Safety, Tolerability and Pharmacokinetics of AZD1613 in Adults With Autosomal Dominant Polycystic Kidney Disease (PIONEER-PKD)

AstraZeneca

Status and phase: Begins enrollment this month; Phase 1

Conditions: Autosomal Dominant Polycystic Kidney Disease

Treatments: Drug: Placebo - Part B; Drug: Placebo - Part A; Drug: AZD1613 - Part B; Drug: AZD1613 - Part A

Study type: Interventional

Funder types: Industry

Identifiers

NCT07228364

D9050C00002

Identifier Number (Registry Identifier)

Details and patient eligibility

About

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

Full description

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.

Enrollment: 40 estimated patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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40 participants in 3 patient groups

Part A - Cohort A1

Experimental group

Description:

Participants will receive 4 doses of AZD1613 or placebo on days 1, 29, 57 and 85.

Treatment:

Drug: AZD1613 - Part A

Drug: Placebo - Part A

Part A - Cohort A2

Experimental group

Description:

Participants will receive 4 doses of AZD1613 or placebo on days 1, 29, 57 and 85.

Treatment:

Drug: AZD1613 - Part A

Drug: Placebo - Part A

Part B - Chinese Cohort

Experimental group

Description:

Participants will receive 4 doses of AZD1613 or placebo on days 1, 29, 57 and 85.

Treatment:

Drug: AZD1613 - Part A

Drug: AZD1613 - Part B

Drug: Placebo - Part B