Short-term growth study in children with asthma treated with fluticasone propionate / formoterol spray (flutiform®).

• Register: EUCTR
• Last refreshed on: 2 February 2015
• Main ID: EUCTR2013-004719-32-DK
• Date of registration: 07/01/2014
• Prospective Registration: Yes
• Primary sponsor: Mundipharma Research Ltd
• Public title: Short-term growth study in children with asthma treated with fluticasone propionate / formoterol spray (flutiform®).
• Scientific title: A single (assessor) - blind, randomised, three-period, cross-over study to compare the safety of flutiform® pMDI, fluticasone pMDI and beclometasone Autohaler® in paediatric subjects aged 5 to less than 12 years with mild persistent asthma by means of knemometry. - FLT2504
• Date of first enrolment: 07/01/2014
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-004719-32
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: yes Double blind: no Parallel group: no Cross over: yes Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no Number of treatment arms in the trial: 3

Countries of recruitment

Denmark

Contacts

• Name: European Medical Operations
• Affiliation: Mundipharma Research Ltd

• Name: European Medical Operations
• Affiliation: Mundipharma Research Ltd

Key inclusion & exclusion criteria

Inclusion criteria:
1.Male and Female subjects 5 to <12 years old. Female subjects must be pre-menarche to be eligible.
2.Subjects must be pre-adolescent without any signs of puberty (acc. to Tanner scale).
3.Subjects are in normal range for their age in height and weight. Weight and height measurements should fall within the percentile range 3-97-% of normal values for age according to Danish growth charts.
4.Known history of mild intermittent or persistent reversible asthma for = 3 months prior to the screening visit.
5.Require:
a.only inhaled SABA therapy (e.g. Bricanyl Turbuhaler) on an as required basis, and/or
b.Regular non-ICS controller medications for asthma (e.g., cromones or leukotriene receptor antagonists) at a stable dose for = 3 months prior to the screening visit.
6.No ICS for >2 weeks prior to the screening visit.
7.Demonstrates adequate spirometry technique and able to use a home PEFR meter.
8.Demonstrated FEV1 of = 80% predicted value at visit 1following appropriate withholding of asthma medications (if applicable) (no SABA use within 6 hours of the PFT).
9.Demonstrated satisfactory technique in the use of the pMDI plus spacer and Autohaler devices.
10.Must be continent of urine and willing to perform (with parental/guardian help) overnight urine collections.
11.Willing and able to complete morning and evening PEFR measures with the help of a parent or guardian, if necessary, and attend all study visits.
12.Willing and able to substitute pre-study prescribed inhaled asthma medication for the entire duration of the study with study medication.
13.Written informed consent obtained as per national laws.

Inclusion Criteria required following run-in:
14.FEV1 within =20% of the visit 1 value following appropriate withholding of rescue medication (no Airomir Autohaler use within 6 hours of the PFT).
15.Rescue medication use on =2 days during the last 7 days of the run in period.

Are the trial subjects under 18? yes
Number of subjects for this age range: 48
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1.Require medications other than inhaled SABAs and/or regular non-ICS controller medications (e.g., cromones or leukotriene receptor antagonists) to maintain asthma control.
2.ICS use within = 2 weeks prior to the screening visit.
3.Any asthma exacerbation of any severity for at least 3 months prior to the screening visit.
4.Any fracture in the leg to be measured by knemometry =6 months prior to the screening visit.
5.Any metabolic disorders or other diseases that may impact on normal growth patterns.
6.Near fatal or life-threatening asthma within the past year.
7.Hospitalisation or an emergency visit for asthma within the past 6 months.
8.History of oral or injectable corticosteroid medication =3 months prior to the screening visit.
9.Evidence of a clinically unstable disease, as determined by medical history, clinical laboratory tests, and physical examination that, in the Investigator’s opinion, preclude entry into the study. “Clinically significant” is defined as any disease that, in the opinion of the Investigator, would put the subject at risk through study participation, or which would affect the outcome of the study.
10.No major surgery requiring general anesthesia for at least 3 months prior to the screening visit.
11.No febrile illnesses with temperature > 39°C within a week of the screening visit.
12.In the Investigator’s opinion a clinically significant upper or lower respiratory infection within 4 weeks prior to the screening visit.
13.Significant, non-reversible active pulmonary disease (e.g. cystic fibrosis, bronchiectasis, tuberculosis).
14.Subjects who have taken ß- blocking agents, tricyclic antidepressants, monoamine oxidase inhibitors, astemizole (Hismanal), quinidine type antiarrythmics, or potent CYP 3A4 inhibitors such as ketoconazole within 1 week prior to the screening visit.
15.Current use of medications, other than those allowed in the protocol.
16.Current evidence of hypersensitivity or idiosyncratic reaction to test medications or components.
17.Receipt of an Investigational medicinal product within 30 days of the screening visit.



