Table 4.
Symptom assessment in phase III clinical trials with telotristat ethyl
| TELESTAR (Kulke, 2016)77 | TELECAST (Pavel, 2018)78 | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Baseline | Treatment (week 12) | Baseline | Treatment (week 12) | ||||||||||
| Telotristat ethyl 250 mg (n=45) |
Telotristat ethyl 500 mg (n=45) |
Placebo (n=45) |
Telotristat ethyl 250 mg (n=36) |
Telotristat ethyl 500 mg (n=37) |
Placebo (n=35) |
Telotristat ethyl 250 mg (n=25) |
Telotristat ethyl 500 mg (n=25) |
Placebo (n=26) |
Telotristat ethyl 250 mg (n=25) |
Telotristat ethyl 500 mg (n=25) |
Placebo (n=35) |
||
| BM frequency per day | Mean (SD) | 6.1 (2.1) | 5.8 (2.0) | 5.2 (1.4) | 4.24 (nr) | 3.83 (nr) | 4.34 (nr) | 2.5 (1.2) | 2.8 (1.6) | 2.2 (0.7) | nr (nr) | nr (nr) | nr (nr) |
| Arithmetic mean reduction from baseline to week 12& | – | – | – | −1.7 | −2.1 | −0.9 | – | – | – | – | – | – | |
| Daily reduction averaged over 12 weeks mean (SD) | – | – | – | −1.43 (1.36) | −1.46 (1.31) | −0.62 (0.83) | – | – | – | −0.45 (0.69) | −0.60 (0.72) | 0.05 (0.33) | |
| p-Valueb | – | – | – | <0.001 | <0.001 | – | – | – | – | 0.004 | <0.001 | – | |
| Abdominal pain score | Mean (SD) | 2.6 (2.3) | 2.6 (2.2) | 2.5 (2.3) | nr (nr) | nr (nr) | nr (nr) | 1.2 (1.5)a | 1.8 (1.7)a | 1.7 (1.7)a | nr (nr) | nr (nr) | nr (nr) |
| Change from baseline over 12 weeks mean (SD) | – | – | – | −0.49 (1.44) | −0.33 (1.18) | −0.23 (1.16) | – | – | – | −0.23 (0.97) | 0.03 (0.77) | −0.06 (0.78) | |
| p-Valueb | – | – | – | 0.28 | 0.87 | – | – | – | – | 0.61 | 0.66 | – | |
| Flushing episodes per day | Mean (SD) | 2.8 (3.7) | 2.7 (3.4) | 1.8 (1.9) | nr (nr) | nr (nr) | nr (nr) | 2.7 (3.7) | 1.8 (2.2) | 3.7 (4.1) | nr (nr) | nr (nr) | nr (nr) |
| Change from baseline over 12 weeks mean (SD) | – | – | – | −0.30 (1.31) | −0.53 (1.34) | −0.16 (1.16) | – | – | – | −0.06 (0.98) | 0.11 (2.10) | −0.33 (1.22) | |
| p-Valueb | – | – | – | 0.39 | 0.84 | – | – | – | – | 0.67 | 0.58 | – | |
| Stool consistency | Mean (SD) | nr (nr) | nr (nr) | nr (nr) | nr (nr) | nr (nr) | nr (nr) | 5.1 (0.8) | 5.3 (0.8) | 5.0 (0.9) | nr (nr) | nr (nr) | nr (nr) |
| Change from baseline over 12 weeks mean (SD) | – | – | – | −0.26 (0.47) | −0.36 (0.41) | −0.22 (0.48) | – | – | – | −0.20 (0.70) | −0.60 (0.86) | 0.01 (0.41) | |
| p-Valueb | – | – | – | 0.57 | 0.052 | – | – | – | – | 0.09 | 0.009 | – | |
| Daily rescue short-acting SSA use | Mean (SD) | nr (nr) | nr (nr) | nr (nr) | nr (nr) | nr (nr) | nr (nr) | nr (nr) | nr (nr) | nr (nr) | nr (nr) | nr (nr) | nr (nr) |
| Change from baseline over 12 weeks mean (SD) | – | – | – | −0.11 (nr) | 0.03 (nr) | 0.18 (nr) | – | – | – | −0.07 (0.35) | 0.01 (0.10) | −0.01 (0.14) | |
| p-Valueb | – | – | – | 0.19 | 0.16 | – | – | – | – | 0.45 | 0.98 | – | |
| Urgency (proportion of days) | Proportion of days mean (SD) | nr (nr) | nr (nr) | nr (nr) | 0.67 (0.34) | 0.60 (0.31) | 0.75 (0.29) | nr (nr) | nr (nr) | nr (nr) | nr (nr) | nr (nr) | nr (nr) |
| p-Valueb | – | – | – | 0.35 | 0.006 | – | – | – | – | – | – | – | |
Notes: aMean weekly abdominal pain rating. bCompared versus placebo arm. &Arithmetic mean reduction in daily BM frequency from baseline to week 12 was only calculated for patients for whom both baseline and week 12 assessments were available.
Abbreviations: BM, bowel movement; nr, not reported; n, number of patients.