BMI category and smoking status. ACQ includes 5 questions about symptoms, 1 about beta 2 -agonist use and 1 about lung function (FEV1% predicted). Participants recall their experiences during the previous 7 days and respond to each question using a 7-point scale. The items are equally weighted and the ACQ score is the mean of 7 items and ranges between 0 (well controlled) and 6 (extremely poorly controlled).Mean scores of =<0.75 indicate well-controlled asthma, scores between 0.76 and < 1.5 indicate partly controlled asthma, and a score >=1.5 indicates uncontrolled asthma. As predefined in the protocol, participants with missing data for any category were not included.

  • Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAE) [ Time Frame: Baseline period (Week -3 up to -1), treatment period (Baseline up to Week 56) ] [ Designated as safety issue: Yes ]
    An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (eg, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. TEAE is defined as an adverse event with an onset that occurs after receiving study drug. AEs included both serious AEs and non-serious AEs. Baseline of double-blind treatment period was defined as the average of the measurements of the last 2 weeks at site prior to first intake of double-blind study medication.

  • Number of Participants Reporting Clinically Significant Change From Baseline in Vital Signs [ Time Frame: Baseline period (Week -3 up to -1), treatment period (Baseline up to Week 56) ] [ Designated as safety issue: No ]
    Vital signs included body temperature, blood pressure (BP) and pulse rate. Normal range for vital signs included: Systolic BP >170 millimeters of mercury (mm Hg) or <85 mm Hg, Diastolic BP >105 mm Hg, resting pulse rate: >120 bpm or <50 bpm, difference in systolic BP at Visit x (increase or decrease) compared with pretreatment >40 mm Hg and difference in pulse rate at Visit x (increase or decrease) compared with pretreatment >30 bpm. Baseline of double-blind treatment period was defined as the average of the measurements of the last 2 weeks at site prior to first intake of double-blind study medication.

  • Number of Participants Reporting Clinically Significant Change From Baseline in Physical Examination Findings [ Time Frame: Baseline period (Week -3 up to -1), treatment period (Baseline up to Week 56) ] [ Designated as safety issue: No ]
    Physical examination consists of examinations of the following body systems: (1) eyes; (2) ears, nose, throat; (3) cardiovascular system; (4) respiratory system; (5) gastrointestinal system; (6) dermatologic system; (7) extremities; (8) musculoskeletal system; (9) nervous system; (10) lymph nodes; and (11) physical examinations other than body systems described in (1) to (10). Baseline of double-blind treatment period was defined as the average of the measurements of the last 2 weeks at site prior to first intake of double-blind study medication.

  • Number of Participants With Markedly Abnormal Laboratory Values [ Time Frame: Baseline period (Week -3 up to -1), treatment period (Baseline up to Week 56) ] [ Designated as safety issue: No ]
    The number of participants with any markedly abnormal standard safety laboratory values collected throughout study. Baseline of double-blind treatment period was defined as the average of the measurements of the last 2 weeks at site prior to first intake of double-blind study medication.


Enrollment: 520
Study Start Date: November 2011
Study Completion Date: August 2014
Primary Completion Date: August 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: CIC 160
Two puffs of 40 mcg ciclesonide inhaled in the morning and the evening (corresponding to a total daily dose of 160 mcg)
Drug: Ciclesonide
During the treatment period subjects will inhale two puffs of either 40, 80 or 160 μg ciclesonide in the morning and the evening (corresponding to a total daily dose of 160, 320 or 640 μg)
Active Comparator: CIC 320
Two puffs of 80 mcg ciclesonide inhaled in the morning and the evening (corresponding to a total daily dose of 320 mcg)
Drug: Ciclesonide
During the treatment period subjects will inhale two puffs of either 40, 80 or 160 μg ciclesonide in the morning and the evening (corresponding to a total daily dose of 160, 320 or 640 μg)
Active Comparator: CIC 640
Two puffs of 160 mcg ciclesonide inhaled in the morning and the evening (corresponding to a total daily dose of 640 mcg)
Drug: Ciclesonide
During the treatment period subjects will inhale two puffs of either 40, 80 or 160 μg ciclesonide in the morning and the evening (corresponding to a total daily dose of 160, 320 or 640 μg)

  Eligibility

Ages Eligible for Study:   12 Years to 70 Years   (Child, Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Written informed consent was provided
  • History of persistent bronchial asthma for at least 6 months
  • Current treatment with an Inhaled Corticosteroid (ICS) at a stable dose in the dose range of 200-1000 μg Fluticasone Propionate (FP)/day or equivalent for a minimum of 12 weeks
  • Good inhalation technique
  • Under the current ICS pre-treatment the ACQ score ranges between ≥ 0.75 and ≥ 2

Exclusion Criteria:

  • Clinically relevant abnormal laboratory values suggesting an unknown disease and requiring further clinical evaluation
  • Concomitant severe diseases (e.g. malignant diseases during the past 5 years [other than basal or squamous cell carcinoma], hepatitis C, acquired immune deficiency syndrome [AIDS])
  • Diseases which are contraindications for the use of ICS (e.g. active or inactive pulmonary tuberculosis or relevant fungal, bacterial or viral infections of the lower respiratory tract demanding specific treatment)
  • Use of systemic glucocorticosteroids within 4 weeks (injectable depot steroids 6 weeks) before entry into the baseline period, or more than 3 times during the last 6 months
  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: NCT01455194

Locations
Argentina
Capital Federal, Buenos Aires, Argentina
Ciudad Autonoma de Buenos Aires, Argentina
Rosario-Santa Fe, Argentina
Rosario, Argentina
Salta, Argentina
Tucuman, Argentina
Brazil
Florianopolis, Brazil
Goiania, Brazil
Porto Alegre, Brazil
Rio de Janiero, Brazil
Santo Andre, Sao Paulo, Brazil
Sao Paulo, Brazil
Sorocaba, Brazil
Germany
Berlin, Germany
Bonn, Germany
Landsberg, Germany
Rudersdorf, Germany
Schwetzingen, Germany
Israel
Beer-Sheva, Israel
Haifa, Israel
Jerusalem, Israel
Kfar Saba, Israel
Petach Tikva, Israel
Rehovot, Israel
Tel Aviv, Israel
Russian Federation
Barnaul, Russian Federation
Moscow, Russian Federation
Novosibirsk, Russian Federation
St. Petersburg, Russian Federation
Tomsk, Russian Federation
Sponsors and Collaborators
Takeda
Investigators
Study Director: Medical Director Takeda
  More Information

Responsible Party: Takeda
ClinicalTrials.gov Identifier: NCT01455194     History of Changes
Other Study ID Numbers: CL-9709-301-RD  2011-000683-99  U1111-1133-6333  CL-9709-301-RDCTID 
Study First Received: October 17, 2011
Results First Received: April 24, 2016
Last Updated: August 29, 2016
Health Authority: Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
Brazil: National Health Surveillance Agency
Germany: Federal Institute for Drugs and Medical Devices
Israel: Ministry of Health
Russia: Ministry of Health of the Russian Federation

Keywords provided by Takeda:
ciclesonide
asthma

Additional relevant MeSH terms:
Asthma
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Ciclesonide
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Anti-Allergic Agents

ClinicalTrials.gov processed this record on December 09, 2016