Effect of a LAMA and a uLABA on the Methacholine Dose-response Curve

Asthma Clinical Trial

Official title:

The Effect of Glycopyrronium and Indacaterol, as Monotherapy and in Combination, on the Methacholine Dose-response Curve

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02953041
• Other study ID #: MCh-DRC-1
• Status: Completed
• Phase: Phase 4
• First received: October 24, 2016
• Last updated: June 12, 2017
• Start date: October 2016
• Est. completion date: January 9, 2017

Study information

• Verified date: June 2017
• Source: University of Saskatchewan
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The study will assess the effects of two drugs, glycopyrronium and indacaterol, taken either as monotherapy or in combination, on the methacholine dose-response curve. This will allow for further elucidation of the mechanisms of each drug in human participants.

Description:

This will be a randomized, double-blind, three-way crossover study testing glycopyrronium (Seebri®) vs. indacaterol (Onbrez®) vs. glycopyrronium+indacaterol. The MCT method used will be the two-minute tidal breathing dosing protocol. The investigators plan to enroll thirty participants, fifteen asthmatics and fifteen non-asthmatics participants.

• Asthmatic Participants Procedure: Each participant will undergo a total of twelve MCh challenges. Each MCh challenge will be stopped when the response to MCh reaches a plateau, when the participant's FEV1 drops 40% from baseline, when the highest concentration of MCh (128mg/mL) has been administered, or if the participant wishes to stop (e.g. due to discomfort). For the purpose of this study, a plateau will be defined as the last 3 consecutive data points falling within 5%. The first day of testing will take approx. 3hrs. and will entail participants undergoing a MCh challenge to determine their baseline MCh PC20. They will then self-administer the contents of two Breezhaler inhalers. If taking one of the monotherapies, one inhaler will contain active treatment (50mcg glycopyrronium or 5mcg indacaterol) and the other inhaler will contain a placebo. For the combination treatment arm, both inhalers will contain active drug (one 50mcg glycopyrronium and one 75mcg indacaterol). The identity of the treatment administered will be unknown to the participants and to the study staff. Participants will then undergo MCT post-treatment at 1 hr., 24 hrs., and 48 hrs. Testing at 24 and 48 hrs. will take approximately 1-1.5 hrs. Therefore, participants must attend the lab at roughly the same time of day for three consecutive days for each treatment arm. Following a minimum 10-day washout between treatment administrations, the same procedure will be repeated with the second study treatment. Following a second 10-day washout, the procedure will be repeated with the third study treatment.

• Non-Asthmatic Participants Procedure: Each non-asthmatic participant will undergo a single MCh challenge, which should take approx. 1-1.5 hrs. This will allow for the generation of a "normal" MCh DRC curve to compare with the asthmatic data. The MCh challenge will be stopped when the response to MCh reaches a plateau, when the participant's FEV1 drops 40% from baseline, when the highest concentration of MCh (128mg/mL) has been administered, or if the participant wishes to stop.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 31
• Est. completion date: January 9, 2017
• Est. primary completion date: January 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• men and women aged 18 or older

• stable mild-to-moderate asthma

• baseline methacholine PC20 less than or equal to 8mg/mL and FEV1 greater than or equal to 65% of predicted (asthmatic participants)

• baseline methacholine PC20 greater than 16mg/mL (healthy participants)

Exclusion Criteria:

• use of long-acting bronchodilators or long-acting muscarinic antagonists within 30 days of Visit 1

• pregnant or lactating

• cardiovascular, prostate, kidney or urinary retention problems

• respiratory illness within 4 weeks of Visit 1

• allergen-induced asthma exacerbating within 4 weeks of Visit 1

• hypokalemia

• diabetes

• glaucoma

• smokers and exsmokers with greater than 10 pack years

Related Conditions & MeSH terms

• Asthma

Intervention

Drug:
• Glycopyrronium
long-acting muscarinic antagonist
• Indacaterol
ultra long-acting beta agonist

Locations

Country	Name	City	State
Canada	Asthma Research Lab, University of Saskatchewan	Saskatoon	Saskatchewan

Sponsors (1)

Lead Sponsor	Collaborator
University of Saskatchewan

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from baseline methacholine bronchoprotection at 1 hour	assessed by dose shift of geometric mean methacholine PC20 data	baseline versus 1 hour post-treatment
Secondary	Change from baseline methacholine bronchoprotection at 24 hours	assessed by dose shift of geometric mean methacholine PC20 data	baseline versus 24 hours post-treatment
Secondary	Change from baseline methacholine bronchoprotection at 48 hours	assessed by dose shift of geometric mean methacholine PC20 data	baseline versus 48 hours post-treatment