Clinical trial NCT04908800: A Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of KRP-A218 in Healthy Subjects
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Kyorin Pharmaceutical Co.,Ltd
Sponsor class: INDUSTRY
First posted: 2021-06-01
Enrollment: 99
Sex: ALL
Minimum age (years): 20
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Part A: Number of Participants With Adverse Events
timeFrame: Screening to follow-up (Approximately 6 weeks)
measure: Part B: Number of Participants With Adverse Events
timeFrame: Screening to follow-up (Approximately 8 weeks)
measure: Part C: Area Under Concentration-time Curve From Time 0 Extrapolated to Infinity (AUC0-infinity)
timeFrame: Days 1 to 11
measure: Part C: Area Under Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-tlast)
timeFrame: Days 1 to 11
measure: Part C: Maximum Observed Concentration (Cmax)
timeFrame: Days 1 to 11
measure: Part C: Time of the Maximum Observed Concentration (Tmax)
timeFrame: Days 1 to 11
measure: Part C: Apparent Terminal Elimination Half-life (t1/2)
timeFrame: Days 1 to 11
measure: Part C: Apparent Total Clearance (CL/F)
timeFrame: Days 1 to 11
measure: Part C: Apparent Volume of Distribution During the Terminal Phase (Vz/F)
timeFrame: Days 1 to 11
Secondary outcomes:
measure: Part A: Area Under Concentration-time Curve From Time 0 Extrapolated to Infinity (AUC0-infinity)
timeFrame: Day 1
measure: Part A: Area Under Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-tlast)
timeFrame: Day 1
measure: Part A: Maximum Observed Concentration (Cmax)
timeFrame: Day 1
measure: Part A: Time of the Maximum Observed Concentration (Tmax)
timeFrame: Day 1
measure: Part A: Apparent Terminal Elimination Half-life (t1/2)
timeFrame: Day 1
measure: Part A: Apparent Total Clearance (CL/F)
timeFrame: Day 1
measure: Part A: Apparent Volume of Distribution During the Terminal Phase (Vz/F)
timeFrame: Day 1
measure: Part B: Area Under the Concentration-time Curve Over a Dosing Interval (AUC0-τ)
timeFrame: Days 1 and 14
measure: Part B: Area Under Concentration-time Curve From Time 0 Extrapolated to Infinity (AUC0-infinity)
timeFrame: Day 1
measure: Part B: Area Under Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-tlast)
timeFrame: Days 1 and 14
measure: Part B: Maximum Observed Concentration (Cmax)
timeFrame: Days 1 and 14
measure: Part B: Minimum Observed Concentration (Cmin)
timeFrame: Day 14
measure: Part B: Time of the Maximum Observed Concentration (Tmax)
timeFrame: Days 1 and 14
measure: Part B: Apparent Terminal Elimination Half-life (t1/2)
timeFrame: Days 1 and 14
measure: Part B: Apparent Total Clearance (CL/F)
timeFrame: Days 1 and 14
measure: Part B: Apparent Volume of Distribution During the Terminal Phase (Vz/F)
timeFrame: Days 1 and 14
measure: Part B: Observed Accumulation Ratio Based on Area Under the Concentration-Time Curve Over a Dosing Interval (ARAUC0-T)
timeFrame: Day 14
measure: Part B: Observed Accumulation Ratio Based on Maximum Observed Concentration During the Dosing Interval (ARCmax)
timeFrame: Day 14
measure: Part C: Number of Participants With Adverse Events
timeFrame: Screening to follow-up (Approximately 7 weeks)
Other outcomes:
Locations:
city: Leeds
country: United Kingdom
facility: Labcorp Clinical Research
Study officials:
affiliation: Kyorin Pharmaceutical Co.,Ltd
name: Yoji Mimaki
role: STUDY_CHAIR
References: