A Study to Characterize Pharmacokinetics of Tiotropium + Olodaterol Fixed-dose Combination in Japanese Patients With COPD.

NCT01703845 | Completed Phase 1 Results

• 1 other identifier: 1237.24
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

The primary objective of this study is to assess pharmacokinetics of tiotropium + olodaterol fixed-dose combination (2.5 µg/ 5 µg, 5 µg/ 5 µg) delivered by the RESPIMAT inhaler after 3 weeks once daily treatment in Japanese patients with COPD.

Conditions

Pulmonary Disease, Chronic Obstructive

Outcome Measures

Primary Outcomes (14)

• Cmax,ss (Olodaterol)

  Maximum measured concentration of olodaterol after multiple inhaled administration of tiotropium+olodaterol in plasma at steady state (Cmax,ss). Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type.

  15 minutes (min) pre-dose and 5, 10, 20, 40 min, 1, 2, 3, and 4 hours (h) following drug administration on day 21

• AUCt1-t2,ss (Olodaterol)

  Area under the concentration-time curve of olodaterol in plasma after multiple inhaled administration of tiotropium+olodaterol over the time interval 0 to 4 hours at steady state (AUCt1-t2,ss). Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type.

  15 min pre-dose and 5, 10, 20, 40 min, 1, 2, 3, and 4 h following drug administration on day 21

• AUC0-tz,ss (Olodaterol)

  Area under the concentration-time curve of olodaterol after multiple inhaled administration of tiotropium+olodaterol in plasma over the time interval from 0 to the time of the last quantifiable data point at steady state (AUC0-tz,ss). Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type.

  15 min pre-dose and 5, 10, 20, 40 min, 1, 2, 3, and 4 h following drug administration on day 21

• Tmax,ss (Olodaterol)

  Time from dosing to the maximum concentration of Olodaterol after multiple inhaled administration of tiotropium+olodaterol in plasma at steady state (tmax,ss). Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type.

  15 min pre-dose and 5, 10, 20, 40 min, 1, 2, 3 and 4 hours (h) following drug administration on day 21

• Aet1-t2,ss (Olodaterol)

  Amount of olodaterol that is eliminated in urine after multiple inhaled administration of tiotropium+olodaterol over the time interval 0 to 4 hours at steady state (Aet1-t2,ss). Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type.

  from 0 to 4 hours following drug administration on day 21

• fe t1-t2,ss (Olodaterol)

  Fraction eliminated in urine from the time point t1 (0 h) to time point t2 (4 h) at steady state (fet1-t2,ss). Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type.

  from 0 to 4 hours following drug administration on day 21

• CLR,t1-t2,ss (Olodaterol)

  Renal clearance from the time point t1 (0 h) until the time point t2 (4 h) at steady state (CLR,t1-t2,ss). Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type.

  from 0 to 4 hours following drug administration on day 21

• Cmax,ss (Tiotropium)

  Maximum measured concentration of tiotropium after multiple inhaled administration of tiotropium+olodaterol in plasma at steady state (Cmax,ss). Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type.

  15 minutes (min) pre-dose and 5, 10, 20, 40 min, 1, 2, 3, and 4 hours (h) following drug administration on day 21

• AUCt1-t2,ss (Tiotropium)

  Area under the concentration-time curve of tiotropium in plasma after multiple inhaled administration of tiotropium+olodaterol over the time interval 0 to 2 hours at steady state (AUCt1-t2,ss). Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type.

  15 min pre-dose and 5, 10, 20, 40 min, 1 and 2 h following drug administration on day 21

• AUC0-tz,ss (Tiotropium)

  Area under the concentration-time curve of tiotropium after multiple inhaled administration of tiotropium+olodaterol in plasma over the time interval from 0 to the time of the last quantifiable data point at steady state (AUC0-tz,ss). Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type.

  15 min pre-dose and 5, 10, 20, 40 min, 1, 2, 3, and 4 h following drug administration on day 21

• Tmax,ss (Tiotropium)

  Time from dosing to the maximum concentration of tiotropium after multiple inhaled administration of tiotropium+olodaterol in plasma at steady state (tmax,ss). Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type.

