Symptoms and General Pathology

All Conditions

Neoplasms

Substance Related Disorders

Rare Diseases

Syndrome

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

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.

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 capsules orally three times daily.

Telotristat etiprate

Pablo LaPuerta, MD

The purpose of the study is to evaluate the safety and tolerability of orally administered telotristat etiprate (LX1606) in participants with symptomatic carcinoid syndrome.

Study of Telotristat Etiprate (LX1606) in Participants With Symptomatic Carcinoid Syndrome

A Phase 2, Open-Label, Multi-Center, Serial Ascending-Dose, Dose-Finding Study to Evaluate the Safety and Tolerability of LX1606 in Subjects With Symptomatic Carcinoid Syndrome

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.

Participants recorded the number of bowel movements in a daily diary. The change from baseline value was calculated as the difference between mean numbers of BMs of the post-baseline interval (Weeks 9 to 12) and baseline. A negative change from baseline indicates improvement. Baseline for the Extension Period was defined as non-missing assessment in Run-in period prior to the first dose of study drug.

Participants assessed stool form/consistency in a daily diary using a 6-point scale (0-none, 1-hard, 2-firm, 3-soft, 4-loose, 5-watery). The change from the baseline value was calculated as the difference between a mean score of the post-baseline interval (Weeks 9 to 12) and baseline. 0 indicates the best score and 5 indicates the worst score. A negative change from baseline indicates improvement. Baseline for the Extension Period was defined as non-missing assessment in Run-in period prior to the first dose of study drug.

Participants assessed the urgency to defecate using a daily diary response to the following question, "Have you felt or experienced a sense of urgency to pass stool today?". The change from the baseline value was calculated as the difference between the mean score (percentage of days) of the post-baseline interval (Weeks 9 to 12) and baseline. Baseline for the Extension Period was defined as non-missing assessment in Run-in period prior to the first dose of study drug.

Sensation/severity of nausea was measured using a 100 mm VAS. Participants rated their perception of the sensation/severity of nausea experienced by marking a single vertical line on a VAS scale from 0 to 100 mm, where 0 = No vomiting and 100 = vomiting. The change from the baseline value was calculated as the difference between the mean score of the post-baseline interval (Weeks 9 to 12) and baseline. 0 indicates the best score, 100 indicates the worst score. Baseline for the Extension Period was defined as non-missing assessment in Run-in period prior to the first dose of study drug.

Participants assessed their symptoms using a weekly subjective response to 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 values for improvement in global assessment of symptoms associated with carcinoid syndrome in the Core Phase were averaged from Weeks 9 to 12.

The severity of abdominal pain was measured using a 100 mm VAS. Participants rated their perception of the sensation/severity of abdominal pain or experienced by marking a single vertical line on a VAS scale from 0 to 100 mm, where 0 = No vomiting and 100 = vomiting. The change from the baseline value was calculated as the difference between the mean score of the post-baseline interval (Weeks 9 to 12) and baseline. 0 indicate the best score, 100 indicates the worst score. Baseline for the Extension Period was defined as non-missing assessment in Run-in period prior to the first dose of study drug.

Participants recorded the number of daily cutaneous flushing episodes experienced in the daily diary. The change from baseline value was calculated as the difference between the mean numbers of cutaneous flushing episodes of the post-baseline interval (Weeks 9 to 12) and baseline. Baseline for the Extension Period was defined as non-missing assessment in Run-in period prior to the first dose of study drug.

Clinically meaningful symptom reduction was defined as either: a) an average of \< 4 bowel movements per day over 15 consecutive days, b) a 50% reduction from baseline in the number of bowel movements, c) a positive response to the question regarding adequate relief, or d) a 50% reduction from baseline in the number of daily flushing episodes.

Urinary 5-HIAA (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. The change from baseline value for the Extension Period was calculated as the difference between mean change in 5-HIAA of the post-baseline interval (Weeks 20 to 21) and baseline. A negative change from baseline indicates improvement. Baseline for the Extension Period was defined as non-missing assessment in Run-in period prior to the first dose of study drug.

Lexicon Pharmaceuticals

Telotristat Etiprate- Core Phase

Telotristat Etiprate- Extension Period

Age, Continuous

Sex: Female, Male

White

Race/Ethnicity, Customized

United Kingdom

Germany

Region of Enrollment

The safety set included all the enrolled participants who received at least 1 dose of study drug.

Pablo Lapuerta, MD

Any TEAE

Drug-Related TEAE

The safety set (SS) included all the enrolled participants who received at least 1 dose of study drug.

Number of Participants With Any Treatment Emergent Adverse Events (TEAEs) and Drug-Related TEAEs in the Core Phase

SS included all enrolled participants who had received at least 1 dose of study drug in the 124-week Extension Period.

Number of Participants With Any Treatment Emergent Adverse Events (TEAEs) and Drug-Related TEAEs in the Extension Period

Efficacy full analysis set (EFAS) in Core Phase included all participants with at least 1 post-Baseline efficacy assessment and full analysis set (FAS) in Extension Period(EP) included all participants in SS with at least 1 post-Baseline efficacy assessment in 124-week EP. Number analyzed is the participants with evaluable data at given time point.

Change From Baseline in Number of Bowel Movements (BMs)

EFAS in the Core Phase included all participants who had at least 1 post-Baseline efficacy assessment and FAS in the Extension period included all participants in the safety set who had at least 1 post-Baseline efficacy assessment in 124-week Extension Period. Number analyzed is the number of participants with evaluable data at given time-point.

Change From Baseline in Stool Form/Consistency

EFAS in Core Phase included all participants who had at least 1 post-Baseline efficacy assessment and FAS in Extension Period included all participants in the safety set who had at least 1 post-Baseline efficacy assessment in the 124-week Extension Period. Number analyzed is the number of participants with evaluable data at the given time-point.

Change From Baseline in Percentage of Days With Sensation of Urgency to Defecate

Change From Baseline in Sensation/Severity of Nausea Using 100 mm Visual Analog Scale (VAS)

Number of Participants With an Improvement in Global Assessment of Symptoms Associated With Carcinoid Syndrome

Change From Baseline in Daily Severity of Abdominal Pain or Discomfort Using 100 mm Visual Analog Scale (VAS)

Change From Baseline in Daily Number of Cutaneous Flushing Episodes

EFAS included all participants who had at least 1 post-baseline efficacy assessment.

Number of Participants Achieving Clinically Meaningful Symptom Reduction in the Core Phase

Pharmacodynamic (PD) analysis set included all participants who had received at least 1 dose of study drug, had a valid baseline PD assessment, and at least 1 valid post-baseline PD assessment (whole blood 5-HT or u5-HIAA) in Core Phase and Extension Period.

Spots Global Cancer Trial Database for Study of Telotristat Etiprate (LX1606) in Participants With Symptomatic Carcinoid Syndrome

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

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