| CTRI Number |
CTRI/2014/01/004370 [Registered on: 31/01/2014] Trial Registered Prospectively |
| Last Modified On: |
30/01/2014 |
| Post Graduate Thesis |
No |
| Type of Trial |
Interventional |
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Type of Study
|
Drug |
| Study Design |
Randomized, Parallel Group, Multiple Arm Trial |
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Public Title of Study
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A clinical trial study of oral Roflumilast 0.5mg Tablet and combination therapy of Roflumilast 0.5 mg tablet plus Salmeterol 25mcg oral inhaler and combination therapy of Roflumilast 0.5 mg tablet plus Tiotropium 9mcg oral inhaler in adult patients with Chronic Obstructive Pulmonary Disease. |
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Scientific Title of Study
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An Open-label, Prospective, Three Arm, Parallel Group, Randomized, Multicentric Phase-III Clinical Study to Evaluate the Efficacy and Safety between monotherapy of oral Roflumilast 0.5mg Tablet and combination therapy of Roflumilast 0.5 mg tablet plus Salmeterol 25mcg oral inhaler and combination therapy of Roflumilast 0.5 mg tablet plus Tiotropium 9mcg oral inhaler in adult patients with Chronic Obstructive Pulmonary Disease. |
| Trial Acronym |
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Secondary IDs if Any
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| Secondary ID |
Identifier |
| NEX-COPD/CT-III/5002/04-2011 (Ver No. 03, dated: 04/06/2013) |
Protocol Number |
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Details of Principal Investigator or overall Trial Coordinator (multi-center study)
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| Name |
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| Designation |
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| Affiliation |
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| Address |
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| Phone |
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| Fax |
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| Email |
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Details of Contact Person
Scientific Query
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| Name |
Dr Amit Bhatt |
| Designation |
President & CEO |
| Affiliation |
Nexus Clinical Research (India) Ltd. |
| Address |
32 A, Nexus Center for Clinical Excellence, Sector- 1, Shiravane Road, Service Industry, Mumbai- Pune Highway, Nerul (E), Navi Mumbai
Mumbai (Suburban)
MAHARASHTRA
400706
India |
| Phone |
02227714204 |
| Fax |
|
| Email |
dramit.bhatt@gmail.com |
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Details of Contact Person
Public Query
|
| Name |
Dr Amit Bhatt |
| Designation |
President & CEO |
| Affiliation |
Nexus Clinical Research (India) Ltd. |
| Address |
32 A, Nexus Center for Clinical Excellence, Sector- 1, Shiravane Road, Service Industry, Mumbai- Pune Highway, Nerul (E), Navi Mumbai
Mumbai (Suburban)
MAHARASHTRA
400706
India |
| Phone |
02227714204 |
| Fax |
|
| Email |
dramit.bhatt@gmail.com |
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Source of Monetary or Material Support
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| MSN Laboratories Pvt. Ltd. |
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Primary Sponsor
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| Name |
MSN Laboratories Pvt Ltd |
| Address |
MSN House, Plot No. C-24, Industrial Estate, Sanath Nagar, Hyderabad- 500018, Andhra Pradesh, India |
| Type of Sponsor |
Pharmaceutical industry-Indian |
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Details of Secondary Sponsor
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Countries of Recruitment
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India |
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Sites of Study
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| No of Sites = 5 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr Ajit Kulkarni |
Aster Aadhar Hospital |
Department of Tuberculosis and Chest Disease, R.S. No. 628, ‘B’ Ward,
Near Shastri Nagar,
Kolhapur
MAHARASHTRA |
02316622747
asteraadharcr@gmail.com |
| Dr Surajit Chatterjee |
Insitute of Post Graduate Medical Education and Research and SSKM Hospital |
244, A.J.C Bose Road,
Kolkata – 700020, West Bengal.