  15 min pre-dose and 5, 10, 20, 40 min, 1, 2, 3, 4 hours following drug administration on day 21

• Aet1-t2,ss (Tiotropium)

  Amount of tiotropium that is eliminated in urine after multiple inhaled administration of tiotropium+olodaterol over the time interval 0 to 4 hours at steady state (Aet1-t2,ss). Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type.

  from 0 to 4 hours following drug administration on day 21

• fe t1-t2,ss (Tiotropium)

  Fraction eliminated in urine from the time point t1 (0 h) to time point t2 (4 h) at steady state (fet1-t2,ss). Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type.

  from 0 to 4 hours following drug administration on day 21

• CLR,t1-t2,ss (Tiotropium)

  Renal clearance from the time point t1 (0 h) until the time point t2 (4 h) at steady state (CLR,t1-t2,ss). Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type. Plasma concentration of tiotropium could not be quantified up to 4 hours for Tiotropium + Olodaterol (2.5μg/5μg).

  from 0 to 4 hours following drug administration on day 21

Secondary Outcomes (2)

• Number of Participants With Adverse Events (Including Assessment Based on Physical Examination)

  up to 6 weeks (3 weeks treatment and 3 weeks follow-up) post dose

• Number of Participants With Clinically Relevant Abnormalities in Vital Signs, Clinical Laboratory Tests and ECG

  up to 6 weeks (3 weeks treatment and 3 weeks follow-up) post dose

Study Arms (2)

Tiotropium + Olodaterol (high dose)

EXPERIMENTAL

Tiotropium and Olodaterol fixed dose combination (FDC) solution for inhalation - RESPIMAT

Drug: Tiotropium (high dose) + Olodaterol

Tiotropium + Olodaterol (low dose)

EXPERIMENTAL

Tiotropium and Olodaterol fixed dose combination (FDC) solution for inhalation - RESPIMAT

Drug: Tiotropium (low dose) + Olodaterol

Interventions

Tiotropium (high dose) + Olodaterol DRUG

Tiotropium + Olodaterol solution for inhalation

Tiotropium + Olodaterol (high dose)

Tiotropium (low dose) + Olodaterol DRUG

Tiotropium + Olodaterol solution for inhalation

Tiotropium + Olodaterol (low dose)

Eligibility Criteria

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

You may qualify if:

• Diagnosis of chronic obstructive pulmonary disease
• Relatively stable airway obstruction with post FEV1=\<30% of predicted normal and\< 80% predicted normal and post FEV1/FVC \<70%
• Male or female Japanese patients, 40 years of age or older
• Smoking history of more than 10 pack years

You may not qualify if:

• Significant disease other than COPD
• Clinically relevant abnormal lab values
• History of asthma
• Diagnosis of thyrotoxicosis
• Diagnosis of paroxysmal tachycardia
• A marked baseline prolongation of QT/QTc interval
• A history of additional risk factors for Torsade de Pointes (TdP)
• History of myocardial infarction within 1 year of screening visit
• Unstable or life-threatening cardiac arrhythmia
• Hospitalization for heart failure within the past year
• Known active tuberculosis
• Malignancy for which patient has undergone resection, radiation therapy or chemotherapy within last five years
• History of life-threatening pulmonary obstruction
• History of cystic fibrosis
• Clinically evident bronchiectasis

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (1)

1237.24.24001 Boehringer Ingelheim Investigational Site

Toshima-ku, Tokyo, Japan

Location

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

Tiotropium Bromide; olodaterol

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

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: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 8, 2012
• First Posted: October 11, 2012
• Study Start: October 1, 2012
• Primary Completion: March 1, 2013
• Study Completion: March 1, 2013
• Last Updated: July 15, 2015
• Results First Posted: July 15, 2015

Record last verified: 2015-06

Locations

JP (1)