First-In-Human (FIH) & Single Ascending Dose (SAD) Studies
First-In-Human Studies include the first administration of a chemical or a biological product, designated as a New Chemical Entity (NCE) or a New Investigational Medicinal Product (IMP), in humans. First-in-Human studies identify a dose range that is both safe to administer in further trials and capable of exerting a pharmacological activity. These studies are commonly associated with Single Ascending Dose (SAD) design, and with Multiple Ascending Dose (MAD) studies which are carried out subsequently or in parallel.
Prior to the initiation of a first-in-human trial, comprehensive preclinical studies are carried out to assess the safety and efficacy of an investigational drug. However, since preclinical models generally cannot encompass the complexity of medical conditions affecting humans, first-in-human studies are associated with inherent safety risks.
Participant safety should be the utmost priority of investigators designing and conducting first-in-human trials. Moreover, there are significant challenges associated with selecting the optimal first dose and dosing schedule for single ascending dose studies, and appropriate observation periods should be maintained between the dosing of individual participants to ensure their safety.
Strategies for Risk Assessment, Mitigation and Study Monitoring
A comprehensive strategy for risk assessment and mitigation and study monitoring is critical for first-in-human studies and should be in place prior to their initiation. BioPharma Services Inc.’s expert team of physicians and Ph.D.-level pharmacologists have developed a standard baseline set of safety assessments that are implemented in the safety monitoring of all investigational drugs entering first-in-human studies.
Based on the preclinical data of our clients and the characteristics of the investigational drug, our team proposes and implements additional safety measures to specifically evaluate any safety signals detected in the preclinical program or relevant for the pharmacology, drug target, or therapeutic target of the drug.
Our risk mitigation strategy is not only well-defined, but also adaptive and responsive to the data collected in the course of first-in-human and single ascending dose studies. In designing the first-in-human study, we can assess the information that researchers will later need for their Phase 2 trial.
Capabilities in Expanding Complexity of First-in-Human Studies
The complexity of clinical trial design and conduct has markedly increased in recent years, including a higher number of more frequently performed procedures and more substantial time commitment for study participants. The complexity of early-phase clinical trials, including first-in-human studies, is also enhanced by the need for extensive safety monitoring and correlative testing.
BioPharma’s expert multidisciplinary team and dedicated, state-of-the-art Phase 1 centers enable us to efficiently design and conduct even the most challenging and complex first-in-human and single ascending dose studies in healthy normal volunteers (HNVs).
An Unparalleled Expert Multidisciplinary Team
The extensive expertise of BioPharma’s medical and scientific teams in designing and conducting first-in-human and single ascending dose studies enables us to successfully manage the studies’ inherent risks and complexity. Our multidisciplinary team consists of physicians, pharmacologists, laboratory scientists, statisticians, and regulatory affair specialists who collaborate closely in the design and conduct of all aspects of the study.
Dr. John Oldenhof
Chief Scientific Officer
Dr. John Oldenhof has extensive senior management experience in Phase 1 clinical pharmacology, product development, biostatistics, clinical trial data management, and regulatory and scientific affairs.
Dr. Fathi Abuzgaya
Chief Medical Officer & Principal Investigator
Our chief medical officer (CMO) Dr. Fathi Abuzgaya has over 15 years of experience serving as a Principal Investigator (PI) or sub-investigator for over 100 clinical trials in a wide range of therapeutic areas.
State-of-the-Art Facilities for Early-Phase Clinical Trials
To ensure the safety of participants in first-in-human and single ascending dose studies, the BioPharma Services’ team relies on our state-of-the-art Phase 1 centers, located in Toronto, Canada and St. Louis, Missouri. The two centers have all necessary infrastructure and equipment for comprehensive safety monitoring, including dedicated Phase 1 clinical trial intensive monitoring units.
