| Primary | Relative Bioavailability of Tiotropium With GSP304 in Comparison to SPIRIVA RESPIMAT 5 μg Based on CmaxSS | The PK endpoint in plasma to assess the relative bioavailability was peak concentrations of tiotropium during the dosing interval at steady-state (CmaxSS) | The PK analysis set consisted of all subjects who were randomized, received at least 1 dose of study treatment, and had at least 1 quantifiable PK sample and did not have an exclusionary major protocol deviation. | Posted | | Mean | Standard Error | pg/mL | | Plasma concentrations on day 21 according to the below schedule: Pre-dose (0 hour), and at 2, 4, 6, 10, 15, 30, and 45, 60, 75, and 90 minutes post-dose, as well as 2, 4, 6, 8, 12, 16, 20 and 24 hours post-dose. | | | | ID | Title | Description |
|---|
| OG000 | GSP304 10 μg | Oral inhalation, once daily (morning) for 21 days | | OG001 | GSP304 20 μg | Oral inhalation, once daily (morning) for 21 days | | OG002 | GSP304 40 μg | Oral inhalation, once daily (morning) for 21 days | | OG003 | SPIRIVA RESPIMAT 5 μg | Oral inhalation, once daily (morning) for 21 days |
| | Units | Counts |
|---|
| Participants | - OG00026
- OG00130
- OG00226
- OG003
|
| | Title | Denominators | Categories |
|---|
| | | Title | Measurements |
|---|
| - OG0004.10± 1.152
- OG0018.00± 1.140
- OG00221.80± 1.152
- OG003
|
|
| | Group IDs | Group Description | Statistical Method | Statistical Comment | P-Value | P-Value Comment | Parameter Type | Parameter Value | Dispersion Type | Dispersion Value | Confidence Interval Sides | Confidence Interval % | CI Lower Limit | CI Upper Limit | CI Lower Limit Comment | CI Upper Limit Comment | Estimate Comment | Tested Non-Inferiority | Non-Inferiority Type | Non-Inferiority Comment | Other Analysis Description |
|---|
| GSP 304 vs SPIRIVA RESPIMAT 5 μg comparison for relative bioavailability data based on CmaxSS was tested and the estimated treatment ratios for the treatment comparisons was presented. | | | | | LS mean ratio (%) | 29.4 | | | 2-Sided | 90 | 21.14 | 41.00 | | | Relative Bioavailability (%) based on CmaxSS for of GSP304 in comparison to SPIRIVA RESPIMAT | | Other | | | |
|
| Primary | Relative Bioavailability of Tiotropium With GSP 304 in Comparison to SPIRIVA RESPIMAT 5 μg Based on AUC0-tauSS | The PK endpoint in plasma to assess the relative bioavailability was area under the plasma concentration-time curve of tiotropium over the dosing interval at steady state (AUC0-tauSS) | The PK analysis set consisted of all subjects who were randomized, received at least 1 dose of study treatment, and had at least 1 quantifiable PK sample and did not have an exclusionary major protocol deviation. | Posted | | Mean | Standard Error | h*pg/mL | | Plasma concentrations on day 21 according to the below schedule: Pre-dose (0 hour), and at 2, 4, 6, 10, 15, 30, and 45, 60, 75, and 90 minutes post-dose, as well as 2, 4, 6, 8, 12, 16, 20 and 24 hours post-dose. | | | | ID | Title | Description |
|---|
| OG000 | GSP304 10 μg | Oral inhalation, once daily (morning) for 21 days | | OG001 | GSP304 20 μg | Oral inhalation, once daily (morning) for 21 days | | OG002 | GSP304 40 μg | Oral inhalation, once daily (morning) for 21 days | | OG003 | SPIRIVA RESPIMAT 5 μg |
|
| Primary | Change From Baseline (Day 1) in Trough FEV1 at 24 Hours After the Last Dose of Treatment on Day 21 in Comparison to Placebo. | Change from baseline (Day 1) at Day 21 (Week 3) in trough FEV1 response at approximately 24 hours after the last dose (average of 23 hours 15 minutes and 23 hours 45 minutes postdose measurements), in comparison with placebo. | | Posted | | Mean | Standard Error | L | | 21 days (Pre- dose trough FEV1 is mean FEV1 at -45 mins and -15 mins pre-morning dose at Day 1. Trough FEV1 is mean FEV1 obtained 23 hrs 15 mins and 23 hrs 45 mins post-morning dose of day 21). | | | | ID | Title | Description |
|---|
| OG000 | GSP304 10 μg | Oral inhalation, once daily (morning) for 21 days | | OG001 | GSP304 20 μg | Oral inhalation, once daily (morning) for 21 days | | OG002 | GSP304 40 μg | Oral inhalation, once daily (morning) for 21 days | | OG003 | Placebo | Oral inhalation, once daily (morning) for 21 days | | OG004 |
|
| Secondary | Amount (Aetau) (Cumulative Amount of Unchanged Drug Excreted Into the Urine Over the Dosing Interval) of Tiotropium Excreted in Urine Over the Dosing Interval on Day 1 | Descriptive statistics for tiotropium urine PK parameter - Amount (Aetau) of tiotropium excreted in urine over the dosing interval on Day 1 | Overall Number of Participants Analyzed is the number of subjects with data in the Pharmacokinetic Analysis Set (PKAS). PKAS included all subjects who were randomized, received at least 1 dose of study drug, and had at least 1 quantifiable PK sample and did not have exclusionary major protocol deviations. | Posted | | Mean | Standard Deviation | pg | | Day 1 | | | | ID | Title | Description |
|---|
| OG000 | GSP304 10 μg | Oral inhalation, once daily (morning) for 21 days | | OG001 | GSP304 20 μg | Oral inhalation, once daily (morning) for 21 days | | OG002 | GSP304 40 μg | Oral inhalation, once daily (morning) for 21 days | | OG003 | SPIRIVA RESPIMAT 5 μg | Oral inhalation, once daily (morning) for 21 days |
|
| Secondary | Amount (Aetau) of Tiotropium Excreted in Urine Over the Dosing Interval on Day 21 | Descriptive statistics for tiotropium urine PK parameter - Amount (Aetau) of Tiotropium Excreted in Urine Over the Dosing Interval on Day 21 | Overall Number of Participants Analyzed is the number of subjects with data in the Pharmacokinetic Analysis Set (PKAS). PKAS included all subjects who were randomized, received at least 1 dose of study drug, and had at least 1 quantifiable PK sample and did not have exclusionary major protocol deviations. | Posted | | Mean | Standard Deviation | pg | | Day 21 | | | | ID | Title | Description |
|---|
| OG000 | GSP304 10 μg | Oral inhalation, once daily (morning) for 21 days | | OG001 | GSP304 20 μg | Oral inhalation, once daily (morning) for 21 days | | OG002 | GSP304 40 μg | Oral inhalation, once daily (morning) for 21 days | | OG003 | SPIRIVA RESPIMAT 5 μg | Oral inhalation, once daily (morning) for 21 days |
|
| Secondary | Fraction of Dose (Fe) of Tiotropium Excreted in Urine Over the Dosing Interval on Day 1 | Descriptive statistics for tiotropium urine PK parameter - Fraction of dose (Fe) of tiotropium excreted in urine over the dosing interval on Day 1 | Overall Number of Participants Analyzed is the number of subjects with data in the Pharmacokinetic Analysis Set (PKAS). PKAS included all subjects who were randomized, received at least 1 dose of study drug, and had at least 1 quantifiable PK sample and did not have exclusionary major protocol deviations. | Posted | | Mean | Standard Deviation | percentage of dose | | Day 1 | | | | ID | Title | Description |
|---|
