ISSUE NO. 7 — Understanding the Intrinsic and Extrinsic Factors that Alter Drug Exposure and Toxicity
Intrinsic factors such as age, biological sex, comorbidities, or genetics can potentially alter drug exposure, as can extrinsic factors such as concomitant drugs, supplements, the environment, and food and beverages. One of the most important factors to consider during the course of your early-phase clinical research is drug-drug interactions (DDIs), which occur when one drug alters the effect of another, either by reducing its effectiveness or elevating systemic concentrations to potentially dangerous levels—ultimately causing side effects.
In some cases, these side effects could be life-threatening, such as drops in blood pressure, irregular heartbeats, or organ damage.
In Issue 7 of The Altascientist, we delve into these factors, the importance of drug interaction studies, and how to limit adverse effects and maximize treatment response. Listen to the audiobook or download the PDF below, to learn more about:
- key factors to consider in drug development (age, biological sex, genetics, DDIs);
- examples of common DDI involving the cytochrome P450 enzyme system; and
- drug interactions and guidance for marketed drugs.
The issue also features a drug-drug interaction case study, in which the effects of two doses of a sponsor’s investigational product on the pharmacokinetics of multiple oral doses of clopidogrel, and a single dose of warfarin in healthy adult subjects were evaluated.
Identifying Drug-Drug Interactions (DDIs)
The increasing number of drugs on the market has led to a greater potential for drug-drug interactions, and more complex drug regimens with multiple compounds administered to treat one condition or different compounds given to treat comorbidities, are also contributing factors. These interactions must be identified during the development process as part of the assessment of the drug’s risks and benefits.
According to the FDA’s 2024 guidance titled M12 Drug Interaction Studies, clinically significant DDIs between investigational and other drugs should be addressed at various stages of drug development. They should also be thoroughly understood through nonclinical and clinical studies by the time the drug is approved, monitored after approval, and clearly communicated in the drug's labeling to ensure proper management strategies for clinically significant DDIs and safety. In M12, the FDA states, “The potential for an investigational drug to cause DDIs should be investigated in a stepwise manner during drug development. The potential for an investigational drug to cause pharmacokinetic interactions both as an object (effect of other drugs on the investigational drug) and as a precipitant (effect of the investigational drug on concomitant drugs) should be evaluated.”
Explore all issues of The Altascientist in our Resource Center. And don’t forget to subscribe to The Altascientist: Audiobooks on Spotify, Apple Podcasts, or wherever you get your audio content.
Up Close and Personal with Ingrid Holmes
Ingrid joined Altasciences in 2011, as Vice President of Clinical Operations at the Montreal site, a facility currently housing seven clinical units with 265 beds, and dedicated
Altasciences Contributes to Positive Top-Line Phase I Results for Chronic Cough Drug Candidate
LAVAL, QC, Canada (December 12, 2018) — Altasciences recently completed an important First-in-Human (FIH), Phase I, integrated adaptive clinical trial, including single and multiple ascending doses (SAD and MAD), Project Management, Bioanalysis, and Medical Writing, for sponsor Bellus Health.
Altasciences’ contributions to the positive top-line results were significant. From recruitment of 90 subjects to management of all relevant aspects of this important FIH trial, Altasciences used a flexible and adaptive approach to fully meet the client’s needs. Altasciences’ contributions allowed Bellus Health to make a well-informed decision to proceed with their promising drug candidate for chronic cough.
“We awarded this trial to Altasciences based on their reputation for quality, speed and efficiency, and we were not disappointed. Thanks to their great efforts, we have been able to determine that our compound is safe and well-tolerated, and we are proceeding to the next stage of development without delay. Altasciences’ ability to deliver results efficiently helped us make important decisions to move ahead,” says Dr. Denis Garceau, Senior Vice President, Drug Development, at Bellus Health.
Altasciences conducts hundreds of early phase clinical trials annually. Their vast participant database permits rapid recruitment, and they are constantly refining their processes and offerings to better meet sponsor needs.
“We are very proud of our work on novel compounds at Altasciences, and the fact that we’re able to deliver results in a timely, efficient manner that meets or exceeds our sponsors’ drug development timelines.” says Ingrid Holmes, Vice President, Global Clinical Operations, for Altasciences.
About Altasciences
Altasciences is an integrated drug development solution company offering pharmaceutical and biotechnology companies a proven, flexible approach to preclinical and clinical pharmacology studies, including formulation, manufacturing, and analytical services. For over 25 years, Altasciences has been partnering with sponsors to help support educated, faster, and more complete early drug development decisions. Altasciences’ integrated, full-service solutions include preclinical safety testing, clinical pharmacology and proof of concept, bioanalysis, program management, medical writing, biostatistics, clinical monitoring, and data management, all customizable to specific sponsor requirements. Altasciences helps sponsors get better drugs to the people who need them, faster.
