Clinical trial NCT03998436
Conditions: Diabetic Foot Ulcer
Sponsor: Novalead Pharma Private Limited
Start date: 2018-12-26; Completion date: 2021-12-06
Enrollment: 176 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of the current Study is to determine the safety and effectiveness of Galnobax® plus Standard of Care versus only Standard of Care, in treating Diabetic Foot Ulcers (DFU). In addition, Study is designed to investigate the safety of Galnobax® vehicle for establishing non-deleterious effects of Vehicle on wound healing in the Subjects with DFU. The study is being conducted in 350 subjects being recruited in about 30 centers in India.

Detailed description:
The current study is a Prospective, Multicenter, Randomized, Double-Blind, Phase 3 Study to Evaluate the Safety and Efficacy of a Gel Formulation of Esmolol Hydrochloride (Galnobax®) in Treating Diabetic Foot Ulcers. The study evaluates the safety and effectiveness of Galnobax® plus Standard of Care versus only Standard of Care, in treating Diabetic Foot Ulcers (DFU). In addition, Study is designed to investigate the safety of Galnobax® vehicle for establishing non-deleterious effects of Vehicle on wound healing in the Subjects with DFU.

Arms: arm 1: Galnobax 14% gel along with Standard of Care (SoC) will be administered twice daily (150 subjects) arm 2: Only Standard of Care will be administered twice daily (150 subjects) arm 3: Vehicle gel along with Standard of Care (SoC) will be administered twice daily (50 subjects)
Interventions: intervention 1: Esmolol Hydrochloride intervention 2: Only Standard of Care intervention 3: Vehicle Gel
Intervention descriptions: intervention 1: Galnobax-14% gel application along with Standard of Care intervention 2: Only Standard of Care treatment intervention 3: Vehicle gel application along with Standard of Care

Protocol documents:
Prot_SAP_000.pdf: 
  
 
i  
A PROSPECTIVE, MULTICENTER, RANDOMIZED, DOUBLE-
BLIND, PHASE 3 STUDY TO EVALUATE THE SAFETY AND 
EFFICACY OF A GEL FORMULATION OF ESMOLOL 
HYDROCHLORIDE (GALNOBAX®) IN TREATING DIABETIC 
FOOT ULCERS 
Protocol Number: NG-A16 
IND Number: 102371 
IND Sponsor: NovaLead Pharma Pvt. Ltd. 
Anaahat, Plot No. 5, Ram Indu Park,  
S.No. 131/1b/2/11, Baner Road,  
Pune 411 045, INDIA  
Tel: +91-20-6410 0335 
Version Number: v 2.1 
28 Nov 2019 
 
 
 
 


  
 
ii  
Summary of Changes from Protocol Version 1.0 to Protocol Version 2.0   
Affected 
Section(s) 
Summary of Revisions Made 
Rationale 
Section 1.1  
Page 2 and  
Section 5.1 
Page 19 
Original Text 
1. Subjects, male or female, aged 18 
to 65 years (inclusive) with Type 1 
or Type 2 diabetes undergoing 
therapy for glycemic control 
Modified Text 
1. Subjects, male or female, aged 18 
to 75 years (inclusive) with Type 1 
or Type 2 diabetes undergoing 
therapy for glycemic control 
Many participating sites reported that 
several potential patients are being denied 
treatment due to upper age limit of 65 years 
in the current protocol. The life expectancy of 
India is about 69 years. In a community based 
cross-sectional study carried out in India, the 
average age of subjects with diabetic foot 
ulcer (DFU) is more than 60 years and 75% 
patients are with age more than 60 years as 
reported in a recent clinical study (Vibha et al. 
BMC Endocrine Disorders (2018) 18:43). 
Compared to patients with age < 50 years, 
the odds of developing DFU among patients 
in age group of 61-70 years was 4.4 and in age 
group of >70 years was 11.6. Thus, more non-
healing ulcers are seen in the elderly or 
geriatric 
population 
than 
in 
young 
population. By including patients up to 75 
years will establish safety and efficacy of 
Galnobax in geriatric population and such 
sub-population analysis will be carried out. 
The Galnobax treatment provided in this 
study is a topical treatment over the wound 
and hence not expected to lead to any severe 
side effects because of low systemic 
circulation of drug. 
 
 
 


  
 
iii  
Summary of Changes from Protocol Version 2.0 to Protocol Version 2.1   
Affected 
Section(s) 
Summary of Revisions Made 
Rationale 
Section 6.3 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Contact 
Details, 
Section 
1.1 
Page No 6, 
Section 
4.1 
Page No 16 
and  
Section 9.4.1 
Page No 43 
 
New Text Added 
In case the Subject  is staying far from the 
site (i.e. 40 km or more from the site) 
and/or Nurse is unable to visit every week 
to the site for treatment compliance check, 
following procedure will be followed for IP 
transport and compliance check: IP will be 
issued to the study Nurse at the time of the 
randomization visit along with study diary in 
an aluminum box having a lock. One key of 
this lock will be with the study Nurse and 
other with the unblinded CRC at the site. At 
the time of weekly site visit of the Subject, 
study Nurse will keep used IP tubes and 
Study diary in this box which will be locked 
and sent to the site with the Subject. Site 
unblinded CRC will take aluminum box from 
the subject and will check IP compliance as 
well as study diary. The IP will be reissued 
to the nurse after weighing the tubes and 
new study diary will also be issued (through 
which new dose of the subject will be 
conveyed to the Nurse). These materials 
will be kept in the aluminum box which will 
be locked and given to the Subject for 
handing over it to the study Nurse. This 
process will continue during all treatment 
visits.   
 
Original Text 
Total number of participating sites: - 20  
Modified Text 
Total number of participating sites: - 40  
In order to make convenient for the subjects 
and study Nurse residing far-off from the 
study site. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
In order to meet recruitment target for study 


  
 
iv  
CONTACT DETAILS 
Sponsor 
NovaLead Pharma Pvt. Ltd. 
Anaahat, Plot No. 5, Ram Indu Park,  
S.No. 131/1b/2/11, Baner Road,  
Pune 411 045, INDIA  
Tel: +91-20-6410 0335 
Sponsor Representative 
Dr. Sudhir Kulkarni 
Anaahat, Plot No. 5, Ram Indu Park,  
S.No. 131/1b/2/11, Baner Road,  
Pune 411 045, INDIA  
Tel: +91-20-6410 0335 
E-mail: sudhirk@novaleadpharma.com 
Clinical Research Organization 
JSS Medical Research India Private Limited  
Address: Plot 12/2, 6th Floor, Vatika Mindscapes Tower- B, 
Sarai Khwaja Metro Station, NH-2, Mathura Road, 
Sector 27 D, Faridabad, Haryana-121003, India 
Phone: +91 11 129 6613500 
Fax: +91 11 129 6613520 
Protocol Author [Medical writer]  
Dr Neha Pawar 
Address: JSS Medical Research India Private Limited 
Address: Plot 12/2, 6th Floor, Vatika Mindscapes Tower- B, 
Sarai Khwaja Metro Station, NH-2, Mathura Road,  
Sector 27 D, Faridabad, Haryana-121003, India 
Phone: +91 11 129 6613500 
Fax: +91 11 129 6613520 
E-mail: neha.pawar@jssresearch.com  
Biostatistician 
 
Mr. Santosh Kumar 
Address: JSS Medical Research India Private Limited 
Plot 12/2, .6th Floor, Vatika Mindscapes Tower-B 
Sarai Khwaja Metro Station, NH-2, Mathura Road 
Sector 27 D, Faridabad, Haryana-121003, India 
Phone: +91 11 129 6613500 
E-mail: santosh1.kumar@jssresearch.com 
Investigator Responsible for Conducting 
the Study 
This information is documented separately in the 
dossier to be submitted to the regulatory authority. 
Clinical Laboratory and other Medical 
and Technical Department(s) and 
Institutions involved in the Study 
This information is documented separately in the 
dossier to be submitted to the regulatory authority. 
Total number of participating sites 
40 






  
 
vii  
INVESTIGATOR’S DECLARATION 
I, the undersigned, declare that I have read and understood this protocol and hereby agree to conduct 
the Study in accordance with this protocol and to comply with all requirements regarding the obligations 
of investigators and all other pertinent requirements of the International Conference on Harmonization 
(ICH) of technical requirements for registration of pharmaceuticals for human use guideline for Good 
Clinical Practice ICH E6 (amended version), in accordance with Declaration of Helsinki (amended version), 
principles on Good Laboratory Practice, and all regulatory requirements for including all elements 
required for an Institutional Review Board to assess Study risks and benefits. 
I further agree to ensure that all associates assisting in the conduct of Study are informed regarding their 
obligations. 
I agree to comply with all relevant standard operating procedures required for the conduct of this Study 
and would document any significant deviation occurring during the Study. 
Principal Investigator: 
Name:  
Signature: 
Date: 
 
 


  
 
viii  
Table of Contents 
Contact details ............................................................................................................................................................ iv 
Table of Contents ................................................................................................................................................. viii 
STATEMENT OF COMPLIANCE ............................................................................................................................. 1 
1 
PROTOCOL SUMMARY ............................................................................................................................... 1 
1.1 
Synopsis ................................................................................................................................................ 1 
1.2 
Schema ................................................................................................................................................. 7 
1.3 
Schedule of Activities (SoA) ............................................................................................................... 8 
2 
INTRODUCTION .......................................................................................................................................... 11 
2.1 
Study Rationale .................................................................................................................................. 11 
2.2 
Background......................................................................................................................................... 11 
2.3 
Risk/Benefit Assessment .................................................................................................................. 13 
2.3.1 
Known Potential Risks ................................................................................................... 13 
2.3.2 
Known Potential Benefits .............................................................................................. 13 
2.3.3 
Assessment of Potential Risks and Benefits .............................................................. 14 
3 
OBJECTIVES AND ENDPOINTS .............................................................................................................. 15 
4 
STUDY DESIGN ........................................................................................................................................... 16 
4.1 
Overall Design .................................................................................................................................... 16 
4.2 
Scientific Rationale for Study Design.............................................................................................. 18 
4.3 
Justification for Dose ......................................................................................................................... 18 
4.4 
End of Study Definition ..................................................................................................................... 19 
5 
STUDY POPULATION ................................................................................................................................ 19 
5.1 
Inclusion Criteria ................................................................................................................................ 19 
5.2 
Exclusion Criteria ............................................................................................................................... 20 
5.3 
Lifestyle Considerations .................................................................................................................... 21 
5.4 
Screen Failures .................................................................................................................................. 21 
5.5 
Strategies for Recruitment and Retention ...................................................................................... 22 
6 
STUDY INTERVENTION ............................................................................................................................ 22 
6.1 
Study Intervention(s) Administration ............................................................................................... 22 
6.1.1 
Study Intervention Description ..................................................................................... 22 
6.1.2 
Dosing and Administration ............................................................................................ 23 
6.2 
Preparation/Handling/Storage/Accountability ................................................................................ 24 
6.2.1 
Acquisition and accountability ...................................................................................... 24 
6.2.2 
Formulation, Appearance, Packaging, and Labeling ................................................ 25 
6.2.3 
Product Storage and Stability ....................................................................................... 25 
6.2.4 
Preparation ...................................................................................................................... 26 
6.3 
Measures to Minimize Bias: Randomization and Blinding ........................................................... 26 
6.4 
Study Intervention Compliance ........................................................................................................ 26 
6.5 
Concomitant Therapy ........................................................................................................................ 27 
6.5.1 
Rescue Medicine ............................................................................................................ 27 
7 
STUDY 
INTERVENTION 
DISCONTINUATION 
AND 
PARTICIPANT 
DISCONTINUATION/WITHDRAWAL ....................................................................................................... 27 
7.1 
Discontinuation of Study Intervention ............................................................................................. 27 
7.2 
Participant Discontinuation/Withdrawal from the Study ............................................................... 27 
7.3 
Lost to Follow-Up ............................................................................................................................... 28 
8 
STUDY ASSESSMENTS AND PROCEDURES ..................................................................................... 29 
8.1 
Assessments and procedures in the study .................................................................................... 35 
8.2 
Adverse Events and Serious Adverse Events ............................................................................... 37 


  
 
ix  
8.2.1 
Definition of Adverse Events (AE) ............................................................................... 37 
8.2.2 
Definition of Serious Adverse Events (SAE) .............................................................. 37 
8.2.3 
Classification of an Adverse Event .............................................................................. 37 
8.2.4 
Time Period and Frequency for Event Assessment and Follow-Up ....................... 39 
8.2.5 
Adverse Event Reporting .............................................................................................. 39 
8.2.6 
Handling of Unresolved Adverse events .................................................................... 40 
8.2.7 
Event not to reported as AE ......................................................................................... 40 
8.2.8 
Serious Adverse Event Reporting ............................................................................... 40 
8.2.9 
Reporting Events to Participants ................................................................................. 41 
8.2.10 
Events of Special Interest ............................................................................................. 41 
8.2.11 
Reporting of Pregnancy ................................................................................................ 41 
8.2.12 
Expedited safety Reporting .......................................................................................... 41 
8.2.13 
Definition of Unanticipated Problems (UP) ................................................................. 41 
8.2.14 
Unanticipated Problem Reporting ................................................................................ 42 
8.2.15 
Reporting Unanticipated Problems to Participants ................................................... 42 
9 
STATISTICAL CONSIDERATIONS .......................................................................................................... 42 
9.1 
Statistical Hypotheses ....................................................................................................................... 42 
9.2 
Sample Size Determination .............................................................................................................. 42 
9.2.1 
Randomization and Stratification of Study Population: ............................................ 43 
9.3 
Populations for Analyses .................................................................................................................. 43 
9.4 
Statistical Analyses............................................................................................................................ 43 
9.4.1 
General Approach .......................................................................................................... 43 
9.4.2 
Analysis of the Primary Efficacy Endpoint .................................................................. 44 
9.4.3 
Analysis of the Secondary EFFICACY Endpoint(s) .................................................. 44 
9.4.4 
Safety Analyses .............................................................................................................. 44 
9.4.5 
Baseline Descriptive Statistics ..................................................................................... 45 
9.4.6 
Planned Interim Analyses ............................................................................................. 46 
9.4.7 
Methods used for Missing Data ................................................................................... 46 
9.4.8 
Handling of Outlier Data ................................................................................................ 46 
9.4.9 
Handling of TREATMENT FAILURE ........................................................................... 46 
9.4.10 
STATISTICAL ANALYSIS OF DATA .......................................................................... 46 
9.4.11 
Sub-Group Analyses ..................................................................................................... 46 
9.4.12 
Tabulation of Individual participant Data .................................................................... 46 
9.4.13 
Exploratory Analyses ..................................................................................................... 46 
10 
SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS .............................. 47 
10.1 
Regulatory, Ethical, and Study Oversight Considerations ........................................................... 47 
10.1.1 
Informed Consent Process ........................................................................................... 47 
10.1.2 
Study Discontinuation and Closure ............................................................................. 47 
10.1.3 
Confidentiality and Privacy ........................................................................................... 48 
10.1.4 
Key Roles and Study Governance .............................................................................. 48 
10.1.5 
Clinical Monitoring .......................................................................................................... 49 
10.1.6 
Quality Assurance and Quality Control ....................................................................... 50 
10.1.7 
Data Handling and Record Keeping ............................................................................ 50 
10.1.8 
Protocol Deviations ........................................................................................................ 51 
10.1.9 
Publication and Data Sharing Policy ........................................................................... 52 
10.1.10 
Conflict of Interest Policy .............................................................................................. 52 
10.2 
Additional Considerations ................................................................................................................. 52 


  
 
x  
10.2.1 
Possible DRUG INTERACTIONS AND PROHIBITED MEDICATIONS ................ 52 
10.3 
Abbreviations ...................................................................................................................................... 54 
10.4 
Protocol Amendment History ........................................................................................................... 56 
11 
APPENDICES ............................................................................................................................................... 57 
12 
REFERENCES ............................................................................................................................................. 64 
 
List of Tables 
Table 1 Subject progression as per condition of Target Ulcer .................................................................... 17 
Table 2 Dosing schedule ............................................................................................................................. 18 
Table 3 Composition of Galnobax® .............................................................................................................. 22 
Table 4 Labelling information of Galnobax® ................................................................................................ 25 
Table 5 Assessment of Intensity ................................................................................................................. 38 
Table 6 List of Abbreviations ....................................................................................................................... 54 


  
 
xi  
Definitions 
Term 
Definition 
Diabetic Foot Ulcer 
(DFU) 
Diabetic foot ulceration is full-thickness penetration of the dermis of the foot 
in a person with diabetes. 
Standard of Care 
(SoC) 
Wound cleaning by normal saline, maintenance of moist wound environment 
and off-loading of the Target Ulcer. In addition, during Site Visits removal of 
necrotic, infected and/or nonviable tissue by debridement and management 
of infection to be done by the Investigator, if required. 
Target Ulcer Closure 
100% re-epithelialization without drainage or dressing requirement (except if 
recommended by the Investigator for covering of the closed wound) to be 
confirmed by two consecutive site visits two weeks apart from first 
observation of closure. 
Time to Target Ulcer 
Closure 
Duration of first observation of closure from Baseline visit for those Target 
Ulcers for which conditions for Target Ulcer Closure were satisfied.  
Intent to Treat (ITT) 
Population (Safety 
Evaluable Population) 
All Subjects who are randomized and received at least one dose of Study 
medication will be included in ITT Population. 
Full Analysis Set (FAS) 
Population (Efficacy 
Evaluable Population) 
All randomized Subjects who had at least 6 weekly Site Visits for the 
assessments of Target Ulcer Closure or had Target Ulcer closed earlier than 6 
weeks.  
Per Protocol (PP) 
Population 
All randomized Subjects who have completed the Study without any major 
protocol deviation.  


A Prospective, Multicenter, Randomized, Double-Blind, Phase 3 Study to Evaluate the Safety and Efficacy of a Gel Formulation 
of Esmolol Hydrochloride (Galnobax®) in Treating Diabetic Foot Ulcers. 
 Version 2.1 
Protocol NG-A16 
28 Nov 2019 
Confidential 
 
1 
STATEMENT OF COMPLIANCE 
The trial will be conducted in accordance with International Council for Harmonization Good Clinical 
Practice (ICH GCP), Declaration of Helsinki and GCP guidelines as per Central Drugs Standard Control 
Organization (CDSCO), Directorate General of Health Services (DGHS), Government of India. The Principal 
Investigator will ensure that no deviation from, or changes to the protocol will take place without prior 
agreement from the Sponsor and documented approval from the Ethics Committee (EC), except where 
necessary to eliminate an immediate hazard(s) to the trial participants. All personnel involved in the 
conduct of this Study have completed Human Subjects Protection and ICH GCP Training. 
The protocol, informed consent form(s), recruitment materials, and all participant materials will be 
submitted to the EC for review and approval. Approval of both the protocol and the consent form must 
be obtained before any participant is enrolled. Any amendment to the protocol will require review and 
approval by the EC before the changes are implemented to the Study. All changes to the consent form will 
be EC approved and a determination will be made regarding whether a new consent needs to be obtained 
from participants who provided consent, using a previously approved consent form. 
1 
 
PROTOCOL SUMMARY 
1.1 
SYNOPSIS  
Title: 
A Prospective, Multicenter, Randomized, Double-Blind, Phase 3 Study 
to Evaluate the Safety and Efficacy of a Gel Formulation of Esmolol 
Hydrochloride (Galnobax®) in Treating Diabetic Foot Ulcers 
Study Description: 
The purpose of the current Study is to determine the safety and 
effectiveness of Galnobax® plus Standard of Care versus only Standard 
of Care, in treating DFU. In addition, Study is designed to investigate 
the safety of Galnobax® vehicle for establishing non-deleterious 
effects of Vehicle on wound healing in the Subjects with DFU. 
Objectives: 
 
The objective of this Study is to evaluate efficacy and safety of 
Galnobax® gel (14% twice daily application) plus Standard of Care 
treatment versus only Standard of Care for healing of DFU. 
 
Primary Objective: 
1. To assess the efficacy of Galnobax® in terms of proportion of 
Subjects achieving Target Ulcer Closure within 12-week 
Treatment Phase upon application of Galnobax® plus Standard 
of Care as against only Standard of Care treatment, as assessed 
by the blinded Investigator.  
 
Secondary Objectives: 
1. To compare Time to Target Ulcer Closure within the 12-week 
Treatment Phase, upon application of Galnobax® plus 
Standard of Care as against only Standard of Care treatment, 
as assessed by the blinded Investigator. 
2. To compare proportion of Subjects achieving Target Ulcer 
Closure till End of Study upon application of Galnobax® plus 
Standard of Care as against only Standard of Care treatment, 
as assessed by the blinded Investigator.  


A Prospective, Multicenter, Randomized, Double-Blind, Phase 3 Study to Evaluate the Safety and Efficacy of a Gel Formulation 
of Esmolol Hydrochloride (Galnobax®) in Treating Diabetic Foot Ulcers. 
 Version 2.1 
Protocol NG-A16 
28 Nov 2019 
Confidential 
 
2 
 
Safety Objectives: 
1. To investigate the safety of Galnobax® treatment during the 
Study.  
2. To investigate the safety of Galnobax® vehicle for establishing 
non-deleterious effects of Vehicle on wound healing.  
Endpoints: 
Primary Endpoint: 
Efficacy endpoint: The efficacy assessment will involve Galnobax® 
plus Standard of Care and only Standard of Care groups 
1. Proportion of Subjects achieving Target Ulcer Closure within 
12-week 
Treatment 
Phase, 
as 
assessed 
by 
blinded 
Investigator. 
Secondary Endpoints:  
Efficacy endpoints: 
1. Time to Target Ulcer Closure during the 12-week Treatment 
Phase, as assessed by the blinded Investigator. 
2. Proportion of Subjects achieving Target Ulcer Closure till End 
of Study, as assessed by the blinded Investigator. 
Safety endpoints:  
1. Proportion of Subjects with treatment emergent adverse 
events (TEAEs). 
2. Proportion of Subjects with events related to the local wound 
assessment of Target Ulcer in Vehicle plus Standard of Care 
group. 
Study Population: 
A maximum of 350 Subjects will be randomized for this Phase 3 clinical 
Study who have DFU and satisfy eligibility criteria given below and in 
Section 5. The break-up of these 350 Subjects is as follows: 
Group 1: Galnobax® + SoC such that minimum number of Subjects in 
this group is 120. 
Group 2: SoC alone such that minimum number of Subjects in this 
group is 120.  
Provision for drop-outs in Groups 1 and 2: 20% i.e. 60 Subjects 
Group 3: Vehicle + SoC such that the maximum number of Subjects in 
this group is 50 to evaluate the safety of Galnobax® vehicle. 
Eligibility Criteria 
a. Inclusion criteria 
The Subjects who satisfy all the following inclusion criteria will be 
enrolled in the Study and subsequently randomized: 


A Prospective, Multicenter, Randomized, Double-Blind, Phase 3 Study to Evaluate the Safety and Efficacy of a Gel Formulation 
of Esmolol Hydrochloride (Galnobax®) in Treating Diabetic Foot Ulcers. 
 Version 2.1 
Protocol NG-A16 
28 Nov 2019 
Confidential 
 
3 
1. Subjects, male or female, aged 18 to 75 years (inclusive) with 
Type 1 or Type 2 diabetes undergoing therapy for glycemic 
control 
2. Subject has glycosylated hemoglobin, HbA1C, ≤ 12% 
3. Subject with diagnosis of neuropathic foot ulcer by 10g 
monofilament test 
4. Subject has adequate vascular perfusion of the affected limb, 
confirmed by Ankle-Brachial Index (ABI) ≥ 0.65 and ≤ 1.3 
Note: If the ABI measurement is >1.30 one of the following 
confirmatory tests must be performed for subject to be considered 
eligible. Prior documented flow Study within the last 3 months of the 
Screening Visit is acceptable. 
a. Great Toe pressure (plethysmography) > 40 mm Hg; 
b. Transcutaneous partial pressure oxygen (TcPO2) at the 
foot > 40 mm Hg; 
c. Skin Perfusion Pressure (SPP) > 40 mm Hg; 
d. Doppler ultrasound (biphasic or triphasic waveforms) 
consistent with adequate blood flow to the affected 
extremity, as determined by the standard practices of the 
Investigator and the site 
5. Presence of at least one DFU that meets all of the following 
criteria: 
a. A full-thickness ulcer of Grade A1 as per Texas classification 
system; 
b. Ulcer is located below or up to 5 cm above the malleoli 
(excluding ulcers between the toes); 
c. Ulcer size (area) is ≥ 2 cm2 and ≤ 15 cm2 (post-
debridement); 
d. There is a minimum 3 cm margin between the qualifying 
Target Ulcer and any other ulcers on the specified foot, 
post-debridement; 
e. No exposed bone, tendon, muscle, ligament or joint 
capsule, and no tunneling, undermining, or sinus tracts; 
f. Unresponsive to ulcer care and open for at least 6 weeks at 
the time of the Screening Visit; 
g. Ulcer is non-infected as determined by clinical assessment 
and complete hemogram; 
h. Ulcer has a clean, granulating base free of adherent slough 
to the greatest extent possible as per Investigator; 
i. 
Ulcer area reduction < 30% from the Screening Visit to 
Baseline visit 
Note: Criterion 4(i) will be evaluated at the time of randomization. If 
the subject has more than one qualifying DFU, the ulcer designated as 


A Prospective, Multicenter, Randomized, Double-Blind, Phase 3 Study to Evaluate the Safety and Efficacy of a Gel Formulation 
of Esmolol Hydrochloride (Galnobax®) in Treating Diabetic Foot Ulcers. 
 Version 2.1 
Protocol NG-A16 
28 Nov 2019 
Confidential 
 
4 
the Target Ulcer should be the ulcer preferably on the plantar region 
which is older, deeper and with a larger area.  
6. Clinically normal resting 12-lead ECG at Screening Visit or, if 
abnormal, considered not clinically significant by the 
Investigator 
7. Subject, if female of child-bearing potential, has a negative 
urine pregnancy test at Screening and willing to use acceptable 
methods of contraception (birth control pills, barriers) or 
abstinence throughout the Study 
8. Subject is able and willing to comply with Study procedures 
including the use of an off-loading device (as applicable for the 
location of the ulcer) and adhere to protocol during the Study 
in the opinion of Investigator 
9. A Subject or LAR agrees to sign informed consent form and 
allow audio visual recording of consent, if applicable 
b. Exclusion criteria 
Subjects will not be eligible for enrolment in the Study if they meet any 
of the exclusion criteria listed below: 
1. Actively infected ulcers with or without purulent discharge, 
ulcers with exposed bone or associated with osteomyelitis  
Note: The osteomyelitis should be ruled out by clinical examination and 
X-ray findings where found necessary by the Investigator. If the 
Investigator is unable to ascertain the condition of osteomyelitis by 
probing of the Target Ulcer or digital X-ray then Investigator may use 
other techniques such as MRI, bone scintigraphy, leukocyte scanning or 
bone biopsy to rule out the presence of osteomyelitis based on 
availability of the investigation facility at the clinical sites. 
Note: If foot has more than one ulcers and one of them is infected, then 
Target Ulcer should not be selected from this foot unless all ulcers on 
the foot are free of infection. If subject has ulcers on both foots and 
infection is seen in the ulcer on non-target foot, subject may be included 
in the Study with prescribing oral antibiotic treatment for non-Target 
Ulcer. 


A Prospective, Multicenter, Randomized, Double-Blind, Phase 3 Study to Evaluate the Safety and Efficacy of a Gel Formulation 
of Esmolol Hydrochloride (Galnobax®) in Treating Diabetic Foot Ulcers. 
 Version 2.1 
Protocol NG-A16 
28 Nov 2019 
Confidential 
 
5 
2. Subjects with more than three ulcers below knee  
3. Subjects with Target Ulcer requiring off-loading that cannot be 
effectively off-loaded; or unable to tolerate the off-loading 
method 
4. Subject has ulcers caused by a disease other than diabetes, 
e.g., fungal ulcerations, malignant ulcerations, and ulcerations 
due to venous or arterial insufficiency, or due to hematological 
disorders, in the opinion of the Investigator 
5. Ulcer, about which the Investigator is suspicious for cancer  
Note: In case of such suspicion, ulcer present more than 1 year will 
require a 3-mm punch biopsy to rule out malignancy. Prior documented 
negative ulcer biopsy within the last 1 year of the Screening Visit is 
acceptable. 
6. Subjects with a gangrenous or ischemic ulcer 
7. Subject with ulcer that in the opinion of the Investigator, may 
need amputation 
8. Subject with Target ulcer where wound measurement is not 
possible, such as ulcers between toes 
9. Body mass index (BMI) > 40 kg/m2 
10. Laboratory values at Screening of:  
a) 
Hemoglobin < 10.0 g/dL 
b) 
White Blood Cells (WBC) < 2.0 X 109 cells/L 
c) 
Liver function studies [Total bilirubin, aspartate 
aminotransferase (AST) and alanine transaminase 
(ALT)] > 3x the upper limit of normal 
d) 
Albumin < 2.5 g/dL  
e) 
eGFR < 25 mL/min 
11. Presence of any existing clinically significant medical 
condition(s) that, in the opinion of the Investigator, could 
interfere with wound healing, including but not limited to the 
following: 
a) 
Vasculitis or connective tissue disease 
b) 
Buerger’s disease, Raynaud's or other peripheral 
vascular disease 
c) 
Clinically significant claudication or peripheral edema 
on the affected limb 
d) 
Acute or unstable Charcot foot 
e) 
Aplastic anemia or exacerbation of sickle cell anemia 
f) 
Current sepsis 
g) 
Congestive heart failure (NYHA Class III or IV), coronary 
heart disease with ST segment elevation, myocardial 
infarction, or coronary artery bypass graft or 
percutaneous transluminal coronary angioplasty 
within the last 6 months  
h) 
End-stage renal disease 
i) 
Immunosuppression 
j) 
Acquired immune deficiency syndrome (AIDS) or HIV 
positive 


A Prospective, Multicenter, Randomized, Double-Blind, Phase 3 Study to Evaluate the Safety and Efficacy of a Gel Formulation 
of Esmolol Hydrochloride (Galnobax®) in Treating Diabetic Foot Ulcers. 
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k) 
Any malignancy history 
12. Subject has received or is currently receiving or scheduled to 
receive any of following medication or therapies during the 
course of the Study 
a) 
Immunosuppressants 
(chronic 
systemic 
corticosteroids) within 30 days of randomization visit 
b) 
Revascularization surgery (e.g., angioplasty, coronary 
artery 
bypass 
surgery, 
transmyocardial 
revascularization) within 30 days of randomization 
visit 
c) 
Growth factors within 30 days of randomization visit 
d) 
Hyperbaric oxygen therapy (HBOT) within last 7 days 
of randomization visit 
e) 
Negative pressure wound therapy (NPWT) within last 
7 days of randomization visit 
f) 
Bioengineered tissue or skin substitutes within 30 days 
of randomization visit 
g) 
Application of topical steroids to the ulcer surface 
within 30 days of randomization visit 
h) 
Use of any investigational drug(s) or therapies within 
30 days of randomization visit 
13. Subject with intolerance to β-blockers at any time in the past 
14. Has any other factor which may, in the opinion of the 
Investigator, compromise participation and/or follow-up in the 
Study 
Phase: 
3 
Description of Sites/Facilities 
Enrolling Participants: 
This Study will be conducted at 40 sites across India with competitive 
recruitment amongst sites.  
Description of Study 
Intervention: 
Galnobax® 14% gel, Twice daily, Topically  
Study Duration: 
16 months 
Participant Duration: 
6 months 


A Prospective, Multicenter, Randomized, Double-Blind, Phase 3 Study to Evaluate the Safety and Efficacy of a Gel Formulation 
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1.2 
SCHEMA 
Screening  
Visit V1  
(Week -1, 
Day -10 to -7) 
 
 
Baseline  
Visit 2 
(Week 0, Day 0) 
[Window period  
7-10 days 
From screening]  
 
 
 
 
 
 
 
  
 
 
 
 
Treatment visits  
Visit 3 to Visit 14 
(Week 1 to  
Week 12) 
Day 7 to Day 84 
[Window period  
±3 days for each 
Scheduled visits] 
 
 
 
Follow-up 
Visits (Week  
14 to Week 24 
[FU1:  
Visit 15/Day 98 
to FU4: Visit 
18/Day 168  
[Window period  
±3/±5 days] 
 
 
Total N: 420 (approx.) Obtain informed consent. Screen potential participants by inclusion 
and exclusion criteria; obtain history and other information refer in Section 1.3, Schedule of 
Activities for detail assessment 
Perform baseline assessments. 
Assessment of vital sign, foot examinations, local examination, infection status of Target 
Ulcer, Ulcer characteristic, Target Ulcer measurement and classification, Debridement of 
Target Ulcer, Measurement of random blood glucose. Dispensing of IP, Dispensing of Study 
Diary, Wound dressing material and offloading footwear to the Subject. Administer initial 
Study intervention.  
Subject education, recording of concomitant medication and assessment of AE. Refer to 
Section 1.3, Schedule of Activities for detail assessment 
Follow-up assessments of Study endpoints and safety 
Assessment of vital sign, Target Ulcer measurement and classification, Ulcer characteristics, 
local examination and infection status, local pain, edema and erythema (at all FU visits). 
Assessment of ECG (only FU1), urine pregnancy test (only FU2), laboratory tests and Foot 
examination (FU4) to be done at specific visits. Assessment of AE, recording of concomitant 
medications, subject education, Collection and Review of Subject diary. For detail 
examination refer to Section 1.3, Schedule of Activities for detail assessment 
Arm 3 
Vehicle plus 
Standard of 
Care  
N 50
Arm 1 
Galnobax® 14% 
plus Standard of 
Care. 
N: 150
Repeat Study intervention as per assigned in group twice daily for up to 12-weeks or until 
complete closure of Target Ulcer, whichever is earlier. Assessment of vital signs, random 
blood glucose, Target Ulcer measurement and classification, local examination, infection 
status, Ulcer characteristics. Dispensing of Subject Diary and Collection and review of Study 
Diary, Subject education, recording of concomitant medication and assessment of AE (visit 3 
to 14). Urine pregnancy test, other laboratory tests, ECG, and foot examination will be done 
after every 4 weeks till visit 14 or EOT. Refer to Section 1.3, Schedule of Activities for detail 
assessment  
Randomize  
Total N: 350 
Arm 2 
Standard of Care 
only 
N: 150  
FU1 Visit 
1st closure 
Verification 
14±3 Days after EOT 
FU2 Visit 
Final closure 
Confirmation 
28±3 Days after EOT 
FU3 Visit 
Observation Period 
56±5 Days after EOT 
FU4 Visit 
Observation Period 
84±5 Days after EOT 


A Prospective, Multicenter, Randomized, Double-Blind, Phase 3 Study to Evaluate the Safety and Efficacy of a Gel Formulation of Esmolol Hydrochloride (Galnobax®) in Treating 
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1.3 
SCHEDULE OF ACTIVITIES (SOA) 


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Screening 
visit 
Baseline 
visit 
Treatment visito 
Follow-up visitp 
Week 
-1 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12/EOTr 
14 
16 
20 
24/EOSs 
Day 
-10 to -7 
0 
7 
14 
21 
28 
35 
42 
49 
56 
63 
70 
77 
84 
98 
112 
140 
168 
Visit 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
13 
14 
15/FU1 
16/FU2 
17/FU3 
18/FU4 
Window period (days) 
 
7-10q 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
±5 
±5t 
ICF 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Inclusion/exclusion criteria 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demography 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Urine Pregnancy test 
X 
 
 
 
 
X 
 
 
 
X 
 
 
 
X 
 
X 
 
 
Medical historya 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Vital signs 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Physical examination with body 
weight 
X 
 
 
 
 
X 
 
 
 
X 
 
 
 
X 
 
 
 
X 
Laboratory 
testsb 
Hematology tests 
X 
 
 
 
 
X 
 
 
 
X 
 
 
 
X 
 
 
 
X 
Biochemistry tests 
X 
 
 
 
 
X 
 
 
 
X 
 
 
 
X 
 
 
 
X 
HbA1C 
X 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
 
 
X 
Random blood 
glucose  
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
ECG/EKG or 2-D ECHOc  
X 
 
 
 
 
X 
 
 
 
X 
 
 
 
X 
X 
 
 
 
Dispensing Study Diary 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Dispensing Subject Diary 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
 
 
 
Collection and review of Study 
Diaryd 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
 
 
 
 
Collection and review of Subject 
Diarye 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
X 
X 
X 
Treatment compliance check 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
Offloading, dressing compliance 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Ankle brachial indexf + 
monofilament test 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Dispensing of Offloading footwear 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X-Rayg 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Foot Examination for (Vascular, 
neurological, dermatological & 
musculoskeletal assessment)  
X 
X 
 
 
 
X 
 
 
 
X 
 
 
 
X 
 
 
 
X 
Target Ulcer classification 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Local examination, infection status 
of Target Ulcer 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 


A Prospective, Multicenter, Randomized, Double-Blind, Phase 3 Study to Evaluate the Safety and Efficacy of a Gel Formulation of Esmolol Hydrochloride (Galnobax®) in Treating 
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Ulcer characteristics (Edge, color, 
peri-ulcer, drainage, granulation 
etc.) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Target Ulcer measurement  
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Randomizationh 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Dispensing of IPi 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Treatment application 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
Subject Educationj 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Recording of concomitant 
medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
AE recordingk 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Debridement of Target Ulcerl 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Nutritional informationm 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Photographs of both legs from 
various angles (medial, lateral, 
dorsal and plantar)n 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Clinical assessment of infection 
status of non-study ulcer(s) 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Assessment of local pain 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Assessment of local edema 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Assessment of local erythema 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Dispensing of Wound dressing 
material* 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 


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a Medical and ulcer history will also include foot specific history such as location and duration of the selected ulcer and other medical conditions of the 
Subject. Events occurring prior to application of first dose of IP will be recorded as medical history and events occurring after the application of first dose of 
IP will be recorded as adverse events 
b Laboratory tests will be performed at Screening Visit V1, V6, V10, V14 or EOT and during follow-up only at V18 or EOS and will include:  
• 
Hematology parameters: CBC: WBC, RBC, Hematocrit, Hemoglobin, MCV, MCH, MCHC, RDW, Platelet Count, Mean Platelet Volume.  
• 
Biochemistry parameters: Glucose, Calcium, Albumin, Total Protein, Sodium, Potassium, CO2, Chloride, BUN, eGFR, ALP, ALT, AST, Bilirubin.  
• 
HbA1C  
• 
Urine pregnancy test will be done in women of child bearing potential at Screening Visit V1, V6, V10, V14 or EOT and during follow-up only at 
V16/FU2 throughout the Study 
c ECG will be done at Screening Visit V1, V6, V10, and V14 or EOT and during follow-up only at V15/FU1 
d Study Diary review will be done by unblinded Investigator during Study Nurse visit to the site 
e Subject Diary review will be done by blinded Investigator for all subjects in follow up Phase 
f Ankle Brachial Index and 5.0 SW monofilament test will be performed at the Screening Visit V1 
g X-ray of the foot under Study will be performed at the Screening Visit and further at the Investigator’s discretion to rule out osteomyelitis. 
h The Investigator will re-assess Subject eligibility at Baseline Visit V2, with emphasis on reduction of ulcer size since Screening Visit V1. If a potential Target 
Ulcer has decreased ≥30% between the Screening and Baseline visits, then this potential Target Ulcer cannot be designated as Target Ulcer. If none of the 
potential Target Ulcer(s) meet eligibility criteria at the Baseline V2, Subject will be considered as screen failure and exit the Study without further evaluation. 
If the Subject has more than one qualifying ulcer, the ulcer designated as the Target Ulcer should be the ulcer on the plantar region which is older, deeper 
and with a larger area 
i Re-dispensing of IP may occur as and when required during Treatment Phase 
j Subject Education and training on Diabetes management and use of off-loading device will be done as and when required 
k The AE reporting will begin from the application of the first dose of the IP from the Baseline Visit 
l Debridement of ulcer as and when necessary during site visit 
m Nutritional information should be provided to Subject as and when necessary 
n Photographs of both the legs will be taken from various angles to ensure that there are no more than three ulcers on both the legs 
o In case the ulcer/wound closes within 12-weeks of Treatment Phase, the Subject will immediately enter the 12-weeks of Follow-Up Phase. In case of the 
Subject, whose Target Ulcer reopens during 12-weeks of Treatment Phase (within 84 days from Baseline) which is prior to the confirmation of Target Ulcer 
closure, the Subject would be given the treatment to complete 12-week of Treatment Phase 
p During Follow-Up Phase, if the Target Ulcer has reopened after confirmation of its closure, the Subject will still be continued with the Follow-up assessment.  
q This window period is from the Screening Visit  
r EOT is at week 12 visit or any visit on which first observation of Target Ulcer closure has happened or treatment is Stopped 
s EOS is at week 24 visit or any visit on which the Subject exits the Study 
t Window period of ±3 days will be allowed for each Treatment visit as well as FU1 and FU2 visits and window period of ±5 will be allowed for FU3 and FU4 
Note: *Dispensing of Wound dressing material will be provided as long as required 


A Prospective, Multicenter, Randomized, Double-Blind, Phase 3 Study to Evaluate the Safety and Efficacy of a Gel 
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2 
 
INTRODUCTION 
2.1 
STUDY RATIONALE  
The scourge of DFU is expected to increase given the increasing global prevalence of type 2 
diabetes mellitus (T2DM). The diabetic population in India which presently is 69.2 million is 
expected to increase to 123.5 million by 2040.1 Among different diabetes related complications, 
DFU is second most common affecting approximately 15% of diabetic patients during their 
lifetime.2 It has been reported that 14% - 24% of DFU patients require amputation. Moreover, 
recurrence of DFU in a subject is reported in more than 50% cases in a span of 2-5 years.3 4 Even 
after 20 weeks of standard care treatment, DFUs remain unhealed at 67% time.5 Notably, diabetes 
is responsible for more than 1 million amputations annually with every 30 seconds a leg is 
amputated for DFU.6 About 85% of lower limb amputations in India as well in USA are preceded by 
a DFU.7-9 Individuals with lower-limb amputations are at risk for developing concomitant medical 
ailments, report a diminished quality of life, and are more likely to die than other individuals with 
diabetes.10 11 Following an amputation, the chance for another amputation is approximately 50% 
within 5 years of period.9 The 5-year mortality rate after lower limb amputation ranges from 39% 
to 68%.12 The cost of DFU treatment in India is about $650-$3250 and every episode of infection in 
DFU costs $1000 in India.13  
DFU can develop because of acute or chronic cutaneous compromise of the skin, arterial 
insufficiency, peripheral neuropathy, or a combination of these factors.14 Despite several 
treatment modalities that have been reported, including advanced moist wound therapy (AMWT), 
bioengineered tissue or skin substitutes, growth factors, electric stimulation and negative pressure 
wound therapy (NPWT), DFU generally does not respond well to treatment.15-18 In its absence, the 
current Standard of care (SoC) for DFU involves pressure relief (off-loading), wound debridement, 
treatment of infection and ischemia, local wound-care comprising cleansing with saline and the 
use of modern wound dressings that promote a moist environment.19  
These statistical data as discussed above provide the rationale for Galnobax® to be investigated as 
there is an urgent need for new treatment options for DFU. 
Galnobax® has potential to provide a safer, effective and affordable treatment option for DFU 
Subjects. This Phase 3 Study of Galnobax® will be conducted with the objective of assessing the 
efficacy of Galnobax® gel in Subjects suffering from DFU from Baseline to Week 12 or wound 
closure whichever is earlier, in a larger population to obtain a statistically significant outcome. The 
Study design maintains same treatment period (12-weeks), same follow-up period (12-weeks), 
similar inclusion and exclusion criteria and similar SoC as in previously conducted Phase 1/2 Study. 
2.2 
BACKGROUND  
Investigational drug product - Galnobax® 
Galnobax® is a new gel formulation to be administered topically containing a pharmaceutically 
approved drug substance Esmolol hydrochloride. Esmolol hydrochloride is a beta1-selective 
(cardioselective) adrenergic receptor blocking agent with a short duration of action (elimination 
half-life is approx. 9 minutes) and no intrinsic sympathomimetic or membrane stabilizing activity 
at therapeutic dosages. Esmolol hydrochloride inhibits the beta1 receptors located chiefly in 
cardiac muscle, but this preferential effect is not absolute and at higher doses it begins to inhibit 
beta2 receptors located chiefly in the bronchial and vascular musculature. Esmolol hydrochloride 
is metabolized by esterase from erythrocytes and is not metabolized by liver or kidney.20  
Non-clinical Studies 


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The non-clinical studies on the drug substance of Galnobax® demonstrates that it is capable of 
pleiotropic actions to heal DFU such as:21  
• 
Aldose reductase inhibition 
• 
Inhibition of sorbitol accumulation in erythrocytes and inhibition of Advanced Glycosylated 
End products formation 
• 
Faster wound closure in scratch assay under high glucose environment 
The non-clinical studies on Galnobax® using globally accepted animal models for evaluating 
pharmacological parameters for healing of DFU such as diabetic Lewis Rats (for pharmacokinetic 
studies) and diabetic Hairless rats have demonstrated that; 
a. Galnobax® closes the diabetic wound faster than the control group for up to 10 days. 
b. While the wound epithelialization in the treatment groups is like the control groups, it is 
amply demonstrated that the Galnobax® group had improved induction of internal healing 
processes such as endogenous nitric oxide production in inflammatory and proliferative 
phase and higher collagen formation and deposition in the remodeling phase of diabetic 
wound healing than the control group resulting in better quality of wound healing. 
c. Better healing in Galnobax® treated wounds is also demonstrated by laser Doppler studies 
which show higher average flux of blood flow in vehicle treated groups.  
d. Galnobax® has multiple therapeutic actions such as Nitric oxide induction, Collagen 
turnover at the wound site, neo-vascularization and anti-oxidant effects contribute to 
faster healing and closure compared to the control.  
Additionally, the non-clinical PK studies evidence that by application of Galnobax®, Esmolol 
hydrochloride is minimally absorbed (less than 10 ng/mL in rats and average maximum 
concentration of 30 ng/mL in minipigs) into systemic circulation, thereby evidencing that 
Galnobax® is safe to use in the treatment of DFU. The above observations and the fact that Esmolol 
hydrochloride is a pharmaceutically approved drug with well elucidated safety profile, suggest that 
Galnobax® has significantly favorable risk/benefit profile.21  
Clinical Studies 
The efficacy analysis of Phase 1/2 clinical Study of Galnobax® numerically establishes that 
Galnobax® 14% treatment has advantage in terms of area and volume reduction over the Vehicle 
and Galnobax® 20%. This advantage of Galnobax® 14% is more pronounced in hard to heal DFU: 
• 
In plantar DFU: Galnobax® 14% showed 98.1% area closure Vs 75.8% for Placebo. The 
median time for complete wound closure was 35 days for Galnobax® 14% Vs 64 days for 
Placebo21  
• 
In older DFU: On DFUs older than 8 weeks at baseline, Galnobax® 14% group showed 
complete closure in 75% Subjects Vs 43% in Placebo group21 
The safety analysis of Phase 1/2 clinical Study establishes and reconfirms the findings of the non-
clinical studies that Galnobax® is safe for long term use (tested for 12-weeks) in both 14% and 20% 
concentrations. Overall 29 adverse events (AEs) were observed in the Study and only two were 
related to the Study treatment. These two AEs were local mild allergic reactions which were found 
to be reversible. The safety of Galnobax® is further reinforced by the pharmacokinetic analysis of 
Phase 1/2 clinical Study which establishes that the systemic concentration of its drug substance 
(Esmolol hydrochloride) was below quantification limit (10 ng/mL) at any time during the 


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treatment period, irrespective of wounds of different sizes and doses of Galnobax®. This 
observation is significantly lower than:  
• 
Systemic concentration of 868-1470 ng/mL observed for approved doses of intravenous 
Esmolol hydrochoride  
• 
Human peak plasma concentration of 500, 1200 and 2500 ng/mL respectively observed for 
the infusion of Esmolol hydrochloride at the rate of 100, 250 and 500 μg/kg/min22 
Considering the above facts, it is proposed to investigate Galnobax® 14% in a Phase 3 Study to 
establish safety and efficacy with statistical significance. 
2.3 
RISK/BENEFIT ASSESSMENT 
2.3.1 KNOWN POTENTIAL RISKS  
Phase 1/2 study of Galnobax® on 44 DFU Subjects reported the following: 
a. No deaths were reported during the study. 
b. There were 4 SAEs (arthritis bacterial, infected skin ulcer, gastroenteritis, and cellulitis) 
reported during the study, all in the Galnobax® 20% group and none determined by the 
Investigator as related to the study drug. All these SAEs were resolved during the study.  
c. There were 29 AEs of which only 2 were determined by the Investigator as related to the 
Study drug (TEAEs) with 1 Subject each in the Galnobax® 14% [TEAE: skin discoloration] 
and Galnobax® 20% [TEAE: erythema] groups. Both these events were non-serious and 
mild in intensity which were reversible on discontinuation of drug. None of the vital signs 
and Electrocardiogram (ECG) abnormalities were reported as TEAEs.  
d. Furthermore, the drug substance used in Galnobax® (Esmolol hydrochloride) is approved 
for intravenous application with all reported AEs being mild, transient and reported to be 
reversible after discontinuation of dosing in spite of systemic concentration of 868-1470 
ng/mL 23 and human peak plasma concentration of 500, 1200 and 2500 ng/mL respectively 
at the infusion rate of 100, 250 and 500 μg/kg/min22. As against this, the clinical 
pharmacokinetic (PK) studies of Galnobax® conducted as part of the Phase 1/2 study 
demonstrated that the systemic concentration of its drug substance (Esmolol 
hydrochloride) through topical administration was below quantification limit (10 ng/mL) 
at any time during the treatment period, irrespective of wounds of different sizes and 
doses of Galnobax®. This low systemic absorption and localized action is also substantiated 
by non-clinical PK studies conducted in Lewis rats and in minipigs.21  
The non-clinical toxicity studies of Galnobax® showed slight irritation in rabbit model which was 
found to be reversible and did not elicit skin sensitization in guinea pig model.  
All of the above is sufficient to conclude that Galnobax® with no deaths, no SAEs related to the 
drug, only 2 drug related AEs which were reversible and minimal systemic absorption (way below 
approved tolerated concentrations) as established in Phase 1/2 study has a favorable human safety 
profile.21  
2.3.2 KNOWN POTENTIAL BENEFITS  
Basic science and translational investigation are intensively researching the key abnormalities 
responsible for altering the wound-healing process in DM.24 Yet, in spite of some available 
therapies, DFU still remains ineffectively treated in 67% of the cases resulting in lower extremity 


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amputations in about 15% of the cases.25 Thus, DFU continues to be a strong medical unmet need 
and calls for a new drug which can comprehensively address the underlying structural and 
functional abnormalities through which DM impairs wound healing. There is a dire need to improve 
the clinical outcomes and improve the quality of life of Subjects with DFUs.  
14% Galnobax®, a gel formulation for topical administration with an approved drug substance 
(Esmolol hydrochloride) with favorable data from the Phase 1/2 clinical study and non-clinical 
studies has not only been found safe, demonstrated more comprehensive ability to address the 
underlying structural and functional abnormalities through which DM impairs would healing but 
has also demonstrated potential to be more effective in delivering better outcomes namely:21 
a. Complete closure in older non-healing DFUs compared to the Vehicle (75% v/s 43%) 
b. Faster complete closure compared to the Vehicle (35 days v/s 64 days)  
c. Higher area reduction over Vehicle in 12-weeks treatment (98.1% v/s 75.8%) 
d. No local reaction or risk of long term use of drug is anticipated  
In addition, Galnobax® provides a tissue adherent thermo-reversible polymeric gel suitable for 
application on chronic wounds.21  
Therefore, there are sufficient known and well evidenced benefits of Galnobax® for the treatment 
of DFU. 
2.3.3 ASSESSMENT OF POTENTIAL RISKS AND BENEFITS  
The fundamentals of good clinical care include adequate off-loading, frequent debridement, moist 
wound care, treatment of infection, and revascularization of ischemic limbs. Even when properly 
managed, the wounds may not heal in a timely fashion thereby leaving them open to getting 
complicated by intervening infection, hospitalization, amputation and, thus, to be costlier because 
of the increased utilization of healthcare resources.26  
Considering the clinically beneficial outcomes established in Phase 1/2 study, findings of non-
clinical pharmacological and toxicological information and ample existing human safety data on its 
drug substance (Esmolol hydrochloride), positions Galnobax® as having a favorable Risk / Benefit 
profile to necessitate the proposed clinical Phase 3 study.  
In this Phase 3 Study, care has been taken to ensure that in the event of any drug related adverse 
event, the Investigator will assess risk/benefit of Galnobax® to the Subject before deciding 
continuation of treatment. In addition, the treatment will be administered to the Subject by a 
trained Nurse, which will further minimize risk to the Subject, if any. 


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3 
OBJECTIVES AND ENDPOINTS 
OBJECTIVES 
ENDPOINTS 
JUSTIFICATION FOR 
ENDPOINTS 
Primary 
 
 
• 
To assess the efficacy of 
Galnobax® in terms of 
proportion of Subjects 
achieving Target Ulcer 
Closure within 12-week 
Treatment Phase upon 
application of Galnobax® 
plus Standard of Care as 
against only Standard of 
Care treatment, as 
assessed by the blinded 
Investigator  
The efficacy assessment 
will involve Galnobax® 
plus Standard of Care and 
only Standard of Care 
groups  
Efficacy endpoints: 
Proportion of subjects 
achieving Target Ulcer 
Closure within 12-week 
Treatment Phase, as 
assessed by blinded 
Investigator  
Complete wound closure of 
a chronic, nonhealing 
wound is one of the most 
important objective and 
clinically meaningful 
wound healing endpoint 
 
Secondary 
 
 
Efficacy 
Efficacy endpoints 
 
• 
To compare Time to Target 
Ulcer Closure within the 12-
week Treatment Phase, 
upon application of 
Galnobax® plus Standard of 
Care as against only 
Standard of Care treatment, 
as assessed by the blinded 
Investigator 
• 
Time to Target 
Ulcer Closure 
during the 12-
week Treatment 
Phase, as assessed 
by the blinded 
Investigator 
This endpoint evaluates 
clinically meaningful 
reduction in the time to 
Target Ulcer Closure using 
a time-to-event analysis 
(the event being first 
observation of complete 
closure)  
 
• 
To compare proportion of 
Subjects achieving Target 
Ulcer Closure till End of 
Study upon application of 
Galnobax® plus Standard of 
Care as against only 
Standard of Care 
treatment, as assessed by 
the blinded Investigator 
• 
Proportion of 
Subjects achieving 
Target Ulcer 
Closure till End of 
Study, as assessed 
by the blinded 
Investigator 
 
This endpoint is for 
evaluating sustained effect 
of the treatment post its 
discontinuation 
Safety 
 
 
• 
To investigate the safety of 
Galnobax® treatment 
during the Study 
• 
Proportion of 
Subjects with 
treatment 
emergent adverse 
events (TEAEs) 
This endpoint evaluates 
safety of Galnobax® by 
assessing TEAEs 


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• 
To investigate the safety of 
Galnobax® vehicle for 
establishing non-
deleterious effects of 
Vehicle on wound healing 
• 
Proportion of 
Subjects with 
events related to 
the local wound 
assessment of 
Target Ulcer in 
Vehicle plus 
Standard of Care 
group 
This endpoint evaluates 
events related to local 
wound assessment of 
Target Ulcer in Vehicle plus 
Standard of Care group 
 
 
 
4 
STUDY DESIGN  
4.1 
OVERALL DESIGN 
This Study is a Phase 3, multicenter, randomized, double-blind, parallel-group Study designed to 
evaluate the safety and efficacy of Galnobax® plus SoC versus only SoC, in treating DFU in adults 
with diabetes mellitus (DM). In addition, Study is designed to evaluate safety of Vehicle plus SoC 
versus only SoC in Subjects with DFU to investigate deleterious effects of Vehicle on wound healing, 
is any. 
For this purpose, the Subjects will be randomized in 3:3:1 ratio into one of the following groups:  
• 
Group 1: Galnobax® 14% gel plus SoC  
• 
Group 2: SoC only 
• 
Group 3: Vehicle plus SoC 
Total number of Subjects in the Study: This Study will have FAS Population (Efficacy Evaluable 
Population) of a minimum of 240 Subjects in Group 1 and Group 2 (minimum of 120 in each Group). 
To ensure this and assuming 20% drop out rate, the population of two groups would be maximum 
of 300 Subjects. In addition, for investigating the effect of vehicle on wound healing, Vehicle plus 
SoC group will recruit up to 50 Subjects. Thus, overall 350 Subjects will be recruited in the Study. 
No. of investigational sites: This Study will be conducted at approximately 40 sites across India 
with competitive recruitment amongst sites.  
Maximum duration of a Subject in the Study: The maximum total duration of Subject in the Study 
will be 25 weeks spread over three phases in following sequence:  
1. Screening Phase of 1-week (7 + 3 days)  
2. Treatment Phase of a maximum of 12-weeks (84±3 days) starting with Baseline visit 
3. Follow-Up Phase of 12-weeks (84±5 days). This will comprise of Closure Confirmation 
period of 4 weeks (28±3 days) and Observation period of 8 weeks (56±5 days). 
Subject Number Assignment: The Subjects will be assigned randomization number using an 
interactive web-based randomization system (IWRS). Prior to randomization, Subjects will be 
stratified by location (plantar or non-plantar) and size (<5 cm2 or ≥5 cm2) of the Target Ulcer solely 
for the purpose of bringing homogeneity among the three treatment Groups in proportionately. 
Once a randomization number has been assigned, it cannot be re-assigned to any other Subject. 
Application of Treatment: Subjects in the Study will receive treatment twice daily during the 12-
weeks of Treatment Phase or up to the Target Ulcer Closure, whichever is earlier. During this 
period, the twice daily treatment to the Subjects in all the arms of the Study will be administered 


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by the Study Nurse. Unless recommended by the Investigator otherwise, SoC during the Follow-Up 
Phase will be self-administered by the Subject.  
Visit Schedule of the Subjects: Subjects in the Study will visit investigational site once a week 
during the 12-week Treatment Phase for wound measurement and for completing Study related 
assessments and procedures. In the Follow-Up (FU) Phase, the Subjects will visit investigational site 
at week 14, 16, 20 and 24. 
Rules for Subject progression in the Study 
The Subject progression in the Study will happen as per rules given in Table 1 
Table 1 Subject progression as per condition of Target Ulcer 
Sr. 
No. 
Target 
Ulcer 
Closure 
within Treatment Phase 
Reopened in Closure 
Confirmation period? 
Action to be taken in the Study 
1 
Not closed  
Not applicable 
Proceed to Follow-Up Phase 
2 
Closed  
No 
Continue the Follow-Up Phase 
Yes 
If reopened within 12-weeks 
from Baseline visit, continue 
treatment till EOT or Target 
Ulcer Closure, whichever is 
earlier and then proceed to 
Follow-Up Phase. If reopened 
after 12-weeks from Baseline 
visit, continue the Follow-Up 
Phase 
The nomenclature used of various Study visits will be as follows: 
Screening Visit: V1 or Day -10 to -7 (minus ten to minus seven) or Week -1 (minus one) 
Treatment Visits:  
V2 or Day 0 or Week 0 (also referred to as Baseline visit) 
V3 or Day 7 or Week 1 
V4 or Day 14 or Week 2  
V5 or Day 21 or Week 3 
V6 or Day 28 or Week 4 
V7 or Day 35 or Week 5 
V8 or Day 42 or Week 6 
V9 or Day 49 or Week 7 
V10 or Day 56 or Week 8 
V11 or Day 63 or Week 9 
V12 or Day 70 or Week 10 
V13 or Day 77 or Week 11 
V14 or Day 84 or Week 12 or End of Treatment (EOT) 
Follow-Up (FU) Visits: 
FU1 or V15 or Day 98 or Week 14 (also referred to as Closure Verification visit) 
FU2 or V16 or Day 112 or Week 16 (also referred to as Closure Confirmation visit) 
FU3 or V17 or Day 140 or Week 20 
FU4 or V18 or Day 168 or Week 24 or End of Study (EOS) 


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4.2 
SCIENTIFIC RATIONALE FOR STUDY DESIGN 
The Study consists of about one week (7 to 10 days) of Screening period to confirm the suitability 
of Subject for the Study and to restrict recruitment of Subjects having healing ulcers. The Study has 
Treatment Phase of up to 12-weeks (84 ± 3 days) or the Target Ulcer Closure, whichever happens 
earlier as the Investigational Product (IP) requires 12-weeks of treatment to establish its efficacy. 
In view of this, if the Target Ulcer re-opens within these 84 days, the Subject will resume the 
treatment, up to completion of the Treatment Phase or the Target Ulcer Closure, whichever is 
earlier. If Target Ulcer closes prior to 12-week, then the Subject enters the 12-week Follow-Up 
phase immediately. The 12-week Follow-Up is required to confirm Target Ulcer closure, assess 
strength of closed Target Ulcer, assess progression of open wounds post Treatment Phase in terms 
of wound size and AEs, if any. 
In this trial, Subjects will be randomized in three Groups viz, Galnobax® plus SoC, only SoC, and 
Vehicle plus SoC in 3:3:1 ratio. A large population is required to achieve statistically significant 
efficacy endpoint for wound closure, whereas relatively smaller number of Subjects are sufficient 
to assess non-deleterious effects of Vehicle gel. During randomization, the Subjects will be 
stratified based on location as well as size of the Target Ulcer to have a proportional population in 
the three groups. Since SoC only is the treatment of choice used in clinical setting for DFU presently, 
this trial uses SoC only as comparator arm to Galnobax® plus SoC treatment for efficacy analysis. 
The parameters of Vehicle plus SoC arm will be compared with only SoC arm to check if Vehicle has 
any deleterious effects on wound healing. 
The FAS Population (Efficacy Evaluable Population) will include all randomized Subjects who have 
at least 6 weekly assessments for Target Ulcer Closure or has Target Ulcer closed earlier than 6 
weeks. The efficacy analysis in this Study will use FAS Population in order to ensure that Subjects 
have received reasonable treatment, and are assessed for Target Ulcer Closure by blinded 
Investigator. 
4.3 
JUSTIFICATION FOR DOSE 
Phase 1/2 clinical study of Galnobax® established that Galnobax® is safe for long term use (tested 
for 12-weeks) in both 14% and 20% concentrations. The efficacy analysis showed that Galnobax® 
treatment has advantage in terms of area and volume reduction over Placebo. The advantage of 
Galnobax® 14% is even more pronounced in hard to heal wounds. Considering this fact, this study 
has been planned to investigate Galnobax® 14% in a phase 3 trial to establish safety and efficacy 
in a larger number of Subjects for statistical significance. 
Each eligible Study Subject will be assigned to one of the three treatment groups as described in 
Table 2 and will receive the next available consecutive randomization number.  
Table 2 Dosing schedule 
Gr. No. 
Study group 
Treatment frequency 
1 
Standard of Care + Galnobax® gel 
Twice daily 
2 
Standard of Care  
Twice daily 
3 
Standard of Care + Vehicle gel 
Twice daily 
Dose Modification for Study Drug  
If any adverse reaction potentially related to Study drug is observed in terms of hypersensitivity or 
local allergic reaction at or around the Target Ulcer site, Investigator may decide to discontinue the 


