pulmonary P aeruginosa infection in patient with cystic fibrosis MedDRA version: 9.1 Level: LLT Classification code 10011762 Term: Cystic fibrosis
Conditions
Interventions
Product Name: Tobramycin Inhalation Powder
Product Code: TIP
Pharmaceutical Form: Inhalation powder
INN or Proposed INN: Tobramycine
Concentration unit: mg milligram(s)
Concentration type: equal
Conce
Sponsors
Novartis Pharma Services AG
Eligibility
Sex/Gender
All
Inclusion criteria
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 =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
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).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 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).;Secondary Objective: to assess the safety and efficacy of TIP when administered to subjects who are dosed for more than one cycle;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 r | — |
Countries
Lithuania
Outcome results
None listed