| OG000 | GSP304 10 μg | Oral inhalation, once daily (morning) for 21 days | | OG001 | GSP304 20 μg | Oral inhalation, once daily (morning) for 21 days | | OG002 | GSP304 40 μg | Oral inhalation, once daily (morning) for 21 days | | OG003 | SPIRIVA RESPIMAT 5 μg | Oral inhalation, once daily (morning) for 21 days |
|
| Secondary | Fraction of Dose (Fe) of Tiotropium Excreted in Urine Over the Dosing Interval on Day 21 | Descriptive statistics for tiotropium urine PK parameter-Fraction of Dose (Fe) of Tiotropium Excreted in Urine Over the Dosing Interval on Day 21 | Overall Number of Participants Analyzed is the number of subjects with data in the Pharmacokinetic Analysis Set (PKAS). PKAS included all subjects who were randomized, received at least 1 dose of study drug, and had at least 1 quantifiable PK sample and did not have exclusionary major protocol deviations. | Posted | | Mean | Standard Deviation | percentage of dose | | Day 21 | | | | ID | Title | Description |
|---|
| OG000 | GSP304 10 μg | Oral inhalation, once daily (morning) for 21 days | | OG001 | GSP304 20 μg | Oral inhalation, once daily (morning) for 21 days | | OG002 | GSP304 40 μg | Oral inhalation, once daily (morning) for 21 days | | OG003 | SPIRIVA RESPIMAT 5 μg | Oral inhalation, once daily (morning) for 21 days |
|
| Secondary | Peak Concentrations During the Dosing Interval (Cmax) on Day 1 | Descriptive statistics for tiotropium plasma PK parameters - (Cmax) on Day 1 | Overall Number of Participants Analyzed is the number of subjects with data in the Pharmacokinetic Analysis Set (PKAS). PKAS included all subjects who were randomized, received at least 1 dose of study drug, and had at least 1 quantifiable PK sample and did not have exclusionary major protocol deviations. | Posted | | Mean | Standard Deviation | pg/mL | | Day 1 | | | | ID | Title | Description |
|---|
| OG000 | GSP304 10 μg | Oral inhalation, once daily (morning) for 21 days | | OG001 | GSP304 20 μg | Oral inhalation, once daily (morning) for 21 days | | OG002 | GSP304 40 μg | Oral inhalation, once daily (morning) for 21 days | | OG003 | SPIRIVA RESPIMAT 5 μg | Oral inhalation, once daily (morning) for 21 days |
| |
| Secondary | Area Under the Plasma Concentration-time Curve Over the Dosing Interval (AUC0-tau) on Day 1 | Descriptive statistics for tiotropium plasma PK parameter - Area under the plasma concentration-time curve over the dosing interval (AUC0-tau) on Day 1 | Overall Number of Participants Analyzed is the number of subjects with data in the Pharmacokinetic Analysis Set (PKAS). PKAS included all subjects who were randomized, received at least 1 dose of study drug, and had at least 1 quantifiable PK sample and did not have exclusionary major protocol deviations. | Posted | | Mean | Standard Deviation | pg*h/mL | | Day 1 | | | | ID | Title | Description |
|---|
| OG000 | GSP304 10 μg | Oral inhalation, once daily (morning) for 21 days | | OG001 | GSP304 20 μg | Oral inhalation, once daily (morning) for 21 days | | OG002 | GSP304 40 μg | Oral inhalation, once daily (morning) for 21 days | | OG003 | SPIRIVA RESPIMAT 5 μg | Oral inhalation, once daily (morning) for 21 days |
|
| Secondary | Time of Peak Drug Concentration Over the Dosing Interval (Tmax) on Day 1 | Descriptive statistics for tiotropium plasma PK parameter - Time of peak drug concentration over the dosing interval (tmax) on Day 1 | Overall Number of Participants Analyzed is the number of subjects with data in the Pharmacokinetic Analysis Set (PKAS). PKAS included all subjects who were randomized, received at least 1 dose of study drug, and had at least 1 quantifiable PK sample and did not have exclusionary major protocol deviations. | Posted | | Median | Full Range | hour | | Day 1 | | | | ID | Title | Description |
