Safety, Tolerability and Pharmacokinetics of BIIL 284 BS in Adult and Pediatric Cystic Fibrosis (CF) Patients

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 36

Inclusion Criteria

Male or female ≥ 6 years (pediatric 6 - 17 years inclusive; adult ≥ 18 years); minimum weight requirement of 20 kg
Confirmed diagnosis of CF (positive sweat chloride ≥ 60 milliequivalents (mEq)/liter (by pilocarpine iontophoresis) and/or a genotype with two identifiable mutations consistent with CF accompanied by one or more clinical features with the CF phenotype
Forced expiratory volume in one second (FEV1) > 25% predicted (using prediction equation's of Knudson et al)
Clinically stable with no evidence of acute upper or lower respiratory tract infection or current pulmonary exacerbation within 2 weeks of screening
Females of child bearing potential must have a negative pregnancy test at screening and, if sexually active, must be willing to use a double-barrier form of contraception for the duration of the study
The patient or the patient's legally acceptable representative must be able to give informed consent in accordance with International Conference on Harmonization (ICH) Good Clinical Practice (GCP) guidelines and local legislation
The patient must be able to swallow the BIIL 284 tablet whole
Patients taking a chronic medication must be willing to continue this therapy for the entire duration of the study

Exclusion Criteria

Patients with a history of allergy/hypersensitivity (including medication allergy) which is deemed relevant to the trial as judged by the Investigator
Patients who have participated in another study with an investigational drug (including BI Trial 543.36) within one month or 6 half-lives (whichever is greater) preceding the screening visit
Patients with known substance abuse, including alcohol or drug abuse, within 30 days prior to screening
Female patients who are pregnant or lactating
Patients who are unable to comply with breakfast requirements prior to dosing
Patients who have received IV, oral or inhaled antibiotics or corticosteroids for a pulmonary exacerbation within 2 weeks of screening
Patients who have started a new chronic medication for CF within 2 weeks of screening
Patients with documented persistent colonization with B. cepacia (defined as more than one positive culture within the past year)
Patients with clinically significant findings on chest x-ray which in the opinion of the Investigator precludes the patient's participation in the trial
Patients with oxyhemoglobin saturation in room air < 90% by pulse oximetry
Patients with hemoglobin < 9.0 g/dL; platelets < 100x10**9/L; prothrombin time (PT) > 1.5 times the upper limit of normal, serum glutamic-oxaloacetic transaminase (ALT) or serum glutamic-pyruvic transaminase (AST) > 2 times the upper limit of normal; creatinine > 1.8 mg/dL (adults) or > 1.4 mg/dL (pediatrics) at screening
Clinically significant disease or medical condition other than CF or CF-related conditions that, in the opinion of the Investigator, would compromise the safety of the patient or the quality of the data. This includes significant hematological, hepatic, renal, cardiovascular, and neurologic disease. Patients with diabetes may participate if their disease is under good control prior to screening.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
BIIL 284 BS, low dose in pediatric patients	BIIL 284 BS, low dose	-
BIIL 284 BS, high dose in adult patients	BIIL 284 BS, high dose	-
Placebo	Placebo	-

Primary Outcome Measures

Name	Time	Method
Changes from baseline in physical examination	Pre-dose and 72 hours after last drug administration
Number of patients with clinically relevant findings in vital signs	Up to 72 hours after last drug administration	blood pressure, pulse rate, respiratory rate, body temperature
Number of patients with clinically relevant changes in spirometry	Pre-dose, up to 72 hours after last drug administration
Number of patients with clinically relevant changes in oximetry	Pre-dose, up to 72 hours after last drug administration
Number of patients with clinically relevant changes in 12-lead ECG	Pre-dose, up to 72 hours after last drug administration
Number of patients with clinically relevant findings in laboratory evaluation	Up to 72 hours after last drug administration
Number of patients with adverse events	Up to 72 hours after last drug administration

Secondary Outcome Measures

Name	Time	Method
Terminal half-life of the analyte in plasma (t1/2)	Up to 72 hours after last drug administration
Maximum measured concentration of the analyte in plasma (Cmax)	Up to 72 hours after last drug administration
Area under the concentration-time curve of the analyte in plasma (AUC)	Up to 72 hours after last drug administration
Time from dosing to the maximum concentration of the analyte in plasma (tmax)	Up to 72 hours after last drug administration
Concentration of the analyte in plasma after 24 hours (C24h)	24 hours after drug administration
Terminal rate constant of the analyte in plasma (λz)	Up to 72 hours after last drug administration
Mean residence time of the analyte in the body at steady state (MRTss)	Up to 72 hours after last drug administration
Apparent volume of distribution during the terminal phase λz following extravascular administration at steady state (Vz,ss/F)	Up to 72 hours after last drug administration
Accumulation ratio for AUC after the 15th dose over the dosing interval compared to the first dose (RA,AUC)	day 1, day 15
Pre-dose concentration of the analyte in plasma immediately before administration of the next dose (Cpre)	Up to day 16
Accumulation ratio for Cmax after the 15th dose over the dosing interval compared to the first dose (RA,Cmax)	day 1, day 15

Safety, Tolerability and Pharmacokinetics of BIIL 284 BS in Adult and Pediatric Cystic Fibrosis (CF) Patients

Recruitment & Eligibility

Study & Design

Instant Trial Alerts

Instant Trial Alerts