Abuse and Neglect, Dermatology, Pharmacology / 11.12.2017

MedicalResearch.com Interview with: Dr. Jonathan L. Silverberg MD PhD MPH Assistant Professor in Dermatology Medical Social Sciences and Preventive Medicine Northwestern University, Chicago, Illinois MedicalResearch.com: What is the background for this study? What are the main findings? Response: Systemic corticosteroids are commonly used as systemic treatments for atopic dermatitis. However, few studies assessed the efficacy and safety of systemic corticosteroids in atopic dermatitis. This systematic review sought to summarize the available evidence for their use in atopic dermatitis. Overall, 52 reviews and 12 studies were included in this systematic review. Most studies suffered from small sample size, low quality. In one of the only randomized-controlled trials performed, systemic corticosteroids were less effective than cyclosporine and led to more rebound flares. There were numerous safety and tolerability concerns with both short and long-term treatment with systemic corticosteroids. One study found that even short-term use of systemic corticosteroids was associated with increased sepsis, venous thromboembolism and fractures. (more…)
Author Interviews, Cancer Research, Orthopedics, Pharmacology / 13.11.2017

MedicalResearch.com Interview with: Charles L.Shapiro MD Professor of Medicine Director of Translational Breast Cancer Research Director of Cancer Survivorship Division of Hematology/Oncology Tisch Cancer Institute New York, NY MedicalResearch.com: What is the background for this study? What are the main findings? Response: The new 2017 ASCO guidelines for the use bone-modifying in individuals with bone metastases recently endorsed every 3-month zoledronic, because of high level evidence from three randomized trials, including our trial (published in Jama in Jan 2017, first author Himelstein et al) that giving zoledronic acid every 3-months was non-inferior to the standard of monthly zoledronic. The guidelines also concluded that there was not one preferred bone modifying agent of the other, despite the fact the comparing monthly zoledronic to monthly denosumab in women with bone metastases, denosumab delayed the time to first skeletal-related event (pathological fractures, necessity for radiation or surgery, and spinal cord compression) and subsequent events by 23% (or in absolute terms about 3 months) . Zoledronic acid became generic in 2013, whereas monthly denosumab is still patented until 2022-25. (more…)
Author Interviews, Autism, Pharmacology / 07.11.2017

MedicalResearch.com Interview with: Dr. Mark E. Gurney, PhD MBA Chairman & CEO, Tetra Discovery Partners Inc. MedicalResearch.com: What is the background for this study? What are the main findings? Response: Fragile X is a genetic condition. Affected patients display a range of behavioral and other symptoms, including seizures, sleep disorders, anxiety, irritability, hyperactivity, autism, mild-to-severe cognitive impairment and intellectual disability. BPN14770 is a novel therapeutic agent that selectively inhibits phosphodiesterase-4D (PDE4D). Inhibition of PDE4 has been validated as a treatment strategy by many research groups in the Fragile X field, but non-selective PDE4 inhibitors have been associated with significant GI side-effects that have limited those drugs’ use. As a selective inhibitor, such side-effects were not seen for BPN14770 in a Phase 1 clinical trial in healthy young and elderly adults. In the current study, daily treatment of Fragile X knock-out (FXS) mice with BPN14770 showed a reduction in hyperarousal, improved social interactions and natural behaviors, and changes in nerve structure in the prefrontal cortex of the brain, the portion of that brain associated with cognition. Moreover, the drug’s benefit persisted for two weeks after all drug was cleared from the mice. At the same time, the behavior of normal mice treated with the drug remained unchanged. Examination of neurons from the prefrontal cortex of the treated FXS mice showed an improvement in dendritic spine morphology. (more…)
AstraZeneca, Author Interviews, Boehringer Ingelheim, Diabetes, Eli Lilly, J&J-Janssen, Merck, Pharmacology / 18.10.2017

MedicalResearch.com Interview with: Melanie J Davies CBE MB ChB MD FRCP FRCGP Professor of Diabetes Medicine NIHR Senior Investigator Emeritus Diabetes Research Centre Leicester Diabetes Centre – Bloom University of Leicester MedicalResearch.com: What is the background for this study? What are the main findings? Response:  This was the first study to test the effectiveness of an oral GLP-1 in patients with type 2 diabetes. The main findings were that compared to both placebo and a GLP-1, Semaglutide, delivered by sub-cutaneous injection weekly, the oral therapy delivered once a day produced better results than placebo and similar results to injectable GLP-1 with regard to reductions in HbA1c and weight loss. (more…)
Author Interviews, Depression, Diabetes, JAMA, Pediatrics, Pharmacology / 17.10.2017

MedicalResearch.com Interview with: Mehmet Burcu, PhD, MS Department of Pharmaceutical Health Services Research University of Maryland, Baltimore  MedicalResearch.com: What is the background for this study? What are the main findings? Response: Antidepressants are one of the most commonly used psychotropic medication classes in U.S. youth, with serotonin reuptake inhibitors representing a large majority of total antidepressant use in youth. The most interesting finding was that the current use of serotonin reuptake inhibitors in youth was associated with an increased risk of type 2 diabetes mellitus, and this increased risk intensified further with the increasing duration of use and with the increasing dose. A secondary analysis also revealed that the risk of incident type 2 diabetes was most apparent in youth who used serotonin reuptake inhibitors for longer durations AND in greater daily doses. (more…)
Author Interviews, Gastrointestinal Disease, Pharmacology / 15.10.2017

MedicalResearch.com Interview with: Brooks D. Cash, M.D., A.G.A.F., F.A.C.G., F.A.S.G.E. Professor of Medicine and Chief of the USA Gastroenterology Division Director, Motility and Physiology Service University of South Alabama Mobile, Alabama  MedicalResearch.com: What is the background for this study? Response: Irritable Bowel Syndrome (IBS) among patients with IBS-M (mixed diarrhea and constipation) is a challenging and difficult to diagnose and treat sub-type of IBS. Patients with IBS-M represent a dissatisfied group of IBS patients due to the lack of proven therapies. It is an area of high unmet medical need. Among adult patients with IBS, a sizeable proportion suffers from IBS-M with prevalence rates estimated to be between 44 to 66 percent of IBS sufferers[1],[2],[3]. IBS-M patients carry a heavy burden, characterized by bouts of constipation interrupted by diarrhea and vice versa. Physicians find IBS-M challenging to manage because of the difficulty in avoiding ‘overshoots’ when diarrhea management can turn into constipation and vice versa.[4]  (more…)
Author Interviews, Mental Health Research, Pharmacology, Psychological Science / 10.10.2017

MedicalResearch.com Interview with: Vanda Faria PhD Department of Psychology Uppsala, Sweden  MedicalResearch.com: What is the background for this study? What are the main findings? Response: It has been debated whether selective serotonin reuptake inhibitors (SSRIs), which are commonly prescribed for depression and anxiety, are more effective than placebo. Concerns have been raised that the beneficial effects of SSRIs, as measured in double-blind clinical trials, may be explained by expectancies (a crucial placebo mechanism) rather than the biochemical compound. But no study has tested experimentally the extent to which the SSRI treatment effect can be influenced by expectancies induced by verbal suggestions. We compared the efficacy of overt vs. covert administration of an SSRI (escitalopram) in patients with social anxiety disorder. Rather than comparing the SSRI with placebo, we compared it with itself while manipulating the patients’ expectations of improvement. This was achieved by informing one group correctly about the SSRI and its effectiveness (overt group) whereas the comparison (covert) group received incorrect information. By use of a cover story, the covert group was led to believe they were treated with a so called “active placebo”, an ineffective neurokinin-1 antagonist yielding similar side effects as the SSRI but lacking anxiety-reducing properties. But the treatment, dosage and duration was in fact identical in both groups. Results showed that overt outperformed covert SSRI treatment, as the number of treatment responders was more than three times higher on the main clinical outcome measure when correct information was given. Using neuroimaging (fMRI) we also noted differences between the overt and covert SSRI groups on objective brain activity measures. There were differences between the groups e.g. with regard to activation of the posterior cingulate cortex with treatment, and the functional coupling between this region and the amygdala which is a brain region crucially involved in fear and anxiety. The fMRI  results may reflect the interaction between cognition and emotion as the brain changes differently with treatment pending on the expectations of improvement. (more…)
Author Interviews, Pharmacology, Toxin Research / 04.10.2017

“Pills” by Victor is licensed under CC BY 2.0MedicalResearch.com Interview with: Tony Wing Lai Mak , MBChB, MBA, FRCPath, FRCPA, FHKCPath, FHKAM(Path  Hospital Authority Toxicology Reference Laboratory Princess Margaret Hospital, Hong Kong MedicalResearch.com: What is the background for this study? What are the main findings? Response: Proprietary Chinese medicines (pCMs) and health products are generally believed to be natural and safe. However, the safety of pCMs and health products has been compromised by the illicit practice of adulteration with undeclared drugs. Such adulteration can have serious and even fatal consequences. Previous reports of pCM and health product adulteration were mainly routine surveillance data or case reports/series with a small number of affected patients. The present study in Hong Kong, to our knowledge, is the largest case series that reports an overview of the use of various adulterated Proprietary Chinese medicine and health products and the resulting adverse effects. From 2005 to 2015, we have identified 404 cases involving the use of 487 adulterated pCMs or health products with a total of 1234 adulterants detected. The adulterants consisted of approved drugs, banned drugs, drug analogues and animal thyroid tissue. The six most common categories of adulterants detected were nonsteroidal ant-inflammatory drugs (18%), anorectics (15%), corticosteroids (14%), diuretics and laxatives (11%), oral antidiabetic agents (10%), and erectile dysfunction drugs (6%). Sibutramine, an anorectic that has been withdrawn from the market owing to its association with increased cardiovascular events and strokes, was the most common adulterant identified. A significant proportion of patients (65.1%) had adverse effects that were attributable to these illicit products, including 14 severe and two fatal cases. These illicit Proprietary Chinese medicine and health products pose severe health hazards to the public. (more…)
Author Interviews, Boehringer Ingelheim, Pharmacology, Pulmonary Disease / 02.10.2017

