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    Summary
    EudraCT Number:2012-001539-30
    Sponsor's Protocol Code Number:C21013
    National Competent Authority:UK - MHRA
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2012-08-21
    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 ConcernedUK - MHRA
    A.2EudraCT number2012-001539-30
    A.3Full title of the trial
    A Study in Japan and Ex-Japan to Characterize the Pharmacokinetic and Pharmacodynamic Response to Orteronel (TAK-700) in Chemotherapy-Naïve Patients with Castration-Resistant Prostate Cancer
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Study to find out the effects and fate of treatment with Orteronel plus prednisone in Japanese and non Japanese people that have not recieved cancer therapy for prostate cancer.
    A.4.1Sponsor's protocol code numberC21013
    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 SponsorMillennium Pharmaceuticals, Inc.
    B.1.3.4CountryUnited States
    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 supportMillenium Pharmaceuticals, Inc.
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationMillenium, Drug Information Call Center
    B.5.2Functional name of contact pointDrug Information Call Center
    B.5.3 Address:
    B.5.3.1Street Address40 Landsdowne Street
    B.5.3.2Town/ cityCambridge, Masachussetts
    B.5.3.3Post codeMA 02139
    B.5.3.4CountryUnited States
    B.5.4Telephone number+1(510)740 2412
    B.5.5Fax number+1(510)881 6092
    B.5.6E-mailmedical@mlnm.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 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 nameRecommended INN-Orteronel
    D.3.2Product code TAK-700
    D.3.4Pharmaceutical form Film-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 INNRecommended INN = Orteronel
    D.3.9.1CAS number 566939-85-3
    D.3.9.2Current sponsor codeTAK-700
    D.3.9.3Other descriptive name6-[(7S)-7-hydroxy-6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-7-yl]-N-methyl-2-naphthamide
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number200
    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 Decortin
    D.2.1.1.2Name of the Marketing Authorisation holderMerck Serono GmbH
    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 nameDecortin
    D.3.2Product code Prednisone
    D.3.4Pharmaceutical form 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 INNPREDNISONE
    D.3.9.1CAS number 53-03-2
    D.3.9.2Current sponsor codeEMD 15216
    D.3.9.3Other descriptive nameDecortin
    D.3.9.4EV Substance CodeSUB10020MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number5
    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 Decortin
    D.2.1.1.2Name of the Marketing Authorisation holder Acis Arzneimittel GmbH
    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 nameDecortin
    D.3.2Product code Prednisone
    D.3.4Pharmaceutical form 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 INNPREDNISONE
    D.3.9.1CAS number 53-03-2
    D.3.9.2Current sponsor codeEMD 15216
    D.3.9.3Other descriptive nameDecortin
    D.3.9.4EV Substance CodeSUB10020MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number5
    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 Decortin
    D.2.1.1.2Name of the Marketing Authorisation holder Ratiopharm GmbH
    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 nameDecortin
    D.3.2Product code Prednisone
    D.3.4Pharmaceutical form 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 INNPREDNISONE
    D.3.9.1CAS number 53-03-2
    D.3.9.2Current sponsor codeEMD 15216
    D.3.9.3Other descriptive nameDecortin
    D.3.9.4EV Substance CodeSUB10020MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number5
    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 placeboFilm-coated 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
    progressive castration-resistant prostate cancer.
    E.1.1.1Medical condition in easily understood language
    Prostate cancer
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 14.1
    E.1.2Level SOC
    E.1.2Classification code 10029104
    E.1.2Term Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    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 whether orteronel 300 mg twice daily (BID) plus prednisone 5 mg BID more effectively reduces serum testosterone levels, compared to placebo plus prednisone 5 mg BID, when administered to patients in Japan
    E.2.2Secondary objectives of the trial
    •To evaluate the reduction in serum testosterone levels in ex-Japan patients administered orteronel 400 mg BID plus prednisone 5 mg BID, when compared to placebo plus prednisone 5 mg BID
    •To determine whether orteronel plus prednisone improves 50% prostate-specific antigen (PSA) response
    •To evaluate the effect of orteronel plus prednisone on endocrine markers of pharmacodynamic response
    •To characterize the pharmacokinetics of orteronel plus prednisone
    •To continue to assess the safety of orteronel plus prednisone in patients with castration resistant prostate cancer (CRPC)
    Exploratory
    •To explore the pharmacokinetic (PK) -pharmacodynamic response to orteronel plus prednisone in patients in Japan and ex-Japan
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1.Male patients 18 years or older.
    2.Voluntary written consent must be given before performance of any study-related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care.
    3.Histologically or cytologically confirmed diagnosis of prostate adenocarcinoma.
    4.Prior surgical castration or concurrent use of an agent for medical castration (eg, GnRH analogue).
    5. PSA ≥ 2 ng/mL at screening.
    6. Progressive disease based on PSA/and or radiographic criteria
    E.4Principal exclusion criteria
    1.Prior therapy with orteronel, ketoconazole, aminoglutethimide, or abiraterone.
    2.Known hypersensitivity to compounds related to orteronel, orteronel excipients, prednisone (or commercially available equivalent), or GnRH analogue.
    3.All antiandrogen therapy (including bicalutamide) is excluded within 4 weeks before the first dose of study drug. Any other therapies for prostate cancer, other than GnRH analogue therapy, such as progesterone, medroxyprogesterone, progestins (megesterol), or 5-alpha reductase inhibitors (eg, finasteride or dutasteride), must be discontinued 2 weeks before the first dose of study drug.
    4.Continuous daily use of oral prednisone (or commercially available equivalent), oral dexamethasone, or other systemic corticosteroids for more than 2 weeks within the 3 months before screening (inhaled, nasal, and local steroids [eg, joint injection] are allowed).
    5.Prior chemotherapy for prostate cancer, with the exception of neoadjuvant/adjuvant therapy as part of initial primary treatment for local disease that was completed 2 or more years before screening.
    E.5 End points
    E.5.1Primary end point(s)
    Percentage of patients in Japan with serum testosterone levels reduced to ≤ 2 ng/dL after 4 weeks of treatment with orteronel 300 mg BID plus prednisone 5 mg BID, when compared to placebo plus prednisone 5 mg BID
    E.5.1.1Timepoint(s) of evaluation of this end point
    Cycle 1 Day 1 through Cycle 2 Day 1 [study Day 29 +/- 1 day]
    E.5.2Secondary end point(s)
    •Percentage of ex-Japan patients with serum testosterone levels reduced to ≤ 2 ng/dL after 4 weeks of treatment with orteronel 400 mg BID plus prednisone 5 mg BID, when compared to placebo plus prednisone 5 mg BID
    •Serum testosterone levels after 4 weeks of treatment with study drug (orteronel plus prednisone or placebo plus prednisone) and after 12 weeks of active treatment with orteronel plus prednisone in all treatment groups
    •PSA reduction ≥ 50% after 4 weeks of treatment with study drug (orteronel plus prednisone or placebo plus prednisone) and after 12 weeks of active treatment with orteronel plus prednisone in all treatment groups
    •Pharmacodynamic effects of orteronel as measured by endocrine markers dehydroepiandrosterone sulfate (DHEA-S), ACTH, corticosterone, and cortisol in all treatment groups
    •PK parameters, including, but not limited to, Cmax, AUC from zero to 24 hours (AUC24hr), AUCinf, single dose first time of occurrence of maximum (peak) concentration (Tmax), and the cumulative amount of unchanged drug excreted into the urine (Ae) in all treatment groups
    •Adverse events (AEs), serious adverse events (SAEs), assessments of clinical laboratory values, vital sign measurements, physical examination findings, and electrocardiograms (ECGs) in all treatment groups
    E.5.2.1Timepoint(s) of evaluation of this end point
    Cycle 1 Day 1 through Cycle 2 Day 1 [study Day 29 +/- 1 day]
    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 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) Yes
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other Yes
    E.7.1.3.1Other trial type description
    Pharmacokinetics and Pharmacodynamics
    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 No
    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 trial3
    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 concerned8
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA29
    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 No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Australia
    Austria
    Germany
    Greece
    Ireland
    Italy
    Japan
    Netherlands
    New Zealand
    Portugal
    United Kingdom
    United States
    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
    Treatment will be considered complete when the required PK pharmacodynamic assessment period of a minimum of 12 weeks of active treatment with orteronel is complete (16 weeks for patients receiving orteronel or 12 weeks for patients receiving placebo). Patients may then remain on treatment and be assessed as clinically indicated at the discretion of the investigator according to standard of care until treatment with study drug is discontinued.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years3
    E.8.9.1In the Member State concerned months10
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years3
    E.8.9.2In all countries concerned by the trial months11
    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.1.2.1Number of subjects for this age range: 124
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 20
    F.2 Gender
    F.2.1Female No
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations No
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception No
    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 state10
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 58
    F.4.2.2In the whole clinical trial 144
    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)
    After completing the PK pharmacodynamic assessment period, patients may remain on treatment and be assessed as clinically indicated at the discretion of the investigator according to standard of care until treatment with study drug is discontinued.
    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 Decision2012-08-07
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2012-11-16
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2016-09-01
    As of 1.2.2020, the UK is no longer an EU Member State. However, EU law still applies to the UK during the transition period
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