A Randomized, Open-label, Multicenter, Phase 3 Trial to Assess the Safety of Tobramycin Inhalation Powder Compared to TOBI® in Cystic Fibrosis Subjects - ASPIRE II

• Register: EUCTR
• Last refreshed on: 24 January 2022
• Main ID: EUCTR2005-003772-37-GR
• Date of registration: 21/01/2008
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma Services AG
• Public title: A Randomized, Open-label, Multicenter, Phase 3 Trial to Assess the Safety of Tobramycin Inhalation Powder Compared to TOBI® in Cystic Fibrosis Subjects - ASPIRE II
• Scientific title: A Randomized, Open-label, Multicenter, Phase 3 Trial to Assess the Safety of Tobramycin Inhalation Powder Compared to TOBI® in Cystic Fibrosis Subjects - ASPIRE II
• Date of first enrolment: 03/06/2008
• Target sample size: 500
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2005-003772-37
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: yes; Single blind: no; Double blind: no; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: yes; Placebo: no; Other: no
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Germany, Greece, Hungary, Ireland, Italy, Spain, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
· Confirmed diagnosis of 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.
· Male and female subjects greater than or equal to 6 years of age at the time of screening.
· FEV1 at screening must be greater than or equal to 25% and less than or equal to 75% of normal predicted values for age, sex, and height based on Knudson criteria.
· P aeruginosa must be 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 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. The definition of effective contraception will be based on the judgment of the investigator or a designated associate. Acceptable methods of contraception include oral, depot and injectable contraceptives, total abstinence and surgical sterilization (e.g., bilateral tubal ligation). Double barrier methods (i.e. combination of: IUD, male or female condom with spermicidal gel, diaphragm, sponge, cervical cap) are acceptable with the exception of a combination of condom and diaphragm. Emergency contraceptive treatment after intercourse, coitus interruptus, single barrier methods and periodic abstinence (e.g. calendar, ovulation, symptothermal, post ovulation methods) are not considered effective forms of contraception.
· Provide written informed consent and assent (as appropriate) prior to the performance of any study-related procedure
Are the trial subjects under 18? yes
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
· History of sputum culture or deep-throat cough 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.
· History of hearing loss or chronic tinnitus deemed clinically significant by the investigator.
· Use of systemic or inhaled antipseudomonal 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 chronic macrolide therapy within 28 days prior to study drug administration (subjects may be taking chronic macrolide therapy at the time of enrollment into CTBM100C2302, but they must have initiated treatment more than 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 CTBM100C2302, but they must have initiated treatment more than 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 CTBM100C2302, but they must have initiated treatment more than 28 days prior to study drug administration).
· Initiation of treatment with inhaled hypertonic saline (HS) within 28 days prior to
study drug administration (subjects may be taking inhaled HS at the time of
enrollment into CTBM100C2302, but they must have initiated treatment more than
28 days prior to study drug administration and be on a stable regimen). In addition,
patients should be instructed to take their HS at least 30 minutes before their PFT.
Patients should be consistent with the timing of taking their HS at home, or clinic
prior to their PFT.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Pulmonary pseudomonas aeruginosa infections in patients with cystic fibrosis
Classification code 10011762

Intervention(s)

Product Name: Tobramycin Inhalation Powder (TIP)
Product Code: TBM100C
Pharmaceutical Form: Inhalation powder, hard capsule
INN or Proposed INN: Tobramycin
CAS Number: 32986-56-4
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 28-

Trade Name: TOBI
Product Name: TOBI
Pharmaceutical Form: Nebuliser solution
INN or Proposed INN: Tobramycin
CAS Number: 32986-56-4
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 60-

Primary Outcome(s)

Secondary Objective: The secondary objectives are: (a) to assess the efficacy of TIP as compared to TOBI, as measured by the relative change in forced expiratory volume at 1 second (FEV1 % predicted) from baseline to the end of cycle 3 dosing; and (b) to assess subject-reported treatment satisfaction by administering the Treatment Satisfaction Questionnaire for Medication (TSQM©).

Main Objective: The primary objective is to evaluate the safety in cystic fibrosis (CF) subjects of a twice-daily (BID) dosing regimen of Tobramycin Inhalation Powder (TIP) delivered by the T-326 Inhaler as compared to TOBI delivered with the PARI LC PLUS™ Jet Nebulizer and DeVilbiss PulmoAide™ compressor or a suitable alternative. Suitable compressors are those that, when attached to a PARI LC PLUS nebulizer, deliver a flow rate of 4 to 6 L/min and/or back pressure of 110 to 217 kPa.

Primary end point(s): Criteria for evaluation:
Safety
· Incidence of treatment-emergent adverse events (AE).
· Clinical laboratory test results.
· Serum tobramycin concentrations.
· Acute change in FEV1% predicted values from pre-dose to 30 minutes post-dose at
visits 2, 3, 5, 7, 8, 9, and 10.

Efficacy
· Relative changes of FEV1 % predicted from baseline to all scheduled posttreatment visits (weeks 2, 5, 9, 13, 17, 21, and 25).
· Area under the curve (AUC) of relative changes of FEV1% predicted from baseline (predose day 1) to all scheduled posttreatment visits (weeks 2, 5, 9, 13, 17, 21, and 25).
· Time from start of first inhalation of study drug to first antipseudomonal antibiotic use (IV alone, oral alone, and IV or oral).
· Time from start of inhalation of study treatment to first hospitalization due to serious respiratory-related AEs.

Treatment Satisfaction
· Treatment Satisfaction Questionnaire for Medication (TSQM) at end of each treatment cycle (weeks 5, 13, and 21) and upon early termination, if applicable.

Microbiology
· Change in P aeruginosa density (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).
· Change in P aeruginosa tobramycin minimum inhibitory concentration (MIC) susceptibility from baseline to weeks 5, 9, 13, 17, 21, and 25.

Administration Time
· For each treatment group, the administration time for doses administered in the clinic at visits 2, 3, 5, 7, 8, 9, and 10 (weeks 1, 2, 4, 9, 13, 17, and 21) will be recorded

Secondary ID(s)

2005-003772-37-GB

CTBM100C2302

Ethics review

Status: Approved
Approval date: 03/06/2008
Contact:

Results

• Results available: Yes
• Date Posted: 21/04/2016
• Date Completed: 12/03/2009
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2005-003772-37/results