Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12622000307707
Ethics application status
Approved
Date submitted
29/10/2021
Date registered
18/02/2022
Date last updated
22/11/2022
Date data sharing statement initially provided
18/02/2022
Type of registration
Retrospectively registered

Titles & IDs
Public title
A study comparing extended release and immediate release formulations of EQ121 following single doses in healthy adult volunteers- Part A
Scientific title
A study comparing the safety, tolerability, and pharmacokinetics of extended release and immediate release formulations of EQ121 following single doses in healthy adult volunteers- Part A
Secondary ID [1] 305093 0
EQ121-010
Universal Trial Number (UTN)
Trial acronym
Linked study record
Part B: ACTRN12622000292774
Part C: ACTRN12622000293763

Health condition
Health condition(s) or problem(s) studied:
Rheumatoid Arthritis 323310 0
Condition category
Condition code
Inflammatory and Immune System 320877 320877 0 0
Rheumatoid arthritis

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
EQ121 immediate release (IR) capsule is an oral solid dosage form manufactured at strengths of 1 mg and 12 mg.
Each EQ121 capsule contains EQ121 drug substance; mannitol, pregelatinized starch and microcrystalline cellulose as diluents; croscarmellose sodium as disintegrant; colloidal silicon dioxide as glidant; and magnesium stearate as lubricant

Part A: It is a single-sequence, two-period crossover, multi-cohort study to evaluate the EQ121 immediate release (IR) capsule formulation and up to 10 different EQ121 extended release (ER) tablet formulations under fasted conditions in adult healthy volunteers
Cohort 1: In period 1 of cohort 1, the participants will receive a single oral dose of 36 mg EQ121 immediate release (IR) capsule on the morning of Day 1 under fasting conditions.
Cohort 2: In period 1 of cohort 2, the participants will receive a single oral dose of 36 mg EQ121 immediate release (IR) capsule on the morning of Day 1 under fasting conditions.
Cohort 3: In period 1 of cohort 3, the participants will receive a single oral dose of 36 mg EQ121 immediate release (IR) capsule on the morning of Day 1 under fasting conditions.
Cohort 4: In period 1 of cohort 4, the participants will receive a single oral dose of 36 mg EQ121 immediate release (IR) capsule on the morning of Day 1 under fasting conditions.
Cohort 5: In period 1 of cohort 5, the participants will receive a single oral dose of 36 mg EQ121 immediate release (IR) capsule on the morning of Day 1 under fasting conditions.

If necessary, up to 5 additional cohorts (Cohorts 6 through 10), consisting of 4 participants per cohort, may be enrolled (for a total of up to 10 cohorts), either in parallel or sequentially, to evaluate additional EQ121 ER tablet formulations or dose levels. The dose for subsequent cohorts (6 through 10) will remain a single oral dose of 36 mg EQ121 immediate release (IR) capsule on the morning of Day 1 under fasting conditions.

Each cohort will enrol distinct group of participants
Adherence will be monitored via clinical site staff recording and reporting all number of pills taken while confined
Intervention code [1] 321524 0
Treatment: Drugs
Comparator / control treatment
EQ121 extended release (ER) tablet formulation is active group
Period 2 of cohort 1: Following a 1-day washout period, the same 4 participants will receive a single oral dose of 40 mg EQ121 extended release (ER) tablet Formulation 1 on the morning of Day 3 under fasting conditions.

Period 2 of cohort 2: Following a 1-day washout period, the same 4 participants will receive a single oral dose of 40 mg EQ121 extended release (ER) tablet Formulation 2 on the morning of Day 3 under fasting conditions.

Period 2 of cohort 3: Following a 1-day washout period, the same 4 participants will receive a single oral dose of 40 mg EQ121 extended release (ER) tablet Formulation 3 on the morning of Day 3 under fasting conditions.

Period 2 of cohort 4: Following a 1-day washout period, the same 4 participants will receive a single oral dose of 40 mg EQ121 extended release (ER) tablet Formulation 4 on the morning of Day 3 under fasting conditions.

Period 2 of cohort 5: Following a 1-day washout period, the same 4 participants will receive a single oral dose of 40 mg EQ121 extended release (ER) tablet Formulation 5 on the morning of Day 3 under fasting conditions.

If necessary, up to 5 additional cohorts (Cohorts 6 through 10), consisting of 4 participants per cohort, may be enrolled (for a total of up to 10 cohorts), either in parallel or sequentially, to evaluate additional EQ121 ER tablet formulations or dose levels. The dose for subsequent cohorts (6 through 10) may be increased, decreased, or repeated based on emerging pharmacokinetic data. However, the highest dose will not exceed 80 mg.

