Early phase program for non-opioid acute pain treatment
Case study
Overview
A leading biotech company developing a groundbreaking non-opioid treatment for moderate-to-severe acute pain partnered with ICON to conduct a series of early-phase trials. Spanning four years, these nine studies followed strict timelines and involved nearly 400 healthy volunteers enrolled in two ICON early phase clinical research units (CRUs) in the U.S.
Challenge
This project faced a series of challenges over the course of the program of studies including:
Expedited timelines
The studies were planned to run sequentially or in partial overlap with little to no buffer between the completion of one and commencement of the next. The aggressive timelines were commercially necessary due to faster approvals driven by the need for non-opioid pain treatments. The impetus for agility and speed had to be balanced against the operational delivery per expected quality standards and management of risks to the study participants. Medical safety was always paramount during every stage of testing.
Global pandemic
The first study began in late 2019, and next studies spanned the COVID-19 pandemic. This necessitated additional screening and protection measures to ensure that the participants and staff were virus-free and remained so. The pandemic also posed challenges to operational capacity, recruitment of healthy participants and logistics such as the limited availability of study materials.
Data availability and reporting requirements
With compressed timelines it was essential that all relevant clinical data was ready and reviewed either within a study before the next study group progressed, or at the end of a study to proceed to the next study.
Solution
A first-in-human single ascending dose (SAD) study involving 40 subjects commenced in November 2019. This was followed by a series of eight clinical pharmacology studies to assess the pharmacokinetic profile of the compound including multiple ascending dose (MAD), bioavailability, drug-to-drug interaction (DDI), dose extension, cardiac safety (TQT) and food effect studies. These were conducted at ICON’s clinical research units (CRUs) in Lenexa (Kansas) and Salt Lake City (Utah) and involved a further 349 healthy volunteers who had to stay for various periods of confinement depending on the study.
The compound was administered via oral suspension in all nine studies, requiring on-site compounding of the IMP due to limited IMP stability. All ICON’s CRUs have GCP USP compliant pharmacies integrated or located nearby, which enable the manufacture of the oral IMP formulation from the API provided by the sponsor. This improves logistics, enhances efficiency and most importantly, allows for timely dosing adjustments within studies if needed.
Transparency and collaboration were paramount during all nine studies. Clear communication between ICON’s study teams and the sponsor ensured that, despite aggressive timelines, study delivery and participant safety were never compromised. Open and honest discussions between the CRUs and the sponsor facilitated prompt issue resolution, keeping all studies within the program on schedule despite the challenges. Additionally, a structured development program was implemented to ensure all necessary information about agreed processes and sponsor expectations was available in advance, to allow sufficient time for review before initiating subsequent studies.
Outcome
Despite some ambitious timelines and operational challenges caused by COVID, all expectations were met, with five of the studies actually reaching completion ahead of schedule. This enabled the overall program to progress seamlessly to the next phase. Just five years after the first healthy volunteer was recruited and enrolled, the compound was approved by the FDA to treat moderate-to-severe acute pain. This is the first new (non-opioid) pain treatment approved in 20 years, offering an alternative to potentially addictive opioids for acute pain management. The sponsor acknowledged ICON’s role in expediting this approval, highlighting our dedication, hard work, and collaboration throughout the process.