跳至主要内容
MedPath Trial logoMedPath TrialMedPath Trial Home
临床试验/NCT07024823
NCT07024823招募中1 期

A Phase I Randomized, Single-Blind, Placebo-Controlled Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AZD4248 Following Single and Multiple Ascending Dose Administration in Healthy Participants and Participants With Chronic Kidney Disease and Type 2 Diabetes and to Assess Home Measurements of Creatinine in a Prospective, Non-interventional Cohort Study

AstraZeneca5 个研究点 分布在 1 个国家目标入组 124 人开始时间: 2025年6月9日最近更新:
Share to TwitterShare to FacebookShare to LinkedInShare to Reddit
适应症
干预措施
相关药物

试验速览

阶段
1 期
状态
招募中
发起方
AstraZeneca
入组人数
124
试验地点
5
主要终点
Parts A, B, and C: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

This study will evaluate safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of single ascending doses (SAD) and multiple ascending doses (MAD) of AZD4248 administered as an oral solution and intravenous (IV) infusion. Additionally, the study investigates the non-interventional feasibility of home measurement of serum creatinine in participants with diabetic kidney disease (DKD).

详细描述

This is a Phase I, first in human (FIH), randomized, single-blind, placebo-controlled study of AZD4248 involving healthy participants (Parts A and B) and participants with DKD (Part C) and to assess home measurements of creatinine in a prospective, non-interventional cohort in participants with DKD (Part D).

The study consists of 4 parts:

  • Part A: SAD. Part A will consist of Parts A1 (single ascending doses in healthy participants), A2 (single dose in healthy Chinese participants), and A3 (IV infusion in healthy participants).
  • Part B: MAD. Part B will consist of Parts B1 (multiple ascending doses in healthy participants) and B2 (multiple ascending doses in healthy participants of Japanese descent).
  • Part C: Multiple dosing in participants with DKD.
  • Part D: Multi-site, non-interventional, prospective cohort evaluation of home-based creatinine self-measurement in participants with DKD.

研究设计

研究类型
Interventional
分配方式
Randomized
干预模型
Sequential
主要目的
Treatment
盲法
Double (Participant, Care Provider)

入排标准

年龄范围
18 Years 至 75 Years（Adult, Older Adult）
性别
All
接受健康志愿者
是

入选标准

  • •- Healthy participants with suitable veins for cannulation or repeated venipuncture.
  • •Parts A and B:
  • •Have a body mass index (BMI) between 18 and 30 kilograms per millimeter (kg/m2), inclusive.
  • •For Chinese participants (Part A2): participants are to be Chinese, defined as having both parents and 4 grandparents who are Chinese. This includes second and third generation participants of Chinese descent whose parents or grandparents are living in a country other than China.
  • •For Japanese participants (Part B2): participants are to be Japanese, defined as having both parents and 4 grandparents who are Japanese. This includes second and third generation participants of Japanese descent whose parents or grandparents are living in a country other than Japan.
  • •Have a BMI between 20 and 40 kg/m2, inclusive.
  • •Have a diagnosis of diabetic kidney disease (DKD).
  • •Hemoglobin A1C (HbA1c) of ≤ 10.5%.
  • •Participants are required to be on a stable dose of angiotensin converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB) for at least 6 weeks prior to Visit 1 and throughout the Screening Period. In addition, participants should be on stable doses of all other medication for ≥ 6 weeks before Screening.
  • •Have a BMI between 20 and 35 kg/m2, inclusive.
  • •Have a diagnosis of DKD as defined by a) diagnosis of type 2 diabetes (T2D) b) eGFR values and c) urine albumin to creatinine ratio (UACR) values.
  • •HbA1c of ≤ 10.5%.
  • •Participants are required to be on a stable dose of ACEi or ARB for at least 6 weeks prior to Visit 1 and throughout the Screening Period. In addition, participants should be on stable doses of all other medication for ≥ 6 weeks before Screening.
  • •Participants must be able and motivated to use the home creatinine device and smartphone independently by successfully performing the test without assistance from site staff.
  • •Participants must be able to read and understand English sufficient to participate in site visits and home testing.

排除标准

  • •History of any clinically important disease or disorder which may put the participant at risk because of participation in the study or influence the results.
  • •Any positive result on Screening for serum hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb), or human immunodeficiency virus (HIV).
  • •Parts A and B:
  • •History or presence of gastrointestinal, hepatic, or renal disease.
  • •Any clinically important illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of study intervention.
  • •History of severe allergy/hypersensitivity or ongoing clinically important allergy/hypersensitivity, or history of hypersensitivity to drugs with a similar chemical structure or class to AZD
  • •Participants who have previously received AZD
  • •History or presence of gastrointestinal, hepatic, or renal disease.
  • •Any clinically important illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of study intervention.
  • •History of severe allergy/hypersensitivity or ongoing clinically important allergy/hypersensitivity, or history of hypersensitivity to drugs with a similar chemical structure or class to AZD
  • •Use of drugs that are strong or moderate CYP3A4 inhibitors/inducers or P-gp inhibitors from within 3 weeks before Screening until the end of the last sample collection.
  • •Participants who have previously received AZD
  • •Participants on serum creatinine-altering drugs should be on long-term treatment at a stable dose prior to study entry.
  • •Expected change of dosing regimen during the study.
  • •History of clinically significant heart or vascular disease.
  • •New York Heart Association Class 2, 3, or 4 or history of hospitalization for heart failure within 6 months of screening.
  • •Ventricular arrhythmias requiring treatment.
  • •Amputation due to peripheral artery disease.
  • •Severe chronic obstructive pulmonary disease as judged by the Investigator or hospitalization for exacerbation in the last 6 months.
  • •Participants on serum creatinine-altering drugs should be on long-term treatment at a stable dose prior to study entry.
  • •Expected change of dosing regimen during the study.

研究组 & 干预措施

Part A3 SAD IV Cohort

Experimental

Participants will receive single IV infusion of AZD4248 or placebo.

干预措施: AZD4248 (Drug)

Part A1 SAD

Experimental

Participants will receive single ascending oral dose of AZD4248 or placebo.

干预措施: Placebo (Drug)

Part A2 SAD Chinese Cohort

Experimental

Participants will receive single oral dose of AZD4248 or placebo.

干预措施: AZD4248 (Drug)

Part A2 SAD Chinese Cohort

Experimental

Participants will receive single oral dose of AZD4248 or placebo.

干预措施: Placebo (Drug)

Part A1 SAD

Experimental

Participants will receive single ascending oral dose of AZD4248 or placebo.

干预措施: AZD4248 (Drug)

Part A3 SAD IV Cohort

Experimental

Participants will receive single IV infusion of AZD4248 or placebo.

干预措施: Placebo (Drug)

Part D Observational Cohort

No Intervention

Participants will participate in home-based creatinine self-measurement.

Part B1 MAD

Experimental

Participants will receive multiple ascending oral doses of AZD4248 or placebo.

干预措施: AZD4248 (Drug)

Part B1 MAD

Experimental

Participants will receive multiple ascending oral doses of AZD4248 or placebo.

干预措施: Placebo (Drug)

Part B2 MAD Japanese

Experimental

Participants will receive multiple ascending oral doses of AZD4248 or placebo.

干预措施: AZD4248 (Drug)

Part B2 MAD Japanese

Experimental

Participants will receive multiple ascending oral doses of AZD4248 or placebo.

干预措施: Placebo (Drug)

Part C Multiple Dosing DKD

Experimental

Participants will receive multiple oral doses of AZD4248 or placebo.

干预措施: AZD4248 (Drug)

Part C Multiple Dosing DKD

Experimental

Participants will receive multiple oral doses of AZD4248 or placebo.

干预措施: Placebo (Drug)

结局指标

主要结局

Parts A, B, and C: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)

时间窗: From Day 1 to Follow Up visit (Part A: up to 12 days; Part B and C: up to 19 days)

To assess the safety and tolerability of AZD4248 following single oral ascending doses or single IV administration to healthy participants and multiple oral ascending doses to healthy participants and participants with CKD and T2D (DKD).

Part D: Intra- and inter-participant variability of estimated glomerular filtration rate (eGFR) derived from home self-testing device measurements

时间窗: Day 1 to Day 169

To assess intra- and inter-participant variability of twice weekly home-based serum creatinine measurements.

Parts A, B, and C: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)

时间窗: From Day 1 to Follow Up visit (Part A: up to 12 days; Part B and C: up to 19 days)

To assess the safety and tolerability of AZD4248 following single oral ascending doses or single IV administration to healthy participants and multiple oral ascending doses to healthy participants and participants with CKD and T2D (DKD).

