Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: AstraZeneca
Trial Summary
What is the purpose of this trial?This trial tests a new drug called AZD1705 in people with abnormal blood lipid levels. It aims to see if the drug is safe and how it behaves in the body. The study involves different doses and includes monitoring to observe effects.
Is the drug AZD1705 a promising treatment for dyslipidemia?The information provided does not mention AZD1705 specifically, so we can't determine if it's promising based on these articles. However, the articles highlight the importance of managing dyslipidemia with effective treatments, suggesting that new drugs like AZD1705 could be valuable if they show similar benefits.1561011
What safety data is available for AZD1705 in treating dyslipidemia?The provided research articles do not mention AZD1705 or provide specific safety data for this treatment. They discuss general safety and efficacy of lipid-lowering therapies, particularly statins, in managing dyslipidemia. Statins are noted for their effectiveness in reducing LDL cholesterol and associated cardiovascular risks, but they can increase the risk of myopathy and hepatotoxicity. The safety of combining statins with fibrates is still under investigation. However, no specific safety data for AZD1705 is available in the provided research.248912
What data supports the idea that AZD1705 for Dyslipidemia is an effective drug?The available research shows that statins, a class of drugs used to treat dyslipidemia, are very effective in lowering bad cholesterol levels and reducing the risk of heart disease. They are well-tolerated and have high patient compliance. While there is no specific data on AZD1705, statins in general have shown promising results in reducing cholesterol and improving heart health. This suggests that AZD1705, if it is similar to statins, could also be effective for treating dyslipidemia.3471314
Do I have to stop taking my current medications for the trial?The trial protocol does not specify that you must stop taking your current medications. However, if you are participating in Parts B1 or B3, you should be on stable medication for at least 3 months before screening and should not plan any medication or dose changes during the study. For Part A, you cannot use any prescribed or nonprescribed medication, including certain over-the-counter drugs, two weeks before the study starts.
Eligibility Criteria
This trial is for Japanese or Chinese adults with dyslipidemia who have stable veins for blood draws, are on a steady statin treatment for at least 3 months, and have a BMI of 18-35. Women must not be able to bear children and need a negative pregnancy test. Smokers or those with recent serious health issues can't join.Inclusion Criteria
I am not pregnant.
I am not able to have children and have veins suitable for frequent needle insertions.
Exclusion Criteria
I have a condition that affects how drugs are broken down in my body.
Treatment Details
The study tests AZD1705's safety and how the body processes it in people with high lipid levels compared to a placebo (a substance with no active drug). Participants will randomly receive either AZD1705 or the placebo.
12Treatment groups
Active Control
Placebo Group
Group I: Part B2 (AZD1705)Active Control1 Intervention
Japanese participants not receiving statin therapy will receive AZD1705 subcutaneously on Day 1 and Day 29.
Group II: Part B3 (AZD1705)Active Control1 Intervention
Participants who may or may not be receiving moderate- or high-intensity statin therapy and with the additional diagnosis of type 2 diabetes will receive AZD1705 subcutaneously on Day 1 and Day 29.
Group III: Part A1 (AZD1705)Active Control1 Intervention
Non-Asian participants will receive AZD1705 subcutaneously on Day 1.
Group IV: Part A2 (AZD1705)Active Control1 Intervention
Japanese participants will receive AZD1705 subcutaneously on Day 1.
Group V: Part A3 (AZD1705)Active Control1 Intervention
Chinese participants will receive AZD1705 subcutaneously on Day 1.
Group VI: Part B1 (AZD1705)Active Control1 Intervention
Non-Asian participants who may or may not be receiving moderate- or high-intensity statin therapy will receive AZD1705 subcutaneously on Day 1 and Day 29.
Group VII: Part A3 (Placebo)Placebo Group1 Intervention
Chinese participants will receive placebo on Day 1.
Group VIII: Part A2 (Placebo)Placebo Group1 Intervention
Japanese participants will receive placebo on Day 1.
Group IX: Part A1 (Placebo)Placebo Group1 Intervention
Non-Asian participants will receive placebo on Day 1.
Group X: Part B2 (Placebo)Placebo Group1 Intervention
Japanese participants not receiving statin therapy will receive placebo on Day 1 and Day 29.
Group XI: Part B3 (Placebo)Placebo Group1 Intervention
Participants who may or may not be receiving moderate- or high-intensity statin therapy and with the additional diagnosis of type 2 diabetes will receive placebo on Day 1 and Day 29.
Group XII: Part B1 (Placebo)Placebo Group1 Intervention
Non-Asian participants who may or may not be receiving moderate- or high-intensity statin therapy will receive placebo on Day 1 and Day 29.
Find a clinic near you
Research locations nearbySelect from list below to view details:
Research SiteSan Antonio, TX
Research SiteJacksonville, FL
Research SiteWinter Park, FL
Research SiteBrooklyn, MD
More Trial Locations
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Who is running the clinical trial?
AstraZenecaLead Sponsor
ParexelIndustry Sponsor
References
Management of blood lipid abnormalities in coronary heart disease patients. [2019]Information obtained from clinical and laboratory research strongly supports a causal relationship between hyperlipidemia (dyslipidemia) and coronary heart disease (CHD), and provides an impetus to develop strategy for control of dyslipidemia. Some recent developments in the field may include the use of: (1) colestipol-niacin to control hypercholesterolemia and induce regression of coronary atherosclerosis; (2) limited amounts of foods rich in stearic or oleic fatty acids to enhance the appeal of cholesterol-lowering regimen; (3) gemfibrozil or lovastatin to inhibit cholesterol synthetic activity; and (4) gemfibrozil to raise atherosclerosis-protective plasma high-density lipoprotein levels. These and other newer developments will stimulate interest in research on dyslipidemia and its control to facilitate primary and secondary prevention of CHD.
Management of dyslipidemia in adults. [2017]The importance of treating dyslipidemias based on cardiovascular risk factors is highlighted by the National Cholesterol Education Program guidelines. The first step in evaluation is to exclude secondary causes of hyperlipidemia. Assessment of the patient's risk for coronary heart disease helps determine which treatment should be initiated and how often lipid analysis should be performed. For primary prevention of coronary heart disease, the treatment goal is to achieve a low-density lipoprotein (LDL) cholesterol level of less than 160 mg per dL (4.15 mmol per L) in patients with only one risk factor. The target LDL level in patients with two or more risk factors is 130 mg per dL (3.35 mmol per L) or less. For patients with documented coronary heart disease, the LDL cholesterol level should be reduced to less than 100 mg per dL (2.60 mmol per L). A step II diet, in which the total fat content is less than 30 percent of total calories and saturated fat is 8 to 10 percent of total calories, may help reduce LDL cholesterol levels to the target range in some patients. A high-fiber diet is also therapeutic. The most commonly used options for pharmacologic treatment of dyslipidemia include bile acid-binding resins, HMG-CoA reductase inhibitors, nicotinic acid and fibric acid derivatives. Other possibilities in selected cases are estrogen replacement therapy, plasmapheresis and even surgery in severe, refractory cases.
Control of lipid disorders in patients with atherosclerotic vascular disease. [2019]The primary dyslipidemias are associated with an increased incidence of atherosclerotic vascular disease in coronary, cerebral, and peripheral vessels. If nonpharmacologic therapy, such as dietary changes and aerobic exercise, fails to achieve the therapeutic goal levels for serum low-density lipoprotein cholesterol, high-density lipoprotein (HDL) cholesterol, and triglycerides suggested by the National Cholesterol Education Program Adult Treatment Panel, pharmacologic intervention is indicated. The choice of the class of lipid-lowering drug(s) for initial therapy and subsequent therapy depends on the nature of the dyslipidemia, e.g., hypercholesterolemia, hypertriglyceridemia, suppressed HDL cholesterol levels, or combinations of these disturbances in lipid metabolism. Appropriate therapy with the highly efficacious agents currently available significantly reduces the associated morbidity and mortality related to atherosclerosis. The clinical applications of these classes of agents are discussed here.
Clinical positioning of HMG-CoA reductase inhibitors in lipid management protocols. [2018]Drug treatment of dyslipidaemia has progressed dramatically over the past decade. Of the available drugs, HMG-CoA reductase inhibitors (statins) have emerged as very effective and important treatments for dyslipidaemia. These agents potently reduce low density lipoprotein (LDL) cholesterol levels (the main lipid target in management protocols and treatment guidelines) and have produced significant reductions in coronary heart disease (CHD) related morbidity and mortality, as well as overall mortality, in large intervention studies. They have also been shown to reduce progression and increase regression of coronary atherosclerosis. Statins are generally well tolerated and are thus associated with high patient compliance in comparison with the other classes of medications used for dyslipidaemia. There are minimal studies to date with these agents in patients with elevated triglycerides, either with or without accompanying elevated cholesterol levels. Preliminary results with statins in patients with hypertriglyceridaemia are promising, with reductions in triglycerides of 26 and 46%, respectively, having been reported following treatment with simvastatin and atorvastatin. Therefore, statins can be considered first-line drugs in many patients with elevated total and/or LDL-cholesterol levels according to treatment guidelines.
Lipid-lowering therapy in diabetes mellitus. [2022]Dyslipidemia emerges as an important modifiable risk factor for cardiovascular disease in diabetes mellitus, especially as part of the metabolic syndrome in type 2 diabetes. In type 1 diabetes mellitus, tight glucose regulation usually will correct dyslipidemia. Both total cholesterol and triglyceride levels predict cardiovascular disease in diabetes, and HDL-cholesterol may prove to be an even better predictor. In type 2 diabetes, increased triglyceride and reduced HDL-cholesterol levels are the key characteristics of dyslipidemia. Increased hepatic VLDL production and impaired catabolism of triglyceride-rich particles contribute to hypertriglyceridemia. Subsequent formation of small dense LDL particles leads to increased atherogenicity. Small dense LDL particles have a longer circulation time, are susceptible to glycoxidation, and are taken up by macrophages and the vessel wall. Post-hoc analysis of diabetic subgroups in primary and secondary prevention trials suggest that individuals with diabetes may enjoy substantial cardiovascular risk reduction from lipid-lowering therapy. Trials prospectively addressing the benefit of lipid lowering therapy in diabetes are under way. Target levels for lipid lowering therapy in diabetes at present stem from pathophysiological plausibility rather than from clinical proof. Intensive lipid-lowering with a statin in adequate dosage or a combination of a statin and a fibrate may be used to lower LDL-cholesterol levels to values
Long-term safety and efficacy of a once-daily niacin/lovastatin formulation for patients with dyslipidemia. [2019]Combination therapy is increasingly recommended for patients with multiple lipid disorders, especially those at high risk for coronary events. We investigated the long-term safety and effectiveness of a new drug formulation containing once-daily extended-release niacin and lovastatin. A total of 814 men and women (mean age 59 years) with dyslipidemia were enrolled in a 52-week multicenter, open-label study. We used 4 escalating doses (niacin/lovastatin in milligrams): 500/10 for the first month, 1,000/20 for the second, 1,500/30 for the third, and 2,000/40 for the fourth month through week 52. Dose-dependent effects were observed for all major lipid parameters. At week 16, mean low-density lipoprotein (LDL) cholesterol and triglycerides were reduced by 47% and 41%, respectively; mean high-density lipoprotein (HDL) cholesterol was increased by 30% (all p 3 times the upper limit of normal was 0.5%. Once-daily niacin/lovastatin exhibits substantial effects on multiple lipid risk factors and represents a significant new treatment option in the management of dyslipidemia.
HDL-C and triglyceride levels: relationship to coronary heart disease and treatment with statins. [2019]The association between low-density lipoprotein cholesterol (LDL-C) levels and risk of coronary heart disease (CHD) is well established and LDL-C-lowering is currently the primary target for the treatment of dyslipidemia. However, low levels of high-density lipoprotein cholesterol (HDL-C), and high levels of triglycerides (TG) are also risk factors for CHD and modifying levels of these lipid subfractions, in addition to LDL-C lowering, may have clinical benefits in many patients. Statins are the first-line drug therapy for the treatment of dyslipidemia because of their efficacy in lowering LDL-C and good tolerability. Statins also have beneficial effects on TG and HDL-C levels although they differ in the degree to which they modify the levels of these lipoproteins. Improvements across the atherogenic components of the lipid profile may be optimized by the co-administration of a statin with a fibrate, niacin or omega-3 fatty acids; however, particular combination therapies have been associated with side effects and may be poorly tolerated. Newer combinations with better tolerability, or new statins with improved efficacy on non-LDL-C lipid subfractions, would be welcome additions to the currently available therapies for the treatment of dyslipidemia.
Management of dyslipidemias in the age of statins. [2019]Evidence for the effectiveness of lipid-lowering therapy in reducing CHD risk continues to emerge. In primary prevention, clinical trials have demonstrated a benefit for middle-aged, high-risk men with high LDL cholesterol and, more recently, for men and women with "average" LDL and low HDL cholesterol. Although low HDL cholesterol, small dense LDL particles, elevated lipoprotein (a), elevated apolipoprotein B, and the dyslipidemia of the metabolic syndrome pose an increased in CHD risk in some patients, the risk reduction with lipid-lowering therapy has not been fully investigated. The CHD risk of isolated hypertriglyceridemia remains uncertain. Very high triglyceride levels, however, should be treated to prevent pancreatitis. A lipid-lowering diet and other appropriate lifestyle changes constitute safe advice for all patients with dyslipidemia. In initiating pharmacologic therapy, physicians should view potential risk reduction in the context of a patient's overall CHD risk. The selection of particular medications can be individualized, considering effectiveness evidence from clinical trials, lipid-lowering potency, adverse effects, drug interactions, costs, and patient preferences.
