Phase 3
Completed N=2,436
A Phase III Parallel Group Study, Comparing the Efficacy, Safety and Tolerability of the Fixed Dose Combination (FDC) of Fluticasone Furoate+Umeclidinium Bromide+Vilanterol (FF/UMEC/VI) With the FDC of FF/VI in Subjects With Inadequately Controlled Asthma
Source: ClinicalTrials.gov NCT02924688 ↗Enrolled (actual)
2,436
Serious AEs
5.4%
Results posted
Feb 2020
Primary outcomePrimary: Mean Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1) at Week 24 — 0.024; 0.120; 0.134; 0.076 Liters — p=<0.001
◆ Published Evidence
Established
30citations · ~10 / year
Clinic vs Home Spirometry for Monitoring Lung Function in Patients With Asthma.
Summary
A once-daily 'closed' triple FDC therapy of FF/UMEC/VI via a single ELLIPTA® dry powder inhaler (DPI) is being developed by GlaxoSmithKline (GSK) with the aim of providing a new treatment option for the management of asthma by improving lung function, health-related quality of life (HRQoL) and symptom control over established combination therapies. This is a phase III, multi-center, active-controlled, double-blind, parallel-group study to compare the efficacy, safety and tolerability of the FDC of FF/UMEC/VI with the FDC of FF/VI. This study has 5 phases: Pre-Screening (Visit 0), Screening/Run-in, Enrolment/Stabilization, Randomization/Treatment, and Follow up. At Visit 1 (Screening), subjects meeting all protocol defined inclusion/exclusion criteria will enter a 3-week run-in period and will receive fixed dose inhaled corticosteroid/long-acting beta agonist (ICS/LABA) (fluticasone/salmeterol, 250/50 micrograms (mcg), via the DISKUS® DPI) one inhalation twice a day. At Visit 2 (Enrolment), eligible subjects will be enrolled into the 2-week stabilization period to receive FF/VI (100/25 mcg via the ELLIPTA DPI once a day, in the morning). At the conclusion of the stabilization period (Visit 3), all subjects who meet the pre-defined randomization criteria will be randomized 1:1:1:1:1:1 during the treatment period to receive either FF/UMEC/VI (100/62.5/25 mcg; 200/62.5/25 mcg; 100/31.25/25 mcg; 200/31.25/25 mcg) or FF/VI (100/25 mcg; 200/25 mcg) via the ELLIPTA DPI once daily in the morning. The duration of the treatment period is variable but will be a minimum of 24 weeks and a maximum of 52 weeks. Subjects will have up to 6 on-treatment clinic visits scheduled at Visits 3, 4, 5, 6, 7 and 8/End of Study (EOS) (Weeks 0, 4, 12, 24, 36 and 52, respectively). A follow-up visit will be conducted approximately 7 days after the end of treatment period or, if applicable, after the early withdrawal visit. Subjects will be provided with short acting albuterol/salbutamol to be used on an as-needed basis (rescue medication) throughout the study. Approximately 2250 subjects will be randomized, with approximately 375 subjects randomized to each of the 6 double-blind treatment arms to ensure approximately 337 evaluable subjects per treatment arm. DISKUS and ELLIPTA are registered trademarks of GSK groups of companies.
Linked Publications (5)
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Clinic vs Home Spirometry for Monitoring Lung Function in Patients With Asthma.
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Effectiveness and tolerability of dual and triple combination inhaler therapies compared with each other and varying doses of inhaled corticosteroids in adolescents and adults with asthma: a systematic review and network meta-analysis.
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Efficacy and safety of once-daily, single-inhaler fluticasone furoate/umeclidinium/vilanterol versus fluticasone furoate/vilanterol in Japanese patients with inadequately controlled asthma: the CAPTAIN study.
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Evaluating Asthma Clinical Remission with Inhaled Therapy: Post Hoc Analyses of CAPTAIN.
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Population Pharmacokinetic Modeling of Fluticasone Furoate, Umeclidinium Bromide, and Vilanterol in Patients with Asthma, Using Data from a Phase IIIA Study (CAPTAIN).
