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The effects of multiple doses of TD4208 for 7 days in COPD

Conditions
Chronic Obstructive Pulmonary Disease (COPD) - GOLD stage 2 or 3
MedDRA version: 14.1Level: LLTClassification code 10010952Term: COPDSystem Organ Class: 100000004855
MedDRA version: 14.1Level: LLTClassification code 10010953Term: COPD exacerbationSystem Organ Class: 100000004855
Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]
Registration Number
EUCTR2012-004949-32-GB
Lead Sponsor
Theravance, Inc.
Brief Summary

Not available

Detailed Description

Not available

Recruitment & Eligibility

Status
ot Recruiting
Sex
All
Target Recruitment
60
Inclusion Criteria

1. Subject is a male or female between the ages of 40 and 75 years (inclusive, at randomisation).
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® nebuliser.
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: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 20
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 10

Exclusion Criteria

1. Subject has had a COPD exacerbation or lung infection within 6 weeks before randomisation.
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 haematologic, 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 screening, including QTcB value >450 msec (males) or >470 msec (females); or shows 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

Study & Design

Study Type
Interventional clinical trial of medicinal product
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Secondary Outcome Measures
NameTimeMethod
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