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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Tiotropium + Olodaterol (high dose) | Experimental | Tiotropium and Olodaterol fixed dose combination (FDC) solution for inhalation - RESPIMAT |
|
| Tiotropium + Olodaterol (low dose) | Experimental | Tiotropium and Olodaterol fixed dose combination (FDC) solution for inhalation - RESPIMAT |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Tiotropium (high dose) + Olodaterol | Drug | Tiotropium + Olodaterol solution for inhalation |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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) |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Adverse Events (Including Assessment Based on Physical Examination) | Outcome data show are the number of patients with an adverse event including the 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 |
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Inclusion criteria:
Exclusion criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Boehringer Ingelheim | Boehringer Ingelheim | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| 1237.24.24001 Boehringer Ingelheim Investigational Site | Toshima-ku, Tokyo | Japan |
This is a randomised, open-label, parallel group trial in which 3 weeks of randomised treatment are preceded by 2-week screening period and followed by 3-week follow-up period.
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| ID | Title | Description |
|---|---|---|
| FG000 | Tiotropium + Olodaterol (5µg/5µg) | Oral inhalation of tiotropium 5 microgram (µg) (high dose) + olodaterol solution 5µg fixed-dose combination (FDC). The patients inhale 2 puffs from the RESPIMAT inhaler, once a day, in the morning up to 3 weeks. |
| FG001 | Tiotropium + Olodaterol (2.5µg/5µg) |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Tiotropium (low dose) + Olodaterol | Drug | Tiotropium + Olodaterol solution for inhalation |
|
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 |
Outcome data show are the number of participants with clinically relevant abnormalities reported as an adverse event (AE) related to the vital signs (pulse rate and blood pressure in supine position), clinical laboratory (routine blood chemistry, haematology, and urinalysis) tests and ECG (12-lead holter monitoring Electrocardiography). Relevant findings or worsening of baseline conditions were reported as adverse events. There were no clinically relevant abnormalities reported as an AE related to the vital signs and ECG. |
| up to 6 weeks (3 weeks treatment and 3 weeks follow-up) post dose |
Oral inhalation of tiotropium 2.5 microgram (µg) (low dose) + olodaterol solution 5µg fixed-dose combination (FDC). The patients inhale 2 puffs from the RESPIMAT inhaler, once a day, in the morning up to 3 weeks. |
| COMPLETED |
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| NOT COMPLETED |
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Treated Set (TS) includes all randomised patients who received at least one dose of trial medication.
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| ID | Title | Description |
|---|---|---|
| BG000 | Tiotropium + Olodaterol (5µg/5µg) | Oral inhalation of tiotropium 5 microgram (µg) (high dose) + olodaterol solution 5µg fixed-dose combination (FDC). The patients inhale 2 puffs from the RESPIMAT inhaler, once a day, in the morning up to 3 weeks. |
| BG001 | Tiotropium + Olodaterol (2.5µg/5µg) | Oral inhalation of tiotropium 2.5 microgram (µg) (low dose) + olodaterol solution 5µg fixed-dose combination (FDC). The patients inhale 2 puffs from the RESPIMAT inhaler, once a day, in the morning up to 3 weeks. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | The Pharmacokinetic (PK) set was defined as all treated patients who have at least 1 PK parameter in the treatment period without PK related important protocol violations. Two patients prematurely stopped the trial medication and had no PK measurement at Visit 3 (day 21) and were excluded from the PK set. Thus, the PK set included 30 patients. | Posted | Geometric Mean | Geometric Coefficient of Variation | picogram/milliliter (pg/mL) | 15 minutes (min) pre-dose and 5, 10, 20, 40 min, 1, 2, 3, and 4 hours (h) following drug administration on day 21 |
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| ||||||||||||||||||||||||||||
| Primary | 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. | The Pharmacokinetic (PK) set. | Posted | Geometric Mean | Geometric Coefficient of Variation | pg*h/mL | 15 min pre-dose and 5, 10, 20, 40 min, 1, 2, 3, and 4 h following drug administration on day 21 |
|
| |||||||||||||||||||||||||||||
| Primary | 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. | The Pharmacokinetic (PK) set. | Posted | Geometric Mean | Geometric Coefficient of Variation | pg*h/mL | 15 min pre-dose and 5, 10, 20, 40 min, 1, 2, 3, and 4 h following drug administration on day 21 |
|
| |||||||||||||||||||||||||||||
| Primary | 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. | The Pharmacokinetic (PK) set. | Posted | Median | Full Range | h | 15 min pre-dose and 5, 10, 20, 40 min, 1, 2, 3 and 4 hours (h) following drug administration on day 21 |
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| |||||||||||||||||||||||||||||
| Primary | 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. | The Pharmacokinetic (PK) set. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanogram (ng) | from 0 to 4 hours following drug administration on day 21 |
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| |||||||||||||||||||||||||||||
| Primary | 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. | The Pharmacokinetic (PK) set. | Posted | Geometric Mean | Geometric Coefficient of Variation | percentage of dose | from 0 to 4 hours following drug administration on day 21 |
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| |||||||||||||||||||||||||||||
