Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12622001300763
Ethics application status
Approved
Date submitted
24/06/2022
Date registered
7/10/2022
Date last updated
21/02/2024
Date data sharing statement initially provided
7/10/2022
Type of registration
Retrospectively registered

Titles & IDs
Public title
A Study to Evaluate the Safety, Tolerability, and Pharmacokinetic/Pharmacodynamic Properties of iN1011-N17 after Oral Administration in Healthy Volunteers and Post-Herpetic Neuralgia (PHN) Patients
Scientific title
A Randomized, Double-blind, Placebo-controlled, Multiple-Ascending Dose Phase 1b Study to Evaluate the Safety, Tolerability, and Pharmacokinetic/Pharmacodynamic Properties of iN1011-N17 after Oral Administration in Healthy Volunteers and Post-Herpetic Neuralgia Patients and to Assess the Relative Bioavailability of Mesylate vs Hydrochloride Salt Capsules in Healthy Volunteers
Secondary ID [1] 307253 0
iN1011-N17102
Universal Trial Number (UTN)
Trial acronym
Linked study record
This is MAD part of the study of already approved ACTRN12620001253998

Health condition
Health condition(s) or problem(s) studied:
Post Hepatic Neuralgia 326506 0
Condition category
Condition code
Inflammatory and Immune System 323770 323770 0 0
Other inflammatory or immune system disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The study will be conducted in 3 parts.
Part1 MAD will consist of approximately 32 healthy subjects enrolled in up to 4 sequential Multiple Ascending Dose (MAD) dose cohorts and each cohort can commence after the corresponding dose Single Ascending Dose (SAD) cohort has been completed and after Safety Review Committee approval.
Each participant in all the 4 cohorts will receive oral doses of iN1011-N17 with matching placebo.
Dosage Form: Capsules
Mode of Administration: Oral
Cohort 1: Healthy participants will receive oral dose of 100 mg iN1011-N17 twice daily (b.i.d) from Day 1 to Day 6, approximately 12 hours apart between the 2 daily doses and receive the morning last dose on Day 7
Cohort 2: Healthy participants will receive oral dose of 200 mg iN1011-N17 twice daily (b.i.d) from Day 1 to Day 6, approximately 12 hours apart between the 2 daily doses and receive the morning last dose on Day 7
Cohort 3: Healthy participants will receive oral dose of 400 mg iN1011-N17 twice daily (b.i.d) from Day 1 to Day 6, approximately 12 hours apart between the 2 daily doses and receive the morning last dose on Day 7
Cohort 4: Healthy participants will receive oral dose of 800 mg iN1011-N17 twice daily (b.i.d) from Day 1 to Day 6, approximately 12 hours apart between the 2 daily doses and receive the morning last dose on Day 7
Each cohort will enrol distinct group of participants
Participants will be confined to the investigational site/institution and supervised for approximately 10 days (Day -1 to Day 9) and will be discharged from the investigational site/institution on Day 9, following satisfactory completion of all procedures and assessments.
iN1011-N17 will be administered as an oral suspension (Cohort 1) and Nano Suspension powder capsule (Cohorts 2-5)
Part 2: Approximately 16 participants will be enrolled into the study. It will be a open label study, cross over bioavailability study which will commence after completion of Part 1 with 2 cohorts. Here the participants in cohort 5 and 6 will receive both Regimen A (single dose of 400 mg iN1011-N17 hydrochloride salt capsule) and Regimen B (single dose of 400 mg iN1011-N17 mesylate salt capsule). Participants will receive a single oral dose of each study treatment (Regimens A and B), one during each of the 2 inpatient periods, in a randomized sequence of administration: AB (Cohort 5) or BA (Cohort 6).
Part 3: MAD Study in Healthy Volunteers and Post-Herpetic Neuralgia Patients with iN1011-N17 Mesylate Salt (14 Days). This will enroll 8 healthy volunteers and 8 PHN patients who will be randomised in a ratio of 3:1 to receive iN1011-N17 or placebo. MAD Cohort 7 will commence after SRC review and assessment of the safety data from Part 2 of the study.
Cohort 7- Healthy volunteers will receive oral dose of 400mg of iN1011-N17 mesylate salt capsule or placebo twice daily (b.i.d) from Day 1 to Day 13, approximately 12 hrs gap between 2 daily doses and receive last dose on Day 14 in the morning.
Cohort 8- Post hepatic Neuralgia participants will an oral dose of 400mg of iN1011-N17 mesylate salt capsule or placebo twice daily (b.i.d) from Day 1 to Day 13, approximately 12 hrs gap between 2 daily doses and receive last dose on Day 14 in the morning.
Intervention code [1] 323691 0
Treatment: Drugs
Comparator / control treatment
Placebo will be matching the active drug suspension and capsules.
Placebo will be dosed as a suspension and capsules as per the description of intervention above.
The composition of the comparator/control treatment is a placebo capsule, 100 mg microcrystalline cellulose in a hard gelatin capsule.
Control group
Placebo

