What are Early Phase Clinical Trials?

Early phase clinical trials are the first stage of testing a new medical treatment, drug, or device in human subjects. The focus of these trials in clinical development is to determine the safety and tolerability of the treatment, as well as to identify any potential side effects.

You might also be interested in learning more about early phase oncology clinical trials or exploring phase I CRO services.

The development of early phase clinical trials

Early phase clinical trials take place following preclinical studies, which are conducted  using animals or in laboratory settings. Both preclinical and early phase studies provide important information about the safety and efficacy of the treatment, and help researchers determine the appropriate dosage for use in human subjects. Early phase clinical development then includes phase I and phase II studies.

1. Preclinical studies

During preclinical studies, researchers conduct a series of studies to determine the safety and efficacy of the new drug. This typically includes in vitro (test tube) studies, in vivo (animal) studies, pharmacokinetic (PK) and pharmacodynamic (PD) studies. The length and design of each study is dependent on the intended clinical use of the final therapeutic. 

For example, a drug intended to be taken daily for the lifetime of a patient, such as those to treat epilepsy, will undergo a far longer preclinical testing program than another which may be taken for a few days once or twice in a patient’s lifetime, such as an antibiotic.

2. In vitro studies 

In vitro studies are often the first step in preclinical testing conducted using cells, tissues, and other biological samples. They are used to determine the basic properties of the drug, such as how it interacts with cells and what its effects are on a cellular level. 

The studies are done outside the cell’s typical biological context so that we can discover properties of the drug without as many variables present.  With greater scientific advances however, such studies are becoming increasingly  sophisticated, and researchers can often use data derived from in vitro studies to help reduce the number of live animals required on a subsequent study, or as a complete replacement for live animal trials

In vivo studies are conducted using live organisms such as mice or rats, to evaluate the safety, efficacy, and potential side effects of the drug. Study designs follow multiple regulatory guidelines and are closely matched to the intended clinical administration protocol.  

This programme of studies can take anything from a few months to several years, depending on how often and for how long the final therapeutic will be taken by the patient. 

Pharmacokinetic (PK) and pharmacodynamic (PD) studies are also conducted during preclinical studies. PK studies evaluate how the body processes a drug, including how it is absorbed, distributed, metabolised, and eliminated. PD studies evaluate the  biochemical, physiological and molecular effects of a drug.

The data generated from preclinical studies are used to determine whether the drug is safe enough to move on to clinical trials in humans. The final decision however is taken by the relevant regulatory authority, such as the FDA in the USA, or the EMA in Europe. 

Their own scientists will independently assess the data submitted and determine if they regard it as safe for the first human trial to go ahead. Once this authorisation is received the drug will progress onto the next phase of clinical development – early phase clinical trials – to further evaluate its safety and efficiency.

3. Early phase clinical trials

Early phase clinical development includes phase I and phase II studies, which usually focus on the safety profile of the treatment, including identifying any potential side effects. The number of participants in these trials are limited, typically ranging from 20-80 volunteers, and the duration of the trial can vary depending on the nature of the treatment, but it typically can take several months from study initiation to production of the draft report.

During a phase I trial, also known as a first-in-human trial, participants are given the drug in escalating doses. This allows researchers to evaluate the safety profile of the drug at different levels.

Phase I trials can also include pharmacokinetic studies, which evaluate how the body processes the drug, including how it is absorbed, distributed, metabolised, and eliminated. From this study the researchers can begin to determine the appropriate drug concentration.

It’s worth mentioning that phase I trials are conducted under strict safety guidelines, with the close monitoring of participants. Participants are carefully screened and selected, and are given detailed information about the trial and the drug before they agree to participate. They are also closely monitored throughout the trial, and any adverse reactions or side effects are carefully recorded and reported.

It’s common for pharma companies to partner with a Clinical Research Organisation (CRO) to conduct the phase I clinical trials. As specialists they can provide the necessary expertise, facilities and support and will have extensive experience in operating under the strict safety guidelines.

There are three stages of clinical trials, and phase I (as the name suggests) is just the first step. Early phase clinical development is often also used to include phase II  trials.

Find out more about our phase II CRO services.

4. Early phase development approval

Not all treatments are approved following the early phase, if they don’t meet the safety standards or if the results are not promising, the drugs won’t be tested and developed further. There are three key criteria that need to be met following early phase clinical trials in order for a drug to be considered suitable to progress to the next stage: Safety, tolerability and efficacy.

Once again, the regulatory bodies have the final word on whether a treatment can proceed to the next phase of testing or not. A report published in 2021 found that of phase I trials conducted in the USA between 2011 to 2020, the success rate was just 52%.

Safety in early phase trials

The drug must be shown to be safe for use in humans, with minimal side effects or adverse reactions.

During the safety testing, the new drug is given to a small group of healthy volunteers, in order to assess its safety profile. The safety profile includes any potential side effects or adverse reactions that may occur as a result of taking the drug.

The safety testing can include a variety of different tests and assessments, such as:

  • Vital sign measurements: Blood pressure, heart rate, and temperature are closely monitored to ensure that the drug is not causing any negative effects on the body’s vital systems.
  • Laboratory tests: Blood and urine samples are taken to check for any changes in the levels of various chemicals or enzymes in the body, which could indicate a potential safety concern.
  • Physical examinations: Patients are examined by a doctor to check for any signs of adverse reactions or side effects, such as rashes or swelling.
  • Questionnaires and interviews: Patients may be asked to fill out questionnaires or participate in interviews. They then provide information about their experiences with the drug, such as any symptoms they may have experienced or any changes in their overall health.

If a drug is found to be unsafe, or if significant side effects are identified, the trial will be stopped and the drug will not be allowed to progress. However, if the drug is found to be safe, it will be approved for further clinical development.

Tolerability in early phase trials

Tolerability is another important aspect that is evaluated during early phase research. It refers to how well the drug is tolerated in human subjects without or with minimal adverse reactions.

During the tolerability testing, the new drug is given to a small group of healthy volunteers, in order to assess its tolerability profile. The tolerability profile includes any negative reactions or side effects that may occur as a result of taking the drug, such as nausea, dizziness, headache, or fatigue.

The tolerability testing can include a variety of different tests and assessments that are similar to the safety tests. The two milestones complement each other because a safe drug is also a tolerable drug.

If a drug is found to have poor tolerability, modifications can be made to the drug, such as changing the dosage, formulation, or administration method in order to improve its tolerability.

Alternatively, the pharmaceutical company may decide to stop the trial completely and discontinue the drug’s clinical development.

Efficacy in early phase trials

Efficacy will likely be investigated in more detail later on in the clinical development process, for example phase II (although this is sometimes included under the umbrella term ‘early phase clinical development’) and phase III

Phase I efficacy tests are primarily intended to give a broad idea of how effective the drug is at producing the desired therapeutic effect. 

The new drug is given to a group of patients with the disease or condition of interest, in order to assess its ability to produce the desired therapeutic effect. The efficacy is evaluated by measuring the change in the disease or condition after taking the drug, compared to a control group that receives a placebo or standard treatment.

The efficacy testing can include a variety of different tests and assessments, such as:

  • Clinical outcome measures: This can include measuring the size of a tumour, changes in blood pressure, or improvement in patient symptoms.
  • Quality of life measurements: Questionnaires can be used to measure the patient’s quality of life, such as their ability to perform daily activities, their emotional well-being, and their level of pain.

If a drug is found to be ineffective, or if it does not produce a significant therapeutic effect compared to the control group, the trial may be stopped and the drug will not be allowed to move on to the next phase of testing. However, if the drug is found to be effective, it will be approved for further clinical development. In phase III, its safety and tolerability will be evaluated in a larger patient population.

Failing phase I trials

If a drug fails phase I trials, the pharmaceutical company that developed it may choose to discontinue its development or make modifications to the drug before attempting to re-test it. The reasons for failure in phase I trials can vary, but it is often due to issues with the milestones we previously mentioned (safety, tolerability, or a lack of efficacy).

When a drug fails phase I trials, the pharmaceutical company will review the data collected during the trials and determine the next steps. Depending on the reason for the failure, the company may decide to discontinue the development of the drug, as the cost of developing a drug is very high and the further the drug goes in development, the higher the cost.

However, if the failure is due to a lack of efficacy, the company may investigate alternative indications for the drug. This looks to uncover whether the drug might be useful for treating different diseases or conditions than originally intended. 

Additionally, the company may also decide to investigate alternative formulations, dosages, or administration methods for the drug, in order to improve its safety or tolerability profile.

Contract research organisations (CROs), such as Simbec-Orion, provide various phase I clinical services to support pharmaceutical and biotechnology companies, such as conducting clinical trials, oncology services, pharmacovigilance  and much more. 

They can offer plenty of advantages to help the trial to be as successful as possible, as they have the expertise and resources to conduct the trial in a safe and efficient manner. They also have vast experience in managing clinical trials, which can help to minimise the risks of failure. 


In conclusion, early phase clinical development includes vital steps in the initial drug development process. These trials are designed to evaluate the safety and tolerability of a new drug, as well as its potential efficacy. This early phase is conducted in small groups of healthy volunteers or patients, and the results of these trials determine whether a drug moves on to the next phase of testing.

Early phase support with Simbec-Orion

CROs can be helpful in making sure that the phase I trial goes well, as they have the expertise and resources to conduct the trial in a safe and efficient manner. 

Simbec-Orion is well-equipped to support these trials with our vast experience in early phase research. We offer a highly adaptive and agile approach to early phase trials, tailored to meet the specific needs of each research project. Our services range from full study design to IMP management. 

We always work to ensure patient safety and maximise likelihood of success of new drug development. With Simbec-Orion’s experience and expertise, companies can have peace of mind knowing that their early phase trials are in capable hands.
Get in touch to find out how we can help today.

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