Clinical trial NCT01704404: 7 Days of TD-4208 in Subjects With Chronic Obstructive Pulmonary Disease
Official title: A Phase 2 Study of the Pharmacodynamics, Safety and Tolerability, and Pharmacokinetics of Multiple Doses of TD-4208 for 7 Days in Subjects Diagnosed With Chronic Obstructive Pulmonary Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: COPD
Keywords: Long acting muscarinic antagonist
Chronic Bronchitis
Emphysema
Chronic Obstructive Pulmonary Disease
COPD
Lead sponsor: Viatris Inc.
Sponsor class: INDUSTRY
Collaborators: name: Theravance Biopharma
First posted: 2012-10-11
Enrollment: 62
Sex: ALL
Minimum age (years): 40
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: This study will characterize the dose response of TD-4208 after 7 days of dosing in subjects with Chronic Obstructive Pulmonary Disease (COPD).


Eligibility criteria: Inclusion Criteria:

1. Subject is a male or female between the ages of 40 and 75 years (inclusive, at randomization).
2. Subject:

   * Has an FEV1/FVC (forced expiratory volume in 1 second/forced vital capacity) \<0.7 at screening; and
   * Has a post-bronchodilator FEV1 at screening of between 30% and 80% (inclusive) of the predicted normal value.
3. 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.
4. 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.
5. Subject (or care giver) is able to properly prepare and administer study medication.
6. Subject is willing and able to give written informed consent to participate.

Exclusion Criteria:

1. Subject has had a COPD exacerbation or lung infection within 6 weeks before randomization.
2. 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.
3. Subject is taking daily maintenance inhaled/systemic corticosteroids (\>1000 μg of fluticasone propionate equivalent or ≥10 mg prednisone).
4. 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.
5. 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 (corrected QT interval) syndrome or has an abnormal clinically significant electrocardiogram (ECG) at screening, including QTcB (QT interval corrected for heart rate using Bazett's formula) value \>450 msec (males) or \>470 msec (females); or shows evidence of clinically significant rhythm abnormality.
6. Subject has a known hypersensitivity to TD-4208 or similar drug class.
7. Subject has a history of alcoholism or drug abuse within 2 years prior to screening.

Primary outcomes:
measure: Change From Baseline to Day 7 in Trough FEV1 (Forced Expiratory Volume in 1 Second)
timeFrame: From baseline to day 7
Secondary outcomes:
Other outcomes:
measure: Cmax
timeFrame: From baseline to day 7
measure: Tmax
timeFrame: From baseline to day 7
measure: Plasma Half-life
timeFrame: From baseline to day 7
Locations:
city: Wellington
country: New Zealand
facility: P3 Research Ltd
Study officials:
affiliation: Theravance Biopharma
name: Medical Monitor
role: STUDY_DIRECTOR
References:
citation: Lo A, Borin MT, Bourdet DL. Population Pharmacokinetics of Revefenacin in Patients with Chronic Obstructive Pulmonary Disease. Clin Pharmacokinet. 2021 Mar;60(3):391-401. doi: 10.1007/s40262-020-00938-3.
citation: Quinn D, Barnes CN, Yates W, Bourdet DL, Moran EJ, Potgieter P, Nicholls A, Haumann B, Singh D. Pharmacodynamics, pharmacokinetics and safety of revefenacin (TD-4208), a long-acting muscarinic antagonist, in patients with chronic obstructive pulmonary disease (COPD): Results of two randomized, double-blind, phase 2 studies. Pulm Pharmacol Ther. 2018 Feb;48:71-79. doi: 10.1016/j.pupt.2017.10.003. Epub 2017 Oct 4.