Evaluation of tolerability and pharmacokinetics of roflumilast, 250μg and 500μg, as add-on to standard COPD treatment to treat severe COPD - OPTIMIZE

Study identifier:RO-2455-302-RD

ClinicalTrials.gov identifier:NCT02165826

EudraCT identifier:2013-001788-21

CTIS identifier:N/A

Study Complete

Official Title

A multicenter, randomized, double-blind phase 3 study to evaluate tolerability and pharmacokinetics of 500 μg roflumilast once daily with an up-titration regimen in COPD, including an open-label down-titration period evaluating tolerability and pharmacokinetics of 250 μg roflumilast once daily in subjects not tolerating 500 μg roflumilast once-daily

Medical condition

Chronic obstructive pulmonary disease (COPD)

Phase

Phase 3

Healthy volunteers

Study drug

Roflumilast, Roflumilast, Roflumilast, Roflumilast Placebo, Standard of Care COPD Treatment, Standard of Care COPD Treatment, Standard of Care COPD Treatment

Sex

All

Actual enrollment

1323

Study type

Interventional

Age

40 Years +

Date

Study Start Date: 01 May 2014

Primary Completion Date: 01 Sept 2015

Study Completion Date: 01 Sept 2015

Study design

Allocation: Randomized
Endpoint Classification: Safety
Intervention Model: Parallel Assignment
Masking: Double Blind
Primary Purpose: Treatment

Verification:

Verified 01 Mar 2017 by AstraZeneca

Collaborators

Inclusion and exclusion criteria

Inclusion Criteria

1. In the opinion of the investigator, the participant is capable of understanding and complying with protocol requirements.
2. The participant or, when applicable, the participant’s legally acceptable representative signs and dates a written, informed consent form and any required privacy authorization prior to the initiation of any study procedures.
3. Has a history of chronic obstructive pulmonary disease (COPD) (according to Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2013) for at least 12 months prior to Screening (Visit V0) associated with chronic productive cough for 3 months in each of the 2 years prior to Screening (Visit V0, with other causes of productive cough excluded).
4. Shows a post-bronchodilator forced expiratory volume in 1 second (FEV1) of ≤50% of predicted.
5. Shows an FEV1/forced vital capacity (FVC) ratio (post-bronchodilator) <70%.
6. Has at least one documented COPD exacerbation within one year prior to Screening (Visit V0).
7. Is on standard of care COPD maintenance treatment including Long Acting β2-Agonist (LABAs), long-acting anticholinergics, or any combination thereof taken on a constant daily dose within 12 weeks prior to Screening (Visit V0).
8. Must be a former smoker (defined as smoking cessation at least one year ago) or current smoker both with a smoking history of at least 10 pack years.11
9. Is male or female and aged 40 or older.
10. A female participant of childbearing potential who is sexually active with a nonsterilized male partner agrees to use routinely adequate contraception from signing of informed consent throughout the duration of the study.

Exclusion Criteria

Criteria affecting the read-out parameters of the study
1. Has a COPD exacerbation ongoing at the Screening (Visit V0), or has a COPD exacerbation between V0 and V1.
2. Has a lower respiratory tract infection not resolved 4 weeks prior to Screening (Visit V0).
3. Has a diagnosis of asthma and/or other relevant lung disease (eg, history of primary bronchiectases, cystic fibrosis, bronchiolitis, lung resection, lung cancer, interstitial lung disease [eg, fibrosis, silicosis, sarcoidosis], or active tuberculosis).
4. Has a known α1-antitrypsin deficiency.
5. Has taken roflumilast within 6 months of Screening (Visit V0).
Criteria within ethical considerations in terms of general health
6. Has clinically relevant abnormal laboratory values suggesting an undiagnosed disease requiring further clinical evaluation (as assessed by the investigator).
7. Has a history of severe psychiatric or neurological disorders.
8. Has a history of depression associated with suicidal ideation or behavior.
9. Has congestive heart failure severity grade IV according to New York Heart Association (NYHA) Functional Classification.
10. Has hemodynamically significant cardiac arrhythmias or heart valve deformations.
11. Has computed tomography (CT) or chest x-ray findings indicating an acute pulmonary disease other than COPD (eg, tuberculosis, severe bronchiectasis, tumors).
12. Has severe immunological diseases (eg, known human immune deficiency virus (HIV) infection, multiple sclerosis, lupus erythematosus, progressive multifocal leukoencephalopathy).
13. Has liver impairment Child-Pugh B or C and/or active viral hepatitis.
14. Has severe acute infectious diseases (eg, tuberculosis, or acute hepatitis).
15. Has a history of malignant disease (except basal cell carcinoma) within 5 years before Screening (Visit V0).
16. Has a history of drug abuse (defined as any illicit drug use) or a history of alcohol abuse within one year before Screening (Visit V0).
17. Has a history of hypersensitivity or allergies to roflumilast or rescue medication or ingredients thereof, or any other contraindication for the use thereof.
18. If female, the participant is pregnant or lactating or intending to become pregnant before, during, or within 12 weeks after participating in this study; or intending to donate ova during such time period.
19. Intends to donate blood, organs, or bone marrow during the course of the study.
20. Has received any investigational compound within 30 days prior to Screening (Visit V0), is currently participating in another interventional clinical study, or has been previously enrolled in this study.
21. Is suspected to be unable or unwilling to comply with study procedures (eg, language problems, psychological disorders, number and timing of visits at the center).
22. Suffers from any concomitant disease that might interfere with study procedures or evaluations.
23. Is required to take excluded medications.
24. Is an immediate family member, study center employee, or is in a dependent relationship with a study site employee who is involved in conduct of this study (eg, spouse, parent, child, sibling), or may consent under duress.

