Combination of Orally Inhaled BI1744CL/Tiotropium Bromide in Patients With Chronic Obstructive Pulmonary Disease ( COPD)

Phase 2

Completed

Conditions: Pulmonary Disease, Chronic Obstructive

Interventions: Drug: BI 1744 CL/tiotropium bromide fixed dose combination
Drug: tiotropium bromide
Device: Respimat® Inhaler

Registration Number: NCT00696020

Lead Sponsor: Boehringer Ingelheim

Brief Summary: The primary objective of this study is to determine the optimum dose(s) of BI 1744 CL administered with 5 micrograms tiotropium bromide solution for inhalation, delivered by the Respimat inhaler, once daily for four weeks in patients with chronic obstructive pulmonary disease (COPD).

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 360

Inclusion Criteria

All patients must sign an informed consent consistent with ICH-GCP guidelines prior to participation in the trial, which includes medication washout and restrictions
All patients must have a diagnosis of chronic obstructive pulmonary disease and must meet the following spirometric criteria:

Patients must have relatively stable airway obstruction with a post-bronchodilator FEV1 greater or equal 30% of predicted normal and <80% of predicted normal and a post-bronchodilator FEV1 / 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 and PEF measurements, and must be able to maintain records (Patient Daily e-Diary) 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 inhaler (MDI).

Further inclusion criteria apply

Exclusion Criteria

Patients with a significant disease other than COPD
Patients with clinically relevant abnormal baseline haematology, blood chemistry, or urinalysis;
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 (e.g. repeated demonstration of a QTcF* interval > 450 ms), a history of additional risk factors for Torsade de Pointes (TdP) (e.g. heart failure, hypokalemia, 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 clinically relevant cardiac arrhythmia, known active tuberculosis, a malignancy for which patient has undergone resection, radiation therapy or chemotherapy within last five years, a history of life-threatening pulmonary obstruction, a history of cystic fibrosis, clinically evident bronchiectasis, a history of significant alcohol or drug abuse
Patients who have undergone thoracotomy with pulmonary resection
Patients who regularly use daytime oxygen therapy for more than one hour per day and in the investigator's opinion will be unable to abstain from the use of oxygen therapy during clinic visits.
Pregnant or nursing women
Women of childbearing potential not using two effective method of birth control (one barrier and one non-barrier). Female patients will be considered to be of childbearing potential unless surgically sterilised by hysterectomy or bilateral tubal ligation, or post-menopausal for at least two years
Patients who have previously been randomized in this study or are currently participating in another study
Patients who are unable to comply with pulmonary medication restrictions prior to randomization
Patients who have taken an investigational drug within one month or six half lives (whichever is greater) prior to Screening Visit

Further exclusion criteria apply

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
BI 1744 CL low dose/tiotropium bromide	BI 1744 CL/tiotropium bromide fixed dose combination	BI 1744 CL low dose plus tiotropium bromide fixed dose combination; Solution for inhalation via Respimat® Inhaler (A5); Oral inhalation
BI 1744 CL low dose/tiotropium bromide	Respimat® Inhaler	BI 1744 CL low dose plus tiotropium bromide fixed dose combination; Solution for inhalation via Respimat® Inhaler (A5); Oral inhalation
BI1744CL medium dose/tiotropium bromide	BI 1744 CL/tiotropium bromide fixed dose combination	BI 1744 CL medium dose plus tiotropium bromide fixed dose combination; Solution for inhalation via Respimat® Inhaler (A5); Oral inhalation
BI1744CL medium dose/tiotropium bromide	Respimat® Inhaler	BI 1744 CL medium dose plus tiotropium bromide fixed dose combination; Solution for inhalation via Respimat® Inhaler (A5); Oral inhalation
BI 1744 CL high dose/tiotropium bromide	BI 1744 CL/tiotropium bromide fixed dose combination	BI 1744 CL high dose plus tiotropium bromide fixed dose combination; Solution for inhalation via Respimat® Inhaler (A5); Oral inhalation
BI 1744 CL high dose/tiotropium bromide	Respimat® Inhaler	BI 1744 CL high dose plus tiotropium bromide fixed dose combination; Solution for inhalation via Respimat® Inhaler (A5); Oral inhalation
tiotropium bromide	tiotropium bromide	tiotropium bromide; Solution for inhalation via Respimat® Inhaler (A5); Oral inhalation
tiotropium bromide	Respimat® Inhaler	tiotropium bromide; Solution for inhalation via Respimat® Inhaler (A5); Oral inhalation

