AZD0780 for Kidney Failure

No longer recruiting at 3 trial locations

Overseen By AstraZeneca Clinical Study Information Center

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: AstraZeneca

Must not be taking: PCSK9 inhibitors, CYP3A4/5 modulators

Disqualifiers: Renal transplant, Major surgery, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

Duration: 11 days

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called AZD0780 to evaluate its safety and behavior in the body for individuals with kidney issues. The trial includes different groups: those with severe kidney problems not on dialysis, those with end-stage kidney disease on dialysis, and those with moderate kidney issues. Individuals with stable kidney conditions who have been on dialysis for at least three months may be suitable candidates. The goal is to understand how AZD0780 interacts with varying levels of kidney function. As a Phase 1 trial, participants will be among the first to receive this treatment, aiding researchers in understanding its effects in people.

Do I have to stop taking my current medications for the trial?

Yes, you may need to stop some medications. Participants with normal renal function must stop using any prescription or non-prescription drugs 7 days before the study, unless approved by the investigator. Participants with renal impairment must avoid certain medications like potassium binders and phosphate binders 10 hours before and after the study dose, and other specific drugs as outlined in the protocol.

Is there any evidence suggesting that AZD0780 is likely to be safe for humans?

Research shows limited safety information for AZD0780 in treating kidney failure. AZD0780 remains in the early testing stages, with scientists just beginning to assess its safety for people. However, treatments at this stage often have about a 74% chance of advancing successfully to the next research phase. While detailed safety results are not yet available, early tests suggest the treatment is promising.

In such trials, researchers closely monitor participants for any side effects or problems. If AZD0780 causes any issues, researchers will quickly identify them. Overall, while more information is needed, the early trial stage indicates potential for AZD0780 and suggests it is on the path to being better understood. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for kidney failure?

Most treatments for kidney failure, like dialysis or kidney transplants, are focused on managing symptoms and replacing lost kidney function. But AZD0780 is different because it targets the underlying mechanisms of renal impairment. Researchers are excited about AZD0780 because it offers a novel approach by potentially improving kidney function directly, rather than just managing symptoms. This could mean a significant shift in how kidney failure is treated, offering hope for better outcomes and improved quality of life for patients with varying degrees of renal impairment.

What evidence suggests that AZD0780 might be an effective treatment for kidney failure?

Research has shown that AZD0780, a PCSK9 inhibitor, can significantly lower LDL cholesterol, often called "bad" cholesterol. One study found that AZD0780 reduced LDL cholesterol by about 51%, a substantial decrease. This result is similar to other medications in the same category, but AZD0780 offers the added advantage of being taken as a pill. While these findings are promising for managing cholesterol, they do not directly address kidney failure. This trial will examine AZD0780 in different groups of participants with varying levels of renal function, including those with severe renal impairment, moderate renal impairment, and end-stage renal disease (ESRD) on dialysis. There is hope that better cholesterol levels might improve kidney health over time. More research is needed to confirm if it specifically helps with kidney failure. ^{1 3 4 6 7}

Who Is on the Research Team?

Kwabena Ayesu, MD

Principal Investigator

Omega Research Orlando

Thomas C Marbury

Principal Investigator

Orlando Clinical Research Center

Juan Carlos Rondon, Medicine

Principal Investigator

Clinical Pharmacology of Miami, Inc.

Joel M Neutel

Principal Investigator

Orange County Research Center

Trisha Shamp, Medicine

Principal Investigator

Nucleus Network

Are You a Good Fit for This Trial?

This trial is for adult men and women with severe kidney impairment or end-stage renal disease, who are not on dialysis or are on intermittent hemodialysis. Women must be of non-childbearing potential. Participants should have no other health conditions that could affect the study's results.

Inclusion Criteria

I am healthy with normal kidney function and no significant medical issues.

For Participants with renal impairment: Diagnosis of chronic kidney disease, stable renal function in the 6 months prior to dosing, Received HD for chronic renal failure for at least 3 months prior to dosing (Group 2), Participants with renal impairment, as follows, based on CKD-EPI equation (BSA-adjusted eGFR) at screening: Group1 eGFR < 30 mL/min, not requiring dialysis, Group 2 ESRD (eGFR < 15 mL/min) on a stable intermittent HD schedule for at least 3 months prior to planned dosing and Group 4 (optional) moderate renal impairment (eGFR ≥ 30 to < 60 mL/min), Male participants: Males must be surgically sterile or using, in conjunction with their female partner, a highly effective method of contraception for the duration of the study (from the time of study intervention administration) until 3 months after discharge to prevent pregnancy in a partner, Female participants of non-childbearing potential: Female participants must not be pregnant and must have a negative pregnancy test at screening and check-in, must not be lactating, and must not be of childbearing potential

