For Resistant HIV: Phase III Trial of Trogarzo Demonstrates Safety and Efficacy

MedicalResearch.com Interview with:
TaiMed BiologicsStanley Lewis, M.D.

TaiMed Biologics
Irvine, CA 92614


MedicalResearch.com: What is the background for this study?

Response: The phase III clinical trial was conducted to assess the efficacy and safety of Trogarzo™ (ibalizumab-uiyk) injection in patients with multidrug resistant HIV-1. The study design was approved by the FDA. Results obtained were included in the New Drug Application submitted to the FDA which approved Trogarzo™ on March 6, 2018.

The phase III, open-label study, enrolled 40 patients with multidrug-resistant (MDR) HIV-1 in whom multiple antiretroviral therapies had failed. All patients at baseline were experiencing viral failure. After a seven-day control period, patients received an intravenous 2000 mg loading dose of Trogarzo™ which was the only change made to their antiretroviral regimen. Through the 24-week treatment period of the study, patients were given a maintenance dose of 800 mg of Trogarzo™ every two weeks along with an optimized background regimen that included at least one additional fully active agent.

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Crohn’s Disease: Positive Findings from Phase III Study of Antibiotic Combination

MedicalResearch.com Interview with:
RedHill Biopharma LtdMr. Gilead Raday, MPhil, MSc
Chief Operating Officer
RedHill Biopharma Ltd

MedicalResearch.com: What is the background for this study? Would you briefly explain what is meant by Crohn’s disease?  How common is it and whom does it affect? 

Response: Crohn’s disease (CD) is a chronic, relapsing inflammatory gastrointestinal disorder characterized by a variety of symptoms, including severe abdominal pain, diarrhea, bleeding, bowel obstruction, fever and weight loss. The underlying cause of Crohn’s is unknown; however, CD is believed to arise secondary to genetic and environmental stimuli. More than 1.5 million people suffer from CD globally and it is prevalent in the U.S., affecting more than 200 people per 100,000.

The current standard of care for Crohn’s disease is limited to anti-inflammatories, immuno-suppressants and biologics that treat auto-immune disorders. These therapies target symptomatic improvement in the inflammation associated with CD, are widely considered to be of limited efficacy in the long term, and are associated with numerous side effects. This speaks to the great unmet need for an effective therapy for this debilitating disease.

Additionally, there is no current therapy that treats the suspected underlying cause of Crohn’s disease. We have developed RHB-104 with the MAP hypothesis in mind, which posits that Crohn’s disease is caused by infection by a bacteria, Mycobacterium avium subspecies paratuberculosis (MAP). This is similar to peptic ulcer disease, a condition that was initially associated with stress, smoking, NSAIDs and other behavioral factors, yet was found to be caused by H. pylori bacterial infection in the 1980s, revolutionizing the field of ulcer treatment. Validation of this theory would revolutionize how Crohn’s disease is viewed and treated by the medical community and RHB-104 is the only therapy in development targeting MAP infection.  Continue reading

Diabetes: Switching to Sulfonylureas from Metformin Linked to Increased Side Effects

MedicalResearch.com Interview with:

Samy Suissa, PhD Director, Centre for Clinical Epidemiology, Lady Davis Institute Professor, Departments of Epidemiology and Biostatistics and of Medicine McGill University

Dr. Suissa

Samy Suissa, PhD
Director, Centre for Clinical Epidemiology, Lady Davis Institute
Professor, Departments of Epidemiology and Biostatistics and of Medicine
McGill University 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Sulfonylureas are widely used oral antidiabetic drugs that are recommended as second-line treatments after first-line metformin to treat patients with type 2 diabetes. While their safety has been studied extensively, studies in patients with poorly controlled diabetes in need of pharmacotherapy escalation have been sparse and limited. Our study evaluated whether adding or switching to sulfonylureas after initiating metformin treatment is associated with increased cardiovascular or hypoglycaemic risks, compared with remaining on metformin monotherapy.

Using a large cohort of over 77,000 patients initiating treatment with metformin monotherapy, we found that adding or switching to sulfonylureas is associated with modest increases of 26% in the risk of myocardial infarction and 28% in the risk of death, as well as an over 7-fold major increase in the risk of severe hypoglycaemia leading to hospitalisation.

