European Commission Approves ellaOne® – 3rd Approval This Year For Target e*CRF®

HRA Pharma, a privately-held, European pharmaceutical company was granted marketing authorization by the European Commission (EC) for its next generation emergency contraceptive product , ellaOne® (ulipristal acetate) (http://www.hra-pharma.com/downloads/PR_ellaOne_approval.pdf). The unanimous decision by all member states enables HRA Pharma to begin marketing throughout the European Union, making it the only approved product to have been specifically designed and developed for use as an emergency contraceptive. 

Target Health is very pleased to announce that this is the 3rd product this year, which used Target e*CRF for EDC for marketing approval. The HRA Pharma approval by the European Commission (EC) comes on top of a US NDA approval for the treatment of head lice (April 2009), and a US PMA approval for the reduction of adhesions in pediatric cardiac surgery patients (March 2009). There are now 17 marketed products that used Target e*CRF® for pivotal trials. For the HRA program, Target Health also performed clinical site monitoring in the US, performed data management, wrote the SAP, performed the statistical analyses, coded AEs using Target Encoder, and wrote the clinical study report. Target Health also provided regulatory support in the US.

For more information about Target Health and any of our software tools for paperless clinical trials, please contact Dr. Jules T. Mitchel (212-681-2100 ext 0) or Ms. Joyce Hays. Target Health’s software tools are designed to partner with both CROs and Sponsors. Please visit the Target Health Website at www.targethealth.com

Bone Marrow Helps Heart Function 

Injecting bone marrow stem cells into the heart helped some patients with a chronic form of heart disease, as reported in JAMA. The infusions helped to increase 1) ___ flow, reduce pain and help patients exercise more. Now trials are needed to see if the therapy helps patients live longer. Bone 2) ___ stem cell therapy is being tested for a range of heart conditions, including for people with blocked arteries that reduce blood supply to the heart. Heart disease – the world’s leading cause of 3) ___ – is caused by fatty deposits that harden and block arteries, high blood pressure which damages blood vessels, and other factors. Jan van Ramshorst of Leiden University Medical Centre in the Netherlands and colleagues looked at 50 people, with an average age of 64, who had chronic ischemia – blocked 4) ___. One group received about eight injections of bone marrow cells and the others received a placebo. After three months, those who received the injections showed signs that their 5) ___ pumped better and that they had improved blood flow compared to those who received placebo. They also had greater improvements in the ability to exercise and scored higher on quality-of-life measurements than those who received the 6) ___. 

ANSWERS

1) blood; 2) marrow; 3) death; 4) arteries; 5) hearts; 6) placebo

The Role of Urine in Medicine 

Many physicians in history have resorted to the inspection and examination of the urine of their patients. Hermogenes wrote about the color and other attributes of urine as indicators of certain diseases. Abdul Malik Ibn Habib of Andalusia d.862 CE, mentions numerous reports of urine examination throughout the Umayyad empire. Diabetes mellitus got its name because the urine is plentiful and sweet. The use of urine therapy as a medical treatment or daily health regimen is uncommon; however, Aztec physicians used urine to clean external wounds to prevent infection, and administered it as a drink to relieve stomach and intestinal problems. The medicinal properties of urine were used in China as a part of holistic medicine, and in India, especially as part of the traditional Indian medicine, Ayurveda. The ancient Romans used urine as a bleaching agent for cleaning clothes and teeth. In Scotland, it was used to wash wool to prevent shrinking. The word “urine” was first used in the 14th century, and is a direct borrowing of the French word descended from the Latin urina and the Greek ouron, all meaning “urine,” both traceable to the postulated Indo-European root word awer, “wet, or to flow.” In Latin there is a curious twist in that whereas urina means “urine” the verb urinare means “to dive,” and to the Romans a urinator was a diver. Galen thought that urine was excreted directly from the vena cava and that the composition of urine was an indication of the nature of blood at any given time. Consequently, meticulous examination of the urine, or uroscopy, as it was then called, since ancient times, has been a strong point in diagnosis. Every medieval physician worthy of the name, carried a small flask in which to collect, and then contemplate, his patient’s urine. In the 14th century, ring worm was treated by washing the scalp with a boy’s urine. Gentile da Foligno an influential professor and teacher of medicine at the Universities of Bologna, Padua, Siena and Perugia in the first part of the 14th century, was one of the first physicians to perform human dissection.. He made a commentary on Carmina de urinarum iudiciis (Songs of urinary judgements) and to De pulsibus (About pulses) composed by Egidius Corbaliensis. This work is more than a commentary: it is a text attempting to conceptualize the physiology of urine formation. According to his writing, urine associated to the blood passes ‘per poros euritides’ (through the porous tubules) of the kidney and is then delivered to the bladder. Commenting and explaining the writing on De pulsibus, he stressed the importance of heart disease on modulating the color and output of urine and the relationship between fast pulse rate and urine output. For the originality of his thought and for the conceptualization of the relationship between pulse rate and urine characteristic, Gentile da Foligno could be considered as the first cardionephrologist. The yellow color of urine was previously thought to come from gold. Alchemists spent much time trying to extract gold from urine, and this effort led to discoveries such as white phosphorus, which was discovered by the German alchemist Hennig Brand in 1669 when he was distilling fermented urine. In 1773 the French chemist Hilaire Rouelle discovered the organic compound urea by boiling urine dry. During World War I, the Germans experimented with numerous poisonous gases for use during war. After the first German chlorine gas attacks, Allied troops were supplied with masks of cotton pads that had been soaked in urine. It was believed that the ammonia in the pad neutralized the chlorine. These pads were held over the face until the soldiers could escape from the poisonous fumes, although it is now known that chlorine gas reacts with urine to produce toxic fumes. Urine has also been historically used as an antiseptic in times of war, and when other antiseptics were unavailable, urine, the darker the better, was utilized on open wounds as an antibacterial agent.

