Effect of High Dose Ciclesonide on Asthma Control (CONTRAST)

• ClinicalTrials.gov Identifier: NCT01455194
• Recruitment Status: Completed
• First Posted: October 19, 2011
• Results First Posted: October 25, 2016
• Last Update Posted: February 10, 2017
• Sponsor: AstraZeneca
• Information provided by (Responsible Party): AstraZeneca

Study Description

Brief Summary:

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 or disease	Intervention/treatment	Phase
Bronchial Asthma	Drug: Ciclesonide	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 520 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, 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.
• Study Start Date: November 2011
• Actual Primary Completion Date: August 2014
• Actual Study Completion Date: August 2014

Arms and Interventions

Arm	Intervention/treatment
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)

Outcome Measures

Primary Outcome Measures :

1. Asthma Control Questionnaire (ACQ) Score at Baseline [ Time Frame: Baseline ]
   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.
2. Change From Baseline in ACQ Score to Tlast [ Time Frame: Week 52 ]
   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 :

1. Time Course of ACQ [ Time Frame: Baseline, Week 52 (Treatment period) ]
   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.
2. Number of Weeks With Well-controlled Asthma Over the Course of the Study [ Time Frame: Baseline up to Week 52 (treatment period) ]
   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.
3. Number of Participants With Well-controlled Asthma and ACQ Improvement at the End of the Study [ Time Frame: Week 52 ]
   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.
4. Number of Participants Reporting Time to First Well-Controlled Asthma and ACQ Improvement [ Time Frame: Baseline up to Week 52 (treatment period) ]
   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.
5. 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) ]
   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.
6. Number of Participants Reporting Time to First Asthma Exacerbation [ Time Frame: Baseline up to Week 52 (treatment period) ]
   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
7. Number of Participants Reporting Asthma Exacerbations Rates [ Time Frame: Baseline up to Week 52 (treatment period) ]
   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.
8. Number of Participants With Markedly High Benefits [ Time Frame: Week 1 up to Week 52 ]
   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.
9. 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) ]
   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.
10. 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) ]
    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.
11. 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) ]
    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.
12. Number of Participants With Markedly Abnormal Laboratory Values [ Time Frame: Baseline period (Week -3 up to -1), treatment period (Baseline up to Week 56) ]
    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.

Eligibility Criteria

• Ages Eligible for Study: 12 Years to 70 Years (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• 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

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

AstraZeneca

Investigators

• Study Director: AstraZeneca AstraZeneca; AstraZeneca

More Information

• Responsible Party: AstraZeneca
• ClinicalTrials.gov Identifier: NCT01455194
• Other Study ID Numbers: CL-9709-301-RD; 2011-000683-99 ( EudraCT Number ); U1111-1133-6333 ( Registry Identifier: WHO ); CL-9709-301-RDCTID ( Registry Identifier: Israel )
• First Posted: October 19, 2011
• Results First Posted: October 25, 2016
• Last Update Posted: February 10, 2017
• Last Verified: December 2016

Keywords provided by AstraZeneca:

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