MedicalResearch.com Interview with: Professor Carlo Vancheri Professor of Respiratory Medicine, University of Catania, Italy and Director of the Regional Referral Centre for Rare Lung Diseases and the Laboratory of Experimental Respiratory Medicine. MedicalResearch.com: What is the background for this study? What are the main findings?  Response: The aim of Boehringer Ingelheim’s INJOURNEY trial was to investigate the safety profile of Ofev (nintedanib) in combination with pirfenidone in treating patients with idiopathic pulmonary fibrosis (IPF). Nintedanib and pirfenidone, the only two FDA-approved drugs for the treatment of IPF, are able to slow down the progression of the disease, reducing the forced vital capacity (FVC) decline of about 50%, but this is not a cure. The target for the future is to have even more effective treatments. In the meanwhile, it is necessary to optimize the use of the available drugs. The medical treatment of other pulmonary diseases such as COPD, asthma or pulmonary hypertension is already based on different combinations of drugs. This 12-week, open-label, randomized study was designed to evaluate the safety, tolerability and pharmacokinetics of nintedanib with add-on pirfenidone, compared with nintedanib alone in patients with IPF. Change in FVC, the established efficacy endpoint in IPF trials, was evaluated as an exploratory endpoint. The primary endpoint of the INJOURNEY trial was the percentage of patients with on-treatment gastrointestinal adverse events from baseline to week 12 of randomized treatment, and the results showed that the combination of nintedanib and add-on pirfenidone resulted in a manageable safety and tolerability profile, similar to the profile of each drug individually in the majority of patients. Results also indicated there may be a slower decline in FVC in patients treated with pirfenidone along with nintedanib compared with nintedanib alone, suggesting a potential benefit of the combination. However, further research will be necessary to fully evaluate the efficacy of the combination. (more…)
Author Interviews, BMJ, Mental Health Research, OBGYNE, Pharmacology / 10.09.2017

MedicalResearch.com Interview with: Xiaoqin Liu, PhD Department of Economics and Business Economics Aarhus University  MedicalResearch.com: What is the background for this study? What are the main findings? Response: Previous research on the long-term neurodevelopmental outcomes of serotonin-reuptake inhibitor (SSRI) use during pregnancy has primarily focused on offspring risk of autism spectrum disorder. Given SSRIs cross the placental barrier and affect the fetal brain, in-utero SSRI exposure may increase risks of other psychiatric disorders as well as autism spectrum disorder. We conducted a population-based study to look at a range of diagnostic groups of psychiatric disorders in children whose mothers used antidepressants during pregnancy. This was possible because of the nature of information available in Danish population registers, allowing us to follow children for many years. We found increased risks of various diagnostic groups of psychiatric disorders in children whose mothers continued antidepressant treatment during pregnancy, in comparison to children whose mothers stopped antidepressant treatment before pregnancy. (more…)
Author Interviews, Diabetes, Heart Disease, Pharmacology / 31.08.2017

MedicalResearch.com Interview with: Todd Hobbs, MD Vice President and Chief Medical Officer Novo Nordisk North America  MedicalResearch.com: Would you tell us a little about liraglutide? How does it work to control diabetes/blood sugar?  Response: Victoza® (liraglutide) is a human glucagon-like peptide-1 (GLP-1) analog that was approved by the U.S. Food and Drug Administration (FDA) in 2010 to help lower blood sugar in adults with type 2 diabetes. Victoza® is the #1 prescribed (GLP-1) receptor agonist. Victoza® is a non-insulin, once-a-day medication that helps lower blood sugar levels in adults with type 2 diabetes by increasing glucose-dependent insulin release, inhibiting glucagon secretion, and slowing gastric emptying. On August 25, the FDA approved a new indication for Victoza®, making it the only type 2 diabetes treatment approved to reduce the risk of major adverse cardiovascular (CV) events, heart attack, stroke and CV death, in adults with type 2 diabetes and established CV disease. (more…)
Author Interviews, Osteoporosis, Pharmacology / 30.08.2017

MedicalResearch.com Interview with: Dieter Bromme, Ph.D. Professor and Canada Research Chair The University of British Columbia Faculty of Dentistry Vancouver, BC MedicalResearch.com: What is the background for this study? What are the main findings? Response: Every three seconds somebody will fracture a bone because of osteoporosis. Several treatments are available to slow down bone loss but all of them have shortcomings ranging from poor bone quality to various side effects. Thus new treatment strategies and novel drug targets are needed that promise efficacy without significant adverse reactions. One of the novel promising targets was cathepsin K, a protease solely responsible for the degradation of our organic bone matrix. Major efforts and funds were spent by the pharmaceutical industry to develop potent and selective cathepsin K inhibitors. These inhibitors were highly effective in preserving bone in clinical trials. Despite the good news, cathepsin K inhibitors were never approved because of various non-skeletal side effects. We hypothesized that these side effects are not caused by off-target effects (drugs react with undesired targets) but by on-target effects. Most drugs that target enzymes are active site-directed compounds and thus will stop the entire activity of the target enzyme. If the target is a multifunctional enzyme, safety problems are preprogrammed. Based on our studies to understand the molecular mechanism of collagen degradation by cathepsin K, we developed the concept of ectosteric enzyme inhibition, which allowed us to identify highly selective collagenase inhibitors of this protease. In our study, we used a red sage-derived small molecule that selectively blocked the collagenase activity of cathepsin K and thus consequently bone degradation in an osteoporosis mouse model without affecting other known functions of the protease. The crucial difference might be that the red sage inhibitor did not block the cathepsin K-mediated degradation of TGF-ß1, a growth factor involved in fibrotic pathologies described in the clinical trials. TGF-ß1 degradation is blocked by these inhibitors and thus accumulates in tissues, causing fibrosis. (more…)
Author Interviews, JNCI, Mental Health Research, Pharmacology, UT Southwestern, Weight Research / 23.08.2017

