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The European Union Clinical Trials Register allows you to search for protocol and results information on:
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    The EU Clinical Trials Register currently displays   43203   clinical trials with a EudraCT protocol, of which   7150   are clinical trials conducted with subjects less than 18 years old.
    The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).


    Phase 1 trials conducted solely in adults and that are not part of an agreed PIP are not public in the EU CTR (refer to European Guidance 2008/C 168/02   Art. 3 par. 2 and   Commission Guideline 2012/C 302/03,   Art. 5) .

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    Summary
    EudraCT Number:2017-003054-16
    Sponsor's Protocol Code Number:DDZ-BOND-2017
    National Competent Authority:Germany - BfArM
    Clinical Trial Type:EEA CTA
    Trial Status:Restarted
    Date on which this record was first entered in the EudraCT database:2018-04-10
    Trial results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedGermany - BfArM
    A.2EudraCT number2017-003054-16
    A.3Full title of the trial
    Randomized double-blind, placebo-controlled parallel group study over 12 months to assess the effects of treatment with benfotiamine on morphometric, neurophysiological, and clinical measures in type 2 diabetes patients with mild to moderate symptomatic polyneuropathy - BOND Study
    Eine randomisierte, doppelblinde, placebokontrollierte Phase-IIa-Studie über 12 Monate zur Beurteilung der Wirksamkeit von Benfotiamin in Hinblick auf morphometrische, neurophysiologische und klinische Parameter in Patienten mit Diabetes Mellitus Typ 2 und leichter bis mittelgradiger symptomatischer Polyneuropathie - BOND Studie
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Study over 12 months to assess the effects of Treatment with benfotiamine on symptoms and consequences in type 2 Diabetes patients with mild to moderate symptomatic polyneuropathy.
    Studie über 12 Monate zur Beurteilung der Wirksamkeit von Benfotiamin in Hinblick auf die Symptome und Folgen einer diabetischen peripheren Neuropathie in Patienten mit Diabetes Mellitus Typ 2 und leichter bis mittelschwerer symptomatischer Polyneuropathie - BOND Studie
    A.3.2Name or abbreviated title of the trial where available
    BOND Study
    BOND Studie
    A.4.1Sponsor's protocol code numberDDZ-BOND-2017
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorWörwag Pharma GmbH & co. KG
    B.1.3.4CountryGermany
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportWörwag Pharma GmbH & Co. KG
    B.4.2CountryGermany
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationWörwag Pharma GmbH & co. KG
    B.5.2Functional name of contact pointClinical Operations Manager
    B.5.3 Address:
    B.5.3.1Street AddressCalwerstraße 7
    B.5.3.2Town/ cityBöblingen
    B.5.3.3Post code71034
    B.5.3.4CountryGermany
    B.5.4Telephone number0049070316204416
    B.5.5Fax number0049070316204419
    B.5.6E-mailclaudia.reule@woerwagpharma.com
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name milgamma mono 300
    D.2.1.1.2Name of the Marketing Authorisation holderWörwag Pharma GmbH & Co. KG
    D.2.1.2Country which granted the Marketing AuthorisationGermany
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product namemilgamma mono 300
    D.3.4Pharmaceutical form Coated tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNBENFOTIAMINE
    D.3.9.1CAS number 22457-89-2
    D.3.9.4EV Substance CodeSUB05716MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number300
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboCoated tablet
    D.8.4Route of administration of the placeboOral use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    diabetic polyneuropathy
    sympthomatische diabetische polyneuropathie
    E.1.1.1Medical condition in easily understood language
    Nerve damaging disorders associated with diabetes mellitus
    Schädigung multipler Nerven (Polyneuropathie), die als Komplikation eines bestehenden Diabetes mellitus entsteht
    E.1.1.2Therapeutic area Diseases [C] - Nervous System Diseases [C10]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.1
    E.1.2Level LLT
    E.1.2Classification code 10012685
    E.1.2Term Diabetic polyneuropathy
    E.1.2System Organ Class 100000004852
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    Effects of 12 months treatment with benfothiamin in comparison to Placebo on Corneal confocal microscopy (CCM): corneal nerve fiber length (CNFL)
    E.2.2Secondary objectives of the trial
    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
    E.2.3Trial contains a sub-study No
    E.3Principal 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 <1SD below the mean of control subjects
    • At least 1 palpable pulse of posterior tibial artery or dorsal artery on each side of the foot
    • Stable diabetes medication without optimizing potential
    • Stable insulin dose for insulin-dependent patients within the last 3 months
    • HbA 1c <9.5%
    • Acceptable contraceptive measures with female patients in childbearing potential
    • Ability to meet the study center visits for the study Duration
    E.4Principal 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
    E.5 End points
    E.5.1Primary end point(s)
    Corneal confocal microscopy (CCM): corneal nerve fiber length (CNFL)
    E.5.1.1Timepoint(s) of evaluation of this end point
    Baseline, after 6 and 12 months
    E.5.2Secondary 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
    E.5.2.1Timepoint(s) of evaluation of this end point
    Baseline, after 6 and 12 months
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy No
    E.6.4Safety No
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic No
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind Yes
    E.8.1.5Parallel group Yes
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo Yes
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial2
    E.8.3 The trial involves single site in the Member State concerned Yes
    E.8.4 The trial involves multiple sites in the Member State concerned No
    E.8.5The trial involves multiple Member States No
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA No
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.7Trial has a data monitoring committee No
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    LVLS
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years4
    E.8.9.1In the Member State concerned months0
    E.8.9.1In the Member State concerned days0
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 18
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 38
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state56
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 56
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    none
    G. Investigator Networks to be involved in the Trial
    G.4 Investigator Network to be involved in the Trial: 1
    G.4.1Name of Organisation Departement of Biometry and Epidemioloy
    G.4.3.4Network Country Germany
    G.4 Investigator Network to be involved in the Trial: 2
    G.4.1Name of Organisation BioTeSys GmbH
    G.4.3.4Network Country Germany
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2018-06-08
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2018-07-27
    P. End of Trial
    P.End of Trial StatusRestarted
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