Indian suspends rosiglitazone (Avandia) studies comparing Actos in diabetes patients on higher heart-risk data

Rosiglitazone (Avandia) has been undergoing clinical studies in patients in 19 sites across India

Indian government has ordered Glaxo Smith Kline to suspend human studies using the controversial anti-diabetic drug rosiglitazone (Avandia) following recent publication of a study implicating the drug with increased risk of heart disease in diabetic patients.

Rosiglitazone (Avandia) has been undergoing clinical studies in patients in 19 sites across India.

GlaxoSmithKline has been given permission by the Drugs Controller General of India (DCGI) Dr Surinder Singh has already given permission to the Glaxo to conduct a trial involving rosiglitazone in ten hospitals in India

Patient enrolement for the study tittled “Thiazolidinedione Intervention in vitamin D Evaluation (TIDE)” trial on rosiglitazone (Avandia) has already begun in some centres including St Johns Medical College, Bangalore, reports said.

TIDE, which began last year, was slated to enroll about 16,000 people globally and run through 2015. Its aim is to test the cardiovascular safety of Avandia versus another leading diabetes drug Actos from Takeda Pharmaceutical Co.

Other Indian trial centres listed for rosiglitazone studies are in Mumbai, Nasik, Pune, Cochin (two), Kottayam, Trichy, Vijayawada and Karnal.

“The DCGI (Drug Controller General of India) has written to Quintiles, the clinical research organisation (CRO) running this trial in India, requesting that it be placed on hold with immediate effect. Accordingly, all sites in India participating on the TIDE study were informed of the hold status by letter on Wednesday 30th June 2010,”a spokesperson for Glaxo Smith Kline (GSK) has said.

The reason stated by the DCGI was recent publication of a cohort observational study and a meta analysis concerning rosiglitazone.

GSK, the principal investigators of TIDE and the CRO involved will provide the DCGI with any further data or information it requires in advance of a final decision on this study being made, the GSK spokesperson said.

A study published in 2009 comparing adverse effects in 39,000 people who used either Avandia or Actos starting between 2002 and 2008, found higher risk of congestive heart failure and death from any cause in patients taking rosiglitazone (Avandia).

It is estimated that one additional hospitalization for heart failure would occur annually for every 120 patients prescribed rosiglitazone (Avandia) rather than Actos, and that one additional death would occur each year for every 269 patients treated with rosiglitazone (Avandia) rather than Actos.

If the trial continues, the health of thousands of patients will be jeopardized. It is unethical to continue this trial, NGOs and other medical experts warned.

GlaxoSmithKline has been facing a lot of criticism from NGOs and other human rights group for promoting rosiglitazone despite several studies proving that the anti-diabetes medication could lead to heart attacks and even death in patients using them to control their blood sugar.

However, several trial sites in US and Europe for conducting rosiglitazone TIDE studies are being closed as they are not getting patients for recruitment.

Glaxo settled thousands more Avandia lawsuits from patients claiming compensation for injuries and deaths allegedly caused by rosiglitazone.

Glaxo has settled an estimated 5,000 of consolidated cases that had been slated for court in Philadelphia in June.

This is the second Avandia settlement in less than a month. Glaxo settled 700 suits in May, promising to pay a total of $60 million to those plaintiffs.

Glaxo now faces some 13,000 claims over the diabetes drug rosiglitazone.

Many physicians stopped prescribing rosiglitazone following a study in 2007 that linked the diabetes drug with an increased risk of heart attack and other cardiovascular side effects.

The Saudi Arabian drug regulatory agency has recently removed Avandia from the market.

US FDA has ordered a black box warning to be placed on Avandia (but not Actos) because of concerns about heart attacks.

Both the American and the European Diabetes Associations advised unanimously advised against using rosiglitazone in 2008, based on unfavourable data on the drug.

However, a U.S. Food and Drug Administration advisory panel voted to keep Avandia on the market, this week, though some panel members voted for its removal.The same panel subsequently voted that the Tide study should continue if Avandia remains on the market.

Since 2007 we have seen results from six controlled clinical trials looking at the cardiovascular safety of Avandia and together they show that this medicine does not increase the overall risk of heart attack, stroke or death, GlaxoSmith Kline said in a recent statement.