LAN 120 mg, a somatostatin analogue (SSA), is approved in the EU and recently in the USA for CS. In two phase 3 trials in CS, TE 250 mg or 500 mg three-times daily (tid) combined with SSA therapy (LAN or octreotide) demonstrated reduced bowel movement (BM) frequency and urinary 5-hydroxyindole acetic acid (u5-HIAA) levels vs. PBO. TE 250 mg is approved by the FDA and EMA for CSD inadequately controlled by SSAs. This post hoc meta-analysis used patient-level data from the two phase 3 studies to further examine the efficacy and safety of TE + LAN.
In the TELESTAR (NCT01677910) and TELECAST (NCT02063659) studies, patients using and continuing stable-dose SSAs were randomly assigned 1:1:1 to PBO, TE 250 mg or TE 500 mg tid for a 12-week double-blind (DB) period. Here, only data for patients using LAN during the run-in periods were included. Endpoints included descriptive changes from baseline in 24-hour u5-HIAA, BMs/day, flushing episodes and incidence of adverse events (AEs).Table: 1314P
|PBO tid||TE 250 mg tid||TE 500 mg tid|
|Number of LAN patients randomly allocated||n = 29||n = 10||n = 15|
|u5-HIAA (mg/24 hour)|
|Patients with levels > upper limit of normal (at randomization): n (%)||15 (51.7)||6 (60.0)||9 (60.0)|
|Baseline: median [95% CI]||24.9 [12.2; 80.9]||57.6 [12.9; 159.8]||31.0 [19.0; 259.2]|
|Week-12 change from baseline: median [95% CI]||1.6 [–6.7; 5.0]||–12.4 [–86.4; 77.2]||–24.6 [–134.6; –10.0]|
|BMs/day: median [95% CI]|
|Baseline||3.5 [2.4; 4.4]||3.1 [1.3; 5.6]||5.3 [3.6; 6.1]|
|Week-12 change from baseline||–0.2 [–1.1; 0.2]||–0.9 [–2.6; –0.0]||–1.29 [–3.3; –0.0]|
|Flushing (counts/day): median [95% CI]|
|Baseline||3.5 [1.5; 5.1]||2.8 [0.5; 4.9]||2.9 [0.8; 4.3]|
|Week-12 change from baseline||0.00 [–1.1; 0.4]||–0.5 [–1.2; 0.7]||–0.5 [–2.0; 0.4]|
|Safety: n (%) patients|
|Any AE||26 (90)||9 (90)||14 (93)|
|Treatment-related AEs||8 (28)||6 (60)||12 (80)|
|Serious AEs||3 (10)||1 (10)||4 (27)|
|Treatment-related serious AEs||1 (3)||0||0|
Of 211 patients in the studies, 54 receiving LAN were included in the analysis (44% women, mean [SD] age 61.8 [10.5] years, mean [SD] BMI 25.7 [5.0] kg/m2; 34 [63%] used LAN 4-weekly, 20 [37%] used LAN 3-weekly). One patient received octreotide instead of LAN during the DB period. Randomization of this cohort is shown with efficacy and safety data in the table.
Changes from baseline in u5-HIAA, BMs and flushing suggest a trend towards meaningful efficacy of TE + LAN in CSD, in a population with moderately elevated baseline BM frequency. The combination TE + LAN was generally well tolerated. No power calculation was performed for this exploratory post hoc analysis; imbalanced groups and low patient numbers preclude any formal comparison with PBO. Evaluation of this TE + LAN regimen as first-line therapy in patients with CSD may be warranted.
Clinical trial identification
TELESTAR: NCT01677910 TELECAST: NCT02063659.
Legal entity responsible for the study
The TELESTAR and TELECAST studies were sponsored by Lexicon Pharmaceuticals. This analysis was sponsored by Ipsen.
Writing and editorial/submission support provided by Emma Leah, PhD (Ipsen); Tom Vizard, PhD, and Richard McDonald (Watermeadow Medical), funded by Ipsen.
D. Hörsch: Consultant: Ipsen, Lexicon, Novartis, Pfizer; Research investigator: Ipsen, Lexicon, Novartis, Pfizer; Speaker’s bureau: Ipsen, Lexicon, Novartis, Pfizer. R. Garcia-Carbonero: Honoraria: AAA, Ipsen, Novartis, Pfizer; Consultant: AAA, Ipsen, Novartis, Pfizer; Grant recipient: Pfizer; Research investigator: Ipsen, Novartis, Pfizer. J.W. Valle: Honoraria: Ipsen. Consultant: Ipsen; Grant recipient: Ipsen; Research investigator: Ipsen. Speaker's bureau: Ipsen. S. Welin: Honoraria: Ipsen, Novartis. L. Keeber: Employee: Ipsen. A. Houchard: Grant recipient, Employee, Stock owner: Ipsen. P. Lapuerta: Employee, Stock owner: Lexicon Pharmaceuticals. All other authors have declared no conflicts of interest.