Clinical Development Solutions 

Case Studies

Selecting the Optimal Device for Metered Dose Inhalers (MDIs)

Backround:

Our client, a large pharmaceutical company, was known for their expertise in the production of generic Metered Dose Inhalers (MDIs) such as Salbutamol. As they branched out into developing Fixed-Dose Combination (FDC) products, they faced a challenge - the selection of the optimal device for their new formulations.

Challenge:

The transition from producing single active ingredient MDIs to FDCs presented the company with a unique challenge. The device needed to ensure efficient delivery of multiple active ingredients, each with distinct physiochemical properties, in a single dose. The device selection became critical, impacting drug delivery, patient adherence, and ultimately, the therapeutic efficacy of the product.

Approach:

Our team of consultants, led by an experienced clinical research professional, adopted a multi-faceted approach to address this challenge.

Firstly, we leveraged cascade impactors to conduct comprehensive lung deposition studies, which were crucial in assessing the particle size distribution of the aerosolized medication. The cascade impactor, a standard instrument in inhaler testing, allowed us to accurately measure the aerodynamic size of the particles, thereby ensuring the drug would reach the intended site of action within the lung.

Secondly, we concentrated on evaluating the performance of various devices in terms of their handling, ease of use, and ability to effectively deliver the combination drug product. This involved rigorous testing of a range of devices with different design features.

Outcome:

After a comprehensive review, we were able to identify the optimal device for the client's new FDC formulation. This device demonstrated superior aerosol performance and consistent dosage delivery, making it an ideal match for the client's product.

The successful identification of the best device underscored the importance of device selection in the development of combination MDIs. It not only boosted the client's confidence in their upcoming product but also facilitated the subsequent stages of the development process, including the design of bioequivalence and pharmacokinetic studies.

Bioequivalence Study Design for Generic Clopidogrel

Client's Situation:

Our client, a generic pharmaceutical manufacturer, had their therapeutic equivalence called into question regarding their generic Clopidogrel product in patients who had undergone stent operations. Despite Clopidogrel being a well-established antiplatelet drug, concerns were raised about the therapeutic equivalence of the client's product, prompting the need for further validation.

Approach:

Our team, led by a seasoned clinical research consultant, chose a bioequivalence study to address these concerns. While it's understood that bioequivalence studies primarily establish comparable pharmacokinetic parameters between the generic and the original drug, the underlying presumption is that similar pharmacokinetics should lead to similar therapeutic outcomes, given the original drug's established efficacy profile.

Our strategy was to design a standard two-period, two-treatment crossover comparative bioavailability study. The study was conducted with healthy adults to minimize the variability that can occur due to differences in disease progression, allowing us to focus strictly on the pharmacokinetic properties of the generic drug.

Outcome:

The bioequivalence study aimed to demonstrate that the generic Clopidogrel released its active ingredient into the bloodstream at the same rate and extent as the original drug. By demonstrating bioequivalence, we sought to substantiate that the client's generic product should provide therapeutic outcomes akin to the original drug, thus revalidating the generic's safety and efficacy profile.

Our approach illustrated the importance of a well-conducted bioequivalence study in reaffirming confidence in a generic product when doubts arise about its therapeutic equivalence. However, it was also communicated to the client that additional studies might be necessary for further direct evidence of the drug's efficacy in the specific patient population if doubts persisted.

Inclusive Clinical Trials: Strategizing for Diversity with Limack – A Case Study

Background

In the contemporary medical landscape, ensuring diversity and inclusion (D&I) in clinical trials has taken on an unprecedented urgency. Clinical trials are the cornerstone for establishing the safety and efficacy of various health interventions, whether pharmaceuticals, biological products, medical devices, or novel techniques. These interventions invariably cater to a diverse, global patient population. Therefore, it is of paramount importance that the demographics of clinical trials accurately reflect the diversity of this population, ensuring the broad applicability of the outcomes.

The COVID-19 pandemic starkly highlighted the health disparities that exist between different demographics. It emerged that the pandemic burden weighed more heavily on ethnic minority groups, who were paradoxically underrepresented in clinical research for vaccine trials. This discord stimulated regulatory bodies to release guidelines for sponsors on D&I in clinical research, further encouraging sponsors to develop and implement strategies to enhance D&I in their trials.

Against this backdrop, the UK arm of a multinational pharmaceutical company sponsored our project, with the aim to surmount barriers to D&I and formulate a best-practice standard for their clinical trials.

Approach

Our comprehensive methodology encompassed an in-depth exploration of literature, secondary sources, and archives to compile a comprehensive list of D&I barriers. We then examined the strategies suggested by these resources and stakeholders to combat these barriers. Applying a thematic analysis to these findings, we identified principal themes, which informed the design of our survey and interviews. These tools were employed to scrutinize the sponsor’s current practices, discern existing gaps, and then construct an effective action plan.

Innovation

What sets this project apart from other similar endeavors is our diverse approach to data collection. While most research tends to focus on a limited set of stakeholders and their individual approaches to D&I, we incorporated a wider variety of data sources including literature, archives, regulatory agencies' guidelines, and input from the sponsoring organization itself. Applying the thematic model to each dataset individually, we then cross-compared the main themes derived from each, offering a unique multi-perspective insight into the topic.

Conclusion

This project has effectively amassed known barriers to D&I in clinical trials and potential countermeasures from a plethora of sources. This knowledge has allowed us to tailor a best-practice standard and action plan to improve D&I, a significant stride towards more representative and equitable clinical trials.