Clinical trial NCT00918957: A Study of Tobramycin Inhalation Powder From a Modified Manufacturing Process Versus Placebo
Official title: A Randomized, Double-Blind, Placebo-Controlled, Multi-Center Phase III Study in Cystic Fibrosis (CF) Subjects to Assess Efficacy, Safety and Pharmacokinetics of Tobramycin Inhalation Powder From a Modified Manufacturing Process (TIPnew).
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Cystic Fibrosis
Keywords: Tobramycin Inhalation Powder
Cystic fibrosis
Lung diseases
Anti-Bacterial Agents
Treatment of infections with P. aeruginosa in cystic fibrosis subjects
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2009-06-11
Enrollment: 62
Sex: ALL
Minimum age (years): 6
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study is designed to show how well tobramycin inhalation powder works and how safe it is when produced by a modified manufacturing process


Eligibility criteria: Inclusion Criteria:

* Written informed consent given by adults or by the parents/legal guardian in combination with the patient's assent, if capable of assenting, before any assessment was performed
* Confirmed diagnosis of Cystic Fibrosis (CF) by the presence of one or more clinical features of CF in addition to:

  * a quantitative pilocarpine iontophoresis sweat chloride test of \>60 mEq/L; or
  * identification of well-characterized disease-causing mutations in each CFTR gene; or
  * an abnormal nasal transepithelial potential difference characteristic of CF.
* Forced Expiratory Volume in one second (FEV1) at screening must have been ≥25% and ≤80% of normal predicted values for age, sex, and height based on Knudson criteria
* P. aeruginosa must have been present in a sputum/deep-throat cough swab culture (or bronchoalveolar lavage \[BAL\]) within 6 months prior to screening and in the sputum/deep-throat cough swab culture at the screening visit
* Able to expectorate a sputum sample or provide a deep throat cough swab at screening
* Able to comply with all protocol requirements
* Use of an effective means of contraception in females of childbearing potential
* Clinically stable in the opinion of the investigator to be treated according to this protocol

Exclusion Criteria:

* FEV1 at baseline (Visit 2) \<25% or \>80% of normal predicted values for age, sex, and height based on Knudson criteria, and/or FEV1 at baseline (Visit 2) deviated by ≥10% from the FEV1 measured at screening (Visit 1)
* Any use of inhaled anti-pseudomonal antibiotics within 4 months prior to screening
* Any use of systemic anti-pseudomonal antibiotics within 28 days prior to study drug administration
* Serum creatinine 2 mg/dL or above, blood urea nitrogen (BUN) 40 mg/dL or above, or an abnormal urinalysis defined as 2+ or greater proteinuria
* Known local or systemic hypersensitivity to aminoglycosides or inhaled antibiotics
* Signs and symptoms of acute pulmonary disease, e.g. pneumonia, pneumothorax
* Administration of any investigational drug within 30 days prior to enrollment
* Any previous exposure to tobramycin dry powder for inhalation (TIP)
* Administration of loop diuretics within 7 days prior to study drug administration
* Initiation of treatment with chronic macrolide therapy within 28 days prior to study drug administration
* Initiation of treatment with dornase alfa within 28 days prior to study drug administration
* Initiation of treatment with inhaled steroids (or increased dose) within 28 days prior to study drug administration
* Initiation of treatment with inhaled hypertonic saline (HS) within 28 days prior to study drug administration
* Personal history of abnormal hearing or family history of abnormal hearing other than typical hearing loss associated with the aging process
* Known abnormal result from any audiology testing (defined as either a unilateral puretone audiometry test showing a threshold elevation \>20 dB at any frequency across the frequency range 0.25 kHz to 8 kHz or the absence of emission at the evoked otoacoustic emission test)
* 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 of more than 60 mL at any time within 30 days prior to study drug administration
* History of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years, regardless of evidence of local recurrence or metastases
* Patients with clinically significant laboratory abnormalities (not associated with the study indication) at screening
* Patients or caregivers with a history of noncompliance to medical regimens and patients or caregivers who are considered potentially unreliable
* Pregnant or nursing (lactating) women
* Women of child-bearing potential unless they used two reliable birth control methods

