RxPG News : Clinical Trials

Probiotics unsafe for severe acute pancreatitis patient's due to its increased mortality.

Thu, 14 Feb 2008 06:59:37 PST

( from http://www.rxpgnews.com ) Probiotics are associated with an increased mortality in patients with severe acute pancreatitis, and do not reduce the risk of infectious complications in these patients. These are the conclusions of authors of an Article published early Online and in an upcoming edition of The Lancet.

Infectious complications and associated mortality are a major concern in acute pancreatitis. Around a fifth of patients with this disease have necrotising pancreatitis, which has a 10-30% mortality rate largely due to infectious complications. These complications are thought to start with overgrowth of small-bowel bacteria. Researchers have previously suggested that prophylaxis using strains of probiotic (‘good’ bacteria) might prevent infectious complications by reducing this small-bowel bacterial overgrowth -- thereby restoring gastrointestinal barrier function, and modulating the immune system.

Professor Hein Gooszen, University Medical Center Utrecht, Netherlands, and colleagues, did a randomised, double-blind, placebo controlled trial of 296 patients with predicted severe acute pancreatitis -- 152 in the probiotics group, and 144 in the placebo group. The patients in each group were similar in terms of characteristics and disease severity. Each of the patients was randomly assigned within 72 hours of onset of symptoms to receive a multispecies probiotic preparation* or placebo, administered enterally** twice daily for 28 days. All were monitored for the occurrence of infectious complications -- ie, infected pancreatic necrosis, bacteraemia, pneumonia, urosepsis, or infected ascites*** -- during both admission and 90 day-follow-up.

They found that the proportions of patients having infectious complications was similar in both groups -- 46 patients (30%) in the probiotics group and 41 (28%) in the placebo group. However, in the probiotics group many more of these patients died -- 24 (16%), versus nine (6%) in the placebo group. Nine patients in the probiotics group developed bowel ischaemia -- eight with fatal outcome -- compared with none in the placebo group.

The authors say: Our findings show that probiotics should not be administered routinely in patients with predicted severe acute pancreatitis, and that the particular composition used here should be banned for the present indication. Whether other combinations of strains might have resulted in different results is debatable, but, until the underlying mechanism is actually revealed, administration of probiotics in patients with predicted severe acute pancreatitis must be regarded as unsafe.

Most importantly, probiotics can no longer be considered to be harmless adjuncts to enteral nutrition, especially in critically ill patients or patients at risk for non-occlusive mesenteric ischaemia.

Start of Second Phase III Trial in MS Neuropathic Pain

Wed, 09 Aug 2006 14:45:37 PST

( from http://www.rxpgnews.com ) GW Pharmaceuticals plc (AIM: GWP) announces the start of a second pivotal Phase III trial in people with multiple sclerosis (MS) suffering from central neuropathic pain. The first patient has now been enrolled in the study.

This Phase III study is a double-blind randomised placebo-controlled study of Sativex in 218 patients with central neuropathic pain due to MS, who have achieved inadequate pain relief with existing therapies. This study therefore aims to address a currently unmet medical need and will be recruiting patients in the UK, Canada, France, Spain and the Czech Republic. The primary outcome measure in the study is the 0-10 Numeric Rating Scale pain score, as recommended by regulatory authorities in both Europe and North America. The study is expected to report headline results in about one year.

GW has previously carried out a similar pivotal Phase III study with positive results. This study, which was published in the peer-reviewed journal, Neurology, showed that Sativex was significantly superior to placebo in reducing pain (p=0.005) and sleep disturbance (p=0.003)1.

It is regulatory convention for two pivotal Phase III trials in the same patient population to be required to support a product approval for a particular indication. This second pivotal Phase III study in MS Neuropathic Pain has a number of important roles in the regulatory strategy for Sativex, as follows:

* In Europe, this second pivotal study will complete a clinical data package to support a regulatory submission for Sativex in the indication of "MS Neuropathic Pain"

* In Europe, this study is intended to enhance the data package arising from GW's two ongoing peripheral neuropathic pain studies, to support a broad indication of "General Neuropathic Pain" as identified in recent EU guidelines

* In Canada, this study is intended to meet the conditions associated with the approval of Sativex in order to obtain a full Notice of Compliance.

Sativex is already approved in Canada as adjunctive treatment for the symptomatic relief of neuropathic pain in MS. Canada was the first country in the world to approve Sativex. Health Canada approved Sativex under the Notice of Compliance with Conditions policy.

