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

NCT00746330 | Completed Phase 2 Results

• 1 other identifier: CMFF258C2204
• Study Type: interventional
• Target: 32
• Locations: 3 countries
• Sites: 9

Brief Summary

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.

Conditions

Asthma

Keywords

Asthma; Children; Persistent asthma

Outcome Measures

Primary Outcomes (1)

• The Standardized Forced Expiratory Volume in 1 Second (FEV1) Using Area Under the Curve (AUC) From 0 to 12 Hours (0-12h) Post-dose by Treatment

  For FEV1 AUC(0-12h) the trapezoidal rule was applied using planned time measurements to calculate the AUC up to and including the last measurement recorded before intake of rescue medication. The AUC was standardized by dividing by the length of time for which measurements of FEV1 were included in the calculation of the AUC thus adjusting for subjects who were unable to complete the measurements during the 12-hour observation period and without inhaling rescue medication. The unit of the AUC was in L, being a weighted average of the acceptable FEV1 measurements recorded over 12 hours post dose

  From 0 to 12 Hours (0-12h) post-dose, after each treatment administered (approximately 1 treatment a week for 4 weeks of treatment).

Secondary Outcomes (5)

• Serial FEV1 Measurement (i.e. at 5, 30 Minutes and 1, 2, 4, 8 and 12 Hours Post-dose) Following Inhalation of a Single Dose of Study Medication to Evaluate the Onset and Duration of the Bronchodilatory Effect

  5, 30 Minutes and 1, 2, 4, 8 and 12 Hours Post-dose

• Serial Forced Vital Capacity (FVC) Measurement (i.e. at 5, 30 Minutes and 1, 2, 4, 8 and 12 Hours Post-dose) Following Inhalation of a Single Dose of Study Medication to Evaluate the Onset and Duration of the Bronchodilatory Effect

  5, 30 Minutes and 1, 2, 4, 8 and 12 Hours Post-dose

• Serial Peak Expiratory Flow Rate (PEF) Measurement (i.e. at 5, 30 Minutes and 1, 2, 4, 8 and 12 Hours Post-dose) Following Inhalation of a Single Dose of Study Medication to Evaluate the Onset and Duration of the Bronchodilatory Effect

  5, 30 Minutes and 1, 2, 4, 8 and 12 Hours Post-dose

• Plasma Formoterol Concentrations (Pmol/L) Following a Single Dose of Formoterol Fumarate Alone and in Combination With Mometasone Furoate Via the pMDI and Formoterol Fumarate Via the Dry Powder Inhaler (DPI)

  5, 30 Minutes and 1, 2, 4, 8 and 12 Hours Post-dose

• Urinary Excretion of Formoterol Following a Single Dose of Formoterol Fumarate Alone and in Combination With Mometasone Furoate Via the pMDI and Formoterol Fumarate Via the Dry Powder Inhaler (DPI)

  0 to 3 hrs and 0-12 hrs

Study Arms (4)

F12M - PL - F12D - MFF

EXPERIMENTAL

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.

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

F12D - F12M - MFF - PL

EXPERIMENTAL

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.

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

MFF - F12D - PL - F12M

EXPERIMENTAL

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.

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

PL - MFF - F12M - F12D

EXPERIMENTAL

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.

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

Interventions

Mometasone furoate/formoterol fumarate (MFF) DRUG

Formoterol fumarate dihydrate / mometasone furoate combination product 10 μg / 100 μg delivered via Pressurized Metered Dose Inhaler (pMDI). One dose consisted of 2 puffs x 5 μg / 50 μg.

F12D - F12M - MFF - PL; F12M - PL - F12D - MFF; MFF - F12D - PL - F12M; PL - MFF - F12M - F12D

Formoterol fumarate 12 μg pMDI (F12M) DRUG

Formoterol fumarate dihydrate 12 μg delivered via Pressurized Metered Dose Inhaler (pMDI) (1 dose = 2 puffs x 6 μg).

F12D - F12M - MFF - PL; F12M - PL - F12D - MFF; MFF - F12D - PL - F12M; PL - MFF - F12M - F12D

Formoterol fumarate 12 μg DPI (F12D) DRUG

Formoterol fumarate dihydrate 12 μg delivered via Dry Powder Inhaler (DPI).

F12D - F12M - MFF - PL; F12M - PL - F12D - MFF; MFF - F12D - PL - F12M; PL - MFF - F12M - F12D

Placebo to F12D DRUG

Placebo to formoterol fumarate DPI delivered via DPI

F12D - F12M - MFF - PL; F12M - PL - F12D - MFF; MFF - F12D - PL - F12M; PL - MFF - F12M - F12D

Placebo to F12M/MFF DRUG

Placebo to formoterol fumarate pMDI and formoterol fumarate / mometasone furoate delivered via pMDI

F12D - F12M - MFF - PL; F12M - PL - F12D - MFF; MFF - F12D - PL - F12M; PL - MFF - F12M - F12D

Eligibility Criteria

• Age: 5 Years - 11 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Novartis: lead
• Schering-Plough: collaborator

Study Sites (9)

Novartis Investigative Site

Mobile, Alabama, 36608, United States

Location

Novartis Investigative Site

Huntington Beach, California, 92647, United States

Location

Novartis Investigative Site

Orange, California, 92868, United States

Location

Novartis Investigative Site

Hialeah, Florida, 33012, United States

Location

Novartis Investigative Site

Pensacola, Florida, 32503, United States

Location

Novartis Investigative Site

Oklahoma City, Oklahoma, 73112, United States

Location

Novartis Investigative Site

Barranquilla, Colombia

Location

Novartis Investigative Site

Bogotá, Colombia

Location

Novartis Investigative Site

Lima, Peru

Location

MeSH Terms

Conditions

Asthma

Interventions

Mometasone Furoate; Formoterol Fumarate

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

862-778-8300

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: September 3, 2008
• First Posted: September 4, 2008
• Study Start: August 1, 2008
• Primary Completion: April 1, 2009
• Study Completion: April 1, 2009
• Last Updated: June 7, 2011
• Results First Posted: April 14, 2011

Record last verified: 2011-06

Locations

US (6); CO (2); PE (1)