Early Antiretroviral Therapy Is Efficacious – Interim Review Ends Clinical Trial in Haiti 

A clinical trial has demonstrated that HIV-infected adults in a resource-limited setting are more likely to survive if they start antiretroviral therapy (ART) before their immune systems are severely compromised. On May 28, 2009, an independent data and safety monitoring board (DSMB) met to conduct an interim review of an ongoing clinical study known as CIPRA HT 001, which is being conducted in Haiti. The DSMB found overwhelming evidence that starting ART at CD4+ T cell counts – a measure of immune health – between 200 and 350 cells/mm3 improves survival compared with deferring treatment until CD4+ T cells drop below 200 cells/mm3. In light of these results, the DSMB recommended that the trial sponsor – the National Institute of Allergy and Infectious Diseases (NIAID) – end the trial immediately, before its scheduled conclusion. NIAID agreed with the DSMB recommendation, and all study participants who have fewer than 350 CD4+ T cells/mm3 will be offered ART. The study investigators say this new finding has the potential to change the standard of care for HIV infection in dozens of countries around the world where ART is initiated only when CD4+ T cell counts drop below 200 cells/mm3. Like the results of several recent epidemiologic studies in developed countries that examined the optimal time to begin ART, the new finding underscores the importance of identifying people who are HIV-infected earlier in the course of their infection and starting ART earlier. The number of people who meet the medical criteria for receiving ART likely will grow as treatment guidelines are revised as a consequence of this finding, challenging the global community to supply antiretroviral drugs to all who need them. Today, only 30% of HIV-infected individuals in low- and middle-income countries who need ART are receiving it. The clinical trial CIPRA HT 001 began in 2005. It is funded by NIAID through the Comprehensive International Program of Research on AIDS (CIPRA) and is being carried out by the Haitian Group for the Study of Kaposi’s Sarcoma and Immune Deficiency Disorders (GHESKIO) Centers in Port-au-Prince, Haiti. The trial enrolled 816 HIV-infected adults ages 18 and older with early HIV disease and CD4+ T cell counts between 200 and 350 cells/mm3. Half of the participants were assigned at random to begin ART within two weeks of enrollment, and the other half were assigned to defer treatment until their CD4+ T cell counts dropped below 200 cells/mm3 or they were diagnosed with AIDS. This deferred treatment is in keeping with the standard of care in Haiti and the current guidelines of the World Health Organization (WHO). The first-line treatment regimen consisted of the anti-HIV drugs zidovudine, lamivudine and efavirenz. At the time of the DSMB interim review, six participants in the early treatment group had died, while 23 participants in the standard-of-care group had died — nearly four times as many. The DSMB also found that, among participants who began the study without tuberculosis (TB) infection, 18 people in the early treatment group had developed TB, while 36 people — twice as many — in the standard-of-care group had developed TB. These results were statistically significant. In light of these results, the DSMB recommended that NIAID end the trial immediately and that the study team offer ART to all participants in the standard-of-care group who have fewer than 350 CD4+ T cells/mm3. The DSMB also recommended that the study team continue to follow all participants for another year and make every effort to ensure that participants receiving ART continue their therapy. NIAID concurred with these recommendations. The study investigators are notifying all participants and have notified institutional review boards and national ethics committees involved with CIPRA HT 001 as well as the Haitian Ministry of Health about the findings of the DSMB. Investigators also have shared the information with WHO, the U.S. President’s Emergency Plan for AIDS Relief, and the Global Fund to Fight AIDS, Tuberculosis and Malaria.