|---|
| OG000 | GSP304 10 μg | Oral inhalation, once daily (morning) for 21 days | | OG001 | GSP304 20 μg | Oral inhalation, once daily (morning) for 21 days | | OG002 | GSP304 40 μg | Oral inhalation, once daily (morning) for 21 days | | OG003 | SPIRIVA RESPIMAT 5 μg | Oral inhalation, once daily (morning) for 21 days |
| |
| Secondary | Time of Peak Drug Concentration Over the Dosing Interval (Tmax) on Day 21 | Descriptive statistics for tiotropium plasma PK parameter - Time of peak drug concentration over the dosing interval (tmax) on Day 21 | Overall Number of Participants Analyzed is the number of subjects with data in the Pharmacokinetic Analysis Set (PKAS). PKAS included all subjects who were randomized, received at least 1 dose of study drug, and had at least 1 quantifiable PK sample and did not have exclusionary major protocol deviations. | Posted | | Median | Full Range | hour | | Day 21 | | | | ID | Title | Description |
|---|
| OG000 | GSP304 10 μg | Oral inhalation, once daily (morning) for 21 days | | OG001 | GSP304 20 μg | Oral inhalation, once daily (morning) for 21 days | | OG002 | GSP304 40 μg | Oral inhalation, once daily (morning) for 21 days | | OG003 | SPIRIVA RESPIMAT 5 μg | Oral inhalation, once daily (morning) for 21 days |
| |
| Secondary | Average Concentration During a Dosing Interval at Steady State (CavSS) on Day 21 | Descriptive statistics for tiotropium plasma PK parameter - Average concentration during a dosing interval at steady state (CavSS) on day 21 | Overall Number of Participants Analyzed is the number of subjects with data in the Pharmacokinetic Analysis Set (PKAS). PKAS included all subjects who were randomized, received at least 1 dose of study drug, and had at least 1 quantifiable PK sample and did not have exclusionary major protocol deviations. | Posted | | Mean | Standard Deviation | pg/mL | | Day 21 | | | | ID | Title | Description |
|---|
| OG000 | GSP304 10 μg | Oral inhalation, once daily (morning) for 21 days | | OG001 | GSP304 20 μg | Oral inhalation, once daily (morning) for 21 days | | OG002 | GSP304 40 μg | Oral inhalation, once daily (morning) for 21 days | | OG003 | SPIRIVA RESPIMAT 5 μg | Oral inhalation, once daily (morning) for 21 days |
|
| Secondary | Accumulation Ratio Rac(Auc) | Descriptive statistics for tiotropium plasma PK parameter-Accumulation ratio Rac(auc). Rac(auc) was calculated as AUC0-tauSS/AUC0-tau. | Overall Number of Participants Analyzed is the number of subjects with data in the Pharmacokinetic Analysis Set (PKAS). PKAS included all subjects who were randomized, received at least 1 dose of study drug, and had at least 1 quantifiable PK sample and did not have exclusionary major protocol deviations. | Posted | | Mean | Standard Deviation | ratio | | Day 21 | | | | ID | Title | Description |
|---|
| OG000 | GSP304 10 μg | Oral inhalation, once daily (morning) for 21 days | | OG001 | GSP304 20 μg | Oral inhalation, once daily (morning) for 21 days | | OG002 | GSP304 40 μg | Oral inhalation, once daily (morning) for 21 days | | OG003 | SPIRIVA RESPIMAT 5 μg | Oral inhalation, once daily (morning) for 21 days |
| |
