AsthmaPhase 1NCT03135899

BI 443651 Methacholine Challenge

A Phase 1 study testing BI 443651 in people with Asthma, run by Boehringer Ingelheim at 1 site in United Kingdom.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Trial summary

The primary objective of this study is to investigate safety and tolerability of three consecutive administrations, 12 hours apart, at three different dose-levels of BI 443651 administered via oral inhalation in male and female mild asthmatic subjects after a bolus methacholine challenge. Read more about this study

Who is it for?: Ages 18 to 60 years
Conditions the study is for: Asthma
What is being tested?: BI 443651
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 37 participants
Where: 1 siteUnited Kingdom
Study dates: 18 May 2017to 21 Feb 2018
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 60 years
All sexes
No healthy volunteers
Adult

Who may be able to join

Male or female subjects must have a diagnosis of asthma by a physician at least 3 months prior to screening. The diagnosis of asthma must meet the following spirometric criteria:
-- Pre-bronchodilator clinic measured FEV1 >=70% of predicted normal (calculated by the Global Lung Function Initiative equation (GLI)) measured >= 8 hours after the last use of short acting bronchodilator at the screening visit and on the day of randomisation.
Age >= 18 <= 60 years. Subjects must be within the eligible age range on the day of signing informed consent.
Diagnosis of asthma must have been made before the subject's age of 40. Or If the subject is >= 40 years and the diagnosis has not yet been recorded in the subject's medical files, the investigator should assess whether the subject's medical history (e.g. symptoms and prescribed medications) confirms the subject suffered from asthma since before the age of 40. If so, this subject may be considered for inclusion after consultation with the sponsor.
ACQ value < 1.5 at the screening visit.
PD20 (Provocative dose causing at least a 20% decline in FEV1) at the screening visit of methacholine <= 1mg
Body mass index (BMI) >= 18.5 and <= 32.0 kg/m2 at the screening visit
Subjects must be able to perform all study related procedures and assessments, including pulmonary function tests, as required by the protocol.

Who cannot join

Significant pulmonary diseases other than asthma (up to GINA treatment step 2) or other medical conditions (as determined by medical history, examination and clinical investigations at screening) that may, in the opinion of the investigator result in any of the following:
Put the subject at risk because of participation in the study
Influence the results of the study
Cause concern regarding the subject's ability to participate in the study.
Respiratory tract infection or asthma exacerbation in the 4 weeks prior to the screening visit. Subjects can be rescreened 4 weeks after resolution of the infection or exacerbation.
Hospitalisation for asthma exacerbation within 3 months or intubation for asthma within 3 years of the screening visit.

Show all 25Show fewer

Serum potassium measurement above the ULN at the screening visit. Any value about the ULN excludes the subject irrespective of clinical relevance.
Blood donation (more than 100mL within 30 days prior to the administration of trial medication or intended during the trial)
Subjects who have been treated with any of the following asthma medications in the given interval prior to Visit 1:
Non-approved asthma therapies such as methotrexate,
Intravenous, intramuscular or oral corticosteroids
Inhaled corticosteroids (iCS) other than low dose iCS (defined as equivalent to equal to, or less than 250 μg fluticasone / day)
A long acting beta agonist or anticholinergic bronchodilator (Visit 1), including fixed dose beta agonist/inhaled corticosteroid combinations and oral bronchodilators.
A biological based antagonist therapy including Omalizumab, or immune modulators
Asthma controller medications (e.g: leukotriene modifier, methylxanthines, nedocromil or cromolyn sodium)
Mucolytics
Systemically available immunomodulatory treatments for allergic rhinitis or atopic dermatitis.
Use of any diuretics (including loop diuretics or potassium sparing diuretics (such as amiloride), renin-angiotensin antihypertensive drugs in the 28 days prior to the screening visit (Visit 1)
Use of drugs that might reasonably influence the results of the trial or that might prolong the QT/QTc interval within 10 days prior to the randomisation visit.
A marked baseline prolongation of QT/QTcF interval (such as QTcF intervals that are repeatedly greater than 450 ms in males or repeatedly greater than 470 ms in females) or any other relevant ECG finding at screening and prior to randomisation
A history of additional risk factors for Torsades de Pointes (such as heart failure, hypokalemia, or family history of Long QT Syndrome)
History of relevant allergies/hypersensitivities (including allergy to the trial medication or its excipients)
Contraceptive measures for male and female patients may be required
Current smokers or ex-smokers who have given up smoking for < 12 months and / or have a smoking pack history of > 5 pack years (1 pack year = 20 cigarettes per day for 1 year of 5 cigarettes per day for 4 years)
Further exclusion criteria apply

Trial locations and contacts

1 site in 1 country.