Dr Stephen Wright, R&D Director, said, "GW has in place a broad regulatory strategy to support the global approval of Sativex across multiple related indications including neuropathic pain and spasticity in multiple sclerosis, peripheral neuropathic pain and cancer pain. One of the principal purposes of this study is to complete the regulatory package required for the approval in Europe of Sativex in the indication of neuropathic pain in MS.

"Neuropathic pain is a debilitating symptom of MS and is often under treated and inadequately controlled. Our data show that Sativex has a valuable role to play in treating this significant unmet medical need."

RISUG (Reversible Inhibition of Sperm Under Guidance) Trial to recruit more volunteers

Fri, 31 Mar 2006 12:42:37 PST

( from http://www.rxpgnews.com ) The trial is studying a new male contraceptive, RISUG (Reversible Inhibition of Sperm Under Guidance): a reversible, nonhormonal contraceptive that provides 10 or more years of protection after a 10-15 minute procedure. Researchers received approval this week to begin enrolling additional study volunteers, after a delay of nearly four years.

"RISUG would be exciting because it would mean that, finally, I could take control of my own future, instead of leaving it to someone else," says Tyler Dunlap, a 27-year-old San Francisco newlywed. "Being in a committed long-term relationship means that I don't want to rely on condoms for birth control. I'm not ready for a vasectomy, though. This new procedure could be the answer that gives men the decisive control we lack with current contraceptives."

In the RISUG study, doctors inject a gel into the tube that sperm travel through after they are produced (known as the vas deferens). The gel then disables the sperm as they swim by. In study animals, male fertility returns if the RISUG is flushed out with another injection that dissolves the gel.

Elaine Lissner, director of the nonprofit Male Contraception Information Project in San Francisco, says she is not surprised that American men are watching the RISUG trial with keen interest. She emphasizes that the method has the potential to be the first truly affordable, reversible, long-term male contraceptive.

In 2002, when enrollment in the Indian study was halted, more than 140 men were already using RISUG. Concern about side effects and insufficiency of safety data caused a temporary suspension of the project. However, expert panels subsequently concluded that the major side effect -- several weeks of non-painful scrotal swelling in about a third of the subjects --was not enough to stop the study.

Additional Safety Tests

Since 2002, researchers have conducted several additional laboratory safety tests on RISUG.

"When we first began using RISUG in volunteers more than 15 years ago, we didn't have access to the more sophisticated toxicity tests available today," says Dr. H. C. Das, one of the lead investigators. "Last year we sent RISUG to an FDA-registered laboratory in the United States for more tests, and the results came back clean. We've also done more studies at the Industrial Toxicology Research Centre in Lucknow, India with the latest equipment. We're glad to be able to provide men this additional reassurance."

Dr. R. S. Sharma, deputy director general of the Indian Council of Medical Research (ICMR), concurs that the safety results were "very satisfactory." The ICMR is working to arrange study sites throughout India, beginning with Jaipur, Ludhiana, Udhampur, and India's capital New Delhi. Three data monitoring committees will watch for any safety concerns.

Next Steps

But Lissner cautions that progress will be slow without sufficient political will. "A reversibility study in men is key," she stresses. "And we're hoping that the Indian government is committed enough to this research to get the next batch of RISUG made to the FDA's latest Good Manufacturing Practice standards. If it is, the results will carry more weight internationally. Then men in other countries -- such as the US -- can hope for faster government approval."

Currently, RISUG's developers are arranging a collaboration with US researchers. Lissner says that to gain FDA approval, US researchers will have to begin with animal tests, so studies in North American men would not start for several years. Still, she notes that "We shouldn't be discouraged. We already know that RISUG works, which is half the battle in drug development. Men in studies in India have been using it for more than a decade. Now we just have to finish our homework."

RISUG's chief developer, Prof. Sujoy Guha of the Indian Institute of Technology, says myths about men not being interested in contraception are just that: myths. "I get letters from men all over the world who beg to come to India and participate in this study at their own expense."

EU clinical trials directive is threatening future of cancer research

Sat, 04 Mar 2006 15:13:37 PST

( from http://www.rxpgnews.com ) A new European directive is threatening the future of cancer research in Europe, warn experts in this weeks BMJ.

The EU clinical trials directive, implemented in 2004, was intended to protect patients and improve research standards. But many investigators were worried that the labour intensive, bureaucratic, and expensive endeavour of running a clinical trial would become worse under the new rules.