| Secondary | Accumulation Ratio Rac(Cmax) | Descriptive statistics for tiotropium plasma PK parameter-Accumulation ratio Rac(cmax). Rac(Cmax) was calculated as CmaxSS/Cmax. | Overall Number of Participants Analyzed is the number of subjects with data in the Pharmacokinetic Analysis Set (PKAS). PKAS included all subjects who were randomized, received at least 1 dose of study drug, and had at least 1 quantifiable PK sample and did not have exclusionary major protocol deviations. | Posted | | Mean | Standard Deviation | ratio | | Day 21 | | | | ID | Title | Description |
|---|
| OG000 | GSP304 10 μg | Oral inhalation, once daily (morning) for 21 days | | OG001 | GSP304 20 μg | Oral inhalation, once daily (morning) for 21 days | | OG002 | GSP304 40 μg | Oral inhalation, once daily (morning) for 21 days | | OG003 | SPIRIVA RESPIMAT 5 μg | Oral inhalation, once daily (morning) for 21 days |
| |
| Secondary | Change From Baseline in Peak FEV1 Within 12 Hours Post-dose on Day 1 | The least square mean change from baseline to peak FEV1 within 12 hours postdose on Day 1. Change from baseline in peak FEV1 within 12 hours postdose on Day 1 was derived from the serial readings taken through 12 hours postdose and calculating the change from baseline. | Full Analysis Set (FAS) included all subjects who were randomized, had received at least 1 dose of study drug and had at least 1 post-baseline PD assessment. | Posted | | Least Squares Mean | Standard Error | Litre | | Day 1 (Pre-dose FEV1 at -45 mins and 15 mins prior to dosing on Day 1. On Day 1 FEV1 at post-dose at 5 mins ±3, 15 mins ±2, 30 mins ±5, 60 mins, 90 mins, and 2 hours; and post-dose at 4, 6, 8, 10, 12 hours after the morning dose). | | | | ID | Title | Description |
|---|
| OG000 | GSP304 10 μg | Oral inhalation, once daily (morning) for 21 days | | OG001 | GSP304 20 μg | Oral inhalation, once daily (morning) for 21 days | | OG002 | GSP304 40 μg | Oral inhalation, once daily (morning) for 21 days | | OG003 | Placebo |
|
| Secondary | Change From Baseline in Peak FEV1 Within 12 Hours Post-dose on Day 21 | The least square mean change from baseline to peak FEV1 within 12 hours postdose on Day 21. Change from baseline in peak FEV1 within 12 hours postdose on Day 21 was derived from the serial readings taken through 12 hours postdose and calculating the change from baseline. | Full Analysis Set (FAS) included all subjects who were randomized, had received at least 1 dose of study drug and had at least 1 post-baseline PD assessment. | Posted | | Least Squares Mean | Standard Error | Litre | | Day 21(Pre-dose FEV1 at -45 mins and 15 mins prior to dosing on Day 21. On Day 21, FEV1 at post-dose at 5 mins ±3, 15 mins ±2, 30 mins ±5, 60 mins, 90 mins, and 2 hours; and post-dose at 4, 6, 8, 10, 12 hours after the morning dose). | | | | ID | Title | Description |
|---|
| OG000 | GSP304 10 μg | Oral inhalation, once daily (morning) for 21 days | | OG001 | GSP304 20 μg | Oral inhalation, once daily (morning) for 21 days | | OG002 | GSP304 40 μg | Oral inhalation, once daily (morning) for 21 days | | OG003 | Placebo |
|
| Secondary | Change From Baseline in Forced Vital Capacity (FVC) on Day 1 | Least Square Mean change from baseline in forced vital capacity (FVC) to end of Day 1. | Full Analysis Set (FAS) included all subjects who were randomized, had received at least 1 dose of study drug and had at least 1 post-baseline PD assessment. | Posted | | Least Squares Mean | Standard Error | Litre | | Day 1 (Pre-dose FVC at -45 mins and 15 mins prior to dosing on Day 1. Postdose timing were relative to the end of dosing.The window for 1 hour spirometry and thereafter was ±5 minutes). | | | | ID | Title | Description |
