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    Summary
    EudraCT Number:2008-002843-18
    Sponsor's Protocol Code Number:AS3201-G000-291
    National Competent Authority:Hungary - National Institute of Pharmacy
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2009-07-20
    Trial results View 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 ConcernedHungary - National Institute of Pharmacy
    A.2EudraCT number2008-002843-18
    A.3Full title of the trial
    A 2-year, Randomized, Double-blind, Placebo-controlled, Multi-center,
    Phase II-III Study to Evaluate the Efficacy and Safety of Oral Ranirestat (40 and
    80 mg) in Mild to Moderate Diabetic Sensorimotor Polyneuropathy
    A.4.1Sponsor's protocol code numberAS3201-G000-291
    A.7Trial is part of a Paediatric Investigation Plan Information not present in EudraCT
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorEisai Limited
    B.1.3.4CountryUnited Kingdom
    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 support
    B.4.2Country
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisation
    B.5.2Functional name of contact point
    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 No
    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 nameRanirestat
    D.3.2Product code AS3201
    D.3.4Pharmaceutical form Tablet
    D.3.4.1Specific paediatric formulation Information not present in EudraCT
    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 INNRanirestat
    D.3.9.1CAS number 147254-64-6
    D.3.9.2Current sponsor codeAS-3201
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number40
    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) Information not present in EudraCT
    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 Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy Information not present in EudraCT
    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 Information not present in EudraCT
    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 placeboTablet
    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 Sensorimotor Polyneuropathy
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 9.1
    E.1.2Level LLT
    E.1.2Classification code 10012685
    E.1.2Term Diabetic polyneuropathy
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To determine the effect of 40 mg and 80 mg ranirestat on peroneal motor nerve conduction velocity relative to placebo in subjects with mild to moderate diabetic
    sensorimotor polyneuropathy
    E.2.2Secondary objectives of the trial
    1. To determine the effect of 40 mg and 80 mg ranirestat relative to placebo on signs and symptoms of diabetic sensorimotor polyneuropathy
    2. To evaluate overall safety and tolerability of 40 mg and 80 mg ranirestat
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Male or female subjects aged between 18 and 75 years old at screening
    2. Subjects with type 1 or type 2, insulin-dependent or non insulin-dependent diabetes mellitus, with a diagnosis at least 12 months prior to screening
    3. Subjects whose glycemic control has been optimized and stable for at least 3 months prior to screening.
    Optimal glycemic control refers to the best possible diabetic control that an individual subject can attain with usual standards of care.
    Stable control refers to no dose changes to existing medications for glycemic control (other than insulin) and no medications being initiated for glycemic control in the 3 months prior to screening
    4. Subjects with a history of distal symmetric polyneuropathy, secondary to diabetes, diagnosed in accordance with the American Academy of Neurology criteria:
    • Abnormal nerve conduction velocity of the sural nerve (≤ 1st percentile, corrected for age; table will provided by the Neurological Core Laboratory in the manual of electrophysiological testing procedures). If recordings are technically acceptable, absent sural nerve responses provide clear evidence of an “abnormal” response.
    • Abnormal peroneal motor nerve conduction velocity (≤ 1st percentile, corrected for age; table will provided by the Neurological Core Laboratory in manual of electrophysiological testing procedures). Peroneal responses must be present, with an evoked compound muscle action potential in the extensor digitorum brevis muscle
    ≥500 μV. Peroneal motor nerve conduction velocity must be greater than a value defined as 20% of the lower limit of normal (e.g. if the lower limit of normal is 40 m/sec, peroneal motor nerve conduction velocity must be ≥ than 32 m/sec). Peroneal motor nerve conduction velocity will be recorded bilaterally on two separate occasions within 1-21 days of each other during the prerandomization period; both sets of recordings must fulfil the above criteria.
    • Decreased/absent ankle reflexes AND/OR decreased distal sensation in the lower limbs
    • Neuropathy Total Symptom Score-6 ≥ 1 (at visit 1 and at visit 2)
    5. Female subjects, who are of non-reproductive potential (≥12 months post-menopausal or surgically sterile) or who are using adequate contraception which includes abstinence or double barrier methods (diaphragm and condom with spermicidal cream, intrauterine device and condom with spermicidal
    cream). Male subjects with partners of child-bearing potential must also use adequate contraception
    6. Subjects must be able to read, understand, and provide written informed consent before enrolling in the study at screening
    E.4Principal exclusion criteria
    1. History of diabetic foot ulcers (Wagner grade ≥1) or lower extremity amputation
    2. Diabetic amyotrophy or non-diabetic cause of lower limb neuropathy/neuropathic symptoms (e.g.sequelae of cerebrovascular disease, lumbar radiculopathy, entrapment neuropathy etc)
    3. Subjects with a history of hypothyroidism or B12/folate deficiency or subjects with a low serum folate, vitamin B12 or elevated thyroid-stimulating hormone at screening, as defined by the central laboratory normal limits range
    4. History or evidence of drug or alcohol abuse
    5. History of known or suspected diagnosis of acquired immune deficiency syndrome, or who have tested seropositive for human immunodeficiency virus antibody or antigen previously
    6. Significant cardiovascular disease such as:
    • Peripheral arterial occlusive disease (Fontaine Stage ≥IIa)
    • Clinically significant (in the opinion of the investigator) abnormal 12-lead electrocardiogram
    • New York Heart Association ≥class III heart failure
    7. Significant hepatic disease, e.g.
    • Repeated alanine aminotransferase, aspartate transaminase, alkaline phosphatase > 2x the upper limit of normal at screening or total bilirubin >1.5x the upper limit of normal at screening
    • Positive result from hepatitis B or C screening tests or a history of a positive test at screening
    8. History of hypoglycaemia resulting in loss of consciousness, diabetic ketoacidosis or hyperglycaemic hyperosmolar non-ketotic coma in the 3 months prior to screening
    9. Morbid obesity (body mass index >40 kg/m2) at screening
    10. Calculated creatinine clearance <50 mL/min at screening (see Appendix 2)
    11. History of carcinoma within 5 years prior to screening, with the exception of basal cell carcinoma
    12. Current major depressive disorder, bipolar disorder or a past history of suicide attempt or deliberate self-harm
    13. Subjects who have received an investigational medicinal product within 3 months prior to the screening visit or subjects who have participated in a previous study with ranirestat
    14. Clinically significant illness (e.g. unstable pulmonary, hematologic, renal, neurological or psychiatric disease etc) which, in the opinion of the investigator, would compromise a subject’s suitability to participate in the study for reasons of safety or would confound the efficacy assessments
    E.5 End points
    E.5.1Primary end point(s)
    Change from baseline in peroneal motor nerve conduction velocity relative to placebo
    at 24 months on the full analysis population.
    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 Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic Yes
    E.6.8Bioequivalence No
    E.6.9Dose response Yes
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic Yes
    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) Yes
    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.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned7
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA41
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA Information not present in EudraCT
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    E.8.7Trial has a data monitoring committee Yes
    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
    As per protocol
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years2
    E.8.9.1In the Member State concerned months2
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years2
    E.8.9.2In all countries concerned by the trial months2
    E.8.9.2In all countries concerned by the trial 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.1.3Elderly (>=65 years) Yes
    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 state70
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 180
    F.4.2.2In the whole clinical trial 750
    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)
    Expected normal treatment
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2009-09-04
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2009-08-26
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2013-01-10
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