MedicalResearch.com Interview with: Chen Liu, Ph.D. Assistant Professor Departments of Internal Medicine and Neuroscience Division of Hypothalamic Research The University of Texas Southwestern Medical Center Dallas, Texas 75390-9077  MedicalResearch.com: What is the background for this study? Response: Atypical antipsychotics are second-generation antipsychotics (SGAs) that have been increasingly used to treat a variety of neuropsychiatric conditions such as schizophrenia, depression, and autism. Many patients taking these medications, however, are left in an agonizing dilemma. On one hand, they rely on these drugs’ psychotropic effect for normal functioning in daily life. On the other, many SGAs, including the most widely prescribed olanzapine and clozapine, can cause a metabolic syndrome that is known for excessive weight gain, dyslipidemia, and type-2 diabetes_ENREF_2. Notably, while full-blown type 2 diabetes and morbid obesity typically take years to unfold in the general population, these conditions progress at a much faster pace (within months) following second-generation antipsychotics treatment. Other factors such as ethnicity, age, and sex can also aggravate SGA-induced metabolic syndrome. Together, these peculiar features strongly suggest a distinct etiology underlying SGA-induced metabolic syndrome that has yet been fully elucidated. Currently, there is no medication specifically targeting SGA-induced metabolic syndrome. For many youths and adults taking second-generation antipsychotics, metabolic complications are difficult to manage as lifestyle changes, nutritional consulting, and commonly used anti-diabetic medications only provide limited relief. (more…)
Author Interviews, Pain Research, Pharmacology, PLoS / 17.08.2017

MedicalResearch.com Interview with: Harsha Shanthanna MBBS, MD, MSc Associate Professor, Anesthesiology Chronic Pain Physician St Joseph's Healthcare,McMaster University Hamilton, Canada Diplomate in National Board, Anesthesiology (India) Fellow in Interventional Pain Practice (WIP) European Diplomate in Regional Anesthesia and Pain MedicalResearch.com: What is the background for this study? Response: Pregabalin (PG) and gabapentin (GB) are increasingly used for nonspecific Chronic Low Back Pain (CLBP) despite a lack of evidence. There have been concerns expressed over their increased prescribing for various non cancer pain indications in recent years. Their use requires slow titration to therapeutic doses and establishing maintenance on a long-term basis. With prolonged treatment, the potential gain over possible adverse effects and risks could become unclear. We searched Cochrane, MEDLINE and EMBASE databases for randomized control trials reporting the use of gabapentinoids for chronic lower back pain treatment of 3 months or more in adult patients. (more…)
ADHD, Author Interviews, JAMA, Pharmacology / 26.07.2017

MedicalResearch.com Interview with: Professor Ian Chi Kei Wong and Kenneth KC Man, Senior Research Assistant Department of Social Work and Social Administration, Faculty of Social Science Department of Pharmacology and Pharmacy, LKS Faculty of Medicine The University of Hong Kong MedicalResearch.com: What is the background for this study? What are the main findings? Response: Patients with attention-deficit/hyperactivity disorder (ADHD) are at higher risk of various mental health problems. Previous studies suggested that individuals with ADHD are having a higher chance of both attempted and completed suicide. Methylphenidate is a psychostimulant that is recommended for the treatment of ADHD. With the increasing usage of methylphenidate over the past decade, there are concerns about the safety of the medication, in particular, psychiatric adverse effects such as suicide attempt. The current study looked into over 25,000 patients aged 6 to 25 years in Hong Kong who were receiving methylphenidate in 2001 to 2015. Using the self-controlled case series design, in which the patients act as their own control, we found that the risk of suicide attempt was 6.5 fold higher during a 90-day period before methylphenidate was initiated, remained elevated 4-fold during the first 90 days of treatment, and returned to the normal level during ongoing treatment. (more…)
Author Interviews, HIV, J&J-Janssen, Merck, Pharmacology / 26.07.2017

