A Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of KRP-A218 in Healthy Subjects

NCT04908800 | Completed Phase 1 Results

• 1 other identifier: KRPA218-T101
• Study Type: interventional
• Target: 99
• Locations: 1 country
• Sites: 1

Brief Summary

This first-in-human study has three parts. In Parts A and B, the safety, tolerability, and pharmacokinetics (PK) will be evaluated following administration of single and multiple doses of KRP-A218, including food-effect. In Part C, the drug-drug interaction (DDI) with itraconazole will be evaluated.

Conditions

Healthy

Outcome Measures

Primary Outcomes (9)

• Part A: Number of Participants With Adverse Events

  A treatment-emergent adverse event (TEAE) was defined as an adverse event that started during or after the first dose, or started prior to the first dose and increased in severity after the first dose. Where a subject experienced multiple TEAEs with the same preferred term for the same treatment, this was counted as 1 TEAE for that treatment under the maximum severity recorded.

  Screening to follow-up (Approximately 6 weeks)

• Part B: Number of Participants With Adverse Events

  A treatment-emergent adverse event (TEAE) was defined as an adverse event that started during or after the first dose, or started prior to the first dose and increased in severity after the first dose. Where a subject experienced multiple TEAEs with the same preferred term for the same treatment, this was counted as 1 TEAE for that treatment under the maximum severity recorded.

  Screening to follow-up (Approximately 8 weeks)

• Part C: Area Under Concentration-time Curve From Time 0 Extrapolated to Infinity (AUC0-infinity)

  The area under concentration-time curve from time 0 extrapolated to infinity (AUC0-infinity) following Oral Dose Administration of KRP-A218 Alone and in Combination with Itraconazole

  Days 1 to 11

• Part C: Area Under Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-tlast)

  The area under concentration-time curve from time 0 extrapolated to last quantifiable concentration following Oral Dose Administration of KRP-A218 Alone and in Combination with Itraconazole

  Days 1 to 11

• Part C: Maximum Observed Concentration (Cmax)

  The maximum observed concentration following Oral Dose Administration of KRP-A218 Alone and in Combination with Itraconazole

  Days 1 to 11

• Part C: Time of the Maximum Observed Concentration (Tmax)

  The time of the maximum observed concentration following Oral Dose Administration of KRP-A218 Alone and in Combination with Itraconazole

  Days 1 to 11

• Part C: Apparent Terminal Elimination Half-life (t1/2)

  The apparent terminal elimination half-life following Oral Dose Administration of KRP-A218 Alone and in Combination with Itraconazole

  Days 1 to 11

• Part C: Apparent Total Clearance (CL/F)

  The apparent total clearance following Oral Dose Administration of KRP-A218 Alone and in Combination with Itraconazole

  Days 1 to 11

• Part C: Apparent Volume of Distribution During the Terminal Phase (Vz/F)

  The apparent volume of distribution during the terminal phase following Oral Dose Administration of KRP-A218 Alone and in Combination with Itraconazole

  Days 1 to 11

Secondary Outcomes (19)

• Part A: Area Under Concentration-time Curve From Time 0 Extrapolated to Infinity (AUC0-infinity)

  Day 1

• Part A: Area Under Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-tlast)

  Day 1

• Part A: Maximum Observed Concentration (Cmax)

  Day 1

• Part A: Time of the Maximum Observed Concentration (Tmax)

  Day 1

• Part A: Apparent Terminal Elimination Half-life (t1/2)

  Day 1

Study Arms (3)

Part A single ascending dose (SAD) and Part B multiple ascending dose (MAD): KRP-A218

EXPERIMENTAL

Administration Route: Oral

Drug: KRP-A218

Part A (SAD) and Part B (MAD): Placebo

PLACEBO COMPARATOR

Administration Route: Oral

Drug: Placebo

Part C drug-drug interaction (DDI): KRP-A218 and itraconazole

EXPERIMENTAL

Administration Route: Oral

Drug: KRP-A218; Drug: itraconazole

Interventions

KRP-A218 DRUG

KRP-A218 tablet

Part A single ascending dose (SAD) and Part B multiple ascending dose (MAD): KRP-A218; Part C drug-drug interaction (DDI): KRP-A218 and itraconazole

