Clinical trial NCT03998436: Phase 3 Study to Evaluate the Safety and Efficacy of Galnobax® in Treating Diabetic Foot Ulcers
Official 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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Diabetic Foot Ulcer
Lead sponsor: Novalead Pharma Private Limited
Sponsor class: INDUSTRY
First posted: 2019-06-26
Enrollment: 176
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Prospective, Multicenter, Randomized, Double-Blind, Parallel groups
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

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
5. Presence of at least one DFU that meets all of the following criteria:

   1. A full-thickness ulcer of Grade A1 as per Texas classification system;
   2. Ulcer is located below or up to 5 cm above the malleoli (excluding ulcers between the toes);
   3. Ulcer size (area) is ≥ 2 cm2 and ≤ 15 cm2 (post-debridement);
   4. There is a minimum 3 cm margin between the qualifying Target Ulcer and any other ulcers on the specified foot, post-debridement;
   5. No exposed bone, tendon, muscle, ligament or joint capsule, and no tunneling, undermining, or sinus tracts;
   6. Unresponsive to ulcer care and open for at least 6 weeks at the time of the Screening Visit;
   7. Ulcer is non-infected as determined by clinical assessment and complete hemogram;
   8. Ulcer has a clean, granulating base free of adherent slough to the greatest extent possible as per Investigator;
   9. Ulcer area reduction \< 30% from the Screening Visit to Baseline visit
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

Exclusion Criteria:

1. Actively infected ulcers with or without purulent discharge, ulcers with exposed bone or associated with osteomyelitis
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
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:

    1. Hemoglobin \< 10.0 g/dL
    2. White Blood Cells (WBC) \< 2.0 X 109 cells/L
    3. Liver function studies \[Total bilirubin, aspartate aminotransferase (AST) and alanine transaminase (ALT)\] \> 3x the upper limit of normal
    4. Albumin \< 2.5 g/dL
    5. 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
12. Subject has received or is currently receiving or scheduled to receive any medication or therapies during the course of the Study that will modulate wound healing
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

Primary outcomes:
measure: Proportion of Subjects Achieving Target Ulcer Closure Within 12-week Treatment Phase, as Assessed by Blinded Investigator
timeFrame: Wound closure assessed up to week 12 and confirmed by 2 visits 2 weeks apart; only participants with wound closure at or before Week 12 and who maintained closure after 4-weeks of follow-up reported
Secondary outcomes:
measure: Proportion of Subjects Achieving Target Ulcer Closure Till End of Study, as Assessed by the Blinded Investigator.
timeFrame: 24-weeks. The ulcers achieving complete closure till end of study
Other outcomes:
measure: Proportion of Subjects With Treatment Emergent Adverse Events (TEAEs)
timeFrame: 24-weeks
Locations:
city: Vijayawada
country: India
facility: Yalamanchi Hospita
state: Andhra Pradesh
city: Bangalore
country: India
facility: M.S. Ramaiah Medical College and Hospital
state: Karnataka
city: Bangalore
country: India
facility: Sapthagiri Institute of Medical Sciences and Research Centre
state: Karnataka
city: Bangalore
country: India
facility: Rajlaxmi Hospital
state: Karnataka
city: Tumkūr
country: India
facility: Sri Siddhartha Medical College
state: Karnataka
city: Nashik
country: India
facility: Sujata Birla Hospital & Medical Research Center
state: Maharashtra
city: Pune
country: India
facility: Deenanath Mangeshkar Hospital and Research Center
state: Maharashtra
city: Pune
country: India
facility: Chellaram Diabetes Institute
state: Maharashtra
city: Chennai
country: India
facility: Appollo Hospital
state: Tamilnadu
city: Chennai
country: India
facility: M.V. Hospital for Diabetes Pvt Ltd
state: Tamilnadu
city: Chennai
country: India
facility: Madras Diabetes Research Foundation
state: Tamilnadu
city: Chennai
country: India
facility: Sri Ramachandra Hospital
state: Tamilnadu
city: Chandigarh
country: India
facility: Post Graduate Institute of Medical Education and Research (PGIMER)
city: New Delhi
country: India
facility: Maharaja Agrasen Hospital
Study officials:
affiliation: Post Graduate Institute of Medical Education and Research, Chandigarh
name: Ashu Rastogi, MD
role: PRINCIPAL_INVESTIGATOR
References: