HHS Report Criticizes FDA’s Human Subject Protection Efforts and Lack of Site Audits

By Steve Zisson

The U.S. Food and Drug Administration (FDA) audited fewer than 1% of investigative sites, the inspector general of the Department of Health and Human Services (HHS), Daniel R. Levinson, found in a report released Friday.

The 41-page report said the FDA has just 200 specially-trained inspectors to audit an estimated 350,000 investigative sites. Others estimate that the number of sites is much lower.

The report found that federal health officials did not even know how many clinical trials were being conducted in the U.S. According to CenterWatch, an estimated 59,000 drug trials, phases I, II and III, were being conducted worldwide in 2006.

The Office of Inspector General (OIG) investigated after receiving a congressional request to review FDA’s oversight of clinical trials  a series of news articles highlighted vulnerabilities, the OIG report said. “The series identified problems with FDA’s oversight of clinical trials, including insufficient informed consent procedures, inadequate training and certification requirements for IRBs, limited Federal regulations, and FDA’s failure to enforce existing regulations,” the OIG report added.

The report said FDA “views its protocol review before a clinical trial commences as the most important step in protecting human subjects. We recognize the important role that FDA’s protocol review plays in protecting human subjects and made several changes to our report to reflect this point. We do note, however, that this report addresses another important part of the system for protecting human subjects: oversight of the trials once they are actually underway.”

Levinson’s report said that when those overburdened inspectors found serious problems in clinical trials, their superiors in Washington downgraded their findings 68% of the time. And the report found that in the remaining cases, the FDA almost never followed up with inspections to determine whether the corrective actions that the agency specified had been done.

“The report issued today by the Department of Health and Human Services Office of Inspector General offers valuable insight into FDA’s program to protect clinical trial participants. The agency agrees with the report and is already acting on all its recommendations. Volunteers play a critical role in making treatments available that help millions of patients and FDA is committed to ensuring strong oversight to protect participants,” said Heidi Rebello, spokesperson for Office of the Commissioner at the FDA.

As its mission has grown, FDA has been widely criticized as underfunded in numerous areas beyond clinical trials, such as drug importation and food safety.

The HHS’ inspector general found the FDA disqualified investigators from conducting clinical trials 26 times from 2000 to 2005 and disqualified their data only twice even though the agency found serious problems at trial sites 348 times during that period.

The inspector general also recommended that the agency create a registry of continuing clinical trials, launch a registry of research ethics boards, build a database to track its research inspections and get more authority to regulate research assistants.

OIG identified five steps that could take to improve its system of oversight:

• Develop a comprehensive internal database of all clinical trials,
• Create a registry of IRBs,
• Create a cross-center database that allows complete tracking of FDA inspections,
• Seek legal authority to provide oversight that reflects current clinical trial practices; and
• Establish a mechanism to provide feedback to FDA district office staff on their inspection reports and findings.

Read the OIG report here.

Steve Zisson, managing editor of Thomson CenterWatch.

Top Stories for the Week of Sept. 24th 2007

Top News

Economic Modeling Company Caro Research Acquired by UBC

Maryland-based contract research organization (CRO) United BioSource Corporation (UBC) continued its acquisition flurry by purchasing Caro Research, a cost modeling and economic simulations provider based in Concord, Mass.

Accenture and Bristol-Myers Squibb Create Joint Pharmacovigilance Center in India

New York-based Accenture, a global consulting and outsourcing firm, and pharmaceutical company Bristol-Myers Squibb (BMS) have established a pharmacovigilance center in Chennai, India the first of its kind to monitor the pharmaceutical company's safety data. Accenture will contribute more than 140 employees to the center.

Other breaking news... 

• Congress passes FDA Revitalization Act...
• Green Mountain Logic inks deal with Qualia Clinical Services...      

Company Profile: An interview with and Mary-Ann Richardson, chief executive officer of African Clinical Research Organisation, and Christopher Whitfield, chief executive officer of Batswadi Pharmaceuticals, African Clinical Research Organisation.

Past weekly article summaries for the year can be found in the CW Weekly Issue archives. To read the full articles for this issue or for more information on these and other breaking stories, please click here!

Promising Results Seen in Lung Cancer Trials

By Tracy Trundle

Merck KGaA reported positive long-term results from a phase II trial of Stimuvax for the treatment of non-small cell lung cancer (NSCLC). The drug is a MUC-1 peptide-based liposomal vaccine, for the potential  treatment of cancers.

This study enrolled 171 subjects with stage IIIB/IV with stable or responding disease after any first-line chemotherapy with or without radiotherapy. The subjects were stratified by disease stage then randomized to receive Stimuvax plus best supportive care (BSC) or BSC alone.

The subjects in the Stimuvax arm received a single intravenous dose of cyclophosphamide 300mg/m2 followed by eight weekly subcutaneous immunizations with Stimuvax (1,000 mg).Although the overall study results did not reach statistical significance, the subjects with stage IIIB cancer receiving Stimuvax showed a median survival of 30.6 months compared with 13.3 months in the control group. At the three year follow-up, 49% of subjects who were treated with Stimuvax were still alive compared with 27% treated with BSC alone, representing a 45% reduction in mortality.

Based on the results, Merck KGaA is currently conducting a phase III trial of Stimuvax for the treatment of stage IIIA or IIIB NSCLC. Merck KGaA and Edmonton-based biotech Biomira entered into a development and commercialization licensing agreement for Stimuvax.

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Also Pfizer released positive preliminary results from a phase II trial of sunitinib (Sutent), a multi-kinase inhibitor for the treatment of NSCLC. Sunitinib is already approved for the treatment of gastrointestinal tumors and renal cell carcinoma.

The trial was designed to compare sunitinib (37.5 mg/day) in combination with erlotinib (150 mg/day) in previously treated subjects with advanced NSCLC. The primary endpoint was safety and tolerability. Secondary endpoints included anti-tumor activity. The combination treatment was generally safe and well tolerated, with all adverse events mild to moderate in nature.

Two subjects had partial response; one which was maintained for more than three months and one which was currently ongoing. In addition, stable disease up to or more than 16 weeks was observed in two subjects. The randomized portion of this trial is currently underway.

Tracey Trundle is a Research Analyst at CenterWatch.

Congress Passes Long Awaited PDUFA Renewal Act

The U.S. House and Senate passed the long awaited FDA Revitalization Act, a five-year renewal of the Prescription Drug User Fee Act of 1992 (PDUFA). PDUFA allows the FDA to collect fees from drug and device companies applying for regulatory approval. That law was set to expire on Sept. 30.

The new bill calls for an increase in those submission fees to bolster FDA’s drug safety review and monitoring activities. Under the bill, pharmaceutical developers would pay nearly $400 million and medical device makers $48 million in fees next year, a 25% increase.

However, the bill would go much further than its predecessor. The proposed law will grant the FDA much more oversight on treatments already approved and give teeth to the agency in enforcing rules that have been ill-defined the past.

The bill would enhance the government’s clinical trial registry (clinicaltrials.gov) by making studies posted there conform to the international standards developed by the World Health Organization. Written into the bill are regulations that require drug developers to publish all clinical trial results used to obtain a drug’s approval, including any trial results used by the review committee, which reviewed the product, and any trial conducted after the product has been approved.

The law would also give the FDA the ability to impose fines on companies that do not conduct any additional studies that the agency mandated upon granting an approval. Historically, these post-approval studies were not tracked. The bill also calls for a generic drug database, a litigation clauses and orphan drug provisions.

A link to the bill can be found here.

Top Stories for the Week of Sept. 17th 2007

Top News

UBC Buys Stake in ClinResearch

Maryland-based contract research organization (CRO) United BioSource Corporation (UBC) bought an ownership stake in ClinResearch, a Germany-based CRO with a strong focus on adaptive clinical trials. No financial details were given.

AstraZeneca Builds Phase I Unit with Peking University

AstraZeneca has launched its first phase I facility in China through a partnership with Peking University Third Hospital.

Other breaking news...      

• Synergy Research in partnership with Neeman Medical...
• Medidata reports second quarter revenue increase...

Company Profile: An interview with Kenneth Kim, founder and chief executive officer, and Yves Grenon, vice president of business development, West Coast Clinical Trials

Past weekly article summaries for the year can be found in the CW Weekly Issue archives. To read the full articles for this issue or for more information on these and other breaking stories, please click here!

Synergy Creates Alliance With Indian CRO Neeman Medical

Russian CRO Synergy Research Group (SynRG) has made its next move to create a global CRO alliance, forming a partnership with Neeman Medical International, an India-based CRO. The alliance will focus on providing international sponsors with monitoring and site and data management services. Neeman Medical was founded in 2001 and is headquartered in New Delhi.

The CRO has about 70 investigative sites in 17 locations across the country, with access to more than 600 trained investigators. In August, SynRG formed a similar alliance with Costa Mesa, Calf.-based Promedica International.

“Our next target is to find a partner in China. We’ve recently taken part in the Russian- Chinese Forum on Biotechnological and Pharmaceutical Industries, and have established a number of good promising contacts,” said Igor Stefanov, director of business development at SynRG.

CenterWatch Monthly: September 2007 Issue

Fraudulent Study Broker At-Large: Cherie Thibodeau

Cherie Thibodeau has posed as a study broker for the past six years, in between her three stints in California State Prison. Working under numerous aliases and nine Social Security numbers, she has bilked numerous investigative sites out of potentially hundreds of thousands of dollars. Cherie Thibodeau has preyed on new and experienced sites alike. Other sites that have not yet fallen victim to her study brokering scam need to learn the warning signs for a dishonest broker. Investigative sites can avoid working with Thibodeau and her ilk.

Abigail Alliance Heading to Supreme Court

Abigail Alliance for Better Access to Developmental Drugs lost its lawsuit against the FDA last month in the U.S. Court of Appeals for the D.C. Circuit. The alliance took the FDA to court to establish that terminally ill patients in this country have a Constitutional right to have access to experimental drugs after phase I. Abigail Alliance now plans to argue its case before the Supreme Court of the United States. Some industry observers believe that if the alliance wins, it will undermine the drug development process by making clinical trials in terminal ill-nesses impossible to recruit for. Although Abigail Alliance lost its latest suit, the organization has had a marked effect on the FDA's expanded access program.

Affymetrix Launches Collaborations in Cancer Research Program in Europe

Affymetrix has partnered with about 30 leading scientists from European cancer institutes, research centers and universities, from countries including Denmark, Finland, Germany, Italy, Spain, The Netherlands and UK, as part of its collaborations in Cancer Research Program. The alliance will mean that Affymetrix will partially fund select research projects.

Eye On: Diabetes

Nearly 21 million Americans have diabetes and about 41 million have pre-diabetes, according to data from the Centers for Disease Control and Prevention (CDC). About 90-95% of patients with diabetes have type 2 diabetes, with increased attendant risk of cardiovascular disease, stroke, high blood pressure, limb amputation, blindness, neuropathy damage and kidney failure. CenterWatch has identified a pipeline of 16 different drugs in various stages of development for diabetes treatment. Some of these are new insulin formulations, and others act via different mechanisms to lower blood glucose.

To read the full articles for this issue or for more information on these and other breaking stories, please click here or contact us at cw.sales@thomson.com.

ARISE Trials Shows Promising Results for Diabetes

By Tracy Trundle

Atherogenics reported positive results from a phase III trial of succinobucol (AGI-1067), an antioxidant oral vascular cell adhesion molecule-1 (VCAM-1) gene expression inhibitor, for the treatment of diabetes and coronary heart disease. This trial, dubbed ARISE (Aggressive Reduction of Inflammation Stops Events), enrolled over 6,000 subjects internationally. Results were reported at the European Society of Cardiology Congress 2007.

Subjects received AGI-1067 or placebo both in conjunction with standard of care. After 12 months of treatment, AGI-1067 significantly lowered levels of glycated hemoglobin A1c, a measure of glycemic control, in subjects with and without diabetes. In addition, the data showed a 59% reduction in the development of new onset diabetes in subjects with impaired fasting glucose (p < 0.0001). ).

In the subjects with diabetes, AGI-1067 showed a 22% reduction in hard cardiovascular events of cardiovascular death, cardiac arrest, myocardial infarction and stroke (p=0.062). Additional phase III trials are currently underway.

In December 2005, AstraZeneca and AtheroGenics signed a $1 billion deal to co-developement and marketwith AGI-1067. However, in April 2007, AstraZeneca terminated the agreement due to initial negative preminary results of the ARISE study for the treatment of heart disease. After initialing failing to meet specific endpoints in the ARISE study for the treatment of heart disease, Atherogeneics stated in May, that the company plans to continue to develop the product for diabetes.

ClinPhone Inks Deal with Japanese Pharma

eClinical technology company ClinPhone has secured a contract with Bayer Yakuhin, the Japanese affiliate of Bayer. ClinPhone has been named the company’s preferred supplier of randomization and trial supply management services, specifically using ClinPhone’s Interactive Voice Response System (IVRS) for a phase III trial in Japan. ClinPhone opened its Asia Pacific offices in Melbourne Australia in late 2006 and credits the move for helping land this new contract.

ClinPhone's director of business development for Asia Pacific expanded on the importance of having a physical presence in the region.

“This important project demonstrates our commitment to serving our clients in this region. The location of the offices in Melbourne means that ClinPhone is able to provide a more consultative service across the Asia Pacific. The availability of business, technical and operational expertise in Asian business hours will really complement our established 24/7 global service and enable us to focus on the needs of our customers as we continue to strengthen our presence in the region,” he stated.

Top Stories for the Week of Sept. 10th 2007

Top News

Quintiles Launches Patient Website iGuard for Drug Safety Service

In an unusual move for a contract research organization (CRO), Research Triangle Park, N.C.,-based Quintiles has created a new service specifically for consumers of prescription drugs. The free service is called iGuard, a drug risk monitoring and personalized safety alert online site, and it’s a significant step toward patient-directed research.

ethica Creates Indian CRO Through Joint Venture

Montreal-based contract research organization (CRO) ethica Clinical Research has created a joint venture with Matrix Group, a healthcare company based in Hyderabad India. The new Indian CRO is called ethicamatrix. The model is similar to other recent partnerships, joint ventures and mergers between Western CROs and local entities in emerging markets such as India, China and countries in Eastern Europe. The strategy works because it leverages the existing local infrastructure with standardized, quality clinical trial management experience.

Other breaking news...      

• Medidata Solutions in contract with H. Lundbeck...
• Encorium Group in joint venture with Prosoft...

Company Profile: An interview with Cristy Anderson, president, Clinical Research Advantage

Past weekly article summaries for the year can be found in the CW Weekly Issue archives. To read the full articles for this issue or for more information on these and other breaking stories, please click here!

Quintiles Launches Patient Website iGuard for Drug Safety Service

By Stephen DeSantis

In an unusual move for a contract research organization (CRO), Research Triangle Park, N.C.-based Quintiles has created a new service specifically for consumers of prescription drugs. The free service is called iGuard, a drug risk monitoring and personalized safety alert online site, and it’s a significant step toward patient-directed research.

Using secure methods through iGuard, patients anonymously provide demographic, disease treatment and medical history information to the site, along with contact information. If there is an issue with a consumer drug, such as a change in its prescription label, a side effect warning, or other warnings from the manufacturer or a medical journal, the system sends patients a form to take to their doctors.

And the site offers patients a simpler way to determine a drug’s general risk. The system uses a series of alert levels, such as ‘Low Risk,’ ‘Guarded,’ or ‘High Risk’ so patients know when to seek more information or ask a doctor more questions. iGuard can also poll the patients online for the occurrence of adverse events or for other useful information.

Where does all that patient data go? Quintiles is banking on sponsors seeing the raw information as a valuable post-approval data windfall, and the CRO believes it can sell the data to clients as a unique service offering.

In the U.S., doctors can voluntarily submit safety monitoring data to the Food and Drug Administration (FDA) through a program known as MedWatch. But according to Quintiles, not many of them do. In addition, patients do not often report adverse events to their physicians.

According to the president of the program, Hugo Stephenson, M.D., phase IV research and post-approval safety studies have been costly and time consuming, and the trials often deliver inadequate data...

Medidata Inks Multiple Contracts in August

New York, N.Y.-based eClinical company Medidata Solutions inked a multi-year contract with Copenhagen-based pharmaceutical firm H. Lundbeck to manage more than 10 psychiatric phase II through IV trials. The studies will use Medidata Rave 5.6, set to launch this month. H. Lundbeck stated it chose Medidata’s electronic data capture (EDC) system based on feedback from clinical research associates and site managers.

“More and more, Medidata Rave is serving as the ‘backbone’ of the clinical research process – and we are pleased Lundbeck will benefit from Rave’s ability to easily integrate with other systems, meet the requirements of both large-and-small scale studies and enable them to rapidly conduct multiple studies in their strategic area of research,” said Tarek Sherif, chief executive officer of Medidata Solutions.

Recently, Boston-based electronic patient reported outcomes provider PHT announced it has integrated its LogPad ePRO system with Medidata Rave’s EDC technology. The companies have landed a deal with Sucampo Pharmaceuticals to manage its pediatric studies for the treatment of gastrointestinal disorders.The trial will enroll 120 patients throughout the U.S.