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study drug administration to the Subject or adjust the frequency per the requirement for a limited 
period.  
4.4 
END OF STUDY DEFINITION 
A participant is considered to have completed the Study if he or she has completed all phases of 
the study including the last visit or the last scheduled procedure shown in the Schedule of Activities 
(SoA), Section 1.3. The end of the study is defined as completion of the last visit or procedure 
shown in the SoA in the trial. In addition, if Subject is discontinued or withdrawn from the Study, 
the last recorded visit of such Subject shall be considered as the End of Study. 
5 
STUDY POPULATION 
The Subjects included in this Phase 3 clinical study are those having DFU which has not healed for 
at least 6 weeks and satisfy eligibility criteria described below. It is made explicitly clear that 
there will be only one Target Ulcer per patient. 
5.1 
INCLUSION CRITERIA 
The Subjects would be included in the Study if they satisfy all of the following inclusion criteria: 
Potential Subjects are required to meet all of the following criteria for enrollment into the Study 
and subsequent randomization: 
1. Subjects, male or female, aged 18 to 75 years (inclusive) with Type 1 or Type 2 diabetes 
undergoing therapy for glycemic control 
2. Subject has glycosylated hemoglobin, HbA1C, ≤ 12% 
3. Subject with diagnosis of neuropathic foot ulcer by 10g monofilament test 
4. Subject has adequate vascular perfusion of the affected limb, confirmed by Ankle-Brachial 
Index (ABI) ≥ 0.65 and ≤ 1.3 
Note: If the ABI measurement is >1.30 one of the following confirmatory tests must be performed 
for Subject to be considered eligible. Prior documented flow study within the last 3 months of the 
Screening Visit is acceptable 
a) 
Great Toe pressure (plethysmography) > 40 mm Hg; 
b) 
Transcutaneous partial pressure oxygen (TcPO2) at the foot > 40 mm Hg; 
c) 
Skin Perfusion Pressure (SPP) > 40 mm Hg; 
d) 
Doppler ultrasound (biphasic or triphasic waveforms) consistent with adequate 
blood flow to the affected extremity, as determined by the standard practices of 
the Investigator and the site 
5. Presence of at least one DFU that meets all of the following criteria: 
a) 
A full-thickness ulcer of Grade A1 as per Texas classification system; 
b) 
Ulcer is located below or up to 5 cm above the malleoli (excluding ulcers between 
the toes); 
c) 
Ulcer size (area) is ≥ 2 cm2 and ≤ 15 cm2 (post-debridement); 
d) 
There is a minimum 3 cm margin between the qualifying Target Ulcer and any 
other ulcers on the specified foot, post-debridement; 
e) 
No exposed bone, tendon, muscle, ligament or joint capsule, and no tunneling, 
undermining, or sinus tracts; 
f) 
Unresponsive to ulcer care and open for at least 6 weeks at the time of the 
Screening Visit; 
g) 
Ulcer is non-infected as determined by clinical assessment and complete 
hemogram; 


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h) 
Ulcer has a clean, granulating base free of adherent slough to the greatest extent 
possible as per Investigator; 
i) 
Ulcer area reduction < 30% from the Screening Visit to Baseline visit 
Note: Criterion 4(i) will be evaluated at the time of randomization. If the Subject has more than 
one qualifying DFU, the ulcer designated as the Target Ulcer should be the ulcer preferably on the 
plantar region which is older, deeper and with a larger area.  
6. Clinically normal resting 12-lead ECG at Screening Visit or, if abnormal, considered not 
clinically significant by the Investigator 
7. Subject, if female of child-bearing potential, has a negative urine pregnancy test at 
Screening and willing to use acceptable methods of contraception (birth control pills, 
barriers) or abstinence throughout the Study 
8. Subject is able and willing to comply with Study procedures including the use of an off-
loading device (as applicable for the location of the ulcer) and adhere to protocol during 
the Study in the opinion of Investigator 
9. A Subject or LAR agrees to sign informed consent form and allow audio visual recording of 
consent, if applicable 
5.2 
EXCLUSION CRITERIA 
Subjects will not be eligible for enrolment in the Study if they meet any of the exclusion criteria 
listed below: 
1. Actively infected ulcers with or without purulent discharge, ulcers with exposed bone or 
associated with osteomyelitis 
Note: The osteomyelitis should be ruled out by clinical examination and X-ray findings where found 
necessary by the Investigator. If the Investigator is unable to ascertain the condition of 
osteomyelitis by probing of the Target Ulcer or digital X-ray then Investigator may use other 
techniques such as MRI, bone scintigraphy, leukocyte scanning or bone biopsy to rule out the 
presence of osteomyelitis based on availability of the investigation facility at the clinical sites. 
Note: If foot has more than one ulcers and one of them is infected, then Target Ulcer should not 
be selected from this foot unless all ulcers on the foot are free of infection. If Subject has ulcers on 
both foots and infection is seen in the ulcer on non-target foot, Subject may be included in the 
Study with prescribing oral antibiotic treatment for non-Target Ulcer. 
2. Subjects with more than three ulcers below knee  
3. Subjects with Target Ulcer requiring off-loading that cannot be effectively off-loaded; or 
unable to tolerate the off-loading method 
4. Subject has ulcers caused by a disease other than diabetes, e.g., fungal ulcerations, 
malignant ulcerations, and ulcerations due to venous or arterial insufficiency, or due to 
hematological disorders, in the opinion of the Investigator 
5. Ulcer, about which the Investigator is suspicious for cancer  
Note: In case of such suspicion, ulcer present more than 1 year will require a 3 mm punch biopsy 
to rule out malignancy. Prior documented negative ulcer biopsy within the last 1 year of 
the Screening Visit is acceptable 
6. Subjects with a gangrenous or ischemic ulcer 
7. Subject with ulcer that in the opinion of the Investigator, may need amputation 
8.  Subject with Target ulcer where wound measurement is not possible, such as ulcers 
between toes 
9. Body mass index (BMI) > 40 kg/m2 
10. Laboratory values at Screening of:  
a) 
Hemoglobin < 10.0 g/dL 


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b) 
White Blood Cells (WBC) < 2.0 X 109 cells/L 
c) 
Liver function studies [Total bilirubin, aspartate aminotransferase (AST) and 
alanine transaminase (ALT)] > 3x the upper limit of normal 
d) 
Albumin < 2.5 g/dL  
e) 
eGFR < 25 mL/min 
11. Presence of any existing clinically significant medical condition(s) that, in the opinion of 
the Investigator, could interfere with wound healing, including but not limited to the 
following: 
a) 
Vasculitis or connective tissue disease 
b) 
Buerger’s disease, Raynaud's or other peripheral vascular disease 
c) 
Clinically significant claudication or peripheral edema on the affected limb 
d) 
Acute or unstable Charcot foot 
e) 
Aplastic anemia or exacerbation of sickle cell anemia 
f) 
Current sepsis 
g) 
Congestive heart failure (NYHA Class III or IV), coronary heart disease with ST 
segment elevation, myocardial infarction, or coronary artery bypass graft or 
percutaneous transluminal coronary angioplasty within the last 6 months  
h) 
End-stage renal disease 
i) 
Immunosuppression 
j) 
Acquired immune deficiency syndrome (AIDS) or HIV positive 
k) 
Any malignancy history 
12. Subject has received or is currently receiving or scheduled to receive any of following 
medication or therapies during the course of the Study 
a) 
Immunosuppressants (chronic systemic corticosteroids) within 30 days of 
randomization visit 
b) 
Revascularization surgery (e.g., angioplasty, coronary artery bypass surgery, 
transmyocardial revascularization) within 30 days of randomization visit 
c) 
Growth factors within 30 days of randomization visit 
d) 
Hyperbaric oxygen therapy (HBOT) within last 7 days of randomization visit 
e) 
Negative pressure wound therapy (NPWT) within last 7 days of randomization visit 
f) 
Bioengineered tissue or skin substitutes within 30 days of randomization visit 
g) 
Application of topical steroids to the ulcer surface within 30 days of randomization 
visit 
h) 
Use of any investigational drug(s) or therapies within 30 days of randomization 
visit 
13. Subject with intolerance to β-blockers at any time in the past 
14. Has any other factor which may, in the opinion of the Investigator, compromise 
participation and/or follow-up in the Study 
5.3 
LIFESTYLE CONSIDERATIONS 
Not applicable 
5.4 
SCREEN FAILURES 
Screen failures are defined as participants who consent to participate in the clinical trial but are 
not subsequently randomly assigned to the study intervention or entered in the study. This will 
occur to those Subject who did not meet the eligibility criteria at Baseline Visit or whose Target 
Ulcer reduces in area by ≥30% during the Screening period. Such Subject is considered screen failed 


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and will exit from the Study without any further evaluation. Subject who has screen-failed once 
may be rescreened at an appropriate time as decided by the Investigator. Only one such re-
screening is allowed for any Subject during the study. 
5.5 
STRATEGIES FOR RECRUITMENT AND RETENTION 
The recruitment and retention strategies would be detailed in the clinical trial management plan 
(CTMP) and monitoring plan (MP) including the site-specific plans as per the site-specific standard 
operating procedure (SOP). The considerations for recruitment and retention strategies would 
include the following but not limited to:  
• 
Target study sample size as consistent with information contained in Sample Size 
Determination 
• 
Anticipated accrual rate 
• 
Anticipated number of sites and participants to be enrolled for the study 
• 
Source of participants 
• 
Recruitment venues 
• 
How potential participants will be identified and approached 
• 
Types of recruitment strategies planned  
• 
Procedures to enhance retention of patient in the study  
• 
Participants compensation/incentives for the study  
6 
STUDY INTERVENTION 
6.1 
STUDY INTERVENTION(S) ADMINISTRATION 
6.1.1 STUDY INTERVENTION DESCRIPTION 
Test IP (Galnobax®) 
Galnobax® is a topical gel containing 14% Esmolol hydrochloride. The gel will be packaged into 
lacquered aluminium tube in the quantity of 15 g per tube for both morning and evening 
application on the Target Ulcer. The composition of the Galnobax® gel is as shown in Table 3 
Table 3 Composition of Galnobax® 
INGREDIENTS 
Active Ingredient 
Esmolol hydrochloride 
Inactive Ingredients 
Benzalkonium chloride solution  
Poloxamer 338  
Sodium Acetate Trihydrate 
Glacial Acetic Acid 
Concentrated Hydrochloric Acid 
Purified water 


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Vehicle gel 
The Vehicle gel to match the IP will be supplied by the Sponsor. The Vehicle gel will be without 
active ingredient but will have all inactive ingredients in the same concentration as used in 
Galnobax® gel.  
Standard of Care 
The SoC includes wound cleaning by normal saline, maintenance of moist wound environment and 
off-loading of the Target Ulcer. In addition, during site visits removal of necrotic, infected and/or 
nonviable tissue by debridement and management of infection will be done by the Investigator, if 
required.  
6.1.2 DOSING AND ADMINISTRATION 
The amount of the IP (Galnobax®) or Vehicle gel to be applied will vary depending upon the area 
and depth of the Target Ulcer. To calculate the length of gel to apply to the Target Ulcer such that 
a uniform layer of IP over the wound surface, refer the Target Ulcer area obtained using advance 
camera in the corresponding visit and use the following formula to calculate the length of gel in 
centimeters to be applied:  
Length of Gel in Centimeters to be applied at each application 
 = Area of ulcer in cm2 (using advance camera) X 0.6 centimeter of gel from 15 g tube 
For example, if the ulcer area measures 10 cm2, then a 6-centimeter length of gel should be used 
from a 15 g tube [10 X 0.6 = 6 cm]. 
Further, depending on the surface area of Target Ulcer, additional amount of IP may be applied to 
ensure formation of uniform layer of IP over the wound bed. 
How to administer treatment (Instructions to unblinded Investigator and Study Nurse): 
a. For group randomized to IP (Galnobax®)/Vehicle + SoC treatment  
For morning application:  
1. 
Remove the dressing  
2. 
Rinse the Target Ulcer using saline 
3. 
Squeeze out the required length of the gel from tube on to a sterile wax paper 
(printed with centimeter scale) provided with the kit 
4. 
Using sterile applicator (provided with the kit) spread the gel over the entire ulcer 
area to yield a thin continuous layer that covers the wound bed, but no peri-wound 
skin 
5. 
The Target Ulcer will then be covered by appropriate dressing and the Subject 
must be advised to leave it in place till next application 
For evening application:  
1. 
Remove the dressing 
2. 
Only the peri ulcer area should be cleaned by cotton dipped in saline (do not rinse 
the Target Ulcer by saline for evening application) 
3. 
Squeeze out the required length of the gel from tube on to a sterile wax paper 
(printed with centimeter scale) provided with the kit 
4. 
Using sterile applicator (provided with the kit) spread the gel over the entire ulcer 
area to yield a thin continuous layer that covers the wound bed, but no peri-wound 
skin 


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5. 
The Target Ulcer will then be covered by appropriate dressing and the Subject 
must be advised to leave it in place till next application 
b. For group randomized to SoC treatment 
For morning application:  
1. 
If the Target Ulcer is already dressed, remove the dressing  
2. 
Rinse the Target Ulcer using saline 
3. 
The Target Ulcer will then be covered by appropriate dressing and the Subject 
must be advised to leave it in place till next application. 
For evening application:  
1. 
The dressing should be removed 
2. 
Only the peri ulcer area should be cleaned by cotton dipped in saline (do not rinse 
the Target Ulcer by saline for evening application) 
3. 
The Target Ulcer will then be covered by appropriate dressing and the Subject 
must be advised to leave it in place till next application 
6.2 
PREPARATION/HANDLING/STORAGE/ACCOUNTABILITY 
6.2.1 ACQUISITION AND ACCOUNTABILITY 
The Sponsor/Contract Research Organization (CRO) will provide IP (Galnobax® as well as Vehicle 
gel) to the site. The accountability of IP will be maintained as follows: 
• 
The Investigator/co-Investigators or designee would acknowledge receipt of Study IP 
supplies for each shipment received 
• 
The unblinded Investigator responsible for dispensing the IP to the Study Nurse must 
maintain a drug accountability log. The IP accountability log records the receipt, dispensing 
and return of the IP 
• 
At any time the sum of quantity of used and unused IP should match with the quantity of 
medication supplied. Account must be given of any discrepancies 
• 
The Study monitor and Sponsor should be notified immediately of details of any IP, which 
is inadvertently damaged or lost 
• 
The used or unused IP tubes will be returned by the Study Nurse to the site. Tubes will be 
replenished as required with identical kit number 
• 
The quantity of IP utilized for the treatment will be monitored by checking the weight of 
the tube at the time of issuing it for the treatment and at the time of collecting the used 
tube 
• 
If all tubes from the kit are consumed, a new kit with identical treatment will be issued 
Handling of Investigational Product: 
Both used and unused IP tubes would be sent back to Sponsor/their representative for destruction 
as per standard procedure. Reconciliation between the amount of IP supplied, used and returned 
to the Sponsor must be performed by the Sites and the CRO. If any discrepancies are found in the 
reconciliation of IP, it will be resolved. This reconciliation will be logged by each site on the IP 
reconciliation form, signed and dated.  


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6.2.2 FORMULATION, APPEARANCE, PACKAGING, AND LABELING 
Formulation and Appearance 
The details of formulation are given in Section 6.1.1. The IP is a colorless gel at room temperature.  
Packaging 
The IP will be packaged in to lacquered aluminium tubes in the quantity of 15 g per tube. The tubes 
will be placed in cartons which has product information and kit number printed on it (Table 4). 
Each carton will contain one tube. Each kit will contain 4 such cartons and two boxes of sterile gel 
measurement strips. Sufficient number of such kits will be made available to ensure sufficient 
supply of IP for the Study. 
Table 4 Labelling information of Galnobax®  
Galnobax® Topical Gel | Study code: NG-A16 
Kit No.:  
Topical gel contains 
Vehicle or Esmolol Hydrochloride  
14% w/w  
Preservative: Benzalkonium chloride solution (50%) 
0.26% w/w 
Net Wt. 
15 g 
Batch No.:  
| 
Mfg. Lic. No.: 
Sponsor: NovaLead Pharma Private Limited, Pune, INDIA 
Manufacturer:  
Store in cool environment 
Mfg. Date: 
 
 
| 
Exp. Date:  
FOR CLINICAL TRIAL USE ONLY. NOT TO BE SOLD. 
FOR EXTERNAL USE ONLY 
Caution:  
Keep out of reach of children. In case of Emergency, contact your study doctor or Local Emergency Services 
Subject No.: To be written by study site 
Investigator’s name: To be written by study site 
Investigator Contact Number: To be written by study site 
Name of the Institution: To be written by study site 
Visit No.: To be written by study site 
Date of dispensing: To be written by study site 
 
Kit No.: 
Subject No.: To be written by study site 
Visit No.: To be written by study site 
Date of dispensing: To be written by study site 
The manufacturer will label the tubes, cartons and kits. In case additional IP is required for any 
Subject, new kit with same treatment will be issued.  
6.2.3 PRODUCT STORAGE AND STABILITY 
IP will be stored at 15 to 25˚C at the warehouse and at the investigational sites. Upon dispensing 
to the Study Nurse, instruction will be given to store in refrigerator as far as possible and if not 
available, in dry and cool environment. 


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6.2.4 PREPARATION 
The IP will be manufactured under Good Manufacturing Practice (GMP) conditions and following 
all regulations of CDSCO as well as State FDA.  
6.3 
MEASURES TO MINIMIZE BIAS: RANDOMIZATION AND BLINDING 
This is a double-blind study wherein the Investigator, the Sponsor, the Subject, the CRO and the 
Study Nurse Coordinator will be kept blinded to the randomization throughout the Study. There 
will be one unblinded Investigator per site who will administer the treatment during each 
treatment visit of the Subject as well as dispense the IP to the Study Nurse and the SoC material to 
the Subject. The Study Nurse who will administer treatment to the Subject (twice daily during 
Treatment Phase) will be unblinded. However, the unblinded Investigator and Study Nurse will still 
remain blinded to whether the Study drug applied is Galnobax® or Vehicle gel. The blinding of the 
Subject will be ensured by the Study Nurse by using shield while treating the Target Ulcer.  
In case the Subject  is staying far from the site (i.e. 40 km or more from the site) and/or Nurse is 
unable to visit every week to the site for treatment compliance check, following procedure will be 
followed for IP transport and compliance check: IP will be issued to the study Nurse at the time of 
the randomization visit along with study diary in an aluminum box having a lock. One key of this 
lock will be with the study Nurse and other with the unblinded CRC at the site. At the time of weekly 
site visit of the Subject, study Nurse will keep used IP tubes and Study diary in this box which will 
be locked and sent to the site with the Subject. Site unblinded CRC will take aluminum box from 
the subject and will check IP compliance as well as study diary. The IP will be reissued to the nurse 
after weighing the tubes and new study diary will also be issued (through which new dose of the 
subject will be conveyed to the Nurse). These materials will be kept in the aluminum box which 
will be locked and given to the Subject for handing over it to the study Nurse. This process will 
continue during all treatment visits.   
While the IP compliance will be verified by the unblinded Investigator, the Target Ulcer Closure will 
be decided and confirmed by the blinded Investigator, thus mitigating any bias. 
Unblinding will be done only if necessary for the welfare of the Subject or in the case of emergency 
suspected to be IP related. If such emergency is clearly not IP-related in the opinion of the 
Investigator, the Subject management can be done without the need of unblinding. Standard 
norms and procedures for unblinding will be followed. 
6.4 
STUDY INTERVENTION COMPLIANCE 
Blank Study diary will be dispensed to the Subject from Baseline Visit (V2). The Study Nurse will 
receive the blank diary from the Subject and record the daily compliance of the following during 
the Treatment Phase (V2-V14) as applicable: 
a. Off-loading 
b. Daily applications of the treatment (to confirm the dose application schedule), 
c. Missed applications,  
d. Excess dose drawing  
e. Completion of dressing of the Target Ulcer 
f. Any unusual happening 
The Study Nurse will not disclose these entries to the Subject and retain the Study diary with her 
before submitting it to the unblinded Investigator. Collection and review of Study diary will 


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continue from V3 till V12 or EOT. The un-blinded Investigator will transcribe the information from 
the Study diary into the CRF. During the Treatment Phase, unblinded Investigator should record 
the weight of single application of treatment prescribed during every Treatment visit of the Subject 
and this basis will be used to check weekly compliance of the dose. The dose to be applied will be 
informed to the Study Nurse by the unblinded Investigator after every weekly Treatment visit. 
During Follow-Up Phase (V15-V18), Subject diary will be filled and handled by the Subject since 
there will be no treatment provided during the Follow-up. The Subject will hand over the 
completed Study Diary to the un-blinded Investigator during Follow-up visits.  
The Subjects with treatment compliance of less than 80% or more than 120% of the IP, during the 
week, will be considered treatment non-compliant for that week. If such non-compliance is 
observed for more than three weeks, and if the blinded Investigator opines that it may affect the 
outcome of the Study, then the Subject shall be considered non-compliant for the Study and shall 
be discontinued from the Study.  
6.5 
CONCOMITANT THERAPY 
Any medication regularly used by the Subject including anti-diabetic medications as prescribed by 
the physician and approved by the Investigator will be permitted to be used.  
If Investigator suspects infection at any wound site of the Subject, oral and/or parenteral 
antibiotics (except topical) and standard of wound care will be permissible to prevent the wound 
from leading to osteomyelitis. It will be at the Investigator’s discretion to decide if it is necessary 
to defer the Study treatment to the Subject during the antibiotic treatment to control the wound 
infection. In case the non-Study ulcer is seen with infection, it will be treated with oral or parenteral 
antibiotics. The local antimicrobial therapy, if required will be permitted to the non-Study ulcer. 
The concomitant medication administered must also be recorded in the CRF with generic name 
and/or trade name of the medication, dose, start and end dates of treatment. 
6.5.1 RESCUE MEDICINE 
Not applicable 
7 
STUDY INTERVENTION DISCONTINUATION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL 
7.1 
DISCONTINUATION OF STUDY INTERVENTION 
The subjects that report Osteomyelitis, cellulitis or SAE/AE where study intervention cannot be 
given, should be discontinued. For all discontinued Subjects, maximum possible and relevant Study 
information shall be gathered and be described in the source. This information can be gathered at 
Site visit or telephonically. If the discontinuation happens during the Treatment /Follow up Phase, 
the last visit prior to discontinuation will be treated as EOT/EOS visit and corresponding CRF will 
be completed by the Investigator.  
7.2 
PARTICIPANT DISCONTINUATION/WITHDRAWAL FROM THE STUDY 
Participants are free to withdraw from participation in the Study at any time. If the withdrawal 
happens during the Treatment /Follow up Phase, the last visit prior to withdrawal will be treated 
as EOT/EOS visit and corresponding CRF will be completed by the Investigator.  
Subjects who sign the informed consent form (ICF) and are randomized but do not receive the 
study intervention will not be replaced and will not be part of ITT Population.  


