Pulmonary Disease, Chronic ObstructivePhase 1NCT02969317

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

A Phase 1 study testing Tiotropium and Olodaterol in people with Pulmonary Disease, Chronic Obstructive, run by Boehringer Ingelheim at 1 site in China.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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. Read more about this study

Who is it for?: Ages 40 years and older
Conditions the study is for: Pulmonary Disease, Chronic Obstructive
What is being tested?: Tiotropium and Olodaterol
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 12 participants
Where: 1 siteChina
Study dates: 24 Feb 2017to 15 Jun 2017
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 40 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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.

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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:
Women who are postmenopausal (12 months with no menses without an alternative medical cause) or who are permanently sterilized (e.g., tubal occlusion, hysterectomy, bilateral oophorectomy or bilateral salpingectomy).

Who cannot join

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)

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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.
Patients who have undergone thoracotomy with pulmonary resection (patients with a history of thoracotomy for other reasons should be evaluated as per exclusion criterion No. 1).
Patients being treated with oral or patch β-adrenergics.
Patients being treated with oral corticosteroid medication at unstable doses (i.e., less than six weeks on a stable dose) or at doses in excess of the equivalent of 10 mg of prednisone per day or 20 mg every other day.
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.
Patients who have completed a pulmonary rehabilitation program in the six weeks prior to the screening visit (Visit 1) or patients who are currently in a pulmonary rehabilitation program.
Patients who have taken an investigational drug within one month or six half lives or within the wash out period (whichever is greater) prior to screening visit (Visit 1).
Patients with known hypersensitivity to β-adrenergics and/or anticholinergic drugs, benzalkonium chloride (BAC), disodium edentate (EDTA) or any other component of the RESPIMAT inhalation solution.
Women who are pregnant, nursing, or who plan to become pregnant while in the trial
Women of childbearing potential not using two highly effective methods of birth control*.
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.
as per ICH M3: a highly effective method of birth control is defined as those which result in a low failure rate (i.e., less than 1% per year) when used consistently and correctly.
Patients who have previously been allocated in this study or are currently participating in another study.
Patients who are unable to comply with pulmonary medication restrictions prior to allocation.

Trial locations and contacts

1 site in 1 country.

China1 site

West China Hospital
Chengdu, 610041

Other trials in China

About this study

Official title: An Open-label Trial to Assess Pharmacokinetics and Safety of Tiotropium + Olodaterol Fixed-dose Combination (5 µg/ 5 µg) Delivered by the RESPIMAT Inhaler After Single and Multiple Dose Treatment in Chinese Patients With Chronic Obstructive Pulmonary Disease (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
Being tested: Tiotropium, Olodaterol
Medical subject headings: Pulmonary Disease, Chronic Obstructive

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

TiotropiumDrug
Also called INSPIOLTO, SPIOLTO, STIOLTO, VAHELVA, YANIMO
Fixed dose combination
OlodaterolDrug
Also called INSPIOLTO, SPIOLTO, STIOLTO, VAHELVA, YANIMO
Fixed dose combination

Study groups in NCT02969317
Study group	Role	What they receive
Tiotropium + olodaterol fixed-dose combination	Experimental	Fixed dose combination Receives: Drug: Tiotropium; Drug: Olodaterol

What is being measured

The primary outcome is the main question the study is designed to answer.

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).
Measured: 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.
Measured: 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.
Measured: 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) (%).
Measured: 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) (%).
Measured: 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) (%).
Measured: 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) (%).
Measured: 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) (%).
Measured: 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) (%).
Measured: 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.
Measured: 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).
Measured: 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
Measured: 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
Measured: 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) (%).
Measured: 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) (%).
Measured: 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) (%).
Measured: 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) (%).
Measured: 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) (%).
Measured: 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) (%).
Measured: 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.
Measured: Day 1 and Day 21

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

24 Feb 201715 Jun 2017

First posted21 Nov 2016 (estimated)
Study start24 Feb 2017
Primary completion15 Jun 2017
Study completion15 Jun 2017

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Pulmonary Disease, Chronic ObstructiveStudies of the same condition, open and under way.
More trials run by Boehringer IngelheimThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 12 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02969317
Sponsor's protocol ID: 1237.30
Status last verified: Dec 2018
First submitted: 10 Nov 2016
Last updated: 29 Mar 2019
Results posted: Yes, on ClinicalTrials.gov
FDA-regulated drug: No
FDA-regulated device: No

Publications

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.
PubMed 32916296

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 29 Mar 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: An Open-label Trial to Assess Pharmacokinetics and Safety of Tiotropium + Olodaterol Fixed-dose Combination (5 µg/ 5 µg) Delivered by the RESPIMAT Inhaler After Single and Multiple Dose Treatment in Chinese Patients With Chronic Obstructive Pulmonary Disease (COPD)
ClinicalTrials.gov ID: NCT02969317
Acronym / sponsor ID: 1237.30
Conditions: Pulmonary Disease, Chronic Obstructive
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 12 participants (actual)
Lead sponsor: Boehringer IngelheimIndustry (pharma, biotech, devices)
Study start: 24 Feb 2017 (actual)
Primary completion: 15 Jun 2017 (actual)
Study completion: 15 Jun 2017 (actual)
First posted: 21 Nov 2016 (estimated)
Results: Posted 29 Mar 2019

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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.

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Tiotropium + olodaterol fixed-dose combination	Experimental	Drug: Tiotropium, Drug: OlodaterolFixed dose combination

Who may qualify

Ages: 40 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (16 listed)

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.

