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    Summary
    EudraCT Number:2004-004055-19
    Sponsor's Protocol Code Number:TMC278-C204
    National Competent Authority:Germany - BfArM
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2005-03-17
    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 ConcernedGermany - BfArM
    A.2EudraCT number2004-004055-19
    A.3Full title of the trial
    A Phase IIb randomized, partially blinded, dose-finding trial of
    TMC278 in antiretroviral naive HIV-1 infected subjects.

    A.3.2Name or abbreviated title of the trial where available
    N/A
    A.4.1Sponsor's protocol code numberTMC278-C204
    A.5.1ISRCTN (International Standard Randomised Controlled Trial) NumberN/A
    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 SponsorTibotec Pharmaceuticals
    B.1.3.4CountryBelgium
    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 nameTMC278 (as the hydrochloric acid salt R314585)
    D.3.2Product code GFI 314585-CA-003, GFI 314585-CA-009, F001
    D.3.4Pharmaceutical form Film-coated 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 INNrilpivirine hydrochloride
    D.3.9.1CAS number 700361-47-3
    D.3.9.2Current sponsor codeTMC278
    D.3.9.3Other descriptive nameR314585
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number25
    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 Information not present in EudraCT
    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.IMP: 2
    D.1.2 and D.1.3IMP RoleComparator
    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 Sustiva
    D.2.1.1.2Name of the Marketing Authorisation holderBristol-Myers Squibb Pharma EEIG
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    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 nameSustiva 600 mg film-coated tablets
    D.3.4Pharmaceutical form Film-coated 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 INNEfavirenz
    D.3.9.1CAS number 154598-52-4
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number600
    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.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 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 nameTMC278 (as the hydrochloric acid salt R314585)
    D.3.2Product code GFI 314585-CA-005, GFI 314585-CA-011, F003
    D.3.4Pharmaceutical form Film-coated 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 INNrilpivirine hydrochloride
    D.3.9.1CAS number 700361-47-3
    D.3.9.2Current sponsor codeTMC278
    D.3.9.3Other descriptive nameR314585
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number50
    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.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 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 nameTMC278 (as the hydrochloric acid salt R314585)
    D.3.2Product code GFI 314585-CA-004, GFI 314585-CA-010, F002
    D.3.4Pharmaceutical form Film-coated 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 INNrilpivirine hydrochloride
    D.3.9.1CAS number 700361-47-3
    D.3.9.2Current sponsor codeTMC278
    D.3.9.3Other descriptive nameR314585
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number100
    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.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 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 nameTMC278 (as the hydrochloric acid salt), R314585
    D.3.2Product code GFI 314585-CA-030, F008
    D.3.4Pharmaceutical form Film-coated 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 INNrilpivirine hydrochloride
    D.3.9.1CAS number 700361-47-3
    D.3.9.2Current sponsor codeTMC278
    D.3.9.3Other descriptive nameR314585
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number75
    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.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 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 nameTMC278 (as the hydrochloric acid salt R314585)
    D.3.2Product code GFI-314585-CA-026 / F006
    D.3.4Pharmaceutical form Film-coated 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 INNrilpivirine hydrochloride
    D.3.9.1CAS number 700361-47-3
    D.3.9.2Current sponsor codeTMC278
    D.3.9.3Other descriptive nameR314585
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number25
    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
    HIV infection
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 12.1
    E.1.2Level LLT
    E.1.2Classification code 10020161
    E.1.2Term HIV infection
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    The primary objective of the trial is to evaluate the dose-response relationship of antiviral activity after 48 weeks treatment with 3 different dose regimens of TMC278.
    E.2.2Secondary objectives of the trial
    The secondary objectives are:
    - To evaluate antiviral activity between the TMC278 dose regimens over 96 weeks.
    - To evaluate antiviral activity of TMC278 mg q.d. from Week 96 onwards
    - To evaluate the safety and tolerability of TMC278.
    - To compare safety and efficacy of TMC278 with the control group (efavirenz).
    - To evaluate immunologic changes (as measured by CD4 and CD8 cells).
    - To evaluate changes in viral genotype and drug susceptibility.
    - To evaluate the pharmacokinetics of TMC278.

    The main objective of the third optional extension phase is to allow continued access to TMC278 to subjects who completed the 240 weeks of treatment with TMC278 in the second open-label extension part of the trial and who continue to benefit from this treatment, and live in a region where TMC278 is not yet commercially available, reimbursed by the public and/or private health system or cannot be accessed from another source (e.g., access program, government program).
    E.2.3Trial contains a sub-study Yes
    E.2.3.1Full title, date and version of each sub-study and their related objectives
    A sub-study of TMC278-C204 to evaluate the pharmacokinetic profile of TMC278 at week 4, 24 and optionally (subject's decision) week 48 of different doses of TMC278 as an addition to an investigator-selected combination of 2 NRTIs. (version 1.0, 15 November 2004)
    E.3Principal inclusion criteria
    Subjects who meet all of the following criteria are eligible for this trial:
    1. Male or female subjects, aged 18 years or above.
    2. Subject having documented HIV-1 infection.
    3. Subject is willing to sign the informed consent form voluntarily.
    4. Cortisol of at least 550 nmol/L (19.9 µg/dL) at least at one of the 3 timepoints (i.e., morning cortisol, 30 or 60 minutes after 250 µg ACTH stimulation) on the screening assessment.
    5. Subject can comply with the protocol requirements.
    6. HIV-1 plasma viral load at screening visit above 5000 HIV-1 RNA copies/mL (assayed by RNA polymerase chain reaction standard specimen procedure).
    7. In the judgement of the investigator, it is appropriate to initiate ARV therapy based on the
    subject's clinical condition and taking into account guidelines for the treatment of HIV-1 infection.
    8. Subject has never been treated with an ARV drug or therapeutic HIV vaccine, or has received ≤ 2 weeks treatment prior to screening with an NRTI and/or PI.
    9. Screening virco®TYPE HIV-1 demonstrates sensitivity to investigator selected nucleosides.
    10. Subject agrees not to start ARV before the baseline visit.
    11. General medical condition, in the investigator’s opinion, does not interfere with the assessments and the completion of the trial.

    Criteria for Entering the Optional Open-Label Extention Part I, II:
    1. The subject has completed the entire 96-week treatment period and has voluntarily agreed to participate (i.e., has signed the updated ICF).
    2. The subject has completed the entire 144-week treatment period and has voluntarily agreed to participate (i.e., has signed the updated ICF).
    3. The subject is willing to comply with the protocol requirements and cooperate with the investigator.

    Criteria for Entering the Optional Open-Label Extension Part III:
    1. The subject has completed the entire 240-week treatment period with TMC278 and has voluntarily agreed to
    participate (i.e., has signed the updated ICF).
    2. The subject continues to benefit from this treatment.
    3. The subject lives in a region where TMC278 is not yet commercially available, reimbursed by the public and/
    or private health system or cannot be accessed from another source (e.g., access program, government program).
    E.4Principal exclusion criteria
    1. Use of disallowed conc. therapy
    2. History of or currently active alcohol or drug use which will likely compromise subjects’ safety and/or compliance with trial procedures.
    3. Life expectancy less than 6 months.
    4. Subject has any currently active AIDS defining illness with the following exception:
    - Stable, cutaneous Kaposi Sarcoma that is unlikely to require any form of systemic therapy during the trial period;
    - Wasting syndrome due to HIV infection if it is not actively progressive and its treatment does not require hospitalization or compromise the subject’s safety or compliance to adhere to the trial protocol procedures.
    5. Any active clinically significant disease or findings during screening of medical history or physical examination that, in the investigator’s opinion, would compromise the outcome of the trial.
    6. Subject has known or suspected acute (primary) HIV-1 infection.
    7. Any use of NNRTIs.
    8. Acute hepatitis A, B, or C infection.
    9. Having documented genotypic evidence of NNRTI resistance at screening or from historical data available in the source documents.
    A098G
    L100I
    K101E
    K101P
    K101Q
    K103H
    K103N
    K103S
    K103T
    V106A
    V106M
    V108I
    Y181C
    Y181I
    Y181V
    Y188C
    Y188H
    Y188L
    G190A
    G190E
    G190S
    P225H
    M230L
    P236L
    K238N
    K238T
    Y318F
    10. Any current or history of adrenal disorder.
    11. Receipt of any investigational drug within 90 days prior to the trial drug administration.
    12. Previously demonstrated clinically significant allergy or hypersensitivity to any of the
    components of the investigational medication.
    13. Pregnant or breastfeeding female.
    14. Female of childbearing potential without the use of effective birth control methods or not willing to continue practicing these birth control methods during the trial and until 14 days after the end of the trial (or after last intake of ARVs).
    Note: Hormonal based contraception may not be reliable when taking TMC278, therefore to be eligible for this trial, women of childbearing potential should either:
    1) use a double barrier method to prevent pregnancy;
    OR
    2) use hormonal based contraceptive in combination with a barrier contraceptive;
    OR
    3) use an intrauterine device in combination with a barrier contraceptive;
    OR
    4) be non-heterosexually active, practice sexual abstinence or have a vasectomized partner.
    Note: Women who are postmenopausal for at least 2 years, women with total
    hysterectomy and women who have had a tubal ligation are considered of nonchildbearing potential.
    15. Heterosexually active males without the use of effective birth control methods or not willing to continue practicing these birth control methods during the trial and until 30 days after the end of the trial (or after last intake of ARVs). All HIV-infected male subjects are advised to use a condom to reduce the risk of transmitting HIV. Since the effects of TMC278 on conception are unknown, non-vasectomized heterosexual male subjects are advised to use one of the following birth control methods:
    - a condom with spermicide, or
    - a condom or a spermicide combined with either hormonal contraceptives, IUD,
    diaphragm, cervical cap or female condom, or
    - refrain from heterosexual intercourse
    from screening onwards until one month after the last study drug administration i.e., until the 30-days follow-up visit or one month after discontinuation of the study medication in case of premature discontinuation.
    The use of the above mentioned birth control methods does not apply if the male HIVinfected subject has been vasectomized minimally one month prior to screening or if the female sexual partner has had a tubal ligation or a hysterectomy or if she is post-menopausal for at least 2 years.
    For more details on the existing data in regards to the reproductive toxicity of TMC278,
    please refer to the current IB.
    16. Any of the abnormal laboratory values listed below:
    - Renal impairment: serum creatinine > 2 x Upper Limit of Normal
    - Hemoglobin toxicity grade 2 or greater according to the Division of AIDS
    grading scale (d 8.4 g/dL)
    - Platelet count < 75 x 109 cells/L (75000/mcL).
    - Absolute neutrophil count < 1.0 x 109 cells/L (1000 cells/mcL).
    - ALT or AST > 3 x ULN.
    - Any grade 3 or 4 toxicity according to the DAIDS grading scale.
    17. Subject with clinical or laboratory evidence of significantly decreased hepatic function or decompensation, irrespective of liver enzyme levels ([INR] > 1.5 or albumin < 30 g/L or bilirubin ≥ 2.5 x ULN).
    18. Chronic hepatitis B or C unless AST and ALT are < 3 x ULN, subject is clinically stable and does not meet the definition of decompensated liver function as in exclusion criteria 17, and AST and ALT have been stable over the 3 months prior to screening and platelets are within laboratory normal range.
    19. Subjects with a CD4 cell count of < 100 cells/mm3
    E.5 End points
    E.5.1Primary end point(s)
    The primary efficacy parameter is the proportion of subjects with undetectable viral load values (< 50 copies/mL) after 48 weeks of treatment (responders).
    The potential effect of switching to TMC278 25 mg q.d. will be evaluated.
    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 Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response Yes
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others Yes
    E.6.13.1Other scope of the trial description
    tolerability
    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 No
    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
    until w96: part. blinded:contr group open label+ TMC278 groups double blinded. After w96: open label
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) Yes
    E.8.2.2Placebo No
    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 concerned4
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA13
    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
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years5
    E.8.9.1In the Member State concerned months0
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years5
    E.8.9.2In all countries concerned by the trial months0
    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 Information not present in EudraCT
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) Information not present in EudraCT
    F.1.1.3Newborns (0-27 days) Information not present in EudraCT
    F.1.1.4Infants and toddlers (28 days-23 months) Information not present in EudraCT
    F.1.1.5Children (2-11years) Information not present in EudraCT
    F.1.1.6Adolescents (12-17 years) Information not present in EudraCT
    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 state13
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 35
    F.4.2.2In the whole clinical trial 368
    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 Decision2005-06-21
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2005-08-03
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2011-12-15
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