Clinical Trials/NCT04059094

NCT04059094

Terminated

Phase 2

A Randomised, Double-blind, Placebo-controlled and Parallel Group Trial to Evaluate Efficacy and Safety of Twice Daily Inhaled Doses of BI 1265162 Delivered by Respimat® Inhaler as add-on Therapy to Standard of Care Over 4 Weeks in Patients With Cystic Fibrosis - BALANCE - CF™ 1

Boehringer Ingelheim26 sites in 8 countries52 target enrollmentSeptember 16, 2019

ConditionsCystic Fibrosis

InterventionsPlacebo BI 1265162

DrugsBI 1265162 Placebo

Overview

Phase: Phase 2
Intervention: Placebo
Conditions: Cystic Fibrosis
Sponsor: Boehringer Ingelheim
Enrollment: 52
Locations: 26
Primary Endpoint: Change From Baseline in Percent Predicted Trough Forced Expiratory Volume in 1 Second (FEV1) After 4 Weeks of Treatment
Status: Terminated
Last Updated: 4 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

The primary objective of this trial is to assess the efficacy, safety and pharmacokinetics of twice daily inhaled doses of BI 1265162 delivered by Respimat® inhaler versus placebo in adolescents and adult patients with cystic fibrosis.

Registry

clinicaltrials.gov

Start Date

September 16, 2019

End Date

April 24, 2020

Last Updated

4 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Boehringer Ingelheim

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Male or female patients, 12 years of age or older at screening;
•Documented diagnosis of cystic fibrosis including:
•positive sweat chloride ≥ 60 mEq/L, by pilocarpine iontophoresis OR
•genotype with 2 identifiable mutations consistent with cystic fibrosis accompanied by one or more clinical features with cystic fibrosis phenotype;
•Patients able to perform acceptable spirometric manoeuvres according to American Thoracic Society (ATS) standards;
•FEV1 ≥ 40% and ≤ 90% of predicted values at screening and predose at Visit 2;
•Women of childbearing potential (WOCBP) must be willing and able to use highly effective methods of birth control per ICH M3 (R2) that result in a failure rate of less than1% per year when used consistently and correctly. A list of contraception methods meeting these criteria is provided in the patient (or patient's legal guardian) information;
•Signed and dated written informed consent and assent in accordance with ICH Harmonized Guideline for Good Clinical Practice (GCP) and local legislation prior to admission in the trial.

Exclusion Criteria

•Evidence of acute upper or lower respiratory tract infection within 4 weeks prior to randomization based on investigator's judgement;
•Pulmonary exacerbation requiring use of i.v./oral/inhaled antibiotics or oral corticosteroids within 4 weeks prior to randomisation;
•Patients with history of Acute Tubular Necrosis (ATN);
•Any documented active or suspected malignancy or history of malignancy within 5 years prior to screening, except appropriately treated basal cell carcinoma of the skin or in situ carcinoma of uterine cervix;
•Patients unable to inhale trial drug in an appropriate manner from the Respimat® inhaler based on investigator's judgement;
•Patients who have started a new chronic medication for CF within 4 weeks of randomisation;
•Patients who have previously received a lung transplant or patients who are currently on a waiting list to receive a lung transplant;
•Patients with a significant history of allergy/hypersensitivity (including medication allergy) which is deemed relevant to the trial as judged by the investigator or with a known hypersensitivity to trial drug or its components. "Significance" in this context refers to any increased risk of hypersensitivity reaction to trial medication;
•Any clinically significant laboratory abnormalities at screening as judged by the investigator, or any of the following:
•Potassium \> upper limit of normal (ULN) in non-haemolysed blood

Arms & Interventions

Placebo

2 puffs ofmatching placebowere inhaledorally via theRespimat®inhaler twice dailyfor a treatmentperiod of 4 weeksin patients withcystic fibrosis.

Intervention: Placebo

BI 1265162 50 μg b.i.d.

