Clinical trial NCT03118765: Pharmacodynamic and Pharmacokinetic Dose Ranging Study of Tiotropium Bromide Administered Via Inhalation Solution in Patients With Chronic Obstructive Pulmonary Disease (COPD)
Official title: 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 Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Mild to Moderate Chronic Obstructive Pulmonary Disease (COPD)
Lead sponsor: Glenmark Specialty S.A.
Sponsor class: INDUSTRY
First posted: 2017-04-18
Enrollment: 155
Sex: ALL
Minimum age (years): 40
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Primary outcomes:
measure: Relative Bioavailability of Tiotropium With GSP304 in Comparison to SPIRIVA RESPIMAT 5 μg Based on CmaxSS
timeFrame: 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.
measure: Relative Bioavailability of Tiotropium With GSP 304 in Comparison to SPIRIVA RESPIMAT 5 μg Based on AUC0-tauSS
timeFrame: 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.
measure: Change From Baseline (Day 1) in Trough FEV1 at 24 Hours After the Last Dose of Treatment on Day 21 in Comparison to Placebo.
timeFrame: 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).
Secondary outcomes:
measure: 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
timeFrame: Day 1
measure: Amount (Aetau) of Tiotropium Excreted in Urine Over the Dosing Interval on Day 21
timeFrame: Day 21
measure: Fraction of Dose (Fe) of Tiotropium Excreted in Urine Over the Dosing Interval on Day 1
timeFrame: Day 1
measure: Fraction of Dose (Fe) of Tiotropium Excreted in Urine Over the Dosing Interval on Day 21
timeFrame: Day 21
measure: Peak Concentrations During the Dosing Interval (Cmax) on Day 1
timeFrame: Day 1
measure: Area Under the Plasma Concentration-time Curve Over the Dosing Interval (AUC0-tau) on Day 1
timeFrame: Day 1
measure: Time of Peak Drug Concentration Over the Dosing Interval (Tmax) on Day 1
timeFrame: Day 1
measure: Time of Peak Drug Concentration Over the Dosing Interval (Tmax) on Day 21
timeFrame: Day 21
measure: Average Concentration During a Dosing Interval at Steady State (CavSS) on Day 21
timeFrame: Day 21
measure: Accumulation Ratio Rac(Auc)
timeFrame: Day 21
measure: Accumulation Ratio Rac(Cmax)
timeFrame: Day 21
measure: Change From Baseline in Peak FEV1 Within 12 Hours Post-dose on Day 1
timeFrame: 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).
measure: Change From Baseline in Peak FEV1 Within 12 Hours Post-dose on Day 21
timeFrame: 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).
measure: Change From Baseline in Forced Vital Capacity (FVC) on Day 1
timeFrame: 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).
measure: Change From Baseline in Forced Vital Capacity (FVC) on Day 21
timeFrame: 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).
measure: Change From Baseline in Time-normalized Area Under the Curve for FEV1 Measured Over 12 Hours on Day 1
timeFrame: 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).
measure: Change From Baseline in Time-normalized Area Under the Curve for FEV1 Measured Over 12 Hours on Day 21
timeFrame: 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).
Other outcomes:
Locations:
city: Andalusia
country: United States
facility: Glenmark Investigational Site 23
state: Alabama
city: Phoenix
country: United States
facility: Glenmark Investigational Site 12
state: Arizona
city: Tempe
country: United States
facility: Glenmark Investigational Site 14
state: Arizona
city: Fullerton
country: United States
facility: Glenmark Investigational Site 17
state: California
city: Edgewater
country: United States
facility: Glenmark Investigational Site 19
state: Florida
city: Miami Lakes
country: United States
facility: Glenmark Investigational Site 10
state: Florida
city: Miami
country: United States
facility: Glenmark Investigational Site 24
state: Florida
city: Miami
country: United States
facility: Glenmark Investigational Site 16
state: Florida
city: Orlando
country: United States
facility: Glenmark Investigational Site 6
state: Florida
city: Ormond Beach
country: United States
facility: Glenmark Investigational Site 20
state: Florida
city: Vero Beach
country: United States
facility: Glenmark Investigational Site 21
state: Florida
city: Winter Park
country: United States
facility: Glenmark Investigational Site 13
state: Florida
city: Las Vegas
country: United States
facility: Glenmark Investigational Site 18
state: Nevada
city: Charlotte
country: United States
facility: Glenmark Investigational Site 9
state: North Carolina
city: Columbus
country: United States
facility: Glenmark Investigational Site 5
state: Ohio
city: Columbus
country: United States
facility: Glenmark Investigational Site 22
state: Ohio
city: Dublin
country: United States
facility: Glenmark Investigational Site 8
state: Ohio
city: Medford
country: United States
facility: Glenmark Investigational Site 11
state: Oregon
city: Easley
country: United States
facility: Glenmark Investigational Site 3
state: South Carolina
city: Greenville
country: United States
facility: Glenmark Investigational Site 2
state: South Carolina
city: Greenville
country: United States
facility: Glenmark Investigational Site 4
state: South Carolina
city: Rock Hill
country: United States
facility: Glenmark Investigational Site 1
state: South Carolina
city: Spartanburg
country: United States
facility: Glenmark Investigational Site 15
state: South Carolina
city: Spartanburg
country: United States
facility: Glenmark Investigational Site 7
state: South Carolina
city: Tomball
country: United States
facility: Glenmark Investigational Site 25
state: Texas
Study officials:
affiliation: Glenmark Pharmaceuticals
name: Cynthia Caracta, MD FCCP
role: STUDY_DIRECTOR
References: