Conditions: Asthma
Keywords: tolerability NEUMOTEROL efficacy budesonide/formoterol fumarate 400/12 mcg safety Asthma pharmacodynamics
Allocation: RANDOMIZED | Intervention model: CROSSOVER
Enrollment: 239
Healthy volunteers: no

Brief summary:
This Phase IV study is an a multi-centre, randomised open label, two way cross-over design to evaluate the efficacy, safety, and tolerability of NEUMOTEROL 400 in subjects with asthma. The study will be used to demonstrate the non-inferiority of Budesonide/Formoterol Fumarate combination (BFF) 400/12 micrograms (mcg) single capsule inhaler (NEUMOTEROL 400) compared with BFF 320/9 mcg SYMBICORT Forte TURBUHALER® inhaler.

The population for this study will be adult subjects (\>=18 and \<=80 years) with a diagnosis of asthma who have a pre-bronchodilator forced expiratory volume in one second (FEV1) of 40% to 85% of the predicted normal value, and are receiving a stable dose of inhaled corticosteroid inhaled corticosteroid (ICS) with or without long-acting beta-adrenergic agonist (LABA) prior to screening.

The study will consist of six phases: Prescreening, Screening/Run-in (4 weeks), Treatment Period 1 (4 weeks), Washout (minimum 4 weeks), Treatment Period 2 (4 weeks) and Follow-up (1 week). The total duration of the study for each subject will be at least 17 weeks. There will be up to 6 study visits and a follow-up telephone call.

Pre-screening Visit will allow subjects who had recent asthma medication changes to be stabilized prior to Screening. During the run-in and wash-out periods, all the subjects will receive budesonide dry powder inhaler (DPI) 400 mcg twice daily (BID) (NEUMOTEX™ 400) and salbutamol 100mcg pressurized metered dose inhaler (pMDI) on demand, as rescue medication. The dose of NEUMOTEROL 400 (400/12 mcg) and SYMBICORT Forte (320/9 mcg) will be one inhalation BID, and each treatment will be given to all subjects for 4 weeks (with a 4-week Washout Period between treatments).

The study will include 300 subjects for screening so that at least 210 will be randomised and a minimum of 168 subjects complete the study/are evaluable. Half the subjects will be on Regimen A in Treatment Period 1and will then be crossed over to Regimen B in Treatment Period 2, and vice versa. Regimen A: BFF (400/12 mcg) by single capsule inhaler. Regimen B: BFF (320/9 mcg) TURBUHALER inhaler. The treatment periods will be separated by a washout Period of 4 weeks.

NEUMOTEROL and NEUMOTEX are trademarks of the GSK group of companies SYMBICORT and TURBUHALER are trademarks of AstraZeneca

Detailed description:

Arms:
arm 1: Subjects will receive Regimen A in Treatment Period 1 followed by Regimen B in Treatment Period 2. The treatment periods will be separated by a wash out period of 4 weeks. Regimen A: Subjects will be instructed to take each morning and evening, 1 inhalation from a single capsule containing BFF (400/12 mcg) by single capsule inhaler. Regimen B: Subjects will be instructed to take each morning and evening,1 inhalation from BFF (320/9 mcg) TURBUHALER inhaler. arm 2: Subjects will receive Regimen B in Treatment Period 1 followed by Regimen A in Treatment Period 2. The treatment periods will be separated by a wash out period of 4 weeks. Regimen A: Subjects will be instructed to take each morning and evening, 1 inhalation from a single capsule containing BFF (400/12 mcg) by single capsule inhaler. Regimen B: Subjects will be instructed to take each morning and evening,1 inhalation from BFF (320/9 mcg) TURBUHALER inhaler.

Interventions: intervention 1: NEUMOTEROL 400 (BFF 400/12 mcg) single capsule inhaler intervention 2: SYMBICORT forte (BFF 320/9mcg) TURBUHALER inhaler intervention 3: NEUMOTEX 400 (Budesonide 400 mcg) intervention 4: Salbutamol 100 mcg pMDI
Intervention descriptions: intervention 1: Micronized 400 mcg budesonide+ 12 mcg formoterol fumarate along with micronized and crystalline lactose monohydrate (excipient), per capsule dispensed by single capsule inhaler, twice daily (administered once in the morning and once in the evening approximately 12 hours later). intervention 2: Unit dose containing 320 mcg budesonide and 9 mcg formoterol fumarate (as dihidrate) along with lactose monohydrate as excipient. Administered as inhalation by TURBUHALER inhaler, twice daily (once in the morning and once in the evening approximately 12 hours later) intervention 3: Budesonide 400mcg will be administered to all the subjects twice daily, during the Run-in and Washout Periods intervention 4: Salbutamol 100mcg will be administered as pMDI on demand, as rescue medication, throughout the entire study period until Visit 5

Protocol document: