A MAD Study to Evaluate the Safety, Tolerability and PK/PD of iN1011-N17 in Healthy Volunteers and PHN Patients.

NCT06218784 | Recruiting Phase 1

• 1 other identifier: iN1011-N17102
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 1

Brief Summary

This study is a 3-part, Double-blind, Randomized, Placebo-controlled, Multiple Ascending Dose Study to Evaluate Safety, Tolerability, Pharmacokinetics/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 of iN1011-N17 in Healthy volunteers.

Conditions

Post Herpetic Neuralgia; Pain; Osteoarthritis; Neuropathic Pain; Chronic Pain; Dorsal Root Ganglion; Nav 1.7

Keywords

Nav 1.7; Nav 1.7 inhibitor; Postoperative pain; Chemotherapy-induced neuropathic pain; Pain; Neurological Pain; Sodium Channel; Action Potential; Voltage Gated Sodium Channel; DRG Voltage Gated Sodium Channel 1.7; Sodium Channel 1.7; Volatage Gated Sodium Channel 1.7

Outcome Measures

Primary Outcomes (6)

• Incidence, severity, and causality of AEs and serious AEs (SAEs)

  Part 1: From baseline until follow-up, an average of 14 days Part 2: From baseline until follow-up, an average of 22 days Part 3: From baseline until follow-up, up to 21 days

• Incidence of Physical examination abnormalities

  Part 1: From baseline until follow-up, an average of 14 days Part 2: From baseline until follow-up, an average of 22 days Part 3: From baseline until follow-up, up to 21 days

• Incidence of Vital signs abnormalities

  Part 1: From baseline until follow-up, an average of 14 days Part 2: From baseline until follow-up, an average of 22 days Part 3: From baseline until follow-up, up to 21 days

• Incidence of 12-lead ECG abnormalities

  Part 1: From baseline until follow-up, an average of 14 days Part 2: From baseline until follow-up, an average of 22 days Part 3: From baseline until follow-up, up to 21 days

• Incidence of Continous cardiac telemetry abnormalities

  Part 1: From baseline until follow-up, an average of 14 days Part 2: From baseline until follow-up, an average of 22 days Part 3: From baseline until follow-up, up to 21 days

• Incidence of Laboratory tests abnormalities

  Part 1: From baseline until follow-up, an average of 14 days Part 2: From baseline until follow-up, an average of 22 days Part 3: From baseline until follow-up, up to 21 days

Secondary Outcomes (20)

• Maximum plasma concentration (Cmax)

  Part 1: Day 1 Part 2: 0-72 hours post dose Part 3: Day 1

• Time to maximum plasma concentration (Tmax)

  Part 1: Day 1 Part 2: 0-72 hours post dose Part 3: Day 1

• Terminal half-life (t1/2)

  Part 1: Day 1 Part 2: 0-72 hours post dose Part 3: Day 1

• Area under the plasma concentration curve (AUC0-12, AUC0-t, AUCinf)

  Part 1: Day 1 and Day 7 Part 2: 0-72 hours post dose Part 3: Day 1 and Day 14

• Percentage of AUCinf based on extrapolation (AUC%extrap)

  Part 1: Day 1 and Day 7 Part 2: 0-72 hours post dose Part 3: Day 1 and Day 14

Other Outcomes (12)

• Daily pain intensity is assessed using the Daily Pain Score (DPS), which is an 11-point numeric scale ranging from 0, indicating 'no pain', to 10, indicating 'pain as bad as you can imagine'.

  From baseline to Day 21

• Score of Short Form McGill Pain Questionnaire (SF-MPQ) (Consists of 11 items. Uses a 4-point numeric scale ranging from 0, indicating 'none', to 4, indicating 'severe'.)

  From baseline to Day 21

• Score of Brief Pain Inventory Short Form (BPI-SF). (measures pain intensity, its effect on functionality and impact of pain. Uses a 11-point numeric scale ranging from 0, indicating 'no pain', to 10, indicating 'pain as bad as you can imagine'.)

  From baseline to Day 21

Study Arms (8)

iN1011-N17 HCl Suspension (Part 1)

EXPERIMENTAL

Oral, Preformulation Suspension, b.i.d, Multiple Ascending Dose (Day 1\~ Day7) Part 1: Participants will receive either iN1011-N17 or placebo in a 3:1 ratio. From Day 1 to Day 6, participants will receive iN1011-N17 or placebo b.i.d in the morning and in the evening, with approximately 12 hours between the 2 daily doses, and receive the last dose on Day 7 in the morning.

Drug: iN1011-N17 HCl Suspension (Part 1)

iN1011-N17 HCl Capsule (Part 1)

EXPERIMENTAL

Oral, Nano Suspension Powder Capsule, b.i.d, Multiple Ascending Dose (Day 1\~ Day7) Part 1: Participants will receive either iN1011-N17 or placebo in a 3:1 ratio. From Day 1 to Day 6, participants will receive iN1011-N17 or placebo b.i.d in the morning and in the evening, with approximately 12 hours between the 2 daily doses, and receive the last dose on Day 7 in the morning.

Drug: iN1011-N17 HCl Capsule (Part 1)

Placebo Capsule (Part 1)

PLACEBO COMPARATOR

Oral, Placebo capsule, b.i.d, Multiple Ascending Dose (Day 1\~ Day7) Part 1: Participants will receive either iN1011-N17 or placebo in a 3:1 ratio. From Day 1 to Day 6, participants will receive iN1011-N17 or placebo b.i.d in the morning and in the evening, with approximately 12 hours between the 2 daily doses, and receive the last dose on Day 7 in the morning.

Drug: Placebo Capsule (Part 1)

iN1011-N17 HCl Capsule (Part 2)

EXPERIMENTAL

Oral, Nano Suspension Powder Capsule, Single dose Part 2: 2-period, randomized, open-label, crossover bioavailability part. Participants will receive a single oral dose of each study treatment (HCl salt and Mesylate salt), one during each of the 2 inpatient periods, in a randomized sequence of administration. There will be a minimum washout period of 5 days between each dose of study treatment.

Drug: iN1011-N17 HCl Capsule (Part 2)

iN1011-N17 Mesylate Capsule (Part 2)

ACTIVE COMPARATOR

Oral, AA10 Capsule, Single dose Part 2: 2-period, randomized, open-label, crossover bioavailability part. Participants will receive a single oral dose of each study treatment (HCl salt and Mesylate salt), one during each of the 2 inpatient periods, in a randomized sequence of administration. There will be a minimum washout period of 5 days between each dose of study treatment.

Drug: iN1011-N17 Mesylate Capsule (Part 2)

iN1011-N17 HCl Capsule (Part 3)

EXPERIMENTAL

Oral, Nano Suspension Powder Capsule, b.i.d, Multiple dose (Day 1\~ Day7) Part 3: 2 cohorts with up to 8 healthy volunteers and 8 PHN patients who will be randomized in a ratio of 3:1 to receive iN1011-N17 or placebo. Each participant in both cohorts will receive oral doses of iN1011-N17/ placebo b.i.d from Day 1 to Day 13, with approximately 12 hours between the 2 daily doses, and receive the last dose on Day 14 in the morning.

Drug: iN1011-N17 HCl Capsule (Part 3)

iN1011-N17 Mesylate Capsule (Part 3)

PLACEBO COMPARATOR

Oral, AA10 Capsule, b.i.d, Multiple dose (Day 1\~ Day14) Part 3: 2 cohorts with up to 8 healthy volunteers and 8 PHN patients who will be randomized in a ratio of 3:1 to receive iN1011-N17 or placebo. Each participant in both cohorts will receive oral doses of iN1011-N17/ placebo b.i.d from Day 1 to Day 13, with approximately 12 hours between the 2 daily doses, and receive the last dose on Day 14 in the morning.

Drug: iN1011-N17 Mesylate Capsule (Part 3)

Placebo Capsule (Part 3)

EXPERIMENTAL

Oral, Placebo capsule, b.i.d, Multiple dose (Day 1\~ Day14) Part 3: 2 cohorts with up to 8 healthy volunteers and 8 PHN patients who will be randomized in a ratio of 3:1 to receive iN1011-N17 or placebo. Each participant in both cohorts will receive oral doses of iN1011-N17/ placebo b.i.d from Day 1 to Day 13, with approximately 12 hours between the 2 daily doses, and receive the last dose on Day 14 in the morning.