Each EQ121 tablet contains EQ121 drug substance; lactose monohydrate as diluent; fumaric acid and tartaric acid as acidulant; hydroxypropyl methylcellulose (HPMC) as matrix; colloidal silicon dioxide as glidant; and magnesium stearate as lubricant. Each formulation will be made up of 15% W/W EQ121 drug substance and differing amounts of the excipients listed above.

Each cohort will enroll distinct group of participants

Adherence will be monitored via clinical site staff recording and reporting all number of pills taken while confined
Control group
Active

Outcomes
Primary outcome [1] 329693 0
To compare the oral bioavailability of initial EQ121 ER tablet formulations to the EQ121 IR capsule formulation in adult healthy volunteers
Pharmacokinetic exposure parameters (Cmax and AUC) will be compared between the ER and IR formulations
Cmax – maximum observed plasma concentration over the entire sampling during obtained directly from the observed plasma concentration-time data without interpolation
• AUC0-t – area under the concentration-time curve from time 0 to time of last quantifiable concentration (t) calculated using linear trapezoidal rule
• AUC0-inf – area under the concentration -time curve from time 0 to infinity
• AUCextra – area under the concentration -time curve from last quantifiable concentration extrapolated to infinity
Timepoint [1] 329693 0
Blood samples collected at pre-dose and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 20, 24, 30, 36, 48, 72 (Part A only) hours post dose and Day 1, 2, 3, 4, 5, 6, 7 and 8
Secondary outcome [1] 400116 0
To evaluate the pharmacokinetic of EQ121 ER tablet formulation following oral single-dose administration in adult healthy volunteers.
The following parameter will be used for evaluation of pharmacokinetic
• AUC0-t – area under the concentration-time curve from time 0 to time of last quantifiable concentration (t) calculated using linear trapezoidal rule
• AUC0-inf – area under the concentration -time curve from time 0 to infinity
• AUCextra – area under the concentration -time curve from last quantifiable concentration extrapolated to infinity
• Cmax – maximum observed plasma concentration over the entire sampling during obtained directly from the observed plasma concentration-time data without interpolation
• Tmax – time to reach maximum observed plasma concentration during obtained directly from the observed plasma concentration-time data without interpolation
• Kel – elimination rate constant
• t½ – terminal half-life
• CL/F – apparent clearance
• Vz/F – apparent clearance
Timepoint [1] 400116 0
EQ121 ER Tablet
Blood samples collected at pre-dose and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 20, 24, 30, 36, 48, 72 (Part A , ER only) hours post dose and Day 1, 2, 3, 4, 5, 6
Secondary outcome [2] 400118 0
Part A: To evaluate the safety, and tolerability of EQ121 ER tablet formulation following oral single-dose administration in adult healthy volunteers through Adverse events (Severity should be recorded and graded according to the Guidance for Industry Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials)
Timepoint [2] 400118 0
Part A: Daily from Baseline to Day 8 post dose
Secondary outcome [3] 403340 0
Part A: To evaluate the pharmacokinetic of EQ121 IR capsule formulation following oral single-dose administration in adult healthy volunteers.
The following parameter will be used for evaluation of pharmacokinetic
• AUC0-t – area under the concentration-time curve from time 0 to time of last quantifiable concentration (t) calculated using linear trapezoidal rule
• AUC0-inf – area under the concentration -time curve from time 0 to infinity
• AUCextra – area under the concentration -time curve from last quantifiable concentration extrapolated to infinity
• Cmax – maximum observed plasma concentration over the entire sampling during obtained directly from the observed plasma concentration-time data without interpolation
• Tmax – time to reach maximum observed plasma concentration during obtained directly from the observed plasma concentration-time data without interpolation
• Kel – elimination rate constant
• t½ – terminal half-life
• CL/F – apparent clearance
• Vz/F – apparent clearance
Timepoint [3] 403340 0
EQ121 IR capsule
Blood samples collected at pre-dose and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 hours post dose and Day 1, 2, 3, 4, 5, 6

