Bioavailability of Tiotropium + Olodaterol Fixed-dose Combination (5 μg/ 5 μg) in Chinese COPD Patients

NCT02969317 | Completed Phase 1 Results

• 1 other identifier: 1237.30
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

The primary objective of this study is to assess the pharmacokinetics of tiotropium + olodaterol fixed-dose combination (FDC) (5 μg/ 5 μg) delivered by the RESPIMAT inhaler after single dose and at steady state in Chinese patients with COPD. The secondary objective is to assess the safety of tiotropium + olodaterol FDC (5 μg/ 5 μg) delivered by the RESPIMAT inhaler after 3 weeks once daily treatment in Chinese patients with COPD.

Conditions

Pulmonary Disease, Chronic Obstructive

Outcome Measures

Primary Outcomes (20)

• Area Under the Concentration Time Curve of Olodaterol in Plasma Over the Time Interval From 0 to 6 Hours After Drug Administration (AUC0-6)

  The descriptive statistics of AUC0-6 could not be evaluated. Since the plasma concentrations of olodaterol and tiotropium was only quantifiable in less than two-thirds of the patients after 4 hours and 1 hour, respectively, and the descriptive statistics is calculated in case that 2/3 patients of total could be evaluated as defined in Clinical trial Protocol (CTP).

  0:05 (hours:minutes) before drug administration and 0:02, 0:05, 0:07, 0:10, 0:20, 0:30, 0:40, 1:00, 2:00, 3:00, 4:00, 6:00 (hours:minutes) after drug administration

• Time From Dosing to the Maximum Concentration of Olodaterol in Plasma (Tmax)

  Tmax, time from dosing to the maximum concentration of olodaterol in plasma after single inhaled administration of tiotropium+olodaterol FDC 5 mg/5 mg is presented as unadjusted geometric mean (gMean) and geometric coefficient of variation (gCV) (%). detailed sampling time points: 0:05 (hours:minutes) before drug administration and 0:02, 0:05, 0:07, 0:10, 0:20, 0:30, 0:40, 1:00, 2:00, 3:00, 4:00, 6:00, 143:45, 144:20, 311:45, 312:20, 407:45, 408:20, 431:45, 432:20, 455:45, 456:20(hours:minutes) after drug administration.

  Day 1, 7, 14, 18, 19 and 20

• Maximum Measured Concentration of Olodaterol in Plasma (Cmax)

  Cmax, maximum measured concentration of olodaterol in plasma after single inhaled administration of tiotropium+olodaterol FDC 5 mg/5 mg is presented as unadjusted geometric mean (gMean) and geometric coefficient of variation (gCV) (%). detailed sampling time points: 0:05 (hours:minutes) before drug administration and 0:02, 0:05, 0:07, 0:10, 0:20, 0:30, 0:40, 1:00, 2:00, 3:00, 4:00, 6:00, 143:45, 144:20, 311:45, 312:20, 407:45, 408:20, 431:45, 432:20, 455:45, 456:20(hours:minutes) after drug administration.

  Day 1, 7, 14, 18, 19 and 20

• Maximum Measured Concentration of Olodaterol in Plasma at Steady State (Cmax,ss)

  Cmax,ss, maximum measured concentration of olodaterol in plasma at steady state of olodaterol after multiple dosing at Visit 4 (day 21) of tiotropium+olodaterol FDC 5 mg/5 mg is presented as unadjusted geometric mean (gMean) and geometric coefficient of variation (gCV) (%).

  Day 21: 0:15 (hours:minutes) before drug administration and 0:02, 0:05, 0:07, 0:10, 0:20, 0:30, 0:40, 1:00, 2:00, 3:00, 4:00, 6:00, 12:00, 24:00 (hours:minutes) after drug administration

• Pre-dose Concentration of Olodaterol in Plasma at Steady State (Cpre,ss)

  Cpre,ss, pre-dose concentration of olodaterol in plasma at steady state after multiple dosing at Day 21 of tiotropium+olodaterol FDC 5 mg/5 mg is presented as unadjusted geometric mean (gMean) and geometric coefficient of variation (gCV) (%).

