Pharmacokinetic and Pharmacodynamic (PK and PD) Study of Fluticasone Propionate and Salmeterol Combination Product Delivered in a Capsule-based Inhaler and in a Multi-dose Dry Powder Inhaler in Moderate Asthma Patients and Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD) Patients.
CompletedPhase 1, PHASE2Results postedLast updated 26 February 2019
What this trial tests
Phase 1, PHASE2 trial testing SERETIDE Rotacaps in Asthma in 60 participants. Completed in 8 June 2011.
Adults 18 to 80, any sex, with Asthma. Patients with the condition only — healthy volunteers not accepted.
Results — posted to ClinicalTrials.gov
Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.
Mean Area Under the Concentration Time Curve Over the Dosing Period (AUC[0-tau]) for FPPrimary· At pre-morning dose; 5, 10, 30 minutes post-dose (PD); and 1, 2, 4, 8, 10, and 12 hours PD on Day 10 of each study period (P): Study Day (SD) 10 (reference day is SD 1 or Randomization day), 20, 30, and 40 (+/-1) for P 1, 2, 3, and 4, respectively
Blood samples of participants (par.) with asthma and chronic obstructive pulmonary disease (COPD) were collected and analyzed for AUC(0-tau), a measure of the amount of drug available at target tissue (in plasma) for a fixed dosing interval (12 hours). Asthma is a disorder that causes the airways of the lungs to swell and narrow, leading to difficulty in breathing. COPD is a chronic lung disease with structural changes in lungs, leading to difficulty in breathing.
Asthma + COPD; n=57, 57
Group
Value
95% CI
FP/Salmeterol From MDPI
376.9
337.0 – 421.6
FP/Salmeterol From Capsule-based Inhaler
573.1
519.3 – 632.5
Asthma; n=33, 33
Group
Value
95% CI
FP/Salmeterol From MDPI
350.5
296.5 – 414.4
FP/Salmeterol From Capsule-based Inhaler
559.1
490.1 – 637.7
COPD; n=24, 24
Group
Value
95% CI
FP/Salmeterol From MDPI
416.4
363.1 – 477.6
FP/Salmeterol From Capsule-based Inhaler
593.0
505.7 – 695.4
Weighted Mean Serum Cortisol (SC) Over 0 to 12 Hours Post DosePrimary· At pre-morning dose; 30 minutes post-dose (PD); and 1, 2, 4, 8, 10, and 12 hours PD on Day 10 of each study period (P): Study Day (SD) 10 (reference day is SD 1 or Randomization day), 20, 30, and 40 (+/-1) for P 1, 2, 3, and 4, respectively
Participants' blood samples were collected and analyzed for SC levels. Weighted mean SC levels are evaluted as a measure of the degree of cortisol suppression, allowing for the determination of whether differences in systemic exposure to the inhaled steroid component of two devices can be significant enough to result in the differences in the body's ability to release cortisol. Weighted means were derived by calculating the AUC over the 0-12 hour period, using the linear trapezoidal rule (statistical technique used for numerical analysis) and then dividing it by the actual time interval.
Asthma + COPD;n=57, 57
Group
Value
95% CI
FP/Salmeterol From MDPI
193.5
178.7 – 209.6
FP/Salmeterol From Capsule-based Inhaler
178.3
164.2 – 193.5
Asthma; n=33, 33
Group
Value
95% CI
FP/Salmeterol From MDPI
187.3
169.1 – 207.6
FP/Salmeterol From Capsule-based Inhaler
166.6
150.4 – 184.7
COPD; n=24, 24
Group
Value
95% CI
FP/Salmeterol From MDPI
202.4
177.0 – 231.4
FP/Salmeterol From Capsule-based Inhaler
195.6
171.1 – 223.7
Mean Plasma AUC(0-tau) and Plasma AUC From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration (AUC[0-tlast]) for SalmeterolSecondary· At pre-morning dose; 5, 10, 30 minutes post-dose (PD); and 1, 2, 4, 8, 10, and 12 hours PD on Day 10 of each study period (P): Study Day (SD) 10 (reference day is SD 1 or Randomization day), 20, 30, and 40 (+/-1) for P 1, 2, 3, and 4, respectively
Blood samples of participants with asthma and COPD were collected and analyzed for AUC(0-tau) and AUC(0-tlast). AUC(0-tau) is a measure of the amount of drug available at target tissue (in plasma) for a fixed dosing interval (12 hours). AUC(0-tlast) is a measure of the plasma drug concentration from pre-dose to the last measurable concentration.
