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COPDPhase 1/2NCT01785433

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

A Phase 1/2 study testing Tiotropium HFA BAI 4.5 mcg, Tiotropium HFA BAI 9.0 mcg and SPIRIVA® HandiHaler® 18 mcg/day in people with COPD, run by Teva Branded Pharmaceutical Products R&D, Inc. at 5 sites in Germany.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 40 to 80 years
Conditions the study is for
COPD
What is being tested?
Tiotropium HFA BAI 4.5 mcg, Tiotropium HFA BAI 9.0 mcg and SPIRIVA® HandiHaler® 18 mcg/day
Could I receive a placebo?
No, everyone receives an active treatment
How many people
36 participants
Where
5 sitesGermany
Study dates
Jan 2013to Aug 2013
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 40 to 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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)
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  • 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
  • Current or ex-smoker with ≥10 pack-year smoking history
  • Subject is free of any concomitant conditions or treatment that could interfere with study conduct, influence the interpretation of study observations/results, or put the subject at increased risk during the study
  • Able to perform technically acceptable and reproducible spirometry per study guidelines as defined in the protocol and study procedures manual.
  • Able to demonstrate the proper inhalation techniques required for correct use of all delivery devices required in the study
  • Capable of understanding the requirements, risks, and benefits of study participation, and, as judged by the investigator, capable of giving informed consent and being compliant with all study requirements

Who cannot join

  • 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.
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  • 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
  • Subjects who have started or stopped an exercise rehabilitation program within 4 weeks of the Screening Visit (SV)
  • Known or suspected hypersensitivity or idiosyncratic reaction to tiotropium, or to any ingredients used in the study medication formulations
  • Severe allergy to milk protein
  • Significant adverse drug reactions, including allergy or hypersensitivity reactions, to atropine or any anticholinergic substance related pharmacologically to atropine (e.g., ipratropium or oxitropium)
  • Use of any prohibited concomitant medications within the prescribed (per protocol) withdrawal periods prior to the Screening Visit
  • Treatment with orally administered (excluding orally inhaled) β-adrenergics (i.e., oral salbutamol)
  • Treatment with β-adrenergic receptor antagonists (e.g. non-selective β-receptor blocking agents like β-blocking anti-hypertensive products) administered by any route. The single exception is that cardioselective β1-adrenergic receptor antagonists (e.g. atenolol, metoprolol, bisoprolol) are permitted provided that subjects have been on a stable dose for at least 1 week prior to the screening visit and subjects are expected to be able to maintain the same dose throughout the study.
  • Treatment with drugs commonly recognized to prolong the QTc interval (e.g., quinolones, amiodarone, disopyramide, quinidine, sotalol, chlorpromazine, haloperidol, ketoconazole, terfenadine, cisapride and terodiline)
  • Treatment with any known cytochrome P450 (CYP) 2D6 or cytochrome P450 (CYP) 3A4 inhibitors (e.g., quinidine, ketoconazole and gestodene) within 30 days prior to the Screening Visit (SV)
  • Initiation or change in dose of inhaled corticosteroids within the last 6 weeks prior to the Screening Visit (SV), and /or not expected to maintain a stable dose of inhaled corticosteroids during the course of the study.
  • Initiation or change in dose of oral or systemic corticosteroids within the last 6 weeks prior to the Screening Visit (SV) , unable to maintain a stable dose of oral or systemic corticosteroids during the course of the study, or a dose of oral or systemic corticosteroids in excess of the equivalent of 10 mg of prednisone per day. [Note that oral steroid bursts completed 6 weeks or more prior to screening are acceptable.]
  • Exposure to any investigational drug within 30 days or six half-lives (whichever is greater) prior to the Screening Visit (SV)
  • Plans to donate or has donated plasma or blood within 1 month prior to the Screening Visit (SV). This does not include small blood volumes taken for diagnostic purposes. Plans to donate plasma or blood within 3 months following study completion
  • Has a history of alcohol and/or substance abuse within the past 5 years
  • Vulnerable subjects (e.g., persons kept in detention)
  • The subject is an employee of the study site or has an immediate family member or household member involved with the conduct of the study (including participation in the study).

Trial locations and contacts

5 sites in 1 country.

5 sites in 1 country

Germany5 sites

  • Teva Investigational Site 32170

    Berlin

  • Teva Investigational Site 32169

    Gauting

  • Teva Investigational Site 32171

    Großhansdorf

  • Teva Investigational Site 32167

    Mannheim

  • Teva Investigational Site 32168

    Wiesbaden

Other trials in Germany

About this study

Official title: A Randomized, Open-Label, Repeat Dosing, Four-Period Crossover Study to Compare the Pharmacokinetics, Efficacy and Safety of Tiotropium Bromide Delivered Via Breath Actuated Inhaler (BAI), SPIRIVA® HandiHaler® and Respimat® Soft Mist™ Inhaler (SMI) in Subjects With COPD

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.

Read the detailed description

This multicenter study consists of a Screening Visit (3 to 14 days prior to randomization); 4 multiple-dose (7-day) Treatment Periods, each consisting of a 2-night/3-day inpatient stay (Day 6 to Day 8); and a Final Visit. A washout period of at least 21 days will occur between each Treatment Period. The Final/ Early Termination Visit will occur 6-8 days following the last Treatment Period or upon early discharge from the study.

Conditions
COPD
Being tested
Tiotropium HFA BAI 4.5 mcg, Tiotropium HFA BAI 9.0 mcg, SPIRIVA® HandiHaler® 18 mcg/day, Spiriva® Respimat® 5 mcg/day
Keywords
COPD, pharmacokinetics, tiotropium
Medical subject headings
Pulmonary Disease, Chronic Obstructive

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Tiotropium HFA BAI 4.5 mcgDrug

  • Tiotropium HFA BAI 9.0 mcgDrug

  • SPIRIVA® HandiHaler® 18 mcg/dayDrug

  • Spiriva® Respimat® 5 mcg/dayDrug

Study groups in NCT01785433
Study groupRoleWhat they receive
Treatment ABCDExperimentalThe 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
Receives: 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 BDACExperimentalThe 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
Receives: 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 CADBExperimentalThe 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
Receives: 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 DCBAExperimentalThe 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
Receives: 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

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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®

    Measured: From time 0 to 24 hours on Day 7

  2. 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®

    Measured: From time 0 to 24 hours on Day 7

Secondary outcomes (3)

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

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

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

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

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

    Measured: From time 0 to 24 hours on Day 7

  3. Occurrence of Adverse Events

    The adverse event frequency, intensity, severity and relationship to the study drug will be recorded.

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Feb 2013 (estimated)
  2. Study startJan 2013
  3. Primary completionJul 2013
  4. Study completionAug 2013

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Crossover
Masking
None (open label)
Enrolment
36 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01785433
Sponsor's protocol ID
TBB-COPD-201
Status last verified
Aug 2014
First submitted
4 Feb 2013
Last updated
11 Aug 2014
Results posted
No
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Tiotropium HFA BAI 4.5 mcg, Tiotropium HFA BAI 9.0 mcg and SPIRIVA® HandiHaler® 18 mcg/day in people with COPD, run by Teva Branded Pharmaceutical Products R&D, Inc. at 5 sites in Germany.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 20 inclusion and 31 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 11 Aug 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Area under the plasma concentration-time curve (AUC0-24h) (time frame: From time 0 to 24 hours on Day 7). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01785433.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Aug 2014.

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