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CTRI Number  CTRI/2011/09/002012 [Registered on: 16/09/2011] Trial Registered Retrospectively
Last Modified On: 27/08/2013
Post Graduate Thesis  No 
Type of Trial  Interventional 
Type of Study   Drug 
Study Design  Randomized, Parallel Group Trial 
Public Title of Study   PHASE II OPEN LABEL, MULTI-CENTERIC CLINICAL TRIAL OF ORAL WCK 2349(1000 mg BID and 1200 mg BID)TO EVALUATE SAFETY AND EFFICACY IN THE TREATMENT OF COMPLICATED SKIN AND SOFT TISSUE INFECTIONS CAUSED BY GRAM POSITIVE BACTERIA. 
Scientific Title of Study   A PHASE II OPEN LABEL, MULTI-CENTER CLINICAL TRIAL TO EVALUATE SAFETY AND EFFICACY OF ORAL WCK 2349 (1000 mg BID and 1200 mg BID) IN THE TREATMENT OF COMPLICATED SKIN AND SOFT TISSUE INFECTIONS CAUSED BY GRAM POSITIVE BACTERIA, INCLUDING METHICILLIN RESISTANT STAPHYLOCOCCUS AUREUS 
Secondary IDs if Any  
Secondary ID  Identifier 
P-II/WCK 2349/Gm+ve cSSTIs/09  NIL 
 
Details of Principal Investigator or overall Trial Coordinator (multi-center study)  
Name  Dr Deven Parmar 
Designation  Vice President - Global Clinical Research, Wockhardt Limited 
Affiliation  Wockhardt Limited 
Address  Wockhardt Towers Bandra Kurla Complex, Bandra - E, Mumbai - 400051
Wockhardt Towers Bandra Kurla Complex, Bandra - E, Mumbai - 400051
Mumbai
MAHARASHTRA
400051
India 
Phone  02226594444  
Fax  02226523885  
Email  devenp@wockhardt.com  
 
Details of Contact Person
Scientific Query
 
Name  Dr Deven Parmar 
Designation  Vice President - Global Clinical Research, Wockhardt Limited 
Affiliation  Wockhardt Limited 
Address  Wockhardt Towers Bandra Kurla Complex, Bandra - E, Mumbai - 400051
Wockhardt Towers Bandra Kurla Complex, Bandra - E, Mumbai - 400051
Mumbai
MAHARASHTRA
400051
India 
Phone  02226594444  
Fax  02226523885  
Email  devenp@wockhardt.com  
 
Details of Contact Person
Public Query
 
Name  Dr. Deven Parmar 
Designation   
Affiliation   
Address  Wockhardt Ltd,Wockhardt Towers,
Bandra- Kurla Complex, Bandra (East),Mumbai-400051
Mumbai
MAHARASHTRA
400051
India 
Phone  02226594444   
Fax  02226523885  
Email  devenp@wockhardt.com  
 
Source of Monetary or Material Support  
Wockhardt Ltd Wockhardt Towers, Bandra- Kurla Complex, Bandra (East) Mumbai- 400051 Phone No.- +91222659 4444 Fax No.- +91222652 3885/ 26534242 
 
Primary Sponsor  
Name  Wockhardt Ltd 
Address  Wockhardt Towers, Bandra Kurla Complex, Bandra - E, Mumbai - 400051 
Type of Sponsor  Pharmaceutical industry-Indian 
 
Details of Secondary Sponsor  
Name  Address 
Wockhardt Ltd   
 
Countries of Recruitment     India  
Sites of Study
Modification(s)  
No of Sites = 17  
Name of Principal Investigator  Name of Site  Site Address  Phone/Fax/Email 
Dr Digvijay Singh Bedi  Bopal Multispeciality Hospital  Bopal Multispeciality Hospital, 1st Floor Abhinandan Complex Opp Inductothern, Bopal, Ahemdabad 380 058, Gujarat
Ahmadabad
GUJARAT 
919824012582

