Single Dose Study of the Effect of Formoterol Fumarate in Combination With Mometasone Furoate Inhaled Via a Pressurized Metered Dose Inhaler (pMDI) in Children Aged 5-11 Years Old With Persistent Asthma

Novartis

Status and phase: Completed; Phase 2

Conditions: Asthma

Treatments: Drug: Placebo to F12D; Drug: Placebo to F12M/MFF; Drug: Formoterol fumarate 12 μg pMDI (F12M); Drug: Formoterol fumarate 12 μg DPI (F12D); Drug: Mometasone furoate/formoterol fumarate (MFF)

Study type: Interventional

Funder types: Industry

Identifiers

NCT00746330

CMFF258C2204

Details and patient eligibility

About

This study is being conducted to compare the pharmacodynamics (bronchodilation, onset and duration of action), of a single dose of formoterol fumarate in combination with mometasone furoate to placebo in children of 5-11 years with persistent asthma. The study will also assess the bronchodilatory effect of a single dose of formoterol fumarate alone and in combination with mometasone furoate delivered via a pressurized metered dose inhaler (pMDI) to the bronchodilatory effect of formoterol fumarate delivered via a dry powder inhaler (DPI). Furthermore, pharmacokinetic assessments of plasma and urine will also be conducted throughout the study to assess systemic exposure following administration of the study medication.

Enrollment: 32 patients

Sex: All

Ages: 5 to 11 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 5 to 11 years of age of either sex and of any race
• A diagnosis (according to the Global Initiative for Asthma [GINA] guidelines) of persistent asthma for a period of at least 6 months prior to screening and must have been on a stable asthma regimen (daily dose unchanged) for at least 4 weeks prior to screening
• β2-agonist reversibility, defined as an increase in absolute FEV1 of ≥12% within 30 minutes after administration of 200μg of salbutamol without the use of a spacer or its equivalent in accordance with ATS/ERS standards
• A child must have an FEV1 of ≥ 60% and ≤ 90% of Polgar predicted when all restricted medications have been withheld for the appropriate intervals

Exclusion criteria

• Use of other investigational drugs at the time of enrolment, or within 30 days or 5 half-lives of enrolment, whichever is longer.
• History of malignancy of any organ system within past 5 years.
• Pre-dose change (increase or decrease) in absolute FEV1 of 15% at Visit 2, compared with value at screening.
• Hospitalized or had an emergency room treatment for an acute asthma exacerbation in the 1 month prior to Visit 1, or who had a clinical deterioration of asthma between Visits 1 and 2 that resulted in emergency treatment, hospitalization, or treatment with excluded asthma medication.
• Significant medication condition or situation.
• QTc > 440 msec (boys) or > 450 msec (girls) on electrocardiogram(ECG) assessment at screening.
• Upper or lower respiratory tract infection within 4 weeks prior to screening.
• Chronic conditions affecting the respiratory tract or chronic lung diseases.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Quadruple Blind

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32 participants in 4 patient groups

F12M - PL - F12D - MFF

Experimental group

Description:

Participants received a single dose of each treatment in the following order, separated by a washout period of 6-7 days: Period 1: Formoterol fumarate 12 μg via pMDI + placebo to formoterol fumarate via DPI; Period 2: Placebo to formoterol fumarate / mometasone furoate via pMDI + placebo to formoterol fumarate via DPI; Period 3: Placebo to formoterol fumarate / mometasone furoate via pMDI + formoterol fumarate via DPI; Period 4: Formoterol fumarate / mometasone furoate 10 μg / 100 μg via pMDI + placebo to formoterol fumarate via DPI. Participants were allowed to continue their regular asthma maintenance inhaled corticosteroid medication throughout the study and were supplied with the short-acting β2-agonist (SABA) salbutamol as rescue medication.

Treatment:

Drug: Formoterol fumarate 12 μg pMDI (F12M)

Drug: Placebo to F12M/MFF

Drug: Formoterol fumarate 12 μg DPI (F12D)

Drug: Mometasone furoate/formoterol fumarate (MFF)

Drug: Placebo to F12D

F12D - F12M - MFF - PL

Experimental group

Description:

Participants received a single dose of each treatment in the following order, separated by a washout period of 6-7 days: Period 1: Placebo to formoterol fumarate / mometasone furoate via pMDI + formoterol fumarate via DPI; Period 2: Formoterol fumarate 12 μg via pMDI + placebo to formoterol fumarate via DPI; Period 3: Formoterol fumarate / mometasone furoate 10 μg / 100 μg via pMDI + placebo to formoterol fumarate via DPI; Period 4: Placebo to formoterol fumarate / mometasone furoate via pMDI + placebo to formoterol fumarate via DPI. Participants were allowed to continue their regular asthma maintenance inhaled corticosteroid medication throughout the study and were supplied with the short-acting β2-agonist (SABA) salbutamol as rescue medication.

Treatment:

Drug: Formoterol fumarate 12 μg pMDI (F12M)

Drug: Placebo to F12M/MFF

Drug: Formoterol fumarate 12 μg DPI (F12D)

Drug: Mometasone furoate/formoterol fumarate (MFF)

Drug: Placebo to F12D

MFF - F12D - PL - F12M

Experimental group

Description:

Participants received a single dose of each treatment in the following order, separated by a washout period of 6-7 days: Period 1: Formoterol fumarate / mometasone furoate 10 μg / 100 μg via pMDI + placebo to formoterol fumarate via DPI; Period 2: Placebo to formoterol fumarate / mometasone furoate via pMDI + formoterol fumarate via DPI; Period 3: Placebo to formoterol fumarate / mometasone furoate via pMDI + placebo to formoterol fumarate via DPI; Period 4: Formoterol fumarate 12 μg via pMDI + placebo to formoterol fumarate via DPI. Participants were allowed to continue their regular asthma maintenance inhaled corticosteroid medication throughout the study and were supplied with the short-acting β2-agonist (SABA) salbutamol as rescue medication.

Treatment:

Drug: Formoterol fumarate 12 μg pMDI (F12M)

Drug: Placebo to F12M/MFF

Drug: Formoterol fumarate 12 μg DPI (F12D)

Drug: Mometasone furoate/formoterol fumarate (MFF)

Drug: Placebo to F12D

PL - MFF - F12M - F12D

Experimental group

Description:

Participants received a single dose of each treatment in the following order, separated by a washout period of 6-7 days: Period 1: Placebo to formoterol fumarate / mometasone furoate via pMDI + placebo to formoterol fumarate via DPI; Period 2: Formoterol fumarate / mometasone furoate 10 μg / 100 μg via pMDI + placebo to formoterol fumarate via DPI; Period 3: Formoterol fumarate 12 μg via pMDI + placebo to formoterol fumarate via DPI; Period 4: Placebo to formoterol fumarate / mometasone furoate via pMDI + formoterol fumarate via DPI. Participants were allowed to continue their regular asthma maintenance inhaled corticosteroid medication throughout the study and were supplied with the short-acting β2-agonist (SABA) salbutamol as rescue medication.

Treatment:

Drug: Formoterol fumarate 12 μg pMDI (F12M)

Drug: Placebo to F12M/MFF

Drug: Formoterol fumarate 12 μg DPI (F12D)

Drug: Mometasone furoate/formoterol fumarate (MFF)

Drug: Placebo to F12D