A leading multinational pharmaceutical company partnered with ICON to conduct a phase 1 obesity study assessing the safety and tolerability of a new investigational oral amycretin therapy. The study enrolled healthy volunteers with overweight or obesity and was completed within just 20 months, from first subject first visit (FSFV) to last subject last visit (LSLV). Study design included four cohorts with single ascending dose (SAD) and multiple ascending dose (MAD). 

The study required the enrollment of 144 overweight or obese but otherwise healthy volunteers that met specific protocol inclusion and exclusion criteria which presented initial challenges in both recruitment and screening. 

Early phase obesity studies have historically high dropout rates which can also be a challenge. Ensuring adherence and minimising dropout rates within the healthy volunteer population was therefore key to maintaining study timelines and data integrity. 

The sponsor also desired a high level of control and oversight, requiring ICON to work within their preferred data flow plans, and to harmonise with their internal Data Management standards and processes. This added a layer of complexity to adjust our database builds and standard operating procedures.

ICON pulled on a full range of services tailored to obesity trial requirements. Our proven success designing, managing, and executing early phase obesity studies helped design the protocol and deliver formulations that supported this four-part SAD/MAD regimen.

Per the protocol, each cohort in Part A (SAD) was designed to include two groups: one with 2 volunteers and another with 6. However, strict eligibility criteria that specified a minimum vitamin D requirement (minimum 25(OH)D level of 20 ng/mL) made enrollment challenging. This led to the creation of an additional cohort to continue enrollment. Despite this, we still faced challenges, and ultimately a final “straggler” cohort was needed to reach the full group of 6 volunteers.

After this experience, the lower acceptable limit of vitamin D was adjusted from 20 ng/mL to 12 ng/mL upon the Principal Investigator’s recommendation. This change allowed us to proceed as originally planned with 2- and 6-volunteer groups as per protocol and facilitated smoother enrollment in the subsequent cohorts in Part A without further issues. We also faced minor enrolment challenges in Part C2. These were also overcome with the introduction of a straggler cohort to dose the final subject. This meant that we successfully adhered to the timelines. 

ICON’s highly experienced team of investigators have successfully managed early phase obesity trials across most mechanisms of action. They used this depth of knowledge to support participants on their trial journey and manage expectations at every stage. This included the provision of advice to manage GI side effects, including food supplements at site visits, additional medications for side effect management, guidance for tolerating nausea, and how to improve success with the at-home component of the study, which included the completion of diaries which would be reviewed at each site visit.   

Frequent meetings between the ICON and sponsor data management teams enabled rapid problem-solving and continuous alignment while prioritising the sponsor’s data flow plans without compromising the speed, efficiency or quality of the data delivery between teams. 

Despite the complexities of enrolment and participant management, ICON successfully completed the study without withdrawing patients due to adverse events (AEs). While some participants self-withdrew, proactive engagement strategies helped mitigate dropout rates and maintain study continuity. 

The successful execution of this phase 1 trial reinforced ICON’s ability to streamline early-phase obesity studies through tailored recruitment, patient-centric support and operational excellence while affording sponsors their desired level of control and oversight.