Safety Study of Albuterol Spiromax® in Subjects With Asthma

Asthma Clinical Trial

Official title:

A Multi-Center 52-Week Study to Assess the Safety of Albuterol Spiromax® in Subjects With Asthma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01698320
• Other study ID #: ABS-AS-307
• Status: Completed
• Phase: Phase 3
• First received: September 14, 2012
• Last updated: August 12, 2015
• Start date: October 2012
• Est. completion date: December 2013

Study information

• Verified date: August 2015
• Source: Teva Pharmaceutical Industries
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the safety of Albuterol Spiromax® over 52 weeks during two dosing periods: (1) a 12-week, double-blind, placebo-controlled QID dosing period followed by (2) a 40-week, open-label PRN dosing period, and to evaluate Albuterol Spiromax® device performance through the life of the device during the study.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 364
• Est. completion date: December 2013
• Est. primary completion date: December 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 12 Years and older

Eligibility

Inclusion Criteria:

• Written informed consent and HIPAA signed and dated by the subject or written informed assent signed and dated both by the subject and/or parent/caregiver/legal guardian before conducting any study related procedure.

• Males or females with asthma ages 12 years or older at screening.

• Documented history of persistent asthma and current use of an MDI containing any short-acting beta-adrenergic agonist (e.g. albuterol, levalbuterol,) on average of at least once/week over the 4-weeks prior to screening. The asthma diagnosis must be consistent with the diagnosis of asthma as per the National Asthma Education and Prevention Program.

• If female, is currently not pregnant, breast feeding, or attempting to become pregnant (for 4 weeks before the screening visit and throughout the duration of the study), and is of Non-childbearing potential, defined as:

• =1 year post-menopausal or

• Surgically sterile (tubal ligation, bilateral oophorectomy, salpingectomy, or hysterectomy) or is of

• Childbearing potential, has a negative serum pregnancy test, and is willing to commit to using a consistent and acceptable method of birth control

• General good health in the opinion of the investigator as indicated by medical history, physical examination, laboratory tests (hematology, serum chemistry and urinalysis) assessed as either normal or abnormal not clinically significant (NCS) per the principal investigator, as well as a 12-lead ECG interpreted as either "Normal" or "Abnormal NCS" as determined by the central cardiologist. Subjects must also be free of any clinically significant, uncontrolled concomitant conditions other than asthma that could interfere with study conduct, influence the interpretation of study observations/results, or put the subject at increased risk during the trial.

• Capable of understanding the requirements, risks, and benefits of study participation, and, as judged by the investigator, and being compliant with all study requirements (visits, record-keeping, etc).

• Non-smoker for at least one year prior to the screening visit and a maximum pack-year (PY) smoking history of 10 years.

• Able to demonstrate proper inhaler technique with study inhaler.

Exclusion Criteria:

• Pregnancy, nursing, or plans to become pregnant or donate gametes (ova or sperm) for in vitro fertilization during the study period or for 30 days following the subject's last study related visit.

• Participation in any investigational drug trial within 30 days preceding the screening visit or planned participation in another investigational drug trial at any time during this trial.

• A known hypersensitivity to albuterol or any of the excipients in the formulations.

• History of severe milk protein allergy

• History of an upper or lower respiratory tract infection or disorder (including, but not limited to bronchitis, pneumonia, acute or chronic sinusitis, otitis media, influenza, etc) which is not resolved at least 1 week prior to the SV.

• History of alcohol or drug abuse within two years preceding the SV.

• Use of any protocol prohibited concomitant medications for asthma (any oral ß2-adrenergic agonists) or any protocol prohibited concomitant non-asthma medications including treatment with ß2-adrenergic receptor antagonists and non-selective ß-receptor blocking agents such as ß-blocking anti-hypertensive products (administered by any route), MAO inhibitors, and/or tricyclic antidepressants. (Subject's own MDI short-acting ß-agonist rescue inhaler should be used until the start of the Run-In period when a study rescue inhaler is provided.)

• Inability or unwillingness to comply with the protocol requirements.

• History of life-threatening asthma [defined here as an asthma episode requiring intubation and/or associated with hypercapnea, respiratory arrest or hypoxic seizures.]

• Any asthma exacerbation within 3 months of the SV requiring oral or systemic corticosteroids or any hospitalization for asthma within 6 months of the SV.

Note: An exacerbation of asthma is defined as any worsening of asthma requiring any treatment other than rescue albuterol or the subject's regular asthma maintenance therapy. This includes requiring the use of systemic corticosteroids and/or emergency room visit or hospitalization or a change in subject's regular asthma maintenance treatment. A subject does not need to be withdrawn from the study due to an asthma exacerbation unless hospitalization is required or unless the principal investigator believes it is in the subjects' best interest to withdraw from the study.

• Previous participation in an inhaled Albuterol Spiromax® (Teva) study, with the exception of the ABS-AS-306 study.

• Study participation by clinical investigator site employees and/or their immediate relatives.

• Study participation by related or non-related individuals living in the same household, i.e. only one subject per household may participate in the study.

• Any clinically significant endocrine, hematological, hepatic, renal, gastrointestinal, neurological, cardiac, metabolic, immunological, any non-asthmatic acute or chronic pulmonary condition (including but not limited to bronchitis, emphysema, active tuberculosis, bronchiectasis, cystic fibrosis), and malignancy other than basal cell carcinoma. Significant is defined for this protocol as any condition that, in the opinion of the investigator, would put the safety of the subject at risk through participation, or which could affect the safety analyses.

