Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12621000848808
Ethics application status
Approved
Date submitted
6/04/2021
Date registered
1/07/2021
Date last updated
1/07/2021
Date data sharing statement initially provided
1/07/2021
Type of registration
Retrospectively registered

Titles & IDs
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
Secondary ID [1] 303663 0
EQ143-101
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Non Small Cell Lung Cancer 321054 0
Condition category
Condition code
Cancer 318856 318856 0 0
Lung - Non small cell

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
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.
Intervention code [1] 319963 0
Treatment: Drugs
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 326807 0
To compare the concentration (called PK) of EQ143 in the blood following a single oral administration in adult, healthy participants.
Timepoint [1] 326807 0
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).
Primary outcome [2] 326871 0
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
Timepoint [2] 326871 0
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 [1] 392739 0
To assess the Incidence of Treatment-Emergent Adverse Events (safety and tolerability) of EQ143 in adult, healthy participants through (CTCAE) v5.0)
Timepoint [1] 392739 0
Adverse events will be monitored throughout the study from screening visit to end of study visit (10 days post-dose).
Secondary outcome [2] 392917 0
To assess blood test results for the hematology
Timepoint [2] 392917 0
Blood samples will be collected at Screening, on Day -1, Day 2, Day 3 and at the EOS visit (Day 10) after dosing.
Secondary outcome [3] 392918 0
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.
Timepoint [3] 392918 0
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).
Secondary outcome [4] 392920 0
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.
Timepoint [4] 392920 0
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 outcome [5] 393092 0
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.
Timepoint [5] 393092 0
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.
Secondary outcome [6] 395625 0
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)
Timepoint [6] 395625 0
Urine samples will be collected at Screening, on Day -1, Day 2, Day 3 and at the EOS visit (Day 10) after dosing.
Secondary outcome [7] 395682 0
To assess blood test results for serum chemistry
Timepoint [7] 395682 0
Blood samples will be collected at Screening, on Day -1, Day 2, Day 3 and at the EOS visit (Day 10) after dosing.
Secondary outcome [8] 395683 0
To assess blood test result for coagulation parameters LDL-C, HDL-C,
Timepoint [8] 395683 0
Blood samples will be collected at Screening, on Day -1, Day 2, Day 3 and at the EOS visit (Day 10) after dosing.
Secondary outcome [9] 395684 0
To assess blood test result for triglycerides
Timepoint [9] 395684 0
Blood samples will be collected at Screening, on Day -1, Day 2, Day 3 and at the EOS visit (Day 10) after dosing.

Eligibility
Key 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.

Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key 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 within 3 months prior to Screening or any
symptoms of infection within 7 days prior to Screening (not applicable to participants
with cutaneous fungal infection);
14. Donated or lost greater than 500ml of blood in the previous 3 months prior to Screening;;
15. Any condition or finding that in the opinion of the Principal Investigator or designee would put the participant or study conduct at risk if the participant were to participate in the study.
16. Pregnant or lactating at Screening or planning to become pregnant (self or partner) at any time during the study, including the Follow-up period.
17. Participants who are regular smokers, i.e., smoke more than five cigarettes per day or more than ten packets per year, and are not willing to refrain from smoking from 48 hours before EQ143 administration through to the final Follow-up visit on Day 10



Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1
Type of endpoint/s
Pharmacokinetics
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
21/06/2021
Date of last participant enrolment
Anticipated
2/08/2021
Actual
Date of last data collection
Anticipated
20/08/2021
Actual
Sample size
Target
30
Accrual to date
7
Final
Recruitment outside Australia
Country [1] 23529 0
New Zealand
State/province [1] 23529 0
Auckland

Funding & Sponsors
Funding source category [1] 308079 0
Commercial sector/Industry
Name [1] 308079 0
EQRx, Inc
Country [1] 308079 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
EQRx, Inc
Address
50 Hampshire Street, Cambridge, MA 02139, USA
Country
United States of America
Secondary sponsor category [1] 308817 0
None
Name [1] 308817 0
Address [1] 308817 0
Country [1] 308817 0
Other collaborator category [1] 281690 0
Commercial sector/Industry
Name [1] 281690 0
Novotech (Australia) Pty Limited
Address [1] 281690 0
Novotech (Australia) Pty Limited
Level 3, 235 Pyrmont Street Sydney, NSW Australia - 2009
Country [1] 281690 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 308068 0
Southern Health and Disability Ethics Committee
Ethics committee address [1] 308068 0
133 Molesworth Street, Thorndon, Wellington 6011, New Zealand
Ethics committee country [1] 308068 0
New Zealand
Date submitted for ethics approval [1] 308068 0
25/03/2021
Approval date [1] 308068 0
04/05/2021
Ethics approval number [1] 308068 0

Summary
Brief summary
This is an open-label and uncontrolled study to evaluate the comparative PK of EQ143 following oral single dose administration in adult healthy volunteers from Caucasian and ethnic Chinese populations.
A total of one (1) single dose cohort is planned at 110 mg of EQ143. EQ143 is an approved therapy in China at the 110 mg dose for the treatment of patients with Epidermal Growth Factor Receptor (EGFR) T790M mutation-positive, metastatic non-small cell lung cancer (NSCLC), who have progressed during or after EGFR tyrosine kinase inhibitor (TKI) therapy.
A total of 30 (15 Caucasian and 15 ethnic Chinese) participants will be evaluated.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 109414 0
Dr Paul Hamilton
Address 109414 0
Auckland Clinical Studies, ACS House, Ground Floor, 3 Ferncroft Street, Grafton, Auckland 1010
Country 109414 0
New Zealand
Phone 109414 0
+64 800 788 3437 147
Fax 109414 0
Email 109414 0
[email protected]
Contact person for public queries
Name 109415 0
Ms Jessie Kane
Address 109415 0
Auckland Clinical Studies, ACS House, Ground Floor,3 Ferncroft Street, Grafton, Auckland 1010
Country 109415 0
New Zealand
Phone 109415 0
+64 9 373 3474 147
Fax 109415 0
Email 109415 0
[email protected]
Contact person for scientific queries
Name 109416 0
Dr Deepal Wakade
Address 109416 0
Novotech (Australia) Pty Limited
Level 3, 235 Pyrmont Street Sydney, NSW 2009, Australia
Country 109416 0
Australia
Phone 109416 0
+612 9171 3219
Fax 109416 0
Email 109416 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.