Safety, Tolerability and Pharmacokinetics of AZD1613 in Adults With Autosomal Dominant Polycystic Kidney Disease

Phase 1RecruitingNCT07228364

AstraZeneca40 enrolled

Overview

A study to investigate safety, tolerability, and pharmacokinetics of AZD1613 following subcutaneous or intravenous administration in participants with autosomal dominant polycystic kidney disease (ADPKD).

This Phase I, randomised, single-blind, placebo-controlled study will assess the safety and tolerability of AZD1613 and characterise the pharmacokinetics (PK) of AZD1613 in participants with autosomal dominant polycystic kidney disease (ADPKD), following subcutaneous (SC) or intravenous (IV) administration. Inclusion of participants receiving placebo is appropriate for benchmarking the safety and tolerability of AZD1613. Furthermore, the safety and PK profile will be evaluated in Chinese participants with ADPKD to assess any potential race effect in this population.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Autosomal Dominant Polycystic Kidney Disease

Interventions

AZD1613 - Part ADRUG

Part A - Participants will be administered doses of AZD1613 on days 1, 29, 57, and 85 according to randomization in IRT.

Placebo - Part ADRUG

Part A - Participants will be administered doses of placebo on days 1, 29, 57, and 85 according to randomization in IRT.

AZD1613 - Part BDRUG

Part B - Participants will be administered doses of AZD1613 on days 1, 29, 57, and 85 according to randomization in IRT.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Patients with ADPKD Mayo Class (IB-IE), as per clinical diagnosis (MIC) assessed centrally. Genetic testing results will not be used for eligibility purposes * eGFR = 45 to 90 mL/min /1.73m2 * Body weight ≥ 45 kg and body mass index within the range 18 to 35 kg/m2 (inclusive). * Females are to be of non-childbearing potential Exclusion Criteria: * As judged by the investigator, any evidence of cardiac, vascular, and other renal conditions which in the investigator's opinion makes it undesirable for the participant to participate in the study. * Positive hepatitis C antibody, hepatitis B virus surface antigen, or human immunodeficiency virus test, at screening. * History of QT prolongation associated with other medications that required discontinuation of that medication. * Congenital long QT syndrome. * History of ventricular arrhythmia requiring treatment. Patients with atrial fibrillation/flutter and controlled ventricular rate HR \< 100 bpm can be eligible as judged by the investigator. * Haemoglobin below the lower limit of the normal range or any other clinically significant haematological abnormality as judged by the investigator. * Any clinically important abnormalities in clinical chemistry, haematology, coagulation, or urinalysis results other than those specifically described as exclusion criteria herein, as judged by the investigator. * Systolic BP \> 160 mmHg or diastolic BP \> 100mmHg or HR \< 50 bpm or \> 100 bpm at screening. Patients taking anti-hypertensive medication should be on a stable treatment regimen of antihypertensive therapy for at least 30 days prior to the screening visit. * Any clinically important abnormalities in rhythm, conduction, or morphology of the resting ECG and any abnormalities in the 12-lead ECG that, as considered by the investigator, may interfere with the interpretation of QTc interval changes, including abnormal ST-T-wave morphology or left ventricular hypertrophy. * Kidney cyst interventions such as cyst aspiration or cyst fenestration within 12 weeks prior to screening and during the screening period, or such interventions planned or anticipated within the follow-up period.

Locations (15)

Research Site

Birmingham, Alabama, United States

NOT_YET_RECRUITING

Research Site

Loma Linda, California, United States

Outcomes

Primary Outcomes

Incidence of Treatment-Emergent Adverse Events (TEAEs)

Number of participants with at least one TEAE and SAE, including events leading to discontinuation or death; coded by system organ class and preferred term. Unit: participants.

Time frame: From randomization (Day 1) through end of follow-up (up to Day 189 ±3 days)

Change From Baseline in Safety 12-Lead ECG QTcF

Change from baseline in QT interval corrected using Fridericia's formula (QTcF) measured on single 12-lead safety ECGs. Unit: milliseconds (ms).

Time frame: Baseline (Day -1) and post-dose at scheduled visits through Day 189 ±3 days

Change From Baseline in Safety 12-Lead ECG PR Interval

Change from baseline in PR interval measured on single 12-lead safety ECGs. Unit: milliseconds (ms).

Time frame: Baseline (Day -1) and post-dose at scheduled visits through Day 189 ±3 days

Change From Baseline in Safety 12-Lead ECG QRS Duration

Change from baseline in QRS duration measured on single 12-lead safety ECGs. Unit: milliseconds (ms).

Time frame: Baseline (Day -1) and post-dose at scheduled visits through Day 189 ±3 days

Change From Baseline in Heart Rate (12-Lead Safety ECG)

Change from baseline in heart rate measured on single 12-lead safety ECGs. Unit: beats per minute (bpm).

Time frame: Baseline (Day -1) and post-dose at scheduled visits through Day 189 ±3 days

Change From Baseline in ALT

Change from baseline in alanine aminotransferase. Unit: U/L.

Time frame: Baseline (Day -1) and post-dose at scheduled visits through Day 189 ±3 days

Change From Baseline in AST

Central Contacts

AstraZeneca Clinical Study Information Center

CONTACT

1-877-240-9479 information.center@astrazeneca.com

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Part B - Participants will be administered doses of placebo on days 1, 29, 57, and 85 according to randomization in IRT.

Research Site

Jacksonville, Florida, United States

RECRUITING

Research Site

Orlando, Florida, United States

RECRUITING

Research Site

Lenexa, Kansas, United States

RECRUITING

Research Site

Baltimore, Maryland, United States

NOT_YET_RECRUITING

Research Site

Rochester, Minnesota, United States

RECRUITING

Research Site

San Antonio, Texas, United States

NOT_YET_RECRUITING

Research Site

Chengdu, China

NOT_YET_RECRUITING

Research Site

Hangzhou, China

NOT_YET_RECRUITING

...and 5 more locations

Change from baseline in aspartate aminotransferase. Unit: U/L.

