A Phase 3, Randomized, Placebo-controlled, Parallel-group, Multicenter, Double-blind Study to Evaluate the Efficacy and Safety of Telotristat Etiprate (LX1606) in Patients with Carcinoid Syndrome Not Adequately Controlled by Somatostatin Analog (SSA) Therapy

Phase 3

Completed

• Conditions: Carcinoid tumor; Carcinoid Syndrome; 10017990

• Registration Number: NL-OMON41315
• Lead Sponsor: exicon Pharmaceuticals Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 29 April 2024

Recruitment & Eligibility

• Status: Completed
• Sex: Not specified
• Target Recruitment: 10

Inclusion Criteria

1.Patients >=18 years of age at the time of the Screening visit;2.Histopathologically-confirmed, well-differentiated metastatic NET with extent documented by computed tomography (CT), magnetic resonance imaging (MRI), or radionuclide imaging;3.A documented history of CS, and currently experiencing an average of >=4 bowel movements per day during the Run-in Period. Confirmation of eligibility will be determined by measuring the mean number of bowel movements;4.Currently receiving a stable-dose SSA therapy. For the purposes of this study, stable-dose SSA therapy is defined as long acting release (LAR) or Depot SSA therapy or a continuous subcutaneous infusion via a pump. Patients must have been receiving the same dose level and frequency for at least 3 months prior to entering the Run-in Period.;5.Minimum dose of LAR or Depot SSA therapy (higher dose or more frequent intervals will fulfill the minimum dose requirement). SSA therapy must be approved for use in CS in the patient*s country of residence or prescribers* country of practice.
a.Octreotide LAR at 30 mg every 4 weeks
b.Lanreotide Depot at 120 mg every 4 weeks
c.Patients who cannot tolerate SSA therapy at a level indicated above will be allowed to enter at their highest tolerated dose;6.Patients of childbearing potential must agree to use an adequate method of contraception (defined as having a failure rate of < 1% per year) during the study and for 12 weeks after the Follow-up visit. Adequate methods of contraception for patients or partner include condoms with spermicide gel, diaphragm with spermicide gel, coil (intrauterine device), surgical sterilization, vasectomy, oral contraceptive pill, depot progesterone injections, progesterone implant, and abstinence during the study and for 12 weeks after the Follow-up Visit.;a. Childbearing potential is defined as those who have not undergone surgical sterilization, or those who are not considered postmenopausal. Postmenopause is defined as absence of menstruation for at least 2 years. If necessary, follicle-stimulating hormone (FSH) results >50 IU/L
at Screening are confirmatory in the absence of a clear postmenopausal history.;7.Ability and willingness to provide written informed consent prior to participation in any study-related procedure

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 more than 12 watery bowel movements 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% ;5.Clinical laboratory values for hematology (at Screening):;a.Absolute neutrophil count (ANC) <=1500 cells/mm3; or
b.Platelets <=750,000 cells/mm3; or
c.Hemoglobin (Hgb) <=9 g/dL for males and <=8 g/dL for females;6.Hepatic laboratory values (at Screening) such that:;a.Aspartate transaminase (AST), or alanine aminotransferase (ALT):
•>=5.5 x upper limit of normal (ULN) if patient has documented history of hepatic metastases; or
•>=2.5 x ULN if patient does not have documented history of hepatic metastases
b.Total bilirubin >1.5 x ULN (unless patient has a documented history of Gilbert*s Syndrome); or
c.Alkaline phosphatase (ALP) >=5 x ULN, if total bilirubin is >ULN
•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);(See Protocol LX1606.301 section Exclusion Criteria)
Clinically significant cardiac arrhytmia, bradycardia or tachycardia that would compromise patient safety or the outcome of the study.

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>The primary objective of the study is to confirm that at least 1 or more doses<br /><br>of telotristat etiprate compared to placebo is effective in reducing the change<br /><br>from baseline in the number of daily BMs averaged over the 12-week double-blind<br /><br>portion of the trial (Treatment Period) in patients with carcinoid syndrome not<br /><br>adequately controlled to current SSA therapy.</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>The secondary objectives of this study are:<br /><br>To assess the effects of telotristat etiprate versus placebo over the 12-week<br /><br>double-blind portion of the study in patients who are not adequately controlled<br /><br>to current SSA therapy as determined by:<br /><br>* Change from baseline in stool consistency averaged across all time points<br /><br>* Change from baseline in the number of cutaneous flushing episodes<br /><br>* Change from baseline in abdominal pain averaged across all time points<br /><br>* Durability, defined as the proportion of responders with >=30% reduction in<br /><br>daily number of BMs for >=50% of time over the double-blind portion of the study<br /><br>* Change in the frequency of rescue short-acting SSA used to treat<br /><br>bowel-related CS symptoms</p><br>