A phase II, multicenter, randomized, double-blind, placebo-controlled, ascending, multidose, U.S. study of oral LX1606 (aka LX1032) in patients with refractory symptomatic carcinoid syndrome.

Abstract

TPS168 Background: Carcinoid tumors are associated with serotonin (5-HT) secretion. High levels of serotonin are thought to contribute to the flushing, diarrhea, and abdominal discomfort observed in patients with carcinoid syndrome (CS). LX1606 (aka LX1032), an oral peripheral tryptophan hydroxylase (TPH) inhibitor that blocks serotonin synthesis, offers a potential novel therapeutic approach to CS. LX1606 has been granted “Fast Track” designation by the FDA. Methods: This study is evaluating the safety, tolerability, and preliminary efficacy of LX1606 in patients with CS. Endpoints include: reduction in daily bowel movements (BM), cutaneous flushing episodes, abdominal discomfort, and use of rescue short-acting octreotide or other rescue medication. Pharmacokinetics and pharmacodynamics (including whole blood 5-HT and urinary 5-HIAA) will also be assessed. Treatment: Patients with octreotide-refractory CS will be sequentially assigned to receive 4-weeks of LX1606 or placebo, in a 3:1 ratio. Oral LX1606 or placebo are administered 3 times daily; dose cohorts are 150 mg, 250 mg, 350 mg, 500 mg. All patients will continue stable-dose octreotide LAR for the duration of the study. After completing the 4-week blinded portion of the study, patients may receive open-label drug at their previously assigned dose level for 32 additional weeks. After completion of the dose escalation phase, 8 additional patients will receive treatment at the identified optimal dose level. Key eligibility: Patients with octreotide-refractory carcinoid syndrome, (defined as >4 BM/day).Current enrollment: 16 patients have been treated in the dose escalation phase. LX1606 500 mg TID has been identified as the optimal dose. As of 2/2011, enrollment is ongoing in the expansion phase. ClinicalTrials.gov registry: NCT00853047.