Telotristat Etiprate for Carcinoid Syndrome Therapy

Phase 3

Completed

Conditions: Carcinoid Syndrome

Interventions: Drug: Telotristat etiprate
Drug: Placebo

Registration Number: NCT02063659

Lead Sponsor: Lexicon Pharmaceuticals

Brief Summary: The purpose of the study is to evaluate the effect of telotristat etiprate versus placebo on the incidence of treatment-emergent adverse events and on 5-hydroxyindoleacetic acid (5-HIAA) levels.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 76

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
Documented history of carcinoid syndrome
Patient is able and willing to provide written informed consent prior to participation

Exclusion Criteria

Presence of diarrhea attributed to any condition other than carcinoid syndrome.
Presence of 12 or more watery bowel movements per day
Positive stool examination for enteric pathogens, pathogenic ova or parasites, of Clostridium difficile at Screening
Karnofsky Performance Status ≤ 60%
Presence of any clinically significant laboratory, medical history, or physical examination findings deemed unacceptable by the Investigator
A history of short bowel syndrome
History of constipation within 2 years of Screening
Life expectancy < 12 months from Screening

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
250 mg Telotristat Etiprate	Telotristat etiprate	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	Telotristat etiprate	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.
250 mg Telotristat Etiprate	Placebo	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	Placebo	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	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.

Primary Outcome Measures

Name	Time	Method
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Open-Label Extension Period	First dose of study drug to within 30 days of last dose of study drug in the Open-Label Extension Period (Up to 52.6 Weeks)	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.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Double-Blind Treatment Period	First dose of study drug to within 30 days of last dose of study drug in the Double-Blind Treatment Period (Up to 17.1 Weeks)	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.
Primary: Percent Change From Baseline in Urinary 5-hydroxyindoleacetic Acid (u5-HIAA) Levels	Baseline and 12 Weeks	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.

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in Abdominal Pain Averaged Across All Time-Points	Baseline and 12 Weeks	Participants recorded abdominal pain in a daily diary. Participants evaluated the level of any abdominal pain using an 11-point numeric rating scale, where: 0=no pain to 10=worst pain ever experienced. The average daily abdominal pain was averaged over the 12-week period. A negative change from Baseline indicates improvement.
Change in the Frequency of Rescue Short-acting, Somatostatin Analog (SSA) Used to Treat Carcinoid Syndrome Symptoms Averaged Across All Time-Points	Baseline and 12 weeks	The frequency (the number of times) the participant used rescue with SSA to control symptoms was recorded in a daily diary. The daily number of rescue treatments with SSA was averaged over the 12- week period. A negative change from Baseline (less use of SSA) indicates improvement.
Change From Baseline in Stool Form/Consistency Averaged Across All Time-Points	Baseline and 12 Weeks	Participants assessed stool form/consistency of a BM using the Bristol Stool Form Scale where: 1=hard lumps to 7=watery liquid. The daily scores were averaged over the 12-week period. A negative change indicates improvement.
Change From Baseline in the Number of Bowel Movements (BMs) Per Day Averaged Over 12 Weeks	Baseline and 12 weeks	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.
Change From Baseline in the Number of Daily Cutaneous Flushing Episodes Averaged Across All Time-Points	Baseline and 12 Weeks	Participants recorded the number daily flushing episodes per day in a daily diary. The total number of flushing episodes per day were averaged over the 12-week period. A negative change from Baseline indicates improvement.
Change From Baseline in the Number of Daily BMs Averaged Over the 12-Week Double-Blind Period, Among Participants Who Were Not Receiving SSA Therapy at Baseline	Baseline and 12 Weeks	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.