Clinical trial NCT02953041: Effect of a LAMA and a uLABA on the Methacholine Dose-response Curve
Official title: The Effect of Glycopyrronium and Indacaterol, as Monotherapy and in Combination, on the Methacholine Dose-response Curve
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Asthma
Lead sponsor: University of Saskatchewan
Sponsor class: OTHER
First posted: 2016-11-02
Enrollment: 31
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Change from baseline methacholine bronchoprotection at 1 hour
timeFrame: baseline versus 1 hour post-treatment
Secondary outcomes:
measure: Change from baseline methacholine bronchoprotection at 24 hours
timeFrame: baseline versus 24 hours post-treatment
measure: Change from baseline methacholine bronchoprotection at 48 hours
timeFrame: baseline versus 48 hours post-treatment
Other outcomes:
Locations:
city: Saskatoon
country: Canada
facility: Asthma Research Lab, University of Saskatchewan
state: Saskatchewan
Study officials:
affiliation: University of Saskatchewan
name: Don Cockcroft, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Blais CM, Davis BE, Cockcroft DW. The effect of glycopyrronium and indacaterol, as monotherapy and in combination, on the methacholine dose-response curve of mild asthmatics: a randomized three-way crossover study. Respir Res. 2017 Aug 2;18(1):146. doi: 10.1186/s12931-017-0628-4.