To Evaluate the Comparative Pharmacokinetics of Orally Administered EQ143 in Caucasian and Ethnic Chinese Populations

• Register: ANZCTR
• Last refreshed on: 5 July 2021
• Main ID: ACTRN12621000848808
• Date of registration: 01/07/2021
• Prospective Registration: No
• Primary sponsor: EQRx, Inc
• Public title: To Evaluate the Comparative Pharmacokinetics of Orally Administered EQ143 in Caucasian and Ethnic Chinese Populations
• Scientific title: A Single Dose Phase 1 Study in Healthy Participants to Evaluate the Comparative Pharmacokinetics of Orally Administered EQ143 in Caucasian and Ethnic Chinese Populations
• Date of first enrolment: 21/06/2021
• Target sample size: 30
• Recruitment status: Recruiting
• URL: https://anzctr.org.au/ACTRN12621000848808.aspx
• Study type: Interventional
• Study design: Purpose: Treatment; Allocation: Non-randomised trial; Masking: Open (masking not used);Assignment: Single group;Type of endpoint: Pharmacokinetics;
• Phase: Phase 1

Countries of recruitment

New Zealand

Contacts

• Name: Ms Jessie Kane

• Name: Dr Deepal Wakade

Key inclusion & exclusion criteria

Inclusion criteria: To be eligible for this study, a participant has to meet all of the following inclusion criteria:
1. Participant self-reports as being of non-Chinese, European descent or participant self-reports as having two Han Chinese biological parents
2. Is capable of giving informed consent and complying with study procedures;
3. Healthy male or female participants, between the ages of 18 and 65 years, inclusive at the time of informed consent;
4. Body mass index (BMI) of 18.0 to 34.9 kg per m2 inclusive and body weight not less than 50 kg;
5. Female participants must have a negative serum pregnancy test result at Screening and negative urine pregnancy test at admission to the study site, are not currently breast-feeding, and meet one of the following criteria:
a. Surgically sterile for at least 3 months prior to Screening by one of the following means:
- Bilateral tubal ligation
- Bilateral salpingectomy (with or without oophorectomy)
- Surgical hysterectomy
- Bilateral oophorectomy (with or without hysterectomy)
b. Postmenopausal, defined as the following:
- Last menstrual period greater than 12 months prior to Screening without an alternative medical cause, And
- Postmenopausal status confirmed by serum FSH concentration at Screening greater than 40 milli-international units per mL
c. Female subjects of childbearing potential must use at least one of the following protocol specified highly effective methods of birth control, And must agree to use barrier
contraception (male condom) during heterosexual intercourse, from the time of Screening
until at least 30 days after EQ143 treatment:
- Partner vasectomy (at least 6 months prior to Screening; vasectomized partner should
be the sole partner of the female subject)
- Combined (estrogen and progestogen containing) hormonal contraception (oral,
intravaginal, transdermal, injectable)
- Progestogen-only hormonal contraception (oral, injectable, implantable)
- Implantable device (implantable rod or intrauterine device)
Alternatively, females of childbearing potential must practice complete abstinence
(defined as refraining from heterosexual intercourse when this is in line with the preferred
and usual lifestyle of the participant; periodic abstinence and withdrawal are not
acceptable) from Screening until at least 30 days after EQ143 treatment. It is not
necessary to use any other method of contraception when complete abstinence is elected.
Women of childbearing potential (WOCBP) who choose complete abstinence must
continue to have pregnancy tests as per protocol. The reliability of sexual abstinence
needs to be evaluated by the Investigator in relation to the duration of the clinical trial and
the preferred and usual lifestyle of the subject.
6. Male participants must agree to utilize a highly effective method of contraception (condom) during heterosexual intercourse from CRU admission until 12 weeks following the final Follow-up visit on Day 10 and must refrain from donating sperm for this same period;
7. Considered healthy by the Investigator, based on participant’s reported medical history, full physical examination, clinical laboratory tests, 12-lead ECG, and vital signs;
8. Willing and able to adhere to study restrictions and to be confined at the clinical research center;
9. Participants willing to defer receiving prophylactic live immunizations during the duration of the study.