Exclusion Criteria

For Participants with normal renal function: Any clinically significant disease or disorder (eg, cardiovascular, pulmonary, gastrointestinal, liver, renal, neurological, musculoskeletal including bone fractures, endocrine including adrenal insufficiency, metabolic, malignant, psychiatric, major physical impairment), Use of any prescription or non-prescription drugs (including vitamins, recreational drugs, and dietary or herbal supplements) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) before study intervention, unless, in the opinion of the investigator and sponsor, the medication will not interfere with the study, History of any major surgical procedure within 30 days prior to study intervention

For Participants with renal impairment: Presence of unstable medical or psychological conditions which, in the opinion of the investigator, would compromise the participant's safety or successful participation in this study, Renal transplant patients (participants on HD with non-functioning renal transplants are not excluded), participants waiting for organ transplant scheduled to occur during the study, and those with a history of acute kidney injury occurring within 3 months prior to screening, History of any major surgical procedure within 30 days prior to study intervention, Current or previous treatment with drugs for reduction or inhibition of PCSK9 (eg, evolocumab, alirocumab, or inclisiran), Use of moderate/strong inhibitors or inducers of CYP3A4/5, Unable to refrain from potassium binders, phosphate binders (eg, aluminium hydroxide and calcium carbonate), cholestyramine/colestipol, and ranitidine/nizatidine within 10 hours before and 10 hours after study intervention, Receiving or has received within 14 days of screening, medication that contains a black box warning for significant QT prolongation. A list of prohibited medications can be found in protocol, Use of concurrent medication which affects calculation of eGFR by affecting serum creatinine (eg, cephalosporin antibiotics, ascorbic acid, trimethoprim, cimetidine, or quinine) within 7 days of Day -1.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

Up to 4 weeks

Treatment

Participants receive a single oral dose of AZD0780 and are confined to the study site for assessments

11 days

Continuous stay at the study site from Day -1 to Day 11

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• AZD0780

Trial Overview The study tests AZD0780 in individuals with different levels of kidney function, including those with normal function, moderate impairment, severe impairment not on dialysis, and end-stage disease on hemodialysis. It's a single-dose study to see how the drug behaves in the body (pharmacokinetics) and its safety.

How Is the Trial Designed?

Group I: Group 4 (optional): AZD0780 Experimental Treatment 1 Intervention

Participants with moderate renal impairment (eGFR ≥ 30 to \< 60 mL/min).

Group II: Group 3: AZD0780 Experimental Treatment 1 Intervention

Participants with normal renal function demographically matched by sex, age, and body mass index (BMI) to the impaired participants (eGFR of ≥ 90 mL/min)

Group III: Group 2: AZD0780 Experimental Treatment 1 Intervention

Participants with ESRD (eGFR \< 15 mL/min) on a stable intermittent HD schedule for at least 3 months prior to planned dosing.

Group IV: Group 1: AZD0780 Experimental Treatment 1 Intervention

Participants with severe renal impairment (eGFR \< 30 mL/min), not on dialysis.

Who Is Running the Clinical Trial?

AstraZeneca

Lead Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Published Research Related to This Trial

In a study of 25 HIV seronegative subjects, including those with severe renal impairment and healthy individuals, zidovudine (AZT) showed increased concentrations in patients with renal issues, indicating altered pharmacokinetics in these populations.

The metabolite glucuronidated zidovudine (G. AZT) had significantly higher levels in uremic patients, leading to a prolonged half-life and suggesting that renal function greatly affects the elimination of this drug and its metabolite.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Pharmacokinetics of zidovudine (AZT) and its metabolite (G-AZT) in healthy subjects and in patients with kidney failure]. Pioger, JC., Taburet, AM., Colin, JN., et al.[2013]

In a study of 6 patients with renal insufficiencies, aztreonam (AZT) showed significantly different pharmacokinetics during hemodialysis compared to nonhemodialysis, with a much shorter serum half-life of 3.44 hours during hemodialysis versus 16.97 hours otherwise.

The results indicate that patients undergoing hemodialysis should start with a standard loading dose of AZT, followed by a reduced daily dose and a supplemental dose after each dialysis session to ensure effective treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Pharmacokinetics of aztreonam on hemodialysis]. Nagasaka, H., Inagaki, O., Nasu, M., et al.[2016]

In HIV-infected patients with end-stage renal disease (ESRD), the clearance of zidovudine (AZT) was similar to that of patients with normal renal function, suggesting that the standard dosing may be appropriate for this group.

However, serum levels of AZT and its metabolite GAZT were significantly higher in ESRD patients, indicating a need for further research on the potential toxicity and effects of these elevated levels on treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of zidovudine in HIV-infected patients with end-stage renal disease. Kimmel, PL., Lew, SQ., Umana, WO., et al.[2018]

In a study of 194 patients with End-Stage Renal Disease (ESRD), 14% experienced mortality within 72 hours of admission, highlighting the serious risks associated with advanced uremia and acidemia.

The most common adverse events included hypotension requiring inotropic support (20.6%) and seizures (16%), indicating that early intervention and referral for ESRD patients can significantly reduce morbidity and mortality.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcome of End-Stage Renal Disease Patients with Advanced Uremia and Acidemia. Rehman, IU., Idrees, MK., Shoukat, .[2017]

In a multicenter study involving 104 patients with chronic kidney disease, biosimilar erythropoiesis-stimulating agents (ESAs) showed a significantly greater increase in hemoglobin levels compared to originator ESAs after 3, 6, and 12 months of treatment.

The safety and risk/benefit profile of biosimilar ESAs were found to be comparable to that of originator ESAs, challenging the common belief that biosimilars are less effective or safe.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative risk/benefit profile of biosimilar and originator erythropoiesis-stimulating agents (ESAs): data from an Italian observational study in nephrology. Motola, D., Vaccheri, A., Roncadori, A., et al.[2018]

In the AFFIRM trial involving 1,199 patients with metastatic castration-resistant prostate cancer, enzalutamide significantly delayed the occurrence of skeletal-related events, with a median time of 16.7 months compared to 13.3 months for placebo (hazard ratio 0.69).

Enzalutamide also improved pain control and health-related quality of life (HRQoL), with 42% of patients reporting overall HRQoL improvement compared to 15% in the placebo group, and a longer median time to HRQoL deterioration (9.0 months vs 3.7 months).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of enzalutamide on time to first skeletal-related event, pain, and quality of life in men with castration-resistant prostate cancer: results from the randomised, phase 3 AFFIRM trial. Fizazi, K., Scher, HI., Miller, K., et al.[2022]

In a phase 3 study with 1150 patients, enzalutamide combined with androgen deprivation therapy (ADT) significantly delayed the time to first confirmed clinically meaningful deterioration in pain and health-related quality of life (HRQoL) compared to ADT alone.

Specific subgroups, such as those with prior radiotherapy or low baseline HRQoL, experienced notable benefits, with enzalutamide delaying the worsening of pain and maintaining high HRQoL scores.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The impact of enzalutamide on quality of life in men with metastatic hormone-sensitive prostate cancer based on prior therapy, risk, and symptom subgroups. Stenzl, A., Szmulewitz, RZ., Petrylak, D., et al.[2022]

In a case study of an HIV-infected male undergoing hemodialysis, zidovudine (AZT) showed pharmacokinetics similar to those in patients with normal kidney function, indicating that its disposition may not be significantly altered by renal impairment.

However, the inactive metabolite G-ZDV was found at significantly higher levels (23-440 times that of zidovudine), and hemodialysis did not effectively reduce the levels of either zidovudine or G-ZDV, raising concerns about the implications of these elevated metabolite levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Zidovudine disposition during hemodialysis in a patient with acquired immunodeficiency syndrome. Tartaglione, TA., Holeman, E., Opheim, K., et al.[2020]

In a study of 488 older adults (average age 72) with advanced chronic kidney disease, nephrology providers' assessments of patients' mortality risk using the surprise question were linked to hospitalization rates, indicating that those deemed at higher risk spent more time hospitalized.

Patients whose providers were 'definitely not surprised' by their potential death had a significantly higher likelihood of being hospitalized compared to those whose providers were 'very surprised', suggesting that provider perceptions can help predict patient outcomes and guide care strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nephrology Provider Surprise Question Response and Hospitalizations in Older Adults with Advanced CKD. Ramer, SJ., Baddour, NA., Siew, ED., et al.[2021]

In a study involving 12 healthy subjects and 30 patients with varying degrees of renal insufficiency, the pharmacokinetics of azithromycin showed no significant changes in plasma concentration or distribution volume due to renal impairment.

This suggests that the dosage of azithromycin can remain the same for patients with renal insufficiency as for those with normal kidney function, indicating its safety and efficacy in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of azithromycin in normal and impaired renal function. Höffler, D., Koeppe, P., Paeske, B.[2019]

In a phase-2 clinical trial using a mouse model, the drugs AZD5438 and dabrafenib were found to significantly reduce kidney injury and improve survival in cisplatin-treated mice, indicating their potential as protective agents against cisplatin-induced nephrotoxicity.

Both drugs not only decreased harmful serum biomarkers associated with kidney damage but also mitigated cell death mechanisms, suggesting they could be effective in preventing both kidney damage and hearing loss caused by cisplatin chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repurposing AZD5438 and Dabrafenib for Cisplatin-Induced AKI. Pushpan, CK., Kresock, DF., Ingersoll, MA., et al.[2023]

In a study of 51 children with frequently-relapsing/steroid-dependent nephrotic syndrome, rituximab was found to significantly reduce relapse rates and improve quality of life compared to cyclophosphamide and tacrolimus after one year.