In particular, academic researchers funded by grants, who have so far performed most cancer trials, were worried that their resources might no longer suffice to meet the requirements of the new directive.

An analysis of research since the directive suggests that many of those fears have been realised. For example, the number of new trials fell from 19 in 2004 to 7 in 2005 (63% decrease), and a third fewer patients were enrolled.

Simultaneously, trial costs increased by 85% and insurance costs from 70 to 140 million euros. Trial initiation was about five months slower than in 2004, while paperwork and documentation increased.

Instead of benefiting patients, the analysis suggests that the directive had hindered their access to new treatments.

Our own experiences are in accordance with these findings, say the authors. The number of approved applications for both academic and company sponsored cancer trials in Helsinki has steadily decreased from 120 in 2002 to 70 in 2005 (42% decrease), but the workload of the ethics committee has increased.

These numbers seem to confirm the initial worries about the future of investigator initiated clinical cancer research, say the authors. Current and future patients with metastatic cancer should be worried. If research is thwarted the newest or most effective therapies may not become available rapidly, they warn.

New directives on clinical research are in preparation. Therefore, now is the time for action by physicians, patients, universities, and politicians to ensure that academic research can continue in Europe. It is in no ones interest if only commercial corporations have the resources to plan and carry out clinical trials, they conclude.

Lessons from natalizumab fast tracking in multiple sclerosis

Fri, 17 Feb 2006 19:04:37 PST

( from http://www.rxpgnews.com ) Concerns over the fast tracking of new drugs for commercial licensing are raised by a senior doctor in this weeks BMJ.

It follows approval of natalizumab, a new drug for multiple sclerosis, and its recall three months later, after three trial patients developed a life threatening condition while being treated.

Natalizumab was licensed by the US Food and Drug Administration in 2004 for use in relapsing multiple sclerosis on the basis of short term results from two unpublished trials. The FDA granted approval before final trial and cumulative safety data were available. Natalizumab was predicted to be the leading drug for multiple sclerosis, with estimated annual sales in excess of $2bn.

Around 3000 patients took part in the trials and nearly 5000 patients have been treated in the United States since it became commercially available. In the United Kingdom, natalizumab was due for appraisal by the National Institute for Health and Clinical Excellence in 2006.

But on 28 February 2005, natalizumab was recalled after three trial patients developed progressive multifocal leucoencephalopathy (PML), a rapidly progressive neurodegenerative disease. Two of the patients died.

The approval of natalizumab and its recall after three months raises questions about the fast tracking of new drugs by the FDA for commercial licensing, says the author, consultant neurologist Abhijit Chaudhuri. It also highlights the potential risks for patients in trials of new drugs where knowledge of long term efficacy, outcome measures, and safety is lacking.

Short term solutions for a chronic disease like multiple sclerosis are not likely to be effective, and experience with natalizumab should be taken as a signal to change the way we treat this disease, he concludes.

First human trial of recombinant ricin vaccine completed

Tue, 31 Jan 2006 19:53:37 PST

( from http://www.rxpgnews.com ) Scientists have completed the first human clinical trial of a recombinant vaccine for the deadly toxin ricin - a potential bioterror threat and the results indicate the vaccine is safe and effective in eliciting ricin-neutralizing antibodies, the UT Southwestern Medical Center researchers report.

The nearly year-long pilot study involved three groups of five volunteers each. Individuals in each group received a series of three injections of various doses of the vaccine, called RiVax, over the study period. As a recombinant vaccine, RiVax is a form of ricin that consists of a genetically modified subunit of the toxin, rather than an inactivated whole toxin.

All five of the individuals in the group receiving the highest vaccine dose produced ricin-neutralizing antibodies in their blood, indicating their immune systems had responded. Four of five in the intermediate dose group produced antibodies, while one of five in the lowest dose group did so.

The human-produced antibodies were then injected along with active ricin toxin into test mice, and the mice survived.

"Our major concern in this trial was safety," said Dr. Ellen Vitetta, director of the Cancer Immunobiology Center at UT Southwestern and lead author of the study. Dr. Vitetta's work with ricin received international attention when she and a team of UT Southwestern researchers in the Cancer Immunobiology Center developed the experimental vaccine for the deadly toxin as an outgrowth of their cancer-therapy work. Dr. Vitetta, Dr. Joan Smallshaw, assistant professor in the center, and their colleagues showed in pre-clinical studies that the subunit of the ricin toxin used to make RiVax was non-toxic but retained the capacity to elicit immunity.