MedicalResearch.com Interview with: Dr. Kathleen Squires MD Professor and Director of Infectious Diseases Thomas Jefferson University Philadelphia, PA  MedicalResearch.com: What is the background for this study? What are the main findings?
  • The pivotal Phase 3 DRIVE-AHEAD study evaluated the safety and efficacy of a once-daily, single tablet, fixed-dose combination containing doravirine, an investigational non-nucleoside reverse transcriptase inhibitor (NNRTI) for the treatment of HIV-1 infection, compared to a fixed-dose combination containing efavirenz.
    • After 48 weeks of treatment, 84 percent of the 364 treatment-naïve patients taking once-daily DOR/3TC/TDF achieved levels of HIV-1 RNA <50 copies/mL compared to 81 percent of the 364 patients taking once-daily EFV/FTC/TDF, with an estimated treatment difference of 3.5 percent.
    • Increases in mean CD4+ T-cell counts from baseline for the DOR/3TC/TDF and EFV/FTC/TDF groups were 198 and 188 cells/mm3, respectively, with an estimated treatment difference of 10.1.
    • In addition, comparable efficacy was observed across both treatment groups among individuals with high viral load (HIV-1 RNA >100,000 copies/mL) at baseline, which consisted of 69 patients in the DOR/3TC/TDF group and 73 patients in the EFV/FTC/TDF group (Observed Failure approach).
      • Of those patients with a high viral load (HIV-1 RNA >100,000 copies/mL) at baseline, 81 percent in the DOR/3TC/TDF group and 81 percent in the EFV/FTC/TDF group achieved the study’s primary endpoint of <50 copies/mL of HIV-1 RNA, with a treatment difference of 1.0 percent.
    • The study also met its primary safety endpoint, showing that treatment with DOR/3TC/TDF resulted in fewer patients reporting events of several pre-specified neuropsychiatric adverse events compared to EFV/FTC/TDF by Week 48, including dizziness (8.8 percent versus 37.1 percent); sleep disorders and disturbances (12.1 percent versus 25.5 percent); and inability to think clearly or concentrate (4.4 percent versus 8.2 percent).
(more…)
Author Interviews, HIV, Merck, Pharmacology / 25.07.2017

MedicalResearch.com Interview with: Dr. Pedro Cahn Chief of the infectious disease unit at Juan A. Fernandez Hospital Buenos Aires, Argentina, and ONCEMRK lead study investigator MedicalResearch.com: What is the background for this study? What are the main findings? The ONCEMRK Phase 3 study was conducted to evaluate the efficacy and safety of once-daily ISENTRESS (raltegravir) HD 1200 mg (given as two 600 mg oral tablets) compared to twice daily raltegravir 400 mg, each in combination therapy with emtricitabine plus tenofovir disoproxil fumarate in previously untreated adults with HIV-1 infection with levels of HIV-1 RNA ≥ 1,000 copies/mL.
  • Week 96 data showed:
    • 5 percent of the 531 patients taking once-daily raltegravir 1200 mg (2 x 600 mg) achieved viral suppression of less than 40 copies/mL of HIV-1 RNA, compared to 80.1 percent of the 266 patients taking twice-daily raltegravir 400 mg, both in combination therapy with emtricitabine plus tenofovir disoproxil fumarate, with a treatment difference of 1.4 percent.
    • Increases in CD4+T-cell counts from baseline were comparable for the two treatment regimens, with an average increase of 261.6 cells/mm3 for once-daily raltegravir (1200 mg) and 262.2 cells/mm3 for twice-daily raltegravir (400 mg).
    • Efficacy was consistent across a variety of patient populations, including those with high viral load at baseline (HIV-1 RNA >100,000 copies/mL).
    • Treatment-emergent viral mutations leading to any drug resistance were detected in less than 1 percent of patients in both treatment arms, with 4/531 (0.8 percent) in the once-daily raltegravir (1200 mg) treatment arm, and 2/266 (0.8 percent) in the twice-daily raltegravir (400 mg) treatment arm through 96 weeks.
    • The rate of discontinuation of therapy due to adverse events through 96 weeks was low (1.3 percent in patients receiving once-daily raltegravir (1200 mg) and 2.3 percent in patients receiving twice-daily raltegravir (400 mg).
(more…)
Annals Internal Medicine, AstraZeneca, Author Interviews, Brigham & Women's - Harvard, Heart Disease, Merck, Pharmacology / 25.07.2017

MedicalResearch.com Interview with: Alexander Turchin, MD,MS Director of Quality in Diabetes Associate Professor, Harvard Medical School Brigham and Women's Hospital Boston, MA MedicalResearch.com: What is the background for this study? Response: Cardiovascular disease is the # 1 cause of death in the U.S. and worldwide. Statins are some of the most effective medications available for prevention of cardiovascular events. However, many patients stop statins, frequently because of adverse reactions. In our study we aimed to assess the risk-benefit balance of trying a statin again after experiencing an adverse reaction. (more…)
Author Interviews, Opiods, Pharmacology / 10.07.2017

