CLINICAL TRIALS PROFILE FOR AVANDIA

All Clinical Trials for avandia

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00006185 ↗	Underlying Abnormalities in Fat and Muscle Leading to Lipodystrophy Syndrome	Completed	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)	Phase 1	1999-09-01	With the advent of highly active anti-retroviral therapy(HAART), patients with HIV disease are developing a series of metabolic abnormalities including peripheral fat wasting, increase in truncal fat, high serum triglyceride levels, insulin(a hormone that controls blood sugar) resistance with an increased incidence of Type 2 Diabetes Mellitus and elevated blood pressure. The premise of this study is that abnormalities in the ability of fat and muscle tissue to respond to the hormone insulin may be the cause of the diabetes mellitus, high serum triglyceride levels and abnormal fat distribution. The purpose of the study is to assess how insulin resistant patients with HIV disease are and if their fat and muscle tissue are responding abnormally to insulin. This is done by administering insulin and taking small tissue samples of fat and muscle from the upper thigh and assessing how good insulin acts in these tissues. Patients with HIV disease will be admitted into the study after undergoing a screening medical history and examination. Once patients qualify, they will have their insulin resistance measured as well as the response of their fat and muscle to insulin; blood levels of glucose (sugar), cholesterol and triglycerides will be measured; body fat will be assessed using radiological tests; a detailed medical history will be obtained to assess risk factors for developing this syndrome. Patients who are found to be insulin resistant will be offered a trial of an insulin sensitizing agent, called Avandia, for 6-12 weeks. It is hoped that the Avandia will restore the body's ability to respond normally to insulin (as it does in patients with Diabetes) and perhaps improve the fat abnormalities as well. All the same measures will be performed at the end of the course of Avandia as were done at baseline. Patients who are not insulin resistant will be asked to come back yearly to assess whether they develop insulin resistance over time. This study will continue to recruit patients over the next 3 years.
NCT00025753 ↗	Rosiglitazone and Exercise Training: Effects on HIV-Infected People With Insulin Resistance, Hypertriglyceridemia, and Adipose Tissue Maldistribution	Completed	The Campbell Foundation	N/A	1969-12-31	Several complications have become prevalent in people living with HIV/AIDS, including increased blood sugar, increased blood fats and cholesterol, and fat tissue redistribution. The causes of these complications are not well understood and effective treatments have not been identified. We propose to test the efficacy and safety of 2 treatments for these complications in people living with HIV/AIDS: aerobic, weight lifting exercise training, and a new insulin-sensitizing agent called rosiglitazone (Avandia). Exercise and rosiglitazone have been effective and moderately safe when used in HIV-seronegative people with diabetes, but a specific trial is needed to test efficacy and safety in people living with HIV/AIDS.
NCT00025753 ↗	Rosiglitazone and Exercise Training: Effects on HIV-Infected People With Insulin Resistance, Hypertriglyceridemia, and Adipose Tissue Maldistribution	Completed	National Center for Research Resources (NCRR)	N/A	1969-12-31	Several complications have become prevalent in people living with HIV/AIDS, including increased blood sugar, increased blood fats and cholesterol, and fat tissue redistribution. The causes of these complications are not well understood and effective treatments have not been identified. We propose to test the efficacy and safety of 2 treatments for these complications in people living with HIV/AIDS: aerobic, weight lifting exercise training, and a new insulin-sensitizing agent called rosiglitazone (Avandia). Exercise and rosiglitazone have been effective and moderately safe when used in HIV-seronegative people with diabetes, but a specific trial is needed to test efficacy and safety in people living with HIV/AIDS.
NCT00032487 ↗	Glycemic Control and Complications in Diabetes Mellitus Type 2 (VADT)	Completed	National Eye Institute (NEI)	Phase 3	2000-12-01	This study is a prospective, 2-arm, randomized controlled trial to determine whether glycemic control, achieved through intensification of treatment, is effective in preventing clinical macrovascular complications in patients with type 2 DM who are no longer responsive to oral agents alone. The study consists of a two-year accrual period and five years of follow-up (7 years total) of 1700 patients across 20 centers. We have powered the study to detect a 21% reduction in the primary event rate. Additional study goals are to determine whether the expenditures, discomfort, and adverse effects associated with intensive intervention are justified in terms of their clinical benefits, considering both macrovascular and microvascular complications.
NCT00032487 ↗	Glycemic Control and Complications in Diabetes Mellitus Type 2 (VADT)	Completed	SmithKline Beecham	Phase 3	2000-12-01	This study is a prospective, 2-arm, randomized controlled trial to determine whether glycemic control, achieved through intensification of treatment, is effective in preventing clinical macrovascular complications in patients with type 2 DM who are no longer responsive to oral agents alone. The study consists of a two-year accrual period and five years of follow-up (7 years total) of 1700 patients across 20 centers. We have powered the study to detect a 21% reduction in the primary event rate. Additional study goals are to determine whether the expenditures, discomfort, and adverse effects associated with intensive intervention are justified in terms of their clinical benefits, considering both macrovascular and microvascular complications.
NCT00032487 ↗	Glycemic Control and Complications in Diabetes Mellitus Type 2 (VADT)	Completed	VA Office of Research and Development	Phase 3	2000-12-01	This study is a prospective, 2-arm, randomized controlled trial to determine whether glycemic control, achieved through intensification of treatment, is effective in preventing clinical macrovascular complications in patients with type 2 DM who are no longer responsive to oral agents alone. The study consists of a two-year accrual period and five years of follow-up (7 years total) of 1700 patients across 20 centers. We have powered the study to detect a 21% reduction in the primary event rate. Additional study goals are to determine whether the expenditures, discomfort, and adverse effects associated with intensive intervention are justified in terms of their clinical benefits, considering both macrovascular and microvascular complications.
NCT00065065 ↗	A Trial of Rosiglitazone for Ulcerative Colitis	Completed	GlaxoSmithKline	Phase 2	2002-09-01	This is a multicenter, randomized, double-blind, placebo-controlled study evaluating rosiglitazone: 4 mg tablets or placebo tablets administered orally twice daily for 12 weeks. The purpose of the study is to evaluate the efficacy and safety of rosiglitazone in the treatment of mild to moderately active ulcerative colitis. Disease activity will be measured using a standard disease activity index. Calculation of the index requires patients to undergo flexible sigmoidoscopy at the start of the study and at week 12.

Clinical Trial Conditions for avandia

Condition Name

Condition Name for avandia
Intervention	Trials
Diabetes Mellitus, Type 2	10
Insulin Resistance	9
Type 2 Diabetes Mellitus	9
HIV Infections	4

Condition MeSH

Condition MeSH for avandia
Intervention	Trials
Diabetes Mellitus	25
Diabetes Mellitus, Type 2	24
Insulin Resistance	12
HIV Infections	4

Clinical Trial Locations for avandia

Trials by Country

Trials by Country for avandia
Location	Trials
United States	187
Germany	30
Canada	23
Mexico	15
Italy	13

Trials by US State

Trials by US State for avandia
Location	Trials
Texas	13
California	12
New York	12
Massachusetts	9
Pennsylvania	9

Clinical Trial Progress for avandia

Clinical Trial Phase

Clinical Trial Phase for avandia
Clinical Trial Phase	Trials
Phase 4	17
Phase 3	13
Phase 2/Phase 3	2

Clinical Trial Status

Clinical Trial Status for avandia
Clinical Trial Phase	Trials
Completed	48
Terminated	5
Unknown status	4

Clinical Trial Sponsors for avandia

Sponsor Name

Sponsor Name for avandia
Sponsor	Trials
GlaxoSmithKline	23
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)	4
Merck Sharp & Dohme Corp.	3

Sponsor Type

Sponsor Type for avandia
Sponsor	Trials
Other	57
Industry	46
NIH	12

Avandia Market Analysis and Financial Projection

Avandia: A Comprehensive Review of Clinical Trials, Market Analysis, and Projections

Introduction

Avandia, also known as rosiglitazone, is a medication developed by GlaxoSmithKline (GSK) to treat Type 2 diabetes. The drug has been at the center of significant controversy and scrutiny, particularly regarding its cardiovascular safety. This article provides an update on the clinical trials, market analysis, and projections for Avandia.

Clinical Trials and Safety Concerns

The RECORD Trial

One of the most pivotal studies on Avandia was the RECORD (Rosiglitazone Evaluated for Cardiovascular Outcomes and Regulation of Glycemia in Diabetes) trial. Conducted over an average of 5.5 years, this large, long-term study compared Avandia to metformin and sulfonylurea. The results showed that the overall rates of cardiovascular hospitalization and death were similar between the two groups, indicating no increased overall cardiovascular risk associated with Avandia compared to other commonly used diabetes medicines[3].

Cardiovascular Risks and Adjudications

Despite the RECORD trial's findings, concerns about Avandia's cardiovascular safety persisted. An independent team from the Duke Clinical Research Institute, commissioned by the FDA, re-evaluated the data from the RECORD trial. This re-adjudication process, which is rare and occurred after the drug's approval, concluded that Avandia did not present a serious cardiovascular risk to diabetes patients. However, it highlighted flaws in the trial's design, such as its unblinded nature, which could have influenced the outcome[1].

Additional Safety Findings

The RECORD trial also noted that Avandia was associated with a higher risk of congestive heart failure (CHF) and bone fractures, particularly in women. These findings were consistent with the known effects of thiazolidinediones (TZDs), the class of drugs to which Avandia belongs[3].

