Hepatic ImpairmentPhase 1NCT03423446
Study to Evaluate the Pharmacokinetics of Telotristat Ethyl in Subjects With Severe Hepatic Impairment
A Phase 1 study testing Telotristat Ethyl in people with Hepatic Impairment, run by Lexicon Pharmaceuticals at 3 sites in United States.
Trial summary
This study is designed to evaluate the effect of severe hepatic impairment on the pharmacokinetics (PK) of telotristat ethyl (TE) ( LP-778902 active moiety, metabolite), following administration of a single dose of TE 250 mg (1 x 250-mg tablet) compared to healthy, demographically-matched subjects with normal hepatic… Read more about this study
- Who is it for?
- Ages 18 to 70 yearsHealthy volunteers can take part
- Conditions the study is for
- Hepatic Impairment
- What is being tested?
- Telotristat Ethyl
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 3 sitesUnited States
- Study dates
- 28 Nov 2017to 15 Jun 2018
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Adult male and female subjects ≥18 to ≤70 years of age, inclusive, at the time of Screening:
- Females of non-childbearing potential are to be surgically sterile (documented hysterectomy, tubal ligation, or bilateral salpingo-oophorectomy) or postmenopausal (defined as at least 12 months of spontaneous amenorrhea). Females of childbearing potential must agree to use an adequate method of contraception during the study from clinical research unit (CRU) admission through Safety Follow-up.
- Adequate methods of contraception for subjects or partner include condom, diaphragm, or cervical cap used in conjunction with spermicidal gel, foam, cream, film, or suppository. Hormonal contraception is NOT acceptable in this study. If necessary, follicle-stimulating hormone (FSH) results >40 IU/L at Screening are confirmatory in the absence of a clear postmenopausal history.
- Nonsterile male subjects with sexual partners of childbearing potential must agree to use adequate methods of contraception from CRU admission through Safety Follow-up. Adequate methods of contraception for subjects or partner include the following: condom with spermicidal gel, diaphragm with spermicidal gel, coil (intrauterine device), surgical sterilization, vasectomy, oral contraceptive pill, depo-progesterone injections, progesterone implant (ie, Implanon®), NuvaRing®, Ortho Evra®; if a subject is not sexually active, but becomes active, he or his partner should use medically accepted forms of contraception.
- Body mass index ≥18.0 to ≤34.0 kg/m2, inclusive, at Screening
- Willing to adhere to the prohibitions and restrictions specified in this protocol
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- Willing and able to provide written informed consent
- Additionally, for subjects with hepatic impairment:
- Clinical diagnosis of chronic hepatic disease (stable for >3 months) with a documented history of underlying hepatic insufficiency with features of cirrhosis and no acute episodes of illness within 30 days prior to Screening, and no significant change in disease status from Screening to CRU admission (Day -1)
- Hepatic impairment classified as severe using C-P criteria
- A stable medication regimen, defined as not starting new therapy(ies) or significant changing dosage(s) within 30 days prior to dosing on planned Day 1, as determined by the Investigator, Medical Monitor, and/or the Sponsor
- Abnormal laboratory values must be clinically acceptable, as judged by the Investigator, Medical Monitor, and/or the Sponsor.
- Additionally, for healthy matched control subjects with normal hepatic function:
- Each subject will be demographically matched to 1 of the subjects with severe hepatic impairment for sex, age (±10 years), and BMI (±20%).
- No clinically significant illness or disease as determined by medical history, including cardiac, pulmonary, hepatic, biliary, gastrointestinal (GI), endocrinologic, or renal disorders, or cancer within the last 5 years (except localized or in situ cancer of the skin), physical examination, clinical laboratory tests, and 12-lead electrocardiograms (ECGs)
- All laboratory values at Screening and CRU admission fall within normal range or are evaluated as not clinically significant (NCS) by the Investigator if outside normal range. A single test repeat at the discretion of the Investigator is allowed during the Screening Period to determine eligibility.