Exclusion criteria: A participant who meets any of the following exclusion criteria must be excluded from the study:
1. Inability to attend all the study visits or comply with study procedures;
2. Evidence of clinically significant history of gastrointestinal, musculoskeletal, endocrine, hematologic, renal, hepatic, neurologic, ophthalmic, immunologic, lipid metabolism disorders, drug hypersensitivity, psychiatric disease and abnormalities or any known history of any gastrointestinal surgery or cholecystectomy that could impact the PK of EQ143 as determined by the Investigator or Sponsor;
3. Evidence of clinically significant history of cardiovascular disease, including myocardial infarction, unstable angina, Torsade de Pointes, clinically significant arrhythmias (including sustained ventricular tachyarrhythmia and ventricular fibrillation), symptomatic congestive heart failure (New York Heart Association class III or IV), cerebrovascular accident, transient ischemic attack, or symptomatic pulmonary embolism or other clinically significant episode of thromboembolic disease;
4. Evidence of clinically significant history of bronchopulmonary disease, including interstitial lung disease (ILD), drug induced ILD, radiation pneumonia requiring steroid treatment and clinical evidence of active ILD;
5. Hospital admission or major surgery within 3 months prior to Screening;
6. Taken any prescription medications (excluding contraceptives) within 14 days or 5 half-lives (whichever is longer) of the study dose or taken an investigational drug within 3 months or 5 half-lives, whichever is longer, from the Screening date;
7. Evidence of hypertension stage 2 despite optimal medical therapy, defined as a systolic BP greater than 140 mmHg and a diastolic BP greater than 90 mmHg at Screening. Blood pressure measurement should be performed in triplicate if initial results exceed these values, and the average value should be used to determine eligibility;
8. Fever (body temperature greater than 38°C) or symptomatic viral or bacterial infection within 2 weeks prior to Screening. Boards/Independent Ethics Committees, and study center policies) and at the discretion of the Investigator, if required;
9. The following ECG criteria at Screening or Admission:
a. A marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a
QTc interval greater than 450 ms)
b. ST segment elevation or depression considered to be clinically significant by the
Investigator or designee;
c. T-wave abnormalities considered to be clinically significant by the Investigator or designee;
If the QTcF interval exceeds 450 ms (males) or 480 ms (females), or the QRS interval exceeds 120 ms, the ECG should be repeated in triplicate and the average of the 3 QTcF or QRS values should be used to determine the patient’s eligibility;
10. Impaired renal function as determined by Investigator following review of clinical
laboratory test results (i.e., eGFR less than 90 mL per min per 1.73m2);
11. Any of the following safety laboratory findings at Screening or Admission:
a. Absolute neutrophil count greater than 1.5 into 109 per L
b. Platelet count greater than 100 into 109 per L
c. Hemoglobin greater than 90 g per L (greater than 9 g per dL);
12. Positive blood screen for HIV, hepatitis B core (IgG and IgM) and surface antigen
(HBsAg), Hepatitis A antibody (IgM), or hepatitis C antibody (IgG) at Screening;
13. Participants with major clinical infections with

Age minimum: 18 Years
Age maximum: 65 Years
Gender: Both males and females

Health Condition(s) or Problem(s) studied

Cancer - Lung - Non small cell

Non Small Cell Lung Cancer;
Non Small Cell Lung Cancer

Intervention(s)

EQ143 tablet is an oral solid dosage form manufactured at a strength of 55 mg. Each EQ143 tablet contains EQ143 drug substance, microcrystalline cellulose (KG802), anhydrous lactose (21AN), sodium carboxymethyl starch (type A), sodium stearyl fumarate and magnesium stearate (MF-2-V). EQ143 is orally administered once at a dose of 110 mg (two tablets) for each single dose.
Participants will ingest EQ143 on an empty stomach after overnight fasting (minimum 8 hours) and will have a total of three overnight stays (admission on Day -1 until 48 hours post-dose on Day 3) during a Treatment period. The total duration of participation in the study for each participant is up to 38 days (which includes up to 28 days of Screening). All doses will be administered as a single dose at the CRU in the presence of the Investigator or their designee. Time of dose will be recorded in the participant’s eCRF. Participants should be advised not to crush, break, chew, or dissolve the tablet and to take the study medication with room temperature water. Water will be allowed as desired except for 1 hour before and 1 hour after EQ143 administration. Participants are to avoid eating for 1 hour after dosing.
The Investigator or designee will be fully responsible for the security, accessibility, and storage of EQ143 while it is at the investigational facility. On completion of the study, any surplus EQ143 supplies will be destroyed upon receipt of written approval from the Sponsor and in accordance with the facility’s standard procedures.
Evidence of the destruction of any surplus EQ143 will be supplied to the study monitor. If no supplies remain, this will be documented in the dispensing record.

