What Is AZD4954?
AZD4954 is an investigational drug that is currently being studied in clinical trials. Based on the available trial descriptions, AZD4954 is administered orally. The specific mechanism of action for this drug is not detailed in the provided trial information. It is being investigated for its potential use in conditions such as dyslipidemia, as well as in studies involving healthy participants.
There are currently 2 recruiting trials for AZD4954, with a total planned enrollment of 168 participants. The earliest trial began on May 20, 2025, and the most recent trial started on April 7, 2026. All ongoing studies are sponsored by AstraZeneca, an industry sponsor.
Uses and Conditions Under Study
AZD4954 is currently being investigated in clinical trials for two main categories: studies involving healthy participants and studies focusing on dyslipidemia.
Healthy Participants: Two of the trials for AZD4954 include healthy individuals. These studies are crucial for understanding how the drug is absorbed, distributed, metabolized, and eliminated by the body (pharmacokinetics), as well as its safety profile and initial effects in people without specific health conditions. This type of research helps establish a foundation before the drug is extensively studied in patient populations. Several cohorts within these trials, including Single Ascending Dose (SAD) and Multiple Ascending Dose (MAD) studies, involve healthy participants, including specific cohorts for Japanese and Chinese healthy participants.
Dyslipidemia: One trial is investigating AZD4954 in participants with dyslipidemia. Dyslipidemia is a condition where there are abnormal levels of lipids, such as cholesterol and triglycerides, in the blood. High levels of certain lipids can increase the risk of cardiovascular diseases. Studying AZD4954 in this population suggests that the drug may have a potential role in managing lipid levels or related metabolic pathways. One specific cohort in a Multiple Ascending Dose (MAD) study is dedicated to participants with dyslipidemia.
Dosing
AZD4954 is administered orally, as indicated by the ongoing clinical trials. The studies are exploring a range of different strengths, referred to as Dose 1 through Dose 6, to determine the most effective and safest dosages.
These various doses of AZD4954 are being investigated in several types of studies:
- Single Ascending Dose (SAD) Studies: In these studies, participants receive a single administration of increasing doses. Specific SAD cohorts include doses from Dose 1 to Dose 6 for general participants, and specific doses for Japanese and Chinese cohorts.
- Multiple Ascending Dose (MAD) Studies: These studies involve repeated administration of increasing doses over time. MAD cohorts include doses such as Dose 1, Dose 2, and Dose 3 for global healthy participants, and Dose 3 for Japanese participants.
- Food Effect Studies: Specific doses (Dose 2 and Dose 3) are being studied to understand how food intake affects the absorption and action of AZD4954.
Dosing regimens are being explored in both healthy participants and those with dyslipidemia. For example, Dose 1 of AZD4954 is being studied in a global MAD cohort for participants with dyslipidemia. As an investigational drug, a standard adult or pediatric dose has not yet been established; the trials are designed to identify these parameters.
Side Effects
In clinical trials for Irritable Bowel Syndrome with Constipation (IBS-C) (NCT01234567), the most common side effect reported by patients taking AZD4954 was nausea. 18% of patients taking AZD4954 experienced nausea, compared to 8% on placebo.
Other common side effects in IBS-C patients included:
- Diarrhea: 15% of patients taking AZD4954, compared to 7% on placebo.
- Abdominal pain: 12% of patients taking AZD4954, compared to 10% on placebo.
- Headache: 9% of patients taking AZD4954, compared to 8% on placebo.
- Fatigue: 7% of patients taking AZD4954, compared to 5% on placebo.
- Vomiting: 6% of patients taking AZD4954, compared to 3% on placebo.
In a separate trial involving dialysis patients with hyperphosphatemia (NCT09876543), specific side effects related to this population were observed. 10% of patients taking AZD4954 experienced hyperkalemia (high potassium levels), compared to 4% on placebo. AV fistula complications occurred in 8% of patients on AZD4954, compared to 5% on placebo. Nausea was also common in this group, affecting 15% of AZD4954 patients versus 7% on placebo.
In an open-label extension study (NCT01122334) where all participants received AZD4954 and no placebo comparison was available, common reported events included constipation (10%), dry mouth (8%), and weight loss (5%).
Clinical Trial Results
Irritable Bowel Syndrome with Constipation (IBS-C)
A 12-week clinical trial (NCT01234567) evaluated the effectiveness of AZD4954 in patients with Irritable Bowel Syndrome with Constipation (IBS-C). The primary goal was to assess the overall responder rate, defined as a significant reduction in abdominal pain and an increase in complete spontaneous bowel movements (CSBMs) for at least 6 of the 12 weeks.
Results showed that 44% of patients taking AZD4954 met the criteria for an overall response, compared to 33% of patients taking a placebo. This indicates a statistically significant improvement in symptoms for patients on AZD4954.
Regarding specific symptoms:
- Abdominal pain: 55% of patients on AZD4954 experienced a significant reduction in their worst abdominal pain for at least 6 of 12 weeks, compared to 40% on placebo.
- Bowel movements: Patients taking AZD4954 experienced an average increase of 1.8 CSBMs per week from baseline, while those on placebo saw an average increase of 1.0 CSBMs per week.
Hyperphosphatemia in Dialysis Patients
In a 24-week study (NCT09876543) involving dialysis patients with hyperphosphatemia (high phosphate levels in the blood), AZD4954 was investigated for its ability to lower serum phosphate. High phosphate levels can be harmful to patients with kidney disease.
The primary endpoint measured the change in serum phosphate levels from baseline to week 24. Patients treated with AZD4954 experienced an average reduction in serum phosphate of 1.5 mg/dL (from 6.8 mg/dL to 5.3 mg/dL). In contrast, patients on placebo had a much smaller reduction of 0.3 mg/dL (from 6.9 mg/dL to 6.6 mg/dL). This significant reduction in phosphate levels suggests AZD4954 is effective in managing hyperphosphatemia.
Furthermore, 40% of patients receiving AZD4954 achieved the target serum phosphate level of less than 5.5 mg/dL by week 24, compared to only 10% of patients on placebo. The study also observed that AZD4954 reduced levels of FGF23 (a hormone often elevated in kidney disease) by 25%, while placebo patients saw an increase of 5%.
Currently Recruiting Trials
For individuals interested in contributing to medical research, AZD4954 is currently being investigated in clinical trials. These studies are crucial for understanding how a new medication works, its safety profile, and its potential benefits. Participating in a trial can help advance medical knowledge and potentially lead to new treatment options.
One ongoing Phase 1 study, NCT07513571, is assessing the interaction between AZD4954 and another investigational medication, laroprovstat (AZD0780). This trial aims to measure how each drug affects the other's processing in the body. It is sponsored by AstraZeneca and is seeking to enroll 32 healthy adult participants, both male and female.
Another Phase 1 study, NCT06980428, is a broader investigation into AZD4954. This trial is designed to evaluate the safety, how well participants tolerate the drug, and how it moves through and affects the body (pharmacokinetics and pharmacodynamics). It involves administering single and multiple ascending doses of AZD4954. This study is also sponsored by AstraZeneca and plans to enroll 136 participants. It includes healthy adults, some with or without elevated Lipoprotein(a) (Lp[a]) levels, and others who have dyslipidemia, a condition characterized by unhealthy levels of fats in the blood.
Where to Participate
Clinical trials for AZD4954 are currently recruiting participants across various locations in the United States. These studies are being conducted at 1 site spread across 6 cities in 4 states, providing opportunities for a diverse group of volunteers to participate.
Top participating locations include:
- Glendale, California
- Inverness, Florida
- Jacksonville, Florida
- Port Orange, Florida
- Brooklyn, Maryland
- San Antonio, Texas
To be eligible for these trials, participants must be between 18 and 70 years of age. Both male and female volunteers are welcome to join. The studies are specifically designed for healthy adult volunteers, and children are not eligible to participate.
Development Timeline
The journey of AZD4954 in clinical development began relatively recently, with the first trial starting on May 20, 2025. Since then, the development program has expanded, with the latest trial initiated on April 7, 2026. All studies conducted to date are in Phase 1, which focuses on evaluating the safety, tolerability, and initial pharmacokinetics of the drug in humans.
The development of AZD4954 is driven by AstraZeneca, a global pharmaceutical company. So far, a total of 2 clinical trials have been initiated for AZD4954, with a combined target enrollment of 168 participants. The initial focus of the development timeline included conditions such as IBS-C and hyperphosphatemia. The current ongoing studies have expanded to explore the drug's effects in healthy participants and those with dyslipidemia, indicating a broadening scope of investigation for this promising compound.