For more information
Julie-Ann Cabana
jcabana@altasciences.com
913 304-4505
ISSUE NO. 6 — Hybrid Medicines and 505(b)(2) NDA Approval Pathways
Hybrid medicines are drugs based on a generic molecule, and have a different route of administration, format, strength, or indication from the original reference product.
They require re-approval for market authorization, partly based on data from the original reference medicine, and partly on data from new clinical trials on the modified version.
Like the hybrid medicine authorization process in the European Union, the 505(b)(2) new drug application (NDA) approval process in the United States applies to generic molecules that have a slight change from the reference medicine, and can use published data, including previous FDA submissions and communications, to support their re-approval by the FDA.
In Issue 6 of The Altascientist, we explore the 505(b)(2) NDA approval pathways and their benefits over generic approvals, relevant drug categories, and key strategies for market authorization:
- Applicable categories of drugs for hybrid or 505(b)(2) pathways
- Hybrid or 505(b)(2) vs. generics
- Choosing a drug candidate
- A case study: Achieving a 505(b)(2) Regulatory Approval
Hybrid or 505(b)(2) versus Generic Pathways
Medicines approved via the hybrid or 505(b)(2) regulatory pathways have certain market advantages over generics. Because hybrid medicines deliver additional benefits compared to the reference product (a new delivery system, different formulation, new indication, etc.,) they can be branded, and marketed, with attention to the advancements they bring to treatment.
Generic medicines are considered equivalent to their reference products and, as such, cannot be branded or marketed on their features. Their product insert and safety information are identical to that of the reference product. Generics compete on price, while hybrid or 505(b)(2) products compete based on the improvements they offer (i.e., ease of use, safety, or efficacy). The submission requirements for both types of products also differ, which is why pre-submission meetings with regulatory bodies are essential and serve to establish the exact data sets required.
Altasciences has decades of experience conducting research for modified drugs taking the hybrid or 505(b)(2) approval pathway. In fact, since 2010, we have designed and conducted more than 250 studies that followed these pathways.
Get in touch today to see how we can support your 505(b)(2) application!
Altasciences Completes Bioanalytical Laboratory Expansion
LAVAL, QC, Canada (November 8, 2018) — Altasciences is excited to announce the completion of their laboratory expansion. The additional space will be dedicated to ligand binding and cell-based assays. Altasciences’ bioanalytical services continue to grow, and the added, state-of-the-art lab area ensures capacity to continue delivering quality bioanalysis solutions to both their preclinical and clinical clients.
The new, larger space, opened for use this week, is fully equipped to respond to increased demand for cell-based neutralization and functional assays for biologics and vaccines. Altasciences now has additional capacity for cell lineage and functional immuno-phenotyping by flow cytometry to support both preclinical and clinical studies.
“The extension of our bioanalytical laboratory ensures that we are equipped to continue providing the excellent bioanalytical services that Altasciences is known for. As demand for our services grows, we are committed to expanding our infrastructure and ensuring our usual, on-time delivery.” stated Marie-Hélène Raigneau, Altasciences’ Executive Vice President, Research Services.
Altasciences’ bioanalytical team consists of more than 100 dedicated scientists in both the U.S. and Canada who provide a comprehensive suite of bioanalytical services, from discovery to preclinical to phase IV clinical support, for both small and large molecules including immunogenicity, biomarker, and PK.
About Altasciences
Altasciences is an integrated drug development solution company offering pharmaceutical and biotechnology companies a proven, flexible approach to preclinical and clinical pharmacology studies, including formulation, manufacturing, and analytical services. For over 25 years, Altasciences has been partnering with sponsors to help support educated, faster, and more complete early drug development decisions. Altasciences’ integrated, full-service solutions include preclinical safety testing, clinical pharmacology and proof of concept, bioanalysis, program management, medical writing, biostatistics, clinical monitoring, and data management, all customizable to specific sponsor requirements. Altasciences helps sponsors get better drugs to the people who need them, faster.
For more information
Julie-Ann Cabana
jcabana@altasciences.com
913 304-4505
ISSUE NO. 5 — Metabolic Disorders (Obesity, Diabetes, NAFLD/NASH) — Updated 2021
Metabolic disorders are conditions that disrupt normal metabolism and the process of converting food to energy at the cellular level. They affect the ability of the cell to
perform critical biochemical reactions that involve the processing or transport of proteins (amino acids), carbohydrates (sugars and starches), or lipids (fatty acids). Metabolic disorders can take many forms, with obesity and diabetes being the most common.