Who cannot join
- Presence of clinically significant physical, laboratory, or ECG findings that, in the opinion of the Investigator, Medical Monitor, and/or the Sponsor, may interfere with any aspect of study conduct or interpretation of results including:
- Any clinically significant abnormal rhythm
- Other ECG abnormalities that are clinically relevant
- Receipt of any investigational agent or study drug within 30 days or 5 half-lives, whichever is longer, prior to CRU admission
- Receipt of any protein- or antibody-based therapeutic agents (eg, growth hormones or monoclonal antibodies) within 3 months prior to dosing on planned Day 1. Note: Influenza vaccine will be allowed if administered >21 days prior to dosing.
- Prior exposure to study drug
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- Smoking more than 20 cigarettes (eg, 1 pack) per day or equivalent (eg, e-vapor cigarette, pipe, cigar, chewing tobacco, nicotine patch, nicotine gum); unable or unwilling to refrain from smoking and tobacco use for 2 hours prior to dosing and 4 hours after dose administration.
- History of any serious adverse reaction or hypersensitivity to any inactive component of study drug, unless the reaction is deemed irrelevant to the study by the Investigator, Medical Monitor, and/or the Sponsor
- Existence of any surgical or medical condition that, in the judgment of the Investigator, Medical Monitor, and/or the Sponsor, might interfere with the absorption, distribution, metabolism, or excretion of TE or LP-778902 (including bariatric surgery, cholecystectomy, or any other GI surgery, excepting appendectomy and hernia repair, which are acceptable)
- History of any major surgery within 6 months or anticipated surgery prior to planned CRU admission
- History of renal disease, or significantly abnormal kidney function test (glomerular filtration rate [GFR] <60 mL/min as calculated using the Cockcroft-Gault equation) at CRU admission
- History of any active infection within 30 days prior to Day 1, if deemed clinically significant by the Investigator, Medical Monitor, and/or the Sponsor
- Donation or loss of >500 mL of blood or blood product within 3 months prior to CRU admission
- Women who are breastfeeding or are planning to become pregnant during the study
- Positive serum pregnancy test (females only)
- Positive urine screen for drugs of abuse (not including cotinine) at Screening or CRU admission, unless the result is due to a prescribed medication and is deemed unrelated to the study by the Medical Monitor and/or Sponsor.
- Consumption of alcohol within 3 days hours prior to CRU admission on Day -1 (as confirmed by alcohol breath screen) and for the duration of the confinement period
- Consumption of caffeine- and/or xanthine-containing products (eg, cola, coffee, tea, chocolate) within 72 hours prior to CRU admission (Day -1) and for the duration of the confinement period
- Consumption of grapefruit, Seville oranges, and grapefruit- or Seville orange-containing products within 72 hours prior to CRU admission (Day -1) and for the duration of the confinement period
- Need for special dietary restrictions, unless the restrictions are approved by the Investigator, Medical Monitor, and/or the Sponsor
- Inability or difficulty swallowing whole tablets
- Poor venous access as defined by the Investigator or a designee
- Any other condition that compromises the ability of the subject to provide informed consent or to comply with the objectives and procedures of this protocol, as judged by the Investigator, Medical Monitor, and/or the Sponsor
- Unable or unwilling to cooperate with the Investigator for any reason
- Employee of the Investigator or study center, with direct involvement in the proposed study or other studies under the direction of that Investigator or study center, as well as family members of the employees or the Investigator
- If heparin is to be used during PK sampling, subjects with a history of sensitivity to heparin, or heparin-induced thrombocytopenia, will not be enrolled.
- Administration of gastric acid suppressing agents or short acting octreotide within 30 days or 5 half-lives of the drug, prior to CRU admission
- Use of agents that are known to alter GI motility including, but not limited to, prokinetic agents, antidiarrheals, opiates, antispasmodics, anticholinergics, and antiemetics.
