To Compare the Pharmacokinetics of Tiotropium in Subjects With Chronic Obstructive Pulmonary Disease (COPD)

NCT01785433 | Completed Phase 1

• 1 other identifier: TBB-COPD-201
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 5

Brief Summary

The primary objective of this study is to assess and compare the pharmacokinetics (PK) of Tiotropium delivered via Breath Actuated Inhaler (BAI) (4.5 mcg/day or 9.0 mcg/day), SPIRIVA®, HandiHaler®, (18 mcg/day) and Respimat® Soft Mist™ Inhaler (SMI) (5.0 mcg/day) following repeat dosing for 7 days in subjects with COPD.

Conditions

COPD

Keywords

COPD, pharmacokinetics, tiotropium

Outcome Measures

Primary Outcomes (2)

• Area under the plasma concentration-time curve (AUC0-24h)

  To evaluate the PK of Tiotropium Hydrofluoroalkane (HFA) Breath Actuated Inhaler (BAI) (4.5 mcg/day and 9 mcg/day) to SPIRIVA® HandiHaler® and Spiriva® Respimat®

  From time 0 to 24 hours on Day 7

• Maximum observed plasma concentration (Cmax)

  To evaluate the PK of Tiotropium HFA BAI (4.5 mcg/day and 9 mcg/day) to SPIRIVA® HandiHaler® and Spiriva® Respimat®

  From time 0 to 24 hours on Day 7

Secondary Outcomes (3)

• Area under the plasma concentration-time curve (AUC 0-t)

  From time 0 to the time of the last quantifiable concentration as measured up to 24 hrs on Day 7

• Time at which the maximum plasma concentration was observed (tmax)

  From time 0 to 24 hours on Day 7

• Occurrence of Adverse Events

  From signing of the Informed Consent Form until the final visit (approximately 6 to 8 days following the last treatment period)

Study Arms (4)

Treatment ABCD

EXPERIMENTAL

The following treatments are to be studied in a 4-period, crossover design with once daily (QD) dosing for 7 days and at least 21 day washout period between treatments: Treatment A: Tiotropium HFA BAI 4.5 mcg/day Treatment B: Tiotropium HFA BAI 9.0 mcg/day Treatment C: SPIRIVA® HandiHaler® 18 mcg/day Treatment D: Spiriva® Respimat® 5 mcg/day

Drug: Tiotropium HFA BAI 4.5 mcg; Drug: Tiotropium HFA BAI 9.0 mcg; Drug: SPIRIVA® HandiHaler® 18 mcg/day; Drug: Spiriva® Respimat® 5 mcg/day

Treatment BDAC

EXPERIMENTAL

The following treatments are to be studied in a 4-period, crossover design with once daily (QD) dosing for 7 days and at least 21 day washout period between treatments: Treatment B: Tiotropium HFA BAI 9.0 mcg/day Treatment D: Spiriva® Respimat® 5 mcg/day Treatment A: Tiotropium HFA BAI 4.5 mcg/day Treatment C: SPIRIVA® HandiHaler® 18 mcg/day

Drug: Tiotropium HFA BAI 4.5 mcg; Drug: Tiotropium HFA BAI 9.0 mcg; Drug: SPIRIVA® HandiHaler® 18 mcg/day; Drug: Spiriva® Respimat® 5 mcg/day

Treatment CADB

EXPERIMENTAL

The following treatments are to be studied in a 4-period, crossover design with once daily (QD) dosing for 7 days and at least 21 day washout period between treatments: Treatment C: SPIRIVA® HandiHaler® 18 mcg/day Treatment A: Tiotropium HFA BAI 4.5 mcg/day Treatment D: Spiriva® Respimat® 5 mcg/day Treatment B: Tiotropium HFA BAI 9.0 mcg/day

Drug: Tiotropium HFA BAI 4.5 mcg; Drug: Tiotropium HFA BAI 9.0 mcg; Drug: SPIRIVA® HandiHaler® 18 mcg/day; Drug: Spiriva® Respimat® 5 mcg/day

Treatment DCBA

EXPERIMENTAL

The following treatments are to be studied in a 4-period, crossover design with once daily (QD) dosing for 7 days and at least 21 day washout period between treatments: Treatment D: Spiriva® Respimat® 5 mcg/day Treatment C: SPIRIVA® HandiHaler® 18 mcg/day Treatment B: Tiotropium HFA BAI 9.0 mcg/day Treatment A: Tiotropium HFA BAI 4.5 mcg/day

Drug: Tiotropium HFA BAI 4.5 mcg; Drug: Tiotropium HFA BAI 9.0 mcg; Drug: SPIRIVA® HandiHaler® 18 mcg/day; Drug: Spiriva® Respimat® 5 mcg/day

