Recruiting
Phase 1
Safety, Tolerability and Pharmacokinetics of AZD1613 in Adults With Autosomal Dominant Polycystic Kidney Disease
Condition(s) studied
Autosomal Dominant Polycystic Kidney Disease
Investigational drug(s) / intervention(s)
AZD1613 - Part APlacebo - Part AAZD1613 - Part BPlacebo - Part B
AZD1613 - Part A: Part A - Participants will be administered doses of AZD1613 on days 1, 29, 57, and 85 according to randomization in IRT.
Placebo - Part A: Part A - Participants will be administered doses of placebo on days 1, 29, 57, and 85 according to randomization in IRT.
AZD1613 - Part B: Part B - Participants will be administered doses of AZD1613 on days 1, 29, 57, and 85 according to randomization in IRT.
Placebo - Part B: Part B - Participants will be administered doses of placebo on days 1, 29, 57, and 85 according to randomization in IRT.
Study summary
A study to investigate safety, tolerability, and pharmacokinetics of AZD1613 following subcutaneous or intravenous administration in participants with autosomal dominant polycystic kidney disease (ADPKD).
Eligibility
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.
Primary outcome measure(s)
- Incidence of Treatment-Emergent Adverse Events (TEAEs) — From randomization (Day 1) through end of follow-up (up to Day 189 ±3 days)
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.
- Change From Baseline in Safety 12-Lead ECG QTcF — Baseline (Day -1) and post-dose at scheduled visits through Day 189 ±3 days
Change from baseline in QT interval corrected using Fridericia's formula (QTcF) measured on single 12-lead safety ECGs.
Unit: milliseconds (ms).
- Change From Baseline in Safety 12-Lead ECG PR Interval — Baseline (Day -1) and post-dose at scheduled visits through Day 189 ±3 days
Change from baseline in PR interval measured on single 12-lead safety ECGs.
Unit: milliseconds (ms).
- Change From Baseline in Safety 12-Lead ECG QRS Duration — Baseline (Day -1) and post-dose at scheduled visits through Day 189 ±3 days
Change from baseline in QRS duration measured on single 12-lead safety ECGs.
Unit: milliseconds (ms).
- Change From Baseline in Heart Rate (12-Lead Safety ECG) — Baseline (Day -1) and post-dose at scheduled visits through Day 189 ±3 days
Change from baseline in heart rate measured on single 12-lead safety ECGs.
Unit: beats per minute (bpm).
- Change From Baseline in ALT — Baseline (Day -1) and post-dose at scheduled visits through Day 189 ±3 days
Change from baseline in alanine aminotransferase.
Unit: U/L.
- Change From Baseline in AST — Baseline (Day -1) and post-dose at scheduled visits through Day 189 ±3 days
Change from baseline in aspartate aminotransferase.
Unit: U/L.
- Change From Baseline in Total Bilirubin — Baseline (Day -1) and post-dose at scheduled visits through Day 189 ±3 days
Change from baseline in total bilirubin.
Unit: mg/dL.
- Change From Baseline in Serum Creatinine — Baseline (Day -1) and post-dose at scheduled visits through Day 189 ±3 days
Change from baseline in serum creatinine.
Unit: mg/dL.
- Change From Baseline in Estimated Glomerular Filtration Rate (eGFR; CKD-EPI 2021) — Baseline (Day -1) and post-dose at scheduled visits through Day 189 ±3 days
Change from baseline in eGFR calculated using CKD-EPI 2021.
Unit: mL/min/1.73 m².
- Change From Baseline in INR — Baseline (Day -1) and post-dose at scheduled visits through Day 189 ±3 days
Change from baseline in international normalized ratio- (INR).
Unit: unitless.
- Change From Baseline in Prothrombin Time (PT) — Baseline (Day -1) and post-dose at scheduled visits through Day 189 ±3 days
Change from baseline in prothrombin time.
Unit: seconds (s).
- Change From Baseline in Activated Partial Thromboplastin Time (aPTT) — Baseline (Day -1) and post-dose at scheduled visits through Day 189 ±3 days
Change from baseline in aPTT.
Unit: seconds (s).
- Change From Baseline in Urinary Albumin-to-Creatinine Ratio (UACR) — Baseline (Day -1) and scheduled visits through Day 189 ±3 days; UACR as triplicate first-morning voids per visit
Change from baseline in UACR (geometric mean of triplicates at each visit).
Unit: mg/g.
- Change From Baseline in Systolic Blood Pressure — Baseline (Day -1) and post-dose at scheduled visits through Day 189 ±3 days
Change from baseline in supine systolic blood pressure.
Unit: mmHg.
- Change From Baseline in Diastolic Blood Pressure — Baseline (Day -1) and post-dose at scheduled visits through Day 189 ±3 days
Change from baseline in supine diastolic blood pressure.
Unit: mmHg.
- Change From Baseline in Heart Rate (Vital Signs) — Baseline (Day -1) and post-dose at scheduled visits through Day 189 ±3 days
Change from baseline in supine heart rate.
Unit: bpm.
- Change From Baseline in Body Temperature — Baseline (Day -1) and post-dose at scheduled visits through Day 189 ±3 days
Change from baseline in oral body temperature.
Unit: °C.
- Change From Baseline in Respiratory Rate — Baseline (Day -1) and post-dose at scheduled visits through Day 189 ±3 days
Change from baseline in respiratory rate.
Unit: breaths per minute.
- Change From Baseline in Oxygen Saturation (SpO2) — Baseline (Day -1) and post-dose at scheduled visits through Day 189 ±3 days
Change from baseline in pulse oximetry oxygen saturation.
Unit: percent (%).
Trial sites (15)
| Facility | City | Region | Status |
|---|
| Research Site |
Birmingham |
Alabama |
Not Yet Recruiting |
| Research Site |
Loma Linda |
California |
Not Yet Recruiting |
| Research Site |
Jacksonville |
Florida |
Recruiting |
| Research Site |
Orlando |
Florida |
Recruiting |
| Research Site |
Lenexa |
Kansas |
Recruiting |
| Research Site |
Baltimore |
Maryland |
Not Yet Recruiting |
| Research Site |
Rochester |
Minnesota |
Recruiting |
| Research Site |
San Antonio |
Texas |
Not Yet Recruiting |
| Research Site |
Chengdu |
China |
Not Yet Recruiting |
| Research Site |
Hangzhou |
China |
Recruiting |
| Research Site |
Nanjing |
China |
Recruiting |
| Research Site |
Shanghai |
China |
Not Yet Recruiting |
| Research Site |
Wuhan |
China |
Not Yet Recruiting |
| Research Site |
Xiamen |
China |
Not Yet Recruiting |
| Research Site |
London |
United Kingdom |
Recruiting |