Randomized, Placebo-controlled, Multi-dose, Study Comparing Budesonide/Formoterol to Symbicort® in Asthmatic Patients

Clinical Trial ID: NCT02495168


A randomized multiple-dose, placebo-controlled, parallel group design consisting of a 2-week run-in period followed by a 6-week treatment period of the placebo, Test product (Budesonide 80 mcg / Formoterol fumarate dihydrate 4.5 mcg), or Reference product Symbicort® inhalation aerosol.

This is a pivotal trial that will examine therapeutic equivalence of a new generic fixed-dose combination product containing Budesonide 80 mcg / Formoterol fumarate dihydrate 4.5 mcg and reference listed drug (RLD) Symbicort® inhalation aerosol in adult patients with chronic but stable asthma as defined in National Asthma Education and Prevention Program Expert Panel Report 3 (NAEPP 3) guidelines. To ensure adequate study sensitivity the test and reference products should both be statistically superior to placebo (p<0.05) with regard to the bioequivalent study primary endpoints.


Inclusion criteria: 1. Adolescent and adult male or female patients (≥12 and ≤75 years of age). 2. Female patients must not be lactating or pregnant at screening, as documented by a negative serum pregnancy test with a minimum sensitivity of 25 IU/L or equivalent units of beta-human chorionic gonadotropin (β-hCG) at screening. 3. Women of childbearing potential (WOCBP) and female partners (WOCBP) of male patients participating in the study, must commit to consistent and correct use of an acceptable method of birth control (at the Investigator's discretion) throughout the study and for 30 days after study drug discontinuation. 4. Male patients and male partners of female patients (WOCBP) must commit to consistent and correct use of an acceptable method of birth control (at the Investigator's discretion) throughout the study and for 30 days after the study drug discontinuation. 5. Diagnosed with asthma as defined by the NAEPP 3 at least 6 months prior to screening. If the patient is new to the study site, the Investigator must confirm the patient's asthma diagnosis. Acceptable means include either medical records or pharmacy records. 6. Moderate to severe asthma with a pre-bronchodilator FEV1 of ≥45% and ≤85% of the predicted normal value during measured at least 6 hours after short-acting β agonist (SABA) and at least 24 hours after the last dose of long-acting β agonist (LABA) at the screening visit (Visit 1) and on the first day of treatment (prior to randomization at Visit 2). 7. Currently non-smoking, negative for urine cotinine at screening, having not used tobacco products (i.e., cigarettes, cigars, pipe tobacco, electronic cigarettes) within the past year, and had ≤10 pack-years of historical use. 8. Body mass index (BMI) between 18 and 40, inclusive, for patients ≥18 years old. For adolescent patients 12 to 17 years old, BMI between 15 and 40 inclusive (in accordance with the BMI range typical for the age). 9. ≥15% and ≥ 0.20 L reversibility of FEV1 within 30 minutes following 360 mcg (4 puffs) of albuterol (400 mcg salbutamol) inhalation (pMDI). If the patient achieves <15%, but ≥10% reversibility at Visit 1, the site may instruct the patient to hold LABA and/or inhaled corticosteroids (ICS) and return up to 7 days later for a repeat test. Only 1 repeat of the Visit 1 spirometry (to retest reversibility) is allowed per screening. 10. Able to perform valid and reproducible spirometry per American Thoracic Society/European Respiratory Society (ATS/ERS) standards at screening. 11. Able to inhale study drug properly. 12. Willing to discontinue asthma medications (ICS and LABAs) during the Run-in Period and for the remainder of the study. 13. Able to replace current regularly scheduled SABAs with albuterol/salbutamol inhaler for use only on as needed basis for the duration of the study (patients should be able to withhold all inhaled SABAs for at least 6 hours prior to lung function assessments on study visits). 14. Able to continue the following medications without a significant adjustment of dosage, formulation, dosing interval for the duration of the study, and judged able by the Investigator to withhold them for the specified minimum time intervals prior to each clinic visit, if applicable: 1. Short-acting forms of theophylline: 12 hours. 2. Twice-a-day controlled-release forms of theophylline: 24 hours. 3. Once-a-day controlled-release forms of theophylline: 36 hours. 15. Able to discontinue the following medications for the specified minimum time intervals prior to the Run-in Period and for the remainder of the study, if applicable: 1. Oral corticosteroids for 30 days. 2. Parenteral corticosteroids for 30 days. 3. Oral (not inhaled) SABAs for 24 hours. 16. Clinical laboratory tests (clinical chemistry, hematology, and urinalysis) and 12-lead electrocardiogram (ECG) conducted at the screening visit within normal limits or abnormal but not clinically significant to the Investigator. The QTc should be calculated using Bazett's formula. 