Time frame: Baseline (Day -1) and post-dose at scheduled visits through Day 189 ±3 days

Change From Baseline in Total Bilirubin

Change from baseline in total bilirubin. Unit: mg/dL.

Time frame: Baseline (Day -1) and post-dose at scheduled visits through Day 189 ±3 days

Change From Baseline in Serum Creatinine

Change from baseline in serum creatinine. Unit: mg/dL.

Time frame: Baseline (Day -1) and post-dose at scheduled visits through Day 189 ±3 days

Change From Baseline in Estimated Glomerular Filtration Rate (eGFR; CKD-EPI 2021)

Change from baseline in eGFR calculated using CKD-EPI 2021. Unit: mL/min/1.73 m².

Time frame: Baseline (Day -1) and post-dose at scheduled visits through Day 189 ±3 days

Change From Baseline in INR

Change from baseline in international normalized ratio- (INR). Unit: unitless.

Time frame: Baseline (Day -1) and post-dose at scheduled visits through Day 189 ±3 days

Change From Baseline in Prothrombin Time (PT)

Change from baseline in prothrombin time. Unit: seconds (s).

Time frame: Baseline (Day -1) and post-dose at scheduled visits through Day 189 ±3 days

Change From Baseline in Activated Partial Thromboplastin Time (aPTT)

Change from baseline in aPTT. Unit: seconds (s).

Time frame: Baseline (Day -1) and post-dose at scheduled visits through Day 189 ±3 days

Change From Baseline in Urinary Albumin-to-Creatinine Ratio (UACR)

Change from baseline in UACR (geometric mean of triplicates at each visit). Unit: mg/g.

Time frame: Baseline (Day -1) and scheduled visits through Day 189 ±3 days; UACR as triplicate first-morning voids per visit

Change From Baseline in Systolic Blood Pressure

Change from baseline in supine systolic blood pressure. Unit: mmHg.

Time frame: Baseline (Day -1) and post-dose at scheduled visits through Day 189 ±3 days

Change From Baseline in Diastolic Blood Pressure

Change from baseline in supine diastolic blood pressure. Unit: mmHg.

Time frame: Baseline (Day -1) and post-dose at scheduled visits through Day 189 ±3 days

Change From Baseline in Heart Rate (Vital Signs)

Change from baseline in supine heart rate. Unit: bpm.

Time frame: Baseline (Day -1) and post-dose at scheduled visits through Day 189 ±3 days

Change From Baseline in Body Temperature

Change from baseline in oral body temperature. Unit: °C.

Time frame: Baseline (Day -1) and post-dose at scheduled visits through Day 189 ±3 days

Change From Baseline in Respiratory Rate

Change from baseline in respiratory rate. Unit: breaths per minute.

Time frame: Baseline (Day -1) and post-dose at scheduled visits through Day 189 ±3 days

Change From Baseline in Oxygen Saturation (SpO2)

Change from baseline in pulse oximetry oxygen saturation. Unit: percent (%).

Time frame: Baseline (Day -1) and post-dose at scheduled visits through Day 189 ±3 days

Secondary Outcomes

Maximum Observed Serum Concentration (Cmax) of AZD1613

Maximum observed serum concentration following subcutaneous or intravenous administration. Unit: µg/mL.

Time frame: Intensive PK sampling from Day 1 through Day 189 per protocol schedule

Area Under the Concentration-Time Curve to Last Quantifiable Concentration (AUClast) of AZD1613

AUC from time zero to last quantifiable concentration. Unit: h·µg/mL (or day·µg/mL; align with bioanalytical report).

Time frame: Intensive PK sampling from Day 1 through Day 189 per protocol schedule

Area Under the Concentration-Time Curve From Time Zero to Infinity (AUCinf) of AZD1613

AUC from time zero extrapolated to infinity. Unit: h·µg/mL (or day·µg/mL).

Time frame: Intensive PK sampling from Day 1 through Day 189 per protocol schedule

Area Under the Concentration-Time Curve Over the Dosing Interval at Steady State (AUCtau) of AZD1613

AUC over the dosing interval at steady state. Unit: h·µg/mL (or day·µg/mL).

Time frame: Over the dosing interval (τ = 28 days) at steady state; sampling through Day 189

Time to Maximum Observed Serum Concentration (Tmax) of AZD1613

Time to reach Cmax after dosing. Unit: hours (h).

Time frame: Intensive PK sampling from Day 1 through Day 189 per protocol schedule

Terminal Elimination Half-Life (t½) of AZD1613

Half-life associated with terminal slope (λz) of the concentration-time curve. Unit: hours (h) or days (d).

Time frame: Intensive PK sampling from Day 1 through Day 189 per protocol schedule

Incidence of Anti-Drug Antibodies (ADA) to AZD1613

Number of participants with ADA-positive response based on validated tiered assay (screen and confirm). Unit: participants.

Time frame: Predose on dosing days and during follow-up through Day 189 ±3 days

ADA Titer to AZD1613

Titer among confirmed ADA-positive samples. Unit: reciprocal dilution (titer).

Time frame: Predose on dosing days and during follow-up through Day 189 ±3 days

Change From Baseline in PD Markers of PAPPA-1 Inhibition

Change from baseline in pharmacodynamic marker of PAPPA-1 inhibition. Unit: ng/mL (or assay-specific unit).

Time frame: Baseline to scheduled post-dose time points through Day 189 ±3 days