Rituximab not only led to fewer relapses and lower cumulative steroid use but also had a better safety profile, with the cyclophosphamide group experiencing twice the frequency of infections compared to the other treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of rituximab, cyclophosphamide, and tacrolimus as first steroid-sparing agents for complicated relapsing/steroid-dependent nephrotic syndrome in children: an evaluation of the health-related quality of life. Wang, L., Zhu, J., Xia, M., et al.[2022]

In a phase III trial involving 950 patients with metastatic castrate-refractory prostate cancer, oral satraplatin significantly reduced the risk of disease progression or death by 33% compared to placebo, indicating its efficacy in delaying disease progression.

While satraplatin did not improve overall survival compared to placebo, it effectively delayed pain progression and was generally well tolerated, although some patients experienced more frequent side effects like myelosuppression and gastrointestinal disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multinational, double-blind, phase III study of prednisone and either satraplatin or placebo in patients with castrate-refractory prostate cancer progressing after prior chemotherapy: the SPARC trial. Sternberg, CN., Petrylak, DP., Sartor, O., et al.[2022]

The combination of aripiprazole and sertraline (ASC) significantly improved depression symptoms more than the placebo and sertraline combination (PSC), with a mean change in the Montgomery-Åsberg Depression Rating Scale (MADRS) score of -9.2 for ASC compared to -7.2 for PSC over 6 weeks.

The ASC treatment was well tolerated, with most side effects being mild or moderate, and low rates of discontinuation due to adverse events (1.9% for ASC and 1.5% for PSC), indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized, double-blind comparison of aripiprazole/sertraline combination and placebo/sertraline combination in patients with major depressive disorder. Kamijima, K., Kimura, M., Kuwahara, K., et al.[2019]

A panel of nephrologists and pharmacists has developed four standardized phenotypes of drug-induced kidney disease, which include acute kidney injury, glomerular, tubular, and nephrolithiasis, to help identify and characterize these disorders more effectively.

These phenotypes provide a consistent framework for evaluating drug nephrotoxicity, which is crucial for clinicians and regulatory agencies to improve the prevention and management of drug-induced kidney disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phenotype standardization for drug-induced kidney disease. Mehta, RL., Awdishu, L., Davenport, A., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06592482

NCT06592482 | A Phase I Study to Investigate the Effect of ... This is a Phase I, multi-centre, single-dose, non-randomised, open-label, parallel-group study to examine the PK, safety, and tolerability of AZD0780 in male ...

2. frfr-prd-astrazeneca-keystone-engage.app-trialscope.com frfr-prd-astrazeneca-keystone-engage.app-trialscope.com/study/D7960C00007/

A Phase I Study to Investigate the Effect of Renal Impairment ... A Phase I Study to Investigate the Effect of Renal Impairment on the Pharmacokinetics, Safety, and Tolerability of AZD0780 ; Age. 18 Years - 85 ...

3. pharmaceutical-technology.com pharmaceutical-technology.com/data-insights/azd-0780-astrazeneca-renal-failure-likelihood-of-approval/

AZD-0780 by AstraZeneca for Renal Failure: Likelihood of ... According to GlobalData, Phase I drugs for Renal Failure have a 74% phase transition success rate (PTSR) indication benchmark for progressing ...

4. astrazeneca-us.com astrazeneca-us.com/media/press-releases/2025/AZD0780-a-novel-oral-PCSK9-inhibitor-demonstrated-significant-LDL-cholesterol-LDL-C-reduction-in-PURSUIT-Phase-IIb-trial.html

AZD0780, a novel oral PCSK9 inhibitor, demonstrated ... Data from PURSUIT are consistent with Phase I findings for AZD0780 which demonstrated a statistically significant reduction of 51% in LDL-C ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S0735109725059078

An Oral PCSK9 Inhibitor for Treatment of ... The phase 2 PURSUIT study showed a favorable efficacy and safety profile of AZD0780, broadly comparable to other PCSK9 inhibitors, with the advantage of a once- ...

6. withpower.com withpower.com/trial/phase-1-renal-insufficiency-7-2024-ae2f6

AZD0780 for Kidney Failure · Info for Participants The provided research does not contain specific safety data for AZD0780 in treating kidney failure. The articles focus on drug-induced kidney disease ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39962632/

The effect of severe renal impairment on ... The aim of this phase 1 trial was to assess the pharmacokinetics, safety and tolerability of balcinrenone (previously AZD9977) in participants with severe ...