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A 12-week Safety and Efficacy Study of Beclomethasone Dipropionate (80 and 160 mcg/Day) Delivered Via Breath-Actuated Inhaler (BAI) in Patients >=12 Years Old With Persistent Asthma

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ClinicalTrials.gov Identifier: NCT02040779
Recruitment Status : Completed
First Posted : January 20, 2014
Results First Posted : December 11, 2017
Last Update Posted : December 11, 2017
Sponsor:
Information provided by (Responsible Party):
Teva Pharmaceutical Industries ( Teva Branded Pharmaceutical Products, R&D Inc. )

Brief Summary:
This is a randomized, double-blind, placebo-controlled parallel-group study. Participants will be randomly assigned to receive treatment with beclomethasone dipropionate at a dosage of 80 or 160 mcg/day delivered via a Breath-Actuated Inhaler (BAI); or a matching BAI placebo, in a 1:1:1 ratio after a 14- to 21-day run-in period. Participants and investigators will remain blinded to randomized treatment assignment during the study

Condition or disease Intervention/treatment Phase
Persistent Asthma Drug: Beclomethasone dipropionate breath-actuated inhaler Drug: Placebo breath-actuated inhaler Drug: albuterol/salbutamol Phase 3

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 273 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, 12-Week Clinical Study to Assess the Efficacy and Safety of Beclomethasone Dipropionate (80 and 160 mcg/Day) Delivered Via Breath-Actuated Inhaler (BAI) in Adolescent and Adult Patients 12 Years of Age and Older With Persistent Asthma
Study Start Date : December 26, 2013
Actual Primary Completion Date : December 24, 2014
Actual Study Completion Date : December 24, 2014

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Asthma

Arm Intervention/treatment
Experimental: BDP 80 mcg BAI
40 mcg beclomethasone dipropionate (BDP) via breath-actuated inhaler (BAI) twice daily for a total of 80 mcg/day.
Drug: Beclomethasone dipropionate breath-actuated inhaler
Beclomethasone dipropionate (BDP) breath-actuated inhaler (BAI) given in dosages of either 40 mcg/inhalation or 80 mcg/inhalation. Study drug was administered twice each day, in the morning and in the evening, after the completion of the asthma symptom score and the PEF measurements, in that order.
Other Name: BDP

Drug: albuterol/salbutamol
Rescue medication (albuterol/salbutamol hydrofluoroalkane (HFA) MDI [90 mcg ex-actuator] or equivalent) for use on an as-needed basis for the immediate relief of asthma symptoms throughout the treatment period
Other Name: bronchodilators

Experimental: BDP 160 mcg BAI
80 mcg beclomethasone dipropionate (BDP) via breath-actuated inhaler (BAI) twice daily for a total of 160 mcg/day.
Drug: Beclomethasone dipropionate breath-actuated inhaler
Beclomethasone dipropionate (BDP) breath-actuated inhaler (BAI) given in dosages of either 40 mcg/inhalation or 80 mcg/inhalation. Study drug was administered twice each day, in the morning and in the evening, after the completion of the asthma symptom score and the PEF measurements, in that order.
Other Name: BDP

Drug: albuterol/salbutamol
Rescue medication (albuterol/salbutamol hydrofluoroalkane (HFA) MDI [90 mcg ex-actuator] or equivalent) for use on an as-needed basis for the immediate relief of asthma symptoms throughout the treatment period
Other Name: bronchodilators

Placebo Comparator: Placebo BAI
Placebo breath-actuated inhaler (BAI) twice daily.
Drug: Placebo breath-actuated inhaler
Placebo was provided in matching breath-actuated inhaler (BAI) devices. The placebo devices were identical to the devices used to deliver active drug. Placebo was administered twice each day, in the morning and in the evening, after the completion of the asthma symptom score and the PEF measurements, in that order.

Drug: albuterol/salbutamol
Rescue medication (albuterol/salbutamol hydrofluoroalkane (HFA) MDI [90 mcg ex-actuator] or equivalent) for use on an as-needed basis for the immediate relief of asthma symptoms throughout the treatment period
Other Name: bronchodilators




Primary Outcome Measures :
  1. Standardized Baseline-Adjusted Trough Morning Forced Expiratory Volume in One Minute (FEV1) Area Under the Effect Curve From Time Zero to 12 Weeks (AUEC(0-12wk)) by Actual Treatment Received [ Time Frame: Baseline (Day 1 predose), weeks 2, 4, 8 and 12 ]

    The primary efficacy variable was the standardized baseline-adjusted trough morning (pre-dose and pre-rescue bronchodilator) FEV1 AUEC(0-12wk). Pulmonary function measurements such as FEV1 were obtained electronically by spirometry at the randomization visit (Day 1), each treatment visit (Weeks 2, 4, 8 and 12) and any unscheduled visit (such as the early termination visit). This summary is based on observed values recorded as 'best attempt'.

    The least-square (LS) means, difference of LS means and its 95% confidence interval (CI), and p-value represent the results obtained from the analysis of covariance with covariate adjustment for baseline, sex, age, current asthma therapy, and treatment.



