Phase 4
Completed N=199
A Non-inferiority Study to Evaluate Efficacy, Safety and Tolerability of NEUMOTEROL® 400 and SYMBICORT® Forte in Adults With Asthma
Source: ClinicalTrials.gov NCT02233803 ↗Enrolled (actual)
199
Serious AEs
0.5%
Results posted
Aug 2017
Primary outcomePrimary: Change From Baseline (BL) in Trough Morning Forced Expiratory Volume in One Second (FEV1) at Day (D)29 — 0.194; 0.150 Litre (L)
◆ Published Evidence
No publication linked
No peer-reviewed publication reporting this trial's results has been linked yet. This can indicate results are unpublished — a known publication-bias signal. We re-check periodically.
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
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Change From Baseline (BL) in Trough Morning Forced Expiratory Volume in One Second (FEV1) at Day (D)29 |
0.194; 0.150 | — |
| SECONDARY FEV1 Area Under the Curve (AUC) (0-10 h) at D1 of Each TP |
24.573; 23.593 | — |
| SECONDARY Change From BL in Asthma Control Test (ACT) at 4 Wks for Each TP |
1.6; 1.0 | — |
Eligibility Criteria
Inclusion Criteria
- Male or female >=18 and 40 milli-international unit/milliliter (mIU/mL) and oestradiol =40% to =12% and >=200 mL reversibility of FEV1 within 10 to 40 minutes after 2 to 4 inhalations of salbutamol inhalation aerosol (or equivalent nebulised treatment with salbutamol solution) at Visit 1 (Screening and Run-in Visit)
- Current anti-asthma therapy: All subjects must be using an ICS with or without LABA for at least 8 weeks and a stable dose for at least 4 weeks before Visit 1 (Screening and Run-in Visit). Two populations are eligible for enrolment: Subjects maintained on ICS monotherapy (Budesonide 400 mcg to 800 mcg BID or equivalent) for at least 8 weeks and a stable dose for at least 4 weeks before Visit 1 (Screening and Run-in Visit) or Subjects maintained on an ICS/LABA combination product (e.g., NEUMOTEROL 200/6 BID or 400/12 mcg BID or equivalent by other combination products or by separate inhalers) for at least 8 weeks and a stable dose for at least 4 weeks before Visit 1 (Screening and Run-in Visit). Subjects taking budesonide/formoterol as needed must switch to maintenance dosing (excluding the highest dose) with use of a SABA for symptom relief at least 8 weeks and a stable dose for at least 4 weeks before Visit 1 (Screening and Run-in Visit). NOTE: Subjects on low dose ICS monotherapy should only be enrolled, if, in the opinion of the investigator, after review of their medical history and clinical examination, they will be able to benefit from both an increase in ICS dose and the addition of LABA therapy arising from and ICS/LABA combination
- Ability to withhold LABA therapy : Other than what is provided during the study, LABA therapy is not permitted on the day of Visit 1(Screening and Run-in Visit) and throughout the entire study. The last dose of pre-study LABA and LABA/ICS combinations are to be taken on the day before Visit 1. According to investigators judgement, patients should be able to withhold LABA therapy during the run-in and wash-out period.
- SABA: All subjects must be able to replace their current SABA treatment with rescue salbutamol at Visit 1 (Screening and Run-in Visit) for use as needed for the duration of the study. Subjects must be able to withhold salbutamol for at least 6 hours before each study visit
- Liver safety criteria: Alanine aminotransferase (ALT) 1.5×ULN is acceptable if bilirubin is fractionated and direct bilirubin is 160 millimeter mercury [mmHg], or diastolic BP >100 mmHg), Recent or poorly controlled peptic ulcer, Haematologic, hepatic, or renal disease, Immunologic compromise, Current malignancy(History of malignancy is acceptable only if subject has been in remission for one year before Visit 1 (Screening and Run-in Visit) (remission = no current evidence of malignancy and no treatment for the malignancy in the 12 months before Visit 1 [Screening and Run-in Visit]), Tuberculosis (current or untreated) (subjects with a history of tuberculosis infection who have completed an appropriate course of anti-tuberculous treatment may be suitable for study entry provided that there is no clinical suspicion of active or recurrent disease), Cushing's disease, Addison's disease, uncontrolled diabetes mellitus, uncontrolled thyroid disorder and recent history of drug or alcohol abuse.
- Evidence of a severe exacerbation, defined as deterioration of asthma requiring the use of systemic corticosteroids (tablets, suspension, or injection) for at least 3 days or an in-patient hospitalisation or emergency department visit due to asthma that required systemic corticosteroids between Visit 1 (Screening and Run-in Visit) and Visit 2 (randomization and Treatment Period 1 Baseline Visit)
- Oropharyngeal examination: A subject will not be eligible for the Run-in if he/she has clinical visual evidence of candidiasis at Visit 1(Screening and Run-in Visit)
- Investigational medications: A subject must not have administered any investigational drug within 30 days before Visit 1(
Data sourced from ClinicalTrials.gov (NCT02233803). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.