Genetic Clues To Blood Pressure Identified

Blood pressure is measured in millimeters of mercury (mm Hg), and expressed with two numbers, for example, 120/80 mm Hg. The first number (systolic pressure) is the pressure when the heart beats while pumping blood. The second number (diastolic pressure) is the pressure in large arteries when the heart is at rest between beats. About 1 in 3 adults (approximately 72 million people) in the US has high blood pressure, which can lead to coronary heart disease, heart failure, stroke, kidney failure, and other health problems. Hypertension causes over 7 million deaths worldwide each year. Blood pressure has a substantial genetic component and hypertension runs in families. Previous attempts to identify genes associated with blood pressure, however, have met with limited success. A number of unsuspected genetic variants associated with systolic blood pressure (SBP), diastolic blood pressure (DBP), and hypertension (high blood pressure), have been identified suggesting potential avenues of investigation for the prevention or treatment of hypertension. The analysis of over 29,000 participants was published online in the journal Nature Genetics on May 10, 2009. In a genome-wide association study (GWAS), millions of common genetic variants of individuals were scanned from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium to find variants associated with blood pressure and hypertension. This extensive resource includes white men and women from the Framingham Heart Study, Atherosclerosis Risk in Communities study, Cardiovascular Health Study, the Rotterdam Study, the Rotterdam Extension Study, and the Age, Gene/Environment Susceptibility Reykjavik Study. The study identified a number of genetic variants or single-nucleotide polymorphisms (SNPs) associated with SBP, DBP, and hypertension. When they jointly analyzed their findings with those from the GWAS of over 34,000 participants in the Global BPgen Consortium (whose results are presented in an accompanying paper in the same issue of Nature Genetics), 11 genes were identified showing significant associations across the genome: four for SBP, six for DBP, and one for hypertension. The blood pressure genes include ATP2B1 which encodes PMCA1, a cell membrane enzyme that is involved in calcium transport; CACNB2, which encodes part of a calcium channel protein; and CYP17A1 which encodes an enzyme that is necessary for steroid production. One detected variant is within the gene SH2B3 and has been associated with autoimmune diseases, hinting that pathways involved with the immune response may influence blood pressure. It was found that the top 10 gene variants, or SNPs, for systolic and diastolic blood pressure were each associated with around a 1 and 0.5 mm Hg increase in systolic and diastolic blood pressure, respectively. The prevalence of hypertension increased as the number of variants increased. People who carry very few blood pressure genetic risk variants have blood pressure levels that are several mm Hg lower than those who carry multiple risk variants. In practical terms this is enough to increase the risk for cardiovascular disease. A prolonged increase in DBP of only 5 mm Hg is associated with a 34% increase in risk for stroke and a 21% increase of coronary heart disease.

Adolescents and MP3 Players: Too Many Risks, Too Few Precautions

According to an article published in Pediatrics (2009;123:e953-e958), a study was performed to assess risky and protective listening behaviors of adolescent users of MP3 players and the association of these behaviors with demographic characteristics and frequency of use. For the study, which was performed in 2007, 1,687 adolescents (12-19 years of age) in 68 classes in 15 Dutch secondary schools were invited to complete questionnaires about their music-listening behaviors. Results showed that 90% of participants reported listening to music through earphones on MP3 players; 32.8% were frequent users, 48.0% used high volume settings, and only 6.8% always or nearly always used a noise-limiter. Frequent users were >4 times more likely to listen to high-volume music than were infrequent users, and adolescents in practical prevocational schools were more than twice as likely to listen to high-volume music as were those attending pre-university education. According to the authors, when using MP3 players, adolescents are very likely to engage in risky listening behaviors and are unlikely to seek protection, and that frequent MP3 player use is an indicator of other risky listening behaviors, such as listening at high volumes and failing to use noise-limiters.


TARGET HEALTH excels in Regulatory Affairs and works closely with many of its clients performing all FDA submissions. TARGET HEALTH receives daily updates of new developments at FDA. Each week, highlights of what is going on at FDA are shared to assure that new information is expeditiously made available. 

FDA Approves Injectable Form of Ibuprofen 

The FDA has approved Caldolor, the first injectable dosage form of the common pain medication ibuprofen, to treat pain and fever. Caldolor will be available for hospital use only. It is approved to be administered in 400 mg to 800 mg doses, over 30 minutes, every 6 hours for acute pain. To treat fever, the drug is approved in a 400 mg dose administered over 30 minutes, followed by 400 mg every 4 to 6 hours, or 100-200 mg every 4 hours, as necessary. In a clinical trial of 319 women who had undergone an elective abdominal hysterectomy, patients were less likely to request morphine for pain on an as-needed basis when administered Caldolor. Caldolor should be used with caution in patients with congestive heart failure, kidney impairment, at risk of blood clots and those who have a prior history of ulcers or gastrointestinal bleeding. When used in such patients, attention to using the lowest effective dose for the shortest time period is important to reduce the risk of serious adverse events. The drug has also been associated with high blood pressure, serious skin reactions, and serious allergic reactions. The most common adverse reactions reported in the controlled clinical trials were nausea, flatulence, vomiting, and headache. Caldolor is manufactured by Cumberland Pharmaceuticals Inc., Nashville, Tenn.