Primary Outcome Measures

Name	Time	Method
Trough FEV1 Response [L] After 4 Weeks of Treatment	Baseline and 4 weeks	Trough FEV1 (Forced expiratory volume in 1 second) was defined as the mean of the two FEV1 values (performed at 1 h and 10 min prior to study medication inhalation) at the end of the dosing interval, 24 hours post-drug administration. Trough FEV1 response was defined as the change from baseline in trough FEV1. Baseline FEV1 was defined as the mean of the 2 pre-treatment FEV1 values measured at Visit 2 (-1 h and -10 min) prior to administration of the first dose of study medication. The means are adjusted, based on ANCOVA with terms for baseline, treatment, and centre (centre random, all other effects fixed).

Secondary Outcome Measures

Name	Time	Method
Trough FEV1 Response [L] After 1 and 2 Weeks of Treatment.	Baseline, 1 week and 2 weeks	Trough FEV1 (forced expiratory volume in 1 second) was defined as the mean of the 2 FEV1 values (performed at 1 h and 10 min prior to study medication inhalation) at the end of the dosing interval, 24 hours post-drug administration. Trough FEV1 response was defined as the change from baseline in trough FEV1. Baseline FEV1 was defined as the mean of the 2 pre-treatment FEV1 values measured at Visit 2 (-1 h and -10 min) prior to administration of the first dose of study medication. The means are adjusted, based on ANCOVA with terms for baseline, treatment, centre (centre random, all other effects fixed). Comparisons between groups are presented for Day 15.
Trough FVC Response [L] After 1, 2 and 4 Weeks of Treatment	Baseline, 1 week, 2 weeks and 4 weeks	Trough FVC (forced vital capacity) was defined as the mean of the 2 FVC values (performed at 1 h and 10 min prior to study medication inhalation) at the end of the dosing interval, 24 hours post-drug administration. Trough FVC response was defined as the change from baseline in trough FVC. Baseline FVC was defined as the mean of the 2 pre-treatment FVC values measured at Visit 2 (-1 h and -10 min) prior to administration of the first dose of study medication. The means are adjusted, based on an ANCOVA with terms for baseline, treatment, centre (centre random, all other effects fixed). Comparisons between groups are presented for Day 29.
FEV1 AUC(0-3h) Response [L] After First Administration and After 1, 2 and 4 Weeks of Treatment	1 h and 10 min prior to inhalation and 5 min (only for week 1 and 2), 30 min, 1 h, 2 h and 3 h after inhalation at baseline and after 1, 2 and 4 weeks	Response is defined as change from the baseline value. AUC(0-3h) (area under the curve) was calculated as the area under the curve from 0 to 3 hours on the various test days using the trapezoidal rule, divided by the full duration (3 hours) to report in litres. Baseline FEV1 was defined as the mean of the 2 pre-treatment FEV1 values measured at Visit 2 (-1 h and -10 min) prior to administration of the first dose of study medication The means are adjusted, based on an ANCOVA with terms for baseline, treatment, centre (centre random, all other effects fixed). Comparisons between groups are presented for Day 29.
FVC AUC(0-3h) Response [L] After First Administration and After 1, 2 and 4 Weeks of Treatment.	1 h and 10 min prior to inhalation and 5 min (only for week 1 and 2), 30 min, 1 h, 2 h and 3 h after inhalation at baseline and after 1, 2 and 4 weeks	FVC (forced vital capacity) AUC(0-3h) response is defined as change from the baseline value. AUC(0-3h) was calculated as the area under the curve from 0 to 3 hours on the various test days using the trapezoidal rule, divided by the full duration (3 hours) to report in litres. Baseline FVC was defined as the mean of the 2 pre-treatment FVC values measured at Visit 2 (-1 h and -10 min) prior to administration of the first dose of study medication. The means are adjusted, based on an ANCOVA with terms for baseline, treatment, centre (centre random, all other effects fixed). Comparisons between groups are presented for Day 29.
