Study of Telotristat Etiprate (LX1606) in Participants With Symptomatic Carcinoid Syndrome Not Managed by Stable-Dose Octreotide Therapy

Lexicon Pharmaceuticals

Status and phase: Completed; Phase 2

Conditions: Carcinoid Syndrome

Treatments: Drug: Placebo; Drug: Telotristat etiprate; Drug: Octreotide LAR Depot

Study type: Interventional

Funder types: Industry

Identifiers

NCT00853047

LX1606.202 (Other Identifier)

LX1606.1-202-CS

Details and patient eligibility

About

The purpose of this study is to evaluate the safety and tolerability of telotristat etiprate (LX1606) versus a placebo control in participants with symptomatic carcinoid syndrome not managed by stable-dose long-acting octreotide therapy. Following determination of the maximally tolerated or effective dose, cohort expansion will occur to confirm effect on symptoms and safety profile.

Enrollment: 23 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Males and females, aged 18 and older
• Biopsy-proven metastatic carcinoid tumor of the gastrointestinal (GI) tract with disease extent confirmed by computed tomography (CT), magnetic resonance imaging (MRI), or radionuclide imaging
• Symptoms not managed by stable-dose long-acting octreotide therapy (≥4 bowel movements per day)
• Ability to provide written informed consent

Exclusion criteria

• ≥12 high volume, watery bowel movements per day associated with a clinical syndrome of volume contraction, dehydration, or hypotension compatible with a "pancreatic cholera"-type clinical syndrome
• Sponsor-unacceptable clinical laboratory values for hematology and liver function tests at screening
• Karnofsky status ≤70% - unable to care for self
• Surgery within 60 days prior to screening
• A history of short bowel syndrome
• Life expectancy <12 months
• History of substance or alcohol abuse within 2 years prior to screening
• Previous exposure to a tryptophan hydroxylase (TPH) inhibitor
• Administration of any investigational drug within 30 days of screening or any therapeutic protein or antibody within 90 days of screening

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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23 participants in 6 patient groups

Telotristat Etiprate 150 mg Core Phase

Experimental group

Description:

Telotristat etiprate capsules,150 mg orally 3 times daily for 28 days in the double-blind treatment period (core phase) in combination with stable-dose octreotide long-acting release (LAR) depot therapy given once per month. Upon completion of 28-days of treatment, participants were eligible to enter the optional open-label extension period.

Treatment:

Drug: Telotristat etiprate

Drug: Octreotide LAR Depot

Telotristat Etiprate 250 mg Core Phase

Experimental group

Description:

Telotristat etiprate capsules, 250 mg orally 3 times daily for 28 days in the double-blind treatment period in combination with stable-dose octreotide LAR depot therapy given once per month. Upon completion of 28-days of treatment, participants were eligible to enter the optional open-label extension period.

Treatment:

Drug: Telotristat etiprate

Drug: Octreotide LAR Depot

Telotristat Etiprate 350 mg Core Phase

Experimental group

Description:

Telotristat etiprate capsules, 350 mg orally 3 times daily for 28 days in the double-blind treatment period in combination with stable-dose octreotide LAR depot therapy given once per month. Upon completion of 28-days of treatment, participants were eligible to enter the optional open-label extension period.

Treatment:

Drug: Telotristat etiprate

Drug: Octreotide LAR Depot

Telotristat Etiprate 500 mg Core Phase

Experimental group

Description:

Telotristat etiprate capsules, 500 mg orally 3 times daily for 28 days in the double-blind treatment period in combination with a stable-dose octreotide LAR depot therapy given once per month. Upon completion of 28-days of treatment, participants were eligible to enter the optional open-label extension period.

Treatment:

Drug: Telotristat etiprate

Drug: Octreotide LAR Depot

Placebo Core Phase

Experimental group

Description:

Placebo-matching telotristat etiprate capsules, orally 3 times daily for 28 days in the double-blind treatment period in combination with stable-dose octreotide LAR depot therapy given once per month. Upon completion of 28-days of treatment, participants were eligible to receive telotristat etiprate in the optional open-label extension period.

Treatment:

Drug: Placebo

Drug: Octreotide LAR Depot

Telotristat Etiprate Open-Label Extension Phase

Experimental group

Description:

Telotristat etiprate at assigned dose level for 8 weeks in combination with stable-dose octreotide LAR depot therapy given once per month in the open-label extension period. Upon completion of the 8-week period, participants could enter an additional extension period of 172 weeks, receiving telotristat etiprate at the assigned dose or maximum tolerated dose (500 mg 3 times daily).

Treatment:

Drug: Telotristat etiprate

Drug: Octreotide LAR Depot