Symptoms and General Pathology

All Conditions

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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.

Change From Baseline in Urinary 5-Hydroxyindoleacetic Acid (HIAA) Levels

Telotristat Etiprate -Extension Period

Core Phase

Extension Period

One telotristat etiprate (250 mg) tablet administered three times daily.

Two telotristat etiprate (250 mg) tablets administered three times daily.

The primary objective of this study is to evaluate the long-term safety and tolerability of orally administered telotristat etiprate.

Telotristat Etiprate - Expanded Treatment for Patients With Carcinoid Syndrome Symptoms

A Multicenter, Long-term Extension Study to Further Evaluate the Safety and Tolerability of Telotristat Etiprate (LX1606)

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.

QLQ-C30 is a standardized 30-item scale to assess health-related quality of life composed of 5 functional scales (physical functioning \[5 items\], role functioning \[2 items\], emotional functioning \[4 items\], cognitive functioning \[2 items\], and social functioning \[2 items\]); 3 symptom scales (fatigue \[3 items\], nausea/vomiting \[2 items\], and pain \[2 items\]); a global health status (GHS) /quality of life (QOL) scale \[2 items\]; 6 single items (dyspnoea, insomnia, appetite loss, constipation, diarrhoea, and financial difficulties). 28 questions answered:1 (not at all) to 4 (very much) and 2 questions on overall health/QOL answered:1 (poor) to 7 (excellent). All of the scales and single-item measures are transformed to a score:0 to 100. For functioning scales and global QOL higher scores indicate better functioning (a positive change from Baseline indicates improvement); for symptom scales higher scores indicate more severe symptoms (a negative change from Baseline indicates improvement).

GI.NET21 is a standardized 21-item scale composed of both multi-item scales and single-item measures that include 5 functional scales (gastrointestinal (GI) \[5 items\], endocrine \[3 items\], treatment-related \[3 items\], social functioning \[3 items\], and disease-related worries scale \[DRWS\] \[3 items\]) and 4 single items (muscle and bone pain symptom (BPS), sexual functioning, communication function (CF), body image and information about the disease). Each item is scored from 1 (not at all) to 4 (very much). All of the scales and single-item measures are transformed to a score of 0 to 100. For functioning scales higher scores indicate better functioning (a positive change from Baseline indicates improvement); for symptom scales higher scores indicate more severe symptoms (a negative change from Baseline indicates improvement).

Participants were asked to respond 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 percentage of participants reporting adequate relief (answered Yes) were reported.

Participants were asked the following question to assess global symptoms associated with carcinoid syndrome (CS) on an 11-point scale: "Rate the severity of your overall carcinoid symptoms over the past 7 days on a scale from 0 to 10, where 0=no symptoms and 10=worst symptoms ever experienced. A negative change from baseline indicated improvement.

Safety population included all participants who received any fraction of a dose of telotristat etiprate during the study.

Participants were treated with telotristat etiprate in a previous study for 9 to 46 months. Participants received one telotristat etiprate (250 mg) tablet three times daily (tid) up to an additional 228 weeks in this long-term extension study.

Telotristat Etiprate 250 mg

Participants were treated with telotristat etiprate in a previous study for 9 to 46 months. Participants received two telotristat etiprate (250 mg) tablets tid up to an additional 204 weeks in this long-term extension study.

Telotristat Etiprate 500 mg

Total

Race

Ethnicity

Canada

Sweden

Netherlands

Belgium

United States

Italy

Israel

France

Australia

Spain

Safety Population included all participants who received any fraction of a dose of telotristat etiprate during the study.

Number of Participants With Treatment-Emergent Adverse Events (TEAEs)