AUC(0-1h,ss) Olodaterol [pg*h/mL]	Pre-dose, 5 min, 10 min, 20 min, 40 min, 1 h, 3 h, and 6 h after the last dose.	Area under the concentration-time curve of Olodaterol in plasma at steady state (AUC(0-1h,ss)) from 0 to 1 hour post dosing after 4 weeks of treatment. No results displayed for Tiotropium+Olodaterol 5/2 μg because there were zero total participants analyzed for this outcome measure.
Cmax,ss Tiotropium [pg/mL]	Pre-dose, 5 min, 10 min, 20 min, 40 min, 1 h, 3 h, and 6 h after the last dose.	Maximum measured concentration of Tiotropium in plasma at steady state (Cmax,ss) after 4 weeks treatment.
PEF AUC(0-3h) Response [L/Min] After First Administration and After 1, 2 and 4 Weeks of Treatment.	1 h and 10 min prior to inhalation and 5 min (only for week 1 and 2), 30 min, 1 h, 2 h and 3 h after inhalation at baseline and after 1, 2 and 4 weeks	PEF (peak expiratory flow rate L/min) AUC(0-3h) response is defined as change from the baseline value. AUC(0-3h) will be calculated as the area under the curve from 0 to 3 hours on the various test days using the trapezoidal rule, divided by the full duration (3 hours) to report in litres/min. Baseline was defined as the mean of the 2 pre-treatment values measured at Visit 2 (-1 h and -10 min) prior to administration of the first dose of study medication. The means are adjusted, based on an ANCOVA with terms for baseline, treatment, centre (centre random, all other effects fixed). Comparisons between groups are presented for Day 29.
FEV1 AUC(0-6h) Response [L] After 4 Weeks of Treatment	1 h and 10 min prior to inhalation at baseline and after 4 weeks and 30 min, 1 h, 2 h, 3 h, 4 h, 5 h and 6h after inhalation at baseline and after 4 weeks (Day 29)	FEV1 (forced expiratory volume in 1 second) AUC(0-6h) response is defined as change from the baseline value. AUC(0-6h) will be calculated as the area under the curve from 0 to 6 hours on test day 29 using the trapezoidal rule, divided by the full duration (6 hours) to report in litres. Baseline was defined as the mean of the 2 pre-treatment values measured at Visit 2 (-1 h and -10 min) prior to administration of the first dose of study medication. The means are adjusted, based on ANCOVA with terms for baseline, treatment, and centre (centre random, all other effects fixed).
FEV1 Peak(0-3h) Response [L] After First Administration and After 1, 2 and 4 Weeks of Treatment	5 min (only for week 1 and 2), 30 min, 1 h, 2 h and 3 h after inhalation at baseline and after 1 week, 2 weeks and 4 weeks	FEV1 (forced expiratory volume in 1 second) peak(0-3h) is the maximum post-dose value during the first 3 hours after first administration and after 1, 2 and 4 weeks of treatment. Response is defined as change from the baseline value. Baseline was defined as the mean of the 2 pre-treatment values measured at Visit 2 (-1 h and -10 min) prior to administration of the first dose of study medication. The means are adjusted, based on an ANCOVA with terms for baseline, treatment, centre (centre random, all other effects fixed). Comparisons between groups are presented for Day 29.
FVC Peak(0-3h) Response [L] After First Administration and After 1, 2 and 4 Weeks of Treatment	5 min (only for week 1 and 2), 30 min, 1 h, 2 h and 3 h after inhalation at baseline and after 1 week, 2 weeks and 4 weeks	FVC (forced vital capacity) peak(0-3h) is the maximum post-dose value during the first 3 hours after first administration and after 1, 2 and 4 weeks of treatment. Response is defined as change from the baseline value. Baseline was defined as the mean of the 2 pre-treatment values measured at Visit 2 (-1 h and -10 min) prior to administration of the first dose of study medication. The means are adjusted, based on an ANCOVA with terms for baseline, treatment, centre (centre random, all other effects fixed). Comparisons between groups are presented for Day 29.
PEF Peak(0-3h) Response [L] After First Administration and After 1, 2 and 4 Weeks of Treatment	5 min (only for week 1 and 2), 30 min, 1 h, 2 h and 3 h after inhalation at baseline and after 1 week, 2 weeks and 4 weeks	PEF (peak expiratory flow rate L/min) peak(0-3h) is the maximum post-dose value during the first 3 hours after first administration and after 1, 2 and 4 weeks of treatment. Response is defined as change from the baseline value. Baseline was defined as the mean of the 2 pre-treatment values measured at Visit 2 (-1 h and -10 min) prior to administration of the first dose of study medication. The means are adjusted, based on an ANCOVA with terms for baseline, treatment, centre (centre random, all other effects fixed). Comparisons between groups are presented for Day 29.