In particular, we found that switching from metformin to sulfonylureas was associated with higher risks of myocardial infarction and death, compared with adding sulfonylureas to metformin.  Continue reading

Positive Topline Results from Phase 3 Study of Cariprazine for the Treatment of Bipolar I Depression

MedicalResearch.com Interview with:
allergan
Gary Sachs, MD
Associate Clinical Professor of Psychiatry
Harvard Medical School 

MedicalResearch.com: What is the background for this data milestone?

Response: Bipolar disorder affects about 5.7 million adults in the United States.  It is a common, often disabling condition in which abnormal mood states impair a person’s ability to carry out everyday tasks. Bipolar disorder touches nearly every family and community in America, because periods of illness, a patient’s symptoms often impact their family, their friends, and their community.

There are a limited number of products approved to treat bipolar depression and even fewer products that have been studied and approved to treat the full spectrum of bipolar disorder, from mania through depression. Having another product proven to treat the full range of bipolar disorder would be a welcome addition to the treatment options currently available to the psychiatry community and patients.

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Why Doesn’t That Medicine Work For Me? Genetic Mutations Affect Drugs’ Efficacy

MedicalResearch.com Interview with:

Alexander S Hauser, PhD student MRC Laboratory of Molecular Biology Cambridge UK Department of Drug Design and Pharmacology, University of Copenhagen Copenhagen, Denmark

Alexander Hauser

Alexander S Hauser, PhD student
MRC Laboratory of Molecular Biology
Cambridge UK
Department of Drug Design and Pharmacology, University of Copenhagen
Copenhagen, Denmark

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: The prevalence and impact of genetic variation among all human G protein coupled receptors (GPCRs) that are targeted by FDA-approved drugs remain unknown. In this study, we present a comprehensive analysis and map of the pharmacogenomics
landscape of GPCR drug targets. The key highlights are:

– GPCRs targeted by drugs show extensive genetic variation in the human population

– Variation occurs in functional sites and may result in altered drug response

– Understanding GPCR genetic variation may help reduce global healthcare expenses

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Tapeworm Drug May Be Repurposed To Fight Parkinson’s Disease

MedicalResearch.com Interview with:

Dr. Youcef Mehellou PhD Lecturer in Medicinal Chemistry Cardiff School of Pharmacy and Pharmaceutical Sciences Cardiff University

Dr. Mehellou

Dr. Youcef Mehellou PhD
Lecturer in Medicinal Chemistry
Cardiff School of Pharmacy and Pharmaceutical Sciences
Cardiff University

MedicalResearch.com: What is the background for this study?

Response: Over the last decade or two, there has been many reports linking genetic mutations to the pathogenesis of Parkinson’s disease (PD). Among the proteins that have been found to be mutated in PD is a protein called PINK1. Indeed, PINK1 mutations that disturb its function in cells were found to be causal of PD in humans. Subsequent studies showed that PINK1 is a major player in maintaining healthy neurons. This is because it is one of the components involved in controlling the quality of the mitochondria, an organelle within the cell, and it does this by triggering the disposal of unhealthy mitochondria. Overall, studies into PINK1 indicated that the activation of PINK1 as a plausible strategy for maintaining health neurons and hence slowing down the development and progress of Parkinson’s disease.

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Database Analyses May Find Supplemental Uses For Established Drugs In Cost-Effective Manner

MedicalResearch.com Interview with:

Michael Fralick, MD FRCPC Research Fellow at the Division of Pharmacoepidemiology and Pharmacoeconomics Harvard University and General Internist at the University of Toronto

Dr. Fralick

Michael Fralick, MD FRCPC
Research Fellow at the Division of Pharmacoepidemiology and Pharmacoeconomics
Harvard University and
General Internist at the University of Toronto

MedicalResearch.com: What is the background for this study?

Response: Manufacturers of Food and Drug Administration (FDA)-approved prescription drugs often apply for additional indications based on randomized trials. “Real-world” data based on a medication’s actual use and outcomes in routine settings of care might help to inform decision-making regarding such supplemental indications.

MedicalResearch.com: What are the main findings?

Response:  In this non-randomized study we were able to replicate the results of the randomized trial that established the supplemental indication for telmisartan using data from a US healthcare database (insurance claims data) available at the time the randomized trial was completed.

We were also able to confirm the known decreased risk of angioedema with telmisartan compared to ramipril.

MedicalResearch.com: What should readers take away from your report?

Response: If done selectively and with principled methodologies, it might be feasible to use non-randomized real-world data to provide supportive evidence in establishing supplemental drug indications. To improve the validity of the studies, they should ideally be registered prior to them starting.