| Primary | 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. | The Pharmacokinetic (PK) set. | Posted | Geometric Mean | Geometric Coefficient of Variation | mL/min | from 0 to 4 hours following drug administration on day 21 |
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| Secondary | Number of Participants With Adverse Events (Including Assessment Based on Physical Examination) | Outcome data show are the number of patients with an adverse event including the assessment based on physical examination. | Treated Set (TS) includes all randomised patients who received at least one dose of trial medication. | Posted | Number | participants | up to 6 weeks (3 weeks treatment and 3 weeks follow-up) post dose |
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| ||||||||||||||||||||||||||||||
| Primary | 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. | The Pharmacokinetic (PK) set. | Posted | Geometric Mean | Geometric Coefficient of Variation | picogram/milliliter (pg/mL) | 15 minutes (min) pre-dose and 5, 10, 20, 40 min, 1, 2, 3, and 4 hours (h) following drug administration on day 21 |
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| |||||||||||||||||||||||||||||
| Primary | 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. | The Pharmacokinetic (PK) set. | Posted | Geometric Mean | Geometric Coefficient of Variation | pg*h/mL | 15 min pre-dose and 5, 10, 20, 40 min, 1 and 2 h following drug administration on day 21 |
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| Primary | 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. | The Pharmacokinetic (PK) set. | Posted | Geometric Mean | Geometric Coefficient of Variation | pg*h/mL | 15 min pre-dose and 5, 10, 20, 40 min, 1, 2, 3, and 4 h following drug administration on day 21 |
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| Primary | 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. | The Pharmacokinetic (PK) set. | Posted | Median | Full Range | h | 15 min pre-dose and 5, 10, 20, 40 min, 1, 2, 3, 4 hours following drug administration on day 21 |
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| Primary | 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. | The Pharmacokinetic (PK) set. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanogram (ng) | from 0 to 4 hours following drug administration on day 21 |
|
| |||||||||||||||||||||||||||||
| Primary | 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. | The Pharmacokinetic (PK) set. | Posted | Geometric Mean | Geometric Coefficient of Variation | percentage of dose | from 0 to 4 hours following drug administration on day 21 |
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| Primary | 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). | The Pharmacokinetic (PK) set. | Posted | Geometric Mean | Geometric Coefficient of Variation | mL/min | from 0 to 4 hours following drug administration on day 21 |
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| Secondary | Number of Participants With Clinically Relevant Abnormalities in Vital Signs, Clinical Laboratory Tests and ECG | Outcome data show are the number of participants with clinically relevant abnormalities reported as an adverse event (AE) related to the vital signs (pulse rate and blood pressure in supine position), clinical laboratory (routine blood chemistry, haematology, and urinalysis) tests and ECG (12-lead holter monitoring Electrocardiography). Relevant findings or worsening of baseline conditions were reported as adverse events. There were no clinically relevant abnormalities reported as an AE related to the vital signs and ECG. | The treated Set (TS). | Posted | Number | participants | up to 6 weeks (3 weeks treatment and 3 weeks follow-up) post dose |
|
up to 44 days (23 days maximum number of days a study treatment was used after first intake and 21 days follow-up)
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Tiotropium + Olodaterol (5µg/5µg) | Oral inhalation of tiotropium 5 microgram (µg) (high dose) + olodaterol solution 5µg fixed-dose combination (FDC). The patients inhale 2 puffs from the RESPIMAT inhaler, once a day, in the morning up to 3 weeks. | 0 | 16 | 4 | 16 | ||
| EG001 | Tiotropium + Olodaterol (2.5µg/5µg) | Oral inhalation of tiotropium 2.5 microgram (µg) (low dose) + olodaterol solution 5µg fixed-dose combination (FDC). The patients inhale 2 puffs from the RESPIMAT inhaler, once a day, in the morning up to 3 weeks. | 0 | 16 | 2 | 16 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Bronchitis | Infections and infestations | MEDDRA 16.0 | Systematic Assessment |
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| Nasopharyngitis | Infections and infestations | MEDDRA 16.0 | Systematic Assessment |
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| Blood creatine phosphokinase increased | Investigations | MEDDRA 16.0 | Systematic Assessment |
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| Blood urine present | Investigations | MEDDRA 16.0 | Systematic Assessment |
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| Dizziness | Nervous system disorders | MEDDRA 16.0 | Systematic Assessment |
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| Haematuria | Renal and urinary disorders | MEDDRA 16.0 | Systematic Assessment |
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Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Boehringer Ingelheim Call Center | Boehringer Ingelheim | 1-800-243-0127 | clintriage.rdg@boehringer-ingelheim.com |
| ID | Term |
|---|---|
| D029424 | Pulmonary Disease, Chronic Obstructive |
| ID | Term |
|---|---|
| D008173 | Lung Diseases, Obstructive |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| D000069447 | Tiotropium Bromide |
| C549647 | olodaterol |
| ID | Term |
|---|---|
| D012602 | Scopolamine Derivatives |
| D014326 | Tropanes |
| D053961 | Azabicyclo Compounds |
| D001372 | Aza Compounds |
| D009930 | Organic Chemicals |
| D000470 | Alkaloids |
| D006571 | Heterocyclic Compounds |
| D019086 | Bridged Bicyclo Compounds, Heterocyclic |
| D006572 | Heterocyclic Compounds, Bridged-Ring |
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