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Subjects who sign the ICF, and are randomized and receive the study intervention, and 
subsequently withdraw, or are withdrawn or discontinued from the study, will not be replaced and 
yet be part of ITT Population. 
Subjects must be discontinued from the Study after randomization if any of the following events 
occur (Stopping or Discontinuation Rules for Individual Subjects):  
1. 
A Subject withdraws consent 
2. 
Investigator recommends that the Subject should discontinue the participation in the 
Study 
3. 
Subject misses two consecutive Weekly Visits during Treatment Phase 
4. 
If the Target Ulcer and the adjoining wound merge together and if the Investigator 
opines that following the Target Ulcer is difficult. A detailed note by the Investigator will 
be recorded in the e-CRF outlining reasons for such merger in line with the preceding 
measurement of Target Ulcer 
5. 
If Subject requires hospitalization for more than two consecutive weeks during the Study 
6. 
The Subjects with treatment compliance of less than 80% or more than 120% during the 
week, will be considered treatment non-compliant for that week. If such non-compliance 
is observed for more than three weeks, and if the blinded Investigator opines that it may 
affect the outcome of the Study, then the Subject shall be considered non-compliant for 
the Study and shall be discontinued from the Study  
7. 
If the blinding of a Subject is compromised 
8. 
Any form of major protocol violation 
9. 
The Target Ulcer increases in size (more than 30%) for two consecutive weeks or requires 
deep, surgical debridement for more than two occasions during the Treatment Phase to 
address Target Ulcer deterioration 
10. 
The Target Ulcer becomes infected requiring topical antimicrobial treatment 
11. 
If Subject develops osteomyelitis or cellulitis during the Study on the foot having the 
Target Ulcer 
12. 
If female Subject becomes pregnant, during the study 
13.  If Subject misses 6 consecutive dressings  
In the event of a Subject withdrawal or discontinuation from the Study, the following information 
must be recorded in the e-CRF 
• 
Date of withdrawal 
• 
Reason for withdrawal  
• 
Last treatment date 
In the event of withdrawal or discontinuation, the Subject will be requested to cooperate for the 
following: 
a. Recording AEs that may occur post withdrawal/discontinuation till End of Study 
b. Follow-up on all SAEs or other AEs that may have occurred prior to 
withdrawal/discontinuation and are considered to be related to the Study IP, until resolved 
or assessed to be chronic or stable by the Investigator. The details would be documented 
in the Subject’s medical records 
7.3 
LOST TO FOLLOW-UP 


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A randomized Subject will be considered lost to follow-up if he or she fails to return for 2 
consecutive scheduled site visits and is unable to be contacted by the Study site staff. In such 
situation, following actions will be taken: 
• 
The site will attempt to contact the Subject and reschedule the missed visit and counsel 
the participant on the importance of maintaining the assigned visit schedule and ascertain 
if the participant wishes to and/or should continue in the study 
• 
Study Nurses would be doing a Subject’s home visit every day during the treatment period 
for wound dressing. In case Subject remains not reachable, the Investigator site team and 
Study Nurses will make every effort to regain contact with the Subject (where possible, 3 
telephone calls and, if necessary, a certified letter to the Subject’s last known mailing 
address or local equivalent methods) before a Subject is deemed lost to follow-up. These 
contact attempts should be documented in the Subject’s medical record or Study file  
• 
Should the Subject continue to be unreachable, he or she will be considered to have 
withdrawn from the Study with a primary reason of lost to follow-up 
• 
For Lost to Follow-Up Subject, the last scheduled Study Visit will be treated as EOT/EOS 
visit and corresponding CRF will be completed by the Investigator 
8 
STUDY ASSESSMENTS AND PROCEDURES 
Screening Visit V1 (Day -10 to Day -7)  
The Screening Phase is designed to determine whether Subjects are eligible to proceed to the 
Treatment Phase of the Study. The activities in this Phase include: 
• 
Obtain written consent from the Subject/LAR  
• 
Investigator or authorized Study staff will explain to the Subject/LAR, the Study procedures 
and signed informed consent will be obtained  
Note: Signed informed consent must be obtained prior to Subject participation in any protocol-
related activities that are not part of routine care. 
The following assessments and procedures will be performed and results will be recorded: 
• 
Inclusion-exclusion criteria evaluation 
• 
Demographic information of the Subject 
• 
Sample collection for Urine pregnancy test (as necessary) 
• 
Initial evaluation including medical history and foot specific history. The ulcer history will 
include the location and duration of all the potential Target Ulcers. In addition to disease 
history [DM (Type 1 or Type 2)], all other medical and social histories, in the opinion of the 
Investigator, that are relevant to the safety of the Subject or could impact safety or efficacy 
results for the Subject will be recorded. Recording of all current and prior 
treatment/therapies used within the 30 days prior to the V1 visit 
• 
Vital signs (blood pressure, pulse rate, respiratory rate, and temperature) 
• 
Systematic physical examination and body weight 
• 
Laboratory tests (hematology tests, biochemistry, and HbA1C) 
• 
ECG or 2 D echocardiography (2D-ECHO only if ECG is not conclusive) 
• 
Ankle-Brachial Index assessment and corresponding eligibility assessments as per Inclusion 
Criteria for ABI (See Attachment 2).  
• 
Assessment of Study foot by SW 5.07 monofilament test. Peripheral neuropathy will be 
assessed by using a 10-g Semmes Weinstein 5.07-gauge monofilament to test 4 points on 


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the foot for touch sensation (Greater toe, 1st, 3rd and 5th metatarsal head) (See Attachment 
3) 
• 
Assessment of all potential Target Ulcers for osteomyelitis. The osteomyelitis should be 
ruled out by clinical examination and X-ray findings. If the Investigator is unable to 
ascertain the condition of osteomyelitis by probing of the Target Ulcer or by digital X-ray 
then Investigator may use other techniques such as MRI, bone scintigraphy, leukocyte 
scanning or bone biopsy to rule out the presence of osteomyelitis based on availability of 
the investigation facility 
• 
Detail Foot Examination to assess vascular, neurological, dermatological and 
musculoskeletal signs and symptoms of the foot(s) with potential Target Ulcers  
• 
Classification of all the potential Target Ulcers will be completed as per Texas system (See 
Attachment 1) 
• 
Local examination and infection status of all potential Target Ulcers for presence of edema, 
warmth, erythema, pain, scaling, pus, exudates, cellulitis, callus, maceration or swelling 
and any signs of infection  
• 
Assessment of all potential Target Ulcers characteristics in terms of wound edge, color, 
drainage amount and type, peri-wound conditions and color and percent wound bed 
covered by granulation tissue, fibrin slough, and necrotic tissue 
• 
Target Ulcer measurement  
• 
Subject education on diabetes management. Counseling on diabetes management will be 
provided as and when required during the Study  
• 
Recording of concomitant medications 
• 
Surgical or Sharp debridement of any of potential Target Ulcers, if required, along with 
documentation of type of debridement (e.g. callus removal, sharp or surgical), reason for 
debridement  
• 
Nutritional information (i.e., the importance of diet in controlling glucose levels) will be 
provided to and reviewed with, each Subject at the Screening Visit (V1). Further counseling 
to the Subject will be available on request during the course of Study 
• 
Photographs of both the legs from various angles (medial, lateral, dorsal, plantar) would 
be captured to verify that not more than three ulcers are present at this visit 
During the Screening Phase, all the potential Target Ulcer will be treated by as per 
recommendation of the Investigator keeping in view the exclusion criteria 
Baseline Visit V2 (Week 0, Day 0) [Window period 7-10 days from Screening Visit] 
The Baseline Visit will take place between 7-10 days after the Screening Visit. Subjects will be re-
checked for eligibility criteria and the Target Ulcer will be selected for the Study from all the 
potential Target Ulcers. Subjects who fail to meet eligibility criteria at Baseline Visit or those 
Subjects whose Potential Target Ulcers reduces in area by ≥30% during Screening period are 
considered screen failures and will exit from the Study without further evaluation.  
The eligible Subjects will be randomized and their Treatment Phase shall begin at this visit. 
Following assessments and procedures will be performed during this visit: 
• 
Vital signs (blood pressure, pulse rate, respiratory rate, and temperature) 
• 
Measurement of random blood glucose. If abnormality is observed, the Investigator may 
recommend pre- and post-prandial blood glucose measurement and modify dose or 
medication for adequate blood sugar control 
• 
Recording of Change in the Medical History 


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• 
Surgical or Sharp debridement of any Target Ulcer, if required, along with documentation 
of type of debridement (e.g. callus removal, sharp or surgical), reason for debridement. 
• 
Photographs of both the legs from various angles (medial, lateral, dorsal, plantar) would 
be captured to verify that not more than three ulcers are present at this visit 
• 
Target Ulcer measurement 
• 
Assessment of local pain in terms of 11-point (0-10) universal pain scale for the Target 
Ulcer (See Attachment 4) 
• 
Assessment of local edema in terms of 5-point (0-4) edema scale for the Target Ulcer (See 
Attachment 4) 
• 
Assessment of local erythema in terms of 5-point (0-4) erythema scale for the Target Ulcer 
(See Attachment 4). 
• 
Clinical assessment of infection status of non-Study ulcer(s) 
 
• 
Dispensing of appropriate off-loading footwear. All Subjects with a plantar Target Ulcer 
will be advised to wear suitable off-loading foot ware (e.g. Darco Ortho-Wedge or Heel-
Wedge or any suitable footwear suggested by Investigator). Investigator may use 
additional or alternative off-loading equipment such felta foam, local plaster, etc. Use of 
casts is not permitted 
• 
Subject education and training on use of off-loading device. 
• 
Nutritional information (i.e., the importance of diet in controlling glucose levels) will be 
provided to the subject 
• 
Recording of concomitant medications 
• 
Dispensing of Study treatment by the unblinded Investigator: Unblinded Investigator will 
issue Study treatment material and communicate to the Study Nurse regarding the 
quantity of IP to be applied to the Target Ulcer during the week 
• 
Dispensing of Study diary: Study Nurse will collect the study diary from the unblinded 
investigator. The study nurse will ensure to record in the diaries, the hours each day that 
the Subject does not wear the off-loading device and the duration of weight-bearing time 
experienced without the offloading/protective device, if relevant. The Study Nurse will also 
record twice daily treatment application and dressing changes done in the diary 
Treatment Visits V3 to V14 (Week 1 to Week 12, Day 7 to Day 84 [Window period ±3 days for 
each scheduled visit])  
The Subjects assigned to Galnobax® plus SoC, Vehicle plus SoC or only SoC Group will receive the 
treatment twice daily from Study Nurse for up to 12-weeks or until complete closure of Target 
Ulcer, whichever is earlier.  
All Subjects will visit the Study site once every week as given in Study calendar. Assessment will be 
done at various Treatment visits as follows: 
• 
Urine pregnancy test will be performed (as applicable) after every 4 weeks till V14 or EOT, 
whichever is earlier 
• 
Vital signs (blood pressure, pulse rate, respiratory rate, and temperature)  
• 
Systematic physical examination and body weight after every 4 weeks till V14 or EOT, 
whichever is earlier 
• 
Laboratory tests (hematology tests and biochemistry) after every 4 weeks till V14 or EOT, 
whichever is earlier 
• 
HbA1C test at V14 or EOT, whichever is earlier 


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• 
Measurement of random blood glucose. If abnormality is observed, the Investigator may 
recommend pre- and post-prandial blood glucose measurement and modify dose or 
medication for adequate blood sugar control 
• 
ECG or 2 D echocardiography (2D-ECHO only if ECG is not conclusive) after every 4 weeks 
till V14 or EOT, whichever is earlier 
• 
X-ray of the foot under the Study will be taken at the Investigator’s discretion for ruling 
out osteomyelitis. Other methods such as bone scan, leukocyte scan or MRI as needed may 
be used by the Investigator, for confirming the osteomyelitis depending on the Target 
Ulcer status 
• 
Detail Foot Examination to assess vascular, neurological, dermatological and 
musculoskeletal signs and symptoms of the foot(s) with Target Ulcer after every 4 weeks 
till V14 or EOT, whichever is earlier 
• 
Grading and staging of Target Ulcer as per Texas system of wound classification (See 
Attachment 1) 
• 
Local examination and infection status of Target Ulcer for presence of edema, warmth, 
erythema, pain, scaling, pus, exudates, cellulitis, callus, maceration or swelling and any 
signs of infection  
• 
Assessment of Target Ulcer characteristics in terms of wound edge, color, drainage amount 
and type, peri-wound conditions and color and percent wound bed covered by granulation 
tissue, fibrin slough, and necrotic tissue 
• 
Surgical or Sharp debridement of Target Ulcer, if required along with documentation of 
type of debridement (e.g. callus removal, sharp or surgical), reason for debridement 
• 
Target Ulcer measurement 
• 
Assessment of local pain in terms of 11-point (0-10) universal pain scale for the Target 
Ulcer (See Attachment 4) 
• 
Assessment of local edema in terms of 5-point (0-4) edema scale for the Target Ulcer (See 
Attachment 4)  
• 
Assessment of local erythema in terms of 5-point (0-4) erythema scale for the Target Ulcer 
(See Attachment 4) 
• 
Clinical assessment of infection status of non-Study ulcer(s) 
• 
Subject education on diabetes management and off-loading as and when required 
• 
Recording of concomitant medications 
• 
AE recording  
• 
Nutritional information (i.e., the importance of diet in controlling glucose levels) will be 
provided to and reviewed. Further counseling to the Subject will be available on request 
during the course of Study 
• 
Study Diary review will be done by unblinded Investigator for treatment compliance check 
and use of offloading device at each visit of the Study Nurse to the investigator Site 
Follow-up Visit Week 14 to Week 24 (FU1 to FU4) [V15/Day 98 to V18/Day 168 (Window period 
±3/±5 days)] 
The Subjects whose Target Ulcer is closed (first observation of Target Ulcer Closure) or the Subject 
who completes the 12-weeks of Treatment Phase, whichever is earlier, will immediately enter the 
Follow-Up (FU) Phase of 12-weeks. All Subjects who enter the Follow-Up Phase are required to 
attend the Follow-up visit FU1-two weeks after EOT; FU2-four weeks after EOT, FU3-eight weeks 
after EOT and FU4-twelve weeks after EOT, regardless of whether the Target Ulcer is 
open/closed/re-opened. 


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For the Subjects whose Target Ulcer has closed within the 12-week Treatment Phase, the 12-week 
Follow-Up Phase is divided in to 4-week Closure Confirmation period and 8-week Observation 
period. The Closure Confirmation period will be of total four weeks with two visits two weeks apart 
for confirming initial closure of the Target Ulcer. The Observation period will be of total eight weeks 
with two visits, four weeks apart for assessing quality of healing, progress of ulcer closure and AEs, 
if observed. 
For the Subjects whose Target Ulcer has not closed within 12-week Treatment Phase, the 12-week 
Follow-Up Phase will be considered as 12-week Observation period. 
Subjects who have entered the Follow-Up Phase will be subjected to SoC treatment as deemed 
necessary by the Investigator. Unless recommended by the Investigator otherwise, SoC during the 
Follow-Up Phase will be self-administered by the Subject. 
The Subject whose Target Ulcer has closed within 12-week Treatment Phase and has entered the 
Follow-Up Phase will continue to use protective covering or bandage (if advised by the Investigator) 
on the Target Ulcer until confirmation of the Target Ulcer closure. If the Target Ulcer remains closed 
during Closure Confirmation period, then the Target Ulcer will be confirmed to be closed. The time 
to Target Ulcer closure will be the time from the Baseline Visit when Target Ulcer was first observed 
closed for which Target Ulcer Closure was confirmed.  
During this follow-up phase, if the Target Ulcer reopens during the Closure Confirmation period 
which lies within 84 ± 3 days from Baseline visit, the Subject would be given the treatment to 
complete 12-week of Treatment Phase. For example, if the Target Ulcer closes before 8 weeks of 
treatment and reopens within 4 weeks of Closure Confirmation period, the Subject will restart the 
treatment and continue only till 12-weeks (84±3 days) of treatment from Baseline visit. On 
completion of that period, Subject will enter the Follow-Up Phase. 
During this follow-up phase, if the Target Ulcer reopens after confirmation of the Target Ulcer 
closure, the Subject will still be continued with the Follow-up assessment period and further 
evaluations would be as per Follow-up visit scheduled.  
During this 12-week Follow-Up phase (84 ± 5 days from EOT), the closed Target Ulcer will be 
monitored to distinguish actual healing from transient wound coverage and for AEs, if any. 
All Subjects will undergo following assessments during FU1 to FU4 visits 
• 
Sample collection for Urine pregnancy test (as necessary) at FU2 
• 
Vital signs (blood pressure, pulse rate, respiratory rate, and temperature)  
• 
Systematic physical examination and body weight at EOS or FU4, whichever is earlier 
• 
Laboratory tests (hematology tests, biochemistry, and HbA1c) at EOS or FU4, whichever is 
earlier  
• 
Measurement of random blood glucose. If abnormality is observed, the Investigator may 
recommend pre- and post-prandial blood glucose measurement and modify dose or 
medication for adequate blood sugar control 
• 
ECG or 2 D echocardiography (2D-ECHO only if ECG is not conclusive) at FU1 
• 
Subject Diary review will be done by blinded Investigator for all subjects in follow up Phase  
• 
Offloading, dressing compliance  
• 
Detail Foot Examination to assess vascular, neurological, dermatological and 
musculoskeletal signs and symptoms of the foot(s) with Target Ulcer at EOS or FU4, 
whichever is earlier 
• 
Classification of Target Ulcer will be completed, if ulcer remains open (See Attachment 1) 