Outcomes
Primary outcome [1] 331529 0
To evaluate the safety and tolerability of iN1011-N17 following escalating multiple doses in healthy volunteers and Post Hepatic Neuralgia (PHN) patients. 1. Vital signs (systolic and diastolic blood pressure measured using a sphygmomanometer, pulse rate, body temperature, and Respiratory rate) 2. 12-lead ECGs, 3. Clinical laboratory tests (hematology, biochemistry, and urinalysis) assessed using blood and urine samples 4. Physical examination includes general appearance, HEENT (head, ears, eyes, nose, and throat), neck (including thyroid and nodes), cardiovascular, respiratory system, gastrointestinal, renal, musculoskeletal, neurological, skin, and other 5. Continuous cardiac telemetry 6. Incidence, severity, and causality of adverse events (AEs) and serious adverse events (SAEs) graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0
Timepoint [1] 331529 0
Monitored daily from Screening Visit until Day 14
Vital Signs:
At Screening, Day -1; pre-dose (within 30 minutes) and 2, 4, and 8 hours (±15 minutes) post-morning dose on Day 1; pre-dose (within 30 minutes) and 4 and 8 hours (±15 minutes) post-morning dose on Days 2 to 6; pre-dose (within 30 minutes) and 2, 4, and 8 hours (±15 minutes) post-morning dose on Day 7; Day 8 and Day 9 prior to PK sampling; Day 14; and at Early Termination (if applicable).

12-lead ECGs:
Single ECG recordings will be performed on Day -1, and at pre-dose (within 60 minutes) and 1 hour (± 15 minutes), 4 hours and 8 hours (± 30 minutes) following iN1011-N17 /placebo dosing on Day 1 and Day 7; pre-dose (within 60 minutes) on Day 4; Day 9 prior to PK sampling; at Day 14; and at Early Termination (if applicable).

Clinical laboratory tests (hematology, biochemistry, and urinalysis):
At Screening, on Day -1, at pre-dose on Day 4 and Day 7 (within 60 minutes), Day 9 prior to discharge, outpatient visit (Day 14), and at Early Termination (if applicable).

Physical examination:
At Screening, and symptom-directed examination at pre-treatment (Day -1), on Days 4 and 7 (within 60 mins pre-dose), Day 9 prior to discharge, on Day 14 (outpatient visit), and at Early Termination visit (if applicable).

Continuous cardiac telemetry:
Continuous cardiac monitoring (telemetry) should run for minimum of 6 hours on Day -1, on Day 1 for 24.5 hours of monitoring (from up to 30 mins prior to morning dosing), and from Day 2 to Day 7 for a minimum of 6.5 hours (from up to 30 mins prior to morning dosing).

Adverse events:
Daily from Screening Visit until Day 14
Secondary outcome [1] 410192 0
To determine the pharmacokinetics (PK) of iN1011-N17 following multiple-ascending doses in healthy volunteers and PHN patients. Blood samples will be collected for pharmacokinetic assessments Parameters for PK assessment: - Maximum plasma concentration - Time to maximum plasma concentration - Area under the plasma concentration curve - Percentage of AUCinf based on extrapolated - Apparent volume of distribution - Apparent plasma elimination rate constant - Apparent clearance - Fraction excreted unchanged in urine - Renal clearance - Amount of drug excreted unchanged in the urine - Terminal half-life - Mean residence time - Maximum (peak) steady-state plasma drug concentration during a dosage interval - Minimum steady-state plasma drug concentration during a dosage interval - Average steady-state plasma drug concentration during multiple-dose administration
Timepoint [1] 410192 0
Blood sampling for PK on Day 1 pre-morning 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 hour through to 0.5 hour, then ± 10 mins from 0.75 hour through to 6 hours, then ± 15 mins from 8 hours through to 12 hours post-morning dose) post Day 1 morning dose.
Days 2, 3, 4, 5, and 6 pre-morning dose (within 30 minutes prior to dosing).
Day 7 pre-morning dose (within 30 mins 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 (± 2 minutes from 0.17 hour through to 0.5 hour, then ± 10 minutes from 0.75 hour through to 6 hours, then ± 15 minutes from 8 hours through to 12 hours post-morning dose), 24 (± 15 minutes), 36 (± 15 minutes) and 48 hours (± 15 minutes) post-final dose (18 timepoints).
Secondary outcome [2] 411584 0
To determine the pharmacokinetics (PK) of iN1011-N17 following multiple-ascending doses in healthy volunteers and PHN patients. Urine samples will be collected for pharmacokinetic assessments Parameters for PK assessment: - Maximum plasma concentration - Time to maximum plasma concentration - Area under the plasma concentration curve - Percentage of AUCinf based on extrapolated - Apparent volume of distribution - Apparent plasma elimination rate constant - Apparent clearance - Fraction excreted unchanged in urine - Renal clearance - Amount of drug excreted unchanged in the urine - Terminal half-life - Mean residence time - Maximum (peak) steady-state plasma drug concentration during a dosage interval - Minimum steady-state plasma drug concentration during a dosage interval - Average steady-state plasma drug concentration during multiple-dose administration
Timepoint [2] 411584 0
Urine sampling for PK on Day 1 pre-morning dose (within 1 hour prior to dosing)
- 0 to 4, 4 to 8, and 8 to 11 hours and 45 minutes post Day 1 morning dose (at 11 hours and 45 minutes collection, collected before evening dose)
- Day 7 pre-morning dose (within 30 minutes prior to dosing)
- 0 to 4, 4 to 8, 8 to 12, 12 to 24, and 24 to 48 hours post morning Day 7 last dose.
- Early Termination visit (if applicable)
Secondary outcome [3] 411986 0
To determine the pharmacodynamics (PD) of iN1011-N17 following escalating multiple doses in healthy volunteers and PHN patients. The following parameters will be tested - Thermal detection thresholds for the perception of cold (CDT) and heat (HDT) - Thermal pain thresholds for cold (CPT) and heat (HPT) stimuli - Mechanical detection threshold (MDT) and mechanical pain threshold (MPT) Method of limits is used to determine HDT, CDT, CPT, and HPT, as well as paradoxical heat sensation using TSA-II analytical software.
Timepoint [3] 411986 0
Pharmacodynamics (PD) will be measured on Day -1 within 24 hours prior to IP dosing, before morning dose (within 90 minutes) on Day 1, and at 3 and 6 hours (± 30 minutes) post-dose on Day 7.

Eligibility
Key inclusion criteria
Healthy Volunteers:
1. Healthy male and female adults, aged 18 to 55 years of age at the time of consent.
2. Body mass index (BMI equal to 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 45 kg.
3. Clinically acceptable blood pressure (BP), pulse, RR, and body temperature (systolic blood pressure [SBP] between 90 and 140 mmHg; diastolic blood pressure [DBP] between 50 and 90 mmHg; pulse between 45 and100 bpm; RR between 12 and 22 breaths/min; body temperature between 35.5°C and 37.7°C at Screening and Day -1. Measurements are to be recorded after a minimum of 5 minutes of resting in sitting or supine position.
4. 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.
5. For all participants (excluding those who are exclusively in same-sex relationships, who are postmenopausal or have an exclusive partner who is postmenopausal) 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 participants must not be breastfeeding, lactating, or 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 carcinoma, hepatic, renal, neurological, pulmonary (except for childhood asthma), endocrine, hematologic, cardiovascular, or genitourinary disease that, in the opinion of the Investigator, may affect the evaluation of the IP or place the participant at undue risk (except for conditions that are stable on medications).
2. Presence of any underlying physical or psychiatric condition (except for conditions that are stable on medications) that, in the opinion of the Investigator, would undermine participant 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. Presence or history of central nervous system disease that may affect assessment of safety and PK characteristics of the IP.
5. Presence of herniated disc (inter-vertebral, cervical or both) or history of related disease that in the opinion of the Investigator, may affect assessment of safety and PK characteristics of the IP.
6. History of hypersensitivity to iN1011-N17 or to any of its components.
7. History of allergy or sensitivity to sulfonamides.
8. Any abnormal 12-lead electrocardiogram (ECG) findings at Screening and Day -1, deemed by the Investigator or designee to be clinically significant.
9. Positive test for hepatitis B surface antigen (HBsAg), hepatitis C (HCV), or human immunodeficiency virus (HIV) at Screening.
10. 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. Repeated tests will be allowed at the discretion of the Investigator for suspected false positives.
11. Any of the following laboratory abnormalities within 14 days of the first treatment day:
- Platelet count less than 100,000 cells/mm3
- Total neutrophil count less than 1500 cells/mm3
- Serum creatinine greater than 1.5 x ULN
- Alanine aminotransferase (ALT) greater than 3.0 x ULN
- Aspartate aminotransferase (AST) greater than 3.0 x ULN
- Alkaline phosphatase greater than 2.0 x ULN
- Bilirubin greater than 1.5 x ULN
- Temperature greater than 38°C or any other evidence of an infection
12. History of fracture in the lower limb or joint under investigation which may impede pain assessment / pain scores or may prevent accurate sensory testing.
13. 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 MM. This includes analgesics such as paracetamol and non-steroidal anti-inflammatories (for HVs only).
14. 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.
15. 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.
16. History of alcoholism, substance or drug abuse-related disorders deemed significant by the Investigator (or designee) (i.e., more than 21 units per week for males and more than 14 units per week for females. One unit of alcohol equals ½ pint [285 mL] of beer or lager, 1 glass [125 mL] of wine, or 1/6 gill [25 mL] of spirits).
17. Use of more than 5 nicotine-based products (including smoking tobacco, smokeless tobacco, and nicotine patches) per week, within 90 days prior to Screening. Volunteers 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.
18. Consumption of beverages or foods that contain grapefruit, star fruit, pomelos, or products containing these fruits, from 7 days, or from the time that is deemed significant by the Investigator, and products containing caffeine (e.g., coffee, green tea, black tea, and sodas) from 48 hours before the first dose of IP until discharge from the study unit.
19. 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.
20. Any other reason that, in the opinion of the Investigator, may affect assessment of safety, PK, or PD characteristics of the IP.
21. Have previously completed or withdrawn from this study or any other study investigating iN1011-N17 or have previously received the IP (only for HVs).
22. Received an investigational vaccine within 6 months, a live attenuated vaccine within 60 days, or a registered vaccine within 14 days prior to the Day -1 (Baseline visit).

