An Open-Label, Single-Dose, Parallel-Group Study of the Pharmacokinetics and Safety of EQ143

NCT05199610 | Completed Phase 1 FDA Drug

• 1 other identifier: EQ143-102
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 3

Brief Summary

Participants aged 18 to 75 years with severe hepatic impairment (Child-Pugh class C) who meet the full study eligibility criteria will be enrolled into the study. For each participant with severe hepatic impairment, a corresponding healthy participant will be enrolled who matches with regard to age, sex, and BMI. A single dose of 55-mg EQ143 tablet will be administered in the morning on Day 1, and participants will remain for 5 days (4 nights) in the study center for collection of blood samples and safety monitoring. Participants will attend outpatient follow-up visits on Days 5, 6, 8, and 9 for additional blood sampling and safety assessments. The study will measure and describe the concentrations of EQ143 and its metabolite (HAS-719) in plasma over the course of 9 days (including calculation of PK parameters), the degree of EQ143 and metabolite HAS-719 (and other metabolites, if applicable) binding to proteins in plasma, and the safety of administering a single dose of EQ143 in severely hepatically impaired and matched healthy participants

Conditions

Severe Hepatic Impairment

Outcome Measures

Primary Outcomes (7)

• Pharmacokinetic (PK) Parameter: Cmax of EQ143

  Cmax is defined as the maximum observed concentration of drug

  Predose and 1, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 168, and 192 hours post dose

• PK Parameter: AUC0-t of EQ143

  AUC0-t is defined as the area under the concentration versus time curve from time zero to the last quantifiable concentration

  Predose and 1, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 168, and 192 hours post dose

• PK Parameter: AUCinf of EQ143

  AUCinf is defined as the area under the concentration versus time curve extrapolated to infinite time

  Predose and 1, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 168, and 192 hours post dose

• PK Parameter: CL/F of EQ143

  CL/F is defined as apparent clearance

  Predose and 1, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 168, and 192 hours post dose

• PK Parameter: Cmax of metabolite, HAS719

  Cmax is defined as the maximum observed concentration of drug

  Predose and 1, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 168, and 192 hours post dose

• PK Parameter: AUC0-t of metabolite, HAS719

  AUC0-t is defined as the area under the concentration versus time curve from time zero to the last quantifiable concentration

  Predose and 1, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 168, and 192 hours post dose

• PK Parameter: AUCinf of metabolite, HAS719

  AUCinf is defined as the area under the concentration versus time curve extrapolated to infinite time

  Predose and 1, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 168, and 192 hours post dose

Secondary Outcomes (15)

• Number of Participants with Adverse Event

  up to 38 Days

• PK Parameter of EQ143: Time to peak concentration (tmax)

  Predose and 1, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 168, and 192 hours post dose

• PK Parameter of EQ143: elimination half-life (t1/2z)

  Predose and 1, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 168, and 192 hours post dose

• PK Parameter of EQ143: apparent volume of distribution (Vz/F)

  Predose and 1, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 168, and 192 hours post dose

• PK Parameter of EQ143: fraction unbound (fu)

  Predose and 1, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 168, and 192 hours post dose

Study Arms (1)

Aumolertinib

EXPERIMENTAL

single dose oral 55mg of aumolertinib

Drug: aumolertinib

Interventions

aumolertinib DRUG

A single dose of 55-mg EQ143 tablet will be administered in the morning on Day 1, and participants will remain for 5 days (4 nights) in the study center for collection of blood samples and safety monitoring. Participants will attend outpatient follow-up visits on Days 5, 6, 8, and 9 for additional blood sampling and safety assessments.

Also known as: HS-10296

Aumolertinib

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants are eligible to be included in the study only if all of the following criteria apply:
• Must be willing to participate in the study and sign the informed consent form (ICF).
• Must be willing and able to complete all study-specific procedures and visits.
• Is 18 to 75 years of age, inclusive, at Screening.
• Is able to take and swallow oral medication.
• BMI of 18.0 to 42.0 kg/m2
• High probability for compliance with and completion of the study, in the opinion of the Investigator.
• Must meet all of the applicable requirements for pregnancy and contraception, as follows:
• If female:
• Is a female participant of childbearing potential who:
• Has a negative serum pregnancy test result within 48 hours before Day -1;
• Is not breastfeeding;
• Agrees to use highly effective contraceptive measures during heterosexual intercourse throughout the study and for 12 weeks following EQ143 administration; AND
• Agrees not to donate ova for the same time period; OR
• Is a participant of non-childbearing potential, as confirmed by meeting both of the following criteria:

You may not qualify if:

• Participants are excluded from the study if any of the following criteria apply:
• Family history of QT prolongation, syncope, seizure, or unexplained cardiac-related death.
• Presence or history of any disorder that may prevent the successful completion of the study.
• Current or recent (within 3 months of Day 1 of the study) gastrointestinal disease that could impact the absorption of EQ143.
• History of drug abuse within 1 year before Day 1 of the study
• Is a regular smoker (ie, smokes more than 5 cigarettes per day or more than 10 packets per year), and is not willing to refrain from smoking from 48 hours before EQ143 administration through the final study visit.
• Allergies and Adverse Drug Reactions
• History of any clinically important drug allergy or adverse drug reaction. Physical and Laboratory Findings
• Plasma potassium and/or magnesium values outside the normal range.
• Note: At the discretion of the Investigator, these tests may be repeated to confirm a result that is outside the normal range; repeat test results must be within normal limits to confirm participant eligibility.
• An automatic ECG absolute QT interval with Fridericia's correction (QTcF) reading at Screening of \> 480 ms (males) or \> 500 ms (females).
• Has evidence of active bacterial, fungal, or viral infection (including human immunodeficiency virus \[HIV\] or SARS-CoV-2, as detailed below) which would preclude safe enrollment as assessed by the treating Investigator.
• Note regarding HIV: Participants with positive serologic finding and detectable HIV are excluded; however, participants with undetectable HIV and a viral load of 0 are not excluded if meeting all other eligibility criteria.
• Note regarding SARS-CoV-2: The study SARS-CoV-2 requirements are determined by institutional standards (and local/country regulations, as applicable).
• At Investigator discretion, any participant who tests positive and/or is symptomatic for SARS-CoV-2 during Screening may either be excluded from the study or delay enrollment until active infection has been excluded per institutional standards.

Sponsors & Collaborators

• EQRx International, Inc.: lead

Study Sites (3)

American Institute Research

Los Angeles, California, 90017, United States

Location

Global Clinical Professionals

St. Petersburg, Florida, 33705, United States

Location

Texas Liver Institute

San Antonio, Texas, 78215, United States

Location

MeSH Terms

Interventions

aumolertinib

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 5, 2021
• First Posted: January 20, 2022
• Study Start: March 30, 2022
• Primary Completion: April 1, 2023
• Study Completion: April 1, 2023
• Last Updated: April 19, 2023

Record last verified: 2023-04

Locations

US (3)