The primary objective of this study is to evaluate the long-term safety and tolerability of orally administered telotristat etiprate.The secondary objective is to evaluate changes in patients* quality of life (QOL) through week 84.
ID
Source
Brief title
Condition
- Malignant and unspecified neoplasms gastrointestinal NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary efficacy endpoint is to evaluate the long-term safety and
tolerability of orally administered telotristat etiprate.
Safety
Safety assessments include monitoring of adverse events, clinical laboratory
tests, vital signs measurements, 12-lead ECG, and physical examinations.
Efficacy
Efficacy assessments will include patient reported quality of life measures as
captured in the European Organization for Research and Treatment of Cancer
(EORTC) Quality of Life Questionnaire QLQ-C30 and the module specific for
gastrointestinal symptoms of carcinoid neuroendocrine tumors (GI.NET21) and
subjective global assessment of symptoms associated with CS
Pharmacodynamics
Pharmacodynamic (PD) assessments include determination of 5-HIAA levels in
plasma.
Secondary outcome
Secondary efficacy endpoint is to evaluate changes in patients* QOL over 84
weeks of therapy.
Background summary
Currently, the standard of care for patients with CS is symptom management
using somatostatin analogs (SSA). As a result of the morbidity associated with
SSAs and the associated tachyphylaxis, there is an unmet medical need to
provide symptom management and modify the pathophysiology of patients with
metastatic CS. Telotristat etiprate is being developed to manage GI symptoms
and possibly other symptoms associated with CS. It could provide significant
benefit as an additional treatment option.
This study will allow for continued access to telotristat etiprate after
patients have completed the required study visits in ongoing Phase 2 and Phase
3 studies. Continuation of CS patients into this study will allow for the
collection of additional long-term safety and efficacy data.
Study objective
The primary objective of this study is to evaluate the long-term safety and
tolerability of orally administered telotristat etiprate.
The secondary objective is to evaluate changes in patients* quality of life
(QOL) through week 84.
Study design
The study will be conducted as a multicenter, open-label, long-term extension
study to further evaluate long-term safety and tolerability of telotristat
etiprate.
Patients currently participating in any LX1606 Phase 2 carcinoid syndrome (CS)
study may enter into this extension study upon institutional or local approval
of the protocol. Patients participating in a Phase 3 CS study may enter into
this extension study at the Week 48 visit. All patients who enter into this
extension study will be exempt from any follow-up visit required by the
original study and will not experience an interruption in study drug due to the
transition from the original study to LX1060.1-302-CS.
Following confirmation of eligibility, patients will complete a series of visit
assessments in order to establish Baseline symptoms. Patients will then
continue on open-label study drug at the same dose level and regimen as
identified in their original study.
Downward dose adjustment will be permitted during the study if evidence of
intolerability emerges. Patients who experience intolerability at the 250 mg
tid dose level must be discontinued from the study. Patients may return to the
previous dosing at the discretion of the Investigator and in consultation with
the Medical Monitor.
Upon completion or early withdrawal from treatment, all patients will be
required to complete a 14-day Follow-up Period, during which no study drug will
be administered.
'All patients will participate in the Treatment Period until such time
telotristat etiprate has received regulatory approval to be marketed and is
available via prescription or 30 June 2018, whichever occurs first. Based upon
the expected dates for eligible patients* entry into this study, overall
duration of participation will last up to 235 weeks including the Treatment
Period and Follow-up Period.
Intervention
Investigational product: Telotristat etiprate tablets
Doses: 250 mg (1 x 250 mg) tid or 500 mg (2 x 250 mg) tid
Mode of administration: oral
Study burden and risks
The patient population concerned in this study is patients with carcinoid
syndrome who are no longer responding to standard Somatostatin Analog (SSA-
currently approved hormone therapy). Telotristat etiprate has the potential to
improve several signs and symptoms of CS. The Phase 2 clinical trial results
indicated that treatment may lead to improvements in BM frequency, stool
consistency, urgency, abdominal pain, diarrhea, flushing, and reductions in
5-HIAA. These potential benefits relate to a unique mechanism of action.
Symptomatic improvement may lead to a better quality of life (QOL) for patients
with few treatment options available, and a reduction in serotonin may help
reduce the risk of carcinoid heart disease. Overall the benefit/risk profile of
telotristat etiprate is expected to be favorable for participation in this
clinical study.
Technology Forest Place 8800
The Woodlands TX 77381
US
Technology Forest Place 8800
The Woodlands TX 77381
US
Listed location countries
Age
Inclusion criteria
Patients must meet all of the following criteria to be considered eligible to participate in the study:;1. Ongoing participation in a Phase 2 study (eg, LX1606.1-202-CS, LX1606.1-203-CS) or Phase 3 study (eg, LX1606.1-301-CS, LX1606.1-303-CS). ;2. 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 Baseline day 1 are confirmatory in the absence of a clear postmenopausal history.;3. 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. Major protocol violations in regard to dosing compliance or telotristat etiprate tolerability concerns in a Phase 2 study (eg, LX1606.1-202-CS, LX1606.1-203-CS) or Phase 3 study (eg, LX1606.1-301-CS, LX1606.1-303-CS).;2. Positive pregnancy test;3. Presence of any clinically significant findings at entry for medical history, laboratory values, 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;4. Patients who are currently committed to an institution by virtue of an order issued either by judicial or administrative authorities
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2013-002596-18-NL |
| ClinicalTrials.gov | NCT02026063 |
| CCMO | NL49418.015.14 |