Primary Outcome(s)

To compare the concentration (called PK) of EQ143 in the blood following a single oral administration in adult, healthy participants.[Pharmacokinetic (PK) blood sampling will be conducted at pre-dose (within 1 hour prior to dosing) on day 1 at an interval of 1 and 2 hours and Day 2, Day 3, Day 4, Day 5, Day 6, and Day 8 post-dose and at the end of study (EOS) visit (10 days post-dose).]

To determine concentrations of EQ143 in the blood before and after it is broken down in the body. This will be assessed through the following parameters:
• Area under the drug concentration-time curve from time 0 to 24 hours (AUC0-24 h)
• Area under the drug concentration-time curve from time 0 to the last quantifiable time
point (AUC0-t)
• Cmax[Blood samples will be collected at day 1 post dose
- At 1, 2, and 3 hours post-dose (within a ± 5 min time frame)
- At 4, 6, 8, 10, and 12 hours post-dose (within a ± 10 min time frame)
and day 1, day 2, day 3, day 4, day 5, day 6 and 8 days post-dose and at end of study (EOS) visit (10 days post-dose).
]

Secondary Outcome(s)

A urinalysis test (dipstick) will be performed to analyze the following parameters:
• pH (PH)
• Specific Gravity (SPGRAV)
• Creatinine (CREATININE)
• Protein (PROT)
• Glucose (GLUC)
• Ketones (KETONES)
• Total Bilirubin (BILI)
• Occult Blood (OCCBLD)
• Nitrite (NITRITE)
• Urobilinogen (UROBIL)
• Leukocytes (WBC)[Urine samples will be collected at Screening, on Day -1, Day 2, Day 3 and at the EOS visit (Day 10) after dosing.]

To assess blood test result for coagulation parameters LDL-C, HDL-C, [Blood samples will be collected at Screening, on Day -1, Day 2, Day 3 and at the EOS visit (Day 10) after dosing.]

To assess blood test result for triglycerides[Blood samples will be collected at Screening, on Day -1, Day 2, Day 3 and at the EOS visit (Day 10) after dosing.]

To assess blood test results for serum chemistry[Blood samples will be collected at Screening, on Day -1, Day 2, Day 3 and at the EOS visit (Day 10) after dosing.]

To assess blood test results for the hematology


[Blood samples will be collected at Screening, on Day -1, Day 2, Day 3 and at the EOS visit (Day 10) after dosing.]

To assess the Incidence of Treatment-Emergent Adverse Events (safety and tolerability) of EQ143 in adult, healthy participants through (CTCAE) v5.0)


[Adverse events will be monitored throughout the study from screening visit to end of study visit (10 days post-dose).]

To assess the safety and tolerability of EQ143 in adult, healthy participants. Outcome is assessed by Electrocardiogram (ECG) which is a recording of the heart's electrical activity:
• Heart rate
• QT interval
• PR interval
• QRS interval
• RR interval
• ST segment
• QTcF (corrected).
ECGs will be performed prior to vital signs with participants in a supine position. Participants must be in this position for at least 5 minutes before the reading is taken.[A resting 12-lead ECG will be completed at Screening, Day -1 at pre-dose and 1, 2, and 4 hours post-dose, Day 2 and at the EOS visit (day 10 post-dose).]

To assess the safety and tolerability of EQ143 in adult, healthy participants. Outcome is assessed by Physical Examination:
• Eyes
• Ears, nose, throat, neck, thyroid
• Cardiovascular system
• Respiratory system
• Gastrointestinal system, mouth
• Dermatologic system
• Extremities
• Musculoskeletal system
• Central and peripheral nervous system
• Lymph nodes.
[Physical examination will be performed at the screening visits and the end of study visit (day 10 post-dose). Also, physical examinations may be performed at various unscheduled time points if deemed necessary by the Investigator.]

To assess the safety and tolerability of EQ143 in adult, healthy participants. Outcome is assessed by Vital signs:
- blood pressure and pulse rate by a Sphygmomanometer
- respiratory rate is observed by a study coordinator.
- oral temperature is taken using a thermometer.

[Vital sign assessments will be done at Screening, on Day -1 (pre dose) and Day 1 (at an interval of 1 and 2 hours), Day 2, Day 3, Day 4, Day 5, Day 6 and Day 8 post dose and End Of Study (EOS) (day 10 post-dose) visit.
]

Secondary ID(s)

EQ143-101

Source(s) of Monetary Support

EQRx, Inc

Ethics review

Status: Approved
Approval date: 04/05/2021
Contact:

Southern Health and Disability Ethics Committee