A Prospective, Randomized, Open-label, Investigator-initiated Study to Evaluate the Short-term and Long-term Efficacy and Safety of Deflazacort Tablets, Prednisolone Tablets and Methylprednisolone Tablets in Patients with COPD

ChronicObstructive Pulmonary Disease (COPD) is a common, lung disorder characterizedby progressive, poorly reversible airflow limitation often with systemicmanifestations, in response to tobacco smoke and/or other harmful inhalationalexposures.†COPD affects more than 400 million people worldwide. According tothe 12-site Burden of Obstructive Lung Disease study, the average prevalence ofCOPD is 10.1%, with wide variations. The estimated burden of COPD in India isabout 15 million cases (males and females contributing to 9.02 and 5.75million, respectively). These figures may however underestimate the true burdensince questionnaire based prevalence rates tend to underestimate the truespirometry-based prevalence of COPD. Globally, COPD is the ninth leading causeof loss of disability adjusted life years (DALYs) according to the baselineprojections made in the Global Burden of Disease Study. In India, chronicrespiratory diseases account for 3% of DALYs, and COPD is the major cause amongchronic respiratory disease. COPD also accounts for more than 3 million deathsper year globally making it the third leading cause of death worldwide. InIndia, COPD causes about 500,000 deaths per year.

Rational of Study

Amongstthe available corticosteroids, prednisolone and methylprednisolone are usedwidely for managing inflammation in COPD patients. Oral administration of thesedrugs has resulted in improvement in lung functions and significant reductionof inflammatory cytokines. Deflazacort which was introduced in late 60s is alsobeing considered now because of its better safety profile with equivalentpotency. In contrast to Prednisolone and Methylprednisolone, Deflazacort do notdeteriorate the glycemic and lipid profile in the patients. In a study,Deflazacort treatment also prevented the excessive bone loss and fataccumulation compared to prednisolone and methyl prednisolone therapy in kidneytransplant patients. The short term efficacy (1-2 weeks) and safety ofprednisolone, methylprednisolone and Deflazacort in COPD patients is very wellestablished through several clinical trials but there is not enough data for thesedrugs in long term efficacy and safety (6-8 weeks). These drugs have been usedsafely for long term in other inflammatory conditions like rheumatoid arthritisand inflammatory bowel disease. Additionally, a study which evaluated effect oflong term use of glucocorticoids reported that COPD were amongst major diseaseconditions for which oral glucocorticoids were used for long term. With thisbackground, this study is proposed to evaluate the short and long termbeneficial effects of Prednisolone, Methylprednisolone and Deflazacort inpatients with COPD

STUDY OBJECTIVES

Primary Efficacy Objectives

To evaluate the efficacy ofDeflazacort, Prednisolone and Methylprednisolone in patients with COPD asassessed by FEV1, FVC and FEV1/FVC% measured after short term treatment from baseline

To evaluate the efficacy of Deflazacort,Prednisolone and Methylprednisolone in patients with COPD as assessed by FEV1,FVC and FEV1/FVC% measured after long term treatment from baseline

Secondary Efficacy Objectives

To evaluate efficacy ofDeflazacort, Prednisolone and Methylprednisolone in patients with COPD asassessed by change in C-reactive protein (CRP) levels after short termtreatment from baseline

To evaluate efficacy ofDeflazacort, Prednisolone and Methylprednisolone in patients with COPD asassessed by change in CRP levels after long term treatment from baseline

Safety Objectives

To evaluate the changes in randomblood sugar in all the treatment groups after short term and long termtreatment from baseline

To evaluate the changes in lipidprofile in all the treatment groups after short term and long term treatmentfrom baseline

To compare the changes in12-lead-ECG, hematology and biochemistry tests after short term and long termtreatment from baseline

To assess safety and tolerabilityof the IP as assessed by treatment emergent adverse events (TEAEs) during shortand long term treatment

STUDY DESIGN

Overview of the Study Design

This is a prospective, randomized, open-label, investigator-initiated study to evaluate the short-term and long-term efficacy and safety of Deflazacort tablets, Prednisolone tablets and Methylprednisolone tablets in Patients with COPD.

Following will be the study site visits during study period:

• Visit 1/Screening period: Up to 4 days

• Visit 2/Randomization

• Visit 3/Interim visit during study treatment period (Day 8 (±4 days) after first dose of study

treatment)

• Visit 4/Interim visit during study treatment period (Day 16 (±4 days) after first dose of study

treatment)

• Visit 5 (Day 21 (±4 days)/End-of-treatment (EOT) study site visit and assessments

• Safety follow-up/End-of-study (EOS)/Visit 6 (Telephonic): Investigator or designee will contact patient telephonically after 10 days (±2 days) from end-of-treatment (EOT) day to collect any

adverse event related information. This will mark the End-of-study (EOS) visit.

Additionally, during the treatment period, patients will be contacted telephonically as per Investigator’s discretion to ascertain compliance to study medication and to collect safety information, if any.