dvsb@indiatimes.com 
Dr MS Srinivasan  Chettinad Hospital and Research Institute  Chettinad Hospital and Research Institute, Kelambakkam, Kanchipuram, Chennai 603 103, Tamil Nadu
Kancheepuram
TAMIL NADU 
919884154232

hamsrini@yahoo.co.in 
Dr Vinod Jain  Chhatrapati Shahuji Maharaj Medical University  Chhatrapati Shahuji Maharaj Medical University, Erstwhile King George Medical College, Chowk, Lucknow 226 003, Uttar Pradesh
Lucknow
UTTAR PRADESH 
919450019566

vinodjainkgmu@yahoo.co.in 
Dr Rakesh Shivhare  CHL- Apollo Hospital, Surgery Department,  AB Road, Near LIG Triangle, Indore 452 008
Indore
MADHYA PRADESH 
919826680273
917314245625
drrakeshshivhare@gmail.com 
Dr Rakesh Shivhare  CHL-Apollo Hospitals  CHL-Apollo Hospitals, AB Rd, Indore 452 008, Madhya Pradesh
Indore
MADHYA PRADESH 
919826680273

drrakeshshivhare@gmail.com 
Dr Raj Gajbhiye  Indira Gandhi Government Medical College  Dept of Surgery, Indira Gandhi Government Medical College, Central Avenue Road, Nagpur 440 018, Maharashtra
Nagpur
MAHARASHTRA 
919422101440

rajgabhiye@hotmail.com 
Dr Maria Kuruvila  Kasturba Medical college and Hospital, Dermatology Department,   Attavar, Mangalore, Karnataka 575 001
Bangalore
KARNATAKA 
918242457169

mariakuruvila@hotmail.com 
Dr Satish Dharap  Lokmanya Tilak Municipal Medical College and General Hospital  Lokmanya Tilak Municipal Medical College and General Hospital, Sion, Mumbai 400 022, Maharashtra
Mumbai
MAHARASHTRA 
919869042629

drdharap@hotmail.com 
Dr NK Bhagavan  Manipal Hospital, Dermatology Department,   Manipal Hospital, 6th floor, Clinical Research Department; 98, Rustom bagh, Old Airport Road, Bangalore 560 017, Karnataka
Bangalore
KARNATAKA 
919844041894

nkbhagavan@yahoo.com 
Dr Vijay Kumar Garg  Maulana Azad Medical College and Lok Nayak Hospital, Dermatology Department  Department of Dermatology & Venerology Maulana Azad Medical College and Lok Nayak Hospital, Bahadur Shah Zafar Marg 110 002, New Delhi
New Delhi
DELHI 
919811410903

vijaykga@gmail.com 
Dr Ramesh Ardhnari  Meenakshi Mission Hospital and Research Centre  Meenakshi Mission Hospital and Research Centre, Lake Area, Melur Road, Madurai 625 107
Madurai
TAMIL NADU 
919842178789

drrameshardhanari@gmail.com 
Dr TK Sumathy  MS Ramaih memorial Hospital, Dermatology Department  Gokula Metropolis Clinical research Centre, M.S Ramaih Memorial Hospital New BEL road , MSRIT Post Bangalore 560 054
Bangalore
KARNATAKA 
919845163009

tksumathy@gmail.com 
Dr Sudhir Bhamre  MVP Samajs Dr. Vasantrao Pawar Medical College, Hospital & Research Centre  MVP Samajs Dr. Vasantrao Pawar Medical College, Hospital & Research Centre, Vasantdadanagar, Adgaon, Nashik 422 003, Maharashtra
Nashik
MAHARASHTRA 
919823079792

sudhir_bhamre@yahoo.com 
Dr Gulab Patel  New Civil Hospital  New Civil Hospital, Ring Road, Manjura Gate, Surat 395 002, Gujarat
Surat
GUJARAT 
919879259001

drgulabpatel2004@yahoo.co.in 
Dr Suresh Deshpande  Ruby Hall Cilnic  Dept of Surgery, Ruby Hall Cilnic, 40 Sasson Road, Pune 411 001, Maharashtra
Pune
MAHARASHTRA 
919822024982