- Additionally, for subjects with hepatic impairment:
- Use of acetaminophen or acetaminophen-containing products within 14 days prior to dosing on planned Day 1 and through Discharge unless deemed acceptable by the Investigator, Medical Monitor, and/or the Sponsor
- Evidence of significant active disease including gastroenterologic (other than hepatic cirrhosis), cardiac (eg, myocardial infarction in the past year, angina, or congestive heart failure), renal, respiratory, endocrine, hematologic, neuropsychiatric, or neoplastic (basal or squamous cell skin cancer is acceptable) disease
- Significant infection or hospitalization within 4 weeks prior to planned Day 1
- Positive for hepatitis B surface antigen (HBsAg; not including hepatitis C virus [HCV] antibody) or positive human immunodeficiency virus (HIV) antibody screens. Note: Subjects with chronic hepatitis C virus (HCV) (duration >6 months) are eligible for enrollment, if stable.
- Primary sclerosing cholangitis or preliminary diagnosed biliary obstruction
- A change in any clinical laboratory value from Screening to Day -1 that is considered by the Investigator, Medical Monitor, and/or the Sponsor to be clinically significant
- History of transplant, portal shunts, recent variceal bleeds, or evidence of hepatorenal syndrome. Note: Creatinine clearance must be ≥60 mL/min using Cockcroft-Gault equation.
- Subjects with a life expectancy less than 3 months
- Additionally, for Healthy Subjects:
- Use of any medications (prescription or over-the-counter), herbal tea, energy drinks, herbal products (eg, St. John's wort, garlic, milk thistle), or supplements/supratherapeutic doses of vitamins within 14 days prior to planned Day 1 and throughout the duration of the study, with the exception of those approved by the Investigator, Medical Monitor, and/or the Sponsor or Sponsor's representative (eg, acetaminophen). Note: The use of typical amounts of garlic used in the preparation of food items is permitted.
- History of hepatic disease, or significantly abnormal liver function tests (>1.5 x upper limit of normal [ULN]) at Screening. Note: Isolated bilirubin >1.5 x ULN is acceptable if bilirubin is fractionated and direct bilirubin is <35%.
- Positive hepatitis panel (including HBsAg and HCV antibody) or positive HIV antibody screens
- History of any clinically relevant psychiatric, renal, hepatic, pancreatic, endocrinologic, cardiovascular, neurological, hematological
- History of alcohol or substance abuse within 2 years prior to Screening per Diagnostic and Statistical Manual of Mental Disorders, 5th Edition criteria
- Concurrent conditions that could interfere with safety and/or tolerability measurements
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Lexicon Investigational Site
Miami, Florida, 33014
Lexicon Investigational Site
Orlando, Florida, 32809
Lexicon Investigational Site
San Antonio, Texas, 78215
About this study
Official title: A Phase 1, Open-label, Parallel-group Study to Evaluate the Single-dose Pharmacokinetics of Telotristat Ethyl in Male and Female Subjects With Severe Hepatic Impairment and Matched Subjects With Normal Hepatic Function
This study is designed to evaluate the effect of severe hepatic impairment on the pharmacokinetics (PK) of telotristat ethyl (TE) ( LP-778902 active moiety, metabolite), following administration of a single dose of TE 250 mg (1 x 250-mg tablet) compared to healthy, demographically-matched subjects with normal hepatic function.
