Diabetic Foot Ulcer
Conditions
Keywords
Diabetic foot ulcer, Diabetic wound, chronic non healing ulcer
Brief summary
The purpose of this study is to determine safety and efficacy of a new gel formulation of Esmolol hydrochloride (Galnobax®) for the treatment of Diabetic Foot Ulcer (DFU). The study will compare number and types of adverse events occured, rates of wound closure and percentage of wounds closed in Galnobax treated groups versus placebo group.
Detailed description
This is an interventional, placebo-controlled, randomized, double-blinded, dose comparison, phase I/II study of Galnobax® in subjects with diabetic foot ulcers. Additionally the effect of dosage and frequency of application will also be studied . The total trial duration per subject is 25 weeks which comprises of 1 week for screening, 12 weeks of treatment and 12 weeks of follow-up.
Interventions
DRUGPlacebo gel
Sponsors
Novalead Pharma Private Limited
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 95 Years
Healthy volunteers
No
Inclusion criteria
* Subjects aged 18 to 95 years, inclusive, with Type 1 or Type 2 diabetes undergoing therapy for glycemic control * Subjects having below knee ulcer of at least 4 week and maximum of 52 weeks duration which is a full thickness ulcer without exposure of bone, muscle, ligaments, or tendons * Ulcer should be clinically non-infected * Ulcer area (length x width) measurement between 1.5 cm2 and 10 cm2, inclusive and post debridement ulcer area less than or equal to 12 cm2. * Full-thickness ulcer of Grade 1 or Grade 2 as per Wagner's classification system * Recently debrided ulcer (2 weeks prior to screening) and post debridement ulcer free of necrotic debris, foreign bodies, sinus tracts, tunneling, and undermining, comprised of healthy vascularized tissue as determined by the Investigator * Inability to perceive 10 grams pressure using Semmes-Weinstein 5.07 monofilament in the peri-ulcer area * Ankle Brachial index between 0.7 and 1.2
Exclusion criteria
* Actively infected ulcers with or without purulent discharge, ulcers with exposed bone or associated with osteomyelitis. * Subjects having cellulitis, ischemic or gangrenous ulcers in the opinion of the Investigator * Glycosylated hemoglobin (HbA1C) \>12% * Diagnosed and/ currently unstable hypotension, heart block, cardiac failure, and other cardiac complications * Subject diagnosed with cancer undergoing chemotherapy * Revascularization surgery 4 weeks prior to signing the ICF * Renal failure as defined by serum creatinine \>3.0 mg/dL or renal insufficiency requiring frequent dialysis * Poor nutritional status as measured by serum albumin \<3.0 g/dL * Active Charcot or other structural deformity that would prevent adequate off-loading of the study foot
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety Outcome | Till end of follow up period (Week 25) | Number of participant with adverse events (AEs) till end of follow-up phase in different groups |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy Outcome | Baseline and end of treatment (Week 12 or 84 +/- 2 days) | To evaluate the percent change in ulcer area and ulcer volume from baseline till end of treatment (Week 12) in different groups |
Other
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetic Measurements | pre-dose (prior to first study drug application), and at 15 and 30 minutes, 1, 3, 6, 12, and 24 hours after the first study drug application on day 0, weeks 1, 4, and 12 (prior to study drug application). | Pharmacokinetic profile of Galnobax® in subset of patients suffering from DFU |
Countries
India, Malaysia, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo gel | 10 |
| Galnobax 20% QD Esmolol Hydrochloride (Galnobax) 20% gel once daily | 9 |
| Galnobax 20% BID Esmolol Hydrochloride (Galnobax) 20% gel twice daily | 14 |
| Galnobax 14% BID Esmolol Hydrochloride (Galnobax) 14% gel twice daily | 11 |
| Total | 44 |
Baseline characteristics
| Characteristic | Placebo | Galnobax 20% QD | Galnobax 20% BID | Galnobax 14% BID | Total |