Eligibility
Key inclusion criteria
1. Are capable of giving informed consent and complying with study procedures;
2. Healthy male or female participants, between the ages of 18 and 65 years, inclusive;
3. BMI of 18.0 to 32.0 kg/m2 inclusive and body weight not less than 50 kg;
4. Female participants must not be currently breast-feeding, and must 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 mIU/mL
c. Women of childbearing potential (WOCBP):
• Must not have a positive serum pregnancy test at Screening and must have a negative urine pregnancy test on admission
• 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 the last dose of study drug:
• Partner vasectomy (at least 6 months prior to Screening; vasectomized partner should be the sole partner of the female participant)
• 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, WOCBP 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 the last dose of study drug. It is not necessary to use any other method of contraception when complete abstinence is elected. 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 PI or designee in relation to the duration of the clinical trial and the preferred and usual lifestyle of the participant.
5. Male participants must agree to utilize a highly effective method of contraception (condom) during heterosexual intercourse from clinic admission until 90 days following the last dose of study drug and must refrain from donating sperm for this same period. Vasectomized males do not need to use additional forms of contraception providing that the procedure was performed at least 12 weeks prior to Screening and an absence of sperm in the ejaculate has been documented. Total sexual abstinence may be considered acceptable at the discretion of the PI or designee;
6. Considered healthy by the PI or designee, based on participant’s reported medical history, full physical examination, clinical laboratory tests, 12-lead ECG, and vital signs;
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. Inability to attend all the study visits or comply with study procedures;
2. Evidence or clinically significant history of gastrointestinal, cardiovascular, musculoskeletal, endocrine, hematologic, psychiatric, renal, hepatic, bronchopulmonary, neurologic, immunologic, lipid metabolism disorders, or drug hypersensitivity as determined by the PI or designee;
3. Hospital admission or major surgery within 3 months prior to Screening;
4. A history of drug abuse, or a positive test at Screening or Admission for drugs of abuse;
5. A history of alcohol abuse according to medical history within 6 months prior to Screening (drinking 14 units of alcohol per week: 1 unit equal to 360 mL of beer, or 37 mL of spirits, or 120 mL of wine) at Screening or upon admission to the clinical site;
6. Positive screen for drugs of abuse or alcohol at Screening or at Admission;
7. A history of organ transplant, including history of bone marrow transplant;
8. Taken any prescription medications within 14 days or 5 half-lives (whichever is longer), or any injectable prescription medications within 30 days or 10 half-lives (whichever is longer), of the first dose of study drug
9. Taken an investigational drug within 3 months or 5 half-live, whichever is longer, from the Screening date
10. Any liver LFT value greater than 1.5 of ULN which includes aspartate aminotransferase (AST), alanine aminotransferase (ALT), bilirubin, alkaline phosphatase, and gamma-glutamyl transferase (GGT) at Screening or at Admission
11. Any white blood cell (WBC), absolute neutrophil count (ANC), hemoglobin, or platelet count less than the lower limit of normal at Screening or at Admission that is clinically significant in the opinion of the PI or designee
12. Serum creatinine more than upper limit of normal (ULN) at Screening or Admission
13. Any condition or finding that in the opinion of the PI or designee would put the participant or study conduct at risk if the participant were to participate in the study

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
Crossover
Other design features
Phase
Phase 1
Type of endpoint/s
Safety
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
6/12/2021
Date of last participant enrolment
Anticipated
23/06/2022
Actual
7/09/2022
Date of last data collection
Anticipated
1/07/2022
Actual
14/09/2022
Sample size
Target
40
Accrual to date
Final
32
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 20452 0
Q-Pharm Pty - Clive Berghofer Research Centre (CBCRC) - Herston
Recruitment postcode(s) [1] 35221 0
4007 - Herston

Funding & Sponsors
Funding source category [1] 309491 0
Commercial sector/Industry
Name [1] 309491 0
EQRx International, Inc.
Country [1] 309491 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
EQRx International, Inc.
Address
50 Hampshire Street, Cambridge, MA 02139, USA
Country
United States of America
Secondary sponsor category [1] 310462 0
None
Name [1] 310462 0
Address [1] 310462 0
Country [1] 310462 0
Other collaborator category [1] 281958 0
Commercial sector/Industry
Name [1] 281958 0
Novotech (Australia) Pty Limited
Address [1] 281958 0
Novotech (Australia) Pty Limited
Level 3, 235 Pyrmont Street Sydney, NSW Australia - 2009
Country [1] 281958 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 309276 0
Alfred Ethics Committee
Ethics committee address [1] 309276 0
Ethics committee country [1] 309276 0
Australia
Date submitted for ethics approval [1] 309276 0
28/10/2021
Approval date [1] 309276 0
09/11/2021
Ethics approval number [1] 309276 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 113594 0
Dr Richard Friend
Address 113594 0
Nucleus Network - Brisbane,
Level 5 Clive Berghofer Cancer Centre Research Centre, 300 Herston Rd, Herston, QLD, 4006, Australia
Country 113594 0
Australia
Phone 113594 0
+61 07 3845 3620
Fax 113594 0
Email 113594 0
[email protected]
Contact person for public queries
Name 113595 0
Katherine (Kitty) Gunn
Address 113595 0
Nucleus Network Pty Ltd
Level 5, 300 Herston Road, Herston, QLD 4006
Country 113595 0
Australia
Phone 113595 0
+61 420 611 503
Fax 113595 0
Email 113595 0
[email protected]
Contact person for scientific queries
Name 113596 0
Ramandeep Sharma
Address 113596 0
Novotech (Australia) Pty Limited
Level 3, 235 Pyrmont Street Sydney, NSW, Australia - 2009
Country 113596 0
Australia
Phone 113596 0
+61 3 9341 1992
Fax 113596 0
Email 113596 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.