FEV1 and PEF (Unsupervised) AUC(0-6h) Response [L] After First Administration and After 1, 2 and 4 Weeks of Treatment	After first administration, 1 week, 2 weeks and 4 weeks	AUC(0-6h) for FEV1, and PEF (unsupervised) were not studied because the pertinent information from the unsupervised pulmonary function tests was for the time interval from 9 to 12 hours post-dosing.
FEV1 (Unsupervised) AUC(6-12h) Response [L] After First Administration and 1,2 and 4 Weeks of Treatment	6 h, 9 h and 12 h after inhalation at baseline and after 1 week, 2 weeks and 4 weeks	FEV1 (forced expiratory volume in 1 second) AUC(6-12h) response is defined as change from the baseline value. AUC(6-12h) will be calculated as the area under the curve from 6 to 12 hours on the various test days using the trapezoidal rule, divided by the full duration (6 hours) to report in litres. Baseline was defined as the mean of the 2 pre-treatment values measured at Visit 2 (-1 h and -10 min) prior to administration of the first dose of study medication. The means are adjusted, based on ANCOVA with terms for baseline, treatment, and centre (centre random, all other effects fixed). Comparisons between groups are presented for Day 29.
Tmax,ss Olodaterol [h]	Pre-dose, 5 min, 10 min, 20 min, 40 min, 1 h, 3 h, and 6 h after the last dose.	Time from last dosing to maximum concentration of Olodaterol in plasma at steady state (tmax,ss) after 4 weeks treatment. No results displayed for Tiotropium+Olodaterol 5/2 μg because there were zero total participants analyzed for this outcome measure.
FVC AUC(0-6h) Response [L] After 4 Weeks of Treatment	1 h and 10 min prior to inhalation at baseline and after 4 weeks and 30 min, 1 h, 2 h, 3 h, 4 h, 5 h and 6h after inhalation at baseline and after 4 weeks (Day 29)	FVC (forced vital capacity) AUC(0-6h) response is defined as change from the baseline value. AUC(0-6h) will be calculated as the area under the curve from 0 to 6 hours on test day 29 using the trapezoidal rule, divided by the full duration (6 hours) to report in litres. Baseline was defined as the mean of the 2 pre-treatment values measured at Visit 2 (-1 h and -10 min) prior to administration of the first dose of study medication. The means are adjusted, based on an ANCOVA with terms for baseline, treatment, centre (centre random, all other effects fixed).
PEF AUC(0-6h) Response [L] After 4 Weeks of Treatment	1 h and 10 min prior to inhalation at baseline and after 4 weeks and 30 min, 1 h, 2 h, 3 h, 4 h, 5 h and 6h after inhalation at baseline and after 4 weeks (Day 29)	PEF (peak expiratory flow rate L/min) AUC(0-6h) response is defined as change from the baseline value. AUC(0-6h) will be calculated as the area under the curve from 0 to 6 hours on test day 29 using the trapezoidal rule, divided by the full duration (6 hours) to report in litres. Baseline was defined as the mean of the 2 pre-treatment values measured at Visit 2 (-1 h and -10 min) prior to administration of the first dose of study medication. The means are adjusted, based on an ANCOVA with terms for baseline, treatment, centre (centre random, all other effects fixed).
Tmax,ss Tiotropium [h]	Pre-dose, 5 min, 10 min, 20 min, 40 min, 1 h, 3 h, and 6 h after the last dose.	Time from last dosing to maximum concentration of Tiotropium in plasma at steady state (tmax,ss) after 4 weeks of treatment.
AUC(0-3h,ss) Tiotropium [pg*h/mL]	Pre-dose, 5 min, 10 min, 20 min, 40 min, 1 h, 3 h, and 6 h after the last dose.	Area under the concentration-time curve of Tiotropium at steady state (AUC(0-3h,ss)) from 0 to 3 hours post dosing after 4 weeks of treatment.
