Phase 1 trials are the first clinical trials to include humans. They are essential in determining the safety and tolerability of a drug in development. A well-designed phase 1 clinical trial is heavily dependent on clinical pharmacology, the medical discipline that bridges preclinical science into data-driven decisions.
Without thorough clinical pharmacology, Phase 1 clinical trials are risky, full of uncertainty and increase the potential for failure. When clinical pharmacology is carried out, early clinical development becomes safer, more efficient and better predictive of later stage success.
What is clinical pharmacology?
Clinical Pharmacology is the scientific study of drugs in humans. It overcomes major scientific challenges of drug development by predicting the efficacy, safety and variability in response to the drug. It’s an essential element of sustaining successful processes and advancing healthcare. Critically, it transitions studies from laboratory and animal-based to first-in-human (FiH) dosing.
Through integrating preclinical findings with modelling and simulation, clinical pharmacology reduces uncertainty and supports rational trial design before the first participant is dosed.
Key outputs of Clinical Pharmacology include:
- Pharmacokinetics
- Pharmacodynamics
- Exposure response relationships
- Biomarkers and target engagements
Why is clinical pharmacology important for phase 1 clinical trials?
Clinical pharmacology underpins first-in-human data by providing the scientific framework required to establish a drug’s safety and tolerability. Leveraging approaches such as No Observed Adverse Effect Level (NOAEL), minimum anticipated biological effect level (MABEL), and pharmacokinetic (PK) modelling, it supports rational starting-dose selection, minimising participant risk and guiding ethical, scientific dose escalation.
By integrating model-informed drug development (MIDD), clinical pharmacology enhances these decisions by using preclinical and clinical data to develop mathematical models of PK, Pharmacodynamic (PD) and drug response. Tools such as physiologically based pharmacokinetic (PBPK) modelling, population PK analysis, and quantitative systems pharmacology (QSP) allow clinicians to predict human drug response, optimise drug dosing strategies and evaluate populations such as paediatric, renal or haematological impairment.
Combining PK/PD analysis with emerging safety data, clinicians can identify the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs), linking adverse events to systemic drug exposure and target engagement. This exposure-based approach ensures informed, scientifically justified decisions on dose escalation, modification or stopping, protecting participant safety while establishing a strong foundation for phase 2 studies.
Phase 1 clinical trials provide the unique opportunity to generate high-quality, actionable data. Embedding clinical pharmacology and MIDD at the core of these studies ensures that the trials are designed intelligently, conducted safely and interpreted meaningfully, reducing risk, enhancing the scientific understanding and building a stronger foundation for successful drug development.
Key Study designs introduced in clinical pharmacology
To generate the data required to characterise the drug’s safety, clinical pharmacology employs a range of well-established study designs, including:
Parallel Group Design:
In this type of clinical trial, subjects are randomised to different treatment arms, either receiving the drug or a placebo. This type of design is ideal for comparing different interventions.
Crossover Designs:
Participants receive both the investigational drug and the placebo replacement in different, randomised sequences, usually with an interval where the subject stops using the medication, allowing it to be cleared from their system before continuing, commonly referred to as a washout period. This sort of clinical trial study design is used in bioequivalence studies because it reduces subject-to-subject variability.
SAD/MAD:
Single/multiple ascending dose studies are used in first-in-human trials to determine maximum tolerated dose safety and pharmacokinetic (PK) parameters
Clinical pharmacology is central to defining escalation steps, decision rules and stopping criteria. The real-time PK analysis allows teams to confirm dose proportionality, identify accumulation with repeat dosing, and adjust escalation strategies based on emerging data.
Specialised PK/PD studies
These are advanced, tailored investigations designed to move from preclinical research to clinical trials, ensuring that drug candidates are safe, effective, and correctly dosed. These types of studies go further than usual Absorption, Distribution, Metabolism, Excretion (ADME), and excretion methods to map how drug concentration in blood and tissues correlates with biological therapeutic or toxic effects.
Translational PK/PD Modelling and Simulation:
Using PBPK, these studies predict human drug behaviour from in vitro and animal data, allowing for simulation of drug – drug interactions and evaluation of specific populations.
H3: Target engagement and Biomarker studies:
These focus on measuring specific PD markers, which are molecular indicators of the drug effects on its target. This usually includes cytokine profiling, receptor occupancy, or pathway inhibition, often using Enzyme linked immunoabsorbent Assay (ELISA), flow cytometry or imaging.
H3: Gene and Stem Cell Therapy Studies:
Gene and stem cell therapy studies are tailored for the long-term effects and complex biodistribution of viral and non-viral vectors.
Clinical Pharmacology and Regulatory Expectations
Clinical pharmacology ensures that your clinical trial design adheres to regulations from authoritative bodies. This includes ensuring that your trial has integrated PK and PD analyses, clear dose justification and robust interpretation of safety data to meet regulatory requirements.
Clinical pharmacology supports:
- Investigational New Drug (IND) and Clinical Trial (CTA) Submissions
- Regulatory interactions and scientific advice
- Transparent justification of study design and outcomes
By providing a strong scientific rationale and interpretable data, clinical pharmacology reduces the risk of regulatory questions, delays and supports confident decision-making during early clinical development. Clinical pharmacology is not only a regulatory requirement but a strategic asset, increasing the likelihood of success in your clinical trial.
Beyond meeting safety requirements, Phase 1 trials generate data that inform critical decisions for later stages of development. Clinical pharmacology enables sponsors to assess not only whether a drug is safe, but whether it has the potential to demonstrate meaningful biological or therapeutic activity.
Reliable and thorough clinical pharmacology data generated early in development are essential to:
- Reduce late-stage attrition
- Optimise dose and regimen selection for Phase 2
- Accelerate overall development timelines
Clinical Pharmacology Services at Simbec- Orion
At Simbec-Orion, we are proud to have a purpose-built MHRA-accredited Clinical pharmacology unit which delivers comprehensive services designed to support you with safe, efficient progression of your drug development programme from the first in human to the following early clinical phases.
With 50 years of experience conducting adaptive and traditional pharmacology studies, our expert team ensures your clinical pharmacology strategy adds value and mitigates risk at every step. Ready to start your clinical pharmacology process? Get in touch with our specialist team today to see how we can help.
Clinical pharmacology: Frequently asked questions
How is clinical pharmacology different from clinical research?
Whilst clinical research focuses on conducting trials and collecting data, clinical pharmacology focuses on interpreting how the drug behaves in humans, using this information to guide development decisions. The two disciplines do work together, especially in early-phase trials, but they are different.
How can clinical pharmacology support the transition to phase 2?
Using data from Phase 1 clinical pharmacology can inform Phase 2 dose selection, regimen design and study endpoints. Understanding exposure-response relationships early helps ensure phase 2 trials are appropriately designed and adequately powered.
What are adaptive designs in clinical pharmacology studies?
Adaptive clinical designs allow modifications to the study based on emerging data, such as adjusting dose levels or cohort sizes. Adaptive designs rely on robust clinical pharmacology input to ensure changes are scientifically justified and regulatory acceptable.