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 |
|---|---|---|---|---|---|---|---|---|---|---|---|
| NCT02991859 | Phase 2a, AMP Challenge, Dose Escalation Study to Assess the Dose Response for Topical Efficacy and Systemic Activity in Asthmatic Subjects | PHASE2 | COMPLETED | 56 | — | — | Feb 9, 2017 | Dec 20, 2018 | Jul 31, 2020 | 3 | Germany, United Kingdom |
The percentage fall in FEV1 was calculated using highest FEV1 (post saline) minus highest FEV1 (post AMP) divided by highest FEV1 (post saline)\*100 where highest FEV1 (post saline) is the highest value of two FEV1 measurements at 60 and 180 seconds after the saline control, highest FEV1 (post AMP) is the highest value of the two FEV1 measurements at 60 and 180 seconds after the dose of AMP. Results are presented treatment wise. The analysis method was a 3 parameter Emax model with log 2 transformed AMP PC20 as the outcome variable, assuming common Emax across FF, FP and BUD, and with an unstructured variance-covariance matrix. Mean and 95% Confidence Interval (CI) presented are predicted estimate.
Blood samples for measurement of plasma cortisol were collected at given time point. The weighted means were derived by calculating the area under the curve (AUC) over the 0-24-hour period using the trapezoidal rule, and then dividing it by the actual time interval. Results are presented treatment wise. Mean and 95% CI presented are predicted estimate. The analysis method was an inhibitory exponential power-law model with log e transformed cortisol as the outcome variable, assuming 100% inhibition at highest doses.
Therapeutic Index was calculated by ED20 for Cortisol Suppression 0-24 Hours Weighted Mean (nanomoles per liter\[nmol/L\]) divided by Dose at which 80% of the maximum effect is reached (ED80) for AMP PC20 for FF 25 mcg, FF 100 mcg, FF 200 mcg, FF 400 mcg, FF 800 mcg. Theraputic index has been presented. Only those participants with data available at the specified time points were analyzed. The timeframe mentioned is for AMP PC20 and Cortisol suppression respectively.
Therapeutic Index was calculated by Dose at which 20% of the maximum effect is reached (ED20) for Cortisol Suppression 0-24 Hours Weighted Mean (nanomoles per liter\[nmol/L\]) divided by ED80 for AMP PC20 for FP 50 mcg, FP 200 mcg, FP 500 mcg, FP 1000 mcg, FP 2000 mcg. Theraputic index has been presented. The timeframe mentioned is for AMP PC20 and Cortisol suppression respectively.
Therapeutic Index was calculated by ED20 for Cortisol Suppression 0-24 Hours Weighted Mean (nanomoles per liter\[nmol/L\]) divided by ED80 for AMP PC20 for BUD 100 mcg, BUD 400 mcg, BUD 800 mcg, BUD 1600 mcg, BUD 3200 mcg. Theraputic index has been presented. The timeframe mentioned is for AMP PC20 and Cortisol suppression respectively.
| Arm | Type | Description |
|---|---|---|
| Arm AB - FF followed by FP | EXPERIMENTAL | Each treatment period (TP) comprises of 5 consecutive 7-day dosing phases with escalating doses of either FF or FP. In TP 1, subjects will receive evening (PM) dose of 1 puff of FF 25 microgram (mcg) (Total daily dose \[TDD\] = 25 mcg) in first phase followed by PM dose of 1 puff of FF 100 mcg (TDD = 100 mcg) in second phase; PM dose of 1 puff of FF 200 mcg (TDD = 200 mcg) in third phase; PM dose of 2 puff of FF 200 mcg (TDD = 400 mcg) in fourth phase and PM dose of 4 puff of FF 200 mcg (TDD = 800 mcg) in fifth phase. In TP 2, subjects will receive PM dose of 1 puff of FP 50 mcg (TDD = 50 mcg) in first phase followed by morning (AM) and PM doses of 1 puff each of FP 100 mcg (TDD = 200 mcg) in second phase; AM and PM doses of 1 puff each of FP 250 mcg (TDD = 500 mcg) in third phase; AM and PM doses of 1 puff each of FP 500 mcg (TDD = 1000 mcg) in fourth phase and AM and PM doses of 2 puffs each of FP 500 mcg (TDD = 2000 mcg) in fifth phase. Washout period will be of 25-42 days. |
