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

• Status: Not yet recruiting
• Trial end date: 2022-12-01
• Target enrollment: 0
• Participant gender: All

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, BMI, and, if possible, smoking habit. 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 blood plasma over the course of 9 days (including calculation of PK parameters), the degree of EQ143 binding to plasma proteins in blood, and the safety of administering a single dose of EQ143 in severely hepatically impaired and matched healthy participants.

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: EQRx, Inc.

Criteria

Inclusion Criteria:

Participants are eligible to be included in the study only if all of the following criteria apply:

Main Criteria for Inclusion: All Participants

1. Must be willing to participate in the study and sign the informed consent form (ICF).

2. Must be willing and able to complete all study-specific procedures and visits.

• If a man or a woman of nonchildbearing potential (WONCBP) aged 18 to 75 years, inclusive, at Screening. Women may be considered WONCBP if they are either surgically sterile (hysterectomy or oophorectomy) or postmenopausal for ≥ 1 year (with follicle-stimulating hormone [FSH] level ≥ 38 mIU/mL) and must have a negative serum pregnancy test result within 48 hours before administration of EQ143. Women who are surgically sterile must provide documentation of the procedure by an operative report or by ultrasound scan.

• Women must not be breastfeeding.

• Men must agree to use a highly effective method of contraception (eg, male condom in addition to hormonal contraception) during heterosexual intercourse from admission to the study center until 12 weeks after the final follow-up visit, and must refrain from donating sperm for the same time period.

3. BMI of 18.0 to 42.0 kg/m2.

4. High probability for compliance with and completion of the study, in the opinion of the Principal Investigator.

Main Criteria for Inclusion: Hepatically Impaired Participants

5. Severe hepatic impairment (Child-Pugh class C according to the Child-Pugh classification).

• Severe hepatic impairment is confirmed and documented based on at least one of the following: medical history, physical examination, computed axial tomography (CT) scan, magnetic resonance imaging (MRI), and/or liver biopsy.

• Screening laboratory test results for serum bilirubin, serum albumin, prothrombin time, and stage of hepatic encephalopathy with or without ascites are consistent with Child-Pugh class C.

• Hepatic impairment etiology should be one of the following: chronic alcoholism, chronic viral hepatitis, nonalcoholic steatohepatitis, autoimmune hepatitis, Wilson disease, alpha-1 antitrypsin deficiency, glycogen storage diseases, galactosemia, or cryptogenic.

6. Participants with concurrent stable medical conditions (in addition to hepatic impairment) may be included if the Investigator, the Clinical Pharmacologist, and the Medical Monitor agree that these conditions will not introduce an additional risk factor and will not interfere with the study objectives and procedures (eg, participants with diabetes without renal complications may be included).

7. Participants taking medications necessary for the management of their hepatic disease, or of concomitant conditions, may be included, provided that their therapeutic regimen has been stable for at least 7 days before EQ143 administration and is not expected to interfere with the PK of EQ143.

Main Criteria for Inclusion: Healthy Matched Participants

8. Normal renal function, defined as estimated glomerular filtration rate of ≥ 90 mL/min/1.73 m2 calculated using the method standard for the institution.

9. Normal hepatic function, as judged by the Investigator.

10. Healthy, as determined by the Investigator on the basis of medical history, physical examination, clinical laboratory test results, vital sign measurements, and 12-lead electrocardiogram (ECG).

11. Matched to the hepatically impaired participants in sex, age (± 10 years), BMI (± 20% of BMI at Screening), and, if possible, smoking habit.

Exclusion Criteria:

Participants are excluded from the study if any of the following criteria apply:

Main Criteria for Exclusion: All Medical History

1. Family history of QT prolongation, syncope, seizure, or unexplained cardiac-related death.

2. Presence or history of any disorder that may prevent the successful completion of the study.

3. Current or recent (within 3 months of Day 1 of the study) gastrointestinal disease that could impact the absorption of EQ143.

4. History of drug abuse within 1 year before Day 1.

5. 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

6. History of any clinically important drug allergy or adverse drug reaction.

Physical and Laboratory Findings

7. Plasma potassium and/or magnesium values below the limits of normal.

• Note: At the discretion of the Investigator, these tests may be repeated to confirm a result that is below but close to the limits of normal; repeat test results must be within normal limits to confirm participant eligibility.

8. An automatic ECG-corrected QT (QTc) interval reading at Screening of > 480 ms.

9. Positive serologic finding for human immunodeficiency virus (HIV).

10. Positive for current infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

11. Positive finding on urine drug screen (eg, amphetamines, barbiturates, enzodiazepines, cocaine, opiates), except cannabinoids.

Prohibited Treatments

12. Consumption of alcoholic beverages from 24 hours before Day 1.

13. Consumption of grapefruit or grapefruit containing products from 72 hours before Day 1 through the final study visit.

14. Donation of blood within 30 days before Day 1.

15. Involvement in another investigational study of any type within 30 days before EQ143 administration.

Main Criteria for Exclusion: Hepatically Impaired Participants

Medical History

16. Evidence of uncontrolled and clinically significant disease other than impaired hepatic function (eg, cardiovascular, gastrointestinal, cerebrovascular, respiratory, or renal disease, or any other comorbidity that, in the judgment of the Principal Investigator, precludes participation in the study).

17. Has received, or is currently waiting for, an organ transplant.

18. Recent history or presence of any disorder that may interfere with the absorption, distribution, metabolism, or excretion of EQ143 (except those conditions associated with the hepatic disease) that may place the participant at risk during participation in the study.

19. Presence of surgically created or transjugular intrahepatic portal systemic shunt.

Physical and Laboratory Findings

20. Evidence of severe hepatorenal syndrome, as shown by calculated creatinine clearance < 40 mL/min (Cockcroft-Gault equation).

21. Unstable liver disease, as shown by any of these factors/parameters:

• Spontaneous bacterial peritonitis within 3 months before Day 1

• Variceal bleeding within 1 month before Day 1

• Severe hyponatremia (sodium level < 125 mmol/L)

• Current evidence of hepatocellular cancer

• Acute hepatic disease caused by an infection or drug toxicity

• Severe encephalopathy (grade 3-4 [Child-Pugh classification])

• Presence of severe ascites or severe edema that precludes participation in the study, as judged by the Investigator

• Hemoglobin level < 9.0 g/dL

• Platelet count < 30 × 109/L for Child-Pugh class C participants

• Total bilirubin level > 900 mmol/L

• Relative increase of prothrombin time by > 50% within the 2 weeks before EQ143 administration

• Positive serologic findings for hepatitis B surface antigen (HBsAg) and/or hepatitis C virus (HCV) antibodies.

• Note: Test outcomes that are reactive to HCV antibody will be followed by an HCV ribonucleic acid (RNA) test (polymerase chain reaction [PCR]).

Prohibited Treatments

22. Prescription and over-the-counter (OTC) medication that is not taken according to a stable regimen for 7 days before EQ143 administration.

23. Use of any treatment known to be a strong CYP3A4 inhibitor or inducer within approximately 30 days or 5 half-lives, whichever is longer, before Day 1, with the exception of grapefruit or grapefruit-containing products (which are prohibited within 72 hours before Day 1, as noted above in Exclusion Criterion #13).

24. Use of any treatment known to be a sensitive CYP3A4 substrate within approximately 4 days (or 5 half lives, whichever is longer) before and 4 days (or 5 half-lives, whichever is longer) after EQ143 administration.

25. Concomitant use of medications known to prolong the QTc interval.

26. Medications that alter gastric pH (eg, proton-pump inhibitors) within 3 days before and 2 days after EQ143 administration.

Main Criteria for Exclusion: Healthy Matched Participants Medical History

27. Any significant cardiovascular, hepatic, renal, respiratory, gastrointestinal, endocrine, immunologic, dermatologic, hematologic, neurologic, or psychiatric disease.

28. Any surgical or medical condition that may interfere with the absorption, distribution, metabolism, or excretion of EQ143.

29. Acute disease state (eg, nausea, vomiting, fever, or diarrhea) within 7 days before Day 1.

30. History of alcoholism within 1 year before Day 1, or consumption of more than 50 g of ethanol per day (12.5 cL glass of 10° [10%] wine = 12 g; 4 cL glass of aperitif; 42° [42%] whiskey = 17 g; 25 cL glass of 3° [3%] beer = 7.5 g; 25 cL glass of 6° [6%] beer = 15 g).

Physical and Laboratory Findings

31. Any clinically important deviation from normal limits in physical examination, vital sign measurements, 12-lead ECGs, or clinical laboratory test results.

32. Positive serologic findings for HBsAg and/or HCV antibodies.

-Note: Test outcomes that are reactive to HCV antibody will be followed by an HCV RNA test (PCR).

Prohibited Treatments

33. Use of any prescription drug within 15 days or 5 half-lives, whichever is longer, before EQ143 administration, except hormone replacement therapy in postmenopausal women or treatments permitted in consultation with Medical Monitor.

34. Use of any OTC drugs, including herbal supplements, within 14 days before Day 1, except for the occasional use of acetaminophen (paracetamol) and vitamins (≤ 100% of the recommended daily allowance).