Figures
- FIGURE 1
Study design. Participants were randomised to receive either 4.8 mg GSK2798745 on Day 1, followed by 2.4 mg once daily for 6 days, or matching placebo once daily for 7 days in the first treatment period, followed by the alternative regimen in the second treatment period.
- FIGURE 2
Consolidated Standards of Reporting Trials participant disposition.
- FIGURE 3
Individual change from baseline cough counts over day-time and 24-h time periods. Individual patient data are plotted on each line.
- FIGURE 4
Patient reported outcome measure results for Severity of Cough visual analogue scale (VAS), Urge to Cough VAS and Leicester Cough Questionnaire (LCQ), presented as mean±95% CI.
Tables
- TABLE 1
Participant baseline demographics (n=17)
Demographics Total Age years# (mean±sd) 61.0±9.85 Age range years# 18–64 10 (59) 65–74 7 (41) Sex Female 15 (88) Male 2 (12) BMI kg·m−2 (mean±sd) 27.61±4.96 Height (cm) (mean±sd) 162.9±6.58 Weight (kg) (mean±sd) 73.19±13.3 Ethnicity Hispanic or Latino 0 Not Hispanic or Latino 17 (100) Race Asian – South East Asian Heritage 1 (6) White – White/Caucasian/European Heritage 16 (94) GSK2798745 Placebo Baseline day-time 10-h cough count (geometric mean (95% CI)) 205.2 (116.7–360.6) 242.5 (144.7–406.4) Baseline Cough Severity VAS (mean±sd) 53.9±18.5 57.2±23.35 Baseline Urge to Cough VAS (mean±sd) 58.6±18.4 56.2±26.81 Baseline LCQ (mean±sd) 12.07±3.6 11.62±3.49 Data are presented as n (%) unless otherwise indicated. BMI: body mass index; VAS: visual analogue scale; LCQ: Leicester Cough Questionnaire. #: birth date was imputed as June 30 in the year of birth.
- TABLE 2
Statistical analysis model adjusted cough count estimates
Treatment N n Posterior median±sd 95% credible interval Day-time 10-h total cough counts treatment estimates Placebo 17 17 180.57±24.76 (137.85–235.45) GSK2798745 16 15 241.11±35.41 (181.38–320.60) 24-h total cough counts treatment estimates Placebo 17 17 413.44±43.56 (336.35–508.34) GSK2798745 16 15 450.68±50.8 (361.50–561.70) Total cough counts were log-transformed prior to analysis. N=number of participants in analysis population; n=number of participants providing data.
- TABLE 3
Statistical analysis treatment comparisons
Treatment comparison Posterior median ratio±sd 90% credible interval Posterior prob. of true Diff <1.0 <0.7 <0.5 Day-time 10-h total cough counts treatment comparison GSK2798745/Placebo 1.34±0.27 (0.97–1.85) 0.0700 0.001 <0.0001 24-h total cough counts treatment comparison GSK2798745/Placebo 1.09±0.17 (0.85–1.40) 0.284 0.003 <0.0001 Note a sensitivity analysis using non-imputed data: 1.31 (0.95–1.80 90% credible interval) for 10 h and 1.09 (0.85–1.40) for 24 h.
- TABLE 4
Most frequent adverse events observed in the study
Placebo GSK2798745 Total Subjects n 17 16 17 Number of participants with any event 9 (53) 11 (69) 13 (76) Number of participants with a drug-related event 2 (12) 2 (13) 4 (24) Most common adverse events: (adverse events occurring in ≥2 participants in any treatment group) Headache 3 (18) 7 (44) 8 (47) Diarrhoea 2 (12) 1 (6) 3 (18) Fatigue 1 (6) 2 (13) 3 (18) Oropharyngeal pain 2 (12) 0 2 (12) Data expressed as n (%) unless otherwise noted. Note: Adverse events were assigned to a treatment group based on the start date of the adverse events in relation to the study treatment period. Adverse events that started during the washout period were assigned to the Period 1 treatment group.
- TABLE 5
Summary of GSK2798745 pharmacokinetic parameters
Parameter Visit# N n Geometric mean 95% CI (lower, upper) %CVb¶ Cmax ng·mL−1 Day 1 16 16 17.862 (14.468–22.052) 41.1 Day 7 15 10.959 (9.425–12.741) 27.7 AUC(0–3.5) h·ng·mL−1 Day 1 16 16 36.156 (28.328–46.148) 48.3 Day 7 15 26.151 (22.479–30.424) 27.8 C24 ng·mL−1 Day 7 16 15 2.4179 (1.7295–3.3803) 66.5 Tmax h+ Day 1 16 16 2.500 (1.00–3.50) NA Day 7 15 2.500 (1.00–3.50) NA AUC: area under the curve. #: day 1 dose 4.8 mg; Days 2–7 dose 2.4 mg. ¶: coefficient of variability between participants. +: Tmax expressed as median and range.