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Mean Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1) at Week 24 |
0.024; 0.120; 0.134; 0.076; 0.157; 0.168 | <0.001 sig |
| SECONDARY Annualized Rate of Moderate and Severe Asthma Exacerbations |
0.70; 0.68; 0.61 | 0.778 |
| SECONDARY Mean Change From Baseline in Clinic FEV1 at 3 Hours Post Study Treatment at Week 24 |
0.132; 0.220; 0.243; 0.168; 0.256; 0.286 | <0.001 sig |
| SECONDARY Mean Change From Baseline in Asthma Control Questionnaire-7 (ACQ-7) Total Score at Week 24 |
-0.678; -0.734; -0.767 | 0.094 |
| SECONDARY Mean Change From Baseline in Saint George's Respiratory Questionnaire (SGRQ) Total Score at Week 24 |
-11.39; -10.29; -11.69 | 0.115 |
| SECONDARY Mean Change From Baseline in Evaluating Respiratory Symptoms (E-RS) Total Score Over Weeks 21 to 24 (Inclusive) of the Treatment Period |
-2.47; -2.60; -2.89 | 0.479 |
| SECONDARY Number of Participants With Any Serious Adverse Event (SAE) and Common (>=3%) Non-SAE |
136; 150; 135; 122; 127; 122 | — |
| SECONDARY Number of Participants With Abnormal Electrocardiogram (ECG) Findings |
115; 118; 109; 109; 106; 108 | — |
| SECONDARY Mean Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Week 24 |
1.6; 0.6; 1.1; 0.2; 0.8; 0.9 | 0.172 |
| SECONDARY Mean Change From Baseline in Pulse Rate at Week 24 |
-1.1; 0.2; -1.0; -0.7; -1.3; -0.5 | 0.034 sig |
| SECONDARY Number of Participants With Abnormal Clinical Chemistry Values |
2; 0; 0; 1; 0; 0 | — |
| SECONDARY Number of Participants With Abnormal Hematology Values |
0; 0; 0; 0; 0; 0 | — |
Eligibility Criteria
Inclusion Criteria for Screening
- Age: 18 years of age or older at the time of signing the informed consent.
- Diagnosis: Subjects with a diagnosis of asthma as defined by the National Institutes of Health at least one year prior to Visit 0.
- Symptomatic: Subjects with inadequately controlled asthma (ACQ-6 score >=1.5) despite ICS/LABA maintenance therapy at Visit 1.
- Asthma Control: In the 1 year prior to Visit 1
- A documented healthcare contact for acute asthma symptoms or
- A documented temporary change in asthma therapy for acute asthma symptoms, according to a pre-specified asthma action plan (or equivalent)
- Current Asthma Maintenance Therapy: Subjects are eligible if they have required daily ICS/LABA for at least 12 weeks prior to Visit 0 with no changes to maintenance asthma medications during the 6 weeks immediately prior to Visit 0 (including no changes to a stable total dose of ICS of >250 mcg/day fluticasone proprionate [FP, or equivalent]).
- Spirometry: A best pre-bronchodilator morning (ante meridian [AM]) FEV1 >=30% and =12% and >=200 milliliter (mL) increase in FEV1 between 20 and 60 minutes following 4 inhalations of albuterol/salbutamol aerosol at Visit 1.
- If the subject does not meet the above reversibility criteria at Visit 1 then the reversibility assessment may be repeated once within 7 days of Visit 1 if either criteria a) or b) are met: a) >=9% increase in FEV1 between 20 and 60 minutes following 4 inhalations of albuterol/salbutamol aerosol at Visit 1. b) Documented evidence of a reversibility assessment within 1 year prior to Visit 1 which demonstrated a post-bronchodilator increase in FEV1 of >=12% and >=200 mL.
Should the subject successfully demonstrate airway reversibility (defined as >=12% and >=200 mL increase in FEV1 between 20 and 60 minutes following 4 inhalations of albuterol/salbutamol aerosol) at the second attempt then, provided that all other eligibility criteria assessed at Visit 1 are met, the subject may enter the 3-week run-in period.
- Short-Acting beta2 Agonists (SABAs): All subjects must be able to replace their current SABA inhaler with albuterol/salbutamol aerosol inhaler at Visit 1 as needed for the duration of the study. Subjects must be judged capable of withholding albuterol/salbutamol for at least 6 hours prior to study visits.
- Male or eligible Female, defined as having documentation of non-reproductive potential or reproductive potential as follows:
A female subject is eligible to participate if she is not pregnant (as confirmed by a negative serum human chorionic gonadotrophin (hCG) test), not lactating, is not planning on becoming pregnant during the study and at least one of the following conditions applies: Non-reproductive potential defined as pre-menopausal females with documented tubal ligation or documented hysteroscopic tubal occlusion procedure with follow-up confirmation of bilateral tubal occlusion or hysterectomy or documented bilateral oophorectomy; Postmenopausal defined as 12 months of spontaneous amenorrhea with an appropriate clinical profile (e.g., age appropriate, >45 years, in the absence of hormone replacement therapy). In questionable cases for women =40 years of age.
- Concurrent respiratory disorders: Subjects with current evidence of pneumonia, active tuberculosis, lung cancer, significant bronchiectasis, sarcoidosis, lung fibrosis, pulmonary hypertension, interstitial lung diseases or other active pulmonary diseases or abnormalities other than asthma.
- Risk Factors for Pneumonia: Immune suppression (e.g., human immunodeficiency virus, Lupus) or other risk factors for pneumonia (e.g., neurological disorders affecting control of the upper airway, such as Parkinson's Disease, Myasthenia Gravis).
- Patients at potentially high risk (e.g., very low body mass index (BMI), severely malnourished, or very low FEV1) will only be included at the discretion of the Investigator.
- Other diseases/abnormalities: Subjects with historical or curre
Data sourced from ClinicalTrials.gov (NCT02924688) and the linked publication. 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.