Pharmacokinetics and Safety of BI 1744 CL Plus Tiotropium Bromide in Chronic Obstructive Pulmonary Disease (COPD)

NCT02231177 | Completed Phase 1 Results

• 1 other identifier: 1237.3
• Study Type: interventional
• Target: 47
• Locations: 0 countries
• Sites: N/A

Brief Summary

The purpose of this study is to compare the systemic exposure to BI 1744 BS and tiotropium at steady state following inhalation of the fixed dose combination (FDC) of 10 μg BI 1744 CL plus 5 μg tiotropium bromide with the systemic exposure to BI 1744 BS and tiotropium at steady state following inhalation of the single agents, i.e., 10 μg BI 1744 CL and 5 μg tiotropium bromide, when administered once-daily via the Respimat® Inhaler for 21 days. The secondary objectives were to compare the safety and tolerability (adverse events, 12-lead electrocardiogram recordings, pulmonary function testing) of BI 1744 CL and tiotropium bromide when administered as fixed dose combination or as single-agent therapy.

Conditions

Pulmonary Disease, Chronic Obstructive

Outcome Measures

Primary Outcomes (3)

• AUC(0-1h,ss) of Olodaterol

  Area under the concentration time curve of Olodaterol in plasma over the time interval t1=0 to t2=1 hour at steady state (AUC(0-1h,ss)). As plasma concentrations were not expected to be quantifiable over the complete dosing interval in all patients, t2 was defined as the time-point where at least 2/3 of the patients reveal quantifiable plasma concentrations of Olodaterol. Based on the given definition AUC(0-1h,ss) was selected as primary endpoint. The displayed values show adjusted gMeans and intra-subject variabilities calculated from the statistical model (ANOVA).

  Within 30 min before drug administration and 0:02, 0:05, 0:10, 0:15, 0:20, 0:40, 1:00, 2:00, 4:00, 6:00, 8:00, 12:00, 24:00 hours after drug administration on Day 21 of the actual treatment period.

• Cmax,ss of Olodaterol

  Maximum measured concentration of Olodaterol in plasma at steady state (Cmax,ss). The displayed values show adjusted gMeans and intra-subject variabilities calculated from the statistical model (ANOVA).

  Within 30 min before drug administration and 0:02, 0:05, 0:10, 0:15, 0:20, 0:40, 1:00, 2:00, 4:00, 6:00, 8:00, 12:00, 24:00 hours after drug administration on Day 21 of the actual treatment period.

• Ae(0-24h,ss) of Tiotropium

  Amount of Tiotropium that was eliminated in urine at steady state from time point 0 to 24 h post-inhalation (Ae(0-24h,ss)). The displayed values show adjusted gMeans and intra-subject variabilities calculated from the statistical model (ANOVA).

  Intervals 0-4, 4-8, 8-12 and 12-24 hours on Day 21 of the actual treatment period.

Secondary Outcomes (20)

• Ae(0-24h,ss) of Olodaterol

  Intervals 0-4, 4-8, 8-12 and 12-24 hours on Day 21 of the actual treatment period.

• AUC(0-6h,ss) of Tiotropium

  Within 30 min before drug administration and 0:02, 0:05, 0:10, 0:15, 0:20, 0:40, 1:00, 2:00, 4:00, 6:00, 8:00, 12:00, 24:00 hours after drug administration on Day 21 of the actual treatment period.

• Cmax,ss of Tiotropium

  Within 30 min before drug administration and 0:02, 0:05, 0:10, 0:15, 0:20, 0:40, 1:00, 2:00, 4:00, 6:00, 8:00, 12:00, 24:00 hours after drug administration on Day 21 of the actual treatment period.

• AUC(0-2h,ss) of Olodaterol

  Within 30 min before drug administration and 0:02, 0:05, 0:10, 0:15, 0:20, 0:40, 1:00, 2:00, 4:00, 6:00, 8:00, 12:00, 24:00 hours after drug administration on Day 21 of the actual treatment period.

• AUC(0-4h,ss) of Tiotropium

  Within 30 min before drug administration and 0:02, 0:05, 0:10, 0:15, 0:20, 0:40, 1:00, 2:00, 4:00, 6:00, 8:00, 12:00, 24:00 hours after drug administration on Day 21 of the actual treatment period.

Study Arms (3)

BI 1744 CL/Tiotropium FDC

EXPERIMENTAL

Drug: BI 1744 CL/Tiotropium FDC

BI 1744 CL

ACTIVE COMPARATOR

Drug: BI 1744 CL

Tiotropium

ACTIVE COMPARATOR

Drug: Tiotropium

Interventions

BI 1744 CL DRUG

BI 1744 CL

BI 1744 CL/Tiotropium FDC DRUG

BI 1744 CL/Tiotropium FDC

Tiotropium DRUG

Tiotropium

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All patients must sign an informed consent consistent with International Conference on Harmonisation (ICH) - Good Clinical Practice (GCP) guidelines and local legislations prior to any study-related procedures, which includes medication washout and restrictions
• All patients must have a diagnosis of COPD and must meet the following spirometric criteria: Patients must have relatively stable airway obstruction with a post-bronchodilator forced expiratory volume in one second (FEV1) ≥ 30 % of predicted normal and \< 80% of predicted normal and a post-bronchodilator FEV1 / forced vital capacity (FVC) \< 70% at Visit 1
• Male or female patients, 40 years of age or older
• Patients must be current or ex-smokers with a smoking history of more than 10 pack years
• Patients must be able to perform technically acceptable pulmonary function tests during the study period as required in the protocol
• Patients must be able to inhale medication in a competent manner from the Respimat® inhaler and from a metered dose inhalator (MDI)

You may not qualify if:

• Patients with a significant disease other than COPD; a significant disease is defined as a disease which, in the opinion of the investigator, may (i) put the patient at risk because of participation in the study, (ii) influence the results of the study, or (iii) cause concern regarding the patient's ability to participate in the study
• Patients with clinically relevant abnormal baseline haematology, blood chemistry or urinalysis; all patients with a serum glutamic oxaloacetic transaminase (SGOT) \> 2.5 x ULN, serum glutamic pyruvic transaminase (SGPT) \> 2.5 x ULN, bilirubin \>2x upper limit of normal (ULN), creatinine \>2 x ULN or creatinine clearance \< 50 mL/min (Estimation of Glomerular Filtration Rate (GFR) by using the Cockcroft-Gault Formula) will be excluded regardless of clinical condition (a repeat laboratory evaluation will not be conducted in these patients)
• Patients with a history of asthma or a total blood eosinophil count ≥600/mm3
• Patients with any of the following conditions:
• a diagnosis of thyrotoxicosis
• a diagnosis of paroxysmal tachycardia (\>100 beats per minute)
• a marked baseline prolongation of QT/QTc interval
• a history of additional risk factors for Torsade de Pointes (TdP) (e.g. heart failure, hypokalaemia, family history of Long QT Syndrome)
• Patients with any of the following conditions:
• a history of myocardial infarction within 1 year of screening visit (Visit 1)
• a diagnosis of cardiac arrhythmia, arterial hypertension or coronary heart disease
• known active tuberculosis
• a malignancy for which patient has undergone resection, radiation therapy or chemotherapy within last five years (patients with treated basal cell carcinoma are allowed)
• a history of life-threatening pulmonary obstruction
• a history of cystic fibrosis

Sponsors & Collaborators

• Boehringer Ingelheim: lead

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

olodaterol; Tiotropium Bromide

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Scopolamine Derivatives; Tropanes; Azabicyclo Compounds; Aza Compounds; Organic Chemicals; Alkaloids; Heterocyclic Compounds; Bridged Bicyclo Compounds, Heterocyclic; Heterocyclic Compounds, Bridged-Ring

Limitations and Caveats

Additional secondary endpoints were listed in the original protocol, but according to internal rules, descriptive statistics would not be calculated unless data from at least 2/3rds of all subjects were available.

Results Point of Contact

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

clintriage.rdg@boehringer-ingelheim.com

1-800-243-0127

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
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 2, 2014
• First Posted: September 4, 2014
• Study Start: June 1, 2008
• Primary Completion: November 1, 2008
• Last Updated: January 7, 2016
• Results First Posted: January 7, 2016

Record last verified: 2015-12