Ricin, which can be administered in food and water or sprayed as an aerosol, is extracted from castor beans. There is currently no approved vaccine to prevent ricin poisoning in humans, and the biological agent has a long history of use in espionage.

Participants in the study, however, reported only mild side effects that were consistent with any intramuscular vaccine injection, such as a sore arm or mild headache that might be experienced with a tetanus or a flu shot, said Dr. Robert Munford, a professor of internal medicine and a collaborator on the study.

Based on the protection they observed in the mice injected with ricin mixed with human-produced antibodies, the researchers projected that a RiVax-vaccinated human could withstand a lethal dose of injected ricin. The results from the UT Southwestern trial justify further development of the vaccine, Dr. Vitetta said.
"We have shown that this vaccine is safe and immunogenic," said Dr. Vitetta. Antibodies were present in the blood of study participants for as long as 127 days after the last vaccine injection, but the longevity of the antibodies in a given volunteer was not related to the dose level of the vaccine he or she received. Dr. Vitetta and her colleagues are now conducting studies on mice that combine the vaccine with an adjuvant, a formulation that may lengthen the time the vaccine is effective. Other common vaccines, such as tetanus, are typically administered with an adjuvant and can confer immunity for years.

Dr. Smallshaw is currently determining whether the vaccine protects against aerosol and oral administrations in mice. "In a recent series of experiments, we have shown that the vaccine protects mice against lethal doses of ricin administered orally just as well as it protects them against injected ricin," she said. Dr. Vitetta noted that, in humans, exposure by aerosol or food may require inducing immunity in the lung and gut by a very different formulation and vaccination schedule.

Because castor beans are readily available more than 50,000 tons of castor bean extract exist around the world as a byproduct of castor oil production public health officials warn that ricin could be used for terrorism. The CDC classifies ricin as a "Category B" biological agent, which means it is "relatively easy to disseminate."

New stem cell study seeks to prevent heart failure

Tue, 24 Jan 2006 18:11:37 PST

( from http://www.rxpgnews.com ) University of Rochester Medical Center researchers today announced the launch of a study that will examine whether transplanted stem cells can be safely used to treat damaged heart muscle in patients just after their first heart attack. As part of the fast emerging science of regenerative medicine, labs worldwide are attempting to replace damaged tissue with new cells, much in the same way as salamanders re-grow limbs.

The first-of-its-kind study in heart attack patients will seek to demonstrate the safety, and roughly measure efficacy, of three intravenous doses of adult human stem cells versus placebo in lessening damage to heart muscle within ten days of first heart attack. The treatment recently passed an early safety test and has been approved for study in more patients at higher doses. That process will get underway shortly in Rochester.

"The potential to re-build damaged heart muscle by implanting stem cells that then become new muscle cells is one of the most exciting in cardiology," said Craig R. Narins, M.D., assistant professor of Cardiology at the medical center and principal investigator for the current study. "This study will seek to ensure that stem cell therapy is safe in treating heart failure, a major cause of death in heart attack survivors."

A human embryo starts with one cell that divides to become many. Early on, stem cells change, or differentiate, from non-specific precursors into specialized cells that make up organs. Within a layer of the embryo called the mesenchyma, for example, mesenchymal stem cells (MSCs) can go on to become either cartilage, bone or muscle cells, depending which genetic signals they receive. Some MSCs persist beyond the fetal stage into adulthood in the bone marrow, where researchers believe they await the call to differentiate and replace damaged tissue.

In the process of regeneration, humans continually replace old blood and skin cells with new ones by re-starting some of the mechanisms (e.g. stem cell differentiation) that allowed those tissues to first develop in the fetus. Other tissues, like heart muscle, have almost no ability to regenerate. When humans receive an injury too serious to repair through regeneration, a process called fibrosis kicks in to patch the wound, but also leaves scar tissue that reduces the organ's performance.

More than half a million Americans each year have their first heart attack, a sudden blockage of an artery that deprives heart muscle of blood and oxygen. The resulting injury and scarring often contribute to a gradual loss of the heart's pumping strength, a condition known as congestive heart failure.

