A study to test the efficacy of a new drug, RBx 10017609 tablets in lung disease which is associated with difficulty in breathing and persistent cough(chronic obstructive pulmonary disease)
Scientific Title of Study
A randomized, double-blind, placebo-controlled, Proof of Concept, study of 12 week treatment with RBx 10017609 in subjects with moderate to severe chronic obstructive pulmonary disease (COPD).
Trial Acronym
Secondary IDs if Any
Secondary ID
Identifier
R17609102003
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Designation
Affiliation
Address
Phone
Fax
Email
Details of Contact Person Scientific Query
Name
Dr. Sanjay K. Sharma
Designation
Affiliation
Address
Associate Director, Medical Affairs and Clinical Research, Ranbaxy Research Laboratories Laboratories, Ltd Plot No.77-B, Sector-18, Gurgaon HARYANA 122015 India
Phone
+911244194221
Fax
+91124107000
Email
sanjayk.sharma2@ranbaxy.com
Details of Contact Person Public Query
Name
Dr. Sanjay K. Sharma
Designation
Affiliation
Address
Associate Director, Medical Affairs and Clinical Research, Ranbaxy Research Laboratories Laboratories, Ltd Plot No.77-B, Sector-18, Gurgaon HARYANA 122015 India
Cerebral Independent Review Board, 14-7-25, Begum Bazar, Hyderabad,500012, AP, India
Approved
Ethics committee- CHL-Apollo Hospitals, Ethics Committee, Convenient Hospital Ltd, A. B. Road, Indore-452008
Approved
Independent ethics committee (primarily associated with Chest Research Foundation), Survey No 15, Marigold premises, Kalayani Nagar, Vadagaon Sheri, Pune- 411014
Approved
Independent Human Ethics Committee, Health and Research Centre, Yamuna, TC 1/1668, Navarangam Lane, North 2, Medical College, P.O.,Trivendrum,695011
Approved
Institutional Ethics Committee of Allergy, Asthma Associates, Mysore
Approved
Institutional Ethics Committee, PSG IMS & R [DCRB], PSG IMS & R [IHEC], Coimbatore
Approved
Institutional Ethics Committee, T.B and Chest Hospital, Goa Medical College, Goa
Approved
Mahalasa Independent Ethics Committee, Abhinav apartment ,778-B-1, Next to congress house, Shivaji Nagar, Pune
Approved
Metro Hospital And Heart Institutes, Metro Multispecialty Hospital, L 94, Sectro 11, NOIDA 201 301, UP
Approved
Sanjeevani Ethics Committee, Show room No. B-2, Near Laxmi Mandir Cinema, Tonk Road, Jaipur-302015, Rajasthan, India
Approved
Swasthya Kalyan Ethics Committee, Swasthya Kalyan Bhawan,Narain Singh Road, Near Trimurti Circle, Jaipur 302004, Rajasthan, India
Approved
Regulatory Clearance Status from DCGI
Status
Approved/Obtained
Health Condition / Problems Studied
Health Type
Condition
Patients
Chronic Obstructive Pulmonary Disease,
Intervention / Comparator Agent
Type
Name
Details
Comparator Agent
Placebo
12 week treatment with placebo (200 mg BID)
Intervention
RBx 10017609
12 week treatment with RBx 10017609 (200 mg BID)
Inclusion Criteria
Age From
40.00 Year(s)
Age To
75.00 Year(s)
Gender
Both
Details
Inclusion Criteria
To be included in this study subjects must satisfy all inclusion and exclusion criteria at Visit 2 and prior to randomization at Visit 3, unless specified otherwise. All relevant medical and non-medical conditions should be taken into consideration when deciding whether this protocol is suitable for a particular subject.
1. Subjects who have signed an informed consent consistent with ICH GCP guidelines prior to participation in the trial at prescreening visit.
2. Male or female subjects, aged 40 to 75 years (both inclusive). Female subjects should be of non-child bearing potential [post menopausal or those who have undergone surgical sterility (hysterectomy or bilateral tubal ligation or bilateral oophorectomy)].
Sexually active male subjects should agree to use a medically accepted form of contraception (barrier method) or must have undergone vasectomy in the past and their partner should be either using a medically acceptable form of contraception (oral contraceptives, intrauterine contraceptive devices) or have undergone tubal ligation in the past.
3. Subjects with clinical diagnosis of COPD as defined by Global Initiative for Chronic Obstructive Lung Disease Guidelines, 2009 and who additionally have
a. Smoking history of at least 10 pack years (current and former smokers)
b. Post bronchodilator FEV1 to FVC ratio of less than 0.70 at screening (Visit 2).
c. Post bronchodilator FEV1 of greater than or equal to 30 percent and less than or equal to 70 percent of the predicted normal value at screening.
Post bronchodilator refers to within 15 to 30 minutes of inhalation of 4 multiplied by100 mcg of salbutamol delivered at mouth piece (Visit 2).
Note: Menopause is defined as the time when there has been no menstrual period for 12 consecutive months and no other biological or physiological cause can be identified (diagnosed on the basis of age appropriateness and history of vasomotor symptoms) or 6 months of spontaneous amenorrhea with FSH levels greater than 40 mIU per mL at screening.
Number of pack years that is (number of cigarettes or bidis smoked per day multiplied by number of years smoked) divided by 20.
ExclusionCriteria
Details
Exclusion criteria
1.Subjects with history of hypersensitivity to study medication or drugs of similar class or beta 2 agonists or any of the excipients contained in any of these formulations.
2.Subjects with Body Mass Index of less than 18 or greater than 35 kg per meter square at screening (Visit 2).
3.Pregnant or nursing women or women of child bearing potential.
Note: Pregnancy is defined as a state of female after conception and until the termination of gestation, confirmed by a positive serum human chorionic gonadotropin (hCG) laboratory test (greater than 5 mIU per mL).
Note: All women who are physiologically capable of becoming pregnant.
4.Subjects having alpha 1 antitrypsin deficiency.
5.Subjects with history of asthma.
Note: History of asthma indicated by, but not limited to: (i) onset of respiratory symptoms suggestive of asthma prior to 40 years of age and (ii) a history of diagnosis of asthma. If the subject had an absolute eosinophil count greater than or equal to 600 per cumm, source documentation is required to verify that the increased eosinophil count is related to a non-asthmatic condition
6.Subjects with active pulmonary tuberculosis, lung or any other malignancy, bronchiectasis, cystic fibrosis or pneumonia
7.Subjects using inhaled corticosteroids and unable to stop these during the screening/run-in period.
8.Subjects who have received treatment with oral or parenteral glucocorticosteroids within 6 weeks of screening or run-in period or depot corticosteroids within 12 weeks of screening/run-in period.
9.Subjects with history of COPD exacerbation requiring systemic glucocorticosteroids and/or antibiotics and/or hospitalization within 6 weeks of screening (Visit 2).
Note: Once stable, these subjects may be reconsidered for the study.
10.Subjects with history of respiratory tract infection within 6 weeks of screening visit (Visit 2).
Subjects who develop a respiratory tract infection between pre screening (Visit 1) and randomization (Visit 3) must discontinue from the trial but may be permitted to re-enroll at a later date once the inclusion/exclusion criteria have been met.
11.Subjects with hypoxemia (SpO2 less than 88% on room air).
12.Subjects with significant disease(s), disorder(s) other than COPD that in the opinion of the Investigator may (i) put the subject at risk because of participation in the study or (ii) interfere with the study evaluations or (iii) cause concern regarding subject’s ability to participate in the study.
13.Subjects having arthritis or connective tissue disorder or any other joint disorder that in the opinion of the Investigator might interfere with the study evaluations
14.Subjects with history of consistent abnormal fasting blood sugar (greater than 250 mg per dl or 14 mmol per L) or HbA1c greater than 8percent at screening (Visit 2).
15.Subjects with family history of long QT syndrome.
16.Subjects with clinically significant abnormal 12 lead ECG or QTc greater than 450 milliseconds as calculated by Fridericia formula.
17.Subjects with history of any lung surgery (e.g.lung resection etc).
18.Subjects with conditions which, in the opinion of the Investigator, prevent subjects from performing spirometry (e.g., hemoptysis of unknown origin, recent eye surgery etc.).