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

Health Condition(s) or Problem(s) studied

Mild persistent asthma
MedDRA version: 16.1 Level: LLT Classification code 10003555 Term: Asthma bronchial System Organ Class: 100000004855

Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]

Intervention(s)

Trade Name: flutiform
Product Name: flutiform pMDI 50ug/5ug
Pharmaceutical Form: Pressurised inhalation, suspension
INN or Proposed INN: Fluticasone propionate
CAS Number: 80474-14-2
Other descriptive name: FLUTICASONE PROPIONATE
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 50-
INN or Proposed INN: Formoterol Fumarate Dihydrate
CAS Number: 43229-80-7
Other descriptive name: FORMOTEROL FUMARATE DIHYDRATE
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 5-

Trade Name: Flixotide
Product Name: fluticasone pMDI 50ug
Pharmaceutical Form: Pressurised inhalation, suspension
INN or Proposed INN: Fluticasone propionate
CAS Number: 80474-14-2
Other descriptive name: FLUTICASONE PROPIONATE
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 50-

Trade Name: Aerobec Autohaler ®
Product Name: Beclometasone Autohaler® 50ug
Pharmaceutical Form: Pressurised inhalation, solution
INN or Proposed INN: BECLOMETASONE DIPROPIONATE
CAS Number: 5534-09-8
Other descriptive name: BELCOMETASONE DIPROPIONATE
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 50-

Primary Outcome(s)

Main Objective: •To show non-inferiority of flutiform pMDI 50/5 µg (2 puffs bid) versus fluticasone pMDI 50 µg (2 puffs bid) based on the mean lower leg growth rates.

Secondary Objective: Secondary Objectives:
•To compare the safety of flutiform pMDI 50/5 µg (2 puffs bid) versus fluticasone pMDI 50 µg (2 puffs bid) based on overnight urinary free cortisol (corrected for creatinine).

Exploratory Objectives:
•To compare mean lower leg growth rates with flutiform pMDI 50/5 µg and fluticasone pMDI 50 µg versus beclometasone Autohaler 50 µg.

•To compare the safety of flutiForm pMDI 50/5 µg and fluticasone pMDI 50 µg to beclometasone Autohaler 50 µg based on overnight urinary free cortisol (corrected for creatinine).

•To compare the efficacy of flutiForm pMDI 50/5 µg, fluticasone pMDI 50 µg and beclometasone Autohaler 50 µg by means of FEV1, PEFR, rescue medication use, asthma exacerbations asthma symptoms and activity limitations.

Timepoint(s) of evaluation of this end point: Subjects randomised to receive one 1 of 3 possible treatment sequences outlined below:-
1)Treatment A:-Flutiform 50/5ug(2 puffs bid) pMDI
2)Treatment B:-Fluticasone 50ug(2 puffs bid) pMDI
3)Treatment C:-Beclometasone 50ug(2 puff bid)

Each Treatment Phase is 14 days, separated by 14 days for the wash-out period.

Measurement of lower leg growth using the knemometer will be taken at each visit by an assessor who is blinded to the study treatment. Knemometry measurements at visits 1 to 7 taken at the same time (+/-1hour) on the same day of the week wherever possible, corresponding to the beginning and the end of each treatment or wash-out period.

Primary end point(s): Mean lower leg growth rate during each period

Secondary Outcome(s)

Secondary end point(s): •Mean 12-hour urinary free cortisol (corrected for creatinine) during each period.
•Spontaneously reported adverse events.
•Mean FEV1 at clinic visits.
•Mean daily PEFR during each period.
•Days of rescue medication use during each period.
•Number (%) of asthma exacerbations during each period.
•Number (%) of asthma symptoms during each period.
•Number % of subjects who experienced any activity limitation due to asthma during each period.
•Study medication use (compliance) during treatment period.

Timepoint(s) of evaluation of this end point: •12-hour urinary free cortisol (corrected for creatinine) during each period - overnight urine collections at end of each treatment phase.
•Spontaneously reported adverse events collected at during of study
•FEV1 at clinic visits.
•Daily PEFR during each period - morning & evening
•Days of rescue medication use during each period.
•Number (%) of asthma exacerbations during each period - day and evening
•Number (%) of asthma symptoms during each period.
•Number % of subjects who experienced any activity limitation due to asthma during each period.
•Study medication use (compliance) during treatment period.

Refer to protocol for full details

Secondary ID(s)

none

FLT2504

Source(s) of Monetary Support

Mundipharma Research Ltd