2 puffs of 25micrograms (μg)BI 1265162(Total: 50μg)were inhaledorally via theRespimat®inhaler twice daily(b.i.d., daily dose:100μg) for atreatment periodof 4 weeks inpatients withcystic fibrosis.

Intervention: BI 1265162

BI 1265162 100 μg b.i.d.

2 puffs of 50micrograms (μg)BI 1265162(Total: 100μg)were inhaledorally via theRespimat®inhaler twice daily(b.i.d., daily dose:200μg) for atreatment periodof 4 weeks inpatients withcystic fibrosis.

Intervention: BI 1265162

BI 1265162 200 μg b.i.d.

2 puffs of 100micrograms (μg)BI 1265162(Total: 200μg)were inhaledorally via theRespimat®inhaler twice daily(b.i.d., daily dose:400μg) for atreatment periodof 4 weeks inpatients withcystic fibrosis.

Intervention: BI 1265162

BI 1265162 20 μg b.i.d.

2 puffs of 10micrograms (μg)BI 1265162(Total: 20μg)were inhaledorally via theRespimat®inhaler twice daily(b.i.d., daily dose:40μg) for atreatment periodof 4 weeks inpatients withcystic fibrosis.

Intervention: BI 1265162

Outcomes

Primary Outcomes

Change From Baseline in Percent Predicted Trough Forced Expiratory Volume in 1 Second (FEV1) After 4 Weeks of Treatment

Time Frame: At 30 minutes prior to dosing in Day 1 (baseline) and Day 29 (end of 4-week treatment period).

Trough FEV1 was measured within 30 minutes prior to dosing of study medication.

Secondary Outcomes

Percentage of Patients With Treatment-emergent Adverse Events (AE) up to Day 36(From Day 1 (baseline) until end of 4 weeks of treatment period (Day 29) plus 7 days of follow-up, up to 36 days.)
Area Under the Concentration-time Curve of BI 1265162 in Plasma From 0 to 4 Hours at Steady State After Dose 15 (AUC0-4,ss,15)(At pre-dose (taken within 60 minutes prior to dosing) and 5 minutes (min), 30 min, 1 hour, and 4 hours post dosing at steady state on Day 8 for dose 15 (morning dose on Day 8).)
Change From Baseline in Lung Clearance Index (LCI) Assessed by N2 Multiple Breath Washout (N2MBW) Procedure After 4 Weeks of Treatment(At pre-dose in Day 1 (baseline) and Day 29 (end of 4-week treatment period).)
Change From Baseline in Cystic Fibrosis Questionnaire Revised (CFQ-R) Total Score After 4 Weeks of Treatment(At Day 1 (baseline) and Day 29 (end of 4-week treatment period).)
Change From Baseline in Cough and Sputum Assessment Questionnaire (CASA-Q) (4 Separate Sub-scores) After 4 Weeks of Treatment(At Day 1 (baseline) and Day 29 (end of 4-week treatment period).)
Concentration of BI 1265162 in Plasma at 0.083 Hour at Steady State Following Dose 57 (C0.083,ss,57)(At 5 minutes (around 0.083 hours) post dosing at steady state on Day 29 for dose 57 (morning dose on Day 29).)
Pre-dose Concentration Measured of BI 1265162 in Plasma at Steady State After Dose 15 (Cpre,ss, 15)(At pre-dose (taken within 60 minutes prior to dosing) at steady state on Day 8 for dose 15 (morning dose on Day 8).)
Concentration of BI 1265162 in Plasma at 0.083 Hour at Steady State Following Dose 15 (C0.083,ss,15)(At 5 minutes (around 0.083 hours) post dosing at steady state on Day 8 for dose 15 (morning dose on Day 8).)
Pre-dose Concentration Measured of BI 1265162 in Plasma at Steady State After Dose 57 (Cpre,ss, 57)(At pre-dose (taken within 60 minutes prior to dosing) at steady state on Day 29 for dose 57 (morning dose on Day 29).)