ClinicalTrials.gov processed this data on March 28, 2024Link to the current ClinicalTrials.gov record.https://clinicaltrials.gov/ct2/show/NCT03118765GSP304-201NCT03118765Pharmacodynamic and Pharmacokinetic Dose Ranging Study of Tiotropium Bromide Administered Via Inhalation Solution in Patients With Chronic Obstructive Pulmonary Disease (COPD)A Dose Ranging, Parallel Group, Active (Spiriva® Respimat®) And Placebo Controlled Study To Assess Relative Bioavailability, Pharmacodynamics And Safety Of Three Doses Of Tiotropium Bromide Inhalation Solution In Subjects With Mild To Moderate Chronic Obstructive Pulmonary DiseaseGlenmark Specialty S.A.IndustryNoYesNo
Pharmacodynamic and Pharmacokinetic Dose Ranging Study of Tiotropium Bromide Administered Via
Inhalation Solution in Patients With Chronic Obstructive Pulmonary Disease (COPD).
CompletedMarch 24, 2017July 31, 2017July 31, 2017Phase 2InterventionalNoRandomizedParallel AssignmentTreatmentQuadruple (Participant, Care Provider, Investigator, Outcomes Assessor)Relative Bioavailability of Tiotropium With GSP304 in Comparison to SPIRIVA RESPIMAT 5 μg Based on CmaxSSPlasma 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.The PK endpoint in plasma to assess the relative bioavailability was peak concentrations of tiotropium during the dosing interval at steady-state (CmaxSS)Relative Bioavailability of Tiotropium With GSP 304 in Comparison to SPIRIVA RESPIMAT 5 μg Based on AUC0-tauSSPlasma 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.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)Change From Baseline (Day 1) in Trough FEV1 at 24 Hours After the Last Dose of Treatment on Day 21 in Comparison to Placebo.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).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.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 1Day 1Descriptive statistics for tiotropium urine PK parameter - Amount (Aetau) of tiotropium excreted in urine over the dosing interval on Day 1Amount (Aetau) of Tiotropium Excreted in Urine Over the Dosing Interval on Day 21Day 21Descriptive statistics for tiotropium urine PK parameter - Amount (Aetau) of Tiotropium Excreted in Urine Over the Dosing Interval on Day 21Fraction of Dose (Fe) of Tiotropium Excreted in Urine Over the Dosing Interval on Day 1Day 1Descriptive statistics for tiotropium urine PK parameter - Fraction of dose (Fe) of tiotropium excreted in urine over the dosing interval on Day 1Fraction of Dose (Fe) of Tiotropium Excreted in Urine Over the Dosing Interval on Day 21Day 21Descriptive statistics for tiotropium urine PK parameter-Fraction of Dose (Fe) of Tiotropium Excreted in Urine Over the Dosing Interval on Day 21Peak Concentrations During the Dosing Interval (Cmax) on Day 1Day 1Descriptive statistics for tiotropium plasma PK parameters - (Cmax) on Day 1Area Under the Plasma Concentration-time Curve Over the Dosing Interval (AUC0-tau) on Day 1Day 1Descriptive statistics for tiotropium plasma PK parameter - Area under the plasma concentration-time curve over the dosing interval (AUC0-tau) on Day 1Time of Peak Drug Concentration Over the Dosing Interval (Tmax) on Day 1Day 1Descriptive statistics for tiotropium plasma PK parameter - Time of peak drug concentration over the dosing interval (tmax) on Day 1Time of Peak Drug Concentration Over the Dosing Interval (Tmax) on Day 21Day 21Descriptive statistics for tiotropium plasma PK parameter - Time of peak drug concentration over the dosing interval (tmax) on Day 21Average Concentration During a Dosing Interval at Steady State (CavSS) on Day 21Day 21Descriptive statistics for tiotropium plasma PK parameter - Average concentration during a dosing interval at steady state (CavSS) on day 21Accumulation Ratio Rac(Auc)Day 21Descriptive statistics for tiotropium plasma PK parameter-Accumulation ratio Rac(auc). Rac(auc) was calculated as AUC0-tauSS/AUC0-tau.Accumulation Ratio Rac(Cmax)Day 21Descriptive statistics for tiotropium plasma PK parameter-Accumulation ratio Rac(cmax). Rac(Cmax) was calculated as CmaxSS/Cmax.Change From Baseline in Peak FEV1 Within 12 Hours Post-dose on Day 1Day 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).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.Change From Baseline in Peak FEV1 Within 12 Hours Post-dose on Day 21Day 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).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.Change From Baseline in Forced Vital Capacity (FVC) on Day 1Day 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).Least Square Mean change from baseline in forced vital capacity (FVC) to end of Day 1.Change From Baseline in Forced Vital Capacity (FVC) on Day 21Day 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).Least Square Mean change from baseline in forced vital capacity (FVC) to end of Day 21Change From Baseline in Time-normalized Area Under the Curve for FEV1 Measured Over 12 Hours on Day 1Day 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).Least Square Mean (SE) change from baseline in time-normalized area under the curve for FEV1 measured over 12 hours on Day 1.Change From Baseline in Time-normalized Area Under the Curve for FEV1 Measured Over 12 Hours on Day 21Day 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).Least Square Mean (SE) change from baseline in time-normalized area under the curve for FEV1 Measured Over 12 Hours on Day 21.5155Mild to Moderate Chronic Obstructive Pulmonary Disease (COPD)Test Treatment T1: GSP304 Inhalation SolutionExperimentalTest Treatment T2: GSP304 Inhalation SolutionExperimentalTest Treatment T3: GSP304 Inhalation SolutionExperimentalTest Treatment T4: GSP304 Placebo Inhalation SolutionPlacebo ComparatorTest Treatment T5: Spiriva® Respimat® inhalation sprayActive ComparatorDrugGSP304 (tiotropium bromide) Inhalation SolutionOnce daily (QD) oral inhalation using a nebulizerTest Treatment T1: GSP304 Inhalation SolutionTest Treatment T2: GSP304 Inhalation SolutionTest Treatment T3: GSP304 Inhalation SolutionDrugGSP304 Placebo Inhalation SolutionOnce daily (QD) oral inhalation using a nebulizerTest Treatment T4: GSP304 Placebo Inhalation SolutionDrugSpiriva® Respimat® inhalation sprayOnce daily (QD) oral inhalationTest Treatment T5: Spiriva® Respimat® inhalation spray
Inclusion Criteria:
- Male and female subjects ≥40 years and ≤85 years of age at the time of consent.
- Subject must have a primary diagnosis of mild or moderate COPD defined as
post-bronchodilator FEV1/FVC ratio of <70% and FEV1 of ≥50% of predicted normal value
as per the NHANES III predicted normal values at screening.
- Willing to stop all other COPD medications or other medications which will interfere
with the study results for the entire duration of the study, except
albuterol/salbutamol as needed.
- Current or ex-smoker with ≥10 pack-year smoking history.
Exclusion Criteria:
- Subjects with a chest x-ray/CT scan that suggests a diagnosis other than COPD (eg,
pneumonia, other infection, atelectasis, or pneumothorax or other active/ongoing
pulmonary conditions) and taken within 6 months prior to study start. If there is no
chest x-ray or CT scan taken within 6 months prior to study start, or if recent
results are unavailable for review, a chest x-ray must be performed.
- Use of oral/parenteral corticosteroids or antibiotics for COPD within 6 weeks or depot
corticosteroids within 3 months prior to screening or subject has had a change in dose
or type of any medications for COPD within 14 days before screening.
- Hospitalization for COPD exacerbation or pneumonia within 3 months prior to screening.
- Subjects with a history of asthma, with the exception of outgrown childhood asthma,
defined as transient wheezers outgrown by 5 years of age.
- Subject has a known history of alpha 1 antitrypsin deficiency-related emphysema.
- Subject requires nocturnal oxygen or continuous supplemental oxygen therapy.
- Subject with history of a positive result for HBsAg or HCV antibody.
- Subject is known to be seropositive for human immunodeficiency virus.
- Female subject is pregnant or lactating.
- Subject has a history of allergic reaction to the anti-cholinergic or any components
of the study medications.
All40 Years85 YearsNoCynthia Caracta, MD FCCPStudy DirectorGlenmark PharmaceuticalsGlenmark Investigational Site 23AndalusiaAlabama36420United StatesGlenmark Investigational Site 12PhoenixArizona85006United StatesGlenmark Investigational Site 14TempeArizona85283United StatesGlenmark Investigational Site 17FullertonCalifornia92835United StatesGlenmark Investigational Site 19EdgewaterFlorida32132United StatesGlenmark Investigational Site 10Miami LakesFlorida33016United StatesGlenmark Investigational Site 24MiamiFlorida33144United StatesGlenmark Investigational Site 16MiamiFlorida33186United StatesGlenmark Investigational Site 6OrlandoFlorida32825United StatesGlenmark Investigational Site 20Ormond BeachFlorida32124United StatesGlenmark Investigational Site 21Vero BeachFlorida32960United StatesGlenmark Investigational Site 13Winter ParkFlorida32789United StatesGlenmark Investigational Site 18Las VegasNevada89119United StatesGlenmark Investigational Site 9CharlotteNorth Carolina28207United StatesGlenmark Investigational Site 5ColumbusOhio43213United StatesGlenmark Investigational Site 22ColumbusOhio43215United StatesGlenmark Investigational Site 8DublinOhio43016United StatesGlenmark Investigational Site 11MedfordOregon97504-9741United StatesGlenmark Investigational Site 3EasleySouth Carolina29640United StatesGlenmark Investigational Site 2GreenvilleSouth Carolina29615United StatesGlenmark Investigational Site 4GreenvilleSouth Carolina29615United StatesGlenmark Investigational Site 1Rock HillSouth Carolina29732United StatesGlenmark Investigational Site 15SpartanburgSouth Carolina29303United StatesGlenmark Investigational Site 7SpartanburgSouth Carolina29303United StatesGlenmark Investigational Site 25TomballTexas77375United StatesUnited StatesJuly 2019April 10, 2017April 17, 2017April 18, 2017June 13, 2019July 5, 2019August 1, 2019July 18, 2018July 18, 2018July 19, 2018July 5, 2019July 5, 2019August 1, 2019SponsorLung DiseasesLung Diseases, ObstructivePulmonary Disease, Chronic ObstructiveBromidesPharmaceutical SolutionsTiotropium BromideStatistical Analysis PlanNoNoYesSeptember 12, 2017https://ClinicalTrials.gov/ProvidedDocs/65/NCT03118765/SAP_000.pdfStudy ProtocolYesNoNoApril 13, 2017https://ClinicalTrials.gov/ProvidedDocs/65/NCT03118765/Prot_001.pdf