• Any medical or psychological condition that in the investigator's opinion should preclude enrollment.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Asthma

Intervention

Drug:
• Placebo MDPI
Placebo MDPI (multi-dose dry powder inhaler) to match the active intervention.
• Albuterol MDPI
Albuterol MDPI (multi-dose dry powder inhaler or Spiromax®) 90 mcg/inhalation.

Locations

Country	Name	City	State
United States	Teva Investigational Site 10146	Bellevue	Nebraska
United States	Teva Investigational Site 10162	Bethesda	Maryland
United States	Teva Investigational Site 10163	Burke	Virginia
United States	Teva Investigational Site 10147	Canton	Ohio
United States	Teva Investigational Site 10143	Cincinnati	Ohio
United States	Teva Investigational Site 10148	Denver	Colorado
United States	Teva Investigational Site 10159	Denver	Colorado
United States	Teva Investigational Site 10155	El Paso	Texas
United States	Teva Investigational Site 10150	Eugene	Oregon
United States	Teva Investigational Site 10154	Gainesville	Georgia
United States	Teva Investigational Site 10164	Greenfield	Wisconsin
United States	Teva Investigational Site 10141	High Point	North Carolina
United States	Teva Investigational Site 10169	Huntington Beach	California
United States	Teva Investigational Site 10161	Louisville	Kentucky
United States	Teva Investigational Site 10158	Miami	Florida
United States	Teva Investigational Site 10168	Miami	Florida
United States	Teva Investigational Site 10151	Minneapolis	Minnesota
United States	Teva Investigational Site 10149	New Braunfels	Texas
United States	Teva Investigational Site 10142	Plymouth	Minnesota
United States	Teva Investigational Site 10156	Portland	Oregon
United States	Teva Investigational Site 10153	Raleigh	North Carolina
United States	Teva Investigational Site 10144	Rochester	New York
United States	Teva Investigational Site 10145	San Antonio	Texas
United States	Teva Investigational Site 10170	San Antonio	Texas
United States	Teva Investigational Site 10157	San Diego	California
United States	Teva Investigational Site 10165	Seattle	Washington
United States	Teva Investigational Site 10160	Skillman	New Jersey
United States	Teva Investigational Site 10152	St. Louis	Missouri
United States	Teva Investigational Site 10167	Sylvania	Ohio
United States	Teva Investigational Site 10166	Wheaton	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
Teva Pharmaceutical Industries

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Composite Measurement of Device Ruggedness From Baseline to Week 52	Device Ruggedness: Reports of any problems/malfunction of the device (e.g., lack of efficacy, problems/malfunction after the device is dropped or sustains physical impact).	Baseline to Week 52	No
Other	Device Invitro Evaluations to Week 52	Device In Vitro Evaluations - All used study inhalers will be collected and a random selection of inhalers will be tested as follows: Fifty (50) Albuterol Spiromax® inhalers used during weeks 0-12 will be randomly selected for in vitro testing; Fifty (50) Albuterol Spiromax® inhalers used during weeks 12-52 will be randomly selected for in vitro performance testing	Baseline to Week 52	No
Other	Daily AM Peak Expiratory Flow (PEF) to Week 52	Daily AM PEF will be recorded throughout the duration of the study to provide information on the subject's asthma status in order to assist in distinguishing between the use of back-up rescue medication related to an increased need for asthma symptom relief from that related to an issue with the Albuterol Spiromax® rescue inhaler.	Baseline to Week 52	No
Primary	Participants With Adverse Experiences During Weeks 0-12 (Double-Blind Period)	Adverse events (AEs) summarized in this table are those that began or worsened after treatment with study drug (treatment-emergent AEs). An adverse event was defined in the protocol 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 AE which prevents normal daily 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 the previously listed serious outcomes.	Day 1 to Week 12	Yes
Primary	Participants With Adverse Experiences During Weeks 13-52 (Open-Label Period)	Adverse events (AEs) summarized in this table are those that began or worsened after treatment with study drug (treatment-emergent AEs). An adverse event was defined in the protocol 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 AE which prevents normal daily 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 the previously listed serious outcomes.	Weeks 13-52	Yes
Primary	Electrocardiogram (ECG) Results At Weeks 0, 12, and 52	A standard 12-lead ECG was performed at screening, week 12, and week 52 or early termination/discontinuation. The ECG recording methods were centralized and standardized across all study participants. A centralized cardiologist was responsible for providing all ECG interpretations.	Weeks 0 (screening visit), 12, and 52	Yes
Primary	Change From Baseline in Blood Pressure Measurements to Week 12 and Week 52	Participants were seated at least 2 minutes before blood pressure measurements were obtained by either an electronic or manual sphygmomanometer.; Week 12 values represent change from Week 0. Week 52 values represent change from Week 12.	Week 0, Week 12 and Week 52	Yes
Primary	Change From Baseline in Pulse Measurements to Week 12 and Week 52	Participants were seated at least 2 minutes before pulse measurements were obtained by radial pulse.; Week 12 values represent change from Week 0. Week 52 values represent change from Week 12.	Week 0, Week 12 and Week 52	Yes
Primary	Participants With Abnormal and Clinically Relevant Physical Exam Findings at Weeks 0, 12 and 52	The physical exam was performed by a qualified healthcare professional, and when possible, the same qualified healthcare professional that performed the physical examination at study screening performed all the scheduled physical examinations. Abnormalities and clinical relevance were determined by the qualified healthcare professional.; HEENT = head, eyes, ears, nose, throat	Weeks 0, 12 and 52	Yes