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

June 12, 2017 updated by: Don Cockcroft, University of Saskatchewan

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

31

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Saskatchewan
      • Saskatoon, Saskatchewan, Canada, S7N 0W8
        • Asthma Research Lab, University of Saskatchewan

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: CROSSOVER
  • Masking: TRIPLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: LAMA Treatment
Inhalation of 50mcg glycopyrronium from Breezhaler device 1 hour prior to methacholine challenge
Drug: Glycopyrronium
long-acting muscarinic antagonist
Other Names:
  • Seebri, Glycopyrrolate, Glycopyrronium bromide
Experimental: uLABA Treatment
Inhalation of 75mcg indacaterol from Breezhaler device 1 hour prior to methacholine challenge
Drug: Indacaterol
ultra long-acting beta agonist
Other Names:
  • Onbrez
Experimental: Combo Treatment
Inhalation of 50mcg glycopyrronium from one Breezhaler device, and 75mcg indacaterol from a second Breezhaler device, all one hour prior to methacholine challenge
Drug: Glycopyrronium
long-acting muscarinic antagonist
Other Names:
  • Seebri, Glycopyrrolate, Glycopyrronium bromide
Drug: Indacaterol
ultra long-acting beta agonist
Other Names:
  • Onbrez

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change from baseline methacholine bronchoprotection at 1 hour
Time Frame: baseline versus 1 hour post-treatment
assessed by dose shift of geometric mean methacholine PC20 data
baseline versus 1 hour post-treatment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change from baseline methacholine bronchoprotection at 24 hours
Time Frame: baseline versus 24 hours post-treatment
assessed by dose shift of geometric mean methacholine PC20 data
baseline versus 24 hours post-treatment
Change from baseline methacholine bronchoprotection at 48 hours
Time Frame: baseline versus 48 hours post-treatment
assessed by dose shift of geometric mean methacholine PC20 data
baseline versus 48 hours post-treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Saskatchewan

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2016

Primary Completion (Actual)

January 1, 2017

Study Completion (Actual)

January 9, 2017

Study Registration Dates

First Submitted

October 24, 2016

First Submitted That Met QC Criteria

November 1, 2016

First Posted (Estimate)

November 2, 2016

Study Record Updates

Last Update Posted (Actual)

June 14, 2017

Last Update Submitted That Met QC Criteria

June 12, 2017

Last Verified

June 1, 2017

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MCh-DRC-1

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Journal Publication

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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