Kolkata
WEST BENGAL |
033-2235181
surajit.chat@gmail.com |
| Dr Amit Gupta |
Pushpanjali Crosslay Hospital |
Department of Emergency Medicine and critical care, W-3 Sector 1, Vaishali- 201012
Ghaziabad
UTTAR PRADESH |
09953787220
amitgupta_f2@yahoo.com |
| Dr Narendra Khippal |
SMS Medical College & Hospital |
Department of Chest & Respiratory Diseases
Subhash Nagar Shopping Center, Shastri Nagar
Jaipur
RAJASTHAN |
01412711299
01414007619
drnkhippal@rediffmail.com |
| Dr R Vijai Kumar |
Yashoda Hospital |
Department of Pulmonary Medicine and Critical Care,Behind Hari Hara Kala Bhavan, S.P. Road-500 003
Hyderabad
ANDHRA PRADESH |
04027610645
04027703999
drvijaipulmo@yahoo.co.in |
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Details of Ethics Committee
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| No of Ethics Committees= 5 |
| Name of Committee |
Approval Status |
| Aster Aadhar Ethics Committee |
Approved |
| Ethics committee of SMS Medical College & Hospital |
Submittted/Under Review |
| IPGME&R Research Oversight Committee |
Submittted/Under Review |
| Pushpanjali Crosslay Ethics Committee |
Submittted/Under Review |
| Yashoda Academy of Medical Education & Research IEC |
Submittted/Under Review |
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Regulatory Clearance Status from DCGI
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Health Condition / Problems Studied
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| Health Type |
Condition |
| Patients |
Adult Patients with Chronic Obstructive Pulmonary Disease, |
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Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Intervention |
Roflumilast |
0.5 mg tablet once daily for 24 weeks |
| Comparator Agent |
SEROBID® [Salmeterol] |
Two inhalations of 25 mcg each, twice daily (total dose 100 mcg per day) for 24 weeks |
| Comparator Agent |
TIOVA® [Tiotropium] |
Two inhalations of 9 mcg each, once daily (total dose 18 mcg per day) for 24 weeks |
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Inclusion Criteria
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| Age From |
35.00 Year(s) |
| Age To |
65.00 Year(s) |
| Gender |
Both |
| Details |
1)Male or female patients aged 35-65 years.
2)Patients willing and able to participate in all aspects of the core study, including use of oral medication, completion of subjective evaluations, attending scheduled clinic visits and compliance with protocol requirements as evidenced by providing written informed consent
3)COPD patients having at least one documented moderate or severe exacerbation within one year prior to baseline visit.
4)FEV1 ≤ 50% of predicted.
5)FEV1/FVC ratio ≤ 70%.
6)Patients already on therapy for COPD with beta2 adrenergic receptor agonists / muscarinic receptor antagonists / Xanthine class of drugs.
7)Presence of respiratory symptoms of COPD including dyspnea, cough and sputum production.
8)Current smokers or patients with a history of smoking.
9)For women of child-bearing potential: women is not pregnant (and has to undergo urine pregnancy test at the time of screening which must be negative) and not nursing, and is practicing an acceptable method of birth control.
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| ExclusionCriteria |
| Details |
1)Inability to adequately perform spirometry.
2)COPD exacerbation indicated by a treatment with systemic corticosteroids and/or antibiotics not stopped within 4 weeks prior to screening visit and remains uncontrolled in between the treatment periods.
3)Diagnosis of asthma and/or other relevant lung disease.
4)Suffering from any concomitant disease that might interfere with study procedures or evaluation.
5)Lower respiratory tract infection not resolved 4 weeks prior to the screening visit.
6)Known clinically significant cardiopulmonary abnormalities (diagnosed clinically or documented by X-ray or ECG) and are not related to COPD and that require further evaluation.
7)Known case of HIV and/or patient currently on cytotoxic drugs.
8)Hepatitis and/or liver insufficiency (SGOT and/or SGPT ≥ 5 times the upper limit of the normal reference range)
9)Renal insufficiency (S. Creatinine ≥ 5 times the upper limit of the normal reference range)
10)Known or suspected hypersensitivity to the study drug or its components.
11)Known or suspected hypersensitivity to milk-proteins.