sgddoc@gmail.com 
Dr Prithi Rodgers  Sahyadri Hospital  Sahyadri Hospital, G&G Towers, S.No. 153/A, Hissa No.,1 to 4 / 21 , Magarpatta, Pune-Solapur Road, Hadapsar, Pune 411 028, Maharashtra
Pune
MAHARASHTRA 
919822038067

pr@sahyadrihospitals.com 
Dr Vijay Aithal  St. Johns Hospital, Dermatology Department  Sarjapur Road, Bangalore 560 034
Bangalore
KARNATAKA 
919880687689

dr.vijay.aithal@gmail.com 
 
Details of Ethics Committee
Modification(s)  
No of Ethics Committees= 16  
Name of Committee  Approval Status 
CHL - Apollo Hospitals - Ethics Committee, CHL-Apollo Hospitals, AB Rd, Indore 452 008, Madhya Pradesh, Dr Rakesh Shivhare  Approved 
Ethical Review Board, MS Ramaiah Medical College and Teaching Hospital, MSR nagar, MSRIT post, Bangalore 560 054, Dr TK Sumathy  Approved 
Ethics Committee Lok Nayak Hospital, Burns and Plastic Surgery Department, New Delhi, Dr Vijay Garg  Approved 
Ethics Committee of Manipal Hospital, Manipal Hospital, 6th floor, Clinical Research Department; 98, Rustom bagh, Old Airport Road, Bangalore - 560017, Karnataka, Dr NK Bhagavan  Approved 
Human Research Ethics Committee, Govt. Medical College, Outside Majura Gate, Surat 395 001, Gujarat, Dr Gulab Patel  Approved 
Institutional Ethics Committee - Office of Research Cell of Chhatrapati Shahuji Maharaj Medical University, Chhatrapati Shahuji Maharaj Medical University, (Erstwhile King George Medical College), Chowk, Lucknow 226 003, Uttar Pradesh, Dr Vinod Jain  Approved 
Institutional Ethics Committee of Chettinad Hospital & Research Institute, Chettinad Hospital and Research Institute, Kelambakkam, Kanchipuram, Chennai 603 103, Tamil Nadu, Dr Srinivasan  Approved 
Institutional Ethics Committee of MVP Samajs Dr. Vasantrao Pawar Medical College, Hospital & Research Centre, MVP Samajs Dr. Vasantrao Pawar Medical College, Hospital & Research Centre, Vasantdadanagar,Adgaon, Nashik 422 003, Dr Sudhir Bhamre  Approved 
Institutional Ethics Committee of Poona Medical Research Foundation, 40 Sasson Road, Dr Suresh Deshpande  Approved 
Institutional Ethics Committee of Sahyadri Hospital, Sahyadri Hospital, G&G Towers, S.No. 153/A, Hissa No.,1 to 4 / 21 , Magarpatta, Pune-Solapur Road, Hadapsar, Dr Prithi Rodgers  Approved 
Institutional Ethics Committee, Kasturba Medical College, Kasturba Medical College, light house, Hampankatta, Mangalore 575 001, Dr Maria Kuruvila  Approved 
Lokmanya Tilak Municipal Medical College and General Hospital Staff and Research Society, Lokmanya Tilak Municipal Medical College and General Hospital, Sion, Mumbai 400 022, Maharashtra, Dr Satish Dharap  Approved 
Meenakshi Mission Hospital and Research Centre Ethical Review Board, Meenakshi Mission Hospital and Research Centre, Lake Area, Melur Road, Madurai 625 107, Tamil Nadu, Dr Ramesh Ardhanari  Approved 
Office of the Ethics Committee for Indira Gandhi Government Medical College, Dept of Surgery, Indira Gandhi Government Medical College, Central Avenue Road, Nagpur 440 018, Maharashtra, Dr Raj Gajbhiye  Approved 
St. Johns Medical College & Hospital Institutional Ethical Review Board, St. Johns Medical College Hospital Sarjapur Road, John Nagar, Koramangala, Bengaluru 560 034, Karnataka, Dr Vijay Aithal  Approved 
Sujlam Independent Ethics Committee, 2nd Floor, AMA House, Near Natraj cinema, Ashram Road Ahmedabad 380 009, Gujarat, Dr Digvijay Singh Bedi  Approved 
 
Regulatory Clearance Status from DCGI  
Status 
Approved/Obtained 
 
Health Condition / Problems Studied  
Health Type  Condition 
Patients  Patient of cSSTIs caused by Gm+ve bacteria, including MRSA. 
 