17. Willing to give written informed consent/assent, and willing and able to follow the study rules and procedures. 18. Stable on chronic asthma treatment regimen for at least 4 weeks prior to enrollment. 19. 19.Ability to perform forced expiratory assessments according to ATS standards. Randomization eligibility criteria: 1. Baseline pre bronchodilator FEV1 should be ≥45% and ≤85% of predicted normal value and not vary by more than ±20% from the screening visit FEV1 value. 2. Compliance during the Run-in Period of at least 75% based on eDiary entries is required for a patient to qualify for randomization. Compliance with the run-in placebo treatment must be between 75% and 125%. 3. Documented total asthma symptom score of ≥1 for at least 2 days during the Run-in Period. Exclusion criteria: 1. Life-threatening asthma, defined as a history of asthma episode(s) requiring intubation, and/or associated with hypercapnea, respiratory arrest or hypoxic seizures, asthma-related syncopal episode(s), or hospitalizations within the past year or during the Run-in Period. 2. Exercise-induced asthma as the only asthma-related diagnosis. 3. Evidence or history of clinically significant disease or abnormality including congestive heart failure, uncontrolled hypertension, uncontrolled coronary artery disease, myocardial infarction, or cardiac dysrhythmia. In addition, historical or current evidence of significant hematologic, hepatic, neurologic, psychiatric, renal, or other diseases that, in the opinion of the Investigator, would put the patient at risk through study participation, or would affect the study analyses if the disease exacerbated during the study. Patients with well-controlled hypertension, diabetes or hypercholesterolemia are not excluded as long as their medication does not interfere with the study. 4. Any other clinically significant pulmonary disease except for asthma, including chronic obstructive pulmonary disease (COPD), interstitial lung disease, cystic fibrosis, bronchiectasis, chronic bronchitis, emphysema, active pulmonary tuberculosis, pulmonary carcinoma, pulmonary fibrosis, or pulmonary hypertension. In addition, obstructive sleep apnea warranting a prescription for continuous or biphasic positive airway pressure (CPAP or BiPAP). 5. Patients who required systemic corticosteroids (for any reason) within the past 4 weeks. 6. Patients with hypersensitivity to any sympathomimetic drug (e.g., formoterol, albuterol/salbutamol, or salmeterol) or any inhaled, intranasal, or systemic corticosteroid therapy. 7. Patients taking medication(s) (either daily or as needed) with the potential to affect the course of asthma or to interact with sympathomimetic amines, e.g.,: 1. Oral β-blockers. 2. Strong cytochrome P450 3A4 inhibitors (e.g., ritonavir). 3. Monoclonal antibodies/Biologic agents which may affect the course of asthma (such as mepolizumab, reslizumab, lebrikizumab, and others). 8. Viral or bacterial, upper or lower respiratory tract infection or sinus or middle ear infection within 2 weeks prior to the screening visit or during the Run-in Period. 9. Factors (e.g., infirmity, disability or geographic location) that the Investigator feels would likely limit the patient's compliance with the study protocol or scheduled clinic visits. 10. Anti-IgE (such as omalizumab) within the 6 months prior to screening. 11. History of alcohol or drug abuse within the last 6 months. 12. A positive urine drug screen at Visit 1. Exceptions are made for a positive urine drug screen at Visit 1 for opiates or stimulants if there is a documented prescription with supporting medical history and diagnosis, and the Principal Investigator assesses there are no safety concerns with patient participation. Screened patients with a urine drug screen positive for Marijuana/Tetrahydrocannabinol are not eligible for study participation, without exceptions. Repeat drug screening is not allowed. 13. Have received any investigational treatment within 30 days (or within 5 terminal half-lives of the investigational drug whichever is longer) of the screening visit or plans to receive investigational treatment within 30 days after the study is completed. 14. Be an Investigator, employee, or otherwise be directly affiliated with the study site, Watson Laboratories Inc. and affiliates, or service provider involved in the study including being an immediate family member of an Investigator or site employee (where immediate family member is defined as spouse, parent, child or sibling, whether biological or legally adopted or in foster care). 15. Non-compliance with the study requirements, rules, and procedures.

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    Actavis Inc.

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