次要结局

  • Area under concentration-time curve from time 0 to infinity (AUCinf)(Part A1 and A2: Days 1-7, Part A3: Days 1-3, Part B: Days 1-17. Part C: Days 1-17)
  • Area under concentration-curve from time 0 to the last quantifiable concentration (AUClast)(Part A1 and A2: Days 1-7, Part A3: Days 1-3, Part B: Days 1-17. Part C: Days 1-17)
  • Dose normalized AUClast (AUClast/D)(Part A1 and A2: Days 1-7, Part A3: Days 1-3, Part B: Days 1-17. Part C: Days 1-17)
  • Dose normalized AUCinf (AUCinf/D)(Part A1 and A2: Days 1-7, Part A3: Days 1-3, Part B: Days 1-17. Part C: Days 1-17)
  • Apparent total body clearance (CL/F)(Part A1 and A2: Days 1-7, Part A3: Days 1-3, Part B: Days 1-17. Part C: Days 1-17)
  • Maximum observed drug concentration (Cmax)(Part A1 and A2: Days 1-7, Part A3: Days 1-3, Part B: Days 1-17. Part C: Days 1-17)
  • Dose normalized Cmax (Cmax/D)(Part A1 and A2: Days 1-7, Part A3: Days 1-3, Part B: Days 1-17. Part C: Days 1-17)
  • Terminal elimination half-life (t½λz)(Part A1 and A2: Days 1-7, Part A3: Days 1-3, Part B: Days 1-17. Part C: Days 1-17)
  • Terminal rate constant (λz)(Part A1 and A2: Days 1-7, Part A3: Days 1-3, Part B: Days 1-17. Part C: Days 1-17)
  • Time delay between drug administration and the first observed concentration (tlag)(Part A1 and A2: Days 1-7, Part A3: Days 1-3.)
  • Time of last quantifiable concentration (tlast)(Part A1 and A2: Days 1-7, Part A3: Days 1-3, Part B: Days 1-17. Part C: Days 1-17)
  • Time to reach maximum observed concentration (tmax)(Part A1 and A2: Days 1-7, Part A3: Days 1-3, Part B: Days 1-17. Part C: Days 1-17)
  • Apparent volume of distribution based on the terminal phase (Vz/F)(Part A1 and A2: Days 1-7, Part A3: Days 1-3, Part B: Days 1-17. Part C: Days 1-17)
  • Absolute bioavailability (F)(Part A1 and A2: Days 1-7, Part A3: Days 1-3.)
  • Total body clearance (CL)(Part A1 and A2: Days 1-7, Part A3: Days 1-3, Part B: Days 1-17. Part C: Days 1-17)
  • Volume of distribution at steady state (Vss)(Part A1 and A2: Days 1-7, Part A3: Days 1-3.)
  • Area under concentration-time curve in the dose interval (AUCtau)(Part B: Days 1-17. Part C: Days 1-17)
  • Dose normalized AUCtau (AUCtau/D)(Part B: Days 1-17. Part C: Days 1-17)
  • Accumulation ratio for AUC (Rac AUC)(Part B: Days 1-17. Part C: Days 1-17)
  • Accumulation ratio for Cmax (Rac Cmax)(Part B: Days 1-17. Part C: Days 1-17)
  • Temporal change parameter (TCP)(Part B: Days 1-17. Part C: Days 1-17)
  • Individual and cumulative amount of unchanged drug excreted into urine from time t1 to time t2 [Ae(t1-t2)](Part A: Days 1-2. Part B: Days 1-4 and 11-14. Part C: Days 1-4 and 11-14)
  • Individual and cumulative percentage of dose excreted unchanged in urine from time t1 to time t2 [fe(t1-t2)](Part A: Days 1-2. Part B: Days 1-4 and 11-14. Part C: Days 1-4 and 11-14)
  • Renal clearance (CLR)(Part A: Days 1-2. Part B: Days 1-4 and 11-14. Part C: Days 1-4 and 11-14)
  • Percentage change from baseline in plasma target engagement marker(Part A: Days 1-5. Part B: Days 1-4 and 11-14. Part C: Days 1-4 and 11-14)
  • Part D: Intra- and inter-participant variability of eGFR derived from laboratory measurements(Day 1 to Day 169)
  • Part D: Changes over longitudinal follow-up in participant-reported experience questionnaire on collective participant satisfaction, usability and device acceptability data(Day 1 to Day 169)
  • Part D: Summary of qualitative insights from optional individual in-depth interview samples(Day 30 to Day 84)
  • Part D: Changes over longitudinal follow-up in site-based staff reported PTSFQ(Day 1 to Day 169)
  • Part D: Estimated glomerular filtration rate (eGFR)(Day 1 to Day 169)
  • Part D: Proportion of completed creatinine tests, with completed assessments(Day 1 to Day 169)
  • Area under concentration-time curve from time 0 to infinity (AUCinf)(Part A1 and A2: Days 1-7, Part A3: Days 1-3, Part B: Days 1-17. Part C: Days 1-17)
  • Area under concentration-curve from time 0 to the last quantifiable concentration (AUClast)(Part A1 and A2: Days 1-7, Part A3: Days 1-3, Part B: Days 1-17. Part C: Days 1-17)
  • Dose normalized AUClast (AUClast/D)(Part A1 and A2: Days 1-7, Part A3: Days 1-3, Part B: Days 1-17. Part C: Days 1-17)
  • Dose normalized AUCinf (AUCinf/D)(Part A1 and A2: Days 1-7, Part A3: Days 1-3, Part B: Days 1-17. Part C: Days 1-17)
  • Apparent total body clearance (CL/F)(Part A1 and A2: Days 1-7, Part A3: Days 1-3, Part B: Days 1-17. Part C: Days 1-17)
  • Maximum observed drug concentration (Cmax)(Part A1 and A2: Days 1-7, Part A3: Days 1-3, Part B: Days 1-17. Part C: Days 1-17)
  • Dose normalized Cmax (Cmax/D)(Part A1 and A2: Days 1-7, Part A3: Days 1-3, Part B: Days 1-17. Part C: Days 1-17)
  • Terminal elimination half-life (t½λz)(Part A1 and A2: Days 1-7, Part A3: Days 1-3, Part B: Days 1-17. Part C: Days 1-17)
  • Terminal rate constant (λz)(Part A1 and A2: Days 1-7, Part A3: Days 1-3, Part B: Days 1-17. Part C: Days 1-17)
  • Time delay between drug administration and the first observed concentration (tlag)(Part A1 and A2: Days 1-7, Part A3: Days 1-3.)
  • Time of last quantifiable concentration (tlast)(Part A1 and A2: Days 1-7, Part A3: Days 1-3, Part B: Days 1-17. Part C: Days 1-17)
  • Time to reach maximum observed concentration (tmax)(Part A1 and A2: Days 1-7, Part A3: Days 1-3, Part B: Days 1-17. Part C: Days 1-17)
  • Apparent volume of distribution based on the terminal phase (Vz/F)(Part A1 and A2: Days 1-7, Part A3: Days 1-3, Part B: Days 1-17. Part C: Days 1-17)
  • Absolute bioavailability (F)(Part A1 and A2: Days 1-7, Part A3: Days 1-3.)
  • Total body clearance (CL)(Part A1 and A2: Days 1-7, Part A3: Days 1-3, Part B: Days 1-17. Part C: Days 1-17)
  • Volume of distribution at steady state (Vss)(Part A1 and A2: Days 1-7, Part A3: Days 1-3.)
  • Area under concentration-time curve in the dose interval (AUCtau)(Part B: Days 1-17. Part C: Days 1-17)
  • Dose normalized AUCtau (AUCtau/D)(Part B: Days 1-17. Part C: Days 1-17)
  • Accumulation ratio for AUC (Rac AUC)(Part B: Days 1-17. Part C: Days 1-17)
  • Accumulation ratio for Cmax (Rac Cmax)(Part B: Days 1-17. Part C: Days 1-17)
  • Temporal change parameter (TCP)(Part B: Days 1-17. Part C: Days 1-17)
  • Individual and cumulative amount of unchanged drug excreted into urine from time t1 to time t2 [Ae(t1-t2)](Part A: Days 1-2. Part B: Days 1-4 and 11-14. Part C: Days 1-4 and 11-14)
  • Individual and cumulative percentage of dose excreted unchanged in urine from time t1 to time t2 [fe(t1-t2)](Part A: Days 1-2. Part B: Days 1-4 and 11-14. Part C: Days 1-4 and 11-14)
  • Renal clearance (CLR)(Part A: Days 1-2. Part B: Days 1-4 and 11-14. Part C: Days 1-4 and 11-14)
  • Percentage change from baseline in plasma target engagement marker(Part A: Days 1-5. Part B: Days 1-4 and 11-14. Part C: Days 1-4 and 11-14)
  • Part D: Intra- and inter-participant variability of eGFR derived from laboratory measurements(Day 1 to Day 169)
  • Part D: Changes over longitudinal follow-up in participant-reported experience questionnaire on collective participant satisfaction, usability and device acceptability data(Day 1 to Day 169)
  • Part D: Summary of qualitative insights from optional individual in-depth interview samples(Day 30 to Day 84)
  • Part D: Changes over longitudinal follow-up in site-based staff reported PTSFQ(Day 1 to Day 169)
  • Part D: Estimated glomerular filtration rate (eGFR)(Day 1 to Day 169)
  • Part D: Proportion of completed creatinine tests, with completed assessments(Day 1 to Day 169)

研究者

发起方
AstraZeneca
申办方类型
Industry
责任方
Sponsor

研究点 (5)

Loading locations...

相似试验

已完成
1 期
A Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AZD0780 in Healthy SubjectsDyslipidemia
NCT05384262AstraZeneca183
已完成
1 期
A Single and Multiple Ascending Dose Study to Investigate Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AZD2389 in Healthy ParticipantsHealthy Participants
NCT06138795AstraZeneca120
尚未招募
1 期
A Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of HS-10510 in Healthy SubjectsDyslipidemia
NCT07001787Jiangsu Hansoh Pharmaceutical Co., Ltd.88
已完成
1 期
A Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AZD4144 Following Single and Multiple Ascending Doses Via Oral Administration to Healthy ParticipantsHealthy Participants
NCT06122714AstraZeneca95
已完成
1 期
Single Ascending Dose Study of ANX105Healthy
NCT05288881Annexon, Inc.23