Safety and Efficacy Study of BC-DN-01 in Painful Diabetic Peripheral Neuropathy

• Status: Withdrawn
• Trial end date: 2014-12-01
• Target enrollment: 0
• Participant gender: All

Summary

A combined Phase 1 & 2 study to evaluate the safety and effectiveness of a new diabetic neuropathy topical cream, containing benfotiamine, will be performed at 5 clinical sites and plans for BC-DN-01 administration in up to 135 volunteer patients using a standard Phase 1 + 2 design. Up to 15 subjects will receive BC-DN-01 in Study Phase 1 and up to 120 subjects will receive BC-DN-01 or placebo in Study Phase 2.

In Phase 1, a BC-DN-01 dose delivering 160mg benfotiamine/day (80mg twice daily) will be administered for the first 7 days. On visit day 0, patients will commence study treatment. Patients will be interviewed by phone on day 3 and return to clinic on day 7 for safety assessments. If the drug is well-tolerated and no significant adverse events experienced, the total daily BC-DN-01 dose will be increased on days 7-14 to 320mg benfotiamine/day (160mg b.i.d.). Patients will be interviewed by telephone on day 10 and return to clinic on day 14 for safety assessments.

Once the safety profile has been determined in Phase 1 as acceptable, the Phase 2 study will be initiated to evaluate clinical efficacy of BC-DN-01. Phase 2 is a randomized, placebo-controlled, double-blind, parallel study. Participants receive placebo or BC-DN-01 based on 1:1 randomization. Each patient will apply 4g of the study medication to each leg twice-a-day administering 320mg benfotiamine dose/day for 12 weeks.

Participants will be evaluated in the clinic at baseline and at 4, 8, and 12-week time points; study staff will interview the patients by telephone on weeks 2, 6, and 10.

The primary endpoint of the phase 2 trial is reduction in DPN pain measured by the Brief Pain Inventory. Phase 2 patients will be invited to give written consent to take part in biopsy sampling and additional gene expression analysis.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: BioChemics, Inc.
• Collaborator: Harrison Clinical Research
• Treatments: Benphothiamine

Criteria

Inclusion Criteria:

1. Current diagnosis of Type I or II diabetes mellitus according to the American Diabetes Association Criteria of FPG≥ 7.0 mmol/l (126 mg/dl)

2. A current or historical reading of HbA1c 6.5-11%, using a test performed in a clinical laboratory using a method that is NGSP certified and standardised to the DCCT assay.

3. Ability to understand the nature of the trial and willingness to participate, documented by written informed consent.

4. Willingness and ability to comply with the study protocol requirements for the duration of the study.

5. Males and females of any ethnic origin and ≥18 years of age.

6. Negative serum pregnancy test at screening and a negative urine pregnancy test at randomisation, for women of childbearing potential only and assurance from the patient (males and females) of using satisfactory contraception methods (refer to section 4.9.6).

7. If on anti-diabetic medication, must have been on a stable therapeutic regimen for at least 30 days prior to randomisation.

8. Phase 2 - Peroneal Motor Nerve Conduction Velocity measurements 30-40 m/s. indicating a mild to moderate case of diabetic peripheral neuropathy

9. Phase 2 - Scores on the Brief Pain Inventory of ≥4.

10. An ability to apply topical medication to both legs from the knee to the toes, either by themselves or have a documentation of an assistant or partner to help with the administration of the trial drug product twice a day for the 12-week treatment period.

11. Patient must be willing to sign a Consent form to participate in this clinical trial.

12. Patient must be willing to sign a consent form to be sent to their primary physician to inform that the patient will stop taking disallowed concomitant medications prescribed by the physician.

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Exclusion Criteria:

1. Participation in any investigational drug study within 4 months preceding randomisation of this study.

2. Pregnancy, lactation, fertility without adequate protection against pregnancy (refer to section 4.9.6).

1. A serum pregnancy test will be performed for women of childbearing potential with the haematological and clinical chemistry evaluations at screening and a urine pregnancy test immediately prior to randomisation.

2. If the patient becomes pregnant during the study, the patient's participation in the remainder of the study will be terminated.

3. Phase 2 - Severe neuropathy (PMNCV < 30 m/s, prior amputations at the foot level and Charcot disease).

4. Current severe peripheral arterial disease requiring surgical intervention (however patients with previous successful intervention 12 weeks or more prior to randomisation will be eligible for the study (See Section 4.2.2.1 Peripheral Arterial Disease Determination).

5. End stage renal failure requiring dialysis or renal transplantation and patients who are expected to receive dialysis or transplantation in the near future should be excluded from the study.

6. Presence of any serious disease, including those of hepatic, hematologic, neurologic, or immune origin or an active malignant disease, which in the opinion of the investigator would affect response to pain relief treatment.

7. Presence of peripheral pain not associated with DPN, mono-neuropathies or proximal neuropathies, or central pain, which in the opinion of the investigator would affect response to pain relief treatment.

8. Presence of a medical condition diagnosed with other known causes of non-Diabetic Peripheral Neuropathy.

9. Known to be currently abusing alcohol or drugs.

10. Presence of acute skin disease or infection such as erysipelas and vasculitis of the lower extremities.

11. Current oral or topical use of benfotiamine or BC-DN-01 products.

12. Hypersensitivity to benfotiamine or any component of BC-DN-01.

13. Concurrent administration or use of Lyrica, Cymbalta, or capsaicin use within the 2 weeks prior to randomisation (see Appendix 12.3 for full list of disallowed concomitant medications).

14. Any factors which, in the opinion of the investigator, will affect the patient's ability to safely participate in the study and meet study objectives.