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• 
Local examination and infection status of Target Ulcer for presence of edema, warmth, 
erythema, pain, scaling, pus, exudates, cellulitis, callus, maceration or swelling and any 
signs of infection, if ulcer remains open  
• 
Assessment of Target Ulcer characteristics in terms of wound edge, color, drainage amount 
and type, peri-wound conditions and color and percent wound bed covered by granulation 
tissue, fibrin slough, and necrotic tissue, if ulcer remains open 
• 
Target Ulcer measurement (if the Target Ulcer still persists). Ulcer will be photographed at 
each Follow-Up visit, even if it is closed  
• 
Subject education on diabetes management and off-loading as and when required  
• 
Recording of concomitant medications 
• 
AE recording 
• 
Surgical or Sharp debridement of the Target Ulcer, if required, along with documentation 
of type of debridement (e.g. callus removal, sharp or surgical), reason for debridement  
• 
Nutritional information (i.e., the importance of diet in controlling glucose levels) will be 
provided to and reviewed. Further counseling to the Subject will be available on request 
during the course of Study 
• 
Assessment of local pain in terms of 11-point (0-10) universal pain scale for the Target 
Ulcer (See Attachment 4) 
• 
Assessment of local edema in terms of 5-point (0-4) edema scale for the Target Ulcer (See 
Attachment 4) 
• 
Assessment of local erythema in terms of 5-point (0-4) erythema scale for the Target Ulcer 
(See Attachment 4) 
• 
Clinical assessment of infection status of non-Study ulcer(s) 
• 
Dispensing wound dressing material to the Subject as and when required 
Note: Subject will be reminded to perform dressing changes if the Target Ulcer persists or as 
recommended by the Investigator. Subject will be reminded to follow off-loading of Target Ulcer 
irrespective of whether it has closed or not  
Unscheduled Visits 
Any visit to site by the Subject other than a regularly scheduled Study visit will be regarded as an 
unscheduled visit. Assessments at such unscheduled visits will be as follows:  
• 
If the unscheduled visit is for recording of the Target Ulcer Closure, then the Investigator 
should complete all assessment as per EOT and proceed to Follow-Up Phase immediately.  
• 
If the unscheduled visit is due to reopening of the Target Ulcer during Closure Confirmation 
period, then the Investigator should assess:  
• 
If the Subject is still within the 12-weeks from Baseline Visit V2, the Investigator should 
restart the treatment till the EOT Phase or re-closure of Target Ulcer, whichever is 
earlier 
• 
If the Subject is beyond 12-weeks of Treatment Phase, the Investigator should 
continue Follow-Up procedures 
• 
If the unscheduled visit is for any other purpose, the Investigator should complete the 
assessments that are relevant to Phase of the Study for the Subject and complete 
corresponding CRF 


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8.1 
ASSESSMENTS AND PROCEDURES IN THE STUDY 
The assessments and procedures in the Study are as follows: 
Ankle-Brachial Index (ABI): Measurement of the ABI will be performed in a clinician’s office using 
a blood pressure (BP) cuff and handheld Doppler device with a vascular probe (See Attachment 2). 
Systolic BP will be determined in both arms and both ankles. ABI will be assessed at Screening Visit 
V1. 
Random blood glucose measurement: Random blood glucose measurement will be done at 
Baseline Visit V2 and all Treatment and Follow-up Visits (V3 to V18). If abnormality is observed, the 
Investigator may recommend pre- and post-prandial blood glucose measurement and modify 
medication for adequate blood sugar control. This test will be performed locally. 
Assessment of study foot: Study foot will be assessed at Screening Visit V1 by Semmes Weinstein 
(SW) 5.07 monofilament test. Peripheral neuropathy will be assessed by using a 10 g SW 5.07-
gauge monofilament to test 4 points on the foot for touch sensation (Greater toe, 1st, 3rd and 5th 
metatarsal head) (See Attachment 3). 
Detail foot examination: Detail foot examination to assess vascular, neurological, dermatological 
and musculoskeletal signs and symptoms of the foot under Study will be done at Screening Visit 
V1, Baseline Visit V2, every 4 weeks thereafter during treatment visits (i.e. at V6, V10, and V14 or 
EOT) and during follow-up at V18 or EOS/FU4, whichever is earlier. 
Local examination and infection status of Target Ulcer for presence of edema, warmth, erythema, 
pain, scaling, pus, exudates, cellulitis, callus, maceration or swelling and any signs of infection will 
be done at all Visits (V1 to V18). 
Target Ulcer classification and its measurement: Classification of all the potential Target Ulcers 
and its measurement will be completed as per Texas system at the screening visit (V1). The 
classification and measurement will be done for selected Target Ulcer at Baseline Visit (V2) as well 
as in all Treatment and Follow-up Visits (V3 to V18) (See Attachment 1). The measurement of the 
Target Ulcer area will be done using advance camera. The parameters captured will be area, 
volume, mean depth and maximal depth. It should however be noted that volume and depth 
measurements may be inaccurate to the extent of the advance camera’s technical limitations. In 
the event of inability to measure wound size by advance camera, the Target Ulcer area 
measurement will be done with the help of wound tracing in conjunction with planimetry software. 
In such situation, only Target Ulcer area will be measured.  
Target Ulcer characteristics: Assessment of Target Ulcer characteristics in terms of wound edge, 
color, drainage amount and type, peri-wound conditions and color and percent wound bed 
covered by granulation tissue, fibrin slough, and necrotic tissue will be done at all Visits (V1 to V18). 
Wound Care: Wound care to be taken during the Study will be explained to the Subject by the 
Investigator at the time of Screening and periodically. This will include following: 
1. A moist wound environment as suitable for the condition of wound (moist bandage should 
not be used in case wound is oozing and highly moist) 
2. Non-adherence of dressing to the wound 
3. Allowance for removal of dressing from the wound without pain or trauma 
4. Role of the dressing to absorb the excess wound exudates 
5. Allowance for gaseous exchange through the protective dressing 
6. Prevent permeance to microorganisms 


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Debridement of Target Ulcer: Debridement of the Target Ulcer, if required along with 
documentation of type of debridement (e.g. callus removal, sharp or surgical), reason for 
debridement will be recorded at Screening Visit V1 and all treatment and Follow-up visits V2 to 
V18 (as and when necessary).  
The Target Ulcer will be surgically debrided, if required as per procedure given below.  
1. Perform sharp debridement to remove all necrotic soft tissue, hyperkeratotic wound 
margins, bacterial burden, cellular debris, sinus tracts, fistulae, undermined borders, and 
callus to produce viable wound margins and a clean ulcer site.  
2. Use sterile saline to remove any debris at the ulcer site. Irrigate the ulcer with saline and 
gently wipe debris from the ulcer with sterile gauze.  
3. Use sterile gauze moist by sterile saline to keep the ulcer environment moist. The moist 
gauze may not be used for oozing or highly moist wound. 
Debridement of tissue will be done till all dead necrotic tissues are removed from Target Ulcer to 
expose healthy tissue which enhances wound healing.  
Target Ulcer dressing: Use a dressing that will maintain a moist wound-healing environment (if 
found appropriate for the condition of wound), manage wound exudates, and protect the peri-
ulcer skin. Cut sterile sponge in the approximate size and shape of the ulcer, moisten the sponge 
with saline, and place it over the ulcer. Place sterile gauze on top of sponge. Then wrap the dressing 
with a non-adherent bandage to secure the wound dressing.  
The Target Ulcer will be dressed in one of the protocol-specified dressings (Aquacel®, TenderWet® 
or sterile gauze dipped in sterile normal saline or sterile Lactated Ringers solution). After the Target 
Ulcer has been designated, protocol-specified dressings should be used only on the Target Ulcer. 
All other ulcers will be treated as per Investigator discretion and per Standard Care. 
Systematic physical examination and vital sign: Physical examination will be assessed at Screening 
Visit V1, V6, V10, V14 or EOT and V18 or EOS. However, vital signs (blood pressure, pulse rate, 
respiratory rate, and temperature) will be assessed at all visits (V1 to V18). 
Laboratory tests: Hematology tests (WBC, RBC, Hematocrit, Hemoglobin, MCV, MCH, MCHC, RDW, 
Platelet Count, Mean Platelet Volume) and Biochemistry tests [Glucose, Calcium, Albumin, Total 
Protein, Sodium, Potassium, CO2, Chloride, Blood Urea Nitrogen (BUN), eGFR, Alkaline phosphatase 
(ALP), Alanine transaminase (ALT), aspartate aminotransferase (AST), Bilirubin] will be done at 
Screening Visit V1, V6, V10, V14 or EOT and V18 or EOS. HbA1c will be performed at Screening Visit 
V1, V14 or EOT and V18 or EOS/FU4, whichever is earlier. Random blood glucose will be measured 
by the glucometer, provided by the sponsor, at Baseline Visit V2 and all Treatment and Follow-up 
visits (V3 to V18). 
Approximately 5 mL blood will be collected from each Subject at visits where laboratory assays are 
to be performed. These visits are Screening visit V1, V6, V10, V14 or EOT visit whichever is earlier 
and V18 or EOS/FU4 whichever is earlier. The laboratory assessments are haematology, 
biochemistry and HbA1c. Thus, total volume of blood that will be withdrawn per Subject during 
the Study will be approximately 25 mL.  
Any additional/unscheduled investigation(s) can be done at the Investigator’s discretion as 
needed. These investigations may also be done at local laboratory, if required. 
Urine pregnancy test will be done locally in women of child bearing potential at Screening Visit V1, 
V6, V10, V14 or EOT whichever is earlier, and V16/FU2 at Follow-Up.  


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ECG and X-ray: ECG will be done at Screening Visit V1, and every 4 weeks after Baseline during 
Treatment visit V6, V10, and V14 or EOT and V15/FU1 at follow-up. X-ray of the foot under Study 
will be performed at the Screening Visit and further at the Investigator’s discretion to rule out 
osteomyelitis.  
Recording and Assessment of adverse events: if there is any clinically significant abnormality or 
signs or symptom detected in the Subject or reported by the Subject after the application of 
treatment, it will be recorded as an adverse event. The AE assessment will be done from Baseline 
Visit V2 to V18 or EOS/FU4, whichever is earlier.  
Assessment of local pain: Local pain at the Target Ulcer site will be measured in terms of 11-point 
universal pain scale as mentioned in Attachment 4.  
Assessment of local edema: Local edema at the Target Ulcer site will be measured in terms of 5-
point edema scale as mentioned in Attachment 4. 
Assessment of local erythema: Local erythema at the Target Ulcer site will be measured in terms 
of 5-point erythema scale as mentioned in Attachment 4. 
The local pain, edema and erythema will be recorded at all the visits from Baseline Visit V2 to V18 
or EOS/FU4, whichever is earlier. 
8.2 
ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS 
8.2.1 DEFINITION OF ADVERSE EVENTS (AE) 
Adverse event means any untoward medical occurrence associated with the use of an intervention 
(Galnobax® plus SoC or only SoC or Vehicle plus SoC) in humans, whether or not considered 
intervention-related.  
8.2.2 DEFINITION OF SERIOUS ADVERSE EVENTS (SAE)  
An adverse event (AE) or suspected adverse reaction is considered "serious" if, in the view of either 
the Investigator or the Sponsor, it results in any of the following outcomes: death, a life-
threatening adverse event, inpatient hospitalization, a persistent or significant incapacity or 
substantial disruption of the ability to conduct normal life functions.  
8.2.3 CLASSIFICATION OF AN ADVERSE EVENT 
8.2.3.1 
SEVERITY OF EVENT 
The intensity of all AEs occurring during the course of the Study will be graded according to NCI-
CTCAE, version 4.0. as provided in Table 5: 


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Table 5 Assessment of Intensity 
Grade 
Description of Intensity Grading  
1 
Mild  
2 
Moderate  
3 
Severe  
4 
Life-threatening or disabling  
5 
Death 
8.2.3.2 RELATIONSHIP TO STUDY INTERVENTION 
Every effort would be made by the Investigator to explain each AE and assess its causal 
relationship, if any, to application of the IP. 
Causality of all AEs would be assessed by the Investigator depending upon various factors like the 
temporal relationship of the AE to Study IP application, whether AE follows a known pattern of 
response to IP, any other cause to which the AE can be attributed or intensity of AE changes. 
Relationship of AEs to Study treatment will be classified as follows: 
1. 
Unrelated – The event is definitely not associated with the Study drug. Other conditions 
including concurrent illness, progression or expression of the disease state, or reaction to 
a concurrent medication explain the reported AE. 
2. 
Unlikely – The temporal association, Subject history and/or circumstances are such that 
the Study drug is not likely to have had an association with the observed event. Other 
conditions including concurrent illness, progression or expression of the disease state, or 
reaction to a concurrent medication, appear to explain the reported AE. 
3. 
Possibly – The event follows a reasonable temporal sequence from Study drug but could 
have been produced by the Subject’s clinical state or other therapies administered to the 
Subject. 
4. 
Probably – The event follows a reasonable temporal sequence from the Study drug, 
abates upon discontinuation of the Study drug or control, and cannot be reasonably 
explained by known characteristics of the Subject’s clinical state. 
5. 
Definitely – The event follows a reasonable temporal sequence from the Study drug, 
abates upon discontinuation or cannot be explained by known characteristics of the 
Subject’s clinical state. 
8.2.3.3 EXPECTEDNESS  
Investigator will be responsible for determining whether an adverse event (AE) is expected or 
unexpected. An AE will be considered unexpected if the nature, severity, or frequency of the event 
is not consistent with the risk information available for the study intervention. The treatment is 
being given topically in this Study, therefore the AEs that are expected at and around the Target 
Ulcer location are: hypersensitivity, irritation, inflammation of ulcer. Since the Target Ulcer is an 
open wound, possibility of infection at the wound site cannot be ruled out. The infection at Target 
or non-Target Ulcer will be reported as AE.  


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8.2.4 TIME PERIOD AND FREQUENCY FOR EVENT ASSESSMENT AND FOLLOW-UP 
The occurrence of an adverse event (AE) or serious adverse event (SAE) may come to the attention 
of Study personnel during Study visits or Study Nurse during visits to Subject and interviews of a 
Study Subject presenting for medical care, or upon review by a study monitor. 
All AEs including local and systemic reactions not meeting the criteria for SAEs will be captured on 
the appropriate electronic case report form (eCRF). Information to be collected includes duration 
(start and end dates), severity/intensity, relationship to IP, specific therapy, results and 
consequences and seriousness. All AEs occurring while on Study must be documented 
appropriately regardless of relationship. All AEs will be followed to adequate resolution.  
Any medical condition that is present at the time that the participant is screened or before 
application of first dose will be considered as baseline and not reported as an AE. However, if the 
Study participant’s condition deteriorates at any time during the study, it will be recorded as an 
AE.  
Changes in the severity of an AE will be documented to allow an assessment of the duration of the 
event at each level of severity to be performed. AEs characterized as intermittent require 
documentation of onset and duration of each episode. 
The Investigator will record all reportable events with start dates occurring any time after informed 
consent is obtained till the last day of Study participation. At each Study visit, the Investigator will 
inquire about the occurrence of AE/SAEs since the last visit. Events will be followed for outcome 
information until resolution or stabilization. An AE can reach one of the following outcomes: 
a. 
Complete recovery (AE/ SAE end date will be captured). 
b. 
Recovered with sequelae. (AE/ SAE end date will be captured and the sequelae will be 
specified). 
c. 
Ongoing 
d. 
Death  
e. 
Unknown: The outcome of the event may be captured as unknown only in the 
exceptional cases when the Subject is lost to follow-up (AE end date will be left blank). 
8.2.5 ADVERSE EVENT REPORTING  
AEs will be assessed during each visit by doing clinical examination, review of the laboratory 
investigations and by directly questioning the Subject/LAR/impartial witness. The increase of 
Target Ulcer size or its worsening will be considered as adverse event. The change from Baseline 
in laboratory values, vital signs and ECG/EKG parameters outside accepted or normal range will be 
reported as adverse event irrespective of Investigator’s opinion on clinical significance of such 
abnormality. 
As far as possible each AE should be described to include: 
• 
Duration (start and end dates) 
• 
Severity/Intensity  
• 
Relationship to IP or Specific therapy 
• 
Results and Consequences 
• 
Seriousness  
Those AEs that are already documented in the CRFs, at a previous assessment and designated as 
‘ongoing’ would be reviewed at subsequent visits, as necessary. If these have resolved, the 
documentation in the CRF would be completed. 


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8.2.6 
HANDLING OF UNRESOLVED ADVERSE EVENTS  
• 
If any AE is present when a Subject completes the Study or if a Subject is prematurely 
withdrawn from the Study, an attempt will be made to follow the Subject up for 12-weeks. 
Amongst the AEs ongoing on the last Study visit as per the Study protocol, all the AEs have 
to be recorded in the AE form 
• 
The Investigator assesses the status of the AEs 
• 
The AEs recorded at the time of exit are to be followed until, 
o 
The AEs are considered to become stable as per the Investigator’s discretion, or 
o 
The AEs are no longer considered to be medically significant by the Investigator, or 
o 
The database of the Study is declared to be locked 
• 
The sponsor reserves the right to ask further information on any AE/SAE, which may be 
considered of interest 
8.2.7 
EVENT NOT TO REPORTED AS AE 
Progression of underlying disease (at Investigator’s discretion) / Study indication/lack of efficacy 
of the IP would NOT be reported as an AE/SAE. 
8.2.8 
SERIOUS ADVERSE EVENT REPORTING  
• 
Any SAE occurring during the course of the Study would be treated by established 
standards of care to protect the life and health of the Subject 
• 
Any SAE, irrespective of causality, must be immediately notified to the safety team at the 
CRO and the Sponsor. It must be followed up within 24 hours on the Study specific SAE 
reporting form with as much detailed information regarding the event that is available 
• 
Investigators would not wait to receive additional information to fully document the event, 
before notifying SAE to the CRO. 
• 
The SAE reporting form should detail all relevant aspects of the AEs in question. Where 
applicable, information from relevant hospital case records and autopsy reports would be 
obtained and provided, in a blinded fashion, to the CRO. 
• 
All SAEs would be reported within 24 hours of Investigator’s knowledge of the event to the 
CRO. and to the respective EC and Regulatory authorities (CDSCO) by the Investigator as 
soon as possible as per applicable regulations. The Investigator site and the sponsor would 
have to copy all SAE related communications on safety@jssresearch.com while 
communicating with the CRO and galnobax@novaleadpharma.com for communicating 
with the Sponsor. The SAE forms should be shared via E-mail as scanned attachments  
• 
The event must also be recorded on the CRF AE page 
• 
The follow up SAE form also should be filled and sent to the CRO, the Sponsor, CDSCO and 
EC within 24 hours of updated information on SAE 
• 
Communicate filled CIOMS-I MedWatch form within 14 calendar days to CDSCO 
The CRO does not prefer Fax as the mode of communication for SAEs. However, if a site would 
insist on using fax then the site should have to send an email stating the information that the fax 
has been sent. In the event of any technical issue wherein the site would not be able to send the 


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Email, then a phone call should be made to the concerned medical monitor to inform that SAE 
form sent via fax.  
Fax: + 91-11-1296613510 
All the events will be monitored by the Investigator until the event has subsided or, in a case of 
permanent impairment, until the event stabilizes and the overall clinical outcome has been 
ascertained. 
8.2.9 
REPORTING EVENTS TO PARTICIPANTS  
Not-applicable 
8.2.10 EVENTS OF SPECIAL INTEREST  
Not-applicable 
8.2.11 REPORTING OF PREGNANCY  
In event of a pregnancy during the Study, the same is required to be reported to the CRO safety 
team immediately via telephone and in the form of Pregnancy Report Form (PRF) within 24 hours 
from the knowledge of the Investigator about the pregnancy. The Subject would be discontinued 
from the Study and the End of Study visit procedure would be completed. 
A Pregnancy Outcome form (POF) will then be sent to the site from the CRO/the Sponsor, which 
should be filed and a copy of which will be faxed back to the CRO/the Sponsor safety team within 
24 hours from the knowledge of the pregnancy reaching its outcome 
Pregnancy during a clinical trial itself is not regarded as an AE/ SAE unless pregnancy falls in the 
following types: 
• 
Ectopic pregnancy 
• 
Molar pregnancy 
• 
The concerned pregnancy results in one of the following outcomes: 
• 
Miscarriage/late spontaneous abortion 
• 
Stillbirth 
• 
Congenital Malformation/Anomaly 
• 
Neonatal death (within 28 days from birth) 
• 
Infant death (after 28 days from birth but assessed as related to the IP by the Investigator) 
In case for any pregnancy reported during a clinical trial, results in one of the above outcomes, the 
Investigator is required to fill the AE form and the corresponding SAE form and report to the 
CRO/the Sponsor safety team within same timelines as mentioned above.  
8.2.12 EXPEDITED SAFETY REPORTING 
Any serious AE, which is unexpected and at least possibly related to the IP calls for expedited 
reporting to the regulatory authorities and the ECs as per CDSCO requirements. 
As the CRO acts on behalf of the Sponsor, the regulatory reporting time clock starts when any 
member of the CRO safety team qualifies a SAE as an expedited SAE, in consultation with the 
Sponsor.  
8.2.13 DEFINITION OF UNANTICIPATED PROBLEMS (UP) 


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Not-applicable 
8.2.14  UNANTICIPATED PROBLEM REPORTING  
Not-applicable 
8.2.15 REPORTING UNANTICIPATED PROBLEMS TO PARTICIPANTS  
Not-applicable 
9 
STATISTICAL CONSIDERATIONS 
9.1 
STATISTICAL HYPOTHESES 
Primary Efficacy Endpoint(s):  
Proportion of Subjects achieving Target Ulcer closure within 12-week Treatment Phase, as assessed 
by blinded Investigator. 
Secondary Efficacy Endpoint(s): 
• 
Time to Target Ulcer Closure during the 12-week Treatment Phase, as assessed by the 
blinded Investigator 
• 
Proportion of Subjects achieving Target Ulcer Closure till End of study, as assessed by the 
blinded Investigator 
 
9.2 
SAMPLE SIZE DETERMINATION 
This Study will have FAS Population (Efficacy Evaluable Population) of minimum of 240 Subjects 
(minimum of 120 each in Group 1 and Group 2). To ensure this and assuming 20% drop out rate, 
the population of two groups would be up to 300 Subjects. For safety analysis of Vehicle of 
Galnobax®, maximum of 50 Subjects will be recruited in Vehicle plus SoC group. Thus, overall 
population of maximum of 350 Subjects will be recruited in the Study. 
Sample Size Determination and Rationale:  
The sample size calculation has two components. One is based on statistical power and the other 
is based on clinical judgment. 
The sample size calculation is based on the primary endpoint for the Study that is proportion of 
Subjects achieving complete closure of Target Ulcer within 12-week Treatment Phase, as 
determined by blinded Investigator’s assessment. 
The sample size is obtained based on the assumption that there will be a clinically meaningful 
difference of 21%, (i.e., 39% of SoC vs 60% of Galnobax®-treated achieved complete closure of 
Target Ulcer, odds ratio of 0.65). This assumption is based on the following: 
a. Literature reports from various DFU trials showed that average percent wounds closed 
using SoC treatment is 24% globally.5 27 However, percent wounds closed using SoC 
treatment in recently completed DFU trial in India is reported to be 37.8%.28 In view of this, 
it is assumed that 39% wounds may close in the SoC group.  
b. In Phase 1/2 study of Galnobax®, 60% wounds closed within 12-week of Galnobax® 
treatment. Furthermore, 67% wounds were closed in Galnobax® arm for wounds with 
wound age > 6 weeks. In view of this, the inclusion criterion is revised to include Subjects 
with wounds of at least 6 weeks (which was 4 weeks in Phase 1/2 study) and it is assumed 
that 60% wounds may close in the Galnobax® treatment group.  


