Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02953041
Recruitment Status : Completed
First Posted : November 2, 2016
Last Update Posted : June 14, 2017
Sponsor:
Information provided by (Responsible Party):
Don Cockcroft, University of Saskatchewan

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.

Condition or disease Intervention/treatment Phase
Asthma Drug: Glycopyrronium Drug: Indacaterol Phase 4

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 31 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: The Effect of Glycopyrronium and Indacaterol, as Monotherapy and in Combination, on the Methacholine Dose-response Curve
Study Start Date : October 2016
Actual Primary Completion Date : January 2017
Actual Study Completion Date : January 9, 2017

Resource links provided by the National Library of Medicine


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 Name: 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 Name: 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 Name: Seebri, Glycopyrrolate, Glycopyrronium bromide

Drug: Indacaterol
ultra long-acting beta agonist
Other Name: Onbrez




Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. 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

  2. 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



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02953041


Locations
Layout table for location information
Canada, Saskatchewan
Asthma Research Lab, University of Saskatchewan
Saskatoon, Saskatchewan, Canada, S7N 0W8
Sponsors and Collaborators
University of Saskatchewan
Investigators
Layout table for investigator information
Principal Investigator: Don Cockcroft, MD University of Saskatchewan

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Don Cockcroft, MD, Professor, University of Saskatchewan
ClinicalTrials.gov Identifier: NCT02953041     History of Changes
Other Study ID Numbers: MCh-DRC-1
First Posted: November 2, 2016    Key Record Dates
Last Update Posted: June 14, 2017
Last Verified: June 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Journal Publication
Additional relevant MeSH terms:
Layout table for MeSH terms
Glycopyrrolate
Methacholine Chloride
Adjuvants, Anesthesia
Muscarinic Antagonists
Cholinergic Antagonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Miotics
Autonomic Agents
Peripheral Nervous System Agents
Parasympathomimetics
Bronchoconstrictor Agents
Respiratory System Agents
Muscarinic Agonists
Cholinergic Agonists