A Phase 2, Randomized, Double-Blind, Multiple-Dose, Five-Period, Incomplete-Block, Crossover Study to Examine the Pharmacodynamics, Safety and Tolerability, and Pharmacokinetics of Multiple Doses of TD-4208 for 7 Days in Subjects Diagnosed With Chronic Obstructive Pulmonary Disease
Effects of Multiple Doses of TD-4208 for 7 Days on Forced Expiratory Volume in one second (FEV1) in Subjects With Chronic Obstructive Pulmonary Disease (COPD)
Theravance Biopharma R & D, Inc.
60 participants
Dec 13, 2012
Interventional
Conditions
Summary
There are five (5) periods in the study. Study treatments are to be administered once daily for seven (7) days in each of the five (5) periods. All participants will receive seven (7) daily doses of placebo for one of the five (5) treatment periods. The duration of the study is up to 134 days: - participants will receive study medication for up to 35 days (28 days active drug and 7 days placebo) - the remaining 99 days consist of: the screening period; each washout period between the five (5) dosing periods (i.e., the period when participants are not taking study medication); and the safety follow-up visit.
Eligibility
Inclusion Criteria6
- Subject is a male or female between the ages of 40 and 75 years (inclusive, at randomization).
- Subject has an FEV1/FVC <0.7 at screening; and has a post-bronchodilator FEV1 at screening of between 30% and 80% (inclusive) of the predicted normal value.
- Subject demonstrates at screening at least a 120 mL increase in FEV1 within 1 hour of receiving 500 microgram of ipratropium bromide from a PARI LC Sprint 'Registered Trademark' Nebulizer.
- Females of non-childbearing potential. 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.
- Subject (or care giver) is able to properly prepare and administer study medication.
- Subject is willing and able to give written informed consent to participate.
Exclusion Criteria7
- Subject has had a COPD exacerbation or lung infection within 6 weeks before randomization.
- 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.
- Subject is taking daily maintenance inhaled/systemic corticosteroids (>1000 microgram of fluticasone propionate equivalent or > or =10 mg prednisone).
- 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.
- 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.
- Subject has a known hypersensitivity to TD-4208 or similar drug class.
- Subject has a history of alcoholism or drug abuse within 2 years prior to screening.
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Interventions
This study will evaluate the bronchodilatory effect, tolerability, and pharmacokinetics of multiple doses of TD-4208 for 7 days in subjects with a clinical diagnosis of COPD. Each subject will receive four of six possible doses of TD-4208 (22 micro g, 44 micro g, 88 micro g, 175 micro g, 350 micro g, or 700 micro g) and placebo once per day via a nebulizer over five 7-day study periods in an incomplete crossover study design. Each period of treatment will be separated a washout period of 10 days up to a maximum of 16 days dependent on logistic considerations for the next dosing period. A final safety follow-up assessment will be completed for all subjects 7 to 14 days after their last study treatment dose.
Locations(2)
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ACTRN12612001235897