Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
| NCT ID | Title | Phase | Status | Enrollment | Velocity | Design | Start | Completion | Last Updated | Sites | Countries |
|---|---|---|---|---|---|---|---|---|---|---|---|
| NCT02257385 | Comparative Study of Umeclidinium/Vilanterol (UMEC/VI) in a Fixed Dose Combination With Indacaterol Plus Tiotropium | PHASE3 | COMPLETED | 967 | — | — | Oct 15, 2014 | May 4, 2015 | Mar 1, 2018 | 84 | Argentina, Chile +10 |
| NCT02152605 | A Phase IIIb Study to Evaluate the Efficacy of Umeclidinium/Vilanterol (UMEC/VI) in Subjects With Chronic Obstructive Pulmonary Disease (COPD) | PHASE3 | COMPLETED | 498 | — | — | Sep 1, 2014 | Mar 5, 2015 | Nov 9, 2017 | 54 | United States, Bulgaria +5 |
| NCT01879410 | A Study to Compare the Efficacy and Safety of Umeclidinium/Vilanterol With Fluticasone Propionate/Salmeterol in Subjects With Chronic Obstructive Pulmonary Disease (COPD) | PHASE3 | COMPLETED | 700 | — | — | Jun 13, 2013 | Jan 9, 2014 | Nov 8, 2017 | 72 | United States, Chile +5 |
| NCT01899638 | Pharmacokinetics Of Umeclidinium and Vilanterol in Healthy Chinese, a Randomized, Open Label, 3 Crossover Study. | PHASE1 | COMPLETED | 20 | — | — | May 20, 2013 | Jul 25, 2013 | Jun 7, 2017 | 1 | China |
| NCT01691547 | A Study to Assess the Systemic Exposure, Systemic Pharmacodynamics and Safety and Tolerability of FluticasoneFuroate, Umeclidinium and Vilanterol in Healthy Subjects | PHASE1 | COMPLETED | 44 | — | — | Dec 17, 2012 | Mar 8, 2013 | Jul 26, 2017 | 1 | United States |
FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in 1 second. BL was the mean of the 2 assessments made 30 and 5 minutes (min) pre-dose (PD) on Day 1. Trough FEV1 measurements were taken electronically by spirometry on Days 2, 28, 56, 84 and 85. Trough FEV1 on Day 85 is defined as the mean of the FEV1 values obtained at 23 and 24 hours (hr) after dosing on Day 84 (at Week 12 + 1 day). Analysis was performed using mixed model repeated measures (RM) with covariates of trt, BL FEV1 (mean of values measured at 30 and 5 min PD on Day 1), center group, day, day by BL interaction and day by trt interaction, where day was nominal.
The SGRQ is a disease-specific questionnaire, self-completed by participants(par), used to evaluate the effect of UMEC/VI on health-related quality of life as compared to placebo in par with COPD. The scores range from 0 (minimum, best possible health status) to 100 (maximum, worst possible health status). The SGRQ contains 76 items grouped into three domains (symptoms, activity and impacts). Analysis was performed using mixed model repeated measures with covariates of Baseline (scores recorded prior to dosing on Day 1) SGRQ total score, centre group, smoking status, Day, treatment(trt), Day by Baseline interaction and Day by trt interaction, where Day is nominal. Change from Baseline at a particular visit was calculated as the SGRQ total score at that visit minus Baseline. Change from Baseline in total score of -4 units or lower is considered as clinically meaningful improvement in quality of life.
FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. The weighted mean was calculated from the pre-dose FEV1 and post-dose FEV1 measurements at 5 and 15 minutes and 1, 3, 6, 9, 12 hours (pre-evening dose), 13, 15, 18, 23, and 24 hours after the morning dose. Baseline is defined as the mean of the assessments made 30 and 5 minutes (min) pre-dose on treatment Day 1. Analysis was performed using an analysis of covariance model with covariates of baseline FEV1 (mean of the two assessments made 30 mins and 5 mins pre-dose on Day 1), smoking status, and treatment. Change from baseline was calculated as the value at Day 84 minus the value at Baseline.