Intervention / Comparator Agent  
Type  Name  Details 
Comparator Agent  NIL  NIL 
 
Inclusion Criteria  
Age From  19.00 Year(s)
Age To  65.00 Year(s)
Gender  Both 
Details  1.Subjects of either sex with 18 -70 years of age.
2.Weighing at least 40 kgs
3.Clinical diagnosis of cSSTIs as one of the conditions given below
(i)infections involving deeper soft tissues such as subcutaneous tissue, fascia and skeletal muscles.
(ii)requiring significant surgical intervention such as infected ulcers, burns upto 30%, and deep abscess.
(iii)SSTIs with a significant underlying disease state (such as diabetes) that complicates the response to treatment.
(iv)superficial infection or abscess in rectal area.
4.Suspected or proven Gm +ve bacterial infection as per following criteria:
i.Subject receiving antimicrobial therapy in last 72 hrs or on long acting antimicrobial therapy and not responding to antimicrobial therapy for cSSTIs will be considered microbiologically eligible can be enrolled, but to be continued only if the results of tissue culture show growth of gram positive bacteria by central laboratory.
ii.Naïve cases with no antimicrobial therapy in last 72 hrs and not on long acting antimicrobial therapy will be enrolled in the study if direct smear or tissue culture growth confirms the presence of the Gm +ve bacteria by gram staining or bacterial identification.
4.Subjects with at least one of the following symptoms or sign:
(i)Fever, i.e., oral temperature > 38 degree centigrade or 100.4 degree fahrenheit hypothermia i.e., oral temperature <36 degree centigrade or 96.8 degree fahrenheit
(iii)Respiratory rate more than 20/minute
(iv)Heart rate > 90/minute hypotension (SBP < 90 mm of Hg)
(vi)a white blood cell count of >12,000/mm3 or < 4000/ mm3
(vii)>10% immature neutrophils regardless of white blood cell count
5.Justified need of antimicrobial therapy for cSSTIs with Gm +ve bacteria as judged by investigator.
6.Subjects, who in the opinion of the PI, are most likely to tolerate oral therapy
7.Subject willing to participate in the study and subject or legally acceptable representative willing to give written informed consent.
 
 
ExclusionCriteria 
Details  1.Subjects not requiring antimicrobial therapy
2.Medical conditions leading to difficulty in interpreting response such as superinfected eczema and atopic dermatitis.
3.Diagnosed subjects of immunosuppressive conditions like AIDS.
4.Subjects receiving or requiring immunosuppressive therapy.
5.Subjects with osteomyelitis, septic arthritis, necrotizing fasciitis, gas gangrene and infected prosthetic device or foreign body at the infected site.
6.Subjects with endocarditis or meningitis
7.Diagnosed subjects of active complicated cardiovascular disease like IHD, CCF,arrhythmias and severe hypertension (Systolic Blood Pressure more than or equal to 160 mmHg OR Diastolic Blood Pressure more than or equal to 100 mmHg)
8.Subjects with any of the following abnormality in clinical laboratory parameters
a.SGOT (AST) and SGPT (ALT): more than 3 times the upper limit of normal laboratory range, Serum bilirubin and Serum alkaline phosphatase 15% of upper limit of normal laboratory range.
b.Blood urea and Serum creatinine 15% of upper limit of normal laboratory range.
c.Subjects with uncontrolled diabetes as determined by post prandial plasma or random(casual) plasma glucose 200 mg/dl (11.1 mmol/l)
d.Subjects with platelet count 100, 000/ cu.mm.
9.Subjects with history of Seizures,
10.History of hypersensitivity to fluoroquinolones or quinolones
11.Treatment within last 30 days with an investigational new drug.
12.Previous treatment with WCK 2349 or WCK 771.
13.Pregnant women or nursing mothers and women not practicing effective contraception, including but not limited to implants, injectables, combined oral contraceptives, intrauterine device, sexual abstinence or a vasectomized partner during the trial.
 
 
Method of Generating Random Sequence   Computer generated randomization 
Method of Concealment   Centralized 
Blinding/Masking   Open Label 
Primary Outcome  
Outcome  TimePoints 
Clinical outcome is the primary efficacy variable at test of cure visit.  Test of Cure (Day 25) 
 
Secondary Outcome  
Outcome  TimePoints 
Microbiological Outcome.
 
End of treatment (Day 14) and test of cure (Day 25) visit 
 
Target Sample Size   Total Sample Size="120"
Sample Size from India="120" 
Phase of Trial   Phase 2 
Date of First Enrollment (India)   09/05/2011 
Date of First Enrollment (Global)  No Date Specified 
Estimated Duration of Trial   Years="1"
Months="0"
Days="0" 
Recruitment Status of Trial (Global)
Modification(s)  
Not Applicable 
Recruitment Status of Trial (India)  Completed 
Publication Details    
Brief Summary  

Title

:

A Phase II Open Label, multicenter clinical trial to evaluate the safety and efficacy of oral WCK 2349 (1000 mg BID and 1200 mg BID) in the treatment of complicated Skin and Soft Tissue Infections caused by Gram Positive Bacteria, including Methicillin Resistant Staphylococcus aureus (MRSA)

 

Project Number

:

WCK 2349/P-II/Gm +ve cSSTIs/09

 

Investigational Medicinal Product

:

WCK 2349

 

Sponsor

:

Wockhardt Ltd, Mumbai, India

 

Study Centres

:

10

 

Planned Study Period

:

November 2010 to April 2011

 

Clinical Phase

:

Phase IIa

 

Background

:

WCK 2349 is a proprietary molecule of Wockhardt Ltd. It is an oral antibacterial agent belonging to fluoroquinolone class. WCK 2349, a mesylate salt of alanine ester of Levonadifloxacin, is an oral prodrug of Levonadifloxacin as it gets converted to Levonadifloxacin in the body after oral administration. WCK 771, an arginine salt of Levonadifloxacin, is an intravenous prodrug of Levonadifloxacin, as it gets converted to Levonadifloxacin in the body after intravenous administration. WCK 771 is also a propriety molecule of Wockhardt Ltd.

Subject Population

:

Adult subjects of either sex with complicated skin and soft tissue infections (cSSTIs) caused by Gram positive (Gm+ve) bacteria, including MRSA of sufficient severity that can be treated with oral antibiotics and may or may not require hospitalization.

Study Objectives

 

:

Primary Objective:

To evaluate the safety and efficacy of oral WCK 2349 at test of cure (TOC) in the treatment of cSSTIs caused by Gm+ve bacteria, including MRSA.

 

 

 

 

Secondary Objective:

·         To evaluate the efficacy of WCK 2349 in terms of clinical and bacteriological cure rates at End of Treatment (EOT) and TOC in the treatment of cSSTIs caused by Gm+ve bacteria, including MRSA.

·         To evaluate Pharmacokinetics of WCK 2349 in selected Subjects with cSSTIs caused by Gm+ve bacteria including MRSA

·         To evaluate the overall safety and tolerability of WCK 2349

·         To explore the association of pharmacokinetic/ pharmacodynamic variables of WCK 2349 with its efficacy and safety.

