ble-dose long-acting SSA therapy for the duration of the DBT period. Xermelo was taken within 15 minutes before, or within 1 hour after food.
Table 2: BM response (TELESTAR Study)
Parameter
Placebo
Telotristat ethyl 250 mg tid
BMs/day at baseline
Number of patients
45
45
Baseline mean (SD)
5.2 (1.35)
6.1 (2.07)
Primary endpoint: change from baseline in BMs/day averaged over 12 weeks
Number of patients
45
45
Change averaged over 12 weeks: mean (SD)
˗0.6 (0.83)
˗1.4 (1.37)
ANCOVAa
Least Square mean difference
---
-0.6
97.5% CL for difference
---
-1.16, -0.06
p value
---
0.01
Percentage of patients with durable responseb
Number of patients
45
45
Responder, n (%)
9 (20.0)
20 (44.4)c
BM = bowel movement; CL=confidence limit; tid=three times daily; SD=standard deviation.
a. Analysis of covariance including treatment group and urinary 5-HIAA stratification at randomisation as fixed effects, and the baseline number of BM as a fixed covariate.
b. Defined as the proportion of responders with ≥30% reduction in daily number of BMs for ≥50% of time over the DBT period.
c. p=0.01
When the full effect of telotristat is observed (during the last 6 weeks of the DBT period) the proportion of responders with at least 30% BM reduction was 51% (23/45) in the 250 mg group versus 22% (10/45) in the placebo group (post-hoc analysis).
In the 12-week DBT period of the study, average weekly reductions in BM frequency on telotristat were observed as early as 3 weeks, with the greatest reductions occurring during the last 6 weeks of the DBT period, compared with placebo (refer to Figure 1).
Figure 1 - Mean change from baseline in BMs by study week during the DBT period, Intent-to-Treat Population
The proportions of patients reporting reductions from baseline in daily BM frequency (averaged over 12 weeks) were:
- Patients with a mean reduction of at least 1 BM per day: 66.7% (telotristat ethyl 250 mg) and 31.1% (placebo);
- Patients with a mean reduction of at least 1.5 BM per day: 46.7% (telotristat ethyl 250 mg) and 20.0% (placebo);
- Patients with a mean reduction of at least 2 BM per day: 33.3% (telotristat ethyl 250 mg) and 4.4% (placebo).
Table 3: u5-HIAA excretion at baseline and week 12 (TELESTAR Study)
Parameter
Placebo
Telotristat ethyl 250 mg tid
u5-HIAA excretion (mg/24 hours) at baseline
Number of Patients
44
42
Baseline Meana (SD)
81.0 (161.01)
92.6 (114.90)
Percent change from baseline in u5-HIAA excretion (mg/24 hours) at week 12
Number of Patients
28
32
Percent Change at Week 12: Mean (SD)
14.4 (57.80)
-42.3 (41.96)
Estimate of Treatment Difference (95% CL)b
---
-53.4 c
(-69.32, -38.79)
CL=confidence limit; tid=three times daily; SD=standard deviation; u5-HIAA = urinary 5--hydroxyindoleacetic acid.
a. Baseline data based on all patients with data at baseline.
b. Statistical tests used a blocked 2-sample Wilcoxon Rank Sum statistic (van Elteren test) stratified by the u5-HIAA stratification at randomization. CLs were based on the Hodges-Lehmann estimator of the median paired difference.
c. p<0.001
There was no significant difference between treatment groups for the endpoints of flushing and abdominal pain.
A post-hoc analysis showed that the average number of daily short-acting SSA injections used for rescue therapy over the 12-week DBT period was 0.3 and 0.7 in the telotristat ethyl 250 mg and placebo groups, respectively.
A pre-sp |