Secondary Outcome Measures :
  1. Change From Baseline in Weekly Average of Daily Trough Morning Peak Expiratory Flow (PEF) Rate Over the 12-Week Treatment Period [ Time Frame: Baseline (Days -6 to Day 1 pre-dose), daily up to Week 12 ]

    Change from baseline in the weekly average of daily trough morning (pre-dose and pre-rescue bronchodilator) PEF by handheld spirometer over the 12-week treatment period.

    PEF were determined twice daily, in the morning and in the evening, before administration of study drug or rescue medications. A handheld spirometer was provided to patients and used to determine the morning and evening PEF throughout the study. The spirometer was programmed to record the highest PEF obtained from 3 valid attempts.

    Baseline was defined as the average of recorded trough morning PEF assessments over the 7 days prior to the first dose of double-blind study treatment, including the morning assessment at the randomization visit.

    The LS means, difference of LS means and its 95% confidence interval, and p value are obtained from the mixed model for repeated measures analysis with covariate adjustment for baseline, sex, age, current asthma therapy, treatment, week, and treatment by week interaction.


  2. Change From Baseline in Weekly Average of Daily Evening Peak Expiratory Flow (PEF) Over the 12-Week Treatment Period [ Time Frame: Baseline (Days -6 to Day 1 pre-dose), daily up to Week 12 ]

    A hand-held peak flow meter was provided to patients at the screening visit and used to determine the morning and evening PEF throughout the course of the study. The patient recorded the highest value of 3 measurements obtained in the morning and evening in the patient diary.

    Baseline in evening PEF is defined as the average of recorded evening PEF assessments over the 7-day window before randomization.

    The LS means, difference of LS means and its 95% confidence interval, and p value are obtained from the mixed model for repeated measures analysis with covariate adjustment for baseline, sex, age, current asthma therapy, treatment, week, and treatment by week interaction.


  3. Change From Baseline in Weekly Average of Total Daily Use of Albuterol/Salbutamol Inhalation Aerosol Over Weeks 1-12 [ Time Frame: Baseline (Days -6 to Day 1 pre-dose), daily up to Week 12 ]

    Change from baseline in the use of rescue medication, albuterol/salbutamol, during the treatment period offers an indication of asthma control.

    The LS means, difference of LS means and its 95% CI, and p-value are obtained from the mixed model for repeated measures analysis with covariate adjustment for baseline, sex, age, current asthma therapy, treatment, week and treatment by week interaction.

    Baseline was defined as the average of recorded daily usage of albuterol/salbutamol inhalation aerosol over the 7 days prior to the first dose of double-blind study treatment, including morning usage at the randomization visit.


  4. Change From Baseline in Weekly Average of Total Daily Asthma Symptom Score Over the 12-Week Treatment Period [ Time Frame: Baseline (Days -6 to Day 1 pre-dose), daily up to Week 12 ]

    Asthma symptom scores were recorded in the patient's diary each morning and evening before determining FEV1 and PEF and before administration of study or rescue medications.

    The Daytime Symptom Score was recorded in the evening on a scale of 0 (No symptoms during the day) to 5 (Symptoms so severe that I could not go to work or perform normal daily activities) plus the Nighttime Symptom Score in the morning on a scale of 0 (No symptoms during the night) to 4 (Symptoms so severe that I did not sleep at all) for a total score range of 0-9.

    Baseline was defined as the average of recorded daily asthma symptom scores (average of daytime and nighttime score) over the 7 days prior to the first dose of study treatment, including the morning assessment at the randomization visit.

    The LS means, difference of LS means and its 95% CI, and p value are obtained from the mixed model for repeated measures analysis with covariate adjustment for baseline, sex, age, current asthma therapy,


  5. Kaplan-Meier Estimates of Time to Study Drug Treatment Withdrawal Due to Meeting Stopping Criteria for Worsening Asthma During the 12-Week Treatment Period [ Time Frame: Treatment period: daily from Day 1 up to Week 12 ]

    The time to patient study drug treatment withdrawal due to worsening asthma was defined as the number of days elapsed from the date of randomization to the date of withdrawal due to meeting stopping criteria. Alert criteria for individual patients with worsening asthma were designed to ensure patient safety. The investigator determined whether the patient's overall clinical picture is consistent with worsening asthma and if the patient should be withdrawn from study drug treatment (but not the study) and be placed on appropriate asthma therapy in the interest of patient safety.

    An example of alert criteria is:

    • FEV1 as measured at the study center is below the FEV1 stability limit value calculated at randomization visit (Day 1).
    • Other criteria as defined in the protocol.

  6. Number of Participants Withdrawn From Study Due to Meeting Stopping Criteria for Worsening Asthma During the 12-Week Treatment Period [ Time Frame: Treatment period: Day 1 up to Week 12 ]

    A count of participants who were withdrawn from the study due to meeting stopping criteria. Alert criteria for individual patients with worsening asthma were designed to ensure patient safety. The investigator determined whether the patient's overall clinical picture is consistent with worsening asthma and if the patient should be withdrawn from study drug treatment (but not the study) and be placed on appropriate asthma therapy in the interest of patient safety.

    An example of alert criteria is:

    • FEV1 as measured at the study center is below the FEV1 stability limit value calculated at randomization visit (Day 1).
    • Other criteria as defined in the protocol.

  7. Participants With Treatment-Emergent Adverse Events (TEAEs) [ Time Frame: Day 1 up to Week 12 ]
    An adverse event was defined as any untoward medical occurrence that develops or worsens in severity during the conduct of a clinical study and does not necessarily have a causal relationship to the study drug. Severity was rated by the investigator on a scale of mild, moderate and severe, with severe= an inability to carry out usual activities. Relation of AE to treatment was determined by the investigator. Serious AEs include death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, OR an important medical event that jeopardized the patient and required medical intervention to prevent 1 of the outcomes listed in this definition.

  8. Participants With Potentially Clinically Relevant Abnormal Vital Sign Results During the Treatment Period [ Time Frame: Baseline (Day 1 predose), Visits at weeks 2, 4, 8, 12 ]

    Criteria for the select vital signs that showed a potentially clinically relevant abnormal result are:

    • Sitting systolic BP (low); <=90 mm Hg and decrease of >=20 mm Hg from baseline
    • Sitting diastolic BP (high): >=105 mm Hg and increase of >=15 mm Hg from baseline

    Baseline is defined as the last available assessment prior to the first dose of double-blind study treatment (usually Day 1 predose).


  9. Participants With Findings During Oropharyngeal Examination During Treatment [ Time Frame: Visits at weeks 2, 4, 8, 12 ]
    Oropharyngeal examinations were performed at every visit by a qualified healthcare professional: during treatment visits are summarized. Any visual evidence of oral candidiasis during the treatment period of the study was evaluated by obtaining and analyzing a swab of the suspect area for culturing. Appropriate therapy was to be initiated immediately at the discretion of the investigator and was not to be delayed for culture confirmation.



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Ages Eligible for Study:   12 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Severity of Disease: The patient has persistent asthma, with an forced expiratory volume in 1 second (FEV1) 40%-85% of the value predicted for age, height, sex, and race as per the National Health and Nutrition Examination Survey (NHANES III) reference values at screening visit (SV) (Hankinson et al 1999).
  • Current asthma therapy: The patient is currently being treated with 1 of the following:

    1) inhaled corticosteroids (ICSs) at a stable daily dose of less than or equal to 220 mcg/day fluticasone propionate via metered dose inhaler (MDI) or equivalent for a minimum of 4 weeks (28 days) before screening visit, or 2) a stable daily dosage of non-corticosteroid therapy, including leukotriene modifiers, theophylline, chromones, or short-acting beta-2 agonists (SABAs) alone or in combination for a minimum of 4 weeks (28 days) before screening visit (SV).

  • Reversibility of disease: The patient has demonstrated at least 15% and at least 200 mL increase from baseline FEV1 (patients age 18 and older) within 30 minutes after 2-4 inhalations of albuterol/salbutamol hydrofluoroalkane (HFA) MDI (90 mcg ex-actuator) or equivalent at SV or on retesting. - Other criteria apply, please contact the investigator for more information

Exclusion Criteria:

  • The patient has a history of life-threatening asthma, defined for this protocol as an asthma episode that required intubation and/or was associated with hypercapnea, respiratory arrest, or hypoxic seizures.
  • The patient is a pregnant or lactating female or plans to become pregnant.
  • The patient has a known hypersensitivity to any corticosteroid or any of the excipients in the study drug or rescue medication formulation.
  • The patient currently smokes or has a smoking history of 10 pack-years or more (a pack-year is defined as smoking 1 pack of cigarettes/day for 1 year). The patient may not have used tobacco products within the past year.
  • The patient has had an asthma exacerbation requiring oral corticosteroids within 1 month before SV, or has had any hospitalization for asthma within 2 months before SV.
  • The patient has historical or current evidence of a clinically significant disease. Significant disease is defined as any disease that in the medical judgment of the investigator would put the safety of the patient at risk through participation or that could affect the efficacy or safety analysis if the disease/condition worsened during the study.
  • Other criteria apply, please contact the investigator for more information

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02040779


  Show 47 Study Locations
Sponsors and Collaborators
Teva Branded Pharmaceutical Products, R&D Inc.
Investigators
Study Director: Medical Director, MD Teva Pharmaceuticals USA

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Teva Branded Pharmaceutical Products, R&D Inc.
ClinicalTrials.gov Identifier: NCT02040779     History of Changes
Other Study ID Numbers: BDB-AS-304
First Posted: January 20, 2014    Key Record Dates
Results First Posted: December 11, 2017
Last Update Posted: December 11, 2017
Last Verified: November 2017

Keywords provided by Teva Pharmaceutical Industries ( Teva Branded Pharmaceutical Products, R&D Inc. ):
asthma
breath-actuated inhaler
beclomethasone

Additional relevant MeSH terms:
Asthma
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Albuterol
Beclomethasone
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
Anti-Inflammatory Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists