What Is Ataciguat?
Ataciguat is an investigational drug currently being studied in clinical trials. It is being explored for its potential to address cardiovascular conditions, particularly those affecting the aortic valve. Researchers are investigating if Ataciguat can slow the progression of valve calcification, which is a hardening of the heart valves. Studies also aim to determine if it can reduce systemic inflammation and prevent left ventricular dysfunction, a condition where the heart's main pumping chamber does not function optimally. Additionally, Ataciguat is being studied for its effects on blood pressure and orthostatic tolerance, which is the body's ability to maintain blood pressure when changing positions, such as standing up.
Uses and Conditions Under Study
Ataciguat is currently being investigated for several conditions, primarily focusing on cardiovascular health. A total of 5 clinical trials have been conducted or are ongoing, involving 1,970 participants.
- Aortic Valve Stenosis: This condition involves the narrowing of the aortic valve, which can restrict blood flow from the heart to the rest of the body. Ataciguat is being studied for its potential to slow the progression of valve calcification and improve heart function in patients with calcific aortic valve stenosis. A total of 3 trials are investigating Ataciguat for aortic valve stenosis, including those with moderate forms of the condition.
- Intermittent Claudication: This condition causes pain in the legs during exercise due to reduced blood flow, often caused by peripheral artery disease. One trial is exploring whether Ataciguat could offer benefits for individuals experiencing intermittent claudication, possibly by improving blood flow or reducing inflammation.
- Pain: Ataciguat is also being studied in one trial for its potential role in managing pain. The specific type of pain or mechanism of action in this context is under investigation.
Dosing
Ataciguat has been studied for oral administration in clinical trials. The dosage forms investigated include Ataciguat and Ataciguat (HMR1766), along with other forms denoted as 1, 2, 3, 4, and 5 in trial records, suggesting different presentations or strengths. One trial specifically investigated an oral dose of 200 mg taken once daily for a period of 28 days. Another study involved daily administration for an extended duration, up to 156 weeks. The specific dosing regimen, including strength and duration, is determined by the condition being studied and the objectives of each clinical trial. All clinical trials for Ataciguat have focused on adult participants.
Side Effects
In a clinical trial, the most common side effects reported by patients taking Ataciguat were fatigue, rash/dry skin, and shortness of breath (dyspnea). These effects were generally more frequent in patients receiving Ataciguat compared to those on placebo.
- Tiredness or Fatigue: 25.0% of patients taking Ataciguat experienced fatigue, compared to 8.3% on placebo.
- Rash or Dry Skin: 25.0% of patients on Ataciguat reported rash or dry skin, while no patients on placebo experienced these symptoms.
- Shortness of Breath (Dyspnea): 25.0% of patients taking Ataciguat experienced shortness of breath, compared to 16.7% on placebo.
- Diarrhea: 16.7% of patients on Ataciguat reported diarrhea, while no patients on placebo experienced this.
- Ankle Swelling (Edema): 16.7% of patients taking Ataciguat experienced ankle swelling, compared to 8.3% on placebo.
- Chest Pain or Tightness: 16.7% of patients on Ataciguat reported chest pain or tightness, compared to 8.3% on placebo.
- Dry Mouth: 8.3% of patients taking Ataciguat experienced dry mouth, while no patients on placebo reported this symptom.
Clinical Trial Results
Clinical trials have investigated Ataciguat for its effects on aortic valve calcification, a condition where calcium builds up on the heart's aortic valve, potentially leading to narrowing and impaired heart function. One completed study, NCT02481258, evaluated the effects of Ataciguat (also known as HMR1766) on various measures related to aortic valve health.
Aortic Valve Calcification
In the study, patients taking Ataciguat showed a significantly smaller increase in aortic valve calcium levels over time compared to those taking placebo. On average, patients on Ataciguat experienced an increase of 65 arbitrary units in calcium levels, while those on placebo saw an increase of 215 arbitrary units. This suggests that Ataciguat may slow the progression of calcification on the aortic valve.
