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

Healthy Clinical Trial

Official 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04908800
• Other study ID #: KRPA218-T101
• Status: Completed
• Phase: Phase 1
• Start date: May 27, 2021
• Est. completion date: April 21, 2022

Study information

• Verified date: March 2023
• Source: Kyorin Pharmaceutical Co.,Ltd
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 99
• Est. completion date: April 21, 2022
• Est. primary completion date: April 21, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 20 Years to 55 Years

Eligibility

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

Related Conditions & MeSH terms

• Healthy

Intervention

Drug:
• KRP-A218
KRP-A218 tablet
• Placebo
Placebo tablet
• itraconazole
10 mg/mL oral solution

Locations

Country	Name	City	State
United Kingdom	Labcorp Clinical Research	Leeds

Sponsors (1)

Lead Sponsor	Collaborator
Kyorin Pharmaceutical Co.,Ltd

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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)
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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	Part A: Area Under Concentration-time Curve From Time 0 Extrapolated to Infinity (AUC0-infinity)	Area under concentration-time curve from time 0 extrapolated to infinity following single oral dose of KRP-A218	Day 1
Secondary	Part A: Area Under Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-tlast)	Area under curve from time 0 to the time of the last quantifiable concentration following single oral dose of KRP-A218	Day 1
Secondary	Part A: Maximum Observed Concentration (Cmax)	Maximum observed concentration following single oral dose of KRP-A218	Day 1
Secondary	Part A: Time of the Maximum Observed Concentration (Tmax)	Time of the maximum observed concentration following single oral dose of KRP-A218	Day 1
Secondary	Part A: Apparent Terminal Elimination Half-life (t1/2)	Apparent terminal elimination half-life following single oral dose of KRP-A218	Day 1
Secondary	Part A: Apparent Total Clearance (CL/F)	Apparent total clearance following single oral dose of KRP-A218	Day 1
Secondary	Part A: Apparent Volume of Distribution During the Terminal Phase (Vz/F)	Apparent volume of distribution during the terminal phase following single oral dose of KRP-A218	Day 1
Secondary	Part B: Area Under the Concentration-time Curve Over a Dosing Interval (AUC0-t)	Assessment of the area under the concentration-time curve over a dosing interval (AUC0-t)	Days 1 and 14
Secondary	Part B: Area Under Concentration-time Curve From Time 0 Extrapolated to Infinity (AUC0-infinity)	Assessment of the area under concentration-time curve from time 0 extrapolated to infinity (AUC0-infinity)	Day 1
Secondary	Part B: Area Under Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-tlast)	Assessment of the area under curve from time 0 to the time of the last quantifiable concentration (AUC0-tlast)	Days 1 and 14
Secondary	Part B: Maximum Observed Concentration (Cmax)	Assessment of the maximum observed concentration (Cmax)	Days 1 and 14
Secondary	Part B: Minimum Observed Concentration (Cmin)	Assessment of the minimum observed concentration (Cmin)	Day 14
Secondary	Part B: Time of the Maximum Observed Concentration (Tmax)	Assessment of the time of the maximum observed concentration (Tmax)	Days 1 and 14
Secondary	Part B: Apparent Terminal Elimination Half-life (t1/2)	Assessment of the apparent terminal elimination half-life (t1/2)	Days 1 and 14
Secondary	Part B: Apparent Total Clearance (CL/F)	Assessment of the apparent total clearance (CL/F)	Days 1 and 14
Secondary	Part B: Apparent Volume of Distribution During the Terminal Phase (Vz/F)	Assessment of the apparent volume of distribution during the terminal phase (Vz/F)	Days 1 and 14
Secondary	Part B: Observed Accumulation Ratio Based on Area Under the Concentration-Time Curve Over a Dosing Interval (ARAUC0-T)	Observed accumulation ratio based on area under the concentration-time curve over a dosing interval (ARAUC0-T) in Part B	Day 14
Secondary	Part B: Observed Accumulation Ratio Based on Maximum Observed Concentration During the Dosing Interval (ARCmax)	Observed accumulation ratio based on maximum observed concentration during the dosing interval (ARCmax) in Part B	Day 14
Secondary	Part C: 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 7 weeks)