PEF (Unsupervised) AUC(6-12h) Response [L/Min] After First Administration and 1,2 and 4 Weeks of Treatment	6 h, 9 h and 12 h after inhalation at baseline and after 1 week, 2 weeks and 4 weeks	PEF (peak expiratory flow rate L/min) AUC(6-12h) response is defined as change from the baseline value. AUC(6-12h) will be calculated as the area under the curve from 6 to 12 hours on the various test days using the trapezoidal rule, divided by the full duration (6 hours) to report in litres/min. Baseline was defined as the mean of the 2 pre-treatment values measured at Visit 2 (-1 h and -10 min) prior to administration of the first dose of study medication. The means are adjusted, based on ANCOVA with terms for baseline, treatment, and centre (centre random, all other effects fixed). Comparisons between groups are presented for Day 29.
Weekly Mean Pre-dose Morning PEF [L/Min]	Throughout the 4 week treatment period	The patient will record twice daily peak flow measurements using an Asthma Monitor®Am2+ (AM2+) device. Morning measurements will be performed immediately upon arising after the patient has cleared out mucus, prior to administration of trial and/or rescue medication. The means are adjusted, based on an ANCOVA with terms for baseline, treatment, centre (centre random, all other effects fixed).
Weekly Mean Evening PEF [L/Min]	Throughout the 4 weeks treatment period	The patient will record twice daily peak flow measurements using an AM2+ device. The evening measurement will be performed at bedtime. The means are adjusted, based on an ANCOVA with terms for baseline, treatment, centre (centre random, all other effects fixed).
Weekly Mean Number of Occasions of Rescue Therapy Used Per Day	Throughout the 4 weeks treatment period	The means are adjusted, Based on an ANCOVA with terms for baseline, treatment, centre (centre random, all other effects fixed).
Physician's Global Evaluation	1 week, 2 weeks and 4 weeks	Measured a 8-point scale, from 1 (poor) to 8 (excellent), as judged by the physician, over 4 weeks of treatment. The physician made a global evaluation at the end of the Baseline Period (Test Day 1) and at each visit thereafter. These assessments were made prior to pulmonary function testing and reflected the physician's opinion of the patient's overall clinical condition. This evaluation was based on the need for concomitant medication, number and severity of COPD exacerbations since the last visit, severity of cough, ability to exercise, amount of wheezing, and other relevant clinical observations. The means are adjusted, based on an ANCOVA with terms for baseline, treatment, centre (centre random, all other effects fixed).
Patient's Global Rating	4 weeks	Patient's Global Rating at the end of the 4 week treatment period. Patients rated their health (respiratory condition) at Day 29 (compared to the day before they commenced treatment with study medication) on a 7-point scale as "very much better (1), much better (2), a little better (3), no change (4), a little worse (5), much worse (6), or very much worse (7)". The assessment was made prior to pulmonary function testing and all other study procedures. The Patient's Global Rating was also completed before the Physician's Global Evaluation. The means are adjusted, based on an ANCOVA with terms for treatment, centre (centre random, treatment effect fixed).
Clinically Significant Anormalities (Laboratory Data); Marked Changes From Baseline for Vital Signs, Notable Change in ECG and New Onset of ECG Abnormalities	From first dose up to 21 days after last dose of study medication.	Possible clinically significant anormalities (laboratory data); marked changes from baseline for vital signs, notable change in ECG and new onset of ECG abnormalities. New abnormal findings or worsening of baseline conditions were reported as Adverse Events (AEs). All AEs with an onset after the first dose of study medication up to 21 days after the last dose of study medication were to have been assigned to the Treatment Period.
Cmax,ss Olodaterol [pg/mL]	Pre-dose, 5 min, 10 min, 20 min, 40 min, 1 h, 3 h, and 6 h after the last dose.	Maximum measured concentration of Olodaterol in plasma at steady state (Cmax,ss) after 4 weeks of treatment. No results displayed for Tiotropium+Olodaterol 5/2 μg because there were zero total participants analyzed for this outcome measure.

