Study to Examine the Efficacy, Safety and Tolerability, and Pharmacokinetics of Multiple Doses of TD-4208 for 7 Days in Subjects Diagnosed With Chronic Obstructive Pulmonary Disease
- Conditions
- Chronic obstructive pulmonary disease (COPD)MedDRA version: 15.1Level: LLTClassification code 10010952Term: COPDSystem Organ Class: 100000004855Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]
- Registration Number
- EUCTR2012-004949-32-DE
- Lead Sponsor
- Theravance, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Not Recruiting
- Sex
- All
- Target Recruitment
- 62
1. Subject is a male or female between the ages of 40 and 75 years (inclusive, at randomization).
2. Subject has a current or past smoking history >10 pack-years.
3. Subject:
• Is capable of performing reproducible spirometry maneuvers as described by current ATS Guidelines;
• Has an FEV1/FVC <0.7 at screening; and
• Has an FEV1 at screening post-ipratropium of between 30% and 80% (inclusive) of the predicted normal value after withholding short acting bronchodilators for at least 6 hours and long acting bronchodilators for at least 24 hours.
4. Subject demonstrates at screening at least a 120 mL increase in FEV1 within 1 hour of receiving 500 µg of ipratropium bromide from a PARI LC Sprint® nebulizer.
5. Women who are of non-childbearing potential. Women are considered to not be of childbearing potential if they have had a hysterectomy or tubal ligation (documentation for either must be provided before enrollment) or are at least 2 years postmenopausal.
All male subjects must agree to use a highly effective method of birth control with partners of childbearing potential during the study and for 1 month after completion of study dosing.
6. Subject (or care giver) is able to properly prepare and administer study medication based on a hands-on demonstration in the presence of experienced site staff, at the investigator’s discretion.
7. Subject is willing and able to give written informed consent to participate.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 60
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 60
1. Subject has had a COPD exacerbation or lung infection within 6 weeks before randomization.
2. Subject has a history of cor pulmonale or has any other significant respiratory disease, other than COPD, and/or requires daily long-term oxygen therapy.
3. Subject has had an initiation of treatment, or a change in dose, of an inhaled or oral corticosteroid, or long-acting beta2 agonist (LABA), or long-acting muscarinic antagonist (LAMA) within 4 weeks before the qualifying ipratropium bromide response test.
4. Subject is taking daily maintenance inhaled/systemic corticosteroids (>1000 µg of fluticasone propionate equivalent or =10 mg prednisone).
5. Subject has taken any of the following prior to the first dose or is not willing to abstain from their use for the designated times:
• Salbutamol or similar short-acting beta2 agonists (SABAs) <12 hours before the first and seventh dose administered in each Period , however salbutamol or albuterol will be provided for rescue/maintenance;
• Long-acting QD beta2 agonists (LABA) e.g., indacaterol <5 days before the first dose administered in Period 1 through Period 5;
• Ipratropium bromide <24 hours before the first dose administered in each period (Day 1) through the end of each period (morning of Day 8);
• Long-acting muscarinic antagonists (LAMA), e.g., tiotropium (Spiriva®, Handihaler or Respimat, glycopyrronium bromide, other newly approved LAMAs) <5 days before the first dose administered in Period 1 through Period 5;
• Long-acting, twice-daily bronchodilating products (e.g., fluticasone propionate/salmeterol combination product (Advair®), budesonide/formoterol fumarate dihydrate combination product (Symbicort®), salmeterol, formoterol fumarate, arformoterol tartrate, aclidinium bromide, etc.) <48 hours before the first
dose administered in Period 1 through Period 5; and/or
• Oral leukotriene antagonists, other oral bronchodilators (roflumilast (Daxas®)), or theophylline <48 hours before the first dose administered in Period 1 through Period 5;.
6. Subject is taking other antimuscarinic medications (e.g., atropine, cyclopentolate, hyoscine, Toviaz® [fesoterodine fumarate], or Ditropan, Lyrinel XL [oxybutynin], etc.),
7. Subject has symptomatic prostatic hypertrophy or bladder neck obstruction.
8. Subject has a history of narrow angle glaucoma.
9. Subject has an uncontrolled hematologic, immunologic, renal, neurologic, hepatic, endocrine, or other disease or condition based on information gathered from the medical history, physical examination, or laboratory findings that might place the subject at
undue risk or potentially compromise the results or interpretation of the study.
10. Subject has a history of significant cerebrovascular disease, coronary artery disease, or cardiac arrhythmias. Subject has a history (or family history) of congenital prolonged QTc syndrome or has an abnormal clinically significant electrocardiogram (ECG) at
evidence of clinically significant rhythm abnormality.
11. Subject has a history of active cancer (excludes basal cell or cancer in remission for more than 5 years).
12. Subject has a known hypersensitivity to TD-4208 or similar drug class.
13. Subject has a history of alcoholism or drug abuse within 2 years prior to screening.
14. Subject has participated in another investigational drug study where they received an investigational drug within 30 days before the screening visit.
15. Subject has a potential for
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To characterize the dose response curve of TD-4208 after 7 days of dosing in subjects with COPD with the intent to identify an effective dose, a minimal-effect dose, and a no-effect dose, measured by spirometry (forced expiratory volume in 1 second [FEV1]);Secondary Objective: • To evaluate the safety and tolerability profile of nebulized TD-4208 administered once per day for 7 days<br><br>• To evaluate the steady-state pharmacokinetics of TD-4208 and its active metabolite in male and female subjects with COPD;Primary end point(s): Primary (pharmacodynamic) endpoint:<br>Trough FEV1 after the seventh dose of each treatment period (Trough is the mean of the 23- and 24-hour postdose FEV1 time points.);Timepoint(s) of evaluation of this end point: Day 8 (23h and 24h after dose of Day 7) of each of five study periods
- Secondary Outcome Measures
Name Time Method