diabetic polyneuropathy MedDRA version: 21.1 Level: LLT Classification code 10012685 Term: Diabetic polyneuropathy System Organ Class: 100000004852
Conditions
Interventions
Trade Name: milgamma mono 300
Product Name: milgamma mono 300
Pharmaceutical Form: Coated tablet
INN or Proposed INN: BENFOTIAMINE
CAS Number: 22457-89-2
Concentration unit: mg milligram(s)
Concentrat
Sponsors
Wörwag Pharma GmbH & co. KG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Informed consent signed and dated • Diabetes mellitus type 2 according to the American Diabetes Association criteria (2017), lasting =1 year • Stable diabetes metabolism, defined as no metabolic decompensation within the last 3 months (severe hypoglycemia with unconsciousness, ketoacidosis) • According to the investigator’s opinion no further optimizing potential in diabetic control • Age: =18 years • Neuropathic symptoms =6 months • Presence of mild to moderate diabetic sensorimotor polyneuropathy (DSPN) with Neuropathy Disability Score (NDS) 3-8 points confirmed by at least one of the following: reduced sural sensory nerve conduction velocity (SNCV), sural sensory nerve action potential (SNAP), peroneal motor nerve conduction velocity (MNCV), tibial MNCV • Measurable sural SNCV, peroneal MNCV or tibial MNCV above detection limit • CNFL =65 years) yes F.1.3.1 Number of subjects for this age range 38
Exclusion criteria
Exclusion criteria: • Subjects with secondary forms of diabetes such as due to pancreatitis • Contraindications, known allergy, or hypersensitivity to benfotiamine or other ingredients of the study medication or local anesthetics • Neuropathy of any cause other than diabetes which might interfere with neurological assessment • Severe pain other than of neuropathic origin that might impair the assessment of neuropathic pain • Diseases with mixed pain components • Pain level >9 over 24 h on a numerical 11-Point rating scale • Proximal asymmetric neuropathy or neuropathic symptoms of the trunk or proximal lower limbs • Foot ulcer or infection • Currently active or history of alcohol abuse (defined as an intake of more than 24 units of alcohol per week; one unit of alcohol equals approximately 250 ml of beer, 100 ml of wine or 35 ml of spirits) or drug addiction (including soft drugs like cannabis products) • Peripheral arterial occlusive disease Fontaine stage II-IV • Neoplasms • Renal failure (serum creatinine > (above) 120 µmol/l or 1.4 mg/dl) • As judged by the investigator, serious and/or unstable coronary heart disease (unstable angina, myocardial infarction within the preceding 6 months), congestive heart failure of New York Heart Association Class III or worse, uncontrolled hypertension, history of congenital QT-syndrome within family, history of stroke (within the preceding 6 months) • Uncontrolled high blood pressure (DBP >95 mmHg and/or SBP >160 mmHg), unless clearly documented to be white-coat hypertension • Clinical or laboratory evidence of hepatic dysfunction or disease; laboratory evidence defined as any of the following parameters: alkaline phosphatase, ALT, AST or bilirubin >3x ULN, except for a mild rise in bilirubin considered to be due to Gilbert’s condition. • Generalized immune diseases (e.g. HIV-positive, autoimmune diseases, connective tissue diseases) • Endocrine diseases like hyper- or hypothyroidism • Treatment, lasting at least 5 days or longer, with alpha-lipoic acid, B-vitamins, evening primrose oil, or deproteinized hemoderivates of calf blood, containing low-molecular weight compounds of up to 5.000 Da or with other substances with interaction to the study product (e.g. 5-fluorouracil) or affecting study endpoints within the last 3 months before screening, except for daily intake of B-vitamins amounting to less than 1500 % of the recommended daily allowance (RDA) lasting until one month prior to screening. • Treatment with cutaneous electrical nerve stimulation, muscle stimulation or acupuncture within the last month • Treatment of neuropathic pain with antidepressants, anticonvulsants, sodium channel blockers, opioids, neuroleptics, and capsaicin 8% patch within the last 3 months prior to screening , except for a monotherapy with Gabapentin, Pregabalin or Duloxetin without relevant dose change within the last 2 months prior to screening and during the study. • Mental, psychiatric or other conditions compromising data collection and understanding of written or oral instructions during the study • Present or previous chronic alcohol abuse and/or abuse of other drugs • Pregnant women or nursing mothers • Participation in another clinical trial study within the last 3 months • Ability and willingness to abstain from alcohol and from engaging in strenuous physical activity from 24 hours prior to each visit until discharge from the unit • Blood donation within the last 3 months before or during the study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Effects of 12 months treatment with benfothiamin in comparison to Placebo on Corneal confocal microscopy (CCM): corneal nerve fiber length (CNFL);Secondary Objective: Effects of 12 months treatment with benfothiamin in comparison to Placebo on : •Corneal nerve fiber density •Skin biopsy •Motor and sensory nerve conduction velocity •Vibration perception threshold •Warm and cold thermal detection thresholds •Cardiovascular autonomic function tests •Spontaneous baroreflex sensitivity •Pupillography •Neuropad •Sudoscan •Lightguide tissue spectrophotometry •Neuropathy Disability Score •Neuropathy Impairment Score – Lower Limbs •Michigan Neuropathy Screening Instrument •Modified Toronto Clinical Neuropathy Score •Neuropathy Symptom Score •Total Symptom Score (TSS) •Neuropathic Pain Symptom Inventory •11-Point numerical pain rating scale •Brief Pain Inventory •Survey of Autonomic Symptoms •Patient Global Impression of Change •Physical functioning • Quality of life • safety Routine Parameters • Thiamin analytics;Primary end point(s): Corneal confocal microscopy (CCM): corneal nerve fiber length (CNFL);Timepoint(s) of evaluation of this end point: Baseline, after 6 and 12 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Corneal nerve fiber density • Skin biopsy • Motor and sensory nerve conduction velocity • Vibration perception threshold • Warm and cold thermal detection thresholds • Cardiovascular autonomic function tests • Spontaneous baroreflex sensitivity • Pupillography • Neuropad • Sudoscan • Lightguide tissue spectrophotometry • Neuropathy Disability Score • Neuropathy Impairment Score – Lower Limbs • Michigan Neuropathy Screening Instrument • Modified Toronto Clinical Neuropathy Score • Neuropathy Symptom Score • Total Symptom Score • Neuropathic Pain Symptom Inventory • 11-Point pain rating scale • Brief Pain Inventory • Survey of Autonomic Symptoms • Patient Global Impression of Change • Physical functioning • Quality of life • safety Routine Parameters • Thiamin analytics ;Timepoint(s) of evaluation of this end point: Baseline, after 6 and 12 months | — |
Countries
Germany
Contacts
Public ContactClinical Operations Manager
Wörwag Pharma GmbH & co. KG
Outcome results
None listed