A Study of Tobramycin Inhalation Powder From a Modified Manufacturing Process Versus Placebo

NCT ID: NCT00918957

Last Updated: 2012-10-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 62 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-06-30
• Study Completion Date: 2011-05-31

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

Conditions

Cystic Fibrosis

Keywords

Tobramycin Inhalation Powder; Cystic fibrosis; Lung diseases; Anti-Bacterial Agents; Treatment of infections with P. aeruginosa in cystic fibrosis subjects

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

TIP (Tobramycin Inhalation Powder)

Tobramycin 28 mg powder. The TIP dose of 112 mg twice a day (bis in diem = b.i.d.), given in a cycle of 28 days on treatment followed by 28 days off treatment.

Group Type: EXPERIMENTAL

Tobramycin Inhalation Powder

Intervention Type: DRUG

Tobramycin Inhalation Powder as produced by a modified manufacturing process TIP. TIP was provided in hard capsules each containing 28 mg active ingredient (tobramycin); Capsules were packaged in blister cards and administered by the T-326 Inhaler.

Placebo

Placebo 20 mg powder capsules. The dose regimen for the reference product was inhaling the contents of four capsules twice a day (bis in diem = b.i.d.), in the morning and in the evening for 28 days (on treatment), followed by 28 days of no study treatment (off treatment).

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo inhalation powder consisting of the excipients used for TIP. Placebo was provided in hard capsules, containing 20 mg placebo powder, which were packaged in blister cards, matching in appearance to TIP. Capsules were administered by the T-326 Inhaler.

Interventions

Tobramycin Inhalation Powder

Tobramycin Inhalation Powder as produced by a modified manufacturing process TIP. TIP was provided in hard capsules each containing 28 mg active ingredient (tobramycin); Capsules were packaged in blister cards and administered by the T-326 Inhaler.

Intervention Type: DRUG

Placebo

Placebo inhalation powder consisting of the excipients used for TIP. Placebo was provided in hard capsules, containing 20 mg placebo powder, which were packaged in blister cards, matching in appearance to TIP. Capsules were administered by the T-326 Inhaler.

Intervention Type: DRUG

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

• Minimum Eligible Age: 6 Years
• Maximum Eligible Age: 21 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

Novartis Investigative Site

Pleven, , Bulgaria

Novartis Investigative Site

Plovdiv, , Bulgaria

Novartis Investigative Site

Sofia, , Bulgaria

Novartis Investigative Site

Varna, , Bulgaria

Novartis Investigative Site

Alexandria, , Egypt

Novartis Investigative Site

Giza, , Egypt

Novartis Investigative Site

Tallinn, , Estonia

Novartis Investigative Site

Tartu, , Estonia

Novartis Investigative Site

Chandigarh, , India

Novartis Investigative Site

Hyderabad, , India

Novartis Investigative Site

New Delhi, , India

Novartis Investigative Site

Vellore, , India

Novartis Investigative Site

Riga, , Latvia

Novartis Investigative Site

Kaunas, , Lithuania

Novartis Investigative Site

Vilnius, , Lithuania

Novartis Investigative Site

Bucharest, , Romania

Novartis Investigative Site

Timișoara, , Romania

Novartis Investigative Site

Kazan', , Russia

Novartis Investigative Site

Moscow, , Russia

Novartis Investigative Site

Saint Petersburg, , Russia

Novartis Investigative Site

Samara, , Russia

Novartis Investigative Site

Voronezh, , Russia

Novartis Investigator Site

Yaroslavi, , Russia

Novartis Investigative Site

Durban, , South Africa

Countries

Bulgaria; Egypt; Estonia; India; Latvia; Lithuania; Romania; Russia; South Africa

References

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.

Reference Type: DERIVED

PMID: 23672633 (View on PubMed)

Other Identifiers

2008-002318-22

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CTBM100C2303

Identifier Type: -

Identifier Source: org_study_id