"By integrating multiple data streams, sponsors are able to take advantage of real efficiencies gained by using reliable electronic systems," said Phil Lee, president and chief executive officer of PHT.

Heart Drug Combo Reduces "Flushing"

By Tracy Trundle

Merck reported positive results from a phase III trial of Cordaptive for the treatment of dyslipidemia. Cordaptive was shown to lower LDL --or bad -- cholesterol and raise HDL -- or good -- cholesterol, while lowering some of the side effects of such drugs.

The drug is a combination of extended-release niacin and an investigative compound called laropiprant (MK-0524). laropiprant is an inhibitor of niacin-induced flushing, a common side effect of some cholesterol drugs. The combo is being investigated for the prevention of coronary heart disease (CHD, coronary artery disease) and atherosclerosis.

The double-blind, randomized trial enrolled 1,613 subjects who received Cordaptive (1 gram/day), extended-release niacin alone (1 gram/day) or placebo. After four weeks, the active treatment groups doubled their respective doses to 2 grams per day for an additional 20 weeks.

The co-primary endpoints were the effects of 2 grams of Cordaptive versus placebo on percent changes in LDL-cholesterol (LDL-C) across weeks 12 to 24, and the effects of 1 gram of Cordaptive versus extended-release niacin on flushing symptom severity during the first week of treatment. In the subjects who advanced to 2 grams of Cordaptive, LDL-C levels were reduced from baseline by an average of 19% (versus a reduction of 0.5% with placebo). In addition, in the subjects receiving 1 mg of Cordaptive, 69% reported either no flushing symptoms or mild flushing symptoms during the first week of treatment compared to 44% of those who received extended-release niacin alone.

Secondary endpoints included the effects of 2 grams of Cordaptive versus placebo on HDL-cholesterol (HDL- C) levels, triglyceride levels and other lipid parameters, and the flushing frequency and intensity of 2 grams of Cordaptive compared to extended-release niacin alone.  In the subjects receiving Cordaptive 2 mg their HDL-C levels increased by an average of 19% (versus a reduction of 1.2% with placebo), and their triglyceride levels were reduced by an average of 22% (versus an increase of 3.6% with placebo). By week 24, the frequency of moderate or greater flushing was 2 days/week for subjects receiving 2 grams of Cordaptive or a placebo versus 7 days/week among those treated with 2 grams of extended-release niacin.

A New Drug Application (NDA) for Cordaptive for the treatment of dyslipidemia is currently under review by the FDA. A decision is expected by mid 2008.

Top Stories for the Week of Sept. 4th 2007

Top News

Medpace Expands in Eastern Europe with Acquisition

Cincinnati-based contract research organization (CRO) Medpace made its first acquisition with the purchase of Monax, a CRO based in Prague, that it has worked with previously. The deal was a classic partnership turned purchase for the CRO. But the acquisition was a departure from Medpace’s stated organic growth-only philosophy. However, according to Dr. August Troendle, chief executive officer at Medpace, it was a cementing of a working partnership rather than a merger. 

Promedica Forms Alliance with Russian CRO Synergy Research Group

Less than a year ago, Costa Mesa, Calf.-based contract research organization (CRO) Promedica International set out to find a suitable Russian CRO to form an alliance that would expand its geographical reach. Its plan was to tap into the emerging Russian clinical trials market by working with a local company already familiar with the country's clinical research environment. Just about the same time, Moscow-based Synergy Research Group began looking for the same type of partnership: a U.S.-based CRO with a large pool of international clients and the capability of conducting large trials in the West.

Other breaking news...     

• ClinPhone reduces 2007 revenue forecast...
• Averion inks deal with BIOCANCER...

Company Profile: An interview with Charles H. Ballow, PharmD, director, Buffalo Clinical Research Center

Recent Industry Personnel News

• Clinsys Clinical Research appointed Hartmut Schmied, M.D., to vice president, European Operations. He will be based in Dusseldorf, Germany. Prior to Clinsys, Schmied was Medifacts International’s executive director of European Operations and global head of clinical research. He also served in clinical development positions at Bayer AG.

• Zurich-based CRO PFC Pharma Focus appointed Ran Frenkel to vice president of business development. He is already the chief executive officer of PFC’s Israel subsidiary. Prior to joining PFC, Frenkel founded Israeli-based Actelion Pharmaceuticals.