MedicalResearch.com: Is there anything else you would like to add?

Response: We used real-world data to recreate both the benefits and the harms found in a randomized controlled trial. The randomized trial costed 10s of millions of dollars and took over 7 years to complete. By contrast, our study took a few months to complete and was a small fraction of the cost of the randomized trial.

MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community.

Citation:

Michael Fralick, Aaron S. Kesselheim, Jerry Avorn, Sebastian Schneeweiss. Use of Health Care Databases to Support Supplemental Indications of Approved Medications. JAMA Intern Med. Published online November 20, 2017. doi:10.1001/jamainternmed.2017.3919

Note: Content is Not intended as medical advice. Please consult your health care provider regarding your specific medical condition and questions.

 

 

 

 

 

Does Brand Name 17P Work Better Than Generic In Reducing Preterm Births?

MedicalResearch.com Interview with:

Andrew L. Beam, PhD Instructor in Biomedical Informatics Department of Biomedical Informatics Harvard Medical School

Dr. Beam

Andrew L. Beam, PhD
Instructor in Biomedical Informatics
Department of Biomedical Informatics
Harvard Medical School

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: This study is one piece of a larger story regarding the use of 17-alpha-hydroxyprogesterone caproate (17P) to treat recurrent preterm birth. This drug was originally only available in a compounded form, but since receiving an orphan drug designation in 2011, a branded and manufactured form was marketed under the name “Makena”. This branded form was then sold for a much higher price than the compounded version, but a study that provided concrete data on pricing and outcomes had not been done.
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ONCEMRK Study: Once Daily Raltegravir In Combination With Other Antivirals Effective For Some HIV Patients

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

Dr. Pedro Cah

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).

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Restrictions on Pharmaceutical Detailing Linked To Increase in Generic Drug Prescription

MedicalResearch.com Interview with:

Ian Larkin, PhD</strong> Assistant Professor of Strategy UCLA Anderson School of Management

Dr. Ian Larkin

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.

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Guselkumab Potentially Increases Treatment Choices For Psoriasis

MedicalResearch.com Interview with:

Prof. Dr. med. Kristian Reich Dermatologie, Allergologie Psoriasis- und Neurodermitis-Trainer Hamburg

Prof.  Kristian Reich

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.   
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Antidepressants Have Variable Effects On Symptom Clusters

MedicalResearch.com Interview with:

Adam Chekroud PhD Candidate Human Neuroscience Lab

Adam Chekroud

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.

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SWORD Study Demonstrates Two-Drug Control of HIV

MedicalResearch.com Interview with:

Kati Vandermeulen Senior Director, Global Regulatory Leader and Compound Development Team Lead IDV Janssen

Kati Vandermeulen

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.
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Ketamine Before Stressful Event May Reduce Risk of PTSD

MedicalResearch.com Interview with:

Christine Ann Denny, Ph.D. Assistant Professor Department of Psychiatry Columbia University Division of Integrative Neuroscience Research Foundation for Mental Hygiene, Inc. New York, NY 10032-2695

Dr. Christine Ann Denny

Christine Ann Denny, Ph.D.
Assistant Professor
Department of Psychiatry
Columbia University
Division of Integrative Neuroscience
Research Foundation for Mental Hygiene, Inc.
New York, NY 10032-2695

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Post-traumatic stress disorder (PTSD) is one of the most common psychiatric illnesses, affecting about 8 million adult Americans, and an annual prevalence of about 3.5% worldwide. At-risk populations such as soldiers and veterans are at a higher risk to develop PTSD. Stress exposure is one of the major risk factors for PTSD and major depressive disorder (MDD), a disorder which is often co-morbid with PTSD.

There are currently very limited treatments for PTSD and MDD. In addition, these disorders are treated in a symptom-suppression approach, which only mitigate symptoms and work in only a small fraction of patients. Prevention is rarely an approach considered except in the form of behavioral intervention. However, pharmacological approaches to preventing psychiatric diseases has not yet been developed.

Our laboratory has previously found that ketamine, a general anesthetic and rapid-acting antidepressant, administered sub-anesthetically prior to stress can prevent against stress-induced depressive-like behaviors. We decided to delve into the literature to determine whether ketamine has any effects on PTSD in the clinic. We found numerous reports linking ketamine to PTSD, but the results were varied. We realized that the main difference in all of these studies was the timing of administration. We decided to systematically test the efficacy of ketamine in mice at various time points relative to a stressor to determine when would be the most effective window to buffer against heightened fear expression.

