Study to Evaluate the Pharmacokinetics of Telotristat Ethyl in Subjects With Severe Hepatic Impairment

Completed · Phase 1

Conditions studied: Hepatic Impairment

In brief

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.

Key facts

Study ID

NCT03423446

Run by

Lexicon Pharmaceuticals

People needed

16

Starts

2017-11-28

Expected to finish

2018-06-15

Last updated by the study team

2018-10-15

Who can join

Age: 18 and older, up to 70. Sex: any. Healthy volunteers: accepted.

You may qualify if…

• 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
• 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.

You may not qualify if…

• 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
• 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

Where it is running

• Lexicon Investigational Site — Miami, Florida, United States
• Lexicon Investigational Site — Orlando, Florida, United States
• Lexicon Investigational Site — San Antonio, Texas, United States

Full record on ClinicalTrials.gov

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