The capabilities of our clinical centers include a limited number of beds, a nursing station in the rooms, 24-hour monitoring, a telemetric option, a crash cart, ALCS-trained staff, and PIs with extensive experience, including ER physicians and anesthesiologists.
Comprehensive Support for Starting Dose Selection and Dose Acceleration Schedule
The starting dose selection for first-in-human studies is a complex process due to the challenges associated with extrapolating preclinical findings to humans and selecting a dose that minimizes the toxicity risk but is still relevant as a starting point for subsequent dose acceleration studies.
At BioPharma Services, we thoroughly review our clients’ preclinical data and provide feedback and suggestions regarding all safety aspects of the study. Moreover, we help our clients with the starting dose selection for first-in-human studies in an individualized manner, based on the specific needs of their studies and the extent of their previous experience.
Our expert team also helps clients with the pharmacokinetic design of single ascending dose studies. We start with a sufficiently low dose to ensure patient safety, and then escalate the dose at a safe rate. Moreover, we ensure that the acceleration schedule covers doses expected to exert pharmacological effects in future trials.
BioPharma Services’ pharmacokinetic team plays a key role in the selection of appropriate pharmacokinetic time points for the trial. We use pharmacokinetic modeling to examine the preclinical data and to model the dosing for the subsequent multiple ascending dose study.
Our team can also help with the selection of pharmacodynamic endpoints of a trial in order to provide a better understanding of the drug. This may include biomarkers or cognitive endpoints that evaluate the effects of the drug in HNVs. Moreover, we can work with various early formulations selected by the study sponsors. Our team has extensive pharmacy capabilities and can perform complex compounding and sterile preparations.
Experience With Challenging Routes of Administration
Our multidisciplinary team has designed and conducted studies with various administration routes, including oral, intravenous, intraperitoneal, and topical skin administration. Moreover, we have experience conducting clinical trials with medical devices. Notably, we collaborate with a network of experts with experience in challenging administration routes that help us accommodate the unique needs of our clients.
Multidisciplinary Management of First-in-Human
and Single Ascending Dose Studies
BioPharma Services has established a large database of study volunteers, including over 18,000 HNVs and individuals from special populations. The strong rapport that we have established with our study volunteers greatly facilitates the recruitment for our clients’ clinical trials. Moreover, our recruitment procedure is comprehensive and sets participants’ safety as our top priority.
Our in-house bioanalytical laboratory analyzes biological samples from bioequivalence and bioavailability bioequivalence/bioavailability and clinical pharmacokinetic studies. Our bioanalytical team performs state-of-the-art liquid chromatography with tandem mass spectrometry (LC/MS/MS) analysis to confirm and quantify low-abundance analytes in a variety of matrices.
Dr. Nicki Hughes, who has over 20 years of experience in bioanalytical research, oversees our R&D, validation, and production groups. Our good laboratory practice (GLP) of our bioanalytical services laboratory has been certified by the Standards Council of Canada (SCC).
Exhaustive Statistical Design & Analysis
Our biostatisticians’ team has expertise in the development of statistical analysis plans (SAPs), safety clinical trial data management, and medical coding for first-in-human studies. Moreover, all statistical analysis aspects of the first-in-human studies designed by our team strictly comply with the requirements of the Clinical Data Interchange Standards Consortium (CDISC).
Expert Team of Regulatory Support
BioPharma Services’ team of regulatory experts ensures that all study aspects comply with the requirements of regulatory agencies. The expertise of our team has been confirmed by over 30 successful regulatory inspections by a number of regulatory agencies, including the United States FDA, United Kingdom MHRA, French ANSM, Danish Medicines Agency, Brazilian ANVISA, Health Canada, and the World Health Organization.
First-in-human and single ascending dose studies present significant challenges, especially in regard to participants’ safety. Partnering with an experienced and innovative full-service clinical research organization (CRO) like BioPharma Services will ensure all aspects of your studies are designed and performed with participants’ safety as a top priority and in compliance with all regulatory guidelines.
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