Drug: Placebo Capsule (Part 3)

Interventions

iN1011-N17 HCl Suspension (Part 1) DRUG

Dose: 100 mg b.i.d for 7 days (Multiple Ascending Dose)

iN1011-N17 HCl Suspension (Part 1)

iN1011-N17 HCl Capsule (Part 1) DRUG

Dose: 200, 400, 800 mg b.i.d for 7 days (Multiple Ascending Dose)

iN1011-N17 HCl Capsule (Part 1)

Placebo Capsule (Part 1) DRUG

Dose: b.i.d for 7 days

Placebo Capsule (Part 1)

iN1011-N17 HCl Capsule (Part 2) DRUG

Dose: 400 mg QD

iN1011-N17 HCl Capsule (Part 2)

iN1011-N17 Mesylate Capsule (Part 2) DRUG

Dose: 400 mg QD

iN1011-N17 Mesylate Capsule (Part 2)

iN1011-N17 HCl Capsule (Part 3) DRUG

Dose: 400 mg b.i.d for 14 days

iN1011-N17 HCl Capsule (Part 3)

iN1011-N17 Mesylate Capsule (Part 3) DRUG

Dose: 400 mg b.i.d for 14 days

iN1011-N17 Mesylate Capsule (Part 3)

Placebo Capsule (Part 3) DRUG

Dose: b.i.d for 14 days

Placebo Capsule (Part 3)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Healthy Volunteers
• Healthy male and female adults, aged 18 to 55 years of age (inclusive) at the time of consent.
• Body mass index (BMI = 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 (inclusive).
• Clinically acceptable pulse rate, RR, and tympanic body temperature (pulse rate between 45 and 100 beats per minute \[bpm\]; SBP between 90 and 140 mmHg; DBP between 50 and 90 mmHg; RR between 12 and 22 breaths/min; tympanic 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
• For Healthy Volunteers and Post-Herpetic Neuralgia Patients
• 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.
• 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 IP. Female participants must not be breastfeeding, lactating, or pregnant during the study period.
• Female participants are required to be on their chosen contraceptive for at least 7 days before dosing.
• Female participants, where their sole, male sexual partner is vasectomized, must provide a verbal confirmation of azoospermia (90 days following the procedure) which should be recorded in the source documents by the Investigator.
• The minimum timeframe for pre-dose vasectomy for male participants is ≥ 12 weeks, unless they are the sole sexual partner of a female participant as outlined above.
• Male participants who are sexually active must use a condom combined with use of a highly-effective method of contraception for the female partner (excluding those who have had a vasectomy or whose partner is postmenopausal). Confirmation of the female partner's contraceptive information must be provided verbally by the male participant and should be recorded in the source documents by the Investigator. The postmenopausal status of the female partner must be confirmed verbally by the male participant and should be recorded in the source documents by the Investigator.
• Cognitively capable of understanding the provided information and able to fully comply with protocol requirements.
• Written informed consent prior to the commencement of any study procedures.
• Willing and able to perform the necessary visits to the investigational site/institution.
• 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.

You may not qualify if:

• For Healthy Volunteers and Post-Herpetic Neuralgia Patients
• 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).
• 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.
• 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 PK characteristics of the IP.
• Presence or history of central nervous system disease that may affect assessment of safety and PK characteristics of the IP.
• 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.
• History of hypersensitivity to iN1011-N17 or to any of its components.
• Any abnormal 12-lead ECG findings at Screening and Day -1, deemed by the Investigator or designee to be clinically significant.
• Positive test for hepatitis B surface antigen (HBsAg), hepatitis C (HCV), or human immunodeficiency virus (HIV) at Screening.
• Positive urine drug screen test (including methamphetamines, opiates, cocaine, cannabinoids, phencyclidine, benzodiazepines, barbiturates, methadone, tricyclic antidepressants, and amphetamines) or alcohol breath test at Screening and Day -1. Repeated tests will be allowed at the discretion of the Investigator for suspected false positives.
• Any of the following laboratory abnormalities within 14 days of the first treatment day:
• Platelet count \< 100,000 cells/mm3
• Total neutrophil count \< 1500 cells/mm3
• Serum creatinine ≥ 1.5 x upper limit of normal (ULN)
• Alanine aminotransferase (ALT) \> 3.0 x ULN

Sponsors & Collaborators

• iN Therapeutics Co., Ltd.: lead

Study Sites (1)

CMAX Clinical Research

Adelaide, South Australia, 5000, Australia

RECRUITING

MeSH Terms

Conditions

Neuralgia, Postherpetic; Pain; Osteoarthritis; Neuralgia; Chronic Pain; Pain, Postoperative

Condition Hierarchy (Ancestors)

Peripheral Nervous System Diseases; Neuromuscular Diseases; Nervous System Diseases; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Postoperative Complications; Pathologic Processes

Central Study Contacts

Yeseul Shin

CONTACT

+82313328425; hangsu1208@intherapeutics.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 20, 2023
• First Posted: January 23, 2024
• Study Start: November 11, 2022
• Primary Completion: July 29, 2024
• Study Completion: July 29, 2024
• Last Updated: June 24, 2024

Record last verified: 2024-06

Locations

AU (1)