Interventions

Tiotropium HFA BAI 4.5 mcg DRUG

Treatment ABCD; Treatment BDAC; Treatment CADB; Treatment DCBA

Tiotropium HFA BAI 9.0 mcg DRUG

Treatment ABCD; Treatment BDAC; Treatment CADB; Treatment DCBA

SPIRIVA® HandiHaler® 18 mcg/day DRUG

Treatment ABCD; Treatment BDAC; Treatment CADB; Treatment DCBA

Spiriva® Respimat® 5 mcg/day DRUG

Treatment ABCD; Treatment BDAC; Treatment CADB; Treatment DCBA

Eligibility Criteria

• Age: 40 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent signed and dated by the subject before conducting any study related procedure
• Male or female subjects 40 -80 years of age, as of the Screening Visit
• Diagnosis of COPD as defined by the GOLD (Global Initiative for Chronic Obstructive Lung Disease) Guidelines
• A pre-bronchodilator Peak Inspiratory Flow (PIF) rate≥ 30 L/ min as measured with the In-Check™ DIAL training device.
• A measured post-bronchodilator (ipratropium bromide) forced expiratory volume in one second (FEV1) \>30% and \<80% of predicted normal for height, age and gender at the Screening Visit (SV). Third National Health and Nutrition Examination Survey 1988-1994 (NHANES III) predicted values will be used and adjustments to predicted values will be made for African-American subjects.
• A measured post-bronchodilator (ipratropium bromide) FEV1/Forced Vital Capacity (FVC) \<0.70 at the Screening Visit (SV)
• If female, is currently not pregnant, breast feeding, or attempting to become pregnant (for 4 weeks before the Screening Visit (SV) and throughout the duration of the study), and is of
• Non-childbearing potential, defined as:
• ≥1 year post-menopausal or
• Surgically sterile (tubal ligation, bilateral oophorectomy, salpingectomy, or hysterectomy) or is of
• Childbearing potential, has a negative serum pregnancy test, and is willing to commit to using a consistent and acceptable method of birth control as defined below for the duration of the study:
• Systemic contraception used for ≥1 month prior to screening, including birth control pills, transdermal patch, vaginal ring, implants, or injectables or
• Double barrier methods (condoms, cervical cap, diaphragm, and vaginal contraceptive film with spermicide) or
• Intrauterine device (IUD) with a low failure rate defined as \<1% per year (use of copper IUDs are excluded) or is of
• Childbearing potential and not sexually active, has a negative serum pregnancy test, and is willing to commit to using a consistent and acceptable method of birth control as defined above for the duration of the study, in the event the subject becomes sexually active

You may not qualify if:

• Pregnancy, nursing, or plans to become pregnant or donate gametes (ova or sperm) for in vitro fertilization during the study period or for 30 days following the subject's last study related visit (for eligible subjects only, if applicable).
• History or current evidence (as determined by medical history, physical examination, clinical laboratory assessments and ECG) of a clinically significant or uncontrolled disease including, but not limited to: cardiovascular (e.g., uncontrolled hypertension, congestive heart failure, known aortic aneurysm, clinically significant cardiac arrhythmia or coronary heart disease), hepatic, renal, haematological, neuropsychological, endocrine (e.g., uncontrolled diabetes mellitus, uncontrolled thyroid disorder, Addison's disease, Cushing's syndrome), gastrointestinal (e.g., poorly controlled peptic ulcer, gastroesophageal reflux disease) or pulmonary (other than COPD such as asthma, sarcoidosis, non-cystic fibrosis (CF) bronchiectasis, cystic fibrosis, bronchopulmonary dysplasia or a diagnosis of alpha 1-antitrypsin deficiency). Significant is defined as any disease that, in the opinion of the investigator, would put the safety of the subject at risk through participation, or which could affect the endpoint analysis if the disease/condition exacerbated during the study.
• History of and/or current diagnosis of asthma
• History of a life-threatening COPD exacerbation - defined for this protocol as a COPD episode that required intubation and/or was associated with hypercapnia, respiratory arrest or hypoxic seizures
• Thoracotomy with pulmonary resection
• Current congestive heart failure, history or current evidence of myocardial infarction (within 3 yrs of the Screening Visit \[SV\]), or history or current evidence of ischemic heart disease, including a diagnosis on screening ECG.
• History or current evidence of clinically significant cardiac arrhythmia, including a diagnosis on screening ECG.
• Presence of angle-closure glaucoma
• History of malignancy (excluding basal cell carcinoma) within the past 5 years, regardless of the clinical significance or current stability of the disease
• Known history or any current evidence of renal impairment or urinary retention (e.g., bladder outlet obstruction). This includes abnormal renal function test results at screening.
• Presence of symptomatic prostatic hyperplasia
• History of silent infections, including positive tests for human immunodeficiency virus 1, human immunodeficiency virus 2, Hepatitis B, Hepatitis C, or tuberculosis.
• Occurrence of any upper or lower respiratory infection, including but not limited to the common cold and flu, sinusitis,tonsillitis, pneumonia, bronchitis, or an ear infection (including otitis media and externa) which is not resolved by 14 days prior to randomization
• Occurrence of a COPD exacerbation which is not resolved by 14 days prior to randomization i. Note: An exacerbation of COPD is defined as any worsening of the subject's baseline COPD symptoms requiring any treatment other than rescue albuterol/salbutamol/ipratropium or the subject's regular maintenance treatment. This includes requiring the use of systemic corticosteroids and/or emergency room visit or hospitalization, a change in subject's regular, or the addition of other medications used to treat COPD symptoms.
• Subjects who require oxygen therapy and in the investigator's opinion, will be unable to abstain from the use of oxygen therapy during testing

Sponsors & Collaborators

• Teva Branded Pharmaceutical Products R&D, Inc.: lead

Study Sites (5)

Teva Investigational Site 32170

Berlin, Germany

Location

Teva Investigational Site 32169

Gauting, Germany

Location

Teva Investigational Site 32171

Großhansdorf, Germany

Location

Teva Investigational Site 32167

Mannheim, Germany

Location

Teva Investigational Site 32168

Wiesbaden, Germany

Location

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 4, 2013
• First Posted: February 7, 2013
• Study Start: January 1, 2013
• Primary Completion: July 1, 2013
• Study Completion: August 1, 2013
• Last Updated: August 11, 2014

Record last verified: 2014-08

Locations

DE (5)