United Kingdom1 site

The Medicines Evaluation Unit
Manchester, M23 9QZ

Other trials in United Kingdom

About this study

Official title: A Two Part Phase I, Multiple-dose, Single- and Double-blind, Randomised, Double-dummy, Placebo-controlled, Four-way Crossover Study to Assess Safety and Tolerability of BI 443651 Via Respimat® Versus Placebo Via Respimat® in Subjects With Mild Asthma Following Methacholine Challenge.

Conditions: Asthma
Being tested: BI 443651, Placebo
Medical subject headings: Asthma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

BI 443651Drug
Three doses, each 12 hours apart
PlaceboDrug
Three doses, each 12 hours apart

Study groups in NCT03135899
Study group	Role	What they receive
BI 443651	Experimental	Not described Receives: Drug: BI 443651
Placebo	Placebo comparator	Not described Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

Absolute Change From Baseline in Maximum Forced Expiratory Volume Within 1 Second (FEV1) Reduction Following Bolus Methacholine Challenge in Part 1
Absolute change from baseline in maximum forced expiratory volume within 1 second (FEV1) reduction following bolus methacholine challenge in Part 1 was defined as the difference between the maximum reduction in FEV1 obtained during the treatment challenge and during the baseline challenge.
Measured: Baseline and Day 2
Absolute Change From Baseline in Maximum Forced Expiratory Volume Within 1 Second (FEV1) Reduction Following Bolus Methacholine Challenge in Part 2.
Absolute change from baseline in maximum FEV1 reduction following bolus methacholine challenge in Part 2 was defined as the difference between the maximum reduction in FEV1 obtained during the treatment challenge and during the baseline challenge.
Measured: Baseline and Day 2

Secondary outcomes (4)

Relative Change From Baseline in FEV1 Area Under the Curve Over the Time Interval From 0 to Timepoint tz (FEV1 AUC0-tz) Following Bolus Methacholine Challenge in Part 1
Relative change from baseline in FEV1 area under the curve over the time interval from 0 to timepoint tz (FEV1 AUC0-tz) following bolus methacholine challenge in Part 1 was defined as the ratio of FEV1 AUC0-tz obtained during the treatment challenge and during the baseline challenge, where the time tz refers to the last time point before recovery of FEV1 to within 95% of post-diluent value.
Measured: Baseline and Day 2
Relative Change From Baseline in FEV1 Area Under the Curve Over the Time Interval From 0 to Timepoint tz (FEV1 AUC0-tz) Following Bolus Methacholine Challenge in Part 2
Relative change from baseline in FEV1 area under the curve over the time interval from 0 to timepoint tz (FEV1 AUC0-tz) following bolus methacholine challenge in Part 2 was defined as the ratio of FEV1 AUC0-tz obtained during the treatment challenge and during the baseline challenge, where the time tz refers to the last time point before recovery of FEV1 to within 95% of post-diluent value. Geometric mean is actually adjusted geometric mean. Standard error presented here is a geometric standard error.
Measured: Baseline and Day 2
Time to Recovery of FEV1 to Within 95% of Post-diluent Value in Part 1
Time to recovery of FEV1 to within 95% of post-diluent value in Part 1 was defined as the time from maximum reduction to last time before recovery to within 95% of the value obtained pre-methacholine challenge during the respective challenge.
Measured: Day 2
Time to Recovery of FEV1 to Within 95% of Post-diluent Value in Part 2
Time to recovery of FEV1 to within 95% of post-diluent value in Part 2 was defined as the time from maximum reduction to last time before recovery to within 95% of the value obtained pre-methacholine challenge during the respective challenge. Median is actually model-based median.
Measured: Day 2

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

18 May 201721 Feb 2018

First posted2 May 2017
Study start18 May 2017
Primary completion7 Feb 2018
Study completion21 Feb 2018