We found that ketamine administered 1 week, but not 1 month or 1 day, prior to a stressor was the most effective time point to administer the drug to buffer fear. This is critical, as it suggests that a pharmacological approach to enhance resilience can be more effective at protecting against PTSD symptoms than attempting to mitigate symptoms after it has already affected an individual.

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Metformin Associated With Lower Mortality in CKD, CHF and Chronic Liver Disease

MedicalResearch.com Interview with:

Matthew J. Crowley, MD, MHS Assistant Professor of Medicine Member in the Duke Clinical Research Institute Duke University Medical Center

Dr. Matthew Crowley

Matthew J. Crowley, MD, MHS
Assistant Professor of Medicine
Member in the Duke Clinical Research Institute
Duke University Medical Center

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Although metformin is widely considered to be the first-line drug for type 2 diabetes, concerns about lactic acidosis have traditionally limited its use in some populations. However, FDA now indicates that metformin may be used safely for patients with mild-moderate chronic kidney disease and other historical contraindications like congestive heart failure. With the lactic acidosis question addressed for these groups, this review asked “what do we know about how metformin affects mortality and other outcomes for patients with historical contraindications and precautions?”

The main take-home message is that metformin appears associated with lower mortality in patients with mild-moderate chronic kidney disease, congestive heart failure, and chronic liver disease.

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PCSK9 Inhibitor Praluent Substantially Reduced LDL-C Cholesterol

MedicalResearch.com Interview with:

Dr. Eli M. Roth MD, FACC President, Medical Director Sterling Research Group Cincinnati, OH

Dr. Eli Roth

Dr. Eli M. Roth MD, FACC
President, Medical Director
Sterling Research Group
Cincinnati, OH

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: At this year’s AHA 2016, we presented a pharmacodynamics analysis of ODYSSEY CHOICE I, which evaluated the effects of Praluent 300 mg administered every four weeks (Q4W) for 24 weeks in hypercholesterolemia patients at moderate to very high cardiovascular risk who were on maximally tolerated statin or no statin and/or other lipid-lowering therapies.

The pharmacodynamic analysis of CHOICE I in patients on statins supports the use of Praluent 300 mg Q4W as an alternative starting dose for patients who prefer a Q4W dosing regimen and demonstrates the value of LDL-C based dosing interval adjustment. The findings from this analysis were consistent with prior ODYSSEY Phase 3 studies, showing that Praluent substantially reduced circulating free PCSK9 concentration, resulting in significant LDL-C reductions. Additionally, Praluent was generally well tolerated.

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New Ibuprofen Formulation May Avoid Cardiac Side Effects

MedicalResearch.com Interview with:

Dr Nicholas Kirkby BHF Intermediate Fellow | Vascular Biology National Heart & Lung Institute | Imperial College London London

Dr Nicholas Kirkby

Dr Nicholas Kirkby
BHF Intermediate Fellow | Vascular Biology
National Heart & Lung Institute | Imperial College London
London

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: We know drugs like ibuprofen, called ‘non-steroidal anti-inflammatory drugs’ cause an increase in the risk of heart attacks. These side effects cause very real concerns for the many millions of people who rely on them. They are also the reason why there are no new drugs in this class and why they have been withdrawn (2011) for use as a preventative treatment for colon cancer. Previous research from our group suggests that L-arginine supplements may prevent the cardiovascular side effects caused by these drugs. Our findings here suggest that a particular formulations of ibuprofen, called ibuprofen arginate, which is already available in many parts of the world, can act like an L-arginine supplement and that this could potentially protect the cardiovascular system.

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Autoimmune Specialty Drug Spending Doubles, Accounting for 10 Percent of Drug Expenses

MedicalResearch.com Interview with:

Kevin Bowen MD MBA Senior Health Outcomes Researcher Prime Therapeutics LLC 1305 Corporate Center Drive Eagan, MN 55121

Dr. Kevin Bowen

Kevin Bowen MD MBA
Senior Health Outcomes Researcher
Prime Therapeutics LLC
1305 Corporate Center Drive
Eagan, MN 55121

MedicalResearch.com: What is the background for this study? What are the main findings?