|---|
| OG000 | GSP304 10 μg | Oral inhalation, once daily (morning) for 21 days | | OG001 | GSP304 20 μg | Oral inhalation, once daily (morning) for 21 days | | OG002 | GSP304 40 μg | Oral inhalation, once daily (morning) for 21 days | | OG003 | Placebo | Oral inhalation, once daily (morning) for 21 days | |
|
| Secondary | Change From Baseline in Forced Vital Capacity (FVC) on Day 21 | Least Square Mean change from baseline in forced vital capacity (FVC) to end of Day 21 | Full Analysis Set (FAS) included all subjects who were randomized, had received at least 1 dose of study drug and had at least 1 post-baseline PD assessment. | Posted | | Least Squares Mean | Standard Error | Litre | | Day 21 (Pre-dose FVC at -45 mins and 15 mins prior to dosing on Day 21. Postdose timing were relative to the end of dosing. The window for 1 hour spirometry and thereafter was ±5 minutes). | | | | ID | Title | Description |
|---|
| OG000 | GSP304 10 μg | Oral inhalation, once daily (morning) for 21 days | | OG001 | GSP304 20 μg | Oral inhalation, once daily (morning) for 21 days | | OG002 | GSP304 40 μg | Oral inhalation, once daily (morning) for 21 days | | OG003 | Placebo | Oral inhalation, once daily (morning) for 21 days | |
|
| Secondary | Change From Baseline in Time-normalized Area Under the Curve for FEV1 Measured Over 12 Hours on Day 1 | Least Square Mean (SE) change from baseline in time-normalized area under the curve for FEV1 measured over 12 hours on Day 1. | Full Analysis Set (FAS) included all subjects who were randomized, had received at least 1 dose of study drug and had at least 1 post-baseline PD assessment. | Posted | | Least Squares Mean | Standard Error | Litre | | Day 1 (Pre-dose FEV1 at -45 mins and 15 mins prior to dosing on Day 1. On Day 1 FEV1 at post-dose at 5 mins ±3, 15 mins ±2, 30 mins ±5, 60 mins, 90 mins, and 2 hours; and post-dose at 4, 6, 8, 10, 12 hours after the morning dose). | | | | ID | Title | Description |
|---|
| OG000 | GSP304 10 μg | Oral inhalation, once daily (morning) for 21 days | | OG001 | GSP304 20 μg | Oral inhalation, once daily (morning) for 21 days | | OG002 | GSP304 40 μg | Oral inhalation, once daily (morning) for 21 days | | OG003 | Placebo | Oral inhalation, once daily (morning) for 21 days |
|
| Secondary | Change From Baseline in Time-normalized Area Under the Curve for FEV1 Measured Over 12 Hours on Day 21 | Least Square Mean (SE) change from baseline in time-normalized area under the curve for FEV1 Measured Over 12 Hours on Day 21. | Full Analysis Set (FAS) included all subjects who were randomized, had received at least 1 dose of study drug and had at least 1 post-baseline PD assessment. | Posted | | Least Squares Mean | Standard Error | Litre | | Day 21(Pre-dose FEV1 at -45 mins and 15 mins prior to dosing on Day 21. On Day 21, FEV1 at post-dose at 5 mins ±3, 15 mins ±2, 30 mins ±5, 60 mins, 90 mins, and 2 hours; and post-dose at 4, 6, 8, 10, 12 hours after the morning dose). | | | | ID | Title | Description |
|---|
| OG000 | GSP304 10 μg | Oral inhalation, once daily (morning) for 21 days | | OG001 | GSP304 20 μg | Oral inhalation, once daily (morning) for 21 days | | OG002 | GSP304 40 μg | Oral inhalation, once daily (morning) for 21 days | | OG003 | Placebo | Oral inhalation, once daily (morning) for 21 days |
|