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    Summary
    EudraCT Number:2009-018118-21
    Sponsor's Protocol Code Number:OXN2503
    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:2010-05-21
    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 number2009-018118-21
    A.3Full title of the trial
    An exploratory, randomised, double-blind, placebo-controlled, parallel group, pilot study to assess the analgesic efficacy of oxycodone/naloxone prolonged release tablets (OXN PR) compared to placebo in opioid-naïve Subjects suffering from severe pain due to Bladder Pain Syndrome.
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    not applicable
    A.3.2Name or abbreviated title of the trial where available
    not applicable
    A.4.1Sponsor's protocol code numberOXN2503
    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 SponsorMundipharma Research 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 supportMundipharma Research GmbH & Co. KG
    B.4.2CountryGermany
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationMundipharma Research GmbH & Co. KG
    B.5.2Functional name of contact pointMichael Hopp
    B.5.3 Address:
    B.5.3.1Street AddressHoehenstrasse 10
    B.5.3.2Town/ cityLimburg / Lahn
    B.5.3.3Post code65594
    B.5.3.4CountryGermany
    B.5.4Telephone number+496431701438
    B.5.5Fax number+4964317018438
    B.5.6E-mailmichael.hopp@mundipharma-rd.eu
    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 Targinact 5mg/2.5 mg prolonged-release tablets
    D.2.1.1.2Name of the Marketing Authorisation holderNapp Pharmaceuticals Limited
    D.2.1.2Country which granted the Marketing AuthorisationUnited Kingdom
    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 nameoxycodone/naloxone prolonged release tablets 5/2.5 mg
    D.3.2Product code OXN 5/2.5 mg PR
    D.3.4Pharmaceutical form Prolonged-release 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.3.9.1CAS number 124-90-3
    D.3.9.3Other descriptive nameOXYCODONE HYDROCHLORIDE
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number5.0
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.9.1CAS number 357-08-4
    D.3.9.3Other descriptive nameNALOXONE HYDROCHLORIDE
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number2.5
    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.IMP: 2
    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 Targinact 10 mg/5 mg prolonged-release tablets
    D.2.1.1.2Name of the Marketing Authorisation holderNapp Pharmaceuticals Limited
    D.2.1.2Country which granted the Marketing AuthorisationUnited Kingdom
    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 nameoxycodone/naloxone prolonged release tablets 10/5 mg
    D.3.2Product code OXN 10/5 mg PR
    D.3.4Pharmaceutical form Prolonged-release 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.3.9.1CAS number 124-90-3
    D.3.9.3Other descriptive nameOXYCODONE HYDROCHLORIDE
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number10.0
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.9.1CAS number 357-08-4
    D.3.9.3Other descriptive nameNALOXONE HYDROCHLORIDE
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number5.0
    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.IMP: 3
    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 Targinact 20mg/10 mg prolonged-release tablets
    D.2.1.1.2Name of the Marketing Authorisation holderNapp Pharmaceuticals Limited
    D.2.1.2Country which granted the Marketing AuthorisationUnited Kingdom
    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 nameoxycodone/naloxone prolonged release tablets 20/10 mg
    D.3.2Product code OXN 20/10 mg PR
    D.3.4Pharmaceutical form Prolonged-release 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.3.9.1CAS number 124-90-3
    D.3.9.3Other descriptive nameOXYCODONE HYDROCHLORIDE
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number20.0
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.9.1CAS number 357-08-4
    D.3.9.3Other descriptive nameNALOXONE HYDROCHLORIDE
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number10.0
    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.IMP: 4
    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 Targinact 5mg/2.5 mg prolonged-release tablets
    D.2.1.1.2Name of the Marketing Authorisation holderNapp Pharmaceuticals Limited
    D.2.1.2Country which granted the Marketing AuthorisationUnited Kingdom
    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 nameoxycodone/naloxone prolonged release tablets 5/2.5 mg
    D.3.2Product code OXN 5/2.5 mg PR
    D.3.4Pharmaceutical form Prolonged-release 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.3.9.1CAS number 124-90-3
    D.3.9.3Other descriptive nameOXYCODONE HYDROCHLORIDE
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number5.0
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.9.1CAS number 357-08-4
    D.3.9.3Other descriptive nameNALOXONE HYDROCHLORIDE
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number2.5
    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.IMP: 5
    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 Targinact 10 mg/5 mg prolonged-release tablets
    D.2.1.1.2Name of the Marketing Authorisation holderNapp Pharmaceuticals Limited
    D.2.1.2Country which granted the Marketing AuthorisationUnited Kingdom
    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 nameoxycodone/naloxone prolonged release tablets 10/5 mg
    D.3.2Product code OXN 10/5 mg PR
    D.3.4Pharmaceutical form Prolonged-release 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.3.9.1CAS number 124-90-3
    D.3.9.3Other descriptive nameOXYCODONE HYDROCHLORIDE
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number10.0
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.9.1CAS number 357-08-4
    D.3.9.3Other descriptive nameNALOXONE HYDROCHLORIDE
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number5.0
    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.IMP: 6
    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 Targinact 20mg/10 mg prolonged-release tablets
    D.2.1.1.2Name of the Marketing Authorisation holderNapp Pharmaceuticals Limited
    D.2.1.2Country which granted the Marketing AuthorisationUnited Kingdom
    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 nameoxycodone/naloxone prolonged release tablets 20/10 mg
    D.3.2Product code OXN 20/10 mg PR
    D.3.4Pharmaceutical form Prolonged-release 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.3.9.1CAS number 124-90-3
    D.3.9.3Other descriptive nameOXYCODONE HYDROCHLORIDE
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number20.0
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.9.1CAS number 357-08-4
    D.3.9.3Other descriptive nameNALOXONE HYDROCHLORIDE
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number10.0
    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 placeboProlonged-release tablet
    D.8.4Route of administration of the placeboOral use
    D.8 Placebo: 2
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboProlonged-release tablet
    D.8.4Route of administration of the placeboOral use
    D.8 Placebo: 3
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboProlonged-release 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
    Bladder Pain Syndrome (BPS), formerly addressed as IC/PBS (interstitial cystitis /Painful Bladder Syndrome)
    E.1.1.1Medical condition in easily understood language
    Bladder Pain Syndrome
    E.1.1.2Therapeutic area Diseases [C] - Female diseases of the urinary and reproductive systems and pregancy complications [C13]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 14.1
    E.1.2Level LLT
    E.1.2Classification code 10008927
    E.1.2Term Chronic interstitial cystitis
    E.1.2System Organ Class 10038359 - Renal and urinary disorders
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    The aim of this study is to investigate the efficacy and safety of OXN PR in the treatment of BPS and to further support the evidence for the use of opioids in this indication. The main objective is to estimate the Subjects’ average pain over the last 24 Hours assessed at each study Visit during treatment with OXN PR compared with placebo as measured by the Pain Intensity Scale (NRS 0 – 10).
    E.2.2Secondary objectives of the trial
    - To assess the frequency of pain rescue medication intake.
    - To assess BPI-SF at each clinic Visit during treatment with study medication.
    - To assess the efficacy based on the O’Leary-Sant Interstitial Cystitis Symptom Index (ICSI) score/ O’Leary-Sant Interstitial Cystitis Problem Index (ICPI) score.
    - To assess overall health based on the SF-36 v2.
    - To assess micturition (volume and time) based on 24 hours patient diary assessing 2 days in the last week prior to Visits 6, 8, 10 and 16.
    - To assess urinary urgency using the Patients' Perception of Intensity of Urgency Scale (PPIUS).
    E.2.3Trial contains a sub-study Yes
    E.2.3.1Full title, date and version of each sub-study and their related objectives
    Pharmacogenomic sub-study (compare protocol section 12.2):
    All subjects enrolled in the study OXN2503 will be considered for enrollment into the pharmacogenomic sub-study sponsored by Mundipharma Research GmbH. Pharmacogenomic samples will be stored at the clinical laboratory to provide a resource for future studies which will examine why subjects may respond differently to certain drugs by analyzing specific genetic markers. Genetic variants in genes of the drug targets such as the opioid receptors or genes involved in their signaling pathways could affect the drug efficacy. Similarly, variations in genes involved in the metabolism of the compounds, e.g. Cytochrome P450 2D6, can have an influence on the bioavailability of the compounds which could lead to an increased level of side effects or an alteration of the drug efficacy. Therefore some drugs may be more effective in certain subject groups or they more cause more side effects in certain subjects depending on their genetic makeup. All pharmacogenomic samples will be used by the sponsor or designees and research will be monitored and reviewed by a committee of scientists and clinicians.
    Pharmacogenomic samples will be collected in other opioid trials and may be combined with pharmacogenomic samples collected from this study in order to assess a wider group of subjects response to treatment.
    E.3Principal inclusion criteria
    Inclusion criteria:
    1. Females, 18 years of age or older.
    2. Females less than one year post-menopausal must have a negative serum or urine pregnancy test recorded prior to the first dose of study medication, be non-lactating, and willing to use adequate and highly effective methods of contraception throughout the study. A highly effective method of birth control is defined as those which result in a low failure rate (i.e. less than 1% per year) when used consistently and correctly such as sterilisation, implants, injectables, combined oral contraceptives, some IUDs (Intrauterine Device, hormonal), sexual abstinence or vasectomised partner).
    3. Subjects with a history of severe pain due to BPS for at least 6 months (mean average BPS pain over last 6 months ≥ 5, NRS 0 – 10) prior to entry into the study and based on the Investigators’ judgement and clinical experience the Subjects are likely to benefit from WHO step III opioid therapy for the duration of the study.
    4. Subjects who experience the complaint of suprapubic pain related to bladder filling, accompanied by all of the following 3 criteria, in the absence of proven urinary infection or other obvious pathology:
    • Must have a total score of ≥ 8 on the O'Leary-Sant Interstitial Cystitis Symptom Index (ICSI) and a score of > 0 on each of the 4 questions on the ICSI.
    • Must have a total score of ≥ 8 on the O'Leary-Sant Interstitial Cystitis Problem Index (ICPI) and a score of > 0 on each of the 4 questions on the ICPI.
    • Must have an average of ≥ 8 voids per day and an average of ≥ 2 voids at night (nocturia) within the last month.
    5. Subject’s treatment of pain due to BPS is insufficient (insufficient efficacy or tolerability, based on a clinical judgement).
    6. Subjects with a documented history of attempts to optimise the treatment of pain due to BPS.
    7. Subject’s pre-study BPS treatment is expected to remain stable throughout the duration of the study (OXN PR or matching placebo are given as add-on therapy).
    8. Subjects must not have received opioid containing medication in the last 6 months or ibuprofen (Ibu) during the last 2 weeks on a regular basis (i.e. prescribed medication or more than occasional self medication use for cough, cold etc).
    9. Subjects taking pre-study, non-opioid analgesics, and any other concomitant medications, including medications for the treatment of depression and are considered necessary for the Subject’s welfare, and are anticipated to remain stable throughout the Double-blind Phase of the study, and are to be continued under the supervision of the investigator.
    10. Subjects willing and able to participate in all aspects of the study and comply with the use of study medication.
    Criteria for entry into the Double-blind Phase:
    1. Subjects continue to comply with Screening Inclusion/Exclusion criteria.
    2. Subjects must have an average of ≥ 8 voids per day and an average of ≥ 2 voids (nocturia) at night as assessed in a diary recording 2 periods of 24 hours during the Screening Period.
    3. Subjects must not have any indication for current acute bacterial cystitis based on urinalysis (urine dipstick) assessed at Visit 2.
    4. Subjects with a mean pain value of ≥ 5 (average pain value over the last 24 hours) as assessed during the last 7 days prior to Visit 2.
    E.4Principal exclusion criteria
    Exclusion criteria:
    1. Females who are pregnant (positive β-hCG test) or lactating.
    2. Subjects with any contraindication/history of hypersensitivity to oxycodone, naloxone, ibuprofen (Ibu), related products or other ingredients.
    3. Subjects who previously received ibuprofen regularly for treatment of BPS pain without demonstrating any relevant analgesic effect.
    4. Subjects with a history of, or existing peptic ulceration that would place the Subject at risk upon exposure to ibuprofen or that may confound the analysis and/or interpretation of the study results.
    5. Subjects with a history of bronchospasm, rhinitis, urticaria, particularly associated with therapy with aspirin or other non-sterioidal anti-inflammatory drugs (NSAIDs).
    6. Subjects with any situation in which opioids are contraindicated like severe respiratory depression with hypoxia and/or hypercapnia, severe chronic obstructive lung disease, cor pulmonale, severe bronchial asthma or paralytic ileus.
    7. Subjects with myxoedema, untreated hypothyroidism, Addison`s disease or increase of intracranial pressure.
    8. Subjects with uncontrolled seizures or convulsive disorder.
    9. Evidence of clinically significant cardiovascular, renal, hepatic, gastrointestinal (e.g. paralytic ileus), or psychiatric disease, as determined by medical history, clinical laboratory tests, ECG results, and physical examination, that would place the Subject at risk upon exposure to the study medication or that may confound the analysis and/or interpretation of the study results.
    10. Abnormal aspartate aminotransferase (AST; SGOT), alanine aminotransferase (ALT; SGPT), or alkaline phosphatase levels (> 3 times the upper limit of normal), gamma glutamyl transpeptidase (GGT or GGTP) > 3 times the upper limit of normal.
    11. Abnormal total bilirubin and/or creatinine level(s) (> 1.5 times the upper limit of normal).
    12. Active alcohol or drug abuse and/or history of opioid abuse.
    13. Subjects with a positive urine drug test at screening Visit 1, which indicates unreported illicit drug use or unreported use of a concomitant medication not required to treat the Subjects’ medical condition(s).
    14. Subjects suffering from documented confusable diseases for bladder pain syndrome (see Appendix 12.5) determined by the medical history/physical examination, urine dip stick test or if needed ultrasound.
    15. Chronic or intermittent pain that results from pain conditions other than Bladder Pain Syndrome (BPS) requiring opioid analgesics.
    16. Subjects who received a botulinum toxin injection in the bladder wall within the last 6 months prior to the Screening Visit.
    17. Subjects who received a hydrodistension within the last 4 months prior to the Screening Visit.
    18. Subjects who have had cystoscopic evaluation within 4 weeks prior to the Screening Visit.
    19. Subjects presently taking, or who have taken, naloxone ≤ 30 days prior to the Screening Visit.
    20. Subjects presently taking or who have taken monoamine oxidase inhibitors (MAOI) ≤ 2 weeks prior to the Screening Visit.
    21. Subjects receiving hypnotics or other central nervous system (CNS) depressants that, in the investigator’s opinion, may pose a risk of additional CNS depression with opioid study medication.
    22. Subjects who participated in a clinical research study involving a new chemical entity or an experimental drug within 30 days prior to the Screening Visit.
    23. Surgery within 2 months prior to the Screening Visit, or planned surgery during the 8-week Double-blind Phase that may affect GI motility, bladder function or pain.
    E.5 End points
    E.5.1Primary end point(s)
    The Efficacy Variable of main interest is the Pain Intensity Scale – Average pain over the last 24 hours, as assessed at each study Visit during the Double-blind phase
    E.5.1.1Timepoint(s) of evaluation of this end point
    Evaluation after study end. No interim analysis planned
    E.5.2Secondary end point(s)
    - Frequency of analgesic rescue medication use.
    - The ICSI and the ICPI measure urinary and pain symptoms and assesses how problematic symptoms are for patients with interstitial cystitis (IC). Psychometric performance of both instruments is good, with the ICSI demonstrating excellent ability to discriminate characteristics between patients and controls. Both indices have been useful in the evaluation and management of patients with IC and should be particularly useful in clinical trials of new therapies for this condition, where reliable, validated, and reproducible outcome measures are critically important. The ICSI contains 4 items that measure urgency and frequency of urination, night-time urination, and pain or burning. The ICSI index score is the sum of the item scores (range: 0 – 20) and it is a valid, reliable, and responsive measure of change in IC symptoms.
    - Pain severity subscale score and interference of pain subscale score from the Brief Pain Inventory- Short Form (modified BPI-SF). The Pain severity subscale score is the mean of the (non-missing scores from the) 4 pain intensity items and the Interference subscale score is the mean of the (non-missing scores from the) 7 interference items. Further detail on the computation of these subscale scores will be specified in the statistical analysis plan. The SF-36 v2 health survey. The summary scores to be employed are the SF-36 v2 scores for the 8 subscales (physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health, the health transition question, and 2 summary measures of physical health (aggregate of physical functioning, role-physical, bodily pain and general health scales) and mental health (aggregate of the vitality, social functioning, role-emotional and mental health scales). The scoring algorithms for the subscale scores are described in the statistical analysis plan.
    - Micturition diary (volume and time).PPIUS. The PPIUS is a validated, 5-point scale designed to assess patient perception of intensity of urgency. The scale ranges from 0 to 4 with grades 3 and 4 representing urgency and urgency incontinence.
    - Pain Intensity Scale – Average pain over the last 24 hours, as assessed at each study Visit during the Open-label Phase.
    E.5.2.1Timepoint(s) of evaluation of this end point
    Evaluation after study end. No interim analysis planned
    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 No
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    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) 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 Yes
    E.8.1.7.1Other trial design description
    Open label phase
    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 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 concerned6
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA30
    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 years0
    E.8.9.1In the Member State concerned months9
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years0
    E.8.9.2In all countries concerned by the trial months9
    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.1.1Number of subjects for this age range: 0
    F.1.1.1In Utero No
    F.1.1.1.1Number of subjects for this age range: 0
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.2.1Number of subjects for this age range: 0
    F.1.1.3Newborns (0-27 days) No
    F.1.1.3.1Number of subjects for this age range: 0
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.4.1Number of subjects for this age range: 0
    F.1.1.5Children (2-11years) No
    F.1.1.5.1Number of subjects for this age range: 0
    F.1.1.6Adolescents (12-17 years) No
    F.1.1.6.1Number of subjects for this age range: 0
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 70
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 70
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male No
    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 For clinical trials recorded in the database before the 10th March 2011 this question read: "Women of childbearing potential" and did not include the words "not using contraception". An answer of yes could have included women of child bearing potential whether or not they would be using contraception. The answer should therefore be understood in that context. This trial was recorded in the database on 2010-05-21. Yes
    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 state35
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 70
    F.4.2.2In the whole clinical trial 70
    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)
    The objective of the Open-label Phase is to ensure a safe transfer of all Subjects to a subsequent therapy of their BPS pain after the study. The treatment after study end is expected to be the normal treatment of that condition.
    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 Decision2010-08-04
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2010-07-26
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2013-03-25
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