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

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT02976519
• Date of registration: 25/11/2016
• Prospective Registration: Yes
• Primary sponsor: Boehringer Ingelheim
• Public title: BI 443651 Multiple Rising Dose in Healthy Volunteers Followed by a Cross-over in CF Subjects
• Scientific 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.
• Date of first enrolment: February 15, 2017
• Target sample size: 64
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02976519
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Double (Participant, Investigator).
• Phase: Phase 1

Countries of recruitment

Germany, United Kingdom

Contacts

• Name: Boehringer Ingelheim
• Affiliation: Boehringer Ingelheim

Key inclusion & exclusion criteria

Inclusion criteria:

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.)

- 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.

Exclusion criteria:

- 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

- 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



Age minimum: 18 Years
Age maximum: 55 Years
Gender: All

Health Condition(s) or Problem(s) studied

Cystic Fibrosis

Intervention(s)

Drug: Placebo

Drug: BI 443651

Primary Outcome(s)

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)]

Secondary Outcome(s)

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)]

Secondary ID(s)

1363.2

2016-001504-31

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 27/11/2019
• URL: https://clinicaltrials.gov/ct2/show/results/NCT02976519