Complicated skin ulceration on the foot in patients with diabetes. MedDRA version: 14.1 Level: LLT Classification code 10067106 Term: Multiple skin ulcers System Organ Class: 10040785 - Skin and subcutaneous tissue disorders
Conditions
Interventions
Trade Name: Isoniazid Tablets BP 100 mg
Product Name: Isoniazid
Product Code: BBR-012
Pharmaceutical Form: Tablet
INN or Proposed INN: ISONIAZID
CAS Number: 54-85-3
Current Sponsor code: BBR-012
Other
Sponsors
Bridge BioResearch Rights (Jersey) Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Is a man or woman aged >or=18 2. Has diabetes mellitus, according to the American Diabetes Association criteria. 3. Has an ischaemic or neuro-ischaemic DFU below the malleolus that has a minimum length and perpendicular width of 1 cm x 1 cm. Patients with multiple DFUs may be enrolled but only one DFU (designated the target DFU) is to be studied. 4. Has received appropriate surgical and antibiotic intervention to remove all necrotic and infected bone, if previously diagnosed with osteomyelitis. Patients must be evaluated for visible signs of bone involvement (including "probe to bone") and must have had an X-ray, or other radiological investigation, of any previously osteomyelitic area to confirm resolution. 5. Patients without a detectable pedal pulse can only be enrolled if, in the opinion of investigator or vascular specialist, the patient has sufficient circulation to the affected extremity that will allow effective treatment, the patient will not require immediate or urgent amputation and the patient does not have reconstructable distal disease. 6. tcpO2 on the target DFU is >/= 25 and /= 1 complete menstrual cycle before the baseline visit). . Intrauterine device. . Double barrier method (condoms, sponge, diaphragm or vaginal ring with spermicidal jellies or cream). Female and not of childbearing potential is defined as postmenopausal for >/= 1 year or surgically sterile (bilateral tubal ligation, bilateral oophorectomy or hysterectomy). 10. Willing to return to the study centre for the final (follow-up) visit. 11. Provide written informed consent to participate in the study. Patients must be able to speak English fluently and to understand English. 12. Has a BMI =65 years) yes F.1.3.1 Number of subjects for this age range 35
Exclusion criteria
Exclusion criteria: 1. Has a known history of hypersensitivity to any part or constituent of the BBR-012 tablet. 2. Has any uncontrolled illnesses (e.g. active malignancy, vasculitis) that, in the opinion of the investigator, would interfere with interpreting the results of the study. 3. Has an infected DFU based on the IDSA guidelines2, i.e. presence of purulent secretions or at least two of the manifestations of inflammation (erythema, warmth, swelling or induration and pain or tenderness), and for whom, in the investigator’s judgment, intravenous or oral antibiotic therapy is required. 4. Has active osteomyelitis. 5. Has suspected gangrenous tissue of the affected limb that cannot be removed with a single debridement. 6. Has a DFU associated with prosthetic material or a device. 7. Has received any potentially effective systemic antibiotic therapy for more than 24 hours during the 72-hour period before the screening visit. 8. Is receiving, or has received within the 14 days prior to the screening visit, any concomitant topical wound therapy (e.g., topical antimicrobial therapy, topical debriding agent, topical growth factor, topical skin replacement, larvae therapy, Vacuum Assisted Closure [VAC] system therapy, or hyperbaric oxygen). 9. Has received systemic corticosteroids, immunosuppressive agents, radiation therapy or chemotherapy within the 30 days prior to the screening visit. 10. Has any condition other than peripheral neuropathy for which isoniazid use is contraindicated, i.e., hepatic impairment, renal impairment (defined as estimated glomerular filtration rate <10 mL/minute/1.73m2), hypersensitivity to isoniazid. Patients with slow acetylator status, epilepsy, history of psychosis, alcohol dependence, malnutrition, human immunodeficiency virus, or acute porphyria may be enrolled at the discretion of the investigator. 