Challenges and Benefits of Patient-Based Phase I Trials

Pharma IQ held a Q&A session with Dr. James Dow, Director of Clinical Pharmacology & DMPK, (OSI) Prosidion  to gain a few insights into phase I clinical development and patient-based phase I trials.

How do you feel the clinical trial landscape changed in the past 5 years?

Clearly the trend to include patients in early clinical studies has changed this landscape. This is now widely accepted by pharma companies and regulatory authorities, also the regulatory landscape has changed. Regulatory authorities are actively encouraging the use of more innovative study designs. For example micro-dosing and exploratory INDs, where you can take more than one compound into the clinic. This allows us to select the best compound at a very early stage of drug development. 

What do you feel are the key drivers for maximising phase I clinical trials?

Well clearly, including patient population and availability of appropriate biomarkers. If I can give an early read out of potential clinical efficacy, after one or two weeks multiple dosing. I think all these things have been key drivers. 

Leading on from that what are the main limitations of present phase I clinical trial designs?

Limitations in trial designs are still related to availability of suitable patient populations, or biomarkers that can be measured in healthy volunteers. I think these are the main limitations that we come across.

What would you say the key challenges in conducting phase I in patients are?

Challenges still remain the availability and ease of recruitment, also patients can be on a number of drugs, which for ethical and therapeutic reasons cannot always be washed out prior to initiation of phase I studies. For example, it wouldn’t be appropriate to study stop use of an anti-hypertensive agent for a clinical trial.

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What do you see as the benefits of combining DDI studies in phase I?

Well I think there are huge advantages in combining DDI studies in phase I, from in vitro studies, you can already get indication of which sup enyzmes are at risk of being inhibited, and you can follow it up by using a single probe, multiple probe or drug cultural approach in healthy volunteers. If there is no evidence for a DDI in using probe approaches, then this allows you to use patients who can continue to take their usual medication during the clinical trial, so that there are huge advantages of doing these DDI studies early in phase I.

How are you seeking to reduce attrition in the clinical trial process?

I think attrition will always be an issue, reducing attrition clearly involves choosing the most appropriate compounds for phase I studies. However, I think that it is equally important to make sure that attrition takes place as early as possible in the development process, where costs are relatively low, rather than at a later stage where development costs can be extremely high. 

Which companies out there do you think are offering services to support patient-based phase I trials?

I feel that phase I CROs have been relatively slow to recognise the advantages of including patients in clinical studies. They need to improve their recruitment procedures and logistics for this to happen. However, recently I have been very impressed by Eastern European and South African phase I CROs, who have clearly identified the business need, and have huge patient numbers in their databases.   

Finally to round off, what do you think are the likely future trends for phase I clinical trials?

Good question, I think that traditional boundaries between phase I and phase IIa will disappear. For example, is a 14 day MAD study in patients with measurement of biomarkers phase I, or is it really a phase 2a study? These boundaries are artificial and a handicap to innovation is phase I studies.

Interview conducted by Andrea Charles