Trial Locations

Locations (37): 1237.4.0204 Boehringer Ingelheim Investigational Site
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Sherbrooke, Quebec, Canada
1237.4.0203 Boehringer Ingelheim Investigational Site
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Winnipeg, Manitoba, Canada
1237.4.0104 Boehringer Ingelheim Investigational Site
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Coeur d'Alene, Idaho, United States
1237.4.4904 Boehringer Ingelheim Investigational Site
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Rüdersdorf, Germany
1237.4.0202 Boehringer Ingelheim Investigational Site
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Toronto, Ontario, Canada
1237.4.0103 Boehringer Ingelheim Investigational Site
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San Diego, California, United States
1237.4.0112 Boehringer Ingelheim Investigational Site
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Minneapolis, Minnesota, United States
1237.4.4902 Boehringer Ingelheim Investigational Site
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Gauting, Germany
1237.4.4908 Boehringer Ingelheim Investigational Site
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Halle, Germany
1237.4.0118 Boehringer Ingelheim Investigational Site
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Riverside, California, United States
1237.4.0115 Boehringer Ingelheim Investigational Site
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Wheat Ridge, Colorado, United States
1237.4.0110 Boehringer Ingelheim Investigational Site
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Deland, Florida, United States
1237.4.0105 Boehringer Ingelheim Investigational Site
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Clearwater, Florida, United States
1237.4.0120 Boehringer Ingelheim Investigational Site
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Edina, Minnesota, United States
1237.4.0119 Boehringer Ingelheim Investigational Site
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St. Charles, Missouri, United States
1237.4.0114 Boehringer Ingelheim Investigational Site
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Raleigh, North Carolina, United States
1237.4.0106 Boehringer Ingelheim Investigational Site
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Spartanburg, South Carolina, United States
1237.4.0102 Boehringer Ingelheim Investigational Site
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Philadelphia, Pennsylvania, United States
1237.4.0122 Boehringer Ingelheim Investigational Site
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Killeen, Texas, United States
1237.4.0109 Boehringer Ingelheim Investigational Site
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New Braunfels, Texas, United States
1237.4.0101 Boehringer Ingelheim Investigational Site
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Morgantown, West Virginia, United States
1237.4.0121 Boehringer Ingelheim Investigational Site
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Tacoma, Washington, United States
1237.4.0208 Boehringer Ingelheim Investigational Site
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Toronto, Ontario, Canada
1237.4.0201 Boehringer Ingelheim Investigational Site
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Mississauga, Ontario, Canada
1237.4.0205 Boehringer Ingelheim Investigational Site
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Toronto, Ontario, Canada
1237.4.0207 Boehringer Ingelheim Investigational Site
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Saskatoon, Saskatchewan, Canada
1237.4.0206 Boehringer Ingelheim Investigational Site
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Sainte-Foy, Quebec, Canada
1237.4.4907 Boehringer Ingelheim Investigational Site
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Erfurt, Germany
1237.4.4901 Boehringer Ingelheim Investigational Site
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Weinheim, Germany
1237.4.0123 Boehringer Ingelheim Investigational Site
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Knoxville, Tennessee, United States
1237.4.0107 Boehringer Ingelheim Investigational Site
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Spartanburg, South Carolina, United States
1237.4.4906 Boehringer Ingelheim Investigational Site
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Neuruppin, Germany
1237.4.4903 Boehringer Ingelheim Investigational Site
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Berlin, Germany
1237.4.0117 Boehringer Ingelheim Investigational Site
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Tampa, Florida, United States
1237.4.0111 Boehringer Ingelheim Investigational Site
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Charleston, South Carolina, United States
1237.4.0108 Boehringer Ingelheim Investigational Site
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Richmond, Virginia, United States
1237.4.0116 Boehringer Ingelheim Investigational Site
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Spokane, Washington, United States