• Autoimmune specialty drugs now account for about one of every 10 dollars of combined drug expense through the medical and pharmacy benefits in a commercially insured population.
• The autoimmune drug class is one of the fastest growing, with this study finding a doubling in autoimmune drug expenditures and a 38 percent increase in utilization, in the most recent four years.
• Integrated analysis of medical and pharmacy claims is essential for this category of drugs because more than 25 percent of autoimmune specialty drug use is paid through the medical benefit and medical claims diagnosis coding provides a means of determining what conditions were treated with drugs covered by pharmacy claims.
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Long-Acting Beta-Agonists-Steroid Combination in Pediatric Asthma

MedicalResearch.com Interview with:
David A Stempel, MD
Medical Affairs Lead
US Medical Affairs
GlaxoSmithKline

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Long-acting beta-agonists (LABAs) have been shown to increase the risk of asthma-related death among adults and the risk of asthma-related hospitalization among children.

It is unknown whether the concomitant use of inhaled glucocorticoids
with LABAs mitigates those risks. This trial prospectively evaluated the safety of the LABA salmeterol, added to fluticasone propionate, in a fixed-dose combination in children.

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Systematic Review Finds PCSK9 Inhibitors Reduce LDL-C and Are Well Tolerated

MedicalResearch.com Interview with:

Prof. Dr. Ioana Gouni-Berthold MD

Dr. Gouni Gerthold

Prof. Dr. Ioana Gouni-Berthold MD
Center for Endocrinology, Diabetes and Preventive Medicine (ZEDP)
University of Cologne
Cologne, Germany

MedicalResearch.com: What is the background for this study?

Response: In Europe, up to half of the population aged between 35 and 64 has hypercholesterolemia (high levels of low-density lipoprotein cholesterol [LDL-C]), putting them at risk of heart disease. Despite increased treatment rates in recent years, many patients still do not receive adequate therapy, and heart disease remains the biggest cause of death in the USA and most European countries.

Two drugs, alirocumab and evolocumab, have recently been approved for lowering LDL-C in patients with hypercholesterolaemia as an ‘add-on’ therapy to other lipid-lowering medication, or for use alone in patients unable to tolerate statins. These drugs have a unique mode of action– they inhibit proprotein convertase subtilisin/kexin type 9 (PCSK9), a protein that binds to LDL receptors and targets them for degradation. In the absence of PCSK9, the LDL receptor recycling is restored and the receptors are able to remove LDL from the blood.

Both alirocumab and evolocumab have been tested in numerous patient populations in phase 3 trials; albeit evolocumab has an additional indication of homozygous familial hypercholesterolemia. We therefore felt that there was a need to collate the available data to assess the efficacy and safety of each agent. We chose reduction in LDL-C as our outcome of interest, because this was the primary endpoint of the pivotal clinical trials.

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Study By Quest Diagnostics Finds Half of Americans Misuse Their Drugs

MedicalResearch.com Interview with:

F. Leland McClure III, MSci, PhD, F-ABFT Medical science liaison director Quest Diagnostics

Dr. F. Leland McClure

F. Leland McClure III, MSci, PhD, F-ABFT
Medical science liaison director
Quest Diagnostics

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Many physicians associate Quest Diagnostics with their lab service needs because of our leadership in laboratory testing. But Quest is more than a lab, which is why we refer to ourselves as a diagnostic information services provider. This means that we help providers, health plans and even patients use the insights we derive from our lab testing data to deliver better care, quality and outcomes, both for the patient and the managed population.

Our 2016 Quest Diagnostics Health Trends(TM) Prescription Drug Monitoring Report is an example of how we provide important health insights from Quest’s laboratory data. Prescription drug misuse is a major epidemic in the United States. Laboratory testing can help identify if a patient is using or misusing prescribed medications. For instance, lab tests can show evidence of additional medications and other drugs in a patient’s urine specimen, suggesting potentially dangerous drug combinations. Earlier this year, the CDC issued guidelines that call for laboratory testing for patients prescribed certain medications, such as opioids, that carry a risk of abuse.

Quest’s prescription drug monitoring services help the physician identify if a patient is taking or not taking up to about four dozen drugs, such as oxycodone, Adderall XR® and Percocet®. For the Quest analysis, we analyzed more than 3 million de-identified lab test results.

In this report, we found that 54 percent of patients’ results tested in 2015 showed evidence of drug misuse, slightly above the 53 percent misuse rate in 2014. That is certainly unacceptably high, but it’s a significant decline from the high of 63 percent we observed in 2011.

We also found that an increasing proportion of patients who misuse medications combine their prescription medication with non-prescribed drugs. Among patients with inconsistent test results, forty-five percent of these patients showed evidence of one or more other drug(s) in addition to their prescribed drug regimen. That’s much higher than our findings of 35 percent in 2014 and 2013, 33 percent in 2012, and 32 percent in 2011.

Finally, we were alarmed by the data showing the connection between heroin and benzodiazepines misuse. Our data showed one in three heroin users combine their drug use with benzodiazepines, the vast majority of which were unprescribed. This is an extremely dangerous practice given that benzodiazepines can have strong respiratory depressant effects when combined with other substances. Drug combinations, but particularly of heroin with benzodiazepines, can be potentially very dangerous, leading to coma and even death in some cases.

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Outpatient Diuretic Protocol Can Keep Some Heart Failure Patients Out of Hospital

MedicalResearch.com Interview with:

Leo F. Buckley, PharmD Virginia Commonwealth University Richmond, Virginia

Dr. Leo Buckley

Leo F. Buckley, PharmD
Virginia Commonwealth University
Richmond, Virginia

MedicalResearch.com: What is the background for this study?

Response: As the prevalence and costs of heart failure are expected to increase through the year 2030, significant efforts have been devoted towards devising alternatives to inpatient hospitalization for the management of heart failure decompensations. Since loop diuretics are the mainstay of treatment during the majority of hospitalizations, administration of high doses of loop diuretics in the outpatient setting has increased in popularity.

We intended to answer two questions with his study: first, can a patient-specific dosing protocol based on a patient’s usual diuretic dose achieve safe decongestion? and second, does this strategy alter the usual course of heart failure decompensation, which oftentimes culminates in inpatient hospitalization?

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Study of Topical Minocycline For Acne Demonstrates No Phototoxicity or Absorption

MedicalResearch.com Interview with:
Kin F. Chan, PhD

Executive Vice President of Research and Technology
BioPharmX Corporation

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: There were two studies in this series.  The purpose is to get a better understanding of the blood plasma and skin levels of minocycline in a relevant animal model (minipig) for both the oral form of minocycline (Solodyn) and topical BPX-01, and to elucidate the same for oral minocycline only in a clinical study.

The results provided valuable guidance and assurance to our upcoming Clinical Phase 2b dose-ranging study design.

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Lymphoma Drug Shows Promising Results in Phase 3 Trial

MedicalResearch.com Interview with:

Dirk Huebner, MD Senior Medical Director Oncology Therapeutic Area Unit Takeda Pharmaceutical Company

Dr. Dirk Huebner

Dirk Huebner, MD
Senior Medical Director
Oncology Therapeutic Area Unit
Takeda Pharmaceutical Company

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Cutaneous lymphomas are a category of non-Hodgkin lymphoma that primarily involve the skin. Cutaneous T-cell lymphoma, also known as CTCL, is the most common type of cutaneous lymphoma and typically presents with red, scaly patches or thickened plaques of skin that often mimic eczema or chronic dermatitis.

ADCETRIS® (brentuximab vedotin) is an antibody-drug conjugate directed to CD30, which is expressed on skin lesions in approximately 50 percent of patients with CTCL. The Phase 3 ALCANZA trial compared the use of single-agent ADCETRIS to a control arm of investigator’s choice of standard therapies, methotrexate or bexarotene, in 131 patients with CD30-expressing CTCL who received prior systemic or radiation therapy.

The study met its primary endpoint, demonstrating a highly statistically significant improvement in the rate of objective response lasting at least four months (ORR4). The ORR4 was 56.3 percent in the ADCETRIS arm compared to 12.5 percent in the control arm.

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Concomitant Use of Clopidogrel and PPIs Still Prescribed Despite Safety Warnings

MedicalResearch.com Interview with:
Willemien J. Kruik-Kollöffel, PharmD
Medisch Spectrum Twente in Enschede
Netherlands,

MedicalResearch.com: What is the background for this study?

Response: Safety concerns of the concomitant use of clopidogrel and proton pump inhibitors (PPIs) were published in 2009 and 2010 by the medicines regulatory agencies, including a direct healthcare professional communication. Those publications caused a lot of turmoil. We examined the association between various safety statements and prescription behavior for gastroprotective drugs in naïve patients in the Netherlands during the years 2008–2011.

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