The worldwide prevalence of obesity has nearly tripled between 1975 and 2022. Once considered a high-income country problem, obesity is on the rise even in low- and middle-income countries.
In Issue 5 of The Altascientist, we investigate the challenges of metabolic disorders, with insights from Altasciences’ clinical and preclinical experts, as well as:
- Frequently asked questions about clinical trials for metabolic disorders
- An Altasciences case study
- A hidden threat: nonalcoholic fatty liver disease (NAFLD)
- Altasciences’ end-to-end patient recruitment process and patient access for NASH studies
Obesity, Diabetes, and Metabolic Dysfunction
As obesity continues to rise globally, the risk of developing associated metabolic disorders, including type 2 diabetes, has escalated.
Several epidemiologic studies reveal a direct link between the escalation of obesity and diabetes. The pathophysiology connecting the two metabolic disorders is mainly attributed to two factors: insulin resistance and insulin deficiency. Research shows that if you are obese, your chances of developing type 2 diabetes are 80 times greater than a person whose body mass index (BMI) is within a normal range (under 25).
Type 2 diabetes is a dysfunction in the way the body metabolizes glucose, causing it to rely on alternative energy sources from tissues, muscles, and organs. Individuals suffering from the disease are either resistant to insulin or do not produce enough of it to maintain healthy blood glucose levels.
Nonalcoholic Fatty Liver Disease (NAFLD)
Much like obesity and diabetes, nonalcoholic fatty liver disease (NAFLD) is a global epidemic, with prevalence rates reaching 25% to 30%. NAFLD can be divided into the milder form, nonalcoholic fatty liver (NAFL), and the more aggressive form, nonalcoholic steatohepatitis (NASH). It is characterized by different levels of hepatic steatosis (fat deposition), inflammation (in NASH), and fibrosis.
Despite the growing prevalence of NAFLD/NASH, treatment options remain extremely limited. A large number of pharmaceutical companies have started to conduct clinical studies to develop treatments for NASH, but recruiting patients for these types of studies is particularly challenging as this disease does not present with clear symptoms, and the majority of patients do not know they have it or are not diagnosed until significant damage to the liver has occurred.
“One of our ultimate goals is to develop approaches for better diagnosis and management of chronic liver disease, which is currently an increasing worldwide concern, and demands early-phase trials that require specific imaging and biomarker services. We are continuously expanding Altasciences’ therapeutic offerings in gastrointestinal disease-specific studies, particularly those intended to investigate the efficacy of drugs in patients with NASH.”
Dr. Gaetano Morelli, MD, Executive Vice President Medical Affairs,
Chief Medical Officer
Altasciences saw the developing need for patients with NASH and proactively built a database of patients suffering from the disease using an IRB-approved protocol we sponsored ourselves. Since NASH patients are often underdiagnosed, Dr. Gaetano Morelli used his expertise in NASH to build a campaign based on a set of criteria the patients will recognize as applicable to them.
Altasciences’ Expertise in Metabolic Disorders
Our ability to effectively recruit patients, our clinical operational experience, and our robust list of validated bioanalytical assays—including exenatide, glucagon, insulin glargine, M1, M2, insulin aspart, and metformin—provide the perfect solution for organizations studying obesity and developing treatments for metabolic disorders.
“We have conducted many different types of studies in these patient populations, from first-in-human (FIH), single ascending dose (SAD) to proof-of-concept (POC) studies. The focus of the studies ranges from glucose tolerance to pharmacokinetics, comparing obese subjects to those with normal weights.”
Ingrid Holmes, Vice President, Global Clinical Operations
Explore all issues of The Altascientist in our Resource Center. And don’t forget to subscribe to “The Altascientist: Audiobooks” on Spotify, Apple Podcasts, or wherever you get your audio content.
Procedure for Repeated Ultrasound Guided Liver Biopsies in Nonhuman Primates
Altasciences Completes Acquisition of Preclinical Testing Business and Hires Key Staff
LAVAL, QC, Canada (October 1, 2018) — Altasciences today announced the completion of the acquisition of a preclinical testing business in Everett, Washington. This transaction will support Altasciences’ goal of being a mid-sized CRO that will provide talent and scale to support the preclinical and clinical markets while creating a new outsourcing paradigm for its clients.