12)Participation in another clinical trial within the last 30 days, simultaneous participation in
another clinical trial, or previous participation in this trial.
13)History of, or known current problem with, substance abuse, or any medical, psychological, and/or social condition that may interfere with the patients participation in the study, or with evaluation of the study results.
14)Mentally incompetent or unable or unwilling to provide informed consent or comply with study procedures.
15)Have any condition or situation that, in the opinion of the investigator, would prevent proper evaluation of the safety of the study drug according to the study protocol (e.g., poorly compliant subject).
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Method of Generating Random Sequence
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Computer generated randomization |
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Method of Concealment
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An Open list of random numbers |
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Blinding/Masking
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Open Label |
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Primary Outcome
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| Outcome |
TimePoints |
1)Mean change in the pre-bronchodilator Forced Expiratory Volume in 1 second (FEV1) between the treatment arms
2)Mean change in the post-bronchodilator Forced Expiratory Volume in 1 second (FEV1) between the treatment arms |
From baseline visit to end of the therapy i.e. Week 24±2 days |
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Secondary Outcome
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| Outcome |
TimePoints |
| Mean change in the reduction of COPD exacerbations between the treatment arms |
From baseline visit to each post randomization visit |
| Changes in the mean FEV1/FVC ratio between the treatment arms |
From baseline to end of the therapy i.e. Week 24±2 days |
Percentage of the subjects reporting AE and/or ADR.
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At visit 2, 3, 4, 5, 6 and 7 |
| Assessment of clinical laboratory parameters |
At visit 1 (baseline) and visit 7 (end of therapy) |
| General examination and assessment of vital signs. |
At every visit |
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Target Sample Size
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Total Sample Size="300"
Sample Size from India="300"
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" |
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Phase of Trial
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Phase 3 |
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Date of First Enrollment (India)
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20/02/2014 |
| Date of Study Completion (India) |
Applicable only for Completed/Terminated trials |
| Date of First Enrollment (Global) |
Date Missing |
| Date of Study Completion (Global) |
Applicable only for Completed/Terminated trials |
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Estimated Duration of Trial
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Years="1"
Months="3"
Days="0" |
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Recruitment Status of Trial (Global)
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Not Applicable |
| Recruitment Status of Trial (India) |
Not Yet Recruiting |
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Publication Details
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Individual Participant Data (IPD) Sharing Statement
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Will individual participant data (IPD) be shared publicly (including data dictionaries)?
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Brief Summary
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Roflumilast is a drug which acts as a selective, long-acting
inhibitor of the enzyme PDE-4. It has anti-inflammatory effects and is under
development as an orally administered drug for the treatment of inflammatory
conditions of the lungs such as asthma, and chronic obstructive pulmonary
disease (COPD).[11,12,13,14]
While Roflumilast was found to be effective in clinical trials, it produced
several dose-limiting side effects including nausea, diarrhea and headache, and
development is continuing in an attempt to minimize the incidence of side
effects while retaining clinical efficacy.[15]
Roflumilast especially alter the underlying inflammation of
COPD or disease progression. The anti-inflammatory activity of
the selective PDE4 inhibitor Roflumilast has been proven in vitro and in
several animal models of inflammation and includes, among other activities,
inhibition of the synthesis of leukotriene B4 and reactive oxygen species in neutrophils,
as well as partial inhibition of tumor necrosis factor α (TNF- α) from mononuclear
cells. The therapeutic utility of previous PDE4 inhibitors in development was
limited due to intolerability and an inadequate demonstration of efficacy in
COPD.
In contrast, clinical studies have demonstrated higher
pharmacologic activity and better tolerability of Roflumilast as compared to
earlier PDE4-inhibitors in development. Therefore, Roflumilast has been
developed as an innovative once-daily oral treatment for COPD, targeting the
inflammatory processes that are relevant to the disease. Roflumilast is
expected to provide more targeted anti-inflammatory activity in COPD than corticosteroids,
which do not suppress a predominantly neutrophilic inflammatory response in
this patient population. (Barnes, 2003)
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