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Trial registered on ANZCTR


Registration number
ACTRN12619001239156
Ethics application status
Approved
Date submitted
21/08/2019
Date registered
9/09/2019
Date last updated
2/09/2021
Date data sharing statement initially provided
9/09/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Phase I Study to Evaluate the Safety, Tolerability, Pharmacokinetic Properties of DWN12088 following Oral Administration in Healthy Volunteers
Scientific title
A Randomized, Double-blind, Placebo-controlled, Single- and Multiple-ascending Dose Phase I Study to Evaluate the Safety, Tolerability, Pharmacokinetic Properties of DWN12088 following Oral Administration in Healthy Volunteers
Secondary ID [1] 298579 0
DW_DWN12088101
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Idiopathic Pulmonary Fibrosis (IPF) 313419 0
Condition category
Condition code
Respiratory 311854 311854 0 0
Other respiratory disorders / diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This first in human (FIH) Phase I study and this study will be conducted in two parts.
• Part 1: SAD: 48 subjects (6 cohorts)
• Part 2: MAD: 32 subjects (4 cohorts)

Part 1:
Part 1 will be conducted in healthy subjects. Forty Eight(48) subjects will be enrolled, 8 subjects in each of 6 cohorts, including 2 receiving placebo (as oral solution or enteric-coated capsule or enteric-coated tablets) and 6 receiving DWN12088 (as oral solution or enteric-coated capsule or enteric-coated tablets), after at least 10 hours of fasting, 10 hour fast from solids is required, fasting requirements will be discussed during visits, fasting state will also be maintained during participant inpatient stay and observation. The proposed doses of DWN12088 are between 100 ~ 800 mg. An intermediate dose level may be administered in place of the planned dose levels, if it is deemed appropriate to ensure the safety or increase the scientific value of this Phase I study. Approximate escalation varies and the planned dose levels are – 100mg & 200mg DWN12088/placebo provided as enteric-coated capsules, and 500 mg and 800 mg with DWN12088/placebo provided as enteric-coated tablets. Dose escalation or dose expansion can be done based on safety recommendations from each SRC.
Duration of Treatment: Part 1- SAD cohort will be Day 8 (+2 days).

Part 2
Part 2 will be conducted in healthy subjects, Thirty-two (32) subjects will be enrolled, 8 subjects in each of 4 sequential dose groups, including 2 receiving placebo and 6 receiving DWN12088 (enteric coated tablets) will be administered twice per day from Day 1 to Day 13 and only in the morning on Day 14. Doses within the same day are to be administered 12 hours apart, and if there is any delay in dosing, the next DWN12088/placebo dosing should revert to Day 1 dosing timing.
On Day 1 and Day 14 only, the morning oral dose of DWN12088/placebo will be administered after at least 10 hours of fasting. The proposed doses of DWN12088 are between 25 ~ 300 mg. These doses and/or schedule may be adjusted based on review of the safety data by the SRC. However, the maximum dose will not exceed the maximum dose determined by SRC in Part 1. An intermediate dose level may be administered in place of the planned dose levels, if it is deemed appropriate to ensure the safety or increase the scientific value of this Phase I study. Approximate escalation varies and the planned dose levels are – 25mg, 75mg, 150mg, 300mg. Additional cohort(s) may be planned based on SRC recommendations. Dose escalation or dose expansion can be done based on safety recommendations from SRC.
Duration of Treatment: Part 2- MAD cohort will be 21 (+2 days).
Study populations are distinct and participants can only participant in Part 1 or Part 2. Study drug compliance will be checked by direct observation by study personnel.
Intervention code [1] 314838 0
Treatment: Drugs
Comparator / control treatment
Placebo will be in the form of solution and composed of Ora-Sweet and Baxter Water.
Placebo will be in the form of enteric coated capsule and composed of Lactose Monohydrate
Placebo will be in the form of enteric coated tablets and composed of Microcrystalline Cellulose and Lactose Monohydrate.
Control group
Placebo

Outcomes
Primary outcome [1] 320525 0
To assess the safety and tolerability of DWN12088 following escalating single and multiple doses of DWN12088 in healthy subjects. Outcome is assessed by Physical examination, vital signs, ECGs, BMI and Adverse events. It is a composite outcome.
Timepoint [1] 320525 0
Screening, assessed during inpatient stay (Day -1 to Day 4 in Part 1 and Day -1 to Day 17 in Part 2) and during final follow up visit (Day 8 in Part 1 and Day 21 in Part 2).
Secondary outcome [1] 371937 0
To determine the PK of DWN12088 following escalating single and multiple doses of DWN12088 in healthy subjects. The following PK parameters will be assessed Cmax, Tmax, AUClast, AUCinf, T1/2, CL/F, Vz/F, MRT fe
Timepoint [1] 371937 0
Part 1: Blood sampling at Day 1 pre-dose, then at 0.25, 0.5, 0.75 and 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, and 72 hours from end of dosing on Day 1. Urine sampling at Day 1 pre-dose, then at 0-4, 4-8, 8-12, 12-24, 24-48 and 48-72 hours post Day 1 dose.


Part 2: Blood sampling at Day 1 pre- morning dose and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12 hours post Day 1 morning dose (before the administration of the evening dose. At pre- morning dose on Days 2, 3, 4, 7, 10 and 13. At Day 14 pre-dose, at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, and 72 hours from end of dosing on Day 14. Urine sampling at pre-dose on Day 1 only, then at 0-4, 4-8 and 8-12 hours post Day 1 morning dose (before the administration of the evening dose). and Day 14 dose. 0- 4, 4-8, 8-12, 12-24, 24-48, and 48-72 hours post Day 14 dose. (Note: on day 14, dosing will only occur in the morning).

