Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12620001253998
Ethics application status
Approved
Date submitted
27/07/2020
Date registered
23/11/2020
Date last updated
16/02/2022
Date data sharing statement initially provided
23/11/2020
Type of registration
Retrospectively registered

Titles & IDs
Public title
Phase 1 study to evaluate the safety, tolerability, and pharmacokinetics/pharmacodynamics properties of iN1011N17
Scientific title
A randomized, double-blind, placebo-controlled, single-ascending dose Phase 1 study to evaluate the safety, tolerability, and pharmacokinetics/pharmacodynamics properties of iN1011N17 after oral administration in healthy volunteers
Secondary ID [1] 301874 0
DW_DWP17061101
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
osteoarthritis pain 318370 0
Condition category
Condition code
Musculoskeletal 316389 316389 0 0
Osteoarthritis
Anaesthesiology 316914 316914 0 0
Pain management

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This study will be conducted in approximately 80 healthy subjects in up to 10 sequential dose cohorts. Ten cohorts will consist of up to 8 subjects, including 2 subjects receiving placebo and 6 subjects receiving iN1011 N17, after at least 10 hours of fasting. iN1011 N17 will be administered as a capsule with active pharmaceutical ingredient (API), or as a suspension, with matching placebo.
For API-in Capsules:
Single Ascending Dose (SAD) 1: 10 mg of iN1011-N17 single dose will be orally administered in the morning with about 240mL of water following 10 hours of fasting
Single Ascending Dose (SAD) 2: 100 mg of iN1011-N17 single dose will be orally administered in the morning with about 240mL of water following 10 hours of fasting
Single Ascending Dose (SAD) 3: 200 mg of iN1011-N17 single dose will be orally administered in the morning with about 240mL of water following 10 hours of fasting
Each cohort consist of distinct group of participants
For the preformulation:
iN1011-N17 is provided as a 100 mL suspension containing 100, 200, 400, 600, 800, or 1200 mg/100 mL for oral administration
Single Ascending Dose (SAD) 3b: 100 mg of iN1011-N17 single dose will be orally administered in the morning on Day 1 with about 240mL of water following 10 hours of fasting
Single Ascending Dose (SAD) 4: 200 mg of iN1011-N17 single dose will be orally administered in the morning on Day 1 with about 240mL of water following 10 hours of fasting
Single Ascending Dose (SAD) 5: 400 mg of iN1011-N17 single dose will be orally administered in the morning on Day 1 with about 240mL of water following 10 hours of fasting
Single Ascending Dose (SAD) 6: 600 mg of iN1011-N17 single dose will be orally administered in the morning on Day 1 with about 240mL of water following 10 hours of fasting
Each cohort consist of distinct group of participants
Separate cohorts will receive only one capsule dose or one oral suspension dose.
The container of IP shall be rinsed with about 50 mL of water, which will be also consumed. An additional 90 mL of water will be consumed following IP administration. No food may be consumed for 4 hours following IP administration., however a lozenge or piece of candy may be taken to eradicate the bitter taste. No additional water may be consumed one hour before or for one hour following IP administration.
The Safety Review Committee (SRC) will conduct a review of safety data from each cohort prior to commencement of the proceeding cohort.
Strategy used to assess or monitor adherence to the intervention- Subjects will be inpatients at Phase I unit. Mouth check and IP accountability.
The expected overall duration of the study is approximately 16 months after first subject enrolment.
Intervention code [1] 318163 0
Treatment: Drugs
Comparator / control treatment
Matching placebo- hard gelatin capsules

Only hard-gelatin capsules for placebo and active are manufactured.
Control group
Placebo