No locations available

Arms	Assigned Interventions
Experimental: Roflumilast 500 μg once daily Roflumilast 500 μg tablets, orally, once daily for 12 weeks. Any participants not tolerating study treatment will be prematurely discontinued and will receive roflumilast 250 μg, tablets, orally, once daily for 8 weeks.	Drug: Roflumilast Roflumilast tablets Other Name: Daxas, Daliresp, Libertek Drug: Standard of Care COPD Treatment The participant is on standard of care COPD maintenance treatment including LABAs, long-acting anticholinergics, or any combination thereof taken on a constant daily dose within 12 weeks prior to Screening (Visit V0) Examples of LABA containing products are: Formoterol, Salmeterol, Indacaterol, Formoterol/Budesonide, Salmeterol/Fluticasone, Treatment including lon-acting anticholinergics: Tiotropium, Aclidinium.
Experimental: Roflumilast 500 μg every other day Roflumilast 500 μg, tablets, orally, every other day, and roflumilast placebo-matching tablets, orally, every other day on non-treatment days, for 4 weeks, followed by roflumilast 500 μg, tablets, orally, once daily, for 8 weeks. Any participants not tolerating study treatment will be prematurely discontinued and will receive roflumilast 250 μg, tablets, orally, once daily for 8 weeks.	Drug: Roflumilast Roflumilast tablets Other Name: Daxas, Daliresp, Libertek Drug: Roflumilast Placebo Roflumilast placebo-matching tablets Drug: Standard of Care COPD Treatment The participant is on standard of care COPD maintenance treatment including LABAs, long-acting anticholinergics, or any combination thereof taken on a constant daily dose within 12 weeks prior to Screening (Visit V0) Examples of LABA containing products are: Formoterol, Salmeterol, Indacaterol, Formoterol/Budesonide, Salmeterol/Fluticasone, Treatment including lon-acting anticholinergics: Tiotropium, Aclidinium.
Experimental: Roflumilast 250 μg once daily Roflumilast 250 μg, tablets, orally, once daily for 4 weeks, followed by roflumilast 500 μg, tablets, orally, once daily, for 8 weeks. Any participants not tolerating study treatment will be prematurely discontinued and will receive roflumilast 250 μg, tablets, orally, once daily for 8 weeks.	Drug: Roflumilast Roflumilast tablets Other Name: Daxas, Daliresp, Libertek Drug: Standard of Care COPD Treatment The participant is on standard of care COPD maintenance treatment including LABAs, long-acting anticholinergics, or any combination thereof taken on a constant daily dose within 12 weeks prior to Screening (Visit V0) Examples of LABA containing products are: Formoterol, Salmeterol, Indacaterol, Formoterol/Budesonide, Salmeterol/Fluticasone, Treatment including lon-acting anticholinergics: Tiotropium, Aclidinium.

Contacts

Contact

AstraZeneca Clinical Study Information Center

1-877-240-9479

[email protected]

Investigators

Principal Investigator

AstraZeneca AstraZeneca

AstraZeneca