• Michael Troullis has become the new chief financial officer of CRO Quintiles. He was acting CFO for the company since 2006, replacing John Ratliff when he became Quintiles’ chief operating officer. Troullis joined Quintiles in 1992 as director of finance, Europe. He previously held several positions at CooperVision, one of the largest makers of contact lenses, most recently as European Finance Director; and six years with global accounting firm KPMG in the UK. Troullis will report to directly to Dennis Gillings.

• DSG, a Malvern, Penn.-based eClinical company, hired Suzanne Lamerand as vice president, clinical data management. Prior to joining DSG, Lamerand was associate director of data management at McNeil Consumer Healthcare. She also was a consultant positions at Trilogy Consulting.

• Cypress, Calif.,-based early stage CRO West Coast Clinical Trials (WCCT) hired Yves Grenon as vice president of business development and strategic planning. Grenon was executive director of business development at Pharmanet – formally SFBC – prior to joining WCCT. He also served as senior director of business development at MDS Pharma for its European and Japanese markets.

• eClinical company Omnicomm Systems  appointed Dr. Yvonne Rollinger director of clinical operations. He will be based in Bonn, Germany. Rollinger came from rival EDC company Datatrak, where she was director of clinical service in Europe for seven years. She also served as a project coordinator for a U.S. based CRO.

• Waltham, Mass.-based CRO Parexel International’s consulting unit Parexel Consulting –appointed Dr. Hans Van Bronswijk to the position of principal consultant in its European Drug Development Practice. He will advise clients on clinical development and regulatory affairs. He served as head of clinical assessment for the Dutch Medicines Evaluation Board for nine years. Bronswijk served on the European Medicines Agency (EMEA) committee for Medical Products for Human Use (CHMP) for the Netherlands for six years. He also held regulatory positions at Novartis.

• Clinical Site Services (CSS), a Maryland-based patient enrollment company, appointed Kristen Chumley as senior media planner and buyer. Prior to CSS, Chumley worked for a large advertising agency as an assistant account executive.

Be sure to send your organization's latest personnel news via email to the editors at Clinical Trials Today!

First Parkinson's Disease Therapy Conference Planned

The Michael J. Fox Foundation for Parkinson’s Research (MJFF) and The New York Academy of Sciences will co-host the inaugural PD Therapeutics Conference on Thursday, October 25, in New York City. This meeting is the first and only major scientific symposium exclusively focused on the development of innovative drugs to target Parkinson’s disease.

The conference will bring together academic and industry scientists to assess and discuss how novel scientific advances can be applied to accelerate the development of innovative drug discovery approaches to Parkinson’s disease.

“Our primary objectives for the conference are twofold: to discuss scientific progress on drug discovery initiatives aimed at better treating Parkinson’s disease, and to provide a new networking opportunity for scientists to share information and resources,” said conference chair C. Warren Olanow, M.D.

Cardium's Heart Drug Shows Mixed Results

By Tracy Trundle

Cardium reported mixed results from two phase IIb/III trials of Generx (alferminogene tadenovec, Ad5FGF-4) for the treatment of chronic angina. These randomized, double-blind, placebo-controlled trials were dubbed AGENT (Angiogenic GENe Therapy -3 and -4 and enrolled a total of 532 subjects in the US and Europe.  Subjects received a low dose or high dose of Generx, administered via intracoronary infusion or placebo for 12 weeks. The primary endpoint was the change from baseline in exercise treadmill time (ETT) at 12 weeks and at secondary time points of 4 weeks and 6 months. Secondary endpoints included time to 1 mm ST-segment depression, time to onset of angina and change in Canadian Cardiovascular Society (CCS) class. Pooled data showed no significant difference in the active groups versus placebo in the primary endpoint.

There was a large and significant placebo effect compared with baseline, which persisted over 6 months. In addition, none of the secondary endpoints were achieved with the exception of change in CSS class; significant improvement over placebo only for the high-dose group was observed at week 12, month 6, and month 12 (p< 0.05).

However, in a pooled analysis of pre-specified subgroups statistically significant results were seen among women in all the primary and secondary endpoints as compared to placebo. These were observed at both the three and six month evaluation endpoints for the high dose group (p less than 0.01 to p less than 0.05). In addition, treatment with the low dose of Generx showed statistically significant results over placebo in ETT at three and six months, time to ST-segment depression at six months, and CCS Class at twelve months (p less than 0.05).

Based on the results, Cardium created an FDA approved adjusted clinical protocol and is currently conducting a phase III study in women with angina.