Aortic Valve Function
The trial also assessed changes in aortic valve function. The aortic valve area, which typically decreases as calcification worsens, showed a smaller reduction in patients treated with Ataciguat. The mean change in aortic valve area was a decrease of 0.07 cm2 for patients on Ataciguat, compared to a decrease of 0.129 cm2 for those on placebo. A smaller decrease indicates better preservation of valve opening.
Another measure of valve function, the transvalvular pressure gradient (which reflects the pressure difference across the valve), also showed a more favorable outcome with Ataciguat. The mean increase in pressure gradient was 1.8 mm Hg for Ataciguat patients, compared to an increase of 3.6 mm Hg for placebo patients. A smaller increase in pressure gradient suggests less obstruction to blood flow through the valve.
Left Ventricular Function
The study also examined changes in left ventricular function, a measure of the heart's pumping ability. Patients taking Ataciguat experienced a mean increase of 0.6 percent in left ventricular function, while those on placebo saw a mean decrease of 2.8 percent. This suggests that Ataciguat may help maintain or slightly improve overall heart function, whereas heart function tended to decline in the placebo group.
Currently Recruiting Trials
Ataciguat is currently being investigated in a significant clinical trial aimed at addressing a common heart condition. This study offers an opportunity for eligible patients to contribute to medical research and potentially benefit from a new therapeutic approach.
One pivotal study, sponsored by Kardigan, Inc., is actively recruiting participants. This Phase 2/Phase 3 randomized, placebo-controlled trial, known as NCT07001800, is titled "Ataciguat for Slowing the Progression of Moderate Calcific Aortic Valve Stenosis." The primary goal of this research is to determine if ataciguat can effectively slow down the worsening of moderate calcific aortic valve stenosis in adult patients. The study has an ambitious enrollment target of 1,276 participants, reflecting its importance and the need for robust data. Individuals with moderate aortic valve stenosis who meet specific criteria may be eligible to participate in this important investigation.
Where to Participate
The clinical trial for Ataciguat is designed to be widely accessible, with study sites established across the United States. There are 66 sites located in 60 cities across 24 states, making it convenient for many patients to consider participation.
Top participating locations include:
- Nashville, Tennessee (2 sites)
- Houston, Texas (2 sites)
- Boston, Massachusetts (2 sites)
- Cincinnati, Ohio (2 sites)
- Baltimore, Maryland (2 sites)
- Newport Beach, California (1 site)
- Los Angeles, California (1 site)
- Peoria, Arizona (1 site)
- Atlantis, Florida (1 site)
- Torrance, California (1 site)
Eligibility criteria for the main recruiting study include individuals aged 50 years. The study is open to participants of all genders, but it is not seeking healthy volunteers, nor are children eligible to participate.
Development Timeline
The journey of Ataciguat in clinical development began on March 5, 2007, with its very first clinical trial. Since then, the drug has been explored for various conditions, demonstrating an evolving understanding of its potential therapeutic applications. Initially, early investigations focused on conditions such as Irritable Bowel Syndrome with Constipation (IBS-C) and hyperphosphatemia.
Over time, the development pipeline for Ataciguat expanded significantly. The drug's potential was recognized for other critical areas, leading to studies in moderate aortic valve stenosis and pain management. This expansion reflects a strategic shift in research focus, driven by new scientific insights.
To date, a total of five clinical trials have been conducted or are ongoing, involving 1,970 participants. These studies have progressed through various phases, including one Phase 1 trial, three Phase 2 trials, and one combined Phase 2/Phase 3 trial, which is currently recruiting. Several sponsors have played a role in Ataciguat's development, including Sanofi, Jordan D. Miller, Ph.D., Mayo Clinic, and most recently, Kardigan, Inc., which is sponsoring the latest large-scale study. The latest trial is projected to conclude by June 3, 2025, marking a significant milestone in the drug's ongoing evaluation.