  Day 21: 0:15 (hours:minutes) before drug administration and 0:02, 0:05, 0:07, 0:10, 0:20, 0:30, 0:40, 1:00, 2:00, 3:00, 4:00, 6:00, 12:00, 24:00 (hours:minutes) after drug administration

• Area Under the Concentration Time Curve of Olodaterol in Plasma Over the Time Interval From 0 to 6 Hours at Steady State (AUC0-6,ss)

  AUC0-6,ss, area under the concentration time curve of olodaterol in plasma over the time interval from 0 to 6 hours at steady state after multiple dosing at Day 21 of tiotropium+olodaterol FDC 5 mg/5 mg is presented as unadjusted geometric mean (gMean) and geometric coefficient of variation (gCV) (%).

  Day 21: 0:15 (hours:minutes) before drug administration and 0:02, 0:05, 0:07, 0:10, 0:20, 0:30, 0:40, 1:00, 2:00, 3:00, 4:00, 6:00 (hours:minutes) after drug administration

• Area Under the Concentration-time Curve of Olodaterol in Plasma at Steady State Over a Uniform Dosing Interval τ at Steady State (AUCτ,ss)

  AUCτ,ss, area under the concentration-time curve of olodaterol in plasma at steady state over a uniform dosing interval τ at steady state after multiple dosing at Day 21 is presented as unadjusted geometric mean (gMean) and geometric coefficient of variation (gCV) (%).

  Day 21: 0:15 (hours:minutes) before drug administration and 0:02, 0:05, 0:07, 0:10, 0:20, 0:30, 0:40, 1:00, 2:00, 3:00, 4:00, 6:00, 12:00, 24:00 (hours:minutes) after drug administration

• Time From Dosing to the Maximum Concentration of Olodaterol in Plasma at Steady State (Tmax,ss)

  Tmax,ss,time from dosing to the maximum concentration of olodaterol in plasma at steady state after multiple dosing at Day 21 of tiotropium+olodaterol FDC 5 mg/5 mg is presented as unadjusted geometric mean (gMean) and geometric coefficient of variation (gCV) (%).

  Day 21: 0:15 (hours:minutes) before drug administration and 0:02, 0:05, 0:07, 0:10, 0:20, 0:30, 0:40, 1:00, 2:00, 3:00, 4:00, 6:00, 12:00, 24:00 (hours:minutes) after drug administration

• Accumulation Ratios in Plasma of Olodaterol (RA,Cmax =Cmax,ss/Cmax)

  Accumulation ratios in plasma of olodaterol (RA,Cmax =Cmax,ss/Cmax) after multiple dosing at Day 21 is presented as unadjusted geometric mean (gMean) and geometric coefficient of variation (gCV) (%).

  Day 1 and Day 21

• Accumulation Ratios in Plasma of Olodaterol (RA,AUC =AUC0-6,ss/AUC0-6)

  Regarding AUC0-6 and RA,AUC0-6, the descriptive statistics of AUC0-6 could not be evaluated. Since the plasma concentrations of olodaterol and tiotropium was only quantifiable in less than two-thirds of the patients after 4 hours and 1 hour, respectively, and the descriptive statistics is calculated in case that 2/3 patients of total could be evaluated as defined in Clinical trial Protocol (CTP). And RA,AUC0-6 is the ratio of AUC0-6,ss to AUC0-6. So, the descriptive RA,AUC0-6 was not calculated either.

  Day 1 and Day 21

• Area Under the Concentration Time Curve of Tiotropium in Plasma Over the Time Interval From 0 to 6 Hours After Drug Administration (AUC0-6)

  The descriptive statistics of AUC0-6 could not be evaluated. Since the plasma concentrations of olodaterol and tiotropium was only quantifiable in less than two-thirds of the patients after 4 hours and 1 hour, respectively, and the descriptive statistics is calculated in case that 2/3 patients of total could be evaluated as defined in Clinical trial Protocol (CTP).

  Day 1

• Time From Dosing to the Maximum Concentration of Tiotropium in Plasma (Tmax)

  Tmax, time from dosing to the maximum concentration of Tiotropium in plasma after single inhaled administration of tiotropium+olodaterol FDC 5 mg/5 mgis presented as unadjusted geometric mean (gMean) and geometric coefficient of variation (gCV) (%). Detailed sampling time points:0:05 (hours:minutes) before drug administration and 0:02, 0:05, 0:07, 0:10, 0:20, 0:30, 0:40, 1:00, 2:00, 3:00, 4:00, 6:00, 143:45, 144:20, 311:45, 312:20, 407:45, 408:20, 431:45, 432:20, 455:45, 456:20 (hours:minutes) after drug administration

  Day 1, 7, 14, 18, 19, 20

• Maximum Measured Concentration of Tiotropium in Plasma (Cmax)