Eligibility
Key inclusion criteria
Inclusion criteria:

1. Body mass index between 18.0, lesser than or equal to Body Mass Index (BMI) lesser than or equal to 30.0 at screening
2. Subjects who are determined to be in good health based on the results of medical history, physical examinations, 12-lead ECG, vital signs measurement, and clinical laboratory evaluations (congenital diseases are excluded) at screening or Day -1 as assessed by the Investigator (or designee)
3. Willing to sign ICF on a voluntary basis and to voluntarily participate in the study, after being fully informed of and completely understanding this study, prior to any screening procedure being undertaken.
4. Eligible to participate in the study at the discretion of the investigator following medical examination by interview, physical examination and review of laboratory test results.
5. Female subjects must be either post-menopausal or, if pre-menopausal, must have a negative urinary or serum pregnancy test and agree to use 2 forms of contraception (as below) from screening until 90 days after the last dose of IP.
Male subjects must be surgically sterile (vasectomy at least 6 months prior to screening), or if sexually active and having a pre-menopausal female partner, must agree to use 2 forms of contraception (as below) from the date of dosing and for 90 days after the last dose of the IP. They must also refrain from donating sperm from the date of first dosing until 90 days after the last dose of the IP.
Minimum age
18 Years
Maximum age
64 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Exclusion criteria
1. Significant history or clinical manifestation of any metabolic, allergic, dermatological, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, neurological, respiratory, endocrine, or psychiatric disorder, as determined by the Investigator (or designee).
2. Fasting blood glucose greater than 110 mg/dL (greater than 6.1 mmol/L) (confirmed with repeat testing).
3. History of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance, unless approved by the Investigator (or designee).
4. History of stomach or intestinal surgery or resection, including cholecystectomy, that would potentially alter absorption and/or excretion of orally administered drugs (uncomplicated appendectomy and hernia repair will be allowed).
5. The subject has a substance abuse-related disorder or has a history of drug and/or alcohol and/or substance abuse deemed significant by the Investigator (or designee).
6. Positive urine drug screen (including nicotine) at Screening and Day -1. If result obtained during screening is positive, it can be repeated at Day -1.
7. Use of nicotine-containing products within 90 days prior to screening.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled 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
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Safety
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
10/09/2019
Actual
10/09/2019
Date of last participant enrolment
Anticipated
15/09/2020
Actual
27/10/2020
Date of last data collection
Anticipated
5/10/2020
Actual
16/11/2020
Sample size
Target
80
Accrual to date
Final
72
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 14749 0
CMAX Clinical Research Pty Ltd - Adelaide
Recruitment postcode(s) [1] 27791 0
5000 - Adelaide

Funding & Sponsors
Funding source category [1] 303119 0
Commercial sector/Industry
Name [1] 303119 0
Daewoong Pharmaceutical Co., Ltd.
Country [1] 303119 0
Korea, Republic Of
Primary sponsor type
Commercial sector/Industry
Name
Daewoong Pharmaceutical Co., Ltd.
Address
12, Bongeunsa-ro 114 gil, Gangnam-gu,
Seoul, 06170, Korea
Country
Korea, Republic Of
Secondary sponsor category [1] 303115 0
None
Name [1] 303115 0
Address [1] 303115 0
Country [1] 303115 0
Other collaborator category [1] 280818 0
Commercial sector/Industry
Name [1] 280818 0
Novotech (Australia) Pty Limited
Address [1] 280818 0
Level 3, 235 Pyrmont Street, Pyrmont NSW 2009
Country [1] 280818 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 303670 0
Bellberry HREC
Ethics committee address [1] 303670 0
Ethics committee country [1] 303670 0
Australia
Date submitted for ethics approval [1] 303670 0
03/07/2019
Approval date [1] 303670 0
13/08/2019
Ethics approval number [1] 303670 0

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

Contacts
Principal investigator
Name 94442 0
Dr Nicholas Farinola
Address 94442 0
CMAX clinical research, Level 5/18a North Terrace, Adelaide SA 5000
Country 94442 0
Australia
Phone 94442 0
+61 870740000
Fax 94442 0
Email 94442 0
Nicholas.Farinola@sa.gov.au
Contact person for public queries
Name 94443 0
Sofia Cendrawan
Address 94443 0
Novotech (Australia) Pty Limited
Level 3, 235 Pyrmont Street, Pyrmont NSW 2009
Country 94443 0
Australia
Phone 94443 0
+61 3 9341 1904
Fax 94443 0
Email 94443 0
sofia.cendrawan@novotech-cro.com
Contact person for scientific queries
Name 94444 0
Sofia Cendrawan
Address 94444 0
Novotech (Australia) Pty Limited
Level 3, 235 Pyrmont Street, Pyrmont NSW 2009
Country 94444 0
Australia
Phone 94444 0
+61 3 9341 1904
Fax 94444 0
Email 94444 0
sofia.cendrawan@novotech-cro.com

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
SourceTitleYear of PublicationDOI
EmbaseSafety, tolerability, pharmacokinetic/pharmacodynamic characteristics of bersiporocin, a novel prolyl-tRNA synthetase inhibitor, in healthy subjects.2023https://dx.doi.org/10.1111/cts.13518
N.B. These documents automatically identified may not have been verified by the study sponsor.