AUC(0-tau), asthma + COPD; n=57, 57
Group
Value
95% CI
FP/Salmeterol From MDPI
300.2
273.0 – 330.1
FP/Salmeterol From Capsule-based Inhaler
345.1
310.8 – 383.1
AUC(0-tau), asthma; n=33, 33
Group
Value
95% CI
FP/Salmeterol From MDPI
305.8
274.6 – 340.6
FP/Salmeterol From Capsule-based Inhaler
356.4
315.4 – 402.7
AUC(0-tau), COPD; n=24, 24
Group
Value
95% CI
FP/Salmeterol From MDPI
292.7
244.4 – 350.5
FP/Salmeterol From Capsule-based Inhaler
330.1
272.1 – 400.4
AUC(0-t), asthma + COPD; n=57, 57
Group
Value
95% CI
FP/Salmeterol From MDPI
303.5
277.7 – 331.7
FP/Salmeterol From Capsule-based Inhaler
345.0
310.7 – 383.0
AUC(0-t), asthma; n=33, 33
Group
Value
95% CI
FP/Salmeterol From MDPI
305.2
273.9 – 340.2
FP/Salmeterol From Capsule-based Inhaler
356.4
315.3 – 402.7
AUC(0-t), COPD; n=24, 24
Group
Value
95% CI
FP/Salmeterol From MDPI
301.2
256.9 – 353.2
FP/Salmeterol From Capsule-based Inhaler
330.0
272.0 – 400.3
Mean AUC(0-tlast) for FPSecondary· At pre-morning dose; 5, 10, 30 minutes post-dose (PD); and 1, 2, 4, 8, 10, and 12 hours PD on Day 10 of each study period (P): Study Day (SD) 10 (reference day is SD 1 or Randomization day), 20, 30, and 40 (+/-1) for P 1, 2, 3, and 4, respectively
Blood samples of participants with asthma and COPD were collected and analyzed for AUC(0-tlast). AUC(0-tlast) is a measure of the plasma drug concentration from pre-dose to the last measurable concentration.
Asthma + COPD; n=57, 57
Group
Value
95% CI
FP/Salmeterol From MDPI
380.1
342.7 – 421.6
FP/Salmeterol From Capsule-based Inhaler
580.9
530.2 – 636.3
Asthma; n=33, 33
Group
Value
95% CI
FP/Salmeterol From MDPI
355.7
306.0 – 413.4
FP/Salmeterol From Capsule-based Inhaler
558.4
489.6 – 636.9
COPD; n=24, 24
Group
Value
95% CI
FP/Salmeterol From MDPI
416.5
363.2 – 477.6
FP/Salmeterol From Capsule-based Inhaler
613.2
539.9 – 696.5
Mean Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) of FPSecondary· At pre-morning dose; 5, 10, 30 minutes post-dose (PD); and 1, 2, 4, 8, 10, and 12 hours PD on Day 10 of each study period (P): Study Day (SD) 10 (reference day is SD 1 or Randomization day), 20, 30, and 40 (+/-1) for P 1, 2, 3, and 4, respectively
Blood samples of participants with asthma and COPD were collected and analyzed for Cmax and Cmin of FP in the blood. Cmax and Cmin are used to estimate the time at which the activity of the drug will be at its maximum and minimum, respectively.
Cmax, Asthma + COPD; n= 57, 57
Group
Value
95% CI
FP/Salmeterol From MDPI
54.64
49.70 – 60.08
FP/Salmeterol From Capsule-based Inhaler
105.79
95.70 – 116.95
Cmax, Asthma; n=33, 33
Group
Value
95% CI
FP/Salmeterol From MDPI
53.66
47.36 – 60.80
FP/Salmeterol From Capsule-based Inhaler
109.98
95.79 – 126.27
Cmax, COPD; n=24, 24
Group
Value
95% CI
FP/Salmeterol From MDPI
56.02
47.91 – 65.50
FP/Salmeterol From Capsule-based Inhaler
100.29
86.06 – 116.87
Cmin, Asthma + COPD; n=57, 57
Group
Value
95% CI
FP/Salmeterol From MDPI
15.904
14.025 – 18.035
FP/Salmeterol From Capsule-based Inhaler
21.547
19.198 – 24.183
Cmin, Asthma; n=33, 33
Group
Value
95% CI
FP/Salmeterol From MDPI
13.635
11.448 – 16.239
FP/Salmeterol From Capsule-based Inhaler
18.866
15.979 – 22.273
Cmin, COPD; n=24, 24
Group
Value
95% CI
FP/Salmeterol From MDPI
19.654
16.898 – 22.859
FP/Salmeterol From Capsule-based Inhaler
25.866
22.703 – 29.470
Mean Terminal Phase Half-life (t1/2) for FPSecondary· At pre-morning dose; 5, 10, 30 minutes post-dose (PD); and 1, 2, 4, 8, 10, and 12 hours PD on Day 10 of each study period (P): Study Day (SD) 10 (reference day is SD 1 or Randomization day), 20, 30, and 40 (+/-1) for P 1, 2, 3, and 4, respectively
Blood samples of participants were collected for evaluating t1/2. The t1/2 is the time required for the plasma/blood concentration of the drug to decrease by 50% after the false equilibrium of distribution has been reached.
Asthma + COPD; n=54, 55
Group
Value
95% CI
FP/Salmeterol From MDPI
6.660
6.164 – 7.197
FP/Salmeterol From Capsule-based Inhaler
5.844
5.416 – 6.307
Asthma; n=30, 32
Group
Value
95% CI
FP/Salmeterol From MDPI
5.906
5.402 – 6.458
FP/Salmeterol From Capsule-based Inhaler
5.238
4.789 – 5.729
COPD; n=24, 23
Group
Value
95% CI
FP/Salmeterol From MDPI
7.740
6.915 – 8.663
FP/Salmeterol From Capsule-based Inhaler
6.806
6.089 – 7.607
Time of Occurrence of Cmax (Tmax) for FPSecondary· At pre-morning dose; 5, 10, 30 minutes post-dose (PD); and 1, 2, 4, 8, 10, and 12 hours PD on Day 10 of each study period (P): Study Day (SD) 10 (reference day is SD 1 or Randomization day), 20, 30, and 40 (+/-1) for P 1, 2, 3, and 4, respectively
Blood samples of participants were collected for evaluating Tmax. Tmax is a measure of the time required to reach the maximum concentration of the drug.
Asthma + COPD; n=57, 57
Group
Value
95% CI
FP/Salmeterol From MDPI
1.045
0.08 – 5.00
FP/Salmeterol From Capsule-based Inhaler
0.530
0.08 – 2.04
Asthma; n=33, 33
Group
Value
95% CI
FP/Salmeterol From MDPI
1.000
0.08 – 4.04
FP/Salmeterol From Capsule-based Inhaler
0.335
0.08 – 2.04
COPD; n=24, 24
Group
Value
95% CI
FP/Salmeterol From MDPI
1.173
0.17 – 5.00
FP/Salmeterol From Capsule-based Inhaler
0.673
0.13 – 1.54
Mean Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) for SalmeterolSecondary· At pre-morning dose; 5, 10, 30 minutes post-dose (PD); and 1, 2, 4, 8, 10, and 12 hours PD on Day 10 of each study period (P): Study Day (SD) 10 (reference day is SD 1 or Randomization day), 20, 30, and 40 (+/-1) for P 1, 2, 3, and 4, respectively
Blood samples of participants with asthma and COPD were collected and analyzed for Cmax and Cmin of Salmeterol in the blood. Cmax and Cmin are used to estimate the time at which the activity of the drug will be at its maximum and minimum.
Cmax, Asthma + COPD; n=57, 57
Group
Value
95% CI
FP/Salmeterol From MDPI
59.28
53.45 – 65.74
FP/Salmeterol From Capsule-based Inhaler
92.27
80.52 – 105.75
Cmax, Asthma; n=33, 33
Group
Value
95% CI
FP/Salmeterol From MDPI
64.97
56.53 – 74.66
FP/Salmeterol From Capsule-based Inhaler
110.21
94.76 – 128.19
Cmax, COPD; n=24, 24
Group
Value
95% CI
FP/Salmeterol From MDPI
52.26
44.94 – 60.77
FP/Salmeterol From Capsule-based Inhaler
72.27
57.75 – 90.45
Cmin, Asthma + COPD; n=57, 57
Group
Value
95% CI
FP/Salmeterol From MDPI
12.752
11.504 – 14.134
FP/Salmeterol From Capsule-based Inhaler
14.354
12.859 – 16.024
Cmin, Asthma; n=33, 33
Group
Value
95% CI
FP/Salmeterol From MDPI
12.676
11.097 – 14.479
FP/Salmeterol From Capsule-based Inhaler
14.634
12.806 – 16.723
Cmin, COPD; n=24, 24
Group
Value
95% CI
FP/Salmeterol From MDPI
12.857
10.798 – 15.307
FP/Salmeterol From Capsule-based Inhaler
13.978
11.464 – 17.044
Mean Terminal Phase Half-life (t1/2) for SalmeterolSecondary· At pre-morning dose; 5, 10, 30 minutes post-dose (PD); and 1, 2, 4, 8, 10, and 12 hours PD on Day 10 of each study period (P): Study Day (SD) 10 (reference day is SD 1 or Randomization day), 20, 30, and 40 (+/-1) for P 1, 2, 3, and 4, respectively
Blood samples of participants were collected for evaluating t1/2. t1/2 is the time required for the plasma/blood concentration of the drug to decrease by 50% after the false equilibrium of distribution has been reached.
Asthma + COPD; n=56, 56
Group
Value
95% CI
FP/Salmeterol From MDPI
6.576
6.080 – 7.112
FP/Salmeterol From Capsule-based Inhaler
7.260
6.792 – 7.761
Asthma; n=32, 32
Group
Value
95% CI
FP/Salmeterol From MDPI
6.429
6.021 – 6.865
FP/Salmeterol From Capsule-based Inhaler
7.538
6.840 – 8.308
COPD; n=24, 24
Group
Value
95% CI
FP/Salmeterol From MDPI
6.776
5.727 – 8.018
FP/Salmeterol From Capsule-based Inhaler
6.905
6.309 – 7.558
Tmax for SalmeterolSecondary· At pre-morning dose; 5, 10, 30 minutes post-dose (PD); and 1, 2, 4, 8, 10, and 12 hours PD on Day 10 of each study period (P): Study Day (SD) 10 (reference day is SD 1 or Randomization day), 20, 30, and 40 (+/-1) for P 1, 2, 3, and 4, respectively
Blood samples of participants were collected for evaluating Tmax. Tmax is a measure of the time required to reach the maximum concentration of the drug.
Asthma + COPD; n=57, 57
Group
Value
95% CI
FP/Salmeterol From MDPI
0.750
0.08 – 6.50
FP/Salmeterol From Capsule-based Inhaler
0.080
0.08 – 6.50
Asthma; n=33, 33
Group
Value
95% CI
FP/Salmeterol From MDPI
0.335
0.08 – 6.50
FP/Salmeterol From Capsule-based Inhaler
0.080
0.08 – 1.04
COPD; n=24, 24
Group
Value
95% CI
FP/Salmeterol From MDPI
1.000
0.08 – 2.00
FP/Salmeterol From Capsule-based Inhaler
0.080
0.08 – 6.50
Mean Urine Cortisol Excretion Over 0 to 24 Hours Post Dose for FPSecondary· 0-24 hours post dose on Day 10 of each study period (P): Study Day (SD) 10 (reference day is SD 1 or Randomization day), 20, 30, and 40 (+/-1) for P 1, 2, 3, and 4, respectively
Urine samples of participants were collected to evaluate urine cortisol excretion over 0-24 hours post treatment dose. A 24-hour urine cortisol sample was used to measure the total amount of cortisol excreted in urine in 24 hours. Any differences in systemic exposure as a result of the absorbed steroid component of the two differing inhaled devices should also result in differences in the amount of cortisol excreted in the urine.
Asthma + COPD; n=57, 57
Group
Value
95% CI
FP/Salmeterol From MDPI
63.53
56.71 – 71.17
FP/Salmeterol From Capsule-based Inhaler
59.66
51.45 – 69.18
Asthma; n=33, 33
Group
Value
95% CI
FP/Salmeterol From MDPI
72.86
62.97 – 84.32
FP/Salmeterol From Capsule-based Inhaler
66.28
55.25 – 79.51
COPD; n=24, 24
Group
Value
95% CI
FP/Salmeterol From MDPI
52.62
44.77 – 61.83
FP/Salmeterol From Capsule-based Inhaler
51.62
40.16 – 66.35
Serum Cortisol Minimum (Cmin) for FPSecondary· Day 10 of each study period (Periods 1-4); Study Day 10 (+/-1) (reference day is Study Day 1 or Randomization day), Period 1; Study Day 20 (+/-1), Period 2; Study Day 30 (+/-1), Period 3; Study Day 40 (+/-1), Period 4
Blood samples of participants were collected for the evaluation of minimum serum cortisol. Any differences in systemic exposure as a result of the absorbed steroid component of the two differing inhaled devices should also result in differences in serum cortisol concentrations.
Asthma + COPD; n=57, 57
Group
Value
95% CI
FP/Salmeterol From MDPI
88.6
77.9 – 100.8
FP/Salmeterol From Capsule-based Inhaler
79.6
69.0 – 91.7
Asthma; n=33, 33
Group
Value
95% CI
FP/Salmeterol From MDPI
79.8
67.0 – 95.0
FP/Salmeterol From Capsule-based Inhaler
70.0
57.8 – 84.7
COPD; n=24, 24
Group
Value
95% CI
FP/Salmeterol From MDPI
102.4
85.0 – 123.3
FP/Salmeterol From Capsule-based Inhaler
94.9
77.1 – 116.8
Adverse events — posted to ClinicalTrials.gov
Reporting threshold: 0%.
Adverse-event reports describe events observed during the trial — not all are caused by the drug.
FP/Salmeterol From MDPI 1st Administration (Admin), Asthma
Serious: 0/33 (0%)
Deaths: —
FP/Salmeterol From MDPI 2nd Admin, Asthma
Serious: 0/31 (0%)
Deaths: —
FP/Salmeterol From Capsule-based Inhaler 1st Admin, Asthma
Serious: 0/34 (0%)
Deaths: —
FP/Salmeterol From Capsule-based Inhaler 2nd Admin, Asthma
Serious: 1/33 (3%)
Deaths: —
FP/Salmeterol From MDPI 1st Admin, COPD
Serious: 0/26 (0%)
Deaths: —
FP/Salmeterol From MDPI 2nd Admin, COPD
Serious: 0/25 (0%)
Deaths: —
FP/Salmeterol From Capsule-based Inhaler 1st Admin, COPD
Serious: 0/25 (0%)
Deaths: —
FP/Salmeterol From Capsule-based Inhaler 2nd Admin, COPD
This is a comparative bioavailability study to compare the pharmacokinetics and pharmacodynamic effects of Fluticasone propionate and Salmeterol delivered in a capsule-based inhaler versus a multi-dose dry powder inhaler in patients with moderate asthma and in patients with moderate to severe Chronic obstructive pulmonary disease (COPD).
Co-primary endpoints will be the area under the curve (AUCτ) measured for plasma Fluticasone propionate (pharmacokinetic) and the pharmacodynamic effects of Fluticasone propionate (weighted mean serum cortisol over 0-12h) on the last day of each 10 day study treatment period. Secondary endpoints will include the following pharmacokinetic parameters for both fluticasone propionate and salmeterol: AUClast, AUC(0-t), Cmax, Cmin, tmax, λz, and t1/2 as well as the pharmacodynamic effects of salmeterol (pulse rate, blood pressure, electrocardiogram \[ECG\], potassium and glucose) and Fluticasone propionate (urine cortisol levels). Safety (adverse events and laboratory abnormalities) will also be assessed as a secondary endpoint.
The study is a randomised, double blind, double dummy, four-period cross-over study. Approximately 60 asthma or COPD patients will be randomised. Patients meeting eligibility criteria will receive Fluticasone propionate/salmeterol 250/50mcg bid, from a capsule-based inhaler and from a multi-dose dry powder inhaler for a period of 10 days each in a randomised order. All patients will receive treatment from each device twice. To maintain the double blind, each patient will receive active treatment and placebo at the same time from two separate devices.
Publications & conference data
No peer-reviewed publications indexed yet for this trial. Completed trials usually publish results within 12-18 months.
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Sponsor: as reported to ClinicalTrials.gov by GlaxoSmithKline
Last refreshed: 26 February 2019
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