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
Actual
24/08/2022
Date of last participant enrolment
Anticipated
30/03/2024
Actual
Date of last data collection
Anticipated
30/04/2024
Actual
Sample size
Target
32
Accrual to date
8
Final
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 22463 0
CMAX Clinical Research Pty Ltd - Adelaide
Recruitment postcode(s) [1] 37697 0
5000 - Adelaide

Funding & Sponsors
Funding source category [1] 311549 0
Commercial sector/Industry
Name [1] 311549 0
iN Therapeutics Co., Ltd.
Country [1] 311549 0
Korea, Republic Of
Primary sponsor type
Commercial sector/Industry
Name
iN Therapeutics Co., Ltd.
Address
72, Dugyero, Pogokeup, Yonginsi, Gyenggido, 17028
Country
Korea, Republic Of
Secondary sponsor category [1] 312966 0
None
Name [1] 312966 0
Address [1] 312966 0
Country [1] 312966 0
Other collaborator category [1] 282320 0
Commercial sector/Industry
Name [1] 282320 0
Novotech (Australia) Pty Limited
Address [1] 282320 0
Level 2, 235 Pyrmont Street, Pyrmont NSW 2009
Country [1] 282320 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 311001 0
Bellberry Limited
Ethics committee address [1] 311001 0
123 Glen Osmond Road, Eastwood SA 5063
Ethics committee country [1] 311001 0
Australia
Date submitted for ethics approval [1] 311001 0
Approval date [1] 311001 0
17/06/2022
Ethics approval number [1] 311001 0

Summary
Brief summary
This study is a prospective, randomized, double-blind, placebo-controlled, Phase 1b clinical study to evaluate the safety, tolerability, PK, and PD of oral multiple-ascending doses (MAD) of iN1011-N17 after Oral Administration in Healthy Volunteers and OsteoarthritisPost-Herpetic Neuralgia Patients and to Assess the Relative Bioavailability of Mesylate vs Hydrochloride Salt Capsules in Healthy Volunteers.
The study will be conducted with approximately in 3 parts. 56 healthy volunteers and 8 PHP patients will enrolled in up to 8 sequential MAD dose cohorts (Cohorts 1 to 8), each cohort can commence after the corresponding dose cohort has been completed and after Safety Review Committee (SRC) approval.
Trial website
Trial related presentations / publications
Public notes
The participant must have received at least 2 doses of local healthy authority (HA) approved COVID-19 vaccine.
A COVID-19 rapid antigen test will be performed at Screening and on Day -1 to exclude COVID-19 infection at the discretion of the Investigator.

Contacts
Principal investigator
Name 119650 0
Dr Jonathan Newchurch
Address 119650 0
CMAX Clinical Research
Level 5, 21-24 North Terrace, Adelaide SA 5000
Country 119650 0
Australia
Phone 119650 0
+61 8 7088 7900
Fax 119650 0
Email 119650 0
Jonathan.Newchurch@cmax.com.au
Contact person for public queries
Name 119651 0
Dr Jonathan Newchurch
Address 119651 0
CMAX Clinical Research Level 5, 21-24 North Terrace, Adelaide SA 5000
Country 119651 0
Australia
Phone 119651 0
+61 8 7088 7900
Fax 119651 0
Email 119651 0
Jonathan.Newchurch@cmax.com.au
Contact person for scientific queries
Name 119652 0
Ms Yeseul Shin
Address 119652 0
iN Therapeutics Co., Ltd.
Bongeunsaro 114-gil 12, Gangnam-gu, Seoul 06170
Country 119652 0
Korea, Republic Of
Phone 119652 0
+82 2 550 8280
Fax 119652 0
Email 119652 0
yeseul.shin@intherapeutics.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

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