|---|---|---|---|---|---|
| Age, Continuous | 53.3 years STANDARD_DEVIATION 9.37 | 50.0 years STANDARD_DEVIATION 5.85 | 56.2 years STANDARD_DEVIATION 11.56 | 53.0 years STANDARD_DEVIATION 7.75 | 53.5 years STANDARD_DEVIATION 9.17 |
| Region of Enrollment India | 9 participants | 8 participants | 11 participants | 9 participants | 37 participants |
| Region of Enrollment Malaysia | 1 participants | 1 participants | 2 participants | 1 participants | 5 participants |
| Region of Enrollment United States | 0 participants | 0 participants | 1 participants | 1 participants | 2 participants |
| Sex: Female, Male Female | 2 Participants | 2 Participants | 2 Participants | 3 Participants | 9 Participants |
| Sex: Female, Male Male | 8 Participants | 7 Participants | 12 Participants | 8 Participants | 35 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 9 | 0 / 14 | 0 / 11 |
| other Total, other adverse events | 1 / 10 | 3 / 9 | 6 / 14 | 6 / 11 |
| serious Total, serious adverse events | 0 / 10 | 0 / 9 | 4 / 14 | 0 / 11 |
Outcome results
Primary
Safety Outcome
Number of participant with adverse events (AEs) till end of follow-up phase in different groups
Time frame: Till end of follow up period (Week 25)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Safety Outcome | 1 Participants |
| Galnobax 20% QD | Safety Outcome | 3 Participants |
| Galnobax 20% BID | Safety Outcome | 9 Participants |
| Galnobax 14% BID | Safety Outcome | 6 Participants |
Secondary
Efficacy Outcome
To evaluate the percent change in ulcer area and ulcer volume from baseline till end of treatment (Week 12) in different groups
Time frame: Baseline and end of treatment (Week 12 or 84 +/- 2 days)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Efficacy Outcome | Percent Change in Ulcer Area | 80.67 percent change | Standard Deviation 34.09 |
| Placebo | Efficacy Outcome | Percent Change in Ulcer Volume | 84.57 percent change | Standard Deviation 32.99 |
| Galnobax 20% QD | Efficacy Outcome | Percent Change in Ulcer Volume | 55.41 percent change | Standard Deviation 92.31 |
| Galnobax 20% QD | Efficacy Outcome | Percent Change in Ulcer Area | 82.58 percent change | Standard Deviation 31.57 |
| Galnobax 20% BID | Efficacy Outcome | Percent Change in Ulcer Area | 95.80 percent change | Standard Deviation 9.85 |
| Galnobax 20% BID | Efficacy Outcome | Percent Change in Ulcer Volume | 83.36 percent change | Standard Deviation 39.6 |
| Galnobax 14% BID | Efficacy Outcome | Percent Change in Ulcer Area | 86.56 percent change | Standard Deviation 35.07 |
| Galnobax 14% BID | Efficacy Outcome | Percent Change in Ulcer Volume | 99.40 percent change | Standard Deviation 1.7 |
Secondary
Efficacy Outcome
Time in days taken for closure of wound in different groups from baseline till end of treatment (week 12 or 84 +/- 2 days)
Time frame: From baseline till end of treatment (Week 12 or 84 +/- 2 days)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Efficacy Outcome | 53.5 days |
| Galnobax 20% QD | Efficacy Outcome | 77 days |
| Galnobax 20% BID | Efficacy Outcome | 72 days |
| Galnobax 14% BID | Efficacy Outcome | 49.5 days |
Other Pre-specified
Pharmacokinetic Measurements
Pharmacokinetic profile of Galnobax® in subset of patients suffering from DFU
Time frame: pre-dose (prior to first study drug application), and at 15 and 30 minutes, 1, 3, 6, 12, and 24 hours after the first study drug application on day 0, weeks 1, 4, and 12 (prior to study drug application).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Pharmacokinetic Measurements | 0.0 Cmax (ng/mL) of Esmolol acid | Standard Deviation 0 |
| Galnobax 20% QD | Pharmacokinetic Measurements | 78.451 Cmax (ng/mL) of Esmolol acid | Standard Deviation 83.176 |
| Galnobax 20% BID | Pharmacokinetic Measurements | 113.802 Cmax (ng/mL) of Esmolol acid | Standard Deviation 117.383 |
| Galnobax 14% BID | Pharmacokinetic Measurements | 340.018 Cmax (ng/mL) of Esmolol acid | Standard Deviation 430.944 |