Abstract 4378
Background
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.
Methods
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 |
| Deaths | 1 (3) | 0 | 0 |
Results
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.
Conclusions
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
Lexicon Pharmaceuticals
Funding
The TELESTAR and TELECAST studies were sponsored by Lexicon Pharmaceuticals. This analysis was sponsored by Ipsen.
Editorial Acknowledgement
Writing and editorial/submission support provided by Emma Leah, PhD (Ipsen); Tom Vizard, PhD, and Richard McDonald (Watermeadow Medical), funded by Ipsen.
Disclosure
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.