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

NCT02976519 | Completed Phase 1 Results

• 2 other identifiers: 1363.22016-001504-31
• Study Type: interventional
• Target: 64
• Locations: 2 countries
• Sites: 5

Brief 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).

Conditions

Cystic Fibrosis

Outcome Measures

Primary Outcomes (1)

• 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.

  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

  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

  Day 1 and Day 7 (Please check the measure description for detailed timeframe)

Study Arms (2)

BI 443651

EXPERIMENTAL

Drug: BI 443651

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

BI 443651 DRUG

twice daily

BI 443651

Placebo DRUG

twice daily

Placebo

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (5)

Charité - Universitätsmedizin Berlin

Berlin, 13353, Germany

Location

IKF Pneumologie GmbH & Co. KG

Frankfurt, 60596, Germany

Location

Lungenärztliche Praxis

München-Pasing, 81241, Germany

Location

Celerion Inc

Belfast, BT9 6AD, United Kingdom

Location

The Medicines Evaluation Unit

Manchester, M23 9QZ, United Kingdom

Location

MeSH Terms

Conditions

Cystic Fibrosis

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases

Results Point of Contact

• Title: Boehringer Ingelheim, Call Center
• Organization: Boehringer Ingelheim

clintriage.rdg@boehringer-ingelheim.com

1-800-243-0127

Study Officials

• Boehringer Ingelheim

  Boehringer Ingelheim

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 25, 2016
• First Posted: November 29, 2016
• Study Start: February 15, 2017
• Primary Completion: August 29, 2018
• Study Completion: August 29, 2018
• Last Updated: November 27, 2019
• Results First Posted: November 27, 2019

Record last verified: 2019-11

Locations

DE (3); GB (2)