Skip to main content
OpenTrials
Completed

NCT Number: NCT04908800

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

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.

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Healthy

Age range

20 year–55 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Labcorp Clinical Research

Leeds, LS2 9LH, United Kingdom

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Key Inclusion Criteria:

  • 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.

Key Exclusion Criteria:

  • 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.

Other protocol defined Inclusion/Exclusion criteria may apply

Treatment and study plan

KRP-A218

Drug

KRP-A218 tablet

Placebo

Drug

Placebo tablet

Itraconazole

Drug

10 mg/mL oral solution

Other names: Sporanox

Primary outcomes

  1. Part A: Number of Participants With Adverse Events

    Time frame: Screening to follow-up (Approximately 6 weeks)

    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.

  2. Part B: Number of Participants With Adverse Events

    Time frame: Screening to follow-up (Approximately 8 weeks)

    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.

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

    Time frame: Days 1 to 11

    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

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

    Time frame: Days 1 to 11

    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

  5. Part C: Maximum Observed Concentration (Cmax)

    Time frame: Days 1 to 11

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

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

    Time frame: Days 1 to 11

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

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

    Time frame: Days 1 to 11

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

  8. Part C: Apparent Total Clearance (CL/F)

    Time frame: Days 1 to 11

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

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

    Time frame: Days 1 to 11

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

Secondary outcomes

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

    Time frame: Day 1

    Area under concentration-time curve from time 0 extrapolated to infinity following single oral dose of KRP-A218

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

    Time frame: Day 1

    Area under curve from time 0 to the time of the last quantifiable concentration following single oral dose of KRP-A218

  3. Part A: Maximum Observed Concentration (Cmax)

    Time frame: Day 1

    Maximum observed concentration following single oral dose of KRP-A218

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

    Time frame: Day 1

    Time of the maximum observed concentration following single oral dose of KRP-A218

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

    Time frame: Day 1

    Apparent terminal elimination half-life following single oral dose of KRP-A218

  6. Part A: Apparent Total Clearance (CL/F)

    Time frame: Day 1

    Apparent total clearance following single oral dose of KRP-A218

  7. Part A: Apparent Volume of Distribution During the Terminal Phase (Vz/F)

    Time frame: Day 1

    Apparent volume of distribution during the terminal phase following single oral dose of KRP-A218

  8. Part B: Area Under the Concentration-time Curve Over a Dosing Interval (AUC0-τ)

    Time frame: Days 1 and 14

    Assessment of the area under the concentration-time curve over a dosing interval (AUC0-τ)

  9. Part B: Area Under Concentration-time Curve From Time 0 Extrapolated to Infinity (AUC0-infinity)

    Time frame: Day 1

    Assessment of the area under concentration-time curve from time 0 extrapolated to infinity (AUC0-infinity)

  10. Part B: Area Under Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-tlast)

    Time frame: Days 1 and 14

    Assessment of the area under curve from time 0 to the time of the last quantifiable concentration (AUC0-tlast)

  11. Part B: Maximum Observed Concentration (Cmax)

    Time frame: Days 1 and 14

    Assessment of the maximum observed concentration (Cmax)

  12. Part B: Minimum Observed Concentration (Cmin)

    Time frame: Day 14

    Assessment of the minimum observed concentration (Cmin)

  13. Part B: Time of the Maximum Observed Concentration (Tmax)

    Time frame: Days 1 and 14

    Assessment of the time of the maximum observed concentration (Tmax)

  14. Part B: Apparent Terminal Elimination Half-life (t1/2)

    Time frame: Days 1 and 14

    Assessment of the apparent terminal elimination half-life (t1/2)

  15. Part B: Apparent Total Clearance (CL/F)

    Time frame: Days 1 and 14

    Assessment of the apparent total clearance (CL/F)

  16. Part B: Apparent Volume of Distribution During the Terminal Phase (Vz/F)

    Time frame: Days 1 and 14

    Assessment of the apparent volume of distribution during the terminal phase (Vz/F)

  17. Part B: Observed Accumulation Ratio Based on Area Under the Concentration-Time Curve Over a Dosing Interval (ARAUC0-T)

    Time frame: Day 14

    Observed accumulation ratio based on area under the concentration-time curve over a dosing interval (ARAUC0-T) in Part B

  18. Part B: Observed Accumulation Ratio Based on Maximum Observed Concentration During the Dosing Interval (ARCmax)

    Time frame: Day 14

    Observed accumulation ratio based on maximum observed concentration during the dosing interval (ARCmax) in Part B

  19. Part C: Number of Participants With Adverse Events

    Time frame: Screening to follow-up (Approximately 7 weeks)

    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.

Sponsors and collaborators

Lead sponsor

Kyorin Pharmaceutical Co.,Ltd

Industry

Registry information

Official study title

A First-in-Human, Phase I, Double-blind, Placebo-controlled, Single and Multiple Ascending Oral Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of KRP-A218 in Healthy Subjects, Including Food-Effect and Drug-drug Interaction With Itraconazole

Important dates

Study start
2021
Primary completion
2022
Study completion
2022
First posted
Jun 1, 2021
Registry last updated
Jan 8, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.