Medical Research.com Interview with: Dr. Christian Heidbreder, PhD Chief Scientific Officer Indivior Inc. Richmond, VA 23235, USA MedicalResearch.com: What is the background for this study? What are the main findings? Response: This pivotal Phase 3 clinical trial (RB-US-13-0001) evaluated the efficacy and safety of RBP-6000, an investigational once-monthly injectable buprenorphine in the ATRIGEL® delivery system for the treatment of adults with moderate-to-severe opioid use disorder (OUD) as part of a complete treatment plan to include counseling and psychosocial support1. The 24-week Phase 3 study met its primary and key secondary endpoints, demonstrating statistically significant differences in percentage abstinence and treatment success across both dosage regimens of RBP-6000 versus placebo1. The findings also showed that outcomes with RBP-6000 are consistent across other secondary clinical endpoints, including control of craving and withdrawal symptoms, as compared to placebo. These outcomes were associated with buprenorphine plasma concentrations ≥ 2 ng/mL and predicted whole brain mu-opioid receptor occupancy of ≥ 70%, and were also maintained for the one-month dosing intervals and for the entire treatment duration1. The results were confirmed by exposure-response analyses demonstrating a relationship between buprenorphine plasma concentrations, abstinence, withdrawal symptoms and opioid craving1. RBP-6000 was generally well tolerated and had a safety profile consistent with that of transmucosal buprenorphine. Injection site reactions were not treatment-limiting. The most common (reported in ≥ 5% of subjects) treatment-emergent adverse events (TEAEs) reported in the active total group were constipation, headache, nausea, injection site pruritus, vomiting, increased hepatic enzyme, fatigue and injection site pain1. (more…)
Author Interviews, Diabetes, JAMA, Pharmacology / 05.07.2017

MedicalResearch.com Interview with: Wendy Lane MD Director of Clinical Research Mountain Diabetes and Endocrine Center Asheville, NC MedicalResearch.com: What is the background for this study? What are the main findings? Response: The SWITCH1 trial was the first double blinded insulin trial to compare the rate of severe, nocturnal severe and symptomatic blood glucose-confirmed hypoglycemia between two basal insulins, insulin glargine U100 and insulin degludec U100, in patients with type 1 diabetes. The trial design (double blinded crossover treat-to-target) eliminated any bias in the results, which showed clear-cut reductions in all categories of hypoglycemia with insulin degludec compared to insulin glargine. Severe hypoglycemia has dangerous and greatly feared consequences including cognitive impairment, seizures, coma and death, and it is the main barrier to effective use of insulin in the treatment of type 1 diabetes. Insulin degludec, which was shown to reduce the risk of hypoglycemia compared to insulin glargine in the SWITCH1 trial, should be viewed by clinicians as an advancement in insulin therapy which will increase its safety and improve the quality of life of our patients with type 1 diabetes. (more…)
Author Interviews, Cost of Health Care, Pharmacology / 19.06.2017

MedicalResearch.com Interview with: Kimberly Westrich, MA Vice President, Health Services Research, National Pharmaceutical Council, and Kristina Lunner Principal, Leavitt Partners MedicalResearch.com: What is the background for this study? Response: With the advent of accountable care organizations (ACOs) following passage of the Affordable Care Act in 2010, it became important to understand how success in an ACO world is different from success in a capitated environment, where the focus is only on managing costs. In an ACO, providers are responsible for the quality of care they provide for a defined population in addition to having at least some financial responsibility. We wanted to explore how an ACO can succeed in this environment of dual responsibility for costs and quality, and more specifically, how pharmaceuticals fit into this success. To address these questions, the National Pharmaceutical Council worked with the American Medical Group Association (AMGA), Premier, Inc., and a group of seven leading ACOs to develop a conceptual framework for considering the role of pharmaceuticals in ACOs. This framework shows how optimizing medication use in a value-based healthcare environment, such as an ACO, can help the organization achieve its cost and quality benchmarks. We evaluated ACO readiness to optimize medication use in 2014 and again with our most recent study, published in June 2017 online ahead of print in the Journal of Managed Care & Specialty Pharmacy. For our 2017 study, we worked with Leavitt Partners to survey and interview ACOs to understand how they optimize medication use, determine if there is an association between efforts to optimize medication use and achievement on financial and quality metrics, ascertain organizational factors that correlate with optimized medication use, and identify barriers to optimized medication use. (more…)
Author Interviews, Depression, OBGYNE, Pharmacology / 19.06.2017

MedicalResearch.com Interview with: Samantha Meltzer-Brody, MD, MPH Associate Professor and Associate Chair for Faculty Development Director, Perinatal Psychiatry Program Director, Taking Care of Our Own Program Department of Psychiatry Chapel Hill, NC 2759  MedicalResearch.com: What is the background for this study? What are the main findings? Response: The Lancet published results from a randomized, placebo-controlled, phase 2 clinical trial with the investigational medication, brexanolone, for women with severe postpartum depression (PPD). During the study, which was conducted at multiple sites across the country, physician researchers administered brexanolone in 21 women, 10 of whom were administered a 60-hour infusion of brexanolone. The other 11 women were given a placebo. Results from the trial showed that 70 percent of participants who received the drug saw remission of their PPD symptoms within 60 hours of treatment, an effect that was maintained until the 30-day follow up. (more…)
Author Interviews, Merck, Pharmacology / 13.06.2017

MedicalResearch.com Interview with: Roy F Chemaly, M.D., M.P.H., F.A.C.P., F.I.D.S.A Professor, Department of Infectious Diseases, Director, Infection Control and Employee Health, Division of Internal Medicine Director of the clinical virology research program,Department of infectious diseases Infection control and employee health The University of Texas MD Anderson MedicalResearch.com: Would you briefly explain the significance of CMV infections? What is the background for this study? Response: Cytomegalovirus (CMV) is one of the most important causes of infectious complications following organ transplantation and is a significant cause of illness and death in patients who have undergone allogeneic hematopoietic cell transplantation (allo-HCT). For more than 20 years, we have been managing this infection and trying to develop effective strategies to control it, but to no one’s satisfaction; CMV infection is still associated with significant morbidity and mortality in this high-risk population. Most transplant centers have adopted preemptive antiviral therapy as the strategy of choice for HCT patients.1 While anti-CMV drugs have decreased the incidence of CMV diseases, their use for prophylaxis has not been associated with improved outcomes.1 Demographic and transplant trends heighten the need for new anti-CMV agents. In the U.S, 83% of people aged 60 and older are CMV seropositive. These older patients received 8% of all hematopoietic-cell transplants in 2000-2006, a figure that jumped to 22% in 2007-2013. As Baby Boomers age, many more allogeneic transplant patients will be CMV seropositive. Therefore, prophylactic antiviral compounds that could effectively control viral replication, and restrict some pathologic processes of CMV diseases, could potentially lessen the complications associated with CMV infection and possibly reduce all-cause mortality. (more…)
Author Interviews, Pharmacology / 12.06.2017

MedicalResearch.com Interview with: Huseyin Naci, PhD Assistant Professor of Health Policy LSE Health Department of Social Policy London School of Economics and Political Science London, United Kingdom  MedicalResearch.com: What is the background for this study? What are the main findings? Response: An increasing proportion of novel therapeutic agents are entering the market on the basis of expedited development and approval programs. The Food and Drug Administration's (FDA) Accelerated Approval pathway is one such expedited approval program. In our study, we examined the dynamics of research on drugs receiving accelerated approvals. We were particularly interested in the timing and characteristics of research studies including drugs with accelerated approvals. Our primary findings are the following:
  • First, there is an abundance of research on drugs receiving accelerated approvals. Yet, the majority of this research (about 70%) is of poor quality. Ideally, these drugs are evaluated in so-called randomised controlled trials to establish their efficacy and safety. However, only about a third of all existing studies are randomised controlled trials.
  • Second, a substantial share (about 30%) of the existing research on these drugs is in areas not approved by the FDA. This may be indicative of industry research practices in trying to prioritise identification of new uses for drugs receiving accelerated approvals instead of strengthening their evidence base.
  • Third, when focusing on well-designed studies, only about a half actually evaluate the effectiveness of the accelerated approval drugs. The rest appears to use the accelerated approval drug as background therapy. Interestingly, these two types of studies are conducted concurrently. In other words, while one research group is trying to find out if an accelerated approval drug is effective, other research groups are already using it as part of a background regimen when testing the effectiveness of another, potentially newer drug
(more…)
Author Interviews, Depression, Pharmacology / 12.06.2017

MedicalResearch.com Interview with: Greta A Bushnell, MSPH Doctoral Candidate, Department of Epidemiology UNC, Gillings School of Global Public Health MedicalResearch.com: What is the background for this study? What are the main findings? Response: Patients with depression may be co-prescribed a benzodiazepine at antidepressant initiation for a short period for a variety of reasons. Reasons include reducing concurrent anxiety and insomnia, reducing depression severity more quickly, and improved antidepressant continuation. However, there are concerns with benzodiazepines including dependency. As such, benzodiazepines are usually recommended for only short-term treatment. Prior to our study, little was known about a) how often new simultaneous antidepressant and benzodiazepine prescribing occurred among patients initiating antidepressant treatment for depression or b) whether new simultaneous users became long-term benzodiazepine users. In a large commercial insurance database, we identified adults aged 18-64 years with depression who initiated an antidepressant from 2001 to 2014. We found that 11% of adults simultaneously initiated benzodiazepine treatment, which increased from 6% in 2001 to a peak at 12% in 2012. We observed similar antidepressant treatment length at six months in simultaneous new users and among patients initiating antidepressants only. The majority of simultaneous new users had only one benzodiazepine prescription fill before benzodiazepine discontinuation; however, 12% were identified as long-term benzodiazepine users. (more…)
Author Interviews, JAMA, Karolinski Institute, Pharmacology, Schizophrenia / 09.06.2017

MedicalResearch.com Interview with: Jari Tiihonen, MD, PhD Professor, Department of Clinical Neuroscience Karolinska Institutet Stockholm, Sweden  MedicalResearch.com: What are the limitations of existing analyses of the comparative effectiveness of antipsychotics? Response: It has remained unclear if there are clinically meaningful differences between antipsychotic treatments in relapse prevention of schizophrenia, due to the impossibility of including large unselected patient populations in randomized controlled trials, and due to residual confounding from selection biases in observational studies. (more…)
Author Interviews, Pharmacology, Pulmonary Disease, University of Michigan / 09.06.2017