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for AsthmaStudies of the same condition, open and under way.
More trials run by Boehringer IngelheimThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 37 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03135899
Sponsor's protocol ID: 1363.7
Other IDs: 2016-001506-42, 2016
Status last verified: Nov 2019
First submitted: 26 Apr 2017
Last updated: 27 Nov 2019
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 27 Nov 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Two Part Phase I, Multiple-dose, Single- and Double-blind, Randomised, Double-dummy, Placebo-controlled, Four-way Crossover Study to Assess Safety and Tolerability of BI 443651 Via Respimat® Versus Placebo Via Respimat® in Subjects With Mild Asthma Following Methacholine Challenge.
ClinicalTrials.gov ID: NCT03135899
Acronym / sponsor ID: 1363.7
Conditions: Asthma
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 37 participants (actual)
Lead sponsor: Boehringer IngelheimIndustry (pharma, biotech, devices)
Study start: 18 May 2017 (actual)
Primary completion: 7 Feb 2018 (actual)
Study completion: 21 Feb 2018 (actual)
First posted: 2 May 2017 (actual)
Results: Posted 27 Nov 2019

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: Double blind (participant, investigator)
Number of arms: 2

Arm	Type	Receives
BI 443651	Experimental	Drug: BI 443651
Placebo	Placebo comparator	Drug: Placebo

Who may qualify

Ages: 18 to 60 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult

Key inclusion criteria (8 listed)

Male or female subjects must have a diagnosis of asthma by a physician at least 3 months prior to screening. The diagnosis of asthma must meet the following spirometric criteria:
-- Pre-bronchodilator clinic measured FEV1 >=70% of predicted normal (calculated by the Global Lung Function Initiative equation (GLI)) measured >= 8 hours after the last use of short acting bronchodilator at the screening visit and on the day of randomisation.
Age >= 18 <= 60 years. Subjects must be within the eligible age range on the day of signing informed consent.
Diagnosis of asthma must have been made before the subject's age of 40. Or If the subject is >= 40 years and the diagnosis has not yet been recorded in the subject's medical files, the investigator should assess whether the subject's medical history (e.g. symptoms and prescribed medications) confirms the subject suffered from asthma since before the age of 40. If so, this subject may be considered for inclusion after consultation with the sponsor.
ACQ value < 1.5 at the screening visit.

Key exclusion criteria (25 listed)

Significant pulmonary diseases other than asthma (up to GINA treatment step 2) or other medical conditions (as determined by medical history, examination and clinical investigations at screening) that may, in the opinion of the investigator result in any of the following:
Respiratory tract infection or asthma exacerbation in the 4 weeks prior to the screening visit. Subjects can be rescreened 4 weeks after resolution of the infection or exacerbation.
Hospitalisation for asthma exacerbation within 3 months or intubation for asthma within 3 years of the screening visit.
Serum potassium measurement above the ULN at the screening visit. Any value about the ULN excludes the subject irrespective of clinical relevance.
Blood donation (more than 100mL within 30 days prior to the administration of trial medication or intended during the trial)

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
BI 443651Three doses, each 12 hours apart	Drug	BI 443651
PlaceboThree doses, each 12 hours apart	Drug	Placebo

Primary outcome

Absolute Change From Baseline in Maximum Forced Expiratory Volume Within 1 Second (FEV1) Reduction Following Bolus Methacholine Challenge in Part 1
Time frame: Baseline and Day 2
Absolute change from baseline in maximum forced expiratory volume within 1 second (FEV1) reduction following bolus methacholine challenge in Part 1 was defined as the difference between the maximum reduction in FEV1 obtained during the treatment challenge and during the baseline challenge.
Absolute Change From Baseline in Maximum Forced Expiratory Volume Within 1 Second (FEV1) Reduction Following Bolus Methacholine Challenge in Part 2.
Time frame: Baseline and Day 2
Absolute change from baseline in maximum FEV1 reduction following bolus methacholine challenge in Part 2 was defined as the difference between the maximum reduction in FEV1 obtained during the treatment challenge and during the baseline challenge.

