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Phase 1 Completed N=99 Randomized Double-blind Treatment

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

Healthy
Source: ClinicalTrials.gov NCT04908800 ↗
Enrolled (actual)
99
Serious AEs
0.0%
Results posted
Jan 2024
Primary outcomePrimary: Part A: Number of Participants With Adverse Events — 4; 3; 4; 3 participants

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.

Outcome Measures

OutcomeResultp-value
PRIMARY
Part A: Number of Participants With Adverse Events
4; 3; 4; 3; 2; 2
PRIMARY
Part B: Number of Participants With Adverse Events
6; 3; 7; 5; 5; 0
PRIMARY
Part C: Area Under Concentration-time Curve From Time 0 Extrapolated to Infinity (AUC0-infinity)
191; 360
PRIMARY
Part C: Area Under Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-tlast)
182; 306
PRIMARY
Part C: Maximum Observed Concentration (Cmax)
10.7; 12.2
PRIMARY
Part C: Time of the Maximum Observed Concentration (Tmax)
3.00; 2.00
PRIMARY
Part C: Apparent Terminal Elimination Half-life (t1/2)
15.9; 26.5
PRIMARY
Part C: Apparent Total Clearance (CL/F)
5.24; 2.78
PRIMARY
Part C: Apparent Volume of Distribution During the Terminal Phase (Vz/F)
120; 106
SECONDARY
Part A: Area Under Concentration-time Curve From Time 0 Extrapolated to Infinity (AUC0-infinity)
210; 600; 607; 634; 1230; 2600
SECONDARY
Part A: Area Under Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-tlast)
198; 575; 578; 600; 1160; 2490
SECONDARY
Part A: Maximum Observed Concentration (Cmax)
11.9; 31.6; 30.0; 38.8; 60.3; 146
SECONDARY
Part A: Time of the Maximum Observed Concentration (Tmax)
3.00; 4.00; 3.50; 4.00; 3.50; 3.00
SECONDARY
Part A: Apparent Terminal Elimination Half-life (t1/2)
18.5; 15.0; 15.7; 18.1; 17.6; 16.4
SECONDARY
Part A: Apparent Total Clearance (CL/F)
4.76; 5.00; 4.94; 4.74; 4.89; 4.61
SECONDARY
Part A: Apparent Volume of Distribution During the Terminal Phase (Vz/F)
127; 108; 112; 124; 124; 109
SECONDARY
Part B: Area Under the Concentration-time Curve Over a Dosing Interval (AUC0-τ)
254; 560; 1170; 1760; 395; 813
SECONDARY
Part B: Area Under Concentration-time Curve From Time 0 Extrapolated to Infinity (AUC0-infinity)
367; 800; 1590; 2480
SECONDARY
Part B: Area Under Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-tlast)
253; 558; 1170; 1750; 575; 1170
SECONDARY
Part B: Maximum Observed Concentration (Cmax)
20.0; 44.0; 99.0; 137; 29.9; 60.9
SECONDARY
Part B: Minimum Observed Concentration (Cmin)
9.09; 18.5; 33.0; 59.6
SECONDARY
Part B: Time of the Maximum Observed Concentration (Tmax)
3.00; 3.00; 3.00; 3.50; 3.00; 3.50
SECONDARY
Part B: Apparent Terminal Elimination Half-life (t1/2)
13.0; 12.5; 11.7; 12.6; 18.8; 16.2
SECONDARY
Part B: Apparent Total Clearance (CL/F)
5.45; 5.00; 5.03; 4.44; 5.06; 4.92
SECONDARY
Part B: Apparent Volume of Distribution During the Terminal Phase (Vz/F)
102; 89.9; 84.6; 80.7; 137; 115
SECONDARY
Part B: Observed Accumulation Ratio Based on Area Under the Concentration-Time Curve Over a Dosing Interval (ARAUC0-T)
1.56; 1.45; 1.41; 1.57
SECONDARY
Part B: Observed Accumulation Ratio Based on Maximum Observed Concentration During the Dosing Interval (ARCmax)
1.49; 1.38; 1.21; 1.49
SECONDARY
Part C: Number of Participants With Adverse Events
5; 3; 6; 0; 0; 0

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

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT04908800). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.

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