Diabetic Foot, Foot Ulcer, Diabetic
Conditions
Keywords
Diabetes mellitus, Diabetic neuropathy, Peripheral vascular disease, Infection, Topical application, plantar foot ulcers
Brief summary
The purpose of this study is to assess if the experimental drug, DSC127, is safe, how well it can be tolerated, and how different doses effect the healing of the chronic foot ulcers in diabetic subjects.
Detailed description
This study is designed as a randomized, parallel-group, double-blind, placebo-controlled trial. After a 14-day baseline to evaluate ulcer healing to ensure DU are chronic, a 4-week active treatment followed by 8 weeks of observation and assessment of the treatment will compare the effects of two concentrations of DSC127 and placebo (n = 25 evaluable subjects per group; n=75 total evaluable subjects) to identify the optimal dose of DSC127. Sustained tissue integrity will be evaluated for all subjects during a follow-up period at study weeks 16 and 24. Subjects will be randomized in a 1:1:1 ratio to one of the three treatment groups. Group 1: Placebo Vehicle Control Group 2: 0.03% DSC127 in Vehicle Group 3: 0.01% DSC127 in Vehicle The four week treatment period requires daily application of the treatment to the wound site. First application each week will be at the clinic and for the remainder of the week the patient self-administers the treatment. If wound healing occurs during the treatment or assessment periods a final assessment visit is conducted and the integrity is assessed four and twelve weeks later (usually weeks 16 and 24 of the study).
Interventions
DRUGNorLeu3-A(1-7) in a gel formulation
Gel will be applied to the wound once daily for four weeks (treatment period). Gel will have either no active ingredient (placebo), 0.03% or 0.01% active ingredient.
Sponsors
National Institutes of Health (NIH)
Integra LifeSciences Corporation
US Biotest, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Have at least one chronic non-healing Wagner Grade 1 or Grade 2 plantar neuropathic diabetic ulcer between 1.0-6.0 cm2 on the midfoot or forefoot, including the toes but excluding the heel. * ABI greater than 0.7 for neuroischemic or greater than 0.8 for neuropathic DU * TcPO2 greater than 40 mm Hg or great toe systolic pressure greater than 50 mmHg * Type I or Type II diabetes under metabolic control * Female subjects must have a negative pregnancy test and be willing to use acceptable method of birth control for the duration of the study
Exclusion criteria
* Exposure to any investigational product within the last 30 days, or have known hypersensitivity to any of the study medication components * Chronic renal insufficiency and/or chronic liver dysfunction * Resting blood pressure (at the time of the initial visit of the Screening Period) which exceeds 160 systolic and/or 90 diastolic mmHg on 3 consecutive readings at least 15 minutes apart * Malignancy of any kind * Receiving hemodialysis or CAPD * Current history of drug abuse, and/or known to be HIV positive * Prior radiation therapy of the foot under study * Current use of corticosteroids (within past 8 weeks), immunosuppressants (within past 8 weeks), or use of a biologic agent to include growth factors and skin equivalents (Regranex, Apligraft, or Dermagraft) in the past 90 days * Ulcer is deemed clinically infected and requires topical antimicrobials or agents known to affect wound healing, or the subject has been taking systemic antibiotics for more than 7 days for any reason * Sickle-cell anemia, Raynaud's or other peripheral vascular disease * Wagner Grade 3 or higher DU, deep abscess or infection of the joint or tendon, or gangrene or osteomyelitis * An EKG with a marked baseline prolongation of QT/QTc interval
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The Primary Efficacy Parameter Will be the Proportion of Ulcers Healed by 12 Weeks as Defined as 100 % Epithelialized With no Drainage. | Healing to occur within 12 weeks of first treatment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Proportion of Subjects in Each Treatment Group Reporting Adverse Events. | Duration of subject's participation (24 weeks) | — |
| The Rate of Re-epithelialization of the Ulcer Site. | 12 weeks | The overall healing rate of the ulcers, based on the percent of unhealed ulcer area re-epithelialized per week. |
| The Time to Re-epithelialization of the Ulcer Site. | 24 weeks | Average time to complete re-epithelialization of baseline ulcer area. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Vehicle Control control placebo vehicle | 24 |
| 0.03 % DSC127 0.03% DSC127 in Vehicle Control | 26 |
| 0.01% DSC127 0.01% DSC127 in Vehicle Control | 28 |
| Total | 78 |
Baseline characteristics
| Characteristic | 0.03 % DSC127 | 0.01% DSC127 | Placebo Vehicle Control | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 5 Participants | 4 Participants | 7 Participants | 16 Participants |
| Age, Categorical Between 18 and 65 years | 21 Participants | 24 Participants | 17 Participants | 62 Participants |
| Age Continuous | 56.3 years STANDARD_DEVIATION 10.35 | 53.1 years STANDARD_DEVIATION 12.47 | 56.8 years STANDARD_DEVIATION 12.77 | 55.3 years STANDARD_DEVIATION 11.87 |
| Region of Enrollment United States | 26 participants | 28 participants | 24 participants | 78 participants |
| Sex: Female, Male Female | 7 Participants | 3 Participants | 8 Participants | 18 Participants |
| Sex: Female, Male Male | 19 Participants | 25 Participants | 16 Participants | 60 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 16 / 24 | 15 / 26 | 18 / 28 |
| serious Total, serious adverse events | 5 / 24 | 4 / 26 | 4 / 28 |
Outcome results
Primary
The Primary Efficacy Parameter Will be the Proportion of Ulcers Healed by 12 Weeks as Defined as 100 % Epithelialized With no Drainage.
