Phase 2
N=155
Pharmacodynamic and Pharmacokinetic Dose Ranging Study of Tiotropium Bromide Administered Via Inhalation Solution in Patients With Chronic Obstructive Pulmonary Disease (COPD)
Mild to Moderate Chronic Obstructive Pulmonary Disease (COPD)
Bottom Line
View on ClinicalTrials.gov: NCT03118765 ↗Enrolled (actual)
155
Serious AEs
0.0%
Results posted
Aug 2019
Primary outcome: Primary: Relative Bioavailability of Tiotropium With GSP304 in Comparison to SPIRIVA RESPIMAT 5 μg Based on CmaxSS — 4.10; 8.00; 21.80; 14.00 pg/mL
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- GSP304 (tiotropium bromide) Inhalation Solution (Drug); GSP304 Placebo Inhalation Solution (Drug); Spiriva® Respimat® inhalation spray (Drug)
- Age
- Adult, Older Adult · 40+ yrs
- Sex
- All
- Sponsor
- Glenmark Specialty S.A.
- Primary completion
- Jul 2017
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Relative Bioavailability of Tiotropium With GSP304 in Comparison to SPIRIVA RESPIMAT 5 μg Based on CmaxSS |
4.10; 8.00; 21.80; 14.00 | — |
| PRIMARY Relative Bioavailability of Tiotropium With GSP 304 in Comparison to SPIRIVA RESPIMAT 5 μg Based on AUC0-tauSS |
22.90; 49.10; 122.00; 57.70 | — |
| 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. |
0.14; 0.10; 0.09; 0.08; 0.14 | 0.228 |
| 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 |
138600; 336100; 602900; 247400 | — |
| SECONDARY Amount (Aetau) of Tiotropium Excreted in Urine Over the Dosing Interval on Day 21 |
375400; 647100; 1611000; 775500 | — |
| SECONDARY Fraction of Dose (Fe) of Tiotropium Excreted in Urine Over the Dosing Interval on Day 1 |
1.386; 1.681; 1.507; 4.948 | — |
| SECONDARY Fraction of Dose (Fe) of Tiotropium Excreted in Urine Over the Dosing Interval on Day 21 |
3.754; 3.236; 4.026; 15.51 | — |
| SECONDARY Peak Concentrations During the Dosing Interval (Cmax) on Day 1 |
2.632; 7.119; 14.06; 10.25 | — |
| SECONDARY Area Under the Plasma Concentration-time Curve Over the Dosing Interval (AUC0-tau) on Day 1 |
10.65; 22.94; 52.11; 22.64 | — |
| SECONDARY Time of Peak Drug Concentration Over the Dosing Interval (Tmax) on Day 1 |
0.067; 0.100; 0.108; 0.100 | — |
| SECONDARY Time of Peak Drug Concentration Over the Dosing Interval (Tmax) on Day 21 |
0.075; 0.150; 0.108; 0.100 | — |
| SECONDARY Average Concentration During a Dosing Interval at Steady State (CavSS) on Day 21 |
1.120; 2.436; 6.273; 2.725 | — |
| SECONDARY Accumulation Ratio Rac(Auc) |
2.966; 5.328; 3.667; 3.699 | — |
| SECONDARY Accumulation Ratio Rac(Cmax) |
2.063; 3.492; 2.622; 2.835 | — |
| SECONDARY Change From Baseline in Peak FEV1 Within 12 Hours Post-dose on Day 1 |
0.34; 0.38; 0.33; 0.21; 0.38 | 0.004 sig |
| SECONDARY Change From Baseline in Peak FEV1 Within 12 Hours Post-dose on Day 21 |
0.37; 0.34; 0.31; 0.20; 0.37 | 0.001 sig |
| SECONDARY Change From Baseline in Forced Vital Capacity (FVC) on Day 1 |
0.21; 0.21; 0.18; 0.13; 0.16 | 0.166 |
| SECONDARY Change From Baseline in Forced Vital Capacity (FVC) on Day 21 |
0.16; 0.10; 0.11; 0.11; 0.16 | 0.493 |
| SECONDARY Change From Baseline in Time-normalized Area Under the Curve for FEV1 Measured Over 12 Hours on Day 1 |
0.22; 0.24; 0.24; 0.10; 0.26 | 0.003 sig |
| SECONDARY Change From Baseline in Time-normalized Area Under the Curve for FEV1 Measured Over 12 Hours on Day 21 |
0.23; 0.17; 0.15; 0.08; 0.23 | 0.002 sig |
Summary
Pharmacodynamic and Pharmacokinetic Dose Ranging Study of Tiotropium Bromide Administered Via Inhalation Solution in Patients With Chronic Obstructive Pulmonary Disease (COPD).
Eligibility Criteria
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.
Data sourced from ClinicalTrials.gov (NCT03118765). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.