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

Официальное название

A Phase I Randomised, Single-blind, Placebo-controlled Study to Assess the Safety, Tolerability, and Pharmacokinetics of AZD1613 Following Multiple Ascending Dose Administration in Participants With Autosomal Dominant Polycystic Kidney Disease

Обзор

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

Подробное описание

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.

Вмешательства

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

Первичные конечные точки

• Incidence of Treatment-Emergent Adverse Events (TEAEs) [Срок оценки: From randomization (Day 1) through end of follow-up (up to Day 189 ±3 days)]
• Change From Baseline in Safety 12-Lead ECG QTcF [Срок оценки: Baseline (Day -1) and post-dose at scheduled visits through Day 189 ±3 days]
• Change From Baseline in Safety 12-Lead ECG PR Interval [Срок оценки: Baseline (Day -1) and post-dose at scheduled visits through Day 189 ±3 days]
• Change From Baseline in Safety 12-Lead ECG QRS Duration [Срок оценки: Baseline (Day -1) and post-dose at scheduled visits through Day 189 ±3 days]
• Change From Baseline in Heart Rate (12-Lead Safety ECG) [Срок оценки: Baseline (Day -1) and post-dose at scheduled visits through Day 189 ±3 days]
• Change From Baseline in ALT [Срок оценки: Baseline (Day -1) and post-dose at scheduled visits through Day 189 ±3 days]
• Change From Baseline in AST [Срок оценки: Baseline (Day -1) and post-dose at scheduled visits through Day 189 ±3 days]
• Change From Baseline in Total Bilirubin [Срок оценки: Baseline (Day -1) and post-dose at scheduled visits through Day 189 ±3 days]
• Change From Baseline in Serum Creatinine [Срок оценки: 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) [Срок оценки: Baseline (Day -1) and post-dose at scheduled visits through Day 189 ±3 days]

Вторичные конечные точки (9)

• Maximum Observed Serum Concentration (Cmax) of AZD1613 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: Over the dosing interval (τ = 28 days) at steady state; sampling through Day 189]
• Time to Maximum Observed Serum Concentration (Tmax) of AZD1613 [Срок оценки: Intensive PK sampling from Day 1 through Day 189 per protocol schedule]
• Terminal Elimination Half-Life (t½) of AZD1613 [Срок оценки: Intensive PK sampling from Day 1 through Day 189 per protocol schedule]
• Incidence of Anti-Drug Antibodies (ADA) to AZD1613 [Срок оценки: Predose on dosing days and during follow-up through Day 189 ±3 days]
• ADA Titer to AZD1613 [Срок оценки: Predose on dosing days and during follow-up through Day 189 ±3 days]
• Change From Baseline in PD Markers of PAPPA-1 Inhibition [Срок оценки: Baseline to scheduled post-dose time points through Day 189 ±3 days]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

США · 8 центров

• Research Site — Birmingham
• Research Site — Loma Linda
• Research Site — Jacksonville
• Research Site — Orlando
• Research Site — Lenexa
• Research Site — Baltimore
• Research Site — Rochester
• Research Site — San Antonio

Китай · 6 центров

• Research Site — Чэнду
• Research Site — Ханчжоу
• Research Site — Нанкин
• Research Site — Шанхай
• Research Site — Ухань
• Research Site — Xiamen

Великобритания · 1 центр

• Research Site — London

Идентификаторы

NCT: NCT07228364 · D9050C00002 · Identifier Number

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