A Phase 1, Open-Label, Non-randomized, Parallel-Group Study to Evaluate the Pharmacokinetics, Safety and Tolerability of a Single Oral Dose of 200 mg Elacestrant in Subjects With Normal Hepatic Function or Severe Hepatic Impairment
Overview
- Phase
- Phase 1
- Intervention
- Elacestrant dihydrochloride
- Conditions
- Hepatic Impairment
- Sponsor
- Stemline Therapeutics, Inc.
- Enrollment
- 16
- Locations
- 3
- Primary Endpoint
- Maximum observed plasma concentration (Cmax)
- Status
- Completed
- Last Updated
- last year
Overview
Brief Summary
This is a Phase 1, multi-center, open-label, non-randomized, parallel group study to evaluate the effect of severe hepatic impairment on the PK, safety and tolerability of a single oral dose of Elacestrant.
Detailed Description
A total of 16 subjects will be recruited and divided between the following two Groups: Group 1: 8 subjects with severe hepatic impairment Group 2: 8 subjects with normal hepatic function (control group) On Day 1, subjects will receive a single oral dose of 200 mg Elacestrant (2 x 100 mg tablets). Safety assessment and blood sampling for Elacestrant analysis on plasma will be performed at predefined time points up to 240 hours post. The total duration of study participation for each subject (from screening to the follow up call) is anticipated to be approximately 6 weeks.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Understand the study procedures in the informed consent form (ICF) and be willing and able to comply with the protocol restrictions and requirements.
- •Males and Females older than 18 years.
- •Body mass index between 18.0 and 40.0 kg/m\^2, inclusive.
- •Females must have non-functioning ovaries defined as postmenopausal and/or bilateral salpingo - oophorectomy. All female subjects must have a negative pregnancy test at screening and at check-in.
- •Males who are non-sterilized and sexually active with a female partner of childbearing potential must agree to use highly effective contraception from admission and for 120 days after IMP dose.
- •Males must agree not to donate sperm from admission and for 120 days after investigational medicinal product dose.
- •Non-smoker or light smoker, i.e. no more than 10 cigarettes or 10 mg equivalent use of Nicotine per day by e-vapor cigarette, pipe, cigar, chewing tobacco, nicotine patch, nicotine gum, AND able or willing to refrain from smoking and tobacco use for 2 hours prior to dose and 4 hours after IMP dose.
- •Additional inclusion criteria applicable to subjects with Normal Hepatic Function Only
- •In good health, determined by no clinically significant findings from medical history, physical examination, 12-lead ECG, vital signs measurements, and clinical laboratory evaluations. NOTE: Congenital nonhemolytic hyperbilirubinemia/Gilbert's syndrome based on total and direct bilirubin is not acceptable.
- •Matched to subjects with severe hepatic impairment in gender, age (±10 years), weight (±10 kg) and race.
Exclusion Criteria
- •Presence of any condition or circumstance that prevents the subject from understanding and signing the ICF.
- •Presence or history of any disorder that may prevent the successful completion of the study.
- •History of significant hypersensitivity, intolerance, or allergy to food, or any medical product or relevant excipient, unless approved by the Investigator.
- •History of allergy to Elacestrant or drugs in a similar pharmacology class (selective ER modulator or SERD) or excipients used in the formulations of these drugs.
- •History of stomach or intestinal surgery or resection, or any significant gastrointestinal disease (eg, Crohn's disease) that would potentially alter absorption and/or excretion of orally administered drugs (uncomplicated appendectomy and hernia repair will be allowed). Cholecystectomy will be allowed at the discretion of the Investigator.
- •Acute disease state (eg, nausea, vomiting, fever, diarrhea) within 14 days prior to check-in.
- •History of drug/chemical abuse within 1 year prior to check-in.
- •History of alcohol abuse within 3 months prior to screening and/or consume \> 21 units per week for males and \> 14 units for females. One unit of alcohol equals 12 oz (360 mL) beer, 1 1⁄2 oz (45 mL) liquor, or 5 oz (150 mL) wine.
- •Positive drug screen at screening, or positive alcohol or drug screen at check-in.
- •Participation in a clinical study involving administration of an investigational drug (new chemical entity) or device in the past 28 days or 5 half-lives (whichever is longer) prior to dosing.
Arms & Interventions
Subjects with normal hepatic function
Subjects with normal hepatic function will receive treatment compared to subjects with severe hepatic function
Intervention: Elacestrant dihydrochloride
Subjects with severe hepatic impaired function
Subjects with severe hepatic function will receive treatment compared to subjects with normal hepatic function
Intervention: Elacestrant dihydrochloride
Outcomes
Primary Outcomes
Maximum observed plasma concentration (Cmax)
Time Frame: Predose 240 hours after drug administration
Area under the plasma concentration-time curve from time zero to the last measurable concentration (AUC0-t)
Time Frame: Predose 240 hours after drug administration
AUC from time zero to infinity (AUC0-∞)
Time Frame: Predose 240 hours after drug administration