4 secondary outcomes

Relative Change From Baseline in FEV1 Area Under the Curve Over the Time Interval From 0 to Timepoint tz (FEV1 AUC0-tz) Following Bolus Methacholine Challenge in Part 1
Time frame: Baseline and Day 2
Relative Change From Baseline in FEV1 Area Under the Curve Over the Time Interval From 0 to Timepoint tz (FEV1 AUC0-tz) Following Bolus Methacholine Challenge in Part 2
Time frame: Baseline and Day 2
Time to Recovery of FEV1 to Within 95% of Post-diluent Value in Part 1
Time frame: Day 2
Time to Recovery of FEV1 to Within 95% of Post-diluent Value in Part 2
Time frame: Day 2

Results and safety

Results posted to the registry on 27 Nov 2019, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Placebo/BI 443651 100/400/1200 Micro Gram (μg) - Part 1	1	1
BI 443651 100 μg/Placebo/BI 443651 400/1200 μg - Part 1	1	1
BI 443651 100/400 μg/Placebo/BI 443651 1200 μg - Part 1	1	1
BI 443651 100/400/1200 μg/Placebo - Part 1	1	1
Placebo/BI 443651 100/400/1200 μg - Part 2	8	8
BI 443651 400/1200 μg/Placebo/BI 443651 100 μg - Part 2	9	7
BI 443651 100 μg/Placebo/BI 443651 1200/400 μg - Part 2	8	7
BI 443651 1200/400/100 μg/Placebo - Part 2	8	8

Primary outcome: Absolute Change From Baseline in Maximum Forced Expiratory Volume Within 1 Second (FEV1) Reduction Following Bolus Methacholine Challenge in Part 1

Time frame: Baseline and Day 2. Mean (Standard Deviation). Unit: Litres (L)

Measure	Placebo - Part 1 n = 4	BI 443651 100 μg - Part 1 n = 4	BI 443651 400 μg - Part 1 n = 4	BI 443651 1200 μg - Part 1 n = 4
Value	0.018 (0.554)	0.390 (0.261)	-0.195 (0.431)	0.272 (0.268)

Population analysed: Methacholine set (MCS): The MCS included all patients in the TS who provided at least one pair (baseline and end-of-treatment) of evaluable measures of spirometry parameters that were not excluded due to use of rescue medication within 3 hours (h) after start of bolus methacholine challenge.

Primary outcome: Absolute Change From Baseline in Maximum Forced Expiratory Volume Within 1 Second (FEV1) Reduction Following Bolus Methacholine Challenge in Part 2.

Time frame: Baseline and Day 2. Least squares mean (Standard Error). Unit: Litres (L)

Measure	Placebo - Part 2 n = 31	BI 443651 100 μg - Part 2 n = 31	BI 443651 400 μg - Part 2 n = 32	BI 443651 1200 μg - Part 2 n = 31
Value	0.005 (0.056)	0.064 (0.056)	-0.032 (0.055)	-0.152 (0.056)

Placebo - Part 2 vs BI 443651 100 μg - Part 2: Mean Difference (Final Values): 0.059 (90% CI -0.048 to 0.165), Mixed Models Analysis
Placebo - Part 2 vs BI 443651 400 μg - Part 2: Mean Difference (Final Values): -0.037 (90% CI -0.144 to 0.070), Mixed Models Analysis
Placebo - Part 2 vs BI 443651 1200 μg - Part 2: Mean Difference (Final Values): -0.157 (90% CI -0.266 to -0.047), Mixed Models Analysis

Population analysed: MCS

4 secondary outcomes are reported in the full results.

Adverse events

Time frame: From the first drug administration until 14 days after the last drug administration, up to 16 days.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Placebo - Part 1 & Part 2	0 of 35 (0%)	9 of 35 (25.7%)	0 of 35
BI 443651 100 Microgram (μg) - Part 1 & Part 2	0 of 35 (0%)	21 of 35 (60%)	0 of 35
BI 443651 400 μg - Part 1 & Part 2	0 of 36 (0%)	24 of 36 (66.7%)	0 of 36
BI 443651 1200 μg - Part 1 & Part 2	0 of 36 (0%)	26 of 36 (72.2%)	0 of 36

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 27 Nov 2019.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related InfoLink provided by the sponsor.

Related trials for Asthma

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Boehringer Ingelheim study chair

Boehringer Ingelheim

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing BI 443651 in people with Asthma, run by Boehringer Ingelheim at 1 site in United Kingdom.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 27 Nov 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 27 Nov 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Absolute Change From Baseline in Maximum Forced Expiratory Volume Within 1 Second (FEV1) Reduction Following Bolus Methacholine Challenge in Part 1 (time frame: Baseline and Day 2). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03135899.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Nov 2019.