MedicalResearch.com Interview with: Kevin R. Flaherty, M.D., M.S. Professor, Department of Internal Medicine Associate Director, T32 Multidisciplinary Training Program in Lung Diseases Chair, Pulmonary Fibrosis Foundation Clinical Care Network Steering Committee University of Michigan Medicine  MedicalResearch.com: What is the background for this study? What are the main findings? Response: This is a new post-hoc analysis, recently presented at the 2017 American Thoracic Society (ATS) conference, which sought to further assess the efficacy of Ofev (nintedanib), an FDA-approved drug treatment for idiopathic pulmonary fibrosis (IPF), and its effect on lung function in those with this disease. IPF is a rare and serious lung disease that causes permanent scarring of the lungs and affects as many as 132,000 Americans. The analysis examined pooled data from the two placebo-controlled, global Phase III INPULSIS trials, which evaluated the efficacy and safety of 52 weeks’ treatment with nintedanib in people with IPF. In both trials, a higher proportion of people treated with placebo than nintedanib had disease progression from baseline to week 52, as defined by the proportions of patients with ≥5% or ≥10% declines in lung function, as measured by forced vital capacity (FVC) % predicted. Additionally, a lower proportion of patients treated with placebo than nintedanib had no decline or an improvement in FVC % predicted. These data support the initial findings from the Phase III INPULSIS trials which found that more patients treated with nintedanib versus placebo had an absolute decline in FVC of less than 5%. In this subgroup analysis, we assessed the proportions of patients from the two INPULSIS trials treated with nintedanib and placebo who had no decline or an improvement in lung function from baseline to week 52 using pooled data for this post-hoc analysis. In terms of those who participated, a total of 864 patients were included (519 treated with nintedanib, 345 treated with placebo). Baseline characteristics including age, gender and FVC were similar between the subgroups of patients who had no decline or an improvement in FVC and those whose FVC declined, and between the nintedanib and placebo groups within each subgroup. (more…)
Author Interviews, Pharmacology / 05.06.2017

MedicalResearch.com Interview with: William D. Chey, M.D., F.A.C.G. Director, Division of Gastroenterology Michigan Medicine Gastroenterology Clinic Ann Arbor, Michigan MedicalResearch.com: What is the background for this study? Response: Functional Dyspepsia (FD), which is persistent or recurring upper abdominal pain, burning, or fullness with no known organic cause, is a relatively common and often frustrating condition. The precise causes of this condition are unknown, but problems with mild inflammation, leakiness of the lining of the gut, overactive sensation, and abnormal contractions of the upper digestive tract are thought to play a role in many patients. FD often reoccurs over time and it is an area of high unmet medical need. Functional Dyspepsia can have a significant impact on quality of life. Currently, off-label medications are used to treat FD, as there is no U.S. Food and Drug Administration (FDA)-approved pharmaceutical product for the condition. An estimated 62 percent of FD patients suffer from Epigastric Pain Syndrome (EPS, which is epigastric pain or burning), while an estimated 73 percent of FD patients suffer from Postprandial Distress Syndrome (PDS, which is early fullness, pressure and heaviness); 35 percent suffer from both. In this study, we compared the efficacy of a unique encapsulated formulation of caraway oil and l-Menthol, the primary component in peppermint oil), (COLM-SST) to placebo in patients taking their usual Functional Dyspepsia medications. Caraway oil contains carvone and d-limonene, which have gastroprotective and prokinetic effects; l-Menthol has anti-inflammatory, prokinetic, analgesic and gastroprotective effects. (more…)
Author Interviews, HIV, Pharmacology / 24.05.2017

MedicalResearch.com Interview with: Martin Markowitz MD Clinical Director and Staff Investigator Aaron Diamond AIDS Research Center Aaron Diamond Professor at The Rockefeller University MedicalResearch.com: What is the background for this study? What are the main findings? Response: Cabotegravir ((CAB) is an inhibitor of HIV-1 integrase and is amenable to formulation in both oral and long acting injectable forms. In preclinical studies injectable CAB protected against low dose intrarectal challenge using an HIV-like virus in the rhesus macaque model. These results support the clinical development of CAB as prevention. This study was a first attempt to establish a dosing regimen and evaluate safety and acceptability of intramuscular injections of CAB. The study was a placebo controlled blinded study of approximately 120 subjects with a 5:1 randomization active/placebo. Subjects received 800mg CAB given as 2 2mL injections or placebo every 12 weeks for 3 injections after a 4 week safety lead in of oral therapy. Safety acceptability and PK were assessed. The main findings were that injections were associated with injection site reactions in the vast majority of participants that were mild to moderate and of short duration. Only 4 subjects who entered the injection phase discontinued due to injection intolerance. There were no additional safety signals and the participants considered the injections acceptable when asked to complete questionnaires. PK analysis found that despite modeling that suggested that the 800mg q 12 week dose would be adequate, this was not the case. More rapid uptake and release from the depot resulted in lower than anticipated drug levels at trough. Alternate dosing regimens are under study. Another finding is that there were participants (14%) who had detectable drug in plasma detected at 52 weeks after last injection suggesting the presence of a tail in some individuals. (more…)