Key exclusion criteria (28 listed)

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.
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)

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
TiotropiumAlso: INSPIOLTO, SPIOLTO, STIOLTO, VAHELVA, YANIMOFixed dose combination	Drug	Tiotropium + olodaterol fixed-dose combination
OlodaterolAlso: INSPIOLTO, SPIOLTO, STIOLTO, VAHELVA, YANIMOFixed dose combination	Drug	Tiotropium + olodaterol fixed-dose combination

Primary outcome

Area Under the Concentration Time Curve of Olodaterol in Plasma Over the Time Interval From 0 to 6 Hours After Drug Administration (AUC0-6)
Time frame: 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
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).
Time From Dosing to the Maximum Concentration of Olodaterol in Plasma (Tmax)
Time frame: Day 1, 7, 14, 18, 19 and 20
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.
Maximum Measured Concentration of Olodaterol in Plasma (Cmax)
Time frame: Day 1, 7, 14, 18, 19 and 20
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.
Maximum Measured Concentration of Olodaterol in Plasma at Steady State (Cmax,ss)
Time frame: 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
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) (%).
Pre-dose Concentration of Olodaterol in Plasma at Steady State (Cpre,ss)
Time frame: 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
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) (%).
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)
Time frame: 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
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) (%).
Area Under the Concentration-time Curve of Olodaterol in Plasma at Steady State Over a Uniform Dosing Interval τ at Steady State (AUCτ,ss)
Time frame: 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
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) (%).
Time From Dosing to the Maximum Concentration of Olodaterol in Plasma at Steady State (Tmax,ss)
Time frame: 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
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) (%).
Accumulation Ratios in Plasma of Olodaterol (RA,Cmax =Cmax,ss/Cmax)
Time frame: Day 1 and Day 21
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) (%).
Accumulation Ratios in Plasma of Olodaterol (RA,AUC =AUC0-6,ss/AUC0-6)
Time frame: Day 1 and Day 21
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.
Area Under the Concentration Time Curve of Tiotropium in Plasma Over the Time Interval From 0 to 6 Hours After Drug Administration (AUC0-6)
Time frame: Day 1
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).
Time From Dosing to the Maximum Concentration of Tiotropium in Plasma (Tmax)
Time frame: Day 1, 7, 14, 18, 19, 20
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
Maximum Measured Concentration of Tiotropium in Plasma (Cmax)
Time frame: Day 1, 7, 14, 18, 19, 20
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
Maximum Measured Concentration of Tiotropium in Plasma at Steady State (Cmax,ss)
Time frame: 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
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) (%).
Pre-dose Concentration of Tiotropium in Plasma at Steady State (Cpre,ss)
Time frame: 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
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) (%).
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)
Time frame: 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
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) (%).
Area Under the Concentration-time Curve of Tiotropium in Plasma at Steady State Over a Uniform Dosing Interval τ at Steady State (AUCτ,ss)
Time frame: 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
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) (%).
Time From Dosing to the Maximum Concentration of Tiotropium in Plasma at Steady State (Tmax,ss)
Time frame: 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
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) (%).
Accumulation Ratios in Plasma of Tiotropium (RA,Cmax =Cmax,ss/Cmax)
Time frame: Day 1, 7, 14, 18, 19, 20 and 21
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) (%).
Accumulation Ratios in Plasma of Tiotropium (RA,AUC =AUC0-6,ss/AUC0-6)
Time frame: Day 1 and Day 21
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.

Results and safety

Results posted to the registry on 29 Mar 2019, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Tiotropium+Olodaterol 5 Microgram/5 Microgram	12	12

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

Time frame: 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

Population analysed: Pharmacokinetic analysis set (PKS): This set included all patients in the treated set with at least one evaluable PK parameter in the treatment period without important protocol violations related to PK

Primary outcome: Time From Dosing to the Maximum Concentration of Olodaterol in Plasma (Tmax)

Time frame: Day 1, 7, 14, 18, 19 and 20. Median (Full Range). Unit: Hour [h]

Measure	Tiotropium+Olodaterol FDC 5 mg/5 mg n = 12
Value	0.167 (0.117 to 3.00)

Population analysed: PKS (evaluable cases)

Primary outcome: Maximum Measured Concentration of Olodaterol in Plasma (Cmax)

Time frame: Day 1, 7, 14, 18, 19 and 20. Geometric mean (Geometric Coefficient of Variation). Unit: Picograms per millilitre [pg/mL]

Measure	Tiotropium+Olodaterol FDC 5 mg/5 mg n = 12
Value	1.26 (104)

Population analysed: PKS (evaluable cases)

Primary outcome: Maximum Measured Concentration of Olodaterol in Plasma at Steady State (Cmax,ss)

Time frame: 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. Geometric mean (Geometric Coefficient of Variation). Unit: Picograms per millilitre [pg/mL]

Measure	Tiotropium+Olodaterol FDC 5 mg/5 mg n = 12
Value	2.00 (98.4)

Population analysed: PKS (evaluable cases)

Adverse events

Time frame: From first drug administration through the residual effect period (REP) [[REP, defined as 21 days after last trial medication application], until individual patient's end of trial); up to 6 weeks.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Tiotropium+Olodaterol FDC 5 mg/5 mg	0 of 12 (0%)	3 of 12 (25%)	0 of 12

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 29 Mar 2019.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 32916296Wang 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.
Related InfoLink provided by the sponsor.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Boehringer Ingelheim study chair

Boehringer Ingelheim

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Tiotropium and Olodaterol in people with Pulmonary Disease, Chronic Obstructive, run by Boehringer Ingelheim at 1 site in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 16 inclusion and 28 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 29 Mar 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 29 Mar 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Area Under the Concentration Time Curve of Olodaterol in Plasma Over the Time Interval From 0 to 6 Hours After Drug Administration (AUC0-6) (time frame: 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). The study lists 20 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02969317, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Mar 2019.