E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
pulmonary P aeruginosa infection in patient with cystic fibrosis |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10011762 |
E.1.2 | Term | Cystic fibrosis |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main 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). |
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E.2.2 | Secondary objectives of the trial |
to assess the safety and efficacy of TIP when administered to subjects who are dosed for more than one cycle |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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
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E.4 | Principal 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). |
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E.5 End points |
E.5.1 | Primary 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.
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | 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.8.5 | The trial involves multiple Member States | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial 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
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 7 |