A PK Study Testing Single Oral Dose of Elacestrant in Subjects With Normal or Severely Impaired Hepatic Function

NCT06126575 | Completed Phase 1 FDA Drug

• 1 other identifier: STML-ELA-1023
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 3

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.

Conditions

Hepatic Impairment

Keywords

metastatic breast cancer; breast cancer; elacestrant

Outcome Measures

Primary Outcomes (3)

• Maximum observed plasma concentration (Cmax)

  Predose 240 hours after drug administration

• Area under the plasma concentration-time curve from time zero to the last measurable concentration (AUC0-t)

  Predose 240 hours after drug administration

• AUC from time zero to infinity (AUC0-∞)

  Predose 240 hours after drug administration

Study Arms (2)

Subjects with normal hepatic function

EXPERIMENTAL

Subjects with normal hepatic function will receive treatment compared to subjects with severe hepatic function

Drug: Elacestrant dihydrochloride

Subjects with severe hepatic impaired function

EXPERIMENTAL

Subjects with severe hepatic function will receive treatment compared to subjects with normal hepatic function

Drug: Elacestrant dihydrochloride

Interventions

Elacestrant dihydrochloride DRUG

A single oral dose of 200 mg elacestrant (2 x 100 mg tablets).

Subjects with normal hepatic function; Subjects with severe hepatic impaired function

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.
• Documented chronic stable severe liver disease according to Child Pugh (CP) classification (CP score C) with diagnosis of hepatic impairment due to parenchymal liver disease. This will exclude biliary liver cirrhosis or other causes of hepatic impairment not related to parenchymal disorder.
• 'Documented' is defined by medical history and physical examination, and confirmed by at least 1 of the following: hepatic ultrasound, computed axial tomography scan, magnetic resonance imaging, and/or liver biopsy.
• 'Chronic' is defined as \>6 months.
• 'Stable' is defined as no clinically significant change in disease status within the last 6 weeks, as documented by the subject's recent medical history (eg, no worsening of clinical signs of hepatic impairment, or no worsening of total bilirubin or prothrombin time by more than 50%).
• Subjects with severe hepatic impairment may have medical findings consistent with their hepatic dysfunction as determined by medical history, physical examination, 12-lead ECG, vital sign measurements, and clinical laboratory evaluations at screening and check-in (Day -1), as assessed by the Investigator, provided that the followings are satisfied:
• Non-hepatic impairment-related, abnormal clinical laboratory evaluations must not be clinically relevant, as judged by the Investigator and approved by the study assigned medical monitor.

You may not qualify if:

• 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.
• Received Elacestrant within 60 days prior to dosing.
• Corrected value of the interval between the Q and T waves on the ECG tracing, using Fridericia's formula, is \> 450 ms (for healthy males) or \> 470 ms (for healthy females), is \> 470 ms (for hepatic impairment males) or \> 480 ms (for hepatic impairment females); or has ECG findings deemed abnormal with clinical significance by the Investigator at screening. ECGs will be collected in triplicate.
• Use of any drugs or herbal remedies known to be strong or moderate inhibitors or inducers of CYP3A enzymes for 28 days prior to dosing or 5 half-lives (whichever is longer) and throughout the study.
• Not willing to follow on-study diet requirements.
• Ingestion of Seville orange- or grapefruit- containing foods or beverages within 28 days prior to check-in.

Sponsors & Collaborators

• Stemline Therapeutics, Inc.: lead

Study Sites (3)

Inland Empire Clinical Trials, LLC

Yucaipa, California, 92399, United States

Location

Floridian Clinical Research

Miami, Florida, 33016, United States

Location

American Research Corp

San Antonio, Texas, 78215, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

RAD1901

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 6, 2023
• First Posted: November 13, 2023
• Study Start: March 13, 2023
• Primary Completion: November 11, 2024
• Study Completion: November 11, 2024
• Last Updated: November 19, 2024

Record last verified: 2024-11

Locations

US (3)