The Effect of BEVESPI AEROSPHERE ® Therapy on Exercise Tolerance in COPD

William Stringer, md

Status and phase: Completed; Phase 4

Conditions: Pulmonary Disease, Chronic Obstructive

Treatments: Drug: Glycopyrrolate / Formoterol Inhaler vs Placebo Inhaler

Study type: Interventional

Funder types: Other

Identifiers

NCT03081156

21752-01

Details and patient eligibility

About

The objective of the study is to determine if a dual inhaled bronchodilator (Glycopyrrolate/Formoterol) is effective in increasing exercise time relative to placebo in patients with Chronic Obstructive Pulmonary Disease (COPD).

Full description

Enrolled patients with COPD will be randomized to receive either a dual bronchodilator (Glycopyrrolate/Formoterol) or placebo inhaler, and then crossed over to receive the opposite intervention. The study will consist of two treatment periods of two weeks, seperated by a washout period of two weeks.

Enrollment: 52 patients

Sex: All

Ages: 40 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. All patients must have a clinical diagnosis of chronic obstructive pulmonary disease (COPD) and must meet the following criteria:

   1. Stable state of their disease with no exacerbation (antibiotics, oral steroids, ER visit, or hospitalization for COPD) within the previous 4 weeks; and
   2. At visit 1 Spirometric Values must demonstrate a post-bronchodilator FEV1 between 35% and 80% of predicted normal and a post-bronchodilator FEV1/FVC <70%. [The rationale for the lower limit is to exclude patients unlikely to tolerate withholding of long acting bronchodilators. The rationale for the upper limit is to exclude patients unlikely to be limited in their exercise tolerance by hyperinflation and air trapping.]

2. Male or female patients, between 40 and 80 years (inclusive) of age.

3. Patients must be current or ex-smokers with a smoking history of more than 10 pack-years.

4. Patients must be able to perform technically acceptable pulmonary function tests and a symptom-limited cardiopulmonary cycle ergometry test.

5. Patients must be able to inhale medication in an acceptable manner from the metered dose inhalers used in this study.

Exclusion criteria

1. Patients with a significant disease other than COPD; a significant disease is defined as a disease which, in the opinion of the investigator, may (i) put the patient at risk because of participation in the study, (ii) influence the results of the study, or (iii) cause concern regarding the patient's ability to participate in the study.

2. Patients with a documented personal history of childhood asthma, a clinical presentation consistent with asthma, and a family history of asthma. For patients with allergic rhinitis, atopy, or prior allergy treatment, medical records will be obtained to verify that the patient does not have asthma. The final determination on the possibility of an overlap condition [Asthma-COPD Overlap Syndrome, (Postma and Rabe, 2015)], and thus, appropriateness for entry into the study, will be the principal investigator's decision.

3. Patients with any of the following conditions:

   1. A history of myocardial infarction within 1 year of screening visit.
   2. Unstable or life-threatening cardiac arrhythmia.
   3. Hospitalized for heart failure within the past year.
   4. Known active tuberculosis.
   5. A malignancy for which patient has undergone resection, radiation therapy or chemotherapy within the past 6 months (patients with treated local skin tumors are allowed).
   6. A history of life-threatening COPD exacerbation requiring intubation.
   7. A history of cystic fibrosis.
   8. Clinically significant and active bronchiectasis.
   9. A history of alcohol or drug abuse within the past year.
   10. Any contraindications for exercise testing as outlined below (see contraindications to exercise).
   11. Patients who have undergone thoracotomy with pulmonary resection in the past year.

4. Patients being treated with oral corticosteroid medication at unstable doses (i.e., less than six weeks on a stable dose) or at doses in excess of the equivalent of 10 mg of prednisone per day or 20 mg every other day.

5. Patients who regularly use daytime oxygen therapy for more than 6 hours per day and in the investigator's opinion will be unable to abstain from the use of oxygen therapy during clinic visits and exercise testing.

6. Patients who desaturate to SpO2 <80% on screening incremental exercise testing.

7. Patients who have completed a pulmonary rehabilitation program in the six weeks prior to the screening visit or patients who are currently in a pulmonary rehabilitation program.

8. Patients who have a limitation of exercise performance as a result of factors other than fatigue or exertional dyspnea, such as arthritis in the leg, angina pectoris or claudication or morbid obesity.

9. Patients with a constant power cycle ergometry endurance time less than 4 or greater than 8 minutes after work rate adjustment procedures (described below).

10. Patients who have taken an investigational drug within one month or six half-lives (whichever is greater) prior to screening visit (Visit 1).

11. Pregnant or nursing women.

12. Women of childbearing potential who are not using a highly effective method of birth control. Female patients will be considered to be of childbearing potential unless surgically sterilized by hysterectomy or bilateral tubal ligation, or post-menopausal for at least two years.

13. Patients who are currently participating in another interventional study.

14. Patients who are unable to comply with pulmonary medication restrictions (washout of any LABA/LAMA) prior to randomization.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Quadruple Blind

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52 participants in 2 patient groups, including a placebo group

Glycopyrrolate/Formoterol Inhaler then Placebo Inhaler

Active Comparator group

Description:

Participants receive the Glycopyrrolate/Formoterol inhaler for a two week period. After a two week washout, the participants then received a placebo Glycopyrrolate/Formeterol inhaler for two weeks.

Treatment:

Drug: Glycopyrrolate / Formoterol Inhaler vs Placebo Inhaler

Placebo Inhaler then Glycopyrrolate/Formeterol Inhaler

Placebo Comparator group

Description:

Treatment for 2 weeks with a placebo Glycopyrrolate/Formoterol inhaler. After a two week washout, the participant then received two weeks of the Glycopyrrolate/Formoterol inhaler.

Treatment:

Drug: Glycopyrrolate / Formoterol Inhaler vs Placebo Inhaler