Outcomes
Primary outcome [1] 324541 0
To asses the safety and tolerability of single dose of iN1011-N17 in healthy participants. Outcome is assessed through adverse events, Physical examination, vital signs, ECGs and laboratory testing. It is a composite outcome. samples used for laboratory tests: blood and urine, telemetry and bedside neurological assessments
Timepoint [1] 324541 0
Monitored daily through Screening Visit till throughout the study. Vital signs: Measurement time points: at Screening*, Day 1*; pre-dose (within 30 minutes) and 2, 4 (±15 mins) minutes) and 8 hours (±30 minutes) post-dose on Day 1; Day 2, Day 3* prior to PK sampling; and Day 8*; and at Early Termination (if applicable). BP and pulse should be assessed in both a supine and standing position on Day 1 at pre-dose and 2 hours post-dose, on Day 2 and at Early Termination (if applicable). ECG: Single ECG recording will be performed at Day -1; immediately pre-dose (within 60 minutes) and 1 hour (±15 minutes), 4 and 8 hours (±30 minutes) post-dose on Day 1; on Day 3 prior to PK sampling and Day 8 and at Early Termination (if required). Bedside Neurological Assessments: Measurement time points: pre-dose (within 30 minutes) and 2 hours (±15 minutes) post-dose on Day 1; on Day 2; and at Early Termination (if applicable). Continuous cardiac monitoring (Telemetry) should run for a minimum of 6 hours from the time of dosing on Day 1. Clinical laboratory evaluations (including hematology, urinalysis and biochemistry): at Screening, on Day -1, on Day 3 prior to discharge, at outpatient follow-up visit (Day 8) and at Early Termination (if applicable). Where timepoints coincide with the collection of ECG recordings, the ECG recordings will be collected prior to the lab (blood and urine) samples.
Secondary outcome [1] 384937 0
To characterize pharmacokinetics of single dose of iN1011 N17 in healthy participants. Parameters: maximum plasma concentration, Time to maximum plasma concentration, area under the plasma concentration curve, Apparent volume of distribution, Terminal half-life, Apparent plasma elimination rate constant, Apparent clearance, Fraction excreted unchanged in urine, Renal clearance.
It is a composite outcome.
Timepoint [1] 384937 0
Pharmacokinetic samples (blood and urine) for iN1011 N17 will be collected at the following time points:
Plasma sampling time points (18 points): Day 1 pre-dose (within 30 minutes prior to dosing) and, 0.17 (10 minutes), 0.33 (20 minutes), 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12 hours (± 2 minutes from 0.17 h through to 0.5 h, then ± 10 minutes from 0.75 h through to 6h, then ± 15 minutes from 8 h through to 12 h post-dose), 24 (± 15 minutes), 36 hours (± 15 minutes), and 48 (± 15 minutes), following iN1011 N17/placebo dosing.
Urine collection intervals (5 intervals): Urine samples are collected at pre-dose (within 60 minutes prior to dosing) and over five intervals (0 to 4, 4 to 8, 8 to 12, 12 to 24, and 24 to 48 h post-dose).
Secondary outcome [2] 387904 0
To determine the pharmacodynamics (PD) of iN1011N17 following escalating single dose of iN1011N17 in healthy subjects. Parameters : Thermal detection thresholds for the perception of cold (cold detection threshold [CDT]) and heat (heat detection threshold [HDT]) • Thermal pain thresholds for cold (cold pain threshold [CPT]) and heat (heat pain threshold [HPT]) stimuli • Mechanical detection threshold [MDT] and mechanical pain threshold [MPT] • Vibration detection threshold [VDT]
Timepoint [2] 387904 0
Pharmacodynamic (PD) assessments will be performed in Cohort 2 onwards. No PD assessments will be performed during Cohort 1 (10 mg iN1011 N17/placebo).
PD will be measured within 24 hours prior to IP administration (on Day -1 or Day 1), and at approximately 3 and 6 hours (± 60 minutes) after dosing on Day 1.
Parameters: Cold detection threshold (CDT), Heat detection threshold (HDT), Cold pain threshold (CPT), Heat pain threshold (HPT), Mechanical detection threshold (MDT), Mechanical pain threshold (MPT) and Vibration detection threshold (VDT).
Secondary outcome [3] 387905 0
To elucidate the metabolic characteristics and biomarkers (Olink Proteomics) of iN1011N17 by assessing plasma concentration of metabolites and biomarkers of iN1011N17.
Biomarker yet to be confirmed.
Timepoint [3] 387905 0
From Cohort 2 onwards, additional blood samples will be collected for metabolite identification and biomarker analysis of iN1011 N17 at 1, 1.5, and 2 hours post-dose on Day 1.
Secondary outcome [4] 387906 0
CYP2D6 genotyping to explore the influence of genetic variability on the metabolism
characteristics of iN1011-N17. To evaluate the influence of genetic variability by genotyping.
Timepoint [4] 387906 0
Whole blood samples for CYP2D6 genotyping will be collected on Day 1 pre-dose for all participants.

