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Also known as LX1606, LX1606 Hippurate
Telotristat etiprate · 11 trials · 4 indications
An adverse event (AE) was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. A TEAE was an AE reported after the first dose of randomized treatment on Day 1.
u5-HIAA is a standard test used in clinical practice to assess neuroendocrine tumor (NET) activity and is collected as a 24-hour urine specimen. A negative change from Baseline indicates improvement.
An adverse event (AE) was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. A TEAE was an AE reported after the first dose of randomized treatment on Day 1.
An adverse event (AE) is defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug-related. An AE includes any noxious, pathological, or unintended change in anatomical, physiological, or metabolic functions as indicated by physical signs or symptoms occurring in any phase of the clinical study whether or not considered related to the study medication. A TEAE is an AE that occurs or worsens after receiving study drug.
Participants recorded the number of bowel movements per day in a daily diary. The total number of BMs per day were averaged over the 12-week period. A negative change from Baseline indicates improvement.
An adverse event (AE) was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. A TEAE was an AE reported after the first dose of randomized treatment on Day 1.
An adverse event (AE) was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug-related. Treatment-emergent AEs were defined as any AEs reported after the first dose of treatment on Day 1.
An adverse event (AE) was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug-related. Treatment-emergent AEs were defined as any AEs reported after the first dose of treatment on Day 1.
An adverse event (AE) was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug-related. A TEAE was an AE reported after the first dose of randomized treatment on Day 1.
An AE was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. A TEAE was an AE reported after receiving treatment.
| Arm | Type | Description |
|---|---|---|
| 250 mg Telotristat Etiprate | EXPERIMENTAL | Following a 3 to 4-week run-in period, participants were randomized to receive one 250 mg telotristat etiprate tablet and one placebo-matching telotristat etiprate tablet administered three times daily for 12 weeks, followed by a 36 week open-label extension period. |
| 500 mg Telotristat Etiprate | EXPERIMENTAL | Following a 3 to 4-week run-in period, participants were randomized to receive one 250 mg telotristat etiprate tablet and one placebo-matching telotristat etiprate tablet administered three times daily for one week, followed by two 250 mg telotristat etiprate tablets administered three times daily for 11 weeks in the 12 week double-blind treatment period, followed by a 36 week open-label extension period. |
| Placebo | PLACEBO_COMPARATOR | Following a 3 to 4-week run-in period, participants were randomized to receive two placebo-matching telotristat etiprate tablets administered three times daily for 12 weeks, followed by a 36 week open-label extension period. |
| Telotristat Etiprate Open-Label Extension | EXPERIMENTAL | Patients previously assigned to 250 mg or 500 mg three times daily of telotristat etiprate were administered two 250 mg telotristat etiprate tablets three times daily in a 36 week open-label extension (OLE) period. Patients previously assigned to placebo were administered one 250 mg telotristat etiprate tablet plus one placebo-matching tablet three times daily for one week, followed by two 250 mg telotristat etiprate tablets three times daily for 35 weeks. |
| Low Dose Telotristat Etiprate | EXPERIMENTAL | 500 mg telotristat etiprate (LX1606) administered orally once daily (QD). |
| High Dose Telotristat Etiprate | EXPERIMENTAL | 500 mg telotristat etiprate (LX1606) administered orally three times daily (TID). |
| Telotristat etiprate - Core Phase | EXPERIMENTAL | Following a 2-week Run-In Period, participants received telotristat etiprate capsules at a starting dose of 150 mg, orally three times daily (TID) for 14 days in the Core Phase. Dose escalations (250 mg, 350 mg, 500 mg) occurred serially every 14 days, up to a maximum dosage of telotristat etiprate 500 mg TID, as guided by specific clinical criteria for dose escalation. Upon completion of 12 weeks of treatment, participants were eligible to receive telotristat etiprate in the optional Open-label Extension Period. |
| Telotristat etiprate - Extension Period | EXPERIMENTAL | Participants received telotristat etiprate at their highest tolerated dose (250 mg or 500 mg), orally, TID for 124 weeks in the Open-label Extension Period. If neither dose was tolerated participants were discontinued from the study and completed the 2-week Follow-up Visit. |
| Telotristat Etiprate 150 mg Core Phase | EXPERIMENTAL | Telotristat etiprate capsules,150 mg orally 3 times daily for 28 days in the double-blind treatment period (core phase) in combination with stable-dose octreotide long-acting release (LAR) depot therapy given once per month. Upon completion of 28-days of treatment, participants were eligible to enter the optional open-label extension period. |
| Telotristat Etiprate 250 mg Core Phase | EXPERIMENTAL | Telotristat etiprate capsules, 250 mg orally 3 times daily for 28 days in the double-blind treatment period in combination with stable-dose octreotide LAR depot therapy given once per month. Upon completion of 28-days of treatment, participants were eligible to enter the optional open-label extension period. |
