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Completed

NCT Number: NCT03118765

Pharmacodynamic and Pharmacokinetic Dose Ranging Study of Tiotropium Bromide Administered Via Inhalation Solution in Patients With Chronic Obstructive Pulmonary Disease (COPD)

Pharmacodynamic and Pharmacokinetic Dose Ranging Study of Tiotropium Bromide Administered Via Inhalation Solution in Patients With Chronic Obstructive Pulmonary Disease (COPD).

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Key information

Conditions

Mild to Moderate Chronic Obstructive Pulmonary Disease (COPD)

Age range

40 year–85 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Glenmark Investigational Site 23, Andalusia, Alabama, United States

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

GSP304 (tiotropium bromide) Inhalation Solution

Drug

Once daily (QD) oral inhalation using a nebulizer

GSP304 Placebo Inhalation Solution

Drug

Once daily (QD) oral inhalation using a nebulizer

Spiriva® Respimat® inhalation spray

Drug

Once daily (QD) oral inhalation

Primary outcomes

  1. Relative Bioavailability of Tiotropium With GSP304 in Comparison to SPIRIVA RESPIMAT 5 μg Based on CmaxSS

    Time frame: 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.

    The PK endpoint in plasma to assess the relative bioavailability was peak concentrations of tiotropium during the dosing interval at steady-state (CmaxSS)

  2. Relative Bioavailability of Tiotropium With GSP 304 in Comparison to SPIRIVA RESPIMAT 5 μg Based on AUC0-tauSS

    Time frame: 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.

    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)

  3. Change From Baseline (Day 1) in Trough FEV1 at 24 Hours After the Last Dose of Treatment on Day 21 in Comparison to Placebo.

    Time frame: 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.

Secondary outcomes

  1. 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

    Time frame: Day 1

    Descriptive statistics for tiotropium urine PK parameter - Amount (Aetau) of tiotropium excreted in urine over the dosing interval on Day 1

  2. Amount (Aetau) of Tiotropium Excreted in Urine Over the Dosing Interval on Day 21

    Time frame: Day 21

    Descriptive statistics for tiotropium urine PK parameter - Amount (Aetau) of Tiotropium Excreted in Urine Over the Dosing Interval on Day 21

  3. Fraction of Dose (Fe) of Tiotropium Excreted in Urine Over the Dosing Interval on Day 1

    Time frame: 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

  4. Fraction of Dose (Fe) of Tiotropium Excreted in Urine Over the Dosing Interval on Day 21

    Time frame: 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

  5. Peak Concentrations During the Dosing Interval (Cmax) on Day 1

    Time frame: Day 1

    Descriptive statistics for tiotropium plasma PK parameters - (Cmax) on Day 1

  6. Area Under the Plasma Concentration-time Curve Over the Dosing Interval (AUC0-tau) on Day 1

    Time frame: 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

  7. Time of Peak Drug Concentration Over the Dosing Interval (Tmax) on Day 1

    Time frame: Day 1

    Descriptive statistics for tiotropium plasma PK parameter - Time of peak drug concentration over the dosing interval (tmax) on Day 1

  8. Time of Peak Drug Concentration Over the Dosing Interval (Tmax) on Day 21

    Time frame: Day 21

    Descriptive statistics for tiotropium plasma PK parameter - Time of peak drug concentration over the dosing interval (tmax) on Day 21

  9. Average Concentration During a Dosing Interval at Steady State (CavSS) on Day 21

    Time frame: Day 21

    Descriptive statistics for tiotropium plasma PK parameter - Average concentration during a dosing interval at steady state (CavSS) on day 21

  10. Accumulation Ratio Rac(Auc)

    Time frame: Day 21

    Descriptive statistics for tiotropium plasma PK parameter-Accumulation ratio Rac(auc). Rac(auc) was calculated as AUC0-tauSS/AUC0-tau.

  11. Accumulation Ratio Rac(Cmax)

    Time frame: Day 21

    Descriptive statistics for tiotropium plasma PK parameter-Accumulation ratio Rac(cmax). Rac(Cmax) was calculated as CmaxSS/Cmax.

  12. Change From Baseline in Peak FEV1 Within 12 Hours Post-dose on Day 1

    Time frame: 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).

    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.

  13. Change From Baseline in Peak FEV1 Within 12 Hours Post-dose on Day 21

    Time frame: 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).

    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.

  14. Change From Baseline in Forced Vital Capacity (FVC) on Day 1

    Time frame: 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).

    Least Square Mean change from baseline in forced vital capacity (FVC) to end of Day 1.

  15. Change From Baseline in Forced Vital Capacity (FVC) on Day 21

    Time frame: 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).

    Least Square Mean change from baseline in forced vital capacity (FVC) to end of Day 21

  16. Change From Baseline in Time-normalized Area Under the Curve for FEV1 Measured Over 12 Hours on Day 1

    Time frame: 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).

    Least Square Mean (SE) change from baseline in time-normalized area under the curve for FEV1 measured over 12 hours on Day 1.

  17. Change From Baseline in Time-normalized Area Under the Curve for FEV1 Measured Over 12 Hours on Day 21

    Time frame: 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).

    Least Square Mean (SE) change from baseline in time-normalized area under the curve for FEV1 Measured Over 12 Hours on Day 21.

Sponsors and collaborators

Lead sponsor

Glenmark Specialty S.A.

Industry

Registry information

Official study 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

Important dates

Study start
2017
Primary completion
2017
Study completion
2017
First posted
Apr 18, 2017
Registry last updated
Aug 1, 2019

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.