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    Summary
    EudraCT Number:2005-002035-28
    Sponsor's Protocol Code Number:TBM100C2301 (TIP002)
    National Competent Authority:Lithuania - SMCA
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2005-08-24
    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 ConcernedLithuania - SMCA
    A.2EudraCT number2005-002035-28
    A.3Full title of the trial
    A Randomized, Double-Blind, Placebo-Controlled, Multicenter, Phase 3 Trial to Assess the Efficacy and Safety of Tobramycin Inhalation Powder (TIP) in Cystic Fibrosis (CF) Subjects
    A.4.1Sponsor's protocol code numberTBM100C2301 (TIP002)
    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 SponsorNovartis Pharma Services AG
    B.1.3.4CountrySwitzerland
    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 nameTobramycin Inhalation Powder
    D.3.2Product code TIP
    D.3.4Pharmaceutical form Inhalation powder
    D.3.4.1Specific paediatric formulation Information not present in EudraCT
    D.3.7Routes of administration for this IMPInhalation use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNTobramycine
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number112
    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 Information not present in EudraCT
    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 placeboInhalation powder
    D.8.4Route of administration of the placeboInhalation use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    pulmonary P aeruginosa infection in patient with cystic fibrosis
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 9.1
    E.1.2Level LLT
    E.1.2Classification code 10011762
    E.1.2Term Cystic fibrosis
    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 is to demonstrate the efficacy of a 28-day, twice-daily (BID) dosing regimen of TIP versus placebo, as measured by the relative change in forced expiratory volume at 1 second (FEV1) % predicted from baseline (week 1/cycle 1, day 1) to the end of cycle 1 dosing (week 5/cycle 1, day 28).
    E.2.2Secondary objectives of the trial
    to assess the safety and efficacy of TIP when administered to subjects who are dosed for more than one cycle
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    • Confirmed diagnosis of cystic fibrosis by documented sweat chloride 60 mEq/L or greater by quantitative pilocarpine iontophoresis test (QPIT) or homozygosity for F508 genetic mutation (or heterozygosity for two well-characterized mutations) and two clinical findings consistent with CF.
    • Male and female subjects from  6 to < 20 years of age at the time of screening.
    • FEV1 at screening must be  25% and  75% of normal predicted values for age, sex, and height based on Knudson criteria.
    • P aeruginosa must be present in a sputum/throat culture (or bronchoalveolar lavage [BAL]) within 6 months prior to screening and in the sputum culture at the screening visit.
    • Able to expectorate a sputum sample at screening.
    • Able to comply with all protocol requirements.
    • Clinically stable in the opinion of the investigator.
    • Use of an effective means of contraception in females of childbearing potential.
    Provide written, informed consent and HIPAA authorization (where applicable) prior to the performance of any study-related procedure
    E.4Principal exclusion criteria
    • History of sputum culture or throat swab (or BAL) culture yielding Burkholderia cepacia (B cepacia) within 2 years prior to screening and/or sputum culture yielding B cepacia at screening.
    • Hemoptysis more than 60 cc at any time within 30 days prior to study drug administration.
    • Known local or systemic hypersensitivity to aminoglycosides or inhaled antibiotics.
    • Serum creatinine 2 mg/dl or more, BUN 40 mg/dl or more, or an abnormal urinalysis defined as 2+ or greater proteinuria.
    • Females who are pregnant (positive pregnancy test), lactating, or are planning to become pregnant during the study.
    • Any use of inhaled antipseudomonal antibiotics within 4 months prior to screening.
    • Chronic use of inhaled antipseudomonal antibiotics within 1 year prior to screening. Chronic use is defined as any one of the following:
    - one course of 29 or more consecutive days within the period from 12 months to 4 months prior to screening;
    - more than one course of 28 consecutive days or less within the period from 12 months to 8 months prior to screening;
    - more than one course of 28 consecutive days or less within the period from 8 months to 4 months prior to screening.
    • Use of systemic antipseudomonal antibiotics within 28 days prior to study drug administration.
    • Use of macrolide antibiotics within 28 days prior to study drug administration.
    • Use of loop diuretics within 7 days prior to study drug administration.
    • Use of any investigational treatment within 28 days prior to study drug administration.
    • Initiation of treatment with dornase alpha within 28 days prior to study drug administration (subjects may be taking dornase alpha at the time of enrollment into TIP002, but they must have initiated treatment at least 28 days prior to study drug administration).
    Initiation of treatment with inhaled steroids (or increased dose) within 28 days prior to study drug administration (subjects may be taking inhaled steroids at the time of enrollment into TIP002, but they must have initiated treatment at least 28 days prior to study drug administration).
    E.5 End points
    E.5.1Primary end point(s)
    • Criteria for evaluation:
    Efficacy
    Primary Efficacy Variable
    • Relative change in FEV1 % predicted from baseline (week 1/cycle 1, day 1) to the end of cycle 1 dosing (week 5/cycle 1, day 28).
    Secondary Efficacy Variables
    • Time from start of first inhalation of blinded study drug to first antipseudomonal antibiotic use (IV alone, oral alone, and IV or oral) during either the blinded or open-label treatment periods.
    • Relative changes in FEV1 % predicted from baseline for subjects randomized to TIP, and from week 9 for subjects randomized to placebo, to all subsequent time points.
    • Among subjects randomized to placebo:
    - the relative change in FEV1 % predicted from cycle 1, day 28 (week 5) to cycle 2, day 28 (week 13);
    - the relative change in FEV1 % predicted from the mean of four assessments (weeks 1, 2, 5, and 9) to week 13.
    • Microbiology variables:
    - change in P aeruginosa (log10 colony forming units [CFU] per gm sputum) from baseline to weeks 5, 9, 13, 17, 21, and 25 (refer to Time and Events Table 2.1 1);
    - change in tobramycin minimum inhibitory concentration (MIC) susceptibility from baseline to weeks 5, 9, 13, 17, 21, and 25.
    Exploratory Efficacy Variables
    • Time from start of first inhalation of blinded study drug to first hospitalization due to respiratory events during either the blinded or open-label treatment periods.
    • Incidence of hospitalization and number of days hospitalized for respiratory SAEs.
    • Antipseudomonal antibiotic-free rate at weeks 9 and 25.
    • Hospitalization-free rate at weeks 9 and 25.
    • Antipseudomonal antibiotic-free and hospitalization-free rate at weeks 9 and 25.
    Safety
    • Incidence of treatment-emergent adverse events (AE).
    • Clinical laboratory test results.
    • Serum tobramycin concentrations.
    • Audiology test results (at select CF centers).
    • Acute change in airway reactivity (FEV1 % predicted) from predose to 30 minutes after completion of first dose of study drug.
    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 No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic Information not present in EudraCT
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) No
    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.8.5The trial involves multiple Member States Yes
    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 Information not present in EudraCT
    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 years1
    E.8.9.1In the Member State concerned months6
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years1
    E.8.9.2In all countries concerned by the trial months7
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 Yes
    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) Yes
    F.1.1.6Adolescents (12-17 years) Yes
    F.1.2Adults (18-64 years) Yes
    F.1.3Elderly (>=65 years) No
    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 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 2005-08-24. 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 state10
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 10
    F.4.2.2In the whole clinical trial 220
    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 Decision2005-09-19
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2005-07-13
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2007-02-28
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