Other protocol-defined inclusion/exclusion criteria may apply

Primary outcomes:
measure: Relative Change From Baseline of Forced Expiratory Volume in One Second (FEV1) Percent Predicted to End of Dosing (Day 29)
timeFrame: Baseline, Day 29
measure: Pre-planned Sensitivity Analysis: Absolute Change From Baseline of Forced Expiratory Volume in One Second (FEV1) Percent (%) Predicted to End of Dosing (Day 29)
timeFrame: Baseline, Day 29
measure: Post-hoc: Relative Change From Baseline of Forced Expiratory Volume in One Second (FEV1) Percent Predicted to End of Dosing (Day 29) Without Outlier
timeFrame: Baseline, Day 29
Secondary outcomes:
measure: Change From Baseline of Forced Vital Capacity (FVC) Percent Predicted to End of Dosing (Day 29) and to the End of Off-cycle Period (Day 57)
timeFrame: Baseline, Day 29, Day 57
measure: Change From Baseline of Forced Expiratory Flow Rate Over 25 and 75 Percent. (FEF25-75%) Predicted to End of Dosing (Day 29) and End of Off-cycle Period (Day 57)
timeFrame: Baseline, Day 29, Day 57
measure: Absolute Change From Baseline to End of Dosing (Day 29) and End of Off-cycle Period (Day 57) in Sputum Pseudomonas Aeruginosa Density (log10 Colony Forming Units(CFU) Per Gram Sputum)
timeFrame: Baseline, Day 29, Day 57
measure: Change From Baseline to End of Dosing (Day 29) and End of Off-cycle Period (Day 57) of Pseudomonas Aeruginosa Minimum Inhibitory Concentration (MIC)
timeFrame: Baseline, Day 29, Day 57
measure: Shift From Baseline in Laboratory Parameters to Above Upper/Lower Limit of Normal
timeFrame: Baseline, Study completion
measure: Percentage of Participants With Adverse Events (AEs)
timeFrame: First administration of study drug, study completion
measure: Percentage of Participants With Serious Adverse Events (SAEs)
timeFrame: Time of consent, 4 weeks after study completion
measure: Acute Change in Airways Reactivity (FEV1 Percent Predicted) From Pre-dose to 30 Minutes After Completion of First Dose of Study Drug
timeFrame: Day 1, Day 29
measure: Tobramycin Serum Concentration
timeFrame: Pre-dose, 0 - 1 hour post-dose, 1 -2 hours post-dose, 2 - 6 hours post-dose
Other outcomes:
Locations:
city: Pleven
country: Bulgaria
facility: Novartis Investigative Site
city: Plovdiv
country: Bulgaria
facility: Novartis Investigative Site
city: Sofia
country: Bulgaria
facility: Novartis Investigative Site
city: Varna
country: Bulgaria
facility: Novartis Investigative Site
city: Alexandria
country: Egypt
facility: Novartis Investigative Site
city: Giza
country: Egypt
facility: Novartis Investigative Site
city: Tallin
country: Estonia
facility: Novartis Investigative Site
city: Tartu
country: Estonia
facility: Novartis Investigative Site
city: Chandigarh
country: India
facility: Novartis Investigative Site
city: Hyderabad
country: India
facility: Novartis Investigative Site
city: New Delhi
country: India
facility: Novartis Investigative Site
city: Vellore
country: India
facility: Novartis Investigative Site
city: Riga
country: Latvia
facility: Novartis Investigative Site
city: Kaunas
country: Lithuania
facility: Novartis Investigative Site
city: Vilnius
country: Lithuania
facility: Novartis Investigative Site
city: Bucuresti
country: Romania
facility: Novartis Investigative Site
city: Timisoara
country: Romania
facility: Novartis Investigative Site
city: Kazan
country: Russian Federation
facility: Novartis Investigative Site
city: Moscow
country: Russian Federation
facility: Novartis Investigative Site
city: Saint Petersburg
country: Russian Federation
facility: Novartis Investigative Site
city: Samara
country: Russian Federation
facility: Novartis Investigative Site
city: Voronezh
country: Russian Federation
facility: Novartis Investigative Site
city: Yaroslavi
country: Russian Federation
facility: Novartis Investigator Site
city: Durban
country: South Africa
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: Galeva I, Konstan MW, Higgins M, Angyalosi G, Brockhaus F, Piggott S, Thomas K, Chuchalin AG. Tobramycin inhalation powder manufactured by improved process in cystic fibrosis: the randomized EDIT trial. Curr Med Res Opin. 2013 Aug;29(8):947-56. doi: 10.1185/03007995.2013.805122. Epub 2013 Jun 5.