  Cmax, maximum measured concentration of Tiotropium in plasma after single inhaled administration of tiotropium+olodaterol FDC 5 mg/5 mg is presented as unadjusted geometric mean (gMean) and geometric coefficient of variation (gCV) (%). Detailed sampling time points:0:05 (hours:minutes) before drug administration and 0:02, 0:05, 0:07, 0:10, 0:20, 0:30, 0:40, 1:00, 2:00, 3:00, 4:00, 6:00, 143:45, 144:20, 311:45, 312:20, 407:45, 408:20, 431:45, 432:20, 455:45, 456:20 (hours:minutes) after drug administration

  Day 1, 7, 14, 18, 19, 20

• Maximum Measured Concentration of Tiotropium in Plasma at Steady State (Cmax,ss)

  Cmax,ss, maximum measured concentration of olodaterol in plasma at steady state of Tiotropium after multiple dosing at Visit 4 of tiotropium+olodaterol FDC 5 mg/5 mg is presented as unadjusted geometric mean (gMean) and geometric coefficient of variation (gCV) (%).

  Day 21: 0:15 (hours:minutes) before drug administration and 0:02, 0:05, 0:07, 0:10, 0:20, 0:30, 0:40, 1:00, 2:00, 3:00, 4:00, 6:00, 12:00, 24:00 (hours:minutes) after drug administration

• Pre-dose Concentration of Tiotropium in Plasma at Steady State (Cpre,ss)

  Cpre,ss, pre-dose concentration of Tiotropium in plasma at steady state after multiple dosing at Visit 4 of tiotropium+olodaterol FDC 5 mg/5 mg is presented as unadjusted geometric mean (gMean) and geometric coefficient of variation (gCV) (%).

  Day 21: 0:15 (hours:minutes) before drug administration and 0:02, 0:05, 0:07, 0:10, 0:20, 0:30, 0:40, 1:00, 2:00, 3:00, 4:00, 6:00, 12:00, 24:00 (hours:minutes) after drug administration

• Area Under the Concentration Time Curve of Tiotropium in Plasma Over the Time Interval From 0 to 6 Hours at Steady State (AUC0-6,ss)

  AUC0-6,ss, area under the concentration time curve of Tiotropium in plasma over the time interval from 0 to 6 hours at steady state after multiple dosing at Visit 4 of tiotropium+olodaterol FDC 5 mg/5 mg is presented as unadjusted geometric mean (gMean) and geometric coefficient of variation (gCV) (%).

  Day 21:0:15 (hours:minutes) before drug administration and 0:02, 0:05, 0:07, 0:10, 0:20, 0:30, 0:40, 1:00, 2:00, 3:00, 4:00, 6:00 (hours:minutes) after drug administration

• Area Under the Concentration-time Curve of Tiotropium in Plasma at Steady State Over a Uniform Dosing Interval τ at Steady State (AUCτ,ss)

  AUCτ,ss, area under the concentration-time curve of Tiotropium in plasma at steady state over a uniform dosing interval τ at steady state after multiple dosing at Visit 4 is presented as unadjusted geometric mean (gMean) and geometric coefficient of variation (gCV) (%).

  Day 21: 0:15 (hours:minutes) before drug administration and 0:02, 0:05, 0:07, 0:10, 0:20, 0:30, 0:40, 1:00, 2:00, 3:00, 4:00, 6:00, 12:00, 24:00 (hours:minutes) after drug administration

• Time From Dosing to the Maximum Concentration of Tiotropium in Plasma at Steady State (Tmax,ss)

  Tmax,ss,time from dosing to the maximum concentration of Tiotropium in plasma at steady state after multiple dosing at Visit 4 of tiotropium+olodaterol FDC 5 mg/5 mg is presented as unadjusted geometric mean (gMean) and geometric coefficient of variation (gCV) (%).

  Day 21: 0:15 (hours:minutes) before drug administration and 0:02, 0:05, 0:07, 0:10, 0:20, 0:30, 0:40, 1:00, 2:00, 3:00, 4:00, 6:00, 12:00, 24:00 (hours:minutes) after drug administration

• Accumulation Ratios in Plasma of Tiotropium (RA,Cmax =Cmax,ss/Cmax)

  Accumulation ratios in plasma of Tiotropium (RA,Cmax =Cmax,ss/Cmax) after multiple dosing at Visit 4 is presented as unadjusted geometric mean (gMean) and geometric coefficient of variation (gCV) (%).