Study Design

:

Multicentric, Prospective, Randomized, Parallel, study

Dose cohorts

:

1000 mg, 1200 mg of WCK 2349

Dose and route of administration

:

I) 1000 mg (2 tablets of 400mg & 1 tablet of 200mg) twice a day (BID) at 12 + 1 hrs interval administered orally

II) 1200 mg (3 tablets of 400mg) twice a day (BID) at 12 + 1 hrs interval administered orally

 

 Duration

:

Duration of therapy will be maximum of 14 days. Subjects should come for test of cure visit at 11 + 2 days after the end of treatment.

Number of subjects

:

60 subjects will be assigned to each dose cohort. In all 120 subjects will be enrolled in order to have 100 evaluable subjects

Housing

 

The subjects will be housed in the hospital from start of the treatment till 24 hours after the 8th dose.

Study Assessments

 

 

Assessment of Efficacy:

 

Clinical outcome: Outcome of systemic and local signs and symptoms of infection at EOT and TOC.

 

Microbiological Outcome: Gm+ve bacteria, including

MRSA culture outcome from microbiological specimens such as biopsy, needle aspiration, surgically obtained specimens or fluids/pus of an area contiguous to the infected site at TOC and EOT.

 

Assessment Schedule: Pretherapy, at day 4/5, EOT and TOC

 

 

 

 

Assessment of Safety:

 

Adverse Event, Serious Adverse Event, vital signs, ECG, Clinical Laboratory Evaluation: hematology, blood biochemistry, urine analysis and stool analysis.

Assessment of Pharmacokinetics & Sampling Schedule

 

:

The plasma concentrations of active WCK 2349 (Levonadifloxacin) will be quantified using a validated method to analyze the pharmacokinetics.

 

Dose 6: Blood samples will be collected from all subjects within 30 minutes prior to the ingestion of Investigational Medicinal Product (IMP) and after 1 hour of ingestion of IMP

 

Detailed PK evaluation:

Multiple blood samples for PK evaluation will be collected from 20 subjects in the study (i.e. from 10 subjects receiving 1000 mg of WCK 2349 and from10 subjects receiving 1200 mg of WCK 2349). Two subjects from each centre (one subject from each dose group) will be selected for PK evaluation. The subjects for detailed PK evaluation will be selected after consultations with the principal investigators.

 

A total of 14 venous blood samples, each of 06 mL will be collected from the selected subjects for PK evaluation at the following time points  (considering ingestion of tablet as 0 hour with respect to the doses):

 

within 30 minutes before morning dose and then at 0.5 hrs 1, 1.5, 2, 4, 6, 8, 12, 13, 14, 16, 18 and 24 hours after 7th or 8th dose (whichever is morning dose).

 

 

 

Sample Collection and Processing

(Pharmacokinetics)

 

Blood samples will be collected through an indwelling intravenous cannula placed in the forearm vein of the subjects.  If required, it may also be collected through a fresh vein puncture. Initial 0.5 mL of blood will be discarded and subsequently, 06 mL of blood per sample will be withdrawn and transferred to pre-labeled sample collection tubes tube or vacutainers containing K2EDTA. The blood/plasma samples will be kept in ice-cold water bath, protected from light till the transfer to deep freezer.

Note: All sample collection activities will be carried out in subdued light conditions

 

Blood sample collected for PK analysis will be immediately centrifuged at 3000 ±100 r.p.m (ambient temperature) for 5 minutes to separate plasma. The separated plasma will be transferred to pre-labeled polypropylene tubes, in duplicates of equal volume and stored upright at -20 °C or below until transferred for analysis. 

 

 

Analytical Procedure

 

The plasma concentrations of Levonadifloxacin, and/or the sulphate metabolite of Levonadifloxacin will be quantified using a validated method at CPB Department Wockhardt Ltd., Mumbai.

Ethical Issues

 

The study will commence only after a written approval is obtained from the Institutional Review Board (IRB)/IEC.

 

This study will be conducted in accordance with the protocol, the ethical principles that have their origin in the Declaration of Helsinki (Seoul, 2008), and that are consistent with the principles of the International Conference on Harmonization (ICH) (Step 5) ‘Guidance on Good Clinical Practice’, and with procedures oriented to Good Laboratory Practice, and the applicable regulatory requirement(s).

 
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