11. Known or suspected drug or alcohol abuse or positive drugs of abuse test. If a patient has a positive drugs of abuse test for codeine that results from the patient taking codeine phosphate or a codeine-based compound product (e.g. co-codamol or similar) as prescribed for a licensed indication (analgesia, anti-motility, cough suppression), the patient may be included at the discretion of the investigator. 12. Participating in any clinical study the 12 weeks before the screening visit and that is anticipated to interfere with the objectives of the study, as judged by the investigator. 13. Donation of more than 450 mL of blood in the 3 months before the screening visit, or 1200 mL blood in the 12 months before the screening visit. 14. History of severe hypersensitivity or ongoing hypersensitivity that might affect the patient’s suitability for the study (e.g. hypersensitivity to wound dressings), as judged by the investigator. 15. History of allergy to, or insensitivity to, local anaesthetics. 16. Use of any prescribed or non-prescribed (over-the-counter) medication, including herbal medication (e.g., St. Johns Wort) that could possibly interfere with the objectives of this study (e.g., could affect the closure of chronic dermal ulceration), during 2 weeks (or 5 half-lives of the compound whichever is the longer) before the anticipated first dose of study medication. Occasional paracetamol for pain relief (maximum 2 g per 24 hours) and adrenergic nasal spray for relief of nasal congestion are allowed. 17. Having received BBR-012 or isoniazid within the 6 months prior to the scree
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare the rate of healing of DFUs, measured as percent reduction in wound area per week, after 28-days treatment with BBR-012 or placebo, in combination with standard medical therapy.;Secondary Objective: To compare the rate of healing of DFUs, after 12-weeks treatment, in combination with standard medical therapy. To determine the effect of BBR-012 on clinical DFU assessment criteria over the 12-week treatment period. To compare the number and percent of patients with healed DFU after 12-weeks treatmentin combination with standard medical therapy. To determine the effect of BBR-012 on the level of ischaemia in the DFU after 28 days, 8-weeks- and 12-weeks treatment. To determine whether there is any correlation between the level of ischaemia of the target DFU after 28-days, 8-weeks- and 12-weeks treatment. To determine the effect of BBR-012 on microbiological outcome of baseline wound pathogens over the 12-week treatment period. To evaluate the safety and tolerability of 12-weeks treatment with BBR-012 in patients with DFU. ;Primary end point(s): The primary efficacy endpoint is the rate of healing of the DFU in the BBR-012 group versus the placebo group after 28 days treatment. ;Timepoint(s) of evaluation of this end point: 28 days | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: 28 days, 8 weeks and 12 weeks ;Secondary end point(s): To compare the rate of healing of DFUs, measured as percent reduction in wound area per week, after 12 weeks treatment with isoniazid (BBR012) or placebo, when combined with the standard medical therapy. To determine the effect of BBR012 on clinical DFU assessment criteria (IDSA guidelines, composite severity score, modified ASEPSIS score, TEXAS diabetic wound score and global clinical assessment) over the 12week treatment period. To compare the number and percent of patients with healed DFU after 12weeks treatment with BBR012 or placebo, when combined with the standard medical therapy. To determine the effect of BBR012 on the degree of restriction of blood in the DFU as measured by transcutaneous partial pressure of tissue oxygenation (tcpO2) after 28 days, 8 weeks and 12weeks treatment with BBR012 in patients with DFU. To determine whether there is any relationship between the degree of restriction of blood (ischaemia) in the affected foot as measured by tcpO2 and by ankle brachial pressure index (ABI) after 28 days, 8weeks and 12weeks treatment with BBR012 in patients with DFU. To determine the effect of BBR012 on microbiological outcome of baseline wound pathogens over the 12week treatment period in patients with DFU. To evaluate the safety and tolerability of 12weeks treatment with BBR012 in patients with DFU. | — |
Countries
United Kingdom
Contacts
Public ContactClinical Operations Manager
Illingworth Research Ltd
Outcome results
None listed