Update on dyslipidemia. [2007]Recently, considerable progress has been made in understanding the genetic basis of dyslipidemias and in studying the safety and efficacy of lipid-lowering drugs for coronary heart disease (CHD) prevention. Novel loci have been identified for monogenic hypercholesterolemia, such as low-density lipoprotein (LDL) receptor (LDLR)-associated protein, proprotein convertase subtilisin-like kexin type 9, and ATP-binding cassette transporters ABCG5 and ABCG8. LDLR-associated protein promotes clustering of LDLRs into clathrin-coated pits for LDL uptake; proprotein convertase subtilisin-like kexin type 9 is involved in LDLR degradation; and ABCG5 and 8 pump sterols out of the hepatic and intestinal cells into bile and intestinal lumen, respectively. A novel gene encoding apolipoprotein AV, an activator of lipoprotein lipase, has also been linked to familial hypertriglyceridemia. Linkage of familial combined hyperlipidemia to upstream stimulatory factor 1 remains controversial. Recent guidelines of the Adult Treatment Panel III emphasize intensive reduction of LDL or non-high-density lipoprotein cholesterol in patients at high risk of CHD. However, of the four recently concluded trials comparing high- vs. low-dose statin therapy, only two showed an unequivocal reduction in cardiovascular endpoints. Because intensive statin therapy can increase the risk of myopathy and hepatotoxicity, it is important to consider its risk-benefit ratio in individual patients. Restriction of dietary saturated and trans-fat and cholesterol, along with increased intake of soluble fiber, can also achieve substantial LDL cholesterol lowering. Fibrates may reduce the risk of acute pancreatitis in severely hypertriglyceridemic patients and may be beneficial for CHD prevention. However, the safety and efficacy of combined therapy of fibrates and statins needs to be established.
LDL = 5: Virtues and dangers of multidrug therapy of low-density lipoprotein cholesterol. [2015]Multiple-drug therapy of dyslipidemia is frequently used to achieve treatment goals in high-risk patients with coronary artery disease. The authors report a case of a patient treated with a statin, fibrate, ezetimibe, and niacin in whom a calculated low-density lipoprotein cholesterol level of 5 mg/dL was achieved.
Pharmacokinetics, safety, and tolerability of saroglitazar (ZYH1), a predominantly PPARα agonist with moderate PPARγ agonist activity in healthy human subjects. [2021]Dyslipidaemia is a major cardiovascular risk factor associated with type 2 diabetes mellitus. Saroglitazar (ZYH1) is a novel peroxisome proliferator-activated receptor (PPAR) agonist with predominant PPARα and moderate PPARγ activity. It has been developed for the treatment of dyslipidaemia and has favourable effects on glycaemic parameters in type 2 diabetes mellitus. The objective of this phase 1 study was to evaluate the pharmacokinetics, safety and tolerability of saroglitazar in healthy human subjects.
Dyslipidemia Part 1--Review of Lipid Metabolism and Vascular Cell Physiology. [2022]Dyslipidemia, more specifically, high-serum low-density lipoproteins and low-serum high-density lipoproteins, are known risk factors for cardiovascular disease. The current clinical treatment of dyslipidemia represents the outcome of a large body of fundamental basic science research on lipids, lipid metabolism, and the effects of different lipids on cellular components of the artery, inflammatory cells, and platelets. In general, lower density lipids activate intracellular pathways to increase local and systemic inflammation, monocyte adhesion, endothelial cell dysfunction and apoptosis, and smooth muscle cell proliferation, resulting in foam cell formation and genesis of atherosclerotic plaque. In contrast, higher density lipids prevent or attenuate atherosclerosis. This article is part 1 of a 2-part review, with part 1 focusing on lipid metabolism and the downstream effects of lipids on the development of atherosclerosis, and part 2 on the clinical treatment of dyslipidemia and the role of these drugs for patients with arterial disease exclusive of the coronary arteries.
Management of Dyslipidemia in Type 2 Diabetes: Recent Advances in Nonstatin Treatment. [2023]Dyslipidemia is a major risk factor for cardiovascular disease (CVD), which is the leading cause of morbidity and mortality in type 2 diabetes (T2DM). Statins have played a crucial role in its management, but residual risk remains since many patients cannot achieve their desired low-density lipoprotein cholesterol (LDL-C) level and up to 20% of patients are statin-intolerant, experiencing adverse events perceived to be caused by statins, most commonly muscle symptoms. Recently, great advances have been made in nonstatin treatment with ezetimibe, a cholesterol absorption inhibitor, and proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibodies (mAbs), all showing a proven benefit with an excellent safety profile in cardiovascular outcome trials. This review summarizes the key aspects and the evolving role of these agents in the management of dyslipidemia in patients with T2DM, along with a brief introduction of novel drugs currently in development.
Best practice for treating dyslipidaemia in patients with diabetes based on current international guidelines. [2021]Dyslipidaemia is a major modifiable risk factor for atherosclerotic cardiovascular disease (ASCVD) in type 2 diabetes. We provide an in-context overview of recent trials of lipid-lowering pharmacotherapies and of recommendations from international guidelines for managing dyslipidaemia in patients with diabetes.