Carcinoid Syndrome MedDRA version: 17.1 Level: PT Classification code 10007270 Term: Carcinoid syndrome System Organ Class: 10014698 - Endocrine disorders
Conditions
Interventions
Product Name: Telotristat Etiprate
Product Code: LX1606
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Telotristat Etiprate
CAS Number: 1137608-69-5
Current Sponsor code: LX1606 Hippurat
Sponsors
Lexicon Pharmaceuticals, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patients must meet all of the following criteria to be considered eligible to participate in the study: 1. Patients =18 years of age at the time of the Screening visit 2. All patients of reproductive potential must agree to use an adequate method of contraception (defined as having a failure rate of 50 IU/L at Screening are confirmatory in the absence of a clear postmenopausal history. 3. Histopathologically-confirmed, well-differentiated metastatic (NET confirmed by computed tomography (CT), magnetic resonance imaging (MRI), or radionuclide imaging 4. Documented history of CS and meeting 1 of the following 2 criteria: • If currently receiving LAR/Depot/infusion SSA therapy for the treatment of CS, must be currently receiving a stable dose, averaging ULN • If not currently receiving SSA therapy, must have =1 of the following sign/symptoms of CS: a. Daily stool consistency =5 on Bristol Stool Form Scale9 (Appendix D) for =50% of the days during the Run-in, or b. Average daily flushing frequency of =2, or c. Average daily rating of =3 for abdominal pain, or d. Nausea present =20% of days, or e. u5-HIAA > ULN, or f. Currently averaging =4 BMs per day 5. Patient is able and willing to provide written informed consent prior to participation in any study-related procedure Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 31 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 13
Exclusion criteria
Exclusion criteria: Patients who meet any of the following criteria will be excluded from participating in the study: 1. Presence of diarrhea attributed to any condition(s) other than CS including, but not limited to, fat malabsorption or bile acid malabsorption 2. Presence of >12 watery BMs per day associated with volume contraction, dehydration, or hypotension compatible with a "pancreatic cholera"-type clinical syndrome, as judged by the Investigator 3. Positive stool examination for enteric pathogens, pathogenic ova or parasites, or Clostridium difficile at Screening 4. Karnofsky Performance Status =60% (see Appendix C) 5. Clinical laboratory values for hematology (at Screening): • Absolute neutrophil count (ANC) =1500 cells/mm3; or • Platelets =75,000, cells/mm3; or • Hemoglobin (Hgb) =9 g/dL for males and =8 g/dL for females 6. Hepatic laboratory values (at Screening) such that: • Asparate transaminase (AST) or alanine aminotransferase (ALT): a. =5.5 x ULN if patient has documented history of hepatic metastases, or b. =2.5 x ULN if patient does not have documented history of hepatic metastases • Total bilirubin >1.5 x ULN (unless patient has a documented history of Gilbert's Syndrome); or • Alkaline phosphatase (ALP) =5 x ULN, if total bilirubin is >ULN a. No upper limit on the ALP value if the total bilirubin is =ULN 7. Serum creatinine =1.5 x ULN 8. Treatment with any tumor-directed therapy including, but not limited to: interferon, chemotherapy, mTOR inhibitors <4 weeks prior to Screening, or hepatic embolization, radiotherapy, radiolabelled SSA, and/or tumor debulking <12 weeks prior to Screening 9. Major surgery defined as procedures requiring general anesthesia or major regional anesthesia within 8 weeks prior to Screening 10. A history of short bowel syndrome (SBS) 11. Current complaints of constipation or history of chronic or idiopathic constipation within 2 years prior to Screening 12. Positive pregnancy test or pregnant or nursing (lactating) (female patients only) 13. Life expectancy <12 months from the Screening visit 14. Presence of any clinically significant findings at Screening medical history, or physical examination (relative to patient population) that, in the Investigator's or Medical Monitor's opinion, would compromise patient safety or the outcome of the study 15. Any other clinically significant laboratory abnormality at Screening that would compromise patient safety or the outcome of the study 16. Clinically significant cardiac arrhythmia, bradycardia, or tachycardia that would compromise patient safety or the outcome of the study. 17. A history of substance or alcohol abuse (DSM-IV Criteria for Substance-Related Disorders12) within 2 years prior to Screening 18. Administration of any investigational agent within 30 days of Screening or investigational therapeutic protein or antibody within 90 days prior to Screening 19. Patients who are currently committed to an institution by virtue of an order issued either by judicial or administrative authorities
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the effect of telotristat etiprate versus placebo over the double-blind portion of the study on • The incidence of treatment-emergent adverse events (TEAEs) • Percent (%) change from Baseline in 24-hour urinary 5- hydroxyindoleacetic acid (5-HIAA) levels at Week 12;Secondary Objective: To evaluate the effect of telotristat etiprate versus placebo over the double-blind portion of the study on: • Change from Baseline in the number of daily bowel movements (BMs) averaged over a 12-week treatment period • Change from Baseline in stool consistency, as measured by the Bristol Stool Form Scale averaged across all time points • Change from Baseline in the number of cutaneous flushing episodes • Change from Baseline in abdominal pain averaged across all time points • Change from Baseline in the frequency of rescue short-acting, somatostatin analog (SSA) used to treat carcinoid syndrome (CS) symptoms • Change from Baseline in the number of daily BMs averaged over the 12-week treatment period and at each study week, among patients who are not on an SSA at Baseline ;Primary end point(s): The primary efficacy endpoint is the change from Baseline in the number of daily BMs averaged over a 12-week treatment period. Safety endpoints are as follows: • Incidence of TEAEs, suspected adverse reaction, AEs leading to discontinuation from the study, SAEs, and deaths • Actual and change from Baseline in clinical laboratory results • Actual and change from Baseline in vital signs results • Actual and change from Baseline in physical examinations • Actual and change from Baseline in ECG findings ;Timepoint(s) of evaluation of this end point: at each visit and the final analysis will be done at the end of the study | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary efficacy endpoints include: • Change from Baseline in stool consistency averaged across all time points • Change from Baseline in the number of cutaneous flushing episodes • Change from baseline in abdominal pain averaged across all time points • Change in the frequency of rescue short-acting SSA is used to treat CS symptoms • Change from Baseline in the number of daily BMs averaged over the 12-week treatment period and at each study week, among patients who are not on an SSA at Baseline ;Timepoint(s) of evaluation of this end point: at each visit and the final analysis will be done at the end of the study | — |
Countries
Australia, Belgium, Brazil, Canada, France, Germany, Israel, Italy, Netherlands, Spain, Sweden, United Kingdom, United States
Contacts
Public ContactPenny Logan
Lexicon Pharmaceuticals, Inc.
Outcome results
None listed