19.Subjects requiring assisted ventilation or subjects who regularly use daytime oxygen therapy for more than 1 hour per day.
20.Subjects with clinically significant abnormal haematology, biochemistry, or urinalysis; all subjects with an SGOT (AST) or SGPT (ALT) greater than 2 times ULN or total bilirubin or serum creatinine greater than 1.2 times ULN (Visit 2).
21.Subjects with a history of HIV or positive serology results for Hepatitis B or C in the past 3 months prior to screening (Visit 2).
22.Subjects with history of habitual alcohol consumption exceeding an average weekly intake of greater than 21 units for males and greater than 14 units for females.
Note: 1 unit i.e. 284 mL of beer; 25 mL of spirits or 125 mL of wine
23.Subjects with history of drug abuse.
24.Subjects who have received live attenuated vaccination within 4 weeks prior to screening (Visit 2).
Note: The use of polysaccharide pneumococcal and hemophilus influenzae vaccines is permitted.
25.Subjects who have received any other investigational drug within the last 3 months of screening visit (Visit 2).
26.Subjects who have previously been randomized in this study or are currently participating in another study.
27.Subjects who, in the opinion of the Investigator, are unable to perform spirometry or sputum induction procedures or complete the St George Respiratory Questionnaire.
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
Sequentially numbered, sealed, opaque envelopes
Blinding/Masking
Participant, Investigator and Outcome Assessor Blinded
Primary Outcome
Outcome
TimePoints
To assess the safety and tolerability of 12 week treatment with RBx 10017609 (200 mg BID) in subjects with moderate to severe COPD.
At the end of 12 week
Secondary Outcome
Outcome
TimePoints
Assess efficacy of RBx10017609 wrt change in the following parameters as compared to placebo
1)Sputum neutrophil count
2)FEV1
3)SGRQ
Exploratory Objectives
To assess the effect of RBx10017609 wrt change in the following parameters as compared to placebo
1)Sputum biomarkers (MMP 9 by TIMP ratio, IL 6 and IL 8)
2)Serum biomarker [serum CRP]
3)Urinary desmosine
To evaluate PK of RBx 10017609 and its metabolites
To explore PK PD relationship for efficacy and safety endpoints
At the end of 12 week
Target Sample Size
Total Sample Size="135" Sample Size from India="108" Final Enrollment numbers achieved (Total)= "" Final Enrollment numbers achieved (India)=""
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Brief Summary
This is a randomized, double-blind, placebo-controlled, two-arm, parallel group, comparative study. The study will be of 16 weeks duration consisting of 2 weeks of screening/run-in period followed by 12 weeks of treatment period and 2 weeks of safety follow-up period. The subjects will be randomized in a ratio of 2:1 to either of the two treatment arms: RBx 10017609 (200 mg BID) or placebo. The study medication will be administered with or without food twice daily (morning and evening) at an interval of approximately 12 hours. The study will involve 7 scheduled study visits to the study site [prescreening visit, screening/run-in visit (Day -14), randomization visit (Day 0), 2 (on therapy) visits (Day 28 and Day 56), end of treatment visit (Day 84) and safety follow-up visit (Day 98)]. Being a Global Study, approximately 108 Patients will be enrolled in India and approximately 27 patients will be enrolled in Estonia. All the 12 sites in India have sought Ethics Committee approval from the respective ethics Committees.
Estonia site details:
The name of 3 Investigators in Estonia are 1. Dr. Svetlana Sergejeva (West Tallinn Central Hospital (LTKH), Pelgulinna Hospital, Sõle 16, 10611, Tallinn, Estonia), 2. Dr. Kaiu Prikk (Lasnamäe Health Centre MEDICUM, Ltd, Punane 61, 13619 Tallinn, Estonia) 3. Dr. Erve Sõõru (Pulmonology Department, North Estonia Medical Centre, Foundation, 19 J. Sütiste Str, 13419 Tallinn, Estonia). The 3 sites in Estonia have sought Ethics Committee approval from Tallinn Medical Research Ethics Committee, Estonia. The tentative date of 1st patient enrollment is 31 August 2011.