- Conditions
- Hepatic Impairment
- Being tested
- Telotristat Ethyl
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Telotristat EthylDrug
Also called telotristat etiprate, Xermelo
Telotristat ethyl (TE) 250 mg (1 x 250-mg tablet), single dose
| Study group | Role | What they receive |
|---|---|---|
| Severe Hepatic Impairment | Experimental | Up to 8 subjects with severe hepatic impairment (Child-Pugh Class C, score of 10 to 15 points) Receives: Drug: Telotristat Ethyl |
| Healthy Control | Experimental | Up to 8 healthy control subjects with normal hepatic function Receives: Drug: Telotristat Ethyl |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum observed concentration of telotristat ethyl
Measured: 4 days
Time of maximum observed concentration of telotristat ethyl
Measured: 4 days
Area under the plasma concentration-time curve beginning from the first dose until the last quantifiable concentration of telotristat ethyl
Measured: 4 days
Secondary outcomes (1)
Number of adverse events
Measured: Up to 9 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Feb 2018
- Study start28 Nov 2017
- Primary completion15 Jun 2018
- Study completion15 Jun 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hepatic ImpairmentStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- Lexicon Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Suman Wason, MD, Study director, Lexicon Pharmaceuticals, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03423446
- Sponsor's protocol ID
- LX1606.1-111-HEP
- Other IDs
- LX1606.111
- Status last verified
- Oct 2018
- First submitted
- 24 Oct 2017
- Last updated
- 15 Oct 2018
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 15 Oct 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1, Open-label, Parallel-group Study to Evaluate the Single-dose Pharmacokinetics of Telotristat Ethyl in Male and Female Subjects With Severe Hepatic Impairment and Matched Subjects With Normal Hepatic Function
- ClinicalTrials.gov ID
- NCT03423446
- Acronym / sponsor ID
- LX1606.1-111-HEP
- Conditions
- Hepatic Impairment
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- Lexicon PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 28 Nov 2017 (actual)
- Primary completion
- 15 Jun 2018 (actual)
- Study completion
- 15 Jun 2018 (actual)
- First posted
- 6 Feb 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is designed to evaluate the effect of severe hepatic impairment on the pharmacokinetics (PK) of telotristat ethyl (TE) ( LP-778902 active moiety, metabolite), following administration of a single dose of TE 250 mg (1 x 250-mg tablet) compared to healthy, demographically-matched subjects with normal hepatic function.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Severe Hepatic Impairment | Experimental | Drug: Telotristat EthylUp to 8 subjects with severe hepatic impairment (Child-Pugh Class C, score of 10 to 15 points) |
| Healthy Control | Experimental | Drug: Telotristat EthylUp to 8 healthy control subjects with normal hepatic function |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Adult male and female subjects ≥18 to ≤70 years of age, inclusive, at the time of Screening:
- Adequate methods of contraception for subjects or partner include condom, diaphragm, or cervical cap used in conjunction with spermicidal gel, foam, cream, film, or suppository. Hormonal contraception is NOT acceptable in this study. If necessary, follicle-stimulating hormone (FSH) results >40 IU/L at Screening are confirmatory in the absence of a clear postmenopausal history.
- Body mass index ≥18.0 to ≤34.0 kg/m2, inclusive, at Screening
- Willing to adhere to the prohibitions and restrictions specified in this protocol
- Willing and able to provide written informed consent
Key exclusion criteria (44 listed)
- Presence of clinically significant physical, laboratory, or ECG findings that, in the opinion of the Investigator, Medical Monitor, and/or the Sponsor, may interfere with any aspect of study conduct or interpretation of results including:
- Receipt of any investigational agent or study drug within 30 days or 5 half-lives, whichever is longer, prior to CRU admission
- Receipt of any protein- or antibody-based therapeutic agents (eg, growth hormones or monoclonal antibodies) within 3 months prior to dosing on planned Day 1. Note: Influenza vaccine will be allowed if administered >21 days prior to dosing.
- Prior exposure to study drug
- Smoking more than 20 cigarettes (eg, 1 pack) per day or equivalent (eg, e-vapor cigarette, pipe, cigar, chewing tobacco, nicotine patch, nicotine gum); unable or unwilling to refrain from smoking and tobacco use for 2 hours prior to dosing and 4 hours after dose administration.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Telotristat EthylAlso: telotristat etiprate, XermeloTelotristat ethyl (TE) 250 mg (1 x 250-mg tablet), single dose | Drug | Healthy Control, Severe Hepatic Impairment |
Primary outcome
Maximum observed concentration of telotristat ethyl
Time frame: 4 days
Time of maximum observed concentration of telotristat ethyl
Time frame: 4 days
Area under the plasma concentration-time curve beginning from the first dose until the last quantifiable concentration of telotristat ethyl
Time frame: 4 days
1 secondary outcome
Number of adverse events
Time frame: Up to 9 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Oct 2018.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Suman Wason, MD study director
Lexicon Pharmaceuticals, Inc.
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Telotristat Ethyl in people with Hepatic Impairment, run by Lexicon Pharmaceuticals at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 44 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Oct 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum observed concentration of telotristat ethyl (time frame: 4 days). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Oct 2018.