Pharmacology
26 Jul Once-Daily, Fixed-Dose Combination Tablet Containing Doravirine Achieved HIV-1 Viral Suppression
MedicalResearch.com Interview with: [caption id="attachment_36123" align="alignleft" width="142"]
Dr. Squires[/caption]
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).
25 Jul ONCEMRK Study: Once Daily Raltegravir In Combination With Other Antivirals Effective For Some HIV Patients
MedicalResearch.com Interview with: [caption id="attachment_36099" align="alignleft" width="141"]
Dr. Pedro Cah[/caption]
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).
25 Jul Trying Statins Again After Adverse Effect Linked To Lower Risk of Heart Attack
Posted at 15:28h
in Annals Internal Medicine, AstraZeneca, Author Interviews, Brigham & Women's - Harvard, Heart Disease, Merck, Pharmacology
MedicalResearch.com Interview with:
[caption id="attachment_36047" align="alignleft" width="120"]
Dr. Turchin[/caption]
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.
10 Jul Optimistic Results From Phase 3 Study of RBP-6000 Buprenorphine Monthly Depot for Treatment of Opioid Use Disorder
Medical Research.com Interview with: [caption id="attachment_35821" align="alignleft" width="200"]
Dr. Heidbreder[/caption]
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.
05 Jul Newer Insulin Formulation Reduces Risk of Hypoglycemia
MedicalResearch.com Interview with: [caption id="attachment_35738" align="alignleft" width="150"]
Dr. Lane[/caption]
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.
19 Jun Optimization of Medication Use Critical to Success of ACOs
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.19 Jun Brexanolone Shows Promise in PostPartum Depression
MedicalResearch.com Interview with: [caption id="attachment_35396" align="alignleft" width="150"]
Dr. Meltzer-Brody[/caption]
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.
13 Jun Letermovir Found Highly Effective In Preventing CMV Infection
MedicalResearch.com Interview with: [caption id="attachment_35282" align="alignleft" width="133"]
Dr. Chemaly[/caption]
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.
12 Jun Drugs Receiving Accelerated FDA Approval Often Have Flaws In Their Evidence Base
MedicalResearch.com Interview with: [caption id="attachment_35276" align="alignleft" width="200"]
Dr. Naci[/caption]
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
12 Jun New Simultaneous Antidepressant and Benzodiazepine Use Relatively Common
MedicalResearch.com Interview with: [caption id="attachment_35171" align="alignleft" width="200"]
Greta Bushnell[/caption]
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.
09 Jun Long-acting Injectable Medications Reduce Relapse and Rehospitalizations in Schizophrenia
MedicalResearch.com Interview with: [caption id="attachment_35117" align="alignleft" width="200"]
Prof. Tiihonen[/caption]
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.
09 Jun IPF Patients Treated With Nintedanib (Ofev) More Likely To Have Stable Lung Function
MedicalResearch.com Interview with: [caption id="attachment_35150" align="alignleft" width="174"]
Dr. Flaherty[/caption]
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.
05 Jun FDgard® Demonstrated Rapid Relief of Symptoms in Functional Dyspepsia
MedicalResearch.com Interview with: [caption id="attachment_35036" align="alignleft" width="142"]
Dr. Chey[/caption]
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.
24 May Injectable Cabotegravir Holds Promise as HIV Prevention Stategy
MedicalResearch.com Interview with: [caption id="attachment_34848" align="alignleft" width="119"]
Dr. Markowitz[/caption]
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.
10 May All NSAIDS Raise Risk of Heart Attack, Even When Taken For Short Period of Time
MedicalResearch.com Interview with: Michèle Bally, BPharm, MSc, PhD Epidemiologist, Department of Pharmacy, CHUM Researcher, Health Innovation and Evaluation Hub, CRCHUM MedicalResearch.com: What is the background for this study? Response: The objective of this study was to better understand the risk of heart attack associated with using oral prescription non-steroidal anti-inflammatory drugs or NSAIDs (ibuprofen, diclofenac, celecoxib, and naproxen) the way people usually do to treat pain and inflammation in real life circumstances. A lot of people take medication, but they do not understand that some can be more harmful than beneficial, especially with consistent use. Unfortunately, something like a heart attack can happen anywhere. You could be at work and show signs of an attack. If this does happen, hopefully you have someone who is first aid trained to at least help you deal with these symptoms, until you get to the hospital. This is why having someone who knows that they are doing is beneficial in any environment. If it wasn't for companies like Coast2Coast in Ottawa, the chances of someone who was suffering from a heart attack may not have made it to the hospital if it wasn't for the assistance of someone who was first aid trained. In clinical trials, NSAIDs were typically taken on a continuous basis in high standardized doses, as assigned by the trial protocol. However, the dosages and the treatment durations studied in trials may not represent the reality of many patients who use NSAIDs in low or varying doses, use these drugs on and off, or switch between NSAID medications. We were particularly interested in determining the onset of the risk, that is how soon does the risk of heart attack start increasing? Also, we wanted to investigate the effect of dose and duration of treatment. To do this, we studied the use of a low or high dose level of NSAIDs over certain set periods of time, including taking these medications only for 1 to 7 days.03 May Restrictions on Pharmaceutical Detailing Linked To Increase in Generic Drug Prescription
MedicalResearch.com Interview with: [caption id="attachment_34230" align="alignleft" width="133"]
Dr. Ian Larkin[/caption]
Ian Larkin, PhD
Assistant Professor of Strategy
UCLA Anderson School of Management
MedicalResearch.com: What is the background for this study?
Response: The study examined whether restrictions put in by medical centers on salesperson visits to physicians, known as “detailing,” affected subsequent physician prescribing behavior. Detailing represents the most prominent form of pharmaceutical marketing. Detailing visits allow the sharing of scientific information, but they also often involve small gifts for physicians and their staff, such as meals.
Pharmaceutical companies incur far greater expenditures on detailing visits than they do on direct-to-consumer marketing, or even on research and development of new drugs. Specifically, the study examined detailing restrictions put into place by 19 academic medical centers (AMCs) in five states in the U.S. It compared changes in prescribing by thousands of AMC physicians whose practices limited typical elements of detailing visits, such as provisions of meals and educational gifts, to a carefully matched control group of similar physicians practicing in the same geographic regions but not subject to such detailing restrictions.
The study, which included more than 25,000 physicians and all 262 drugs in eight major drug classes — from statins to sleep aids to antidepressants, representing more than $60 billion in aggregate sales in the United States — was, to date, by far the most comprehensive to examine the impact of detailing restrictions. The comprehensive and quasi-experimental methodology, which compared prescribing behavior before and after implementation of policies, and which included a large matched control group of physicians not subject to policy changes, was an important innovation relative to prior research. The study used prescription data from CVS Caremark, one of the largest pharmacy benefit managers in the United States.
01 May Statins Users May Have Higher Likelihood of Back Disorders
MedicalResearch.com Interview with: [caption id="attachment_34240" align="alignleft" width="70"]
Dr. Makris[/caption]
Una Makris MD, MSc
Clinical Investigator at the VA North Texas Health System
VA North Texas Health Care System
Assistant Professor at UT Southwestern Medical Center
Departments on Internal Medicine and Clinical Sciences
Dr. Makris is a Rheumatologist, clinically, and spends the majority of time focused on clinical research investigating how to improve outcomes for adults with back pain.
MedicalResearch.com: What is the background for this study?
Response: Back pain is the most common type of musculoskeletal (MSK) pain. We know that expenditures for back pain exceed $100 billion each year (and this was in 2005). Back pain results in tremendous disability (including reduced mobility) and impaired quality of life (not exclusive to physical consequences, but also including important psychosocial repercussions). We also know that statins are prescribed very often, and frequently in younger populations who are active. Some reports suggest that statins may have a protective effect on musculoskeletal conditions such as back pain.
11 Apr Animal Study Suggests Lorcaserin (Belviq®) May be Useful to Reduce Opioid Intake
MedicalResearch.com Interview with: Christina R. Merritt and Kathryn A. Cunningham Center for Addiction Research University of Texas Medical Branch Galveston, TX 77555 MedicalResearch.com: What is the background for this study? What are the main findings? Response: Opioid use disorder (OUD) is one of the top public health problems in the United States. Overdoses on prescription opioids, heroin and fentanyl accounted for 33,091 deaths in the U.S. in 2015 (https://www.cdc.gov/mmwr/volumes/65/wr/mm655051e1.htm); each day, 91 Americans die from an opioid overdose. The first-ever Surgeon General’s Report on Alcohol, Drugs and Health (https://addiction.surgeongeneral.gov/ ) observed that more people used prescription opioids than tobacco in 2015. Furthermore, individuals with OUD, the most problematic pattern of opioid abuse, often relapse, particularly in environments associated with past drug use, and new means to help maintain abstinence are needed. Serotonin (5-hydroxytryptamine; 5-HT) function in the brain, particularly through its cognate 5-HT2C receptor, is an important regulator of the abuse liability of cocaine and other psychostimulants. Previous studies suggested that the weight loss medication and selective 5-HT2C receptor agonist lorcaserin (Belviq®) can curb cocaine- and nicotine-seeking in preclinical models, even when tested in tempting environments. We administered lorcaserin to rats who were trained to take the powerful painkiller oxycodone (OxyContin®), a prescription opioid currently approved for treatment of acute and chronic pain with characteristically high abuse potential. Lorcaserin suppressed oxycodone intake as well as the drug-seeking behaviors observed when rats were exposed to cues such as the lights and sounds previously associated with drug intake. Taken together, these findings highlights the therapeutic potential for lorcaserin to extend abstinence and enhance recovery from OUD.07 Apr Thyroid Hormone Medication Should Not Be Taken With Cow’s Milk
MedicalResearch.com Interview with: Deborah Chon MD Endocrinology fellow UCLA David Geffen School of Medicine MedicalResearch.com: What is the background for this study? What are the main findings? Response: Our study shows that drinking cow's milk concurrently with oral levothyroxine significantly reduces the absorption of the medication. Levothyroxine is used for the physiologic replacement of thyroid hormone in patients with hypothyroidism and for serum TSH suppression in patients with thyroid cancer. It is the mostly commonly prescribed medication in the United States as of 2014. Frequent dose adjustments of levothyroxine have been shown to be a costly burden to the national healthcare system. Previous studies have shown that certain foods and medication, such as calcium supplements, can interfere with levothyroxine absorption. However, this is the first study to demonstrate that ingesting cow?s milk, a common breakfast staple, affects oral levothyroxine absorption. To determine the possible effect of cow's milk ingestion, we measured levothyroxine absorption in humans with and without concurrent milk consumption. Pharmacokinetic studies were conducted in healthy adults without allergies to milk or levothyroxine, and who were not pregnant nor using oral contraceptives. All subjects had no history of known thyroid disease and normal thyroid hormone function at baseline. Following an overnight fast, serum total thyroxine T4 (TT4) concentrations were measured at baseline and at 1, 2, 4, and 6 hours after ingestion of 1,000 ?g of oral levothyroxine alone or when co-administered with 12 oz. of milk (2% fat). There was a four-week washout period between the two study visits. Ten subjects (mean age 33.7?10.2 years, 60% male) completed the study. The serum total T4 absorption over six hours, calculated as area under the curve (AUC), was significantly lower when taking cow?s milk concurrently with levothyroxine compared levothyroxine alone (mean?SD: 67.26?12.13 vs. 73.48?16.96; p = 0.02). Also, peak serum TT4 concentrations were significantly lower in those who ingested levothyroxine concurrently with milk, compared to taking levothyroxine alone (p=0.04).20 Mar NSAIDS Diclofenac and Ibuprofen Associated with Increased Risk of Cardiac Arrest
MedicalResearch.com Interview with: [caption id="attachment_33131" align="alignleft" width="133"]
Dr. Søndergaard[/caption]
Kathrine Bach Søndergaard MD, Research Fellow
Gentofte University Hospital
Department of Cardiology
Hellerup
MedicalResearch.com: What is the background for this study?
Response: Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used and have in previous studies been associated with an increased risk of cardiovascular adverse events, such as myocardial infarction and heart failure. Cardiac arrest is the ultimate adverse event; however, no research exists of the association between cardiac arrest and use of NSAIDs, which we aimed to assess in this study.
08 Mar Psoriasis: Efficacy and Safety of Guselkumab vs Humira for Moderate to Severe Disease
MedicalResearch.com Interview with: [caption id="attachment_32763" align="alignleft" width="180"]
Dr. Blauvelt[/caption]
Andrew Blauvelt, M.D., M.B.A.
President and Investigator
Oregon Medical Research Center
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Findings from the Phase 3 VOYAGE 1 study showed that patients with moderate to severe plaque psoriasis receiving guselkumab, an human anti-interleukin (IL)-23 monoclonal antibody, achieved significant improvement in skin clearance and in comparison with Humira® (adalimumab), a TNF blocker. The Phase 3 study and head-to-head analysis of guselkumab vs. adalimumab showed the significant and durable efficacy of guselkumab as maintained through one year when compared with adalimumab, and the robust efficacy of this novel IL-23 targeted therapy in meeting all primary and major secondary endpoints.
03 Mar Regional Variation in Chemotherapy Prescriptions For Metastatic Prostate Cancer
Posted at 14:43h
in ASCO, Author Interviews, Outcomes & Safety, Pharmacology, Prostate Cancer, University of Michigan
MedicalResearch.com Interview with:
[caption id="attachment_32608" align="alignleft" width="128"]
Dr. Caram[/caption]
Megan Elizabeth Veresh Caram MD
Clinical Lecturer
Internal Medicine, Hematology & Oncology
University of Michigan
MedicalResearch.com: What is the background for this study?
Response: Abiraterone and enzalutamide are oral medications that were approved by the Food & Drug Administration in 2011 and 2012 to treat men with metastatic castration-resistant prostate cancer. Most men with advanced prostate cancer are over age 65 and thus eligible for Medicare Part D. We conducted a study to better understand the early dissemination of these drugs across the United States using national Medicare Part D and Dartmouth Atlas data.
01 Mar Flu Treatment With Neuraminidase Inhibitors During Pregnancy Not Linked To Birth Defects
Posted at 18:00h
in Author Interviews, BMJ, Flu - Influenza, Karolinski Institute, OBGYNE, Pediatrics, Pharmacology
MedicalResearch.com Interview with:
[caption id="attachment_32424" align="alignleft" width="146"]
Dr. Graner[/caption]
Dr. Sophie Graner
Department of Women's and Childrens Health
Karolinska Institute, Stockholm, Sweden
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Pregnant women are at increased risks of severe disease and death due to influensa infection, as well as hospitalization. Also influenza and fever increase the risk of adverse pregnancy outcomes for their infants such as intrauterine death and preterm birth. Due to this, the regulatory agencies in Europe and the US recommended post exposure prophylaxis and treatment for pregnant women with neuraminidase inhibitors during the last influenza pandemic 2009-10. Despite the recommendations, the knowledge on the effect of neuraminidase inhibitors on the infant has been limited. Previously published studies have not shown any increased risk, but they have had limited power to assess specific neonatal outcomes such as stillbirth, neonatal mortality, preterm birth, low Agar score, neonatal morbidity and congenital malformations.
28 Feb mGlu2 receptor Agonist ADX71149 Plus Levetiracetam May Reduce Seizures With Fewer Side Effects
MedicalResearch.com Interview with: [caption id="attachment_32486" align="alignleft" width="200"]
Dr. Lutjens[/caption]
Robert Lutjens, PhD
Head of Discovery at Addex Therapeutics
Geneva, Switzerland
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Metabotropic glutamate receptors represent an attractive therapeutic target for various neurologic conditions. In particular, the metabotropic glutamate receptor subtype 2 (mGlu2) can affect excitatory synaptic transmission by decreasing glutamate release. As excess gluatamate is observed in epilepsy, targeting mGlu2 could lead to new avenues of therapy. Positive allosteric modulators (PAMs) of mGlu2 could be valuable candidate drugs as they do not directly activate receptors. Therefore, they may avoid tachyphylaxis and side effects emerging from direct receptor agonism.
The publication summarizes the effects obtained when the mGlu2 receptor is activated using an agonist or PAM, such as ADX71149, in the 6Hz psychomotor seizure test, considered to be the most relevant model of pharmacoresistant limbic seizures. The data show that while seizures are reduced when mGlu2-acting compounds are administered alone, their combination with the antiseizure drug levetiracetam (LEV) result in a potent reduction of doses required to produce full efficacy, which is important because higher doses of LEV are associated with dose-limiting side effects, such as aggression, nervousness/anxiety, somnolence and fatigue. In this study, a fixed dose of ADX71149 was seen to increase the potency of LEV, leading to an approximate 35-fold increase in its potency. Conversely, using a fixed dose of LEV with varying doses of ADX71149 resulted in an approximate 14-fold increase in ADX71149 potency.
