Cystic FibrosisPhase 1NCT02976519

BI 443651 Multiple Rising Dose in Healthy Volunteers Followed by a Cross-over in CF Subjects

A Phase 1 study testing BI 443651 in people with Cystic Fibrosis, run by Boehringer Ingelheim at 5 sites in 2 countries.

Completed

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

Official record

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Trial summary

The objective of this study is to investigate the safety, tolerability, and pharmacokinetics of BI 443651 in male and female healthy volunteers and subjects with Cystic Fibrosis (CF). Read more about this study

Who is it for?: Ages 18 to 55 yearsHealthy volunteers can take part
Conditions the study is for: Cystic Fibrosis
What is being tested?: BI 443651
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 64 participants
Where: 5 sitesin 2 countries
Study dates: 15 Feb 2017to 29 Aug 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 55 years
All sexes
Healthy volunteers accepted
Adult

Who may be able to join

Healthy volunteers:
Signed informed consent
Healthy male or female subjects
- Women of childbearing potential (WOCBP) should only be dosed after a confirmed menstrual period and/or with a progesterone level at Day -5 to Day -3 that demonstrates a dip from baseline, indicating a menstrual bleed prior to dosing.
Age of 18 to 55 years (incl.)
Body mass index (BMI) of 18.5 to 32.0 kg/m2 (incl.)

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Forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) of equal or greater than 80% of predicted normal, at screening and prior to randomisation
Cystic Fibrosis (Cross over part):
Signed informed consent
Males or females with a documented diagnosis of cystic fibrosis
Women of childbearing potential (WOCBP) should only be dosed after a confirmed menstrual period and/or with a progesterone level at Day -5 to Day -3, that demonstrates a dip from baseline, indicating a menstrual bleed prior to dosing. For CF subjects of child bearing potential this must confirmed prior to second treatment period.
Age 18 to 55 years (each inclusive)
BMI of 18 to 32.0 kg/m2 (incl.)
Pre-bronchodilator FEV1 >/= to 70% of predicted normal at screening and prior to randomisation
Clinical stability as defined by no evidence of acute upper or lower respiratory tract infection; no pulmonary exacerbation requiring use of i.v. / oral / inhaled antibiotics, or oral corticosteroids; no change in pulmonary disease therapy; if on cycling antibiotics, these must be initiated within 2 weeks prior to randomisation; no acute (serious or non-serious) illness not related to cystic fibrosis; no infection with an organism associated with more rapid decline in pulmonary function (eg, Burkholderia cenocepacia, B dolosa, or Mycobacterium abscessus).
Able to perform technically acceptable pulmonary functions test (PFTs)
Further inclusion criteria apply.

Who cannot join

Any evidence of a concomitant disease judged as clinically relevant by the investigator including gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological, dermatologic, hematologic, neurological and psychiatric, oncological, coagulation or hormonal disorders 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.
Cast doubt on the subject's ability to participate in the study.
Chronic or relevant acute infections.
History of relevant orthostatic hypotension, fainting spells, or blackouts

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History of myocardial infarction; history of acute coronary syndrome
History of and/or active life-threatening cardiac arrhythmia, as assessed by the investigator
Major surgery (major according to the investigator's assessment)
History of chronic kidney disease (estimate glomerular filtration rate (EGFR) <59 mls/min including corrections as per ethnicity)
History of relevant allergy or hypersensitivity (including allergy to the trial medication or its excipients)
Unsuitable veins for venipuncture (for instance, veins which are difficult to locate, access or puncture, veins with a tendency to rupture during or after puncture) as assessed by the investigator
Any finding in the medical examination (including blood pressure (BP), pulse rate (PR) or electrocardiogram (ECG) is deviating from normal and judged as clinically relevant by the investigator
Any laboratory value outside the reference range that the investigator considers to be of clinical relevance, specifically volunteers with serum potassium > upper limit of normal should be excluded; Safety laboratory screening and Day -7 to Day -3, evaluation can be repeated twice during screening.
For healthy volunteers, repeated measurement (i.e. > 2 measurements) of systolic blood pressure outside the range of 90 to 140 mmHg, diastolic blood pressure outside the range of 50 to 90 mmHg. Volunteers will be excluded with a pulse rate outside the range of 45 to 90 bpm.
A marked baseline prolongation of mean 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 or 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).
Within 10 days prior to administration of trial medication, use of drugs that might reasonably influence the results of the trial or that might prolong the QT/QTcF interval
Intake of drugs with a long half-life (more than 24hrs) within 30 days or less than 10 half-lives of the respective drug prior to administration of trial medication unless this is allowed medications.
CF subjects treated with non-permitted concomitant medication. Specifically medications causing changes in serum potassium are restricted
Current or previous participation in another interventional trial, including where an investigational drug has been or will be administered within 60 days or 5 half-lives (whichever is longer) prior to screening
For healthy volunteers and CF subjects: current smokers or ex-smokers of less than 12 months and/or with a pack year history of more than 5 years
Further exclusion criteria apply

Trial locations and contacts

5 sites in 2 countries.

Country

City, postcode or hospital

5 sites in 2 countries

Germany3 sites

Charité - Universitätsmedizin Berlin
Berlin, 13353
IKF Pneumologie GmbH & Co. KG
Frankfurt, 60596
Lungenärztliche Praxis
München-Pasing, 81241

Other trials in Germany

United Kingdom2 sites

Celerion Inc
Belfast, BT9 6AD
The Medicines Evaluation Unit
Manchester, M23 9QZ

Other trials in United Kingdom

About this study

Official title: A Phase Ib, Multicentre, Double Blind, Randomized, Two-part Study, First Part Multiple Rising Dose and Second Part Two-way Cross-over, to Assess Safety, Tolerability, Efficacy and Pharmacokinetics of BI 443651 Compared to Placebo Via Respimat® in Healthy Volunteers and CF Subjects.

The objective of this study is to investigate the safety, tolerability, and pharmacokinetics of BI 443651 in male and female healthy volunteers and subjects with Cystic Fibrosis (CF).

Conditions: Cystic Fibrosis
Being tested: BI 443651, Placebo
Medical subject headings: Cystic Fibrosis

What participants receive

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

BI 443651Drug
twice daily
PlaceboDrug
twice daily

Study groups in NCT02976519
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.

Percentage of Participants With Treatment-emergent Adverse Events (TEAE) Over the Treatment Period in Part 1 and Part 2
Percentage of participants with treatment-emergent adverse events (TEAE) over the treatment period in Part 1 and Part 2. For Part 1: From the first dose of study medication up to 30 days after the day of last intake of study medication, up to 44 days. For Part 2: From the first dose of study medication up to 30 days after the day of last intake of study medication, up to 51 days.
Measured: Up to 44 days (for Part 1) or 51 days (for Part 2) (Please check the measure description for detailed timeframe)

Secondary outcomes (2)

Maximum Measured Concentration of the BI 443651 in Plasma After the Administration of the First Dose (Cmax) on Day 1 and Over the Time Interval From 0 to 12 h After the 13th Dose (Cmax,13) on Day 7, in Part 1
Maximum measured concentration of the BI 443651 in plasma after the administration of the first dose (Cmax) on day 1 and over the time interval from 0 to 12 h after the 13th dose (Cmax,13) on day 7, in Part 1. Pharmacokinetic samples were collected at 00:15 hours:minutes (h:m) pre-dose and at 00:15, 00:30, 00:45, 1:00, 2:00, 4:00, 6:00, 8:00 and 11:45 h:m after first drug administration on day 1 (for Cmax) and after last drug administration on day 7 (for Cmax,13).
Measured: Day 1 and Day 7 (Please check the measure description for detailed timeframe)
Area Under the Concentration-time Curve of the BI 443651 in Plasma Over the Time Interval From 0 to 12 Hours After the Administration of the First Dose (AUC0-12) on Day 1 and After the 13th Dose (AUC0-12,13) on Day 7 in Part 1
Area under the concentration-time curve of the BI 443651 in plasma over the time interval from 0 to 12 hours (h) after the administration of the first dose (AUC0-12) on day 1 and after the 13th dose (AUC0-12,13) on day 7 in Part 1. Pharmacokinetic samples were collected at 00:15 h:m pre-dose and at 00:15, 00:30, 00:45, 1:00, 2:00, 4:00, 6:00, 8:00 and 11:45 h:m after first drug administration on day 1 (for AUC0-12) and after last drug administration on day 7 (for AUC0-12,13).
Measured: Day 1 and Day 7 (Please check the measure description for detailed timeframe)

Timeline

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

15 Feb 201729 Aug 2018

First posted29 Nov 2016 (estimated)
Study start15 Feb 2017
Primary completion29 Aug 2018
Study completion29 Aug 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 Cystic FibrosisStudies 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: Parallel groups
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 64 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02976519
Sponsor's protocol ID: 1363.2
Other IDs: 2016-001504-31, 2016
Status last verified: Nov 2019
First submitted: 25 Nov 2016
Last updated: 27 Nov 2019
Results posted: Yes, on ClinicalTrials.gov
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

RecruitingPhase 2
A Study of 24 to 52 Weeks Treatment to Evaluate The Efficacy And Safety of Galvokimig in Adult Study Participants With Non-Cystic Fibrosis Bronchiectasis
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Active, not recruitingObservational study
CFTR Modulator Effects on Bone and Muscle in Adults With Cystic Fibrosis
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All Cystic Fibrosis trials

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 Phase Ib, Multicentre, Double Blind, Randomized, Two-part Study, First Part Multiple Rising Dose and Second Part Two-way Cross-over, to Assess Safety, Tolerability, Efficacy and Pharmacokinetics of BI 443651 Compared to Placebo Via Respimat® in Healthy Volunteers and CF Subjects.
ClinicalTrials.gov ID: NCT02976519
Acronym / sponsor ID: 1363.2
Conditions: Cystic Fibrosis
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 64 participants (actual)
Lead sponsor: Boehringer IngelheimIndustry (pharma, biotech, devices)
Study start: 15 Feb 2017 (actual)
Primary completion: 29 Aug 2018 (actual)
Study completion: 29 Aug 2018 (actual)
First posted: 29 Nov 2016 (estimated)
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.

The objective of this study is to investigate the safety, tolerability, and pharmacokinetics of BI 443651 in male and female healthy volunteers and subjects with Cystic Fibrosis (CF).

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
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 55 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (17 listed)

Signed informed consent
Healthy male or female subjects
- Women of childbearing potential (WOCBP) should only be dosed after a confirmed menstrual period and/or with a progesterone level at Day -5 to Day -3 that demonstrates a dip from baseline, indicating a menstrual bleed prior to dosing.
Age of 18 to 55 years (incl.)
Body mass index (BMI) of 18.5 to 32.0 kg/m2 (incl.)

Key exclusion criteria (23 listed)

Any evidence of a concomitant disease judged as clinically relevant by the investigator including gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological, dermatologic, hematologic, neurological and psychiatric, oncological, coagulation or hormonal disorders 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:
Chronic or relevant acute infections.
History of relevant orthostatic hypotension, fainting spells, or blackouts
History of myocardial infarction; history of acute coronary syndrome
History of and/or active life-threatening cardiac arrhythmia, as assessed by the investigator

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 443651twice daily	Drug	BI 443651
Placebotwice daily	Drug	Placebo

Primary outcome

Percentage of Participants With Treatment-emergent Adverse Events (TEAE) Over the Treatment Period in Part 1 and Part 2
Time frame: Up to 44 days (for Part 1) or 51 days (for Part 2) (Please check the measure description for detailed timeframe)
Percentage of participants with treatment-emergent adverse events (TEAE) over the treatment period in Part 1 and Part 2. For Part 1: From the first dose of study medication up to 30 days after the day of last intake of study medication, up to 44 days. For Part 2: From the first dose of study medication up to 30 days after the day of last intake of study medication, up to 51 days.

2 secondary outcomes

Maximum Measured Concentration of the BI 443651 in Plasma After the Administration of the First Dose (Cmax) on Day 1 and Over the Time Interval From 0 to 12 h After the 13th Dose (Cmax,13) on Day 7, in Part 1
Time frame: Day 1 and Day 7 (Please check the measure description for detailed timeframe)
Area Under the Concentration-time Curve of the BI 443651 in Plasma Over the Time Interval From 0 to 12 Hours After the Administration of the First Dose (AUC0-12) on Day 1 and After the 13th Dose (AUC0-12,13) on Day 7 in Part 1
Time frame: Day 1 and Day 7 (Please check the measure description for detailed timeframe)

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 Matching BI 443651	8	8
BI 443651 100 Microgram (μg)	8	7
BI 443651 400 μg	8	8
BI 443651 1200 μg	8	7
BI 443651 1800 μg	8	8
BI 443651 600 μg/ Placebo Matching BI 443651	12	12
Placebo Matching BI 443651/ BI 443651 600 μg	12	12

Primary outcome: Percentage of Participants With Treatment-emergent Adverse Events (TEAE) Over the Treatment Period in Part 1 and Part 2

Time frame: Up to 44 days (for Part 1) or 51 days (for Part 2) (Please check the measure description for detailed timeframe). Number. Unit: Percentage of participants (%)

Measure	Placebo Matching BI 443651 n = 8	BI 443651 100 Microgram (μg) n = 8	BI 443651 400 μg n = 8	BI 443651 1200 μg n = 8	BI 443651 1800 μg n = 8	Placebo Matching BI 443651 600 μg n = 24	BI 443651 600 μg n = 22
Value	37.5	62.5	87.5	100.0	87.5	58.3	59.1

Population analysed: TS

2 secondary outcomes are reported in the full results.

Adverse events

Time frame: From the first dose of study medication until 30 days after the day of last intake of study medication, up to 37 days (for Part 1) and up to 44 days (for Part 2).. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Placebo Matching BI 443651	0 of 8 (0%)	3 of 8 (37.5%)	0 of 8
BI 443651 100 Microgram (μg)	1 of 8 (12.5%)	5 of 8 (62.5%)	0 of 8
BI 443651 400 μg	0 of 8 (0%)	7 of 8 (87.5%)	0 of 8
BI 443651 1200 μg	0 of 8 (0%)	8 of 8 (100%)	0 of 8
BI 443651 1800 μg	0 of 8 (0%)	7 of 8 (87.5%)	0 of 8
Placebo Matching BI 443651 600 μg	1 of 24 (4.2%)	8 of 24 (33.3%)	0 of 24
BI 443651 600 μg	0 of 22 (0%)	9 of 22 (40.9%)	0 of 22

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 Cystic Fibrosis

RecruitingPhase 2
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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

5 sites in 2 countries: 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 Cystic Fibrosis, run by Boehringer Ingelheim at 5 sites in 2 countries.

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 17 inclusion and 23 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 5 sites in Germany, 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?

Percentage of Participants With Treatment-emergent Adverse Events (TEAE) Over the Treatment Period in Part 1 and Part 2 (time frame: Up to 44 days (for Part 1) or 51 days (for Part 2) (Please check the measure description for detailed timeframe)). 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 NCT02976519.

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.