Time frame: Healing to occur within 12 weeks of first treatment
Population: Intent-to-Treat Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | The Primary Efficacy Parameter Will be the Proportion of Ulcers Healed by 12 Weeks as Defined as 100 % Epithelialized With no Drainage. | 8 number of ulcers healed |
| 0.03% DSC127 | The Primary Efficacy Parameter Will be the Proportion of Ulcers Healed by 12 Weeks as Defined as 100 % Epithelialized With no Drainage. | 14 number of ulcers healed |
| 0.01% DSC127 | The Primary Efficacy Parameter Will be the Proportion of Ulcers Healed by 12 Weeks as Defined as 100 % Epithelialized With no Drainage. | 8 number of ulcers healed |
Secondary
The Proportion of Subjects in Each Treatment Group Reporting Adverse Events.
Time frame: Duration of subject's participation (24 weeks)
Population: Safety Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | The Proportion of Subjects in Each Treatment Group Reporting Adverse Events. | Serious Adverse Event | 5 patients |
| Placebo | The Proportion of Subjects in Each Treatment Group Reporting Adverse Events. | All Adverse Event | 23 patients |
| Placebo | The Proportion of Subjects in Each Treatment Group Reporting Adverse Events. | Related to Study Drug | 0 patients |
| 0.03% DSC127 | The Proportion of Subjects in Each Treatment Group Reporting Adverse Events. | Serious Adverse Event | 4 patients |
| 0.03% DSC127 | The Proportion of Subjects in Each Treatment Group Reporting Adverse Events. | All Adverse Event | 26 patients |
| 0.03% DSC127 | The Proportion of Subjects in Each Treatment Group Reporting Adverse Events. | Related to Study Drug | 0 patients |
| 0.01% DSC127 | The Proportion of Subjects in Each Treatment Group Reporting Adverse Events. | All Adverse Event | 28 patients |
| 0.01% DSC127 | The Proportion of Subjects in Each Treatment Group Reporting Adverse Events. | Related to Study Drug | 0 patients |
| 0.01% DSC127 | The Proportion of Subjects in Each Treatment Group Reporting Adverse Events. | Serious Adverse Event | 4 patients |
Secondary
The Rate of Re-epithelialization of the Ulcer Site.
The overall healing rate of the ulcers, based on the percent of unhealed ulcer area re-epithelialized per week.
Time frame: 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | The Rate of Re-epithelialization of the Ulcer Site. | 10.5 percent ulcer area re-epithelialized/wk | Standard Deviation 21.2 |
| 0.03% DSC127 | The Rate of Re-epithelialization of the Ulcer Site. | 14.3 percent ulcer area re-epithelialized/wk | Standard Deviation 12.8 |
| 0.01% DSC127 | The Rate of Re-epithelialization of the Ulcer Site. | 9.0 percent ulcer area re-epithelialized/wk | Standard Deviation 11.1 |
Secondary
The Time to Re-epithelialization of the Ulcer Site.
Average time to complete re-epithelialization of baseline ulcer area.
Time frame: 24 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | The Time to Re-epithelialization of the Ulcer Site. | 16.5 Weeks | Standard Error 1.77 |
| 0.03% DSC127 | The Time to Re-epithelialization of the Ulcer Site. | 12.4 Weeks | Standard Error 1.8 |
| 0.01% DSC127 | The Time to Re-epithelialization of the Ulcer Site. | 17.3 Weeks | Standard Error 1.53 |