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To meet the Type I error rate of 0.05 (95% confidence interval), 2-sided analysis and 90% power, 
120 Efficacy Evaluable Subjects in Group 1 and Group 2 will be required for making the FAS 
Population in the Study as 240. To accommodate the potential drop outs rate of 20%, a total of 
300 Subjects will be randomized in these Groups to ensure more than 90% power for the primary 
endpoint analysis (i.e., proportion of Subjects achieving Target Ulcer Closure within 12-week 
Treatment Phase). 
The safety evaluation of Vehicle of Galnobax® will be done by recruiting population of 50 Subjects 
in the Vehicle plus SoC group. As there is not hypothesis testing or statistical comparison proposed 
for this arm, this population might not be statistically significant, but would enough to give 
reasonable estimate of safety for Vehicle of Galnobax®. 
9.2.1 
RANDOMIZATION AND STRATIFICATION OF STUDY POPULATION: 
Prior to randomization, Subjects will be stratified by location of Target Ulcer (planter or non-
planter), and the Target Ulcer size (<5 cm2 or ≥5 cm2). The randomization will be done at the ratio 
of 3:3:1 in one of the following groups, using an IWRS: 
• 
Galnobax® 14% plus SoC or 
• 
SoC or 
• 
Vehicle plus SoC  
9.3 
POPULATIONS FOR ANALYSES 
For this Study, analysis will be done on ITT Population (Safety Evaluable Population), FAS 
Population (Efficacy Evaluable Population) and PP Population.  
The ITT Population i.e. Safety Evaluable Population will include all those Subjects who are 
randomized and received at least one dose of the study treatment. 
The FAS Population (Efficacy Evaluable Population) will include all randomized Subjects who has 
had at least six weekly assessments for Target Ulcer Closure or has Target Ulcer closed earlier than 
six weeks.  
The PP Population will include all randomized Subjects who have completed the Study without any 
major protocol deviation. 
9.4 
STATISTICAL ANALYSES 
9.4.1 
GENERAL APPROACH 
Before database lock, a statistical analysis plan (SAP) will be issued as a separate document, 
providing the detailed methods for analyses outlined below. Any deviation from the planned 
analyses will be described and justified in the final integrated clinical Study report. 
A maximum of 350 Subjects will be competitively recruited at 40 sites from the DFU Subject 
population as described in section 4.1 
The number and percentage of all the DFU Subjects entering and completing the clinical Study will 
be provided across treatment groups. The summarization of primary reason of discontinuation will 
also be provided across treatment groups. 
For this Study, analysis will be done on ITT Population (Safety Evaluable Population), FAS 
Population (Efficacy Evaluable Population) and PP Population. 


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The continuous data will be summarized by treatment Group using descriptive statistics (number 
of Subjects [n], Mean, Standard Deviation [SD], Median, Minimum and Maximum [Range]). 
Categorical data will be summarized by treatment group using frequency count (n) and 
percentages (%).  
The primary and secondary efficacy analysis will be performed on all Subjects in FAS Population 
(Efficacy Evaluable Population) and PP Population comparing Group 1 (Galnobax® plus SoC) and 
Group 2 (SoC) only. All the statistical analysis will be performed using SAS® version 9.4 or later. 
The Safety analysis will be performed on all Subjects in ITT Population (Safety Evaluable 
Population). 
9.4.2 
ANALYSIS OF THE PRIMARY EFFICACY ENDPOINT 
The primary efficacy analysis will be performed on all Subjects in FAS Population (Efficacy Evaluable 
Population) and PP Population comparing Group 1 (Galnobax® plus SoC) and Group 2 (SoC only) 
only.  
Proportion of Subjects achieving Target Ulcer closure within 12 week Treatment Phase (EOT) = 
[Number of Subjects having Target Ulcer closed by treatment at or before week 12 (84 ± 3 days)]/ 
[Total Number of Subjects in the Population]. 
The logistic regression analysis will be used for the primary efficacy analysis for the proportion of 
Subjects achieving Target Ulcer closure within 12-week Treatment Phase, considering Target Ulcer 
closed (Yes/No) as dependent variable and treatment group, ulcer type (plantar or non-plantar), 
and site as independent factors and baseline ulcer size as continuous covariate. 
9.4.3 
ANALYSIS OF THE SECONDARY EFFICACY ENDPOINT(S) 
The secondary efficacy analysis will be performed on all Subjects in FAS Population (Efficacy 
Evaluable Population) and PP Population comparing Group 1 (Galnobax® plus SoC) and Group 2 
(SoC only) only and are defined as: 
• 
Time to Target Ulcer Closure in days = (Date of Target Ulcer Closure by Week 12 of 
treatment or earlier – Date of first dose of Study treatment) + 1 
• 
Proportion of Subjects achieving Target Ulcer Closure till End of Study = [Number of 
Subjects having Target Ulcer Closure at by week 24 or earlier /Total number of Subjects 
in the Population]. 
For analysis of secondary endpoint of time to Target Ulcer closure during the 12-week Treatment 
Phase, Cox proportional hazards model with treatment group, ulcer type (plantar or non-plantar) 
and site as independent factors and baseline ulcer size as continuous covariate will be used to 
compare between the treatment groups. In addition, Kaplan-Meier analysis will also be used to 
depict the median time (days) to Target Ulcer closure for the two treatment groups.  
The other categorical secondary endpoints comparing proportion of Target Ulcer using different 
criteria will be analyzed using chi-square/fishers exact test as well as the same method described 
for primary efficacy analysis with the same model of logistic regression.  
9.4.4 
SAFETY ANALYSES 
Safety will be analyzed for all Subjects in ITT Population in the three groups. No formal statistical 
analysis will be performed.  


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To investigate the safety of Galnobax® vehicle for establishing non-deleterious effects of Vehicle 
on wound healing, number and percentage of events as well as number and percentage of Subjects 
with events related to local wound assessment (local pain, edema, erythema) of Target Ulcer in 
Vehicle plus SoC group will be tabulated and reported. 
9.4.4.1 TREATMENT EMERGENT ADVERSE EVENT  
Treatment emergent adverse events (TEAE) are undesirable events not present prior to medical 
treatment, or an already present event that worsens either in intensity or frequency following the 
treatment. The TEAEs, which is defined as all AEs on or after the application of first dose of IP will 
be summarized according to the numbers and percentages of TEAEs as well as numbers and 
percentages of Subjects with one or more occurrences of TEAEs during the Study. Number of 
Subjects with TEAEs and number of events of TEAEs will be tabulated by preferred term (PT) and 
system organ class (SOCL). If a Subject had more than one TEAE, event will be counted only once 
in SOCL and once for each PT.  
Summaries of TEAEs by severity grade, relationship to Study medication, leading to death, SAEs of 
study, IP related TEAEs will be provided.  
Also, summarization for SAE, SAEs by severity, SAEs by relationship to Study IP will be provided 
separately.  
Listing will be provided for all Subjects who have at least one adverse event. 
AEs will be coded using the MedDRA, version 20.0 or later. 
9.4.4.2 CLINICAL LABORATORY TEST 
The clinical laboratory tests will be summarized descriptively for each of the continuous parameter 
at Subject’s visits when tests are carried out for the changes from the baseline parameter. Shift 
tables in terms of counts and percentages will be presented at each relevant visit versus baseline 
for categorical laboratory parameters. 
Individual data listings of laboratory results will be presented for each Subject. Clinically significant 
laboratory test abnormalities that are considered AEs by the Investigator will be presented in the 
AE listings. 
9.4.4.3 PHYSICAL EXAMINATION AND VITAL SIGNS 
The vital sign parameters will be summarized descriptively for each of the continuous parameters 
at each visit and for change from baseline.  
The frequency counts and percentages of Normal, Abnormal NCS, and Abnormal CS will be 
provided for each body system of the physical examination. 
Subject wise data listing will be provided for all vital sign parameters and physical examination. 
9.4.5 
BASELINE DESCRIPTIVE STATISTICS 
The demographic and baseline characteristics will be summarized and listed for all Subjects in ITT 
Population.  


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Medical history will be coded using Medical Dictionary for Regulatory Activities (MedDRA) 
dictionary version 20.0. The count and percentage of Subjects will be summarized according to the 
coded terms of system organ class and preferred term across all the treatment groups.  
The prior and concomitant medications will be coded using World Health Organization Drug 
Dictionary (WHODD)-September, 2016 or later. The count and percentage of Subjects will be 
summarized according to the coded terms of system organ class and preferred term across all the 
treatment groups. 
Other baseline parameters like ECG and X-Ray will be listed as appropriate. 
9.4.6 
PLANNED INTERIM ANALYSES 
No interim analysis is planned for this Study. 
9.4.7 
METHODS USED FOR MISSING DATA 
Missing data points will be dealt with using appropriate statistical techniques, depending on the 
nature of the data and will elaborately explained in statistical analysis plan (SAP).  
9.4.8 
HANDLING OF OUTLIER DATA 
The outlier data will be dealt with using appropriate statistical techniques, depending upon the 
nature and type of data and will elaborately explained in statistical analysis plan (SAP).  
9.4.9 
HANDLING OF TREATMENT FAILURE 
Subjects with need for more than two surgical debridement procedures during Treatment Phase 
will be considered as treatment failure for the Subject. 
9.4.10 STATISTICAL ANALYSIS OF DATA 
The CRO will perform the statistical evaluation using appropriate statistical tests. Statistical analysis 
will be performed using SAS® system Version 9.4 software (SAS Institute Inc., NC, and USA) or later. 
9.4.11 SUB-GROUP ANALYSES 
The subgroup analysis for ulcer type (plantar and non-plantar) and ulcer size (<5 cm2 vs. ≥5 cm2) 
will also be performed for the primary efficacy endpoint i.e. proportion of Subject achieving Target 
Ulcer Closure within 12-week Treatment Phase by considering ulcer type (plantar and non-plantar) 
and ulcer size (<5 cm2 vs. ≥5 cm2) as the subgroup strata. 
9.4.12 TABULATION OF INDIVIDUAL PARTICIPANT DATA 
Listing of individual Subject data per visit (wherever applicable) for all key variable will be 
presented.  
9.4.13 EXPLORATORY ANALYSES 
Not applicable 


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10 SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS 
10.1 REGULATORY, ETHICAL, AND STUDY OVERSIGHT CONSIDERATIONS 
10.1.1 INFORMED CONSENT PROCESS 
The method of explanation to the Subject/legally accepted representative (LAR)/impartial witness 
and obtaining their consent would comply with the ICH GCP Guidelines, with GCP for Clinical 
Research in India, 2001; Indian Council of Medical Research’s (ICMR) Ethical Guidelines for 
Biomedical Research on Human Participants, 2006 and Schedule Y, Amended 2005 under Drugs 
and Cosmetics Act and Rules there under, and the ethical principles in the amended Declaration of 
Helsinki version 2013.  
10.1.1.1 CONSENT/ASSENT AND OTHER INFORMATIONAL DOCUMENTS PROVIDED TO 
PARTICIPANTS 
Consent forms describing in detail the Study intervention, Study procedures, and risks are given to 
the potential participant and written documentation of informed consent is required from the 
Subject/LAR prior to starting intervention/administering Study intervention.  
10.1.1.2 CONSENT PROCEDURES AND DOCUMENTATION 
Prior to any Study-related Screening procedures being performed on the Subject, written informed 
consent will be obtained from each Subject before enrolling in the Study. The site should first 
obtain consent from the Subject/LAR on video recording of consent process. The Investigator or 
his/her representative will explain the nature of the Study to the Subject and the LAR (including 
the impartial witness if required) and answer all questions regarding this Study. This consent 
process will be video recorded by the site and stored carefully for any regulatory audit. The 
information and consent form will be reviewed, signed and dated by the Subject/LAR. In case the 
Subject or the LAR is illiterate, the impartial witness will attend the informed consent process and 
sign and date the ICF.  
10.1.1.3 ETHICAL CONSIDERATION 
The Study will be conducted according to the approved protocol (and amendments, if applicable), 
GCP standards (Good Clinical Practice Guidelines for Clinical Trials in India, FDA Title 21 part 312 
and International Conference on Harmonization guidelines) and all applicable Government 
regulations.  
The protocol will be submitted for review to EC of each site and their suggestions on Subject safety 
will be reviewed and adopted. Upon approval of protocol by EC, site will be initiated and Subjects 
will be randomized. 
10.1.2 STUDY DISCONTINUATION AND CLOSURE 
The Sponsor reserves right to terminate the Study at any time. The Principal Investigator (PI) and 
the Sponsor, if appropriate can mutually decide premature termination of the Study. The 
regulatory authorities or ECs may also recommend the Study termination before completion. 
In the event of an early termination of the Study,  
1. Investigators will cease the use of the IP immediately.  


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2. All outstanding electronic case report forms (eCRFs) will be completed and returned to the 
CRO/the Sponsor together with completed IP inventory, records and remaining Study 
material. 
3. The CRO/the Sponsor will inform regulatory authorities reasons for such termination 
4. Investigators will inform to respective ECs 
5. The reason for termination will also be communicated to the Subjects in the trial. 
Stopping or Discontinuation Rules for a Study Site: 
The Study may be halted at any Study site if, 
1. A Study site and/or its participating personnel are non-compliant with respect to 
• 
following the defined clinical Study protocol 
• 
reporting any adverse or unforeseen event to the EC/Regulatory in the minimum 
mandatory time or reporting AEs/Subject non-compliance to the CRO/the Sponsor  
• 
non-cooperation of the Investigator and/or Site with the CRO/the Sponsor  
• 
timely providing SoC to the Subjects 
• 
negligence to Subject’s health and protocol by the Investigator/unblinded 
Investigator/site personnel involved in the Study 
2. There is a significant decrease in the number of compliant Subjects anytime during the 
ongoing Study 
3. If the Study Site / members of the site compromise(s) on the dignity or integrity of a Subject 
recruited into the Study  
4. The EC recommends stop of Study based on occurrence of serious and unforeseen AEs 
Stopping or Discontinuation Rules for a Full Study:  
The Sponsor reserves right to discontinue the Study at any time.  
10.1.3 CONFIDENTIALITY AND PRIVACY  
The CRO and the Sponsor will affirm and uphold the principle of the Subject’s right to protection 
against the invasion of privacy. Throughout this Study and any subsequent data analyses, all data 
reported to the Sponsor will be identified only by protocol number, Subject number and Subject 
initials. 
The records of the Subject’s medical history, physical examination, laboratory results and any other 
information or data generated during the Study will be made available to the Sponsor or its 
designee (auditors, monitors), the EC. It will also be made available to drug regulatory bodies in 
India and possibly other countries, formulary committees of hospitals, at the opinion of the 
Sponsor. A pre-condition for entry into this Study will be Subject’s agreement to release the 
documentation and data for any lawful purpose. In such cases, the Subject’s name will be removed 
from all documentation to ensure anonymity. 
10.1.4 KEY ROLES AND STUDY GOVERNANCE 
Sponsor’s designee JSS India Medical Research Pvt. Ltd. will be responsible. 
Study Management 
Dr. Jayashri Krishnan 
Project Manager 
Dr. Sowmya. K.S 


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Study Monitoring 
JSS Monitors  
Medical Monitor  
Dr. Gursimran Kaur 
Regulatory 
Mr. Harish Chander 
Data Management 
Dr. Neha Pant  
Statistics 
Mr. Santosh Kumar 
Medical Writing 
Ms. Meenakshi Chaudhary  
10.1.5 CLINICAL MONITORING 
10.1.5.1 SITE INITIATION 
Upon obtaining EC approval for a site, a “Site Initiation Visit” will be held before the first Subject is 
enrolled. The Subjects cannot be recruited at the site until occurrence of such visit and its 
documentation. During this visit, requirements of GCP, protocol procedures, and all logistic issues 
will be discussed at length. The availability of IP and supplies at the site will be ensured and 
documented. The training of Investigator, site staff and Study Nurse will be documented. 
The CRO team will also determine the adequacy and readiness of the clinical Study facility to start 
enrolment. The team will discuss the responsibilities of the blinded and unblinded Investigators 
and Study Nurse as well as other personnel involved with the Study with regard to protocol 
adherence. 
10.1.5.2 STUDY MONITORING AND SOURCE DATA VERIFICATION 
After the Study is initiated, Study monitor(s) from the CRO will contact the Investigator to obtain 
information on the performance of the Study. These contacts will be scheduled at regular intervals 
and be either in person or telephonic. 
Subsequent to start of recruitment, the first “Monitoring Visit” would occur as soon as possible 
after recruitment of the first Subject. The monitoring visits will take place at regular intervals during 
the entire Study (once a month or once in two months depending on recruitment rate of the site). 
The Investigator and site staff are obliged to set aside adequate time and place for the monitoring 
visits. All Study related site records where original entries are made will be reviewed to make sure 
that all Study related compliances are met. 
In addition to the monitoring visits, the sites may be audited or inspected. The audit may be carried 
out by the Quality Assurance Department of the CRO and/or independent entity authorized by the 
Sponsor. In addition, regulatory authorities may inspect the Study. The Investigator undertakes to 
expeditiously inform the CRO of an inspection by a regulatory authority. 


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10.1.5.3 CRF COMPLETION  
All Subject data (including Subject information, laboratory values, efficacy parameters etc.) will be 
collected in the source document during each visit of the Subject to the Site. This source data will 
be transcribed to electronic case report form (eCRF) by the site staff within 2-3 days from the visit. 
The entered data will be validated by running logic checks and manual reviews. For any 
discrepancies identified in study database, queries will be generated in the e-CRF for resolution. 
Site staff will be responsible for resolving all queries in the database. The queries raised in the e-
CRF will be first investigated by site from source data and Subject records. Then, appropriate 
corrections will be done to the e-CRF by the Investigator or their authorized designee. When the 
data has been entered, verified, and validated, the database will be locked for analysis. 
Medical Reviewers will review the CRF as well as data discrepancies generated by electronic edit 
check programs. Any discrepancies noted in the data will be queried to the Investigator for 
appropriate resolution. The AEs will be coded using MedDRA, version 20.0 and the concomitant 
Medications will be coded using World Health Organization drug dictionary (WHO-DD) (Version 1st 
March 2017 or later). 
10.1.6 QUALITY ASSURANCE AND QUALITY CONTROL 
In accordance with applicable regulations, ICH-GCP guidelines, The Sponsor or its designee’s 
monitors will contact the Site prior to the start of the Study to review with the site staff the 
protocol, study requirements, and their responsibilities to satisfy regulatory, ethical, and Sponsor’s 
requirements. When reviewing data collection procedures, the discussion will also include 
identification, agreement and documentation of data items for which the CRF will serve as the 
source document. 
The Sponsor and or its designee will monitor the Study for the protocol compliance verifying the 
following, but not limited to:  
• 
Safety and rights of subjects are being protected 
• 
Study is conducted in accordance with the currently approved protocol and any other 
study agreements, ICH-GCP guidelines, and all applicable regulatory requirements 
• 
Data are authentic, accurate, and complete 
The Site Investigator agrees to allow the monitor direct access to all relevant documents for the 
purpose of verification of available data. 
To ensure compliance with ICH-GCP guidelines and all applicable regulatory requirements, the 
Sponsor may conduct a quality assurance audit following intimation and appointment. Regulatory 
agencies may also conduct a regulatory inspection of this Study. Such audits/inspections can occur 
at any time during or after completion of the study. If an audit or inspection occurs, the Site 
Investigator and institution agree to allow the auditor/inspector direct access to all relevant 
documents and to allocate his/her time and the time of his/her staff to the auditor/inspector to 
discuss findings and any relevant issues. 
10.1.7 DATA HANDLING AND RECORD KEEPING  
10.1.7.1 DATA COLLECTION AND MANAGEMENT RESPONSIBILITIES  
Data collection is the responsibility of the clinical trial staff at the Site under the supervision of the 
Site Investigator. The Investigator is responsible for ensuring the accuracy, completeness, legibility, 
and timeliness of the data reported. 


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All source documents should be completed in a neat, legible manner to ensure accurate 
interpretation of data.  
Hardcopies of the study visit worksheets will be provided for use as source document worksheets 
for recording data for each participant enrolled in the Study. Data recorded in the electronic case 
report form (eCRF) derived from source documents should be consistent with the data recorded 
on the source documents.  
10.1.7.2 STUDY RECORDS RETENTION  
All documentation pertaining to the Study will be kept by the Sponsor for the lifetime of the 
product. The final report pertaining to this Study will be kept by the CRO for a further five years. 
The Study monitor will provide each Investigator with a Site Master File, which would be used to 
file the IB, protocol, IP accountability records, correspondence with the EC and national regulatory 
authority, the CRO, the Sponsor and other Study-related documents. 
As required by ICH GCP guidelines, the Investigator would keep essential documents for his/her 
Site until at least 2 years after the last approval of a marketing application in an ICH region, and 
until there are no pending or contemplated marketing applications in an ICH region, or at least 2 
years have elapsed since the formal discontinuation of clinical development of the IP. 
In addition, the Investigator would make provision for the Subject’s medical records to be kept for 
the same period of time. 
No data would be destroyed without the agreement of the Sponsor. The Sponsor will inform the 
Investigator in writing of the need for record retention and will notify the Investigator in writing 
when the trial related records are no longer needed. 
Subjects’ medical records and other original data will be archived in accordance with the local 
regulations and ICH GCP guidelines. 
10.1.8 PROTOCOL DEVIATIONS  
During the conduct of the Study, if any deviation(s) is noticed from the norm mentioned in the 
Protocol, this will be documented as protocol deviation(s). 
The severity of the protocol deviation will be graded as minor if the deviation is not altering the 
integrity of the Study plan or its safety and efficacy outcome. The deviation is said to be major or 
is designated as violation, if it is altering the integrity of the Study plan or its safety and efficacy 
outcome in the opinion of the Investigator. 
Examples of the major deviations or violations of the Protocol shall include: 
• 
Recruitment of a Subject in conflict with the inclusion and exclusion criteria 
• 
If Subject misses two consecutive Treatment visits or maximum of four Treatment visits 
• 
If Subject misses 6 consecutive wound dressings, anytime during the Treatment Phase 
• 
If Subject misses both of the Closure Verification Visit as well as Closure Confirmation visit 
• 
Use of a non-permitted concurrent treatment 
• 
Failure to obtain informed consent prior to initiation of Study related procedures 
Examples of minor deviations of the Protocol shall include:  
• 
Visits that occurred outside the time frame permitted in the protocol 
• 
Subjects have not met with Study drug compliance (80% - 120%) for a week during 
Treatment Phase 


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• 
Laboratory tests not performed as per timelines specified in the protocol 
Protocol Waivers 
There are no protocol waivers proposed for this Study. 
10.1.9 PUBLICATION AND DATA SHARING POLICY 
A Clinical Study Report, per the ICH Guideline for Structure and Content of Clinical Study Reports, 
will be prepared by the CRO in close collaboration with the Sponsor upon full completion of the 
Study. This Clinical Study Report, as well as any discovery and improvement related to IP, shall be 
the property of the Sponsor. The report will include, but not be limited to, a description of the 
study objectives, methodology (including any deviations from protocols), results, and conclusions 
regarding attainment of study objectives (from the standpoint of safety). All significant AEs will be 
described, with the Investigator's assessments as to whether related to Study drug administration. 
Neither the complete nor any part of the results of the study carried out under this protocol, nor 
any of the information provided by the Sponsor for the purposes of performing the Study, will be 
published or passed on to any third party without the prior written consent of the Sponsor. 
Any Investigator involved with this Study is obligated to provide the Sponsor with complete test 
results and all data derived from the Study. The Investigators agree to keep all unpublished 
information and results concerning this Study ‘Strictly Confidential’. Unpublished information must 
not be published or disclosed without Sponsor’s prior written approval 
10.1.10 CONFLICT OF INTEREST POLICY 
Any Investigator who has a conflict of interest with this study (patent ownership, royalties, or 
financial gain greater than the minimum allowable by their institution, etc.) must have the conflict 
reviewed by a properly constituted Conflict of Interest Committee of the Site with a Committee-
sanctioned conflict management plan that has been reviewed and approved by the Study Sponsor 
prior to participation in this study. 
10.2 ADDITIONAL CONSIDERATIONS 
10.2.1 POSSIBLE DRUG INTERACTIONS AND PROHIBITED MEDICATIONS 
Apart from SoC and Study treatment described above, no other topical treatment (such as creams, 
gels, ointments, liquids, sprays, patches, etc.) at the Target Ulcer site is permitted during the Study. 
The drugs that may affect the healing of ulcer for e.g., corticosteroids, immune-suppressants (e.g. 
except inhalers for respiratory disorders) and colchicines will not be permitted to be used during 
the Treatment Phase of the Study. Any medication from alternative medicinal therapy for wound 
healing (e.g. negative pressure or hyperbaric oxygen) will not be permitted during the period of 
Study.  
Contraindicated drugs: Esmolol hydrochloride is contraindicated in Subjects using inotropic agents 
and/or vasopressors to maintain systemic blood pressure. It is also contraindicated in Subjects with 
sinus bradycardia, second and third degree AV block, right ventricular failure secondary to 
pulmonary hypertension, overt cardiac failure or cardiogenic shock.  
Concurrent use of Verapamil with Esmolol hydrochloride: The use of i.v. verapamil with a beta-
blocker may cause severe depression of ventricular function. Accordingly, Subjects with atrial 
fibrillation or atrial flutter who have received Esmolol hydrochloride should only be administered 
verapamil if the benefits outweigh the risk in the opinion of the Investigator. 


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Drugs having interactions with esmolol like other beta-blockers (e.g., propranolol, metoprolol), 
beta agonists (e.g. Formoterol, Clenbuterol, Salbutamol), calcium channel blockers (e.g., 
verapamil, diltiazem, nifedipine), digoxin, morphine, NSAIDs (e.g., ibuprofen), arbutamine, 
dopamine, succinylcholine, epinephrine/norepinephrine, other blood pressure medicine (e.g. 
clonidine), blood thinners (e.g., warfarin) should be administered with due risk/benefit 
consideration by the Investigator. Investigators should look for alternatives (if it is ethically 
acceptable that the Subject can be put on alternative treatment) to above drugs when Galnobax® 
treatment is underway. Investigator can contact the CRO’s Study monitor for any clarification on 
this, if necessary. 
 
 


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10.3 ABBREVIATIONS 
Table 6 List of Abbreviations 
ABI 
Ankle-Brachial Index 
AE 
Adverse Events 
AIDS 
Acquired Immune Deficiency Syndrome 
ALP 
Alkaline Phosphatase 
ALT 
Alanine Aminotransferase 
AMWT 
Advanced Moist Wound Therapy 
AST 
Aspartate Transaminase 
BMI 
Body Mass Index 
BUN 
Blood Urea Nitrogen 
CBC 
Complete Blood Count 
CDSCO 
Central Drugs Standard Control Organization 
CRO 
Contract Research Organization 
CTMP 
Clinical Trial Management Plan 
DFU 
Diabetic Foot Ulcer 
DGHS 
Directorate General Of Health Services 
DM 
Diabetes Mellitus 
EC 
Ethics Committee 
ECG 
Electrocardiogram 
eCRF 
Electronic Case Report Form 
eGFR 
Estimated Glomerulus Filtration Rate 
EKG 
Electrocardiogram 
EOS 
End of Study 
EOT 
End of Treatment 
FAS 
Full Analysis Set 
FDA 
Food and Drug Administration 
FU 
Follow Up 
GCP 
Good Clinical Practice 
GMP 
Good Manufacturing Practice 
HBOT 
Hyperbaric Oxygen Therapy 
HIV 
Human Immunodeficiency Virus 
ICF 
Informed Consent Form 
ICH 
International Council on Harmonization  
ICMR 
Indian Council of Medical Research 
IDF 
International Diabetes Federation 
IND 
Investigational New Drug Application 
IP 
Investigational Product 
ITT 
Intention-to-Treat 
IWRS 
Interactive Web-Based Randomization System 
LAR 
Legally Authorized Representative 
MCH 
Mean Corpuscular Hemoglobin 
MCHC 
Mean Corpuscular Hemoglobin Concentration 
MCV 
Mean Cell Volume 
MedDRA 
Medical Dictionary for Regulatory Activities 
MRI 
Magnetic Resonance Imaging 
MP 
Monitoring Plan 
NCS 
Nerve Conduction Study 
NCT 
National Clinical Trial 


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NO 
Nitric Oxide 
NPWT 
Negative Pressure Wound Therapy 
NYHA 
New York Heart Association 
PI 
Principal Investigator 
PK 
Pharmacokinetic 
POF 
Pregnancy Outcome Form 
PP 
Per Protocol 
PT 
Preferred Term 
QA 
Quality Assurance 
QC 
Quality Control 
RBC 
Red Blood Cell 
RDW 
Red cell Distribution Width 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SD 
Standard Deviation 
SOA 
Schedule of Activities 
SoC 
Standard of Care 
SOCL 
System Organ Class 
SPP 
Skin Perfusion Pressure 
SW 
Semmes-Weinstein 
T2DM 
Type 2 Diabetes Mellitus 
TEAE 
Treatment Emergent Adverse Events 
WBC 
White Blood Cell 
 
 


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10.4 PROTOCOL AMENDMENT HISTORY 
Not applicable 
 
 


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11 APPENDICES 
ATTACHMENT 1 
TEXAS CLASSIFICATION FOR DIABETIC FOOT DISEASE 
Grade-0 
Pre-or post ulcerative site that has healed 
Grade -1 
Superficial wound not involving tendon, capsule, or bone 
Grade -2 
Wound penetrating to tendon or capsule 
Grade -3 
Wound penetrates to bone or joint 
 
 
Stage A 
No infection or ischemia 
Stage B 
Infection present 
Stage C 
Ischemia present 
Stage D 
Infection and ischemia present 


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ATTACHMENT 2 
ANKLE-BRACHIAL INDEX (ABI) 
STEP-BY-STEP INSTRUCTIONS ON HOW TO PERFORM AND INTERPRET THE ABI 
What is the ABI? 
The ankle-brachial index (ABI) is a simple, noninvasive tool used to screen for peripheral arterial 
disease (PAD), a vascular condition affecting more than 8 million adult Americans and associated 
with significant morbidity and mortality.[1] Despite its prevalence and cardiovascular risk 
implications, only 25% of PAD Subjects are undergoing treatment.[1] As only about 10% of Subjects 
with PAD present with classic claudication—40% of Subjects are asymptomatic—clinicians need to 
have a high level of suspicion for this disease in their adult Subject population.[2] According to 
AHA/ACC guidelines, an ABI should be conducted on Subjects presenting with risk factors for PAD 
so that therapeutic interventions known to diminish their increased risk of myocardial infarction 
(MI), stroke, and death may be offered.[2] (Level of Evidence: B) 
How to perform the ABI? 
Measurement of the ABI can be easily performed in a clinician’s office using a blood pressure (BP) 
cuff and handheld Doppler device with a vascular probe. Systolic BP is determined in both arms 
and both ankles. An ABI measurement can usually be performed in less than 10 minutes.  
Tools Needed for Measuring ABI 
• 
Sphygmomanometer with appropriately sized cuff(s) for both arm and ankle  
• 
Handheld Doppler device with vascular probe  
• 
Conductivity gel compatible with the Doppler device 
Step 1: Measure the brachial systolic pressure in both arms [3, 4]: 
• 
Allow Subject to rest for 5-10 minutes in the supine position. 
• 
Place the BP cuff on Subject’s upper arm with the lower edge approximately 1 inch above 
the antecubital fossa. 
• 
Palpate for the brachial pulse and apply conductivity gel over the brachial artery. Place the 
tip of the probe into the gel at a 45-60-degree angle until clear arterial pulse sounds are 
heard. 
• 
Inflate the cuff to the point that pulse sounds disappear, then go 20 mm Hg above that 
point. Slowly deflate at a rate of 2 mm Hg per sec and record the point where arterial pulse 
sounds resume. This is the brachial systolic pressure. 
• 
Repeat this procedure in the other arm. 
• 
The higher of the two brachial systolic pressure readings will be used to calculate the ABI. 
• 
There should be a difference of less than 10 mm Hg between each brachial BP. 
Step 2: Measure the posterior tibial and dorsalis pedis systolic pressures in both legs: 
• 
Place the BP cuff on the Subject’s leg approximately 2 inches above the ankle’s medial 
malleolus. 
• 
Locate the posterior tibial (PT) pulse, apply gel, and position the Doppler probe. Measure 
the systolic pressure following the same procedure described for the brachial artery. 
• 
On the same leg, locate the dorsalis pedis (DP) pulse and measure systolic pressure. 


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• 
Repeat measurement of both the PT and DP systolic pressures on the other leg. 
• 
Select the higher of the two ankle readings for each leg (PT or DP). These numbers will 
serve as the ankle systolic pressures in the ABI calculation. 
• 
If either the PT or DP ankle pulse is absent, use the measurable reading to calculate the 
ABI. 
Step 3: To calculate the ABI, divide each ankle systolic pressure by the brachial systolic pressure. 
• 
Divide the higher of the two systolic pressures for each leg by the higher of the two arm 
pressures to get the right and left ABI. 
For example, consider the table given below. The ABI for this Subject is calculated by using 130 (the 
higher of the two brachial pressures) as the denominator and 95 and 130 as the numerators for 
the right and left legs, respectively. The ABI for the right leg is 0.73 and for the left leg is 1.0. 
ABI results 
 
 
 
 
 
How to interpret the ABI? 
An abnormal ABI may be an independent predictor of mortality, as it reflects the burden of 
atherosclerosis. [5, 6] Most will agree that a normal ABI is >0.9. An ABI <0.9 suggests significant 
narrowing of one or more blood vessels in the leg. The majority of Subjects with claudication have 
ABIs ranging from 0.3 to 0.9. Rest pain or severe occlusive disease typically occurs with an ABI <0.5. 
ABIs <0.2 are associated with ischemic or gangrenous extremities. Conditions such as DM or end 
stage-renal disease can give falsely elevated ABIs (1.3-1.5). The ABI test approaches 95% accuracy 
in detecting PAD. [7] However, a normal ABI value does not absolutely rule out the possibility of 
PAD. Some Subjects with normal or near-normal ABI results may have symptoms suggesting PAD. 
If the resting ABI is normal, an exercise ABI should be conducted. 
ABI Ranges  
Normal: 1.0 - 1.1  
Borderline: 0.91 - 0.99  
Abnormal: <0.9 or >1.3  
Systolic Pressure  
Right  
Left  
Brachial  
130  
129  
Posterior Tibial  
95  
120  
Dorsalis Pedis  
90  
130  
ABI = Ankle systolic/brachial systolic  
 
95/130 
130/130 
ABI  
0.73  
1.0  


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References 
1. American Heart Association. Statistical Fact Sheet—Miscellaneous, 2008 Update. Peripheral 
Arterial Disease—Statistics. 
http://www.heart.org/downloadable/heart/1198011637413FS26PAD08.REVdoc.pdf. 
2. Hirsch AT, et al. ACC/AHA 2005 Practice Guidelines for the Management of Subjects With 
Peripheral Arterial Disease (Lower Extremity, Renal, Mesenteric, and Abdominal Aortic): Executive 
Summary. Circulation. 2006; 113:1474-1547. 
3. Perloff D, et al. Human blood pressure determination by sphygmomanometry. Circulation 1993; 
88; 2460-70. 
4. Pickering TG, et al. AHA Scientific Statement. Recommendations for Blood Pressure 
Measurement in Humans and Experimental Animals Part 1: Blood Pressure Measurement in 
Humans. Circulation. 2005; 111:697-716. 
5. Feringa HH, et al. The long-term prognostic value of the resting and postexercise ankle-brachial 
index. Arch Intern Med 2006; 166:529-35. 
6. Wild SH, et al. Low ankle-brachial pressure index predicts increased risk of cardiovascular disease 
independent of the metabolic syndrome and conventional cardiovascular risk factors in the 
Edinburgh Artery Study. Diabetes Care 2006; 29(3):637-42. 
7. Vascular Disease Foundation. PAD: Diagnosis: ABI. 2008. 
http://www.vdf.org/diseaseinfo/pad/anklebrachial.php. 


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ATTACHMENT 3 
SUGGESTED TECHNIQUE FOR USING THE 10-G MONOFILAMENT 
1. Obtain two or more reusable monofilaments or a packet of disposable monofilaments (MFs) 
from one of the sites listed under “Resources For 10-g Monofilaments.”  
• 
Use the 10-g MF < 100 applications/day, then “rest” it for 24h – thus the need for at least 
2 MFs.  
• 
The accuracy of 10-g MFs obtained as samples from pharmaceutical companies is 
unknown.  
2. Check the 10-g MF for defects. Replace if bowed, kinked, or twisted.  
3. Compress the 10-g MF twice before use each day.  
4. Place the Subject in the supine position for ease of testing.  
5. Tell the Subject that you are testing for loss of protective sensation that increases the risk for 
foot ulcer and amputation.  
6. Demonstrate buckling of the 10-g MF on the Subject’s forearm or hand.  
7. Have the Subject close their eyes.  
8. Test four sites (See diagram) on each foot in random sequence. Avoid scars, calluses, and ulcers.  
a. Test the plantar surface of each great toe.  
b. Test the plantar surfaces of the 1st, 3rd, and 5th metatarsal heads of each foot. 
 
If callus, scar, or ulcer is present, test at adjacent sites on the plantar surface of the foot.  
9. Hold the 10-g MF perpendicular to the test site, and then bow it to a C-shape for one second.  
 
Do not allow the 10-g MF to slide along the skin.  
 
The Subject should sense the 10-g MF by the time that it bows.  
10. Grade the Subject’s response by using the approach suggested by the International Consensus 
Group on the Diabetic Foot:  
• 
Bow the 10-g MF at a designated site, and ask the Subject, “Do you feel it touch you – yes 
or no?”  


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• 
Repeat testing twice at each site and randomly include a “sham” application in which the 
10-g MF is not applied. There will be a total of three applications at each site, one of which 
does not touch the skin.  
• 
Protective sensation is considered to be present if the Subject correctly answers two or 
more of the three applications, one of which was a sham.  
• 
If the Subject correctly answers only one or none of the three applications, return and 
retest that site.  
• 
The Subject is considered to have insensate feet if they fail on retesting at just one or more 
sites on either foot.  
11. Caveats:  
• 
The feet may be falsely insensate when cold or edematous.  
• 
Heel testing does not discriminate ulcer formers.  
• 
Subjects who have normal protective sensation should be retested annually.  
Technically, Subjects who have insensate feet need not be retested. Some clinicians believe that 
repeated testing of the individual with insensate feet may be a useful educational and motivational 
tool. 


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ATTACHMENT 4 
SCALES FOR PAIN, EDEMA AND ERYTHEMA 
Local assessment of pain, edema and erythema by respective scales will be done as follows:  
PAIN SCALE 
Local pain at the Target Ulcer site will be measured in terms of 11 point universal pain scale with 
scale of  
• 
0: No pain 
• 
1-3: Mild pain (Able to adapt to pain) 
• 
4-6: Moderate pain (Interferes with many activities)  
• 
7-10: Severe pain (Subject disable or unable to function independently) 
 
EDEMA SCALE 
Local edema at the Target Ulcer site will be measured in terms of 5 point edema scale as: 
• 
0: No edema 
• 
1: Very slight edema (barely perceptible) 
• 
2: Well defined edema (edges of area well defined raising) 
• 
3: Moderate edema (raised approx. 1 mm) 
• 
4: Severe edema (raised more than 1 mm and beyond exposed area) 
ERYTHEMA SCALE 
Local erythema at the Target Ulcer site will be measured in terms of 5 point erythema scale as: 
• 
0: No erythema 
• 
1: Very slight erythema (barely perceptible) 
• 
2: Well defined erythema 
• 
3: Moderate to severe erythema 
• 
4: Severe erythema (Beet redness to slight eschar formation) 


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