  Day 1, 7, 14, 18, 19, 20 and 21

• Accumulation Ratios in Plasma of Tiotropium (RA,AUC =AUC0-6,ss/AUC0-6)

  Regarding AUC0-6 and RA,AUC0-6, the descriptive statistics of AUC0-6 could not be evaluated. Since the plasma concentrations of olodaterol and tiotropium was only quantifiable in less than two-thirds of the patients after 4 hours and 1 hour, respectively, and the descriptive statistics is calculated in case that 2/3 patients of total could be evaluated as defined in CTP. And RA,AUC0-6 is the ratio of AUC0-6,ss to AUC0-6. So, the descriptive RA,AUC0-6 was not calculated either.

  Day 1 and Day 21

Study Arms (1)

Tiotropium + olodaterol fixed-dose combination

EXPERIMENTAL

Fixed dose combination

Drug: Tiotropium; Drug: Olodaterol

Interventions

Tiotropium DRUG

Fixed dose combination

Also known as: INSPIOLTO, SPIOLTO, STIOLTO, VAHELVA, YANIMO

Tiotropium + olodaterol fixed-dose combination

Olodaterol DRUG

Fixed dose combination

Also known as: INSPIOLTO, SPIOLTO, STIOLTO, VAHELVA, YANIMO

Tiotropium + olodaterol fixed-dose combination

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-Good Clinical Practice (ICH-GCP) guidelines and local legislations prior to any study-related procedures, which includes medication washout and restrictions.
• All patients must have a diagnosis of Chronic Obstructive Pulmonary Disease (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 (ECSC,; and a postbronchodilator 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 who have never smoked cigarettes must be excluded.
• Patients must be able to
• perform technically acceptable pulmonary function tests,
• maintain medication worksheet records during the study period,
• perform all other assessments 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).
• Male or female patients. Women of childbearing potential\* must be ready and able to use highly effective methods of birth control per ICH M3(R2) that result in a low failure rate of less than 1% per year when used consistently and correctly. A list of contraception methods meeting these criteria is provided in the patient information.
• Women of childbearing potential are defined as:
• Any female who has experienced menarche and does not meet the criteria for "women not of childbearing potential" as described below.
• Women not of childbearing potential are defined as:

You may not qualify if:

• Patients with a significant disease other than Chronic Obstructive Pulmonary Disease (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 a, in the opinion of the investigator, clinically relevant abnormal baseline haematology, blood chemistry, or urinalysis; all patients with an Serum Glutamic Oxaloacetic Transaminase (SGOT) \>x 2 Upper Limit of Normal (ULN), Serum Glutamic Pyruvic Transaminase(SGPT) \>x 2 ULN, bilirubin \>x 2 ULN or creatinine \>x 2 ULN will be excluded regardless of clinical condition (a repeat laboratory evaluation will not be conducted in these patients).
• Patients with a history of asthma. For patients with allergic rhinitis or atopy, source documentation is required to verify that the patient does not have asthma. If a patient has a total blood eosinophil count ≥600/mm3, source documentation is required to verify that the increased eosinophil count is related to a non-asthmatic condition.
• Patients with any of the following conditions:
• A diagnosis of thyrotoxicosis (due to the known class side effect profile of ß2-agonists).
• A diagnosis of paroxysmal tachycardia (\>100 beats per minute) (due to the known class side effect profile of ß2-agonists)
• A history of myocardial infarction within 1 year of screening visit (Visit 1).
• Unstable or life-threatening cardiac arrhythmia.
• Hospitalization for heart failure within the past year.
• 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.
• Clinically evident bronchiectasis.
• A history of significant alcohol or drug abuse.

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (1)

West China Hospital

Chengdu, 610041, China

Location

Related Publications (1)

• Wang Z, Tadayasu Y, Hu N, Shu S, Hu C, Luo Z. Pharmacokinetics and safety of tiotropium+olodaterol 5 mug/5 mug fixed-dose combination in Chinese patients with COPD. Pulm Pharmacol Ther. 2020 Aug;63:101944. doi: 10.1016/j.pupt.2020.101944. Epub 2020 Sep 9.

  PMID: 32916296 DERIVED

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 Centre
• 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: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 10, 2016
• First Posted: November 21, 2016
• Study Start: February 24, 2017
• Primary Completion: June 15, 2017
• Study Completion: June 15, 2017
• Last Updated: March 29, 2019
• Results First Posted: March 29, 2019

Record last verified: 2018-12

Locations

CN (1)