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Clinical Investigation of Large Volume Subcutaneous Delivery up to 25 mL for Lean and Non-Lean Subjects

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Abstract

Purpose

To evaluate the clinical feasibility and tolerability of large volume subcutaneous delivery at different injection depths for lean and non-lean subjects.

Methods

A single-center, randomized, subject-blinded, crossover study in 62 healthy subjects was conducted to evaluate delivery of a 10-cP solution containing hyaluronic acid. Subjects were separated into lean and non-lean cohort by SC thickness. A syringe pump was used to study the effect of different volumes (5, 12, 25 mL) of a viscous placebo solution and needle lengths (6, 9 and 12 mm) delivered at 0.5 mL/min.

Results

Across all treatments, injection sites were observed to have negligible leakage, ~34 kPa of back pressure, and VAS of mild pain with higher pain from needle insertion than during injection. While mild to moderate erythema was the most frequently reported ISR and edema was most prominent for 25 mL injections, all ISRs were resolved within 4 hours post injection. Subjects were unbothered by ISRs across all treatments and rated them as low distress scores (average 1.0–1.5 out of 6).

Conclusion

SC injection of 25 mL is feasible and tolerable using a low-pain formulation for abdomen injection irrespective of subcutaneous thickness and injection depths at a delivery rate of 0.5 mL/min.

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Abbreviations

AE:

Adverse Events

BD:

Beckton Dickinson

cP:

Centipoise

CRU:

Clinical Research Unity

DAC:

Data Acquisition Module

DP:

Drug Product

GCP:

Good Clinical Practice

ICH:

International Council for Harmonization

ISP:

Injection Site Pain

ISR:

Injection Site Reaction

LVI:

Large Volume Injector

Ph. Eur.:

European Pharmacopeia

SC:

Subcutaneous

SCIG:

Subcutaneous Immunoglobulin

SE:

Standard Error

USP:

United States Pharmacopeia

VAS:

Visual Analog Scale

WFI:

Water for Injection

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Acknowledgements

The authors would like to thank the volunteers and all investigators involved in this clinical trial study. Andrew M Ratz, Kaoutar Abbou Oucherif, Amita Datta-Mannan, Michelle Yi Xiu Lim, and Rhea Sirkar contributed to the discussions, design, and execution of the studies. Reshma Bharadwaj contributed to the review of the manuscript.

Funding

Funding for the non-clinical and clinical studies was provided by Eli Lilly and Company.

Author information

Authors and Affiliations

  1. Eli Lilly and Company, Cambridge, Massachusetts, 02142, United States of America

    Xiangnan Dang & Kathleen Lin

  2. Eli Lilly and Company, Lilly Technology Center, Indianapolis, Indiana, 46221, United States of America

    Han Shih, Shiven Kapur, Galen H. Shi & David S. Collins

  3. Eli Lilly and Company, Lilly Capability Center India, Bangalore, 560103, Karnataka, India

    Rakesh Sharma & Nagarajan R. Thyagarajapuram

  4. Eli Lilly and Company, Louisville, Colorado, 80027, United States of America

    Daneen T. Angwin-Kaerner

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  1. Xiangnan Dang
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  5. Kathleen Lin
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Correspondence to Han Shih.

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Dang, X., Shih, H., Sharma, R. et al. Clinical Investigation of Large Volume Subcutaneous Delivery up to 25 mL for Lean and Non-Lean Subjects. Pharm Res 41, 751–763 (2024). https://doi.org/10.1007/s11095-024-03683-5

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  • DOI: https://doi.org/10.1007/s11095-024-03683-5

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