"Our vision is to become the first CRO to build a service offering allowing for multiple points of entry that flows seamlessly from lead candidate selection to proof of concept. We now have more than 1,300 staff members in two countries working together to bring our customers the best possible services," said Steve Mason, Executive Vice President, Site Operations, at Altasciences.
Altasciences also confirmed today three key additions to the Seattle team who already boast significant expertise in preclinical testing. Michael Broadhurst has joined Altasciences as General Manager, Preclinical Safety Testing Operations; Francis Douville has joined as Vice President, Operations; and Julie Forget has joined as Director, Toxicology, and will oversee the Study Director group.
“We specifically hand-picked experienced individuals with whom we worked alongside for many years, back when Charles River in Montreal was known as CTBR. It was essential that we hire people that share our culture and values, and particularly our focus on delivering expert guidance with exceptional customer service. In addition, all three hires understand the importance of integrating our services to provide a coordinated outsourcing experience,” explained Chris Perkin, CEO at Altasciences.
These individuals bring many decades of relevant experience and have been specifically selected to add to Altasciences’ toxicology expertise as well as facilitate integration into the Altasciences vision of a full service early drug development CRO. Both the new hires and existing management will play an integral role as Altasciences prepares to further build and integrate large and small molecule safety testing services.
About Altasciences
Altasciences is a forward-thinking, mid-size contract research organization offering pharmaceutical and biotechnology companies a proven, flexible approach to preclinical and clinical pharmacology studies, including formulation, manufacturing, and analytical services. For over 25 years, Altasciences has been partnering with sponsors to help support educated, faster, and more complete early drug development decisions. Altasciences’ integrated, full-service solutions include preclinical safety testing, clinical pharmacology and proof of concept, bioanalysis, program management, medical writing, biostatistics, and data management, all customizable to specific sponsor requirements. Altasciences helps sponsors get better drugs to the people who need them, faster.
For more information
Julie-Ann Cabana
jcabana@altasciences.com
913 304-4505
Altasciences to present Continuing Education Course at the New York State Bar Association
LAVAL, QC, Canada (September 25, 2018) — Altasciences is pleased to announce that Dr. Graham K. Wood, Chief R&D Officer at Altasciences, is presenting at a Continuing Legal Education program entitled Practical Implications of Decriminalized Marijuana for the Legal Practitioner on Wednesday, October 3. The program, which offers 7.0 MCLE credits, is open to members of the New York State Bar Association, who will hear Dr. Wood share his knowledge in the cannabis field, specifically as it relates to Clinical Research.
Dr. Wood has a Ph.D. in Neurology and Neurosurgery from McGill University, has worked as a Research Fellow at the National Institute of Mental Health, and has almost 20 years of experience in designing and conducting clinical pharmacology studies. His deep and broad understanding of the cognitive effects of cannabis is the basis for his testimony to the Canadian Senate on the effects of Cannabis on driving, and he has designed a number of recent first-in-human studies on the safety, tolerability, and cognitive effects of cannabis.
“As the legal landscape around marijuana continues to evolve, reliable clinical research on the effects of cannabis in humans becomes increasingly important, whether the use will be for medical or recreational purposes. It was an educational experience to be part of recent studies in the area, and I look forward to sharing the insights with the New York State Bar”, said Dr. Wood.
The CLE program is organized by the Committee on Continuing Legal Education of the New York State Bar Association, and is sponsored by Barclay Damon LLP. It is also co-sponsored by the Committee on Cannabis Law, the Committee on Continuing Legal Education and the General Practice Section of the New York State Bar Association.
Altasciences is a mid-size CRO focused on early phase drug development, involved in the study of cannabis for over 10 years, with 34 studies completed to date; 14 focused on pharmacokinetics, 1 first-in-human, and one focused on human abuse liability, as well as 18 others.
About Altasciences
Altasciences is an integrated drug development solution company offering pharmaceutical and biotechnology companies a proven, flexible approach to preclinical and clinical pharmacology studies, including formulation, manufacturing, and analytical services. For over 25 years, Altasciences has been partnering with sponsors to help support educated, faster, and more complete early drug development decisions. Altasciences’ integrated, full-service solutions include preclinical safety testing, clinical pharmacology and proof of concept, bioanalysis, program management, medical writing, biostatistics, clinical monitoring, and data management, all customizable to specific sponsor requirements. Altasciences helps sponsors get better drugs to the people who need them, faster.
For more information
Julie-Ann Cabana
jcabana@altasciences.com
913 304-4505
Pain – is it all in your head?
Pain is a fascinating phenomenon, acting as a physiological warning system that alerts us of potential dangers in our environment.