GHS/QOL, Baseline

GHS/QOL, Change at Week 24

GHS/QOL, Change at Week 48

GHS/QOL, Change at Week 72

GHS/QOL, Change at Week 84

Physical functioning, Baseline

Physical functioning, Change at Week 24

Physical functioning, Change at Week 48

Physical functioning, Change at Week 72

Physical functioning, Change at Week 84

Role functioning, Baseline

Role functioning, Change at Week 24

Role functioning, Change at Week 48

Role functioning, Change at Week 72

Role functioning, Change at Week 84

Emotional functioning, Baseline

Emotional functioning, Change at Week 24

Emotional functioning, Change at Week 48

Emotional functioning, Change at Week 72

Emotional functioning, Change at Week 84

Cognitive functioning, Baseline

Cognitive functioning, Change at Week 24

Cognitive functioning, Change at Week 48

Cognitive functioning, Change at Week 72

Cognitive functioning, Change at Week 84

Social functioning, Baseline

Social functioning, Change at Week 24

Social functioning, Change at Week 48

Social functioning, Change at Week 72

Social functioning, Change at Week 84

Fatigue, Baseline

Fatigue, Change at Week 24

Fatigue, Change at Week 48

Fatigue, Change at Week 72

Fatigue, Change at Week 84

Nausea and vomiting, Baseline

Nausea and vomiting, Change at Week 24

Nausea and vomiting, Change at Week 48

Nausea and vomiting, Change at Week 72

Nausea and vomiting, Change at Week 84

Pain, Baseline

Pain, Change at Week 24

Pain, Change at Week 48

Pain, Change at Week 72

Pain, Change at Week 84

Dyspnea, Baseline

Dyspnea, Change at Week 24

Dyspnea, Change at Week 48

Dyspnea, Change at Week 72

Dyspnea, Change at Week 84

Insomnia, Baseline

Insomnia, Change at Week 24

Insomnia, Change at Week 48

Insomnia, Change at Week 72

Insomnia, Change at Week 84

Appetite loss, Baseline

Appetite loss, Change at Week 24

Appetite loss, Change at Week 48

Appetite loss, Change at Week 72

Appetite loss, Change at Week 84

Constipation, Baseline

Constipation, Change at Week 24

Constipation, Change at Week 48

Constipation, Change at Week 72

Constipation, Change at Week 84

Diarrhea, Baseline

Diarrhea, Change at Week 24

Diarrhea, Change at Week 48

Diarrhea, Change at Week 72

Diarrhea, Change at Week 84

Financial difficulties, Baseline

Financial difficulties, Change at Week 24

Financial difficulties, Change at Week 48

Financial difficulties, Change at Week 72

Financial difficulties, Change at Week 84

Participants were treated with telotristat etiprate in a previous study for 9 to 46 months. Telotristat etiprate (250 or 500 mg) one or two tablets administered tid up to an additional 228 weeks (250 mg) or up to an additional 204 weeks (500 mg) in this long-term extension study.

Telotristat Etiprate (All Participants)

Per-Protocol (PP) population=participants who received telotristat etiprate;had no major protocol deviations that interfered with collection/interpretation of efficacy data. Number analyzed=participants with data at given time-point.Participants were combined for this outcome measure as they received dose adjustments per investigator's discretion.

Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30) Score at Each Visit

Endocrine scale, Baseline

Endocrine scale, Change at Week 24

Endocrine scale, Change at Week 48

Endocrine scale, Change at Week 72

Endocrine scale, Change at Week 84

GI symptoms scale, Baseline

GI symptoms scale, Change at Week 24

GI symptoms scale, Change at Week 48

GI symptoms scale, Change at Week 72

GI symptoms scale, Change at Week 84

Treatment scale, Baseline

Treatment scale, Change at Week 24

Treatment scale, Change at Week 48

Treatment scale, Change at Week 72

Treatment scale, Change at Week 84

Social function scale, Baseline

PP population included the participants who received telotristat etiprate; had no major protocol deviations that interfered with collection/interpretation of efficacy data. Number analyzed=participants with data at given time-point. Participants were combined for this outcome measure as they received dose adjustments per investigator's discretion.

Change From Baseline in Gastrointestinal Symptoms of Carcinoid Neuroendocrine Tumors (GI.NET21) Score at Each Visit

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study of Telotristat Etiprate (LX1606) in Participants With Symptomatic Carcinoid Syndrome	NCT01104415	Carcinoid Syndr...	Telotristat eti...	18 Years -	Lexicon Pharmaceuticals
Telotristat Etiprate - Expanded Treatment for Patients With Carcinoid Syndrome Symptoms	NCT02026063	Carcinoid Syndr...	Telotristat eti...	18 Years -	Lexicon Pharmaceuticals
Telotristat Etiprate for Carcinoid Syndrome Therapy	NCT02063659	Carcinoid Syndr...	Telotristat eti... Placebo	18 Years -	Lexicon Pharmaceuticals
AMT-PET in Monitoring Telotristat Etiprate Treatment in Participants With MetastaticNeuroendocrine Neoplasm	NCT03453489	Carcinoid Syndr... Metastatic Nonf...	Carbon C 11 Alp... Laboratory Biom... Positron Emissi... Telotristat Eti...	18 Years -	Barbara Ann Karmanos Cancer Institute
Study of Telotristat Etiprate (LX1606) in Participants With Symptomatic Carcinoid Syndrome Not Managed by Stable-Dose Octreotide Therapy	NCT00853047	Carcinoid Syndr...	Telotristat eti... Octreotide LAR ... Placebo	18 Years -	Lexicon Pharmaceuticals
AMT-PET in Monitoring Telotristat Etiprate Treatment in Participants With MetastaticNeuroendocrine Neoplasm	NCT03453489	Carcinoid Syndr... Metastatic Nonf...	Carbon C 11 Alp... Laboratory Biom... Positron Emissi... Telotristat Eti...	18 Years -	Barbara Ann Karmanos Cancer Institute

Spots Global Cancer Trial Database for telotristat etiprate