Placebo DRUG

Placebo tablet

Part A (SAD) and Part B (MAD): Placebo

itraconazole DRUG

10 mg/mL oral solution

Also known as: Sporanox

Part C drug-drug interaction (DDI): KRP-A218 and itraconazole

Eligibility Criteria

• Age: 20 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Male or female adults, between 20 and 55 years of age, inclusive.
• Body weight ≥50 kg, with body mass index (BMI) between 18.0 and 30.0 kg/m\^2, inclusive.
• In good health, at Screening or Day -1 as assessed by the Investigator.
• Females will not be pregnant or lactating, and females of childbearing potential will agree to use contraception and to not donate eggs (ova, oocytes). Males will agree to use contraception and to not donate sperm.
• Able to comprehend and willing to sign an informed consent form (ICF) and to abide by the study restrictions.

You may not qualify if:

• Significant history or clinical manifestation of any metabolic, allergic, dermatological, hepatic, renal, haematological, pulmonary, cardiovascular, gastrointestinal, neurological, respiratory, endocrine, or psychiatric disorder, as determined by the Investigator.
• Participation in a clinical study involving administration of an investigational drug (new chemical entity) in the past 90 days prior to dosing.
• Use or intend to use any medications/products known to alter drug absorption, metabolism, or elimination processes, including St. John's wort, within 30 days prior to dosing.
• Use or intend to use any prescription medications/products within 14 days or 5 half-lives (whichever is longer) prior to dosing, unless deemed acceptable by the Investigator.
• Use or intend to use slow release medications/products considered to still be active within 14 days prior to dosing, unless deemed acceptable by the Investigator.
• Use or intend to use any nonprescription medications/products including vitamins, minerals, and phytotherapeutic/herbal/plant derived preparations within 7 days prior to dosing, unless deemed acceptable by the Investigator.
• Use of tobacco or nicotine-containing products within 3 months prior to Day -1, or positive cotinine test at screening or Day -1.
• Ingestion of poppy seed-, Seville orange-, or grapefruit-containing foods or beverages within 7 days prior to Day -1.
• Consumption of caffeine- or xanthine-containing foods and beverages within 36 hours prior to Day -1.
• Participation in strenuous exercised within 7 days prior to Day -1.
• Receipt of blood products within 2 months prior to Day -1.
• Donation of blood from 3 months prior to screening, plasma from 2 weeks prior to screening, or platelets from 6 weeks prior to screening.
• Poor peripheral venous access.
• Have previously completed or withdrawn from this study or have previously received the investigational medicinal product (IMP).
• Subject is, in the opinion of the Investigator, unlikely to comply with the protocol or unsuitable to participate in this study for any reason.

Sponsors & Collaborators

• Kyorin Pharmaceutical Co.,Ltd: lead

Study Sites (1)

Labcorp Clinical Research

Leeds, LS2 9LH, United Kingdom

Location

MeSH Terms

Interventions

Itraconazole

Intervention Hierarchy (Ancestors)

Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Piperazines

Results Point of Contact

• Title: Yoji Mimaki
• Organization: Kyorin Pharmaceutical Co.,Ltd

ml-kyorin_clinicaltrials.gov@mb.kyorin-pharm.co.jp

+81-3-3525-4788

Study Officials

• Yoji Mimaki

  Kyorin Pharmaceutical Co.,Ltd

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: May 27, 2021
• First Posted: June 1, 2021
• Study Start: May 27, 2021
• Primary Completion: April 21, 2022
• Study Completion: April 21, 2022
• Last Updated: January 8, 2024
• Results First Posted: January 8, 2024

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)