| Telotristat Etiprate 350 mg Core Phase | EXPERIMENTAL | Telotristat etiprate capsules, 350 mg orally 3 times daily for 28 days in the double-blind treatment period in combination with stable-dose octreotide LAR depot therapy given once per month. Upon completion of 28-days of treatment, participants were eligible to enter the optional open-label extension period. |
| Telotristat Etiprate 500 mg Core Phase | EXPERIMENTAL | Telotristat etiprate capsules, 500 mg orally 3 times daily for 28 days in the double-blind treatment period in combination with a stable-dose octreotide LAR depot therapy given once per month. Upon completion of 28-days of treatment, participants were eligible to enter the optional open-label extension period. |
| Placebo Core Phase | EXPERIMENTAL | Placebo-matching telotristat etiprate capsules, orally 3 times daily for 28 days in the double-blind treatment period in combination with stable-dose octreotide LAR depot therapy given once per month. Upon completion of 28-days of treatment, participants were eligible to receive telotristat etiprate in the optional open-label extension period. |
| Telotristat Etiprate Open-Label Extension Phase | EXPERIMENTAL | Telotristat etiprate at assigned dose level for 8 weeks in combination with stable-dose octreotide LAR depot therapy given once per month in the open-label extension period. Upon completion of the 8-week period, participants could enter an additional extension period of 172 weeks, receiving telotristat etiprate at the assigned dose or maximum tolerated dose (500 mg 3 times daily). |
| All subjects | EXPERIMENTAL | All subjects will receive a single oral dose of fexofenadine on Day 1 while fasting. Days 2 to 5 will be Washout days. On Day 6, subjects will begin a 5 day telotristat etiprate regimen. On Day 10 subjects will be given the morning telotristat etiprate dose concomitantly with a single dose of fexofenadine while fasting. |
| Period 1 | EXPERIMENTAL | Single oral dose of 500 mg telotristat etiprate on Day 1 |
| Period 2 | OTHER | Subcutaneous injections of 200 µg octreotide acetate three times daily with a single oral dose of 500 mg telotristat etiprate on Day 6 |
| Telotristat etiprate | EXPERIMENTAL | Single dose of telotristat etiprate followed by a 7-day washout. |
| Moxifloxacin | ACTIVE_COMPARATOR | Single dose of moxifloxacin followed by a 7-day washout. |
| 500 mg LX606 | EXPERIMENTAL | All subjects will receive a single oral 500 mg dose of \[14C\]-LX1606. |
| Name | Type | Description |
|---|---|---|
| Telotristat etiprate | DRUG | Telotristat etiprate tablets |
| Placebo | DRUG | Placebo-matching telotristat etiprate tablets |
| Placebo-matching telotristat etiprate | DRUG | Placebo-matching telotristat etiprate tablets. |
| Octreotide LAR Depot | DRUG | A stable-dose octreotide LAR depot therapy; administered subcutaneously once per month. |
| Fexofenadine | DRUG | All subjects will receive 180 mg fexofenadine |
| Octreotide acetate | DRUG | 200 µg octreotide acetate three times daily |
| Midazolam | DRUG | All subjects will receive 3 mg (1.5 mL oral syrup \[2mg/mL\]). |
| Moxifloxacin | DRUG | 400 mg moxifloxacin (one 400 mg tablet) |
| 500 mg [14C]-LX1606 | DRUG | 500 mg dose of LX1606 containing a target dose of 3.32 Megabecquerel (MBq) of radiation as \[14C\]-LX1606. |
Inclusion Criteria: * Patients ≥ 18 years of age * All patients of reproductive potential must agree to use an adequate method of contraception during the study and for 12 weeks after the Follow-up visit. * Histopathologically-confirmed, well-differentiated metastatic neuroendocrine tumor * Documen...
Telotristat etiprate is an investigational small molecule being studied in carcinoid syndrome, drug interaction assessments, QT interval evaluation, and ulcerative colitis. It is being developed by Lexicon Pharmaceuticals, Inc. as an oral therapy. The program spans both oncology-related carcinoid syndrome and gastrointestinal and cardiac safety indications.
Telotristat etiprate targets tryptophan hydroxylase 2 (TPH2) and tryptophan hydroxylase 1 (TPH1). It acts as an inhibitor of these enzymes, which are involved in serotonin synthesis. By inhibiting TPH, the drug is designed to reduce peripheral serotonin production, a mechanism relevant to carcinoid syndrome.
Telotristat etiprate is being developed by Lexicon Pharmaceuticals, Inc., which trades on the Nasdaq under the ticker LXRX. Lexicon is the sponsor of the clinical program evaluating the drug across carcinoid syndrome, drug interaction, QT interval, and ulcerative colitis studies.
Telotristat etiprate is in Phase 3 development. It is an investigational agent and has not been approved by the FDA. The clinical program includes completed Phase 1 trials and later-stage evaluation, with five trials recorded in total and no currently active trials.
Completed trials include NCT02195635, a Phase 1 drug-drug interaction study with octreotide acetate; NCT02157558, a Phase 1 interaction study with fexofenadine; NCT02155205, a Phase 1 thorough QT study; and NCT02147808, a Phase 1 interaction study with midazolam. All enrolled healthy volunteers in the United States.
Across the five recorded clinical trials, 373 participants have been enrolled. The studies were randomized, double-blind, and controlled where applicable. Trial sizes ranged from 24 to 48 participants in the Phase 1 studies, which enrolled healthy volunteers aged 18 years and older in the United States.