| Arm AC - FF followed by BUD | EXPERIMENTAL | Each TP comprises of 5 consecutive 7-day dosing phases with escalating doses of either FF or BUD. In TP 1, subjects will receive PM dose of 1 puff of FF 25 mcg (TDD = 25 mcg) in first phase followed by PM dose of 1 puff of FF 100 mcg (TDD = 100 mcg) in second phase; PM dose of 1 puff of FF 200 mcg (TDD = 200 mcg) in third phase; PM dose of 2 puffs of FF 200 mcg (TDD = 400 mcg) in fourth phase and PM dose of 4 puffs of FF 200 mcg (TDD = 800 mcg) in fifth phase. In TP 2, subjects will receive PM dose of 1 puff of BUD 100 mcg (TDD = 100 mcg) in first phase followed by AM and PM doses of 1 puff each of BUD 200 mcg (TDD = 400 mcg) in second phase; AM and PM doses of 1 puff each of BUD 400 mcg (TDD = 800 mcg) in third phase; AM and PM doses of 2 puffs each of BUD 400 mcg (TDD = 1600 mcg) in fourth phase and AM and PM doses of 4 puffs each of BUD 400 mcg (TDD = 3200 mcg) in fifth phase. Washout period will be of 25-42 days. |
| Arm AD - FF followed by ELLIPTA Placebo | EXPERIMENTAL | Each TP comprises of 5 consecutive 7-day dosing phases with escalating doses of either FF or ELLIPTA Placebo. In TP 1, subjects will receive PM dose of 1 puff of FF 25 mcg (TDD = 25 mcg) in first phase followed by PM dose of 1 puff of FF 100 mcg (TDD = 100 mcg) in second phase; PM dose of 1 puff of FF 200 mcg (TDD = 200 mcg) in third phase; PM dose of 2 puffs of FF 200 mcg (TDD = 400 mcg) in fourth phase and PM dose of 4 puffs of FF 200 mcg (TDD = 800 mcg) in fifth phase. In TP 2, subjects will receive PM dose of 1 puff of ELLIPTA Placebo in first, second and third phases followed by PM dose of 2 puffs of ELLIPTA Placebo in fourth phase and PM dose of 4 puffs of ELLIPTA Placebo in fifth phase. Washout period will be of 25-42 days. |
| Arm BA - FP followed by FF | EXPERIMENTAL | Each TP comprises of 5 consecutive 7-day dosing phases with escalating doses of either FP or FF. In TP 1, subjects will receive PM dose of 1 puff of FP 50 mcg (TDD = 50 mcg) in first phase followed by AM and PM doses of 1 puff each of FP 100 mcg (TDD = 200 mcg) in second phase; AM and PM doses of 1 puff each of FP 250 mcg (TDD = 500 mcg) in third phase; AM and PM doses of 1 puff each of FP 500 mcg (TDD = 1000 mcg) in fourth phase and AM and PM doses of 2 puffs each of FP 500 mcg (TDD = 2000 mcg) in fifth phase. In TP 2, subjects will receive PM dose of 1 puff of FF 25 mcg (TDD = 25 mcg) in first phase followed by PM dose of 1 puff of FF 100 mcg (TDD = 100 mcg) in second phase; PM dose of 1 puff of FF 200 mcg (TDD = 200 mcg) in third phase; PM dose of 2 puffs of FF 200 mcg (TDD = 400 mcg) in fourth phase and PM dose of 4 puffs of FF 200 mcg (TDD = 800 mcg) in fifth phase. Washout period will be of 25-42 days. |
| Arm BC - FP followed by BUD | EXPERIMENTAL | Each TP comprises of 5 consecutive 7-day dosing phases with escalating doses of either FP or BUD. In TP 1, subjects will receive PM dose of 1 puff of FP 50 mcg (TDD = 50 mcg) in first phase followed by AM and PM doses of 1 puff each of FP 100 mcg (TDD = 200 mcg) in second phase; AM and PM doses of 1 puff each of FP 250 mcg (TDD = 500 mcg) in third phase; AM and PM doses of 1 puff each of FP 500 mcg (TDD = 1000 mcg) in fourth phase and AM and PM doses of 2 puffs each of FP 500 mcg (TDD = 2000 mcg) in fifth phase. In TP 2, subjects will receive PM dose of 1 puff of BUD 100 mcg (TDD =100 mcg) in first phase followed by AM and PM doses of 1 puff each of BUD 200 mcg (TDD = 400 mcg) in second phase; AM and PM doses of 1 puff each of BUD 400 mcg (TDD = 800 mcg) in third phase; AM and PM doses of 2 puffs each of BUD 400 mcg (TDD =1600 mcg) in fourth phase and AM and PM doses of 4 puffs each of BUD 400 mcg (TDD = 3200 mcg) in fifth phase. Washout period will be of 25-42 days. |
| Arm BE - FP followed by DISKUS Placebo | EXPERIMENTAL | Each TP comprises of 5 consecutive 7-day dosing phases with escalating doses of either FP or DISKUS Placebo. In TP 1, subjects will receive PM dose of 1 puff of FP 50 mcg (TDD = 50 mcg) in first phase followed by AM and PM doses of 1 puff each of FP 100 mcg (TDD = 200 mcg) in second phase; AM and PM doses of 1 puff each of FP 250 mcg (TDD = 500 mcg) in third phase; AM and PM doses of 1 puff each of FP 500 mcg (TDD = 1000 mcg) in fourth phase and AM and PM doses of 2 puffs each of FP 500 mcg (TDD = 2000 mcg) in fifth phase. In TP 2, subjects will receive PM dose of 1 puff of DISKUS Placebo in first phase followed by AM and PM doses of 1 puff each DISKUS Placebo in second, third and fourth phase; AM and PM doses of 2 puffs each of DISKUS Placebo in fifth phase. Each TP will be followed by a washout period of 25-42 days. |
| Arm CA - BUD followed by FF | EXPERIMENTAL | Each TP comprises of 5 consecutive 7-day dosing phases with escalating doses of either BUD or FF. In TP 1, subjects will receive PM dose of 1 puff of BUD 100 mcg (TDD =100 mcg) in first phase followed by AM and PM doses of 1 puff each of BUD 200 mcg (TDD =400 mcg) in second phase; AM and PM doses of 1 puff each of BUD 400 mcg (TDD = 800 mcg) in third phase; AM and PM doses of 2 puffs each of BUD 400 mcg (TDD =1600 mcg) in fourth phase and AM and PM doses of 4 puffs each of BUD 400 mcg (TDD = 3200 mcg) in fifth phase. In TP 2, subjects will receive PM dose of 1 puff of FF 25 mcg (TDD = 25 mcg) in first phase followed by PM dose of 1 puff of FF 100 mcg (TDD = 100 mcg) in second phase; PM dose of 1 puff of FF 200 mcg (TDD = 200 mcg) in third phase; PM dose of 2 puffs of FF 200 mcg (TDD = 400 mcg) in fourth phase and PM dose of 4 puffs of FF 200 mcg (TDD = 800 mcg) in fifth phase. Washout period will be of 25-42 days. |
| Arm CB - BUD followed by FP | EXPERIMENTAL | Each TP comprises of 5 consecutive 7-day dosing phases with escalating doses of either BUD or FP. In TP 1, subjects will receive PM dose of 1 puff of BUD 100 mcg (TDD =100 mcg) in first phase followed by AM and PM doses of 1 puff each of BUD 200 mcg (TDD =400 mcg) in second phase; AM and PM doses of 1 puff each of BUD 400 mcg (TDD = 800 mcg) in third phase; AM and PM doses of 2 puffs each of BUD 400 mcg (TDD =1600 mcg) in fourth phase and AM and PM doses of 4 puffs each of BUD 400 mcg (TDD = 3200 mcg) in fifth phase. In TP 2, subjects will receive PM dose of 1 puff of FP 50 mcg (TDD = 50 mcg) in first phase followed by AM and PM doses of 1 puff each of FP 100 mcg (TDD = 200 mcg) in second phase; AM and PM doses of 1 puff each of FP 250 mcg (TDD =500 mcg) in third phase; AM and PM doses of 1 puff each of FP 500 mcg (TDD = 1000 mcg) in fourth phase and AM and PM doses of 2 puffs each of FP 500 mcg (TDD = 2000 mcg) in fifth phase. Washout period will be of 25-42 days. |
| Arm CE - BUD followed by DISKUS Placebo | EXPERIMENTAL | Each TP comprises of 5 consecutive 7-day dosing phases with escalating doses of either BUD or DISKUS Placebo. In TP 1, subjects will receive PM dose of 1 puff of BUD 100 mcg (TDD =100 mcg) in first phase followed by AM and PM doses of 1 puff each of BUD 200 mcg (TDD =400 mcg) in second phase; AM and PM doses of 1 puff each of BUD 400 mcg (TDD = 800 mcg) in third phase; AM and PM doses of 2 puffs each of BUD 400 mcg (TDD =1600 mcg) in fourth phase and AM and PM doses of 4 puffs each of BUD 400 mcg (TDD = 3200 mcg) in fifth phase. In TP 2, subjects will receive PM dose of 1 puff of DISKUS Placebo in first phase followed by AM and PM doses of 1 puff each DISKUS Placebo in second, third and fourth phase; and AM and PM doses of 2 puffs each of DISKUS Placebo in fifth phase. Washout period will be of 25-42 days. |
| Arm DA - ELLIPTA Placebo followed by FF | EXPERIMENTAL | Each TP comprises of 5 consecutive 7-day dosing phases with escalating doses of either ELLIPTA Placebo or FF. In TP 1, subjects will receive PM dose of 1 puff of ELLIPTA Placebo in first, second and third phase followed by PM dose of 2 puffs of ELLIPTA Placebo in fourth phase and PM dose of 4 puffs of ELLIPTA Placebo in fifth phase. In TP 2, subjects will receive PM dose of 1 puff of FF 25 mcg (TDD = 25 mcg) in first phase followed by PM dose of 1 puff of FF 100 mcg (TDD = 100 mcg) in second phase; PM dose of 1 puff of FF 200 mcg (TDD = 200 mcg) in third phase; PM dose of 2 puffs of FF 200 mcg (TDD = 400 mcg) in fourth phase and PM dose of 4 puffs of FF 200 mcg (TDD = 800 mcg) in fifth phase. Washout period will be of 25-42 days. |
| Arm EB - DISKUS Placebo followed by FP | EXPERIMENTAL | Each TP comprises of 5 consecutive 7-day dosing phases with escalating doses of either DISKUS Placebo or FP. TP 1, subjects will receive PM dose of 1 puff of DISKUS Placebo in first phase followed by AM and PM doses of 1 puff each of DISKUS Placebo in second, third and fourth phase; AM and PM doses of 2 puffs each of DISKUS Placebo in fifth phase. In TP 2, subjects will receive PM dose of 1 puff of FP 50 mcg (TDD = 50 mcg) in first phase followed by AM and PM doses of 1 puff each of FP 100 mcg (TDD = 200 mcg) in second phase; AM and PM doses of 1 puff each of FP 250 mcg (TDD = 500 mcg) in third phase; AM and PM doses of 1 puff each of FP 500 mcg (TDD = 1000 mcg) in fourth phase and AM and PM doses of 2 puffs each of FP 500 mcg (TDD = 2000 mcg) in fifth phase. Washout period will be of 25-42 days. |
| Arm DC - ELLIPTA Placebo followed by BUD | EXPERIMENTAL | Each TP comprises of 5 consecutive 7-day dosing phases with escalating doses of either ELLIPTA Placebo or BUD. In TP 1, subjects will receive PM dose of 1 puff of ELLIPTA Placebo in first, second and third phase followed by PM dose of 2 puffs of ELLIPTA Placebo in fourth phase and PM dose of 4 puffs of ELLIPTA Placebo in fifth phase. In TP 2, subjects will receive PM dose of 1 puff of BUD 100 mcg (TDD =100 mcg) in first phase followed by AM and PM doses of 1 puff each of BUD 200 mcg (TDD =400 mcg) in second phase; AM and PM doses of 1 puff each of BUD 400 mcg (TDD = 800 mcg) in third phase; AM and PM doses of 2 puffs each of BUD 400 mcg (TDD =1600 mcg) in fourth phase and AM and PM doses of 4 puffs each of BUD 400 mcg (TDD = 3200 mcg) in fifth phase. Washout period will be of 25-42 days. |
| Name | Type | Description |
|---|---|---|
| Fluticasone furoate (FF) Dry Powder Inhaler | DRUG | Dry inhalation powder 25 mcg, 100 mcg, and 200 mcg per blister strip will be administered using ELLIPTA for both treatment periods |
| Fluticasone propionate (FP) Dry Powder Inhaler | DRUG | Dry Inhalation powder 50 mcg, 100 mcg, 250 mcg, and 500 mcg per blister strip will be administered using DISKUS for both treatment periods |
| Budesonide (BUD) Turbuhaler | DRUG | Budesonide comprises white to off-white rounded granules, which disintegrate to a fine powder upon slight pressure, will be administered using Turbuhaler for both treatment periods. |
| Placebo (ELLIPTA or DISKUS) | DRUG | Lactose dry powder inhaler will be administered using ELLIPTA or DISKUS for both treatment periods. |
Inclusion Criteria - Subjects must be 18 to 65 years of age inclusive, at the time of signing the informed Consent. - Documented history of bronchial asthma, first diagnosed at least 6 months prior to the screening visit - Pre-bronchodilator FEV1 \>=65% of predicted at screening; the pre-dose baseli...