Symptoms and General Pathology

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Carcinoid Tumor

Malignant Carcinoid Syndrome

Serotonin Syndrome

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Adenocarcinoma

Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Drug-Related Side Effects and Adverse Reactions

Chemically-Induced Disorders

Carcinoid Syndrome

Neuroendocrine Tumor

Neuroepithelioma

Antineoplastic Agents

Gastrointestinal Agents

All Drugs and Chemicals

Octreotide

Antineoplastic Agents, Hormonal

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 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 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 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-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 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).

Telotristat etiprate capsules; orally 3 times daily.

Telotristat etiprate

A stable-dose octreotide LAR depot therapy; administered subcutaneously once per month.

Octreotide LAR Depot

Placebo-matching telotristat etiprate capsules; orally 3 times daily.

Placebo

Pablo Lapuerta, MD

The purpose of this study is to evaluate the safety and tolerability of telotristat etiprate (LX1606) versus a placebo control in participants with symptomatic carcinoid syndrome not managed by stable-dose long-acting octreotide therapy. Following determination of the maximally tolerated or effective dose, cohort expansion will occur to confirm effect on symptoms and safety profile.

Study of Telotristat Etiprate (LX1606) in Participants With Symptomatic Carcinoid Syndrome Not Managed by Stable-Dose Octreotide Therapy

A Phase 2, Multicenter, Randomized, Double-blind, Placebo-controlled, Ascending, Multidose Study To Determine Safety and Tolerability of Orally Administered LX1606 in Subjects With Symptomatic Carcinoid Syndrome Refractory to Stable-Dose Octreotide Long-Acting Release Depot Therapy

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.

Participants recorded the number of BMs per day in a daily diary. The total number of BMs per day were averaged over the 4-week period. A negative change from Baseline indicates improvement.

Participants recorded stool form in a daily diary using a 6-point scale (0-none,1-hard, 2-firm, 3-soft, 4-loose, 5-watery). A negative change from Baseline indicates improvement.

Participants recorded the sensation of urgency to defecate (Yes or No) in a daily diary. A negative change from Baseline indicates improvement.

Participants recorded the number of daily flushing episodes per day in a daily diary. The total number of flushing episodes per day were averaged over the 4-week period. A negative change from Baseline indicates improvement.

Participants recorded the severity of abdominal pain or discomfort in a daily diary assessed using a 4-point scale (0-none, 1-mild, 2-moderate, 3-severe). A negative change from Baseline indicates improvement.

u5-HIAA is a standard test used in clinical practice to assess the neuroendocrine tumor (NET) activity and is collected as a 24-hour urine specimen. A negative change from Baseline indicates improvement.

Blood samples were collected for assessment of Chromogranin A level. A negative change from Baseline indicates improvement.

Participants were asked to answer the following question: "In the past 7 days, have you had adequate relief of your carcinoid syndrome bowel complaints such as diarrhea, urgent need to have a bowel movement, abdominal pain, or discomfort?". The number of participants who answered Yes are reported.

Participants recorded details (location and frequency of injection) of subcutaneous injections of rescue, short-acting octreotide, if taken, in the daily diary. A negative change from Baseline indicates improvement.

Time to the first subcutaneous injections of rescue, short-acting octreotide was determined from the participant's daily diary.

Complete Response to treatment was defined as one of the following: 1. Less than 4 bowel movements per day; or 2. A decrease in daily bowel movements that is ≥ 50% from baseline; or 3. A positive response to the global assessment question ("In the past 7 days, have you had adequate relief of your carcinoid syndrome bowel complaints such as diarrhea, urgent need to have a bowel movement, abdominal pain or discomfort?") for each of the last 2 weeks of the Treatment Period.

Lexicon Pharmaceuticals

Safety Set included all participants who received at least one dose of study drug.

Participants received placebo-matching telotristat etiprate capsules, 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 receive telotristat etiprate in the optional open-label extension period.

Placebo Core Phase

Participants received telotristat etiprate capsules,150 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 150 mg Core Phase

Participants received 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 250 mg Core Phase

Participants received 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 350 mg Core Phase

Participants received 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.

Telotristat Etiprate 500 mg Core Phase

Participants received 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).

Telotristat Etiprate Open-Label Extension Phase

Total

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

The Safety Set, Core Phase included all participants who received at least one dose of study drug.

Any TEAE

Related TEAEs

The Safety Set Core Phase included all participants who received at least one dose of study drug in the core phase.

Number of Participants With Any Treatment-emergent Adverse Event (TEAE) and Any Drug-related TEAE in the Core Phase

The Safety Set Extension Period included all participants who received at least one dose of study drug in the open-label extensions phase.

Number of Participants With Any TEAE in the Open-Label Extension Phase

Participants from the modified Intent to Treat (mITT) Set, Core Phase, all participants who received any fraction of a dose of study drug and had at least 1 week of data recorded in the daily diary after receiving study drug, with data available for analysis.

Change From Baseline in Mean Number of Bowel Movements (BMs) Per Day

Participants from the mITT Set Core Phase, all participants who received any fraction of a dose of study drug and had at least 1 week of data recorded in the daily diary after receiving study drug, with data available for analysis.

Change From Baseline in Weekly Mean Stool Form

Participants from the mITT Set Core Phase, all participants who received any fraction of a dose of study drug and had at least 1 week of data recorded in the daily diary after receiving study drug with data available for analysis.

Change From Baseline in Percentage of Days Per Week Experiencing a Sensation of Urgency to Defecate

Change From Baseline in Number of Cutaneous Flushing Episodes

Participants from the mITT Set Core Phase, all participants who received any fraction of a dose of study drug and had at least 1 week of data recorded in the daily diary after receiving study drug, with data available for analysis. Last Observation Carried Forward (LOCF)

Change From Baseline in Severity of Abdominal Pain or Discomfort

Participants from the Pharmacodynamic (PD) Analysis Set Core Phase, all participants who received any fraction of a dose of study drug and had a valid Baseline and at least 1 valid post-Baseline PD assessment, with data available for analysis.

Change From Baseline in Urinary 5-hydroxyindoleacetic Acid (u5-HIAA)

Change From Baseline in Chromogranin A

Number of Participants Reporting Improvement in the Subjective Global Assessment of Symptoms Associated With Carcinoid Syndrome

Change From Baseline in Frequency of Rescue for Short-acting Octreotide Use/Day

Participants from the mITT Set Core Phase, all participants who received any fraction of a dose of study drug and had at least 1 week of data recorded in the daily diary after receiving study drug, As per protocol only the Placebo Core Phase and Telotristat Etiprate 500 mg Core Phase were included in the analysis.

Time to First Rescue, Short-acting Octreotide

The mITT Set Core Phase included all participants who received any fraction of a dose of study drug and had at least 1 week of data recorded in the daily diary after receiving study drug.

Spots Global Cancer Trial Database for Study of Telotristat Etiprate (LX1606) in Participants With Symptomatic Carcinoid Syndrome Not Managed by Stable-Dose Octreotide Therapy

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