For both single dose and repeat dose
For both single dose and repeat dose
For both single dose and repeat dose
For both single dose and repeat dose
For both single dose and repeat dose
For both single dose and repeat dose
For single dose
For single dose
For both single dose and repeat dose
For repeat dose
For repeat dose
For repeat dose
For repeat dose
For repeat dose
The PK parameters and plasma concentrations: area under the concentration time-curve (AUC) from time zero to infinity (AUC(0-inf)) or AUC from time zero to last time of quantifiable concentration AUC(0-t') and maximum observed plasma concentration (Cmax) will be derived for each treatment group following single inhaled doses (four inhalations) of FF/UMEC/VI, UMEC/VI and FF/VI using the following treatment ratios: FF:FF/UMEC/VI versus FF/VI, UMEC:FF/UMEC/VI versus UMEC/VI, VI: FF/UMEC/VI versus UMEC/VI and VI: FF/UMEC/VI versus FF/VI.
| Arm | Type | Description |
|---|---|---|
| UMEC/VI arm | EXPERIMENTAL | Participants will be instructed to self-administer one dose each morning of UMEC/VI Inhalation Powder 62.5/25 mcg once daily via ELLIPTA DPI, placebo once daily via HANDIHALER inhaler and placebo once daily via BREEZHALER inhaler |
| Tiotropium + Indacaterol arm | PLACEBO_COMPARATOR | Participants will be instructed to self-administer one dose each morning of Tiotropium bromide 18 mcg once daily via HANDIHALER inhaler, Indacaterol 150 mcg once daily via BREEZHALER inhaler and placebo once daily via ELLIPTA DPI |
| Umeclidinium/Vilanterol 62.5/25 mcg once daily | EXPERIMENTAL | The subjects will receive UMEC/VI 62.5/25 mcg, administered as one inhalation once-daily in the morning via a dry powder inhaler (DPI) |
| Placebo once daily | PLACEBO_COMPARATOR | The subjects will receive placebo, administered as one inhalation once-daily in the morning via a DPI |
| UMEC/ VI via NDPI + placebo ACCUHALER/DISKUS arm | EXPERIMENTAL | Subjects will receive one inhalation of UMEC/VI 62.5/25 mcg once-daily in the morning via the NDPI and one inhalation of placebo in the morning and evening via ACCUHALER/DISKUS inhaler |
| FSC via ACCUHALER/DISKUS + placebo NDPI arm | ACTIVE_COMPARATOR | Subjects will receive one inhalation of FSC 250/50 mcg in the morning and evening via ACCUHALER/DISKUS inhaler and one inhalation of placebo administered once-daily in the morning via NDPI |
| UMEC/VI 125/25 mcg | EXPERIMENTAL | Combination in high dose |
| UMEC/VI 62.5/25 mcg | EXPERIMENTAL | Combination in low dose |
| UMEC 125 mcg | EXPERIMENTAL | LAMA mono in high dose |
| UMEC 62.5 mcg | EXPERIMENTAL | LAMA mono in low dose |
| VI 25 mcg | EXPERIMENTAL | LABA mono |
| UMEC/VI+FF | EXPERIMENTAL | UMEC (500 µg)/VI(100 µg) (blended together) and FF (400 µg) will be administered as single dose (4 inhalations); as dry powder in NDPI device once in 7 days in one of the 4 Treatment Periods of the study. |
| UMEC+VI | EXPERIMENTAL | UMEC (500 µg) and VI (100 µg) will be administered as single dose (4 inhalations); as dry powder in NDPI device once in 7 days in one of the 4 Treatment Periods of the study. |
| FF+VI | EXPERIMENTAL | FF (400 µg) and VI (100 µg) will be administered as single dose (4 inhalations); as dry powder in NDPI device once in 7 days in one of the 4 Treatment Periods of the study. |
| FF+UMEC | EXPERIMENTAL | FF (400 µg) and UMEC (500 µg) will be administered as single dose (4 inhalations); as dry powder in NDPI device once in 7 days in one of the 4 Treatment Periods of the study. |
| Name | Type | Description |
|---|---|---|
| UMEC/VI | DRUG | ELLIPTA DPI will be supplied with 30 doses (2 strips with 30 blisters per strip) where first strip contains Umeclidinium bromide (unit dose strengths 62.5 mcg per blister) blended with lactose monohydrate and magnesium stearate 0.6% weight/weight (w/w) of total drug product and second strip contains Vilanterol (unit dose strengths 25 mcg per blister) blended with lactose monohydrate and magnesium stearate 1.0% w/w of total drug product |
| UMEC/VI matching placebo | DRUG | ELLIPTA DPI will be supplied with 30 doses (2 strips with 30 blisters per strip) where first strip contains lactose monohydrate and magnesium stearate 0.6% w/w of total drug product and second strip contains lactose monohydrate and magnesium stearate 1.0% w/w of total drug product |
| Tiotropium | DRUG | Tiotropium (as bromide monohydrate) inhalation capsules 18 mcg per dose will be supplied along with HANDIHALER inhalers manufactured by Boehringer Ingelheim |
| Tiotropium matching placebo | DRUG | Tiotropium matching placebo capsules manufactured by GSK, will contain lactose and will be supplied along with HANDIHALER inhalers |
| Indacaterol | DRUG | Indacaterol inhalation capsules 150 mcg per dose will be supplied by GSK along with BREEZHALER inhalers manufactured by Novartis |
| Indacaterol matching placebo | DRUG | Indacaterol matching placebo capsules manufactured by GSK, will contain lactose and will be supplied along with BREEZHALER inhalers manufactured by Novartis |
| Albuterol/salbutamol Metered Dose Inhaler (MDI) | DRUG | Albuterol/salbutamol MDI or nebules for as needed use will be issued throughout the study. Albuterol/salbutamol will be sourced from local commercial stock. If not available locally, GSK will source centrally |
| Placebo | DRUG | Dry white powder delivered via DPI (2 strips with 30 blisters each, both containing lactose with magnesium stearate), administered as one inhalation of placebo |
| UMEC/VI Inhalation Powder 62.5/25 mcg via NDPI | DRUG | The drug is administered via NDPI as one inhalation once daily in the morning. NDPI has two strips, each containing 30 blisters of medication. The first strip has UMEC blended with lactose and magnesium stearate in the form of dry white powder with a dosage of 62.5 mcg per blister and the second strip has VI blended with lactose and magnesium stearate in the form of dry white powder with a dosage of 25 mcg per blister. |
| FSC Inhalation Powder 250/50 mcg via ACCUHALER/DISKUS | DRUG | The drug is administered via ACCUHALER/DISKUS inhaler as one inhalation each morning and evening. The inhaler contains a single strip with 60 blisters of medication. The strip has 250 mcg of fluticasone propionate and 50 mcg of salmeterol per blister in the form of dry white powder. |
| Placebo DISKUS | DRUG | Placebo is administered via ACCUHALER/DISKUS inhaler as one inhalation each morning and evening. The inhaler contains 1 strip with 60 blisters of placebo in the form of dry white powder. |
| Placebo NDPI | DRUG | Placebo is administered via NDPI as one inhalation once daily in the morning. The inhaler contains 2 strips with 30 blisters of placebo per strip in the form of dry white powder. |
| UMEC/VI 125/25 mcg | DRUG | Combination in high dose |
| UMEC/VI 62.5/25 mcg | DRUG | Combination in low dose |
| UMEC 125 mcg | DRUG | LAMA mono in high dose |
| UMEC 62.5 mcg | DRUG | LAMA mono in low dose |
| VI 25 mcg | DRUG | LABA mono |
| UMEC /VI | DRUG | Umeclidinium is an inhaled long-acting muscarinic antagonist (LAMA) and vilanterol is a long-acting beta2 agonist (LABA). UMEC/VI (blended together) will be available as dry powder in the dose of 125 µg /25 µg per inhalation. |
| UMEC | DRUG | Umeclidinium is an inhaled long-acting muscarinic antagonist (LAMA). UMEC will be available as dry powder in the dose of 125 µg per inhalation. |
| VI | DRUG | Vilanterol is a long-acting beta2 agonist (LABA). VI will be available as dry powder in the dose of 25 µg per inhalation. |
| FF | DRUG | Fluticasone Furoate is a novel inhaled corticosteroid (ICS). FF will be available as dry powder in the dose of 100 µg per inhalation. |
Inclusion Criteria: * Type of subject: Outpatient * Informed Consent: A signed and dated written informed consent prior to study participation. * Participants 40 years of age or older at Visit 1. * Gender: Male or female participants. A female is eligible to enter and participate in the study if sh...