20090613-1

A CDC Image of H1N1 influenza virus

Novartis Produces Swine Flu Vaccine

U.S. Dept. of Health & Human Services, June 12, 2009   —  The Swiss pharmaceutical company Novartis says it has produced a first batch of a vaccine to fight the H1N1 swine flu virus, weeks ahead of expectations.

The company said Friday that producing the vaccine proved to be quicker through cell-based production rather than eggs, the usual method of producing vaccines.

Novartis says clinical trials will begin in July.

More than 30 governments have asked Novartis to supply them with a swine flu vaccine.

The announcement comes a day after the World Health Organization declared the swine flu virus a pandemic as infections climbed to nearly 30,000 cases in 74 countries. This was the first declaration of a global flu pandemic in more than 40 years.

The United Nations agency issued the declaration Thursday after it held an emergency meeting with flu experts in Geneva. WHO Director-General Margaret Chan said that although the virus is now “unstoppable,” the danger that it poses is “moderate.”

Officials note that declaring a pandemic does not mean the disease has become more severe, but that there is an increasing number of infections in different geographical locations. The agency also is reiterating its advice to countries not to close borders or impose travel restrictions, but to be vigilant.

U.N. Secretary-General Ban Ki-moon echoed similar comments, but said the world must be watchful because it is not known what will happen in the coming months. Mr. Ban said he will convene a meeting next Monday of the U.N.’s influenza steering committee to determine what he called “our immediate next steps.”

The World Health Organization says declaring the pandemic will likely get governments to spend more money to contain the outbreak.

The United States has recorded the most cases of the swine flu, with more than 13,000, although Mexico has the most deaths, which currently stand at more than 100.

The WHO says 144 people have died from the virus.

The last time the WHO declared a pandemic was in 1968, following the outbreak of the Hong Kong flu, which killed at least one million people.

HHS.gov, GoogleNews.com, Wall Street Journal, June 14, 2009, by Peter Spiegel  —  WASHINGTON — The administration’s top health-policy official on Sunday said President Barack Obama’s plan to create a government-run health insurance program would bring competition to private insurers and lower health-care costs nationwide.

Health and Human Services Secretary Kathleen Sebelius said that in many markets, private insurers currently have no competitors, giving them wide latitude to raise premiums on customers. She said a government-run option, as long as it followed the same rules as private providers, would force such insurers to lower prices to keep existing customers.

“Most Americans understand that choice and competition is what we want,” Ms. Sebelius said in an interview on CNN’s “State of the Union.” “You can write the rules for a level playing field. The president does not want to dismantle privately owned planned…. He wants to strengthen the marketplace.”

Ms. Sebelius’s remarks came ahead of a major address by Mr. Obama before the American Medical Association scheduled for Monday, in which he is expected to try to bring new momentum to his health-care overhaul plans.

Mr. Obama’s proposal for a government-owned insurer is among the more-controversial elements of his plan. Private insurance companies have voiced opposition to the idea, saying a public plan would have an unfair advantage due to economies of scale and other factors. Some Republicans and moderate Democrats are also resisting the measure, saying it allows for too much public involvement in health care.

In his weekly address on Saturday, Mr. Obama outlined measures that would trim spending on federal health programs for the elderly and poor, by $313 billion over 10 years to help pay for his health-overhaul plan. He proposed trimming federal payments to hospitals by about $200 billion over the next 10 years, saying greater efficiencies and broader insurance coverage would justify the change.

The president has spent the last week traveling across the country to push his health plan, which Democrats hope Congress would pass by October. House leaders last week unveiled a plan that would require almost all Americans to have health insurance and provide subsidies to poor Americans to buy it. Those without insurance could purchase it on a national exchange set up by the government. Senate Democrats have offered similar legislation.

Ms. Sebelius said the administration remained open to other ways to bring public-sector competition to the market, but would resist any proposals put forward by private insurers that would require consumers to buy polices from only private providers.

“I don’t think it’s a big surprise that a lot of insurers say, ‘What we really like is everybody who doesn’t have insurance to be told they must buy it, and buy it only from us,'” she said. “The president feels that having a public option side-by-side — same playing field, same rules — will give Americans choice and help lower costs for everybody