Researchers hope that cellular cardiomyoplasty, the use of transplanted stem cells to replace lost heart muscle cells, will do what current treatments cannot: prevent heart muscle loss after heart attack. Animal studies have shown that MSCs injected into heart muscle following a heart attack decreased the death of muscle cells and increased pumping strength.

The new study is a randomized, double-blind, placebo-controlled, Phase I clinical trial with patients randomized to receive either an injection of 0.5 million, 1.6 million or 5.0 million cultured adult mesenchymal stem cells (tradename: Provacelä) per kilogram of body weight, or placebo. There will be 17 active study sites.

Along with the treatment or placebo, all patients will receive standard treatment, including techniques to maximize blood flow to damaged areas, pain relief, oxygen, anti-coagulants, beta-blockers, nitrates, ace-inhibitors and advice on reducing risk factors.

Forty-eight patients will participate in the trial, 22 of which have already been enrolled. Male and female patients are eligible and must be between the ages of 21 and 85 and in good overall health, with the exception of a recent heart attack. Trial entry must occur within 10 days of first heart attack, and patients will be followed for two years afterward.

The trial, to be conducted according to U.S. Food and Drug Administration guidelines, is designed to evaluate safety of treatment with stem cells obtained from healthy, unrelated, adult donors (not from a fetus, embryo or animal). Provacel, developed by Osiris Therapeutics, Inc., is not yet an approved or marketed therapy.

Experts believe that mesenchymal stem cells for many reasons have tremendous potential to become the basis for a powerful new treatment area in cardiology. For instance, research has shown that MSCs, like Blood Type O, are universally compatible, meaning they can be transplanted from person to person without fear of rejection by the recipient's immune system.

Other approaches like harvesting stem cells from the patients' own tissue can be expensive, time-consuming and limited in the numbers of cells produced. Stem cells donated by other humans (allogeneic) make possible the storage of stem cell supplies ready for immediate use as heart attack patients arrive at hospitals.

From a small sample of bone marrow, researchers can grow billions of allogeneic stem cells in cultures, controlled environments that mimic human tissue. Cultured MSCs (hMSCs) are used already in the treatment of some cancers.

In addition, while initial studies injected cells directly into the heart, the picture emerging is that MSCs can be delivered to the heart by a standard injection in the arm. MSCs actually home in on the tissue damaged by heart attack, according to researchers. It has been shown that higher animals store MSCs in the bone marrow, and release them into the blood stream after injury, where they can rush to the site of damage to aid in wound repair the same way that white blood cells rush in to fight infection.

Also like white blood cells, MSCs home for only a short time following injury, so treatment needs to begin as soon as possible after heart attack.

"This technology makes it possible to mass produce stem cells and transplant them from person to person," Narins said. "All of this may make it possible to bank stem cells ahead of time for later, emergency use the way we store blood in blood banks."

Major challenges remain in making cardiomyoplasty a reality, several of which will be addressed by the current trial. For example, implanted stem cells have been shown in some studies to only partly differentiate, with the end result lacking some of the characteristics of a mature heart muscle cell. While studies show that partially differentiated stem cells still prevent muscle cell loss when implanted, researchers seek ways to push differentiation further.

In addition, early studies also found that most implanted MSCs either re-enter the circulation or die rather than engraft to the heart muscle wall to form new muscle cells. In response, researchers are pursuing gene therapy -- the insertion of desired genes into a cell to increase the number of stem cells that live on as new muscle cells and to drive differentiation.

"We are proud to partner with leading research institutions to bring this exciting new therapy into the clinical setting," said C. Randal Mills, Ph.D., president and CEO of Osiris Therapeutics, Inc.

Electronic health record-based clinical trial alert system increased recruitment rates

Tue, 25 Oct 2005 05:15:38 PST

( from http://www.rxpgnews.com ) An electronic health record-based clinical trial alert system increased recruitment rates and physicians' participation in an ongoing clinical trial, according to a study in the October 24 issue of the Archives of Internal Medicine, one of the JAMA/Archives journals.

The success of clinical trials, critical to the advancement of medical science, depends on the recruitment of enough eligible participants in a timely manner, according to background information in the article. Unfortunately, achieving recruitment goals is difficult and failing to meet these goals can hamper the development and evaluation of new therapies and can increase health care system costs. When treating physicians identify and recruit potentially eligible participants for clinical trials, the likelihood that a given patient will participate in a trial increases.

Peter J. Embi, M.D., M.S., from the University of Cincinnati College of Medicine, and colleagues determined whether a clinical trial alert (CTA) system could increase physicians' participation in the recruitment of patients to a clinical trial. After one year of traditional recruitment to a clinical trial, the researchers used their electronic health record (EHR)-based CTA system at The Cleveland Clinic. When a patient's records met selected trial criteria, the CTA alerted the physician about the ongoing trial.

The researchers found that the CTA intervention was associated with a 10-fold increase in the number of referrals generated by physicians, 5.7 per month before intervention to 59.5 per month after. The number of physicians making referrals also increased, from five before intervention to 42 after. The clinical trial enrollment rate more than doubled from 2.9 participants per month to 6.0 participants per month. During the four-month intervention, all of the 114 participating physicians received at least one CTA. Of the 48 physicians who participated, 42 (88 percent) referred at least one patient to the trial coordinator, and 11 (23 percent) of them generated at least one enrollment.

"Use of an EHR-based CTA led to significant increases in physicians' participation in and recruitment rates to an ongoing clinical trial," the authors write. "Given the trend toward the EHR implementation in health care centers engaged in clinical research, this approach may represent a much-needed solution to the common problem of inadequate trial recruitment."

In an accompanying editorial, Al B. Benson III, M.D., from Northwestern University, Feinberg School of Medicine, Chicago, discusses the clinical trial research process.

"Even under the most optimal circumstances, obstacles confront most clinical research projects that can delay the reporting of important clinical information. Because important obstacles to the successful maintenance of a given clinical trials program include recruitment strategies, costs, and time commitments, the integration of an institution's electronic records system with the research record could help to reduce some of the barriers to the accrual of patients to clinical trials," Dr. Benson writes.

"Our country must weigh the risks vs. benefits of clinical research for current and future generations, as well as the costs, training of health care personnel, donation of human biological specimens for research purposes, regulatory and ethical requirements, and the commitment to actively participate in research trials in far greater numbers. For our clinical research enterprise to thrive and to better promote evidence-based medicine, the public and leaders in medicine, industry, and government must have the will to find the way to guarantee sustainable medical advances."

Study of New, Non-Growth Hormone Treatment for Short Stature

Tue, 13 Sep 2005 21:04:38 PST

( from http://www.rxpgnews.com ) Rush University Medical Center is participating in a clinical trial to evaluate the potential benefit of the first major innovation in 20 years for the treatment of growth failure. The drug, called Increlex, was approved by the FDA August 31 for the most severe form of short stature due to a deficiency of Insulin-like Growth Factor-1 (IGF-1). Ongoing trials will determine if the drug may be used for less severe growth disease.

Insulin-like Growth Factor-1 (IGF-1) is the proximate hormone necessary for statural growth and must be present in order for children's bones, cartilage and organs to grow normally. In healthy individuals, growth hormone is secreted into the bloodstream by the pituitary gland and binds to growth hormone receptors on liver and other cells, where it stimulates the cellular production and secretion of IGF-1 into the bloodstream.

"For decades, the only available drug treatment for short stature has been shots of growth hormone. However, patients who are deficient in IGF-1 and resistant to the effects of growth hormone do not respond well, if at all, to the shots," said Dr. Richard Levy, a pediatric endocrinologist at Rush. "Instead of using growth hormone to stimulate the production of IGF-1, the goal is to replace the IGF-1 directly."

Increlex is a genetically engineered copy of IGF-1. The purified protein has been shown to be structurally and functionally identical to natural human IGF-1. It is injected daily before a meal to provide the catalyst the body needs to grow.

The FDA's approval of Increlex is based on clinical trial data from 71 patients. Data reported at the 2004 Annual Meeting of the Endocrine Society demonstrated a statistically significant increase in growth rate over an eight-year period in response to Increlex therapy. Compared to pre-treatment growth patterns, on average, children gained an additional inch per year for each year of therapy over the course of eight years. In addition, an analysis of safety in the study concluded that long-term treatment appears to be well tolerated and has an acceptable safety profile. The most common adverse events were hypoglycemia, lipohypertrophy and tonsillar hypertrophy.

Primary IGFD afflicts an estimated 30,000 children evaluated for short stature in the United States. A child with short stature is defined as being shorter than 97.5 percent of all children the same age and gender. If untreated, Primary IGFD may lead, in children and adults, to a range of other metabolic disorders, including lipid abnormalities, decreased bone density, obesity, and insulin resistance.