Eligibility
Key inclusion criteria
1. Healthy male and female adults, aged 18 to 55 years (inclusive at the time of written informed consent).
2. Body mass index (BMI equals body weight (kg)/[height (m)]2) between 18 kg/m2 and 32 kg/m2 (inclusive) at the time of Screening, and a minimum weight of 50 kg.
3. Clinical laboratory values within normal range as specified by the testing laboratory at Screening and Day -1, unless deemed not clinically significant by the Investigator.
4. Clinically acceptable blood pressure (BP), pulse, respiratory rate (RR), and body temperature (systolic blood pressure [SBP] between 90 and 140 mmHg; diastolic blood pressure [DBP] between 40 and 90 mmHg; pulse between 40 and100 bpm; RR between 10 and 22 breaths/min; body temperature between 35.5°C and 37.5°C) at Screening and Day -1. Measurements are to be recorded after a minimum of 5 minutes of resting in sitting or supine position.
5. Subjects (excluding who are exclusively in same-sex relationships) must agree to use a highly effective method of contraception throughout the study and for at least 30 days for females or 90 days for males after the last dose of investigational product (IP). Female subjects must not be breastfeeding, lactating or planning pregnancy during the study period.
6. Cognitively capable of understanding the provided information and able to fully comply with protocol requirements.
7. Written informed consent prior to the commencement of any study procedures.
8. Willing and able to perform the necessary visits to the investigational site/institution.
9. In good general health at the Investigator’s discretion, with no significant medical history, and with no clinically significant abnormalities on physical examination at Screening and before the first dose of IP.
Minimum age
18 Years
Maximum age
55 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. Presence or history of hepatic, renal, neurological, pulmonary, endocrine, hematologic, cardiovascular or genitourinary disease.
2. Presence of any underlying physical or psychiatric condition that, in the opinion of the Investigator, would undermine subject compliance to protocol requirements.
3. Presence or history of gastrointestinal disease (e.g., peptic ulcer, gastritis, gastric cramp, gastroesophageal reflex disease, Crohn’s disease) or history of gastrointestinal surgery (except simple appendectomy or herniorrhaphy) that may affect assessment of safety and pharmacokinetic characteristics of the IP.
4. History of hypersensitivity to iN1011N17 or to any of its components.
5. Any abnormal 12-lead electrocardiogram (ECG) findings at Screening and Day -1, deemed by the Investigator or designee to be clinically significant.
6. Positive test for hepatitis B surface antigen (HBsAg), hepatitis C (HCV), or human immunodeficiency virus (HIV) at Screening.
7. Positive urine drug screen test (including: amphetamines, methamphetamines, methadone, barbiturates, benzodiazepines, cocaine, opiates, methylenedioxymethamphetamine, phencyclidine and tetrahydrocannabinol) or alcohol breath test at Screening and Day -1.
8. Any history (i.e., within 5 years) of substance abuse or treatment (including alcohol) or is unwilling to agree to abstain from alcohol and drugs from 48 hours prior to Screening and for the duration of the study.
9. History of fracture or other significant injury to dominant arm or current injury or condition, such as carpel tunnel syndrome, that may prevent accurate sensory testing.
10. Use of any prescription drugs within 14 days and for over the counter (OTC) medications, herbal remedies (including St John’s Wort), dietary supplements or vitamins within 7 days, or five half-lives of the product, whichever is longer, before the first dose of IP and for the duration of the study without prior approval of the Investigator and the Medical Monitor (MM). This includes analgesics such as paracetamol and non-steroidal anti-inflammatories.
11. The use of any IP or investigational medical device within 30 days prior to Screening, or five half-lives of the product, whichever is longer.
12. Blood or plasma donation of more than 450 mL within 90 days before the first dose of IP and for the duration of the study. It is recommended that blood/plasma donations not be made for at least 30 days after study completion.
13. An average weekly alcohol intake that exceeds 21 units per week for males and 14 units per week for females (1 unit equal to 10 g of pure alcohol).
14. Use of more than five nicotine-based products (including smoking tobacco, smokeless tobacco, and nicotine patches) per week, within 90 days prior to Screening. Subjects must have a negative urine cotinine test at both Screening and Day -1 and refrain from the use of any nicotine-based products for the duration of the study.
15. Consumption of beverages or foods that contain alcohol, grapefruit, star fruit, pomelos, or products containing these fruits, from 7 days, and products containing caffeine (e.g., coffee, green tea, black tea and sodas) from 72 hours before the first dose of IP until study completion.
16. Unwilling to refrain from strenuous exercise from 48 hours prior to admission to the investigational site/institution and for the duration of the study, where strenuous exercise is defined as that which requires significant effort, energy, or strength, such as lifting weights or running.
17. Any other reason that, in the opinion of the Investigator, may affect assessment of safety, PK or PD characteristics of the IP.