Market Impact and Analysis

Sales and Market Share

Avandia was once GSK's second-best-selling drug, with global sales of $3.3 billion in the year preceding the major controversy. However, following the publication of a report by the Cleveland Clinic suggesting Avandia increased the risk of heart attacks by 43%, the drug's sales plummeted. In contrast, prescriptions for Actos, a competing drug from Takeda Pharmaceuticals, rose significantly during the same period[2].

Competitive Landscape

The controversy surrounding Avandia significantly benefited its competitor, Actos. Actos saw a 13% increase in sales in the weeks following the Cleveland Clinic's report, while Avandia's prescriptions dropped dramatically. This shift in market share was further exacerbated by the FDA's requirement for both GSK and Takeda to strengthen warnings on their drugs' labeling regarding the risk of heart failure[2].

Regulatory Actions and Implications

FDA Advisory Panels and Restrictions

The FDA imposed tight restrictions on Avandia in 2010 and 2011 due to concerns over its cardiovascular safety. However, following the re-adjudication by the Duke Clinical Research Institute, an FDA advisory panel voted to ease these restrictions in June 2013. Despite this, GSK did not plan to relaunch Avandia in the United States, citing the drug's irreparably damaged reputation[1].

TIDE Trial and Settlements

The FDA advisory panel also recommended the continuation of the TIDE (Thiazolidinedione Intervention with Vitamin D Evaluation) trial, which compared Avandia with Actos. Additionally, GSK agreed to pay $460 million to settle a class action lawsuit related to Avandia's safety concerns[5].

Legacy and Impact on Drug Development

Enhanced Safety Trials

The controversy surrounding Avandia led to a significant change in the FDA's approval process for diabetes drugs. The agency now requires cardiovascular safety trials for all new therapies for Type 2 diabetes, a requirement that adds several years and substantial costs to the drug development process. While this ensures a higher standard of safety, it also consumes valuable resources and may delay the development of other important trials[1].

Market Projections

Current Status

Given the severe damage to Avandia's reputation and the lack of plans by GSK to relaunch it in the United States, the drug's market prospects are bleak. The focus has shifted to other diabetes medications that have not been marred by similar safety concerns.

Future of Diabetes Treatment

The landscape for Type 2 diabetes treatment continues to evolve with new medications and therapies being developed. The emphasis on cardiovascular safety, driven in part by the Avandia controversy, ensures that future treatments will undergo rigorous testing to mitigate potential risks.

Key Takeaways

• Clinical Trials: The RECORD trial and subsequent re-adjudications found no increased overall cardiovascular risk associated with Avandia, but highlighted other safety concerns.
• Market Impact: The controversy led to a significant decline in Avandia's sales and market share, benefiting competitors like Actos.
• Regulatory Actions: The FDA imposed and later eased restrictions on Avandia, but the drug's reputation was irreparably damaged.
• Legacy: The Avandia controversy resulted in stricter safety trials for diabetes drugs, adding time and cost to the development process.
• Market Projections: Avandia's market prospects are limited, with the focus shifting to other diabetes treatments.

FAQs

What were the main findings of the RECORD trial regarding Avandia?

The RECORD trial found that Avandia did not increase the overall cardiovascular risk compared to other commonly used diabetes medicines, but it did show a higher risk of congestive heart failure and bone fractures[3].

How did the controversy around Avandia affect its market share?

The controversy led to a significant decline in Avandia's prescriptions and sales, while its competitor Actos saw an increase in market share[2].

What regulatory actions were taken against Avandia?

The FDA imposed tight restrictions on Avandia in 2010 and 2011, which were later eased in 2013. However, GSK did not plan to relaunch the drug in the United States[1].

How has the Avandia controversy impacted the development of new diabetes drugs?

The controversy led to the requirement for cardiovascular safety trials for all new Type 2 diabetes therapies, adding time and cost to the drug development process[1].

What is the current status of Avandia in the market?

Avandia is no longer being promoted in the United States, and its market prospects are limited due to its damaged reputation[1].

What are the implications of the TIDE trial for Avandia and Actos?

The TIDE trial, which compares Avandia with Actos, was recommended to continue by the FDA advisory panel. However, the trial's outcomes did not change the market dynamics significantly, as Avandia's reputation had already been severely impacted[5].

Sources

1. FDA 'Mea Culpa' Part of a Cautionary Tale - AJMC
2. Actos gains market share at Avandia's expense - MM+M
3. Large, long-term study shows Avandia has no increased overall cardiovascular risk - GSK
4. Avandia Cardiovascular Event Modeling Project - GSK Study Register
5. Avandia to Remain on the Market - U.S. Pharmacist