Evaluation of Tolerability and Pharmacokinetics of Roflumilast, 250μg and 500μg, as add-on to Standard COPD Treatment to Treat Severe COPD

NCT02165826 | Completed Phase 3 Results

• 3 other identifiers: RO-2455-302-RDU1111-1150-24772013-001788-21
• Study Type: interventional
• Target: 1,323
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this study is to evaluate discontinuation rates of roflumilast using an up-titration regimen for the first 4 weeks of treatment compared with continuous treatment of 500 μg one daily (OD) during the entire 12-week main period, and to evaluate if participants who do not tolerate roflumilast 500 μg OD have a drug exposure with 250 μg roflumilast OD similar to that observed in other participants with the 500 μg OD dose.

Conditions

Chronic Obstructive Pulmonary Disease (COPD)

Keywords

Drug therapy

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants Prematurely Discontinuing Study Treatment Due to Any Reason

  The primary endpoint is the percentage of participants prematurely discontinuing study treatment for any reason during the Main Period from Visit 1 (V1) to Last Visit (Vend). Discontinuation is defined as permanently stopping randomized treatment; participants who resume randomized treatment after an interval will not be counted as having discontinued. The analysis used discontinuations occurring during the Main Period, irrespective of whether a participant subsequently entered into the Down-Titration Period.

  Baseline to Week 12 (Main Period)

Secondary Outcomes (17)

• Percentage of Participants With Adverse Events of Interest

  Baseline to Week 12 (Main Period)

• Change From Baseline (V0DT) in Pre-bronchodilator Forced Expiratory Volume in First Second (FEV1) to Final Visit of the Down-Titration Period

  Baseline (V0DT) [assessment at end of main period] and Final Visit of Down-Titration Period (Up to Day 56)

• Percentage of Participants Prematurely Discontinuing Study Treatment Due to Any Reason During Down-Titration Period

  Baseline DT (Day 1 of Down-Titration Period) to Week 8 (Down-Titration Period)

• Change From Baseline in Pre-bronchodilator Forced Expiratory Volume in First Second (FEV1) During the Down-Titration Period

  Baseline DT (Day 1 of Down-Titration Period) to Days 14, 28 and 56 (Down-Titration Period)

• Change From Baseline in Pre-bronchodilator Forced Expiratory Volume in First Second (FEV1) During the Main Period

  Baseline (Day 1 of Main Period) to Days 15, 29, 57 and 84 (Main Period)

Study Arms (3)

Roflumilast 500 μg once daily

EXPERIMENTAL

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; Drug: Standard of Care COPD Treatment

Roflumilast 500 μg every other day

EXPERIMENTAL

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; Drug: Roflumilast Placebo; Drug: Standard of Care COPD Treatment

Roflumilast 250 μg once daily

EXPERIMENTAL

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; Drug: Standard of Care COPD Treatment

Interventions

Roflumilast DRUG

Roflumilast tablets

Also known as: Daxas, Daliresp, Libertek

Roflumilast 250 μg once daily; Roflumilast 500 μg every other day; Roflumilast 500 μg once daily

Roflumilast Placebo DRUG

Roflumilast placebo-matching tablets

Roflumilast 500 μg every other day

Standard of Care COPD Treatment DRUG

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.

Roflumilast 250 μg once daily; Roflumilast 500 μg every other day; Roflumilast 500 μg once daily

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• In the opinion of the investigator, the participant is capable of understanding and complying with protocol requirements.
• 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.
• 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).
• Shows a post-bronchodilator forced expiratory volume in 1 second (FEV1) of ≤50% of predicted.
• Shows an FEV1/forced vital capacity (FVC) ratio (post-bronchodilator) \<70%.
• Has at least one documented COPD exacerbation within one year prior to Screening (Visit V0).
• 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).
• 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
• Is male or female and aged 40 or older.
• 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.

You may not qualify if:

• Criteria affecting the read-out parameters of the study
• Has a COPD exacerbation ongoing at the Screening (Visit V0), or has a COPD exacerbation between V0 and V1.
• Has a lower respiratory tract infection not resolved 4 weeks prior to Screening (Visit V0).
• 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).
• Has a known α1-antitrypsin deficiency.
• Has taken roflumilast within 6 months of Screening (Visit V0).
• Criteria within ethical considerations in terms of general health
• Has clinically relevant abnormal laboratory values suggesting an undiagnosed disease requiring further clinical evaluation (as assessed by the investigator).
• Has a history of severe psychiatric or neurological disorders.
• Has a history of depression associated with suicidal ideation or behavior.
• Has congestive heart failure severity grade IV according to New York Heart Association (NYHA) Functional Classification.
• Has hemodynamically significant cardiac arrhythmias or heart valve deformations.
• Has computed tomography (CT) or chest x-ray findings indicating an acute pulmonary disease other than COPD (eg, tuberculosis, severe bronchiectasis, tumors).
• Has severe immunological diseases (eg, known human immune deficiency virus (HIV) infection, multiple sclerosis, lupus erythematosus, progressive multifocal leukoencephalopathy).
• Has liver impairment Child-Pugh B or C and/or active viral hepatitis.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (2)

Unknown Facility

Bardejov, Slovakia

Location

Unknown Facility

Spišská Nová Ves, Slovakia

Location

Related Publications (1)

• Facius A, Marostica E, Gardiner P, Watz H, Lahu G. Pharmacokinetic and Pharmacodynamic Modelling to Characterize the Tolerability of Alternative Up-Titration Regimens of Roflumilast in Patients with Chronic Obstructive Pulmonary Disease. Clin Pharmacokinet. 2018 Aug;57(8):1029-1038. doi: 10.1007/s40262-018-0671-4.

  PMID: 29797235 DERIVED

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

Roflumilast

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: AstraZeneca Clinical Study Information Center
• Organization: AstraZeneca

information.center@astrazeneca.com

1-877-240-9479

Study Officials

• AstraZeneca AstraZeneca

  AstraZeneca

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 2, 2014
• First Posted: June 18, 2014
• Study Start: May 1, 2014
• Primary Completion: September 1, 2015
• Study Completion: September 1, 2015
• Last Updated: April 20, 2017
• Results First Posted: March 14, 2017

Record last verified: 2017-03

Locations

SL (2)