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
The people assessing the outcomes
Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Safety
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
30/09/2020
Actual
16/11/2020
Date of last participant enrolment
Anticipated
11/05/2022
Actual
Date of last data collection
Anticipated
22/06/2022
Actual
Sample size
Target
80
Accrual to date
60
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 17147 0
Nucleus Network - Melbourne
Recruitment postcode(s) [1] 30826 0
3004 - Melbourne

Funding & Sponsors
Funding source category [1] 306296 0
Commercial sector/Industry
Name [1] 306296 0
iN Therapeutics Co., Ltd.
Country [1] 306296 0
Korea, Republic Of
Primary sponsor type
Commercial sector/Industry
Name
iN Therapeutics Co., Ltd.
Address
72, Dugyero, Pogokeup, Yonginsi, Gyenggido, Republic of Korea- 17028
Country
Korea, Republic Of
Secondary sponsor category [1] 306789 0
None
Name [1] 306789 0
Address [1] 306789 0
Country [1] 306789 0
Other collaborator category [1] 281411 0
Commercial sector/Industry
Name [1] 281411 0
Novotech (Australia) Pty Limited
Address [1] 281411 0
Level 2, 235 Pyrmont Street, Pyrmont NSW 2009, Australia
Country [1] 281411 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 306513 0
Alfred Hospital Ethics Committee
Ethics committee address [1] 306513 0
55 Commercial Rd, Melbourne VIC 3004, Australia
Ethics committee country [1] 306513 0
Australia
Date submitted for ethics approval [1] 306513 0
02/09/2020
Approval date [1] 306513 0
29/09/2020
Ethics approval number [1] 306513 0

Summary
Brief summary
This study is a prospective, randomized, double-blind, placebo-controlled, Phase 1 clinical study to evaluate the safety, tolerability, PK and PD of single oral ascending doses of iN1011 N17 in healthy subjects.
This study will be conducted in approximately 80 healthy subjects in up to 10 sequential dose cohorts. Ten cohorts will consist of up to 8 subjects including 2 subjects receiving placebo and 6 subjects receiving iN1011 N17, after at least 10 hours of fasting. iN1011 N17 will be administered as a capsule or in a suspension formulation, with matching placebo.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 52202 0
Dr Dr. Jason Lickliter
Address 52202 0
Nucleus Network Pty Ltd
Address: Level 5, Burnet Tower, AMREP Precinct, 89 Commercial Road Melbourne, 3004, Victoria, Australia
Country 52202 0
Australia
Phone 52202 0
+61 3 9076 8960
Fax 52202 0
Email 52202 0
J.Lickliter@nucleusnetwork.com.au
Contact person for public queries
Name 52203 0
Ms Lysandra Tassone
Address 52203 0
Novotech (Australia) Pty Ltd
Address: Level 2, 15-31 Pelham Street Carlton VIC 3053 Australia
Country 52203 0
Australia
Phone 52203 0
+61 3 9341 1976
Fax 52203 0
Email 52203 0
Lysandra.Tassone@novotech-cro.com
Contact person for scientific queries
Name 52204 0
Ms Yeseul Shin
Address 52204 0
Bongeunsaro 114-gil 12, Gangnam-gu, Seoul 06170, Republic of Korea
Country 52204 0
Korea, Republic Of
Phone 52204 0
+82 2 550 8280
Fax 52204 0
Email 52204 0
ysshin121@daewoong.co.kr

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.