24 Feb Guselkumab Potentially Increases Treatment Choices For Psoriasis
MedicalResearch.com Interview with: [caption id="attachment_32369" align="alignleft" width="133"]
Prof. Kristian Reich[/caption]
Prof. Dr. med. Kristian Reich
Dermatologie, Allergologie
Psoriasis- und Neurodermitis-Trainer
Hamburg
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Ustekinumab is an antibody against the p40 molecule shared by IL-12 and IL-23. The antibody shows a favorable benfit-risk profile in the treatment of psoriasis. IL-23 is regarded a key driver in psoriasis pathology. It is speculated that antibodies against the IL-23-specific subunit p19 may produce even higher levels of clinical response than ustekinumab or the anti-TNF antagonist adalimumab. Guselkumab is the first IL-23p19 antibody to publish phase III data in psoriasis.
23 Feb Antidepressants Have Variable Effects On Symptom Clusters
MedicalResearch.com Interview with: [caption id="attachment_32285" align="alignleft" width="160"]
Adam Chekroud[/caption]
Adam Chekroud
PhD Candidate
Human Neuroscience Lab
Department of Psychology
Yale University
MedicalResearch.com: What is the background for this study?
Response: We know that depression includes a wide range of symptoms, from low mood and feeling worthless, to problems sleeping, slowed thinking, and suicidal ideation.
We wanted to know whether antidepressants work well in treating all of these symptoms, or whether they are primarily effective on certain kinds of symptoms.
20 Feb SWORD Study Demonstrates Two-Drug Control of HIV
MedicalResearch.com Interview with: [caption id="attachment_32236" align="alignleft" width="200"]
Kati Vandermeulen[/caption]
Kati Vandermeulen
Senior Director, Global Regulatory Leader and Compound Development Team Lead
IDV Janssen
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: SWORD is the first large trial program specifically conducted to look at the combination of dolutegravir and rilpivirine as a complete, two-drug antiretroviral regimen. Results of the two identical Phase III SWORD studies have been positive and demonstrate that the two-drug regimen of dolutegravir and rilpivirine is as effective, with comparable tolerability, to traditional three- or four-drug (integrase inhibitor-, non-nucleoside reverse transcriptase inhibitor-, or boosted protease inhibitor-based) antiretroviral regimens for the maintenance treatment of HIV.
19 Feb 5-alpha reductase inhibitors For BPH Linked to Higher, Not Lower, PSA Levels
MedicalResearch.com Interview with: Teemu J Murtola, MD, PhD, adjunct professor University of Tampere, Faculty of Medicine and Life Sciences Tampere University Hospital, Department of Urology Tampere, Finland MedicalResearch.com: What is the background for this study? Response: A previous study called Prostate Cancer Prevention Trial (PCPT) showed that finasteride, which belongs to a drug group called 5alpha-reductase inhibitors lowers serum PSA and increases sensitivity of PSA to detect high-grade prostate cancer in men who had little or no symptoms of the lower urinary tract. We postulated that this effect would increase the accuracy and benefits of PSA-based prostate cancer screening. Finnish Randomized Study of Screening for Prostate Cancer was a large trial of over 80,000 men randomized either to be screened for prostate cancer with a PSA test at 4-year intervals or to be followed for prostate cancer incidence and mortality via national registries. Three consecutive screening rounds were commenced between 1996-2008. In the current study we compared the effects of PSA-based screening on prostate cancer risk and mortality separately among men who were using 5alpha-reductase inhibitors finasteride or dutasteride and among men who were not.15 Feb Roles of Angiotensin Peptides and Recombinant Human ACE2 in Heart Failure
MedicalResearch.com Interview with: [caption id="attachment_31864" align="alignleft" width="180"]
Dr. Gavin Oudit[/caption]
Gavin Y Oudit, MD, PhD, FRCPC
Associate Professor, Department of Medicine, University of Alberta
Clinician-Scientist
Mazankowski Alberta Heart Institute
Canada Research Chair in Heart Failure
Division of Cardiology
Edmonton, Alberta
Heart specialist Gavin Oudit and his research team discovered a molecule — angiotensin converting enzyme 2 (ACE2)—that works to restore balance to the pathways responsible for chronic and acute heart failure, including in hearts from patients with advanced heart failure who underwent heart transplants.
In developing the new drug, Oudit and his team discovered to an extent not seen before how the renin-angiotensin system (RAS), which regulates the body’s sodium balance, fluid volume, and blood pressure, is at play in both acute and chronic heart failure. In collaboration with Dr. Oudit, recombinant human ACE2 was made by Apeiron Biologics, purchased by GlaxoSmithKline, and has recently completed phase II clinical trial.