Assessing the tolerability of 5 and 15 second injections of 2 ml into different injection sites

Chris Muenzer, Senior Device Engineer, Roche

The purpose of this presentation is to share our experience and learnings with 2 ml injections

Clinical Plan

Device Solution

Results

New autoinjectors are being developed which can deliver up to 2 ml

But how fast should an autoinjector inject 2 ml?

Not Tolerated Hard to Use

We developed a clinical plan to look at the speed of injection

Active DP / Abdomen

5 sec

holdPlacebo / Abdomen

Placebo / Thigh

no hold Placebo / Abdomen

Placebo / Thigh

15 sec

holdPlacebo / Abdomen

Placebo / Thigh

no holdPlacebo / Abdomen

Placebo / Thigh

48 Total Subjects

• Pain (VAS) – Primary End Point

• Local Site Assessment

• Delivered Volume

• Injection Site Leakage

• Pharmacokinetics (PK)

The study evaluated a range of clinical endpoints

Infusion pumps could be used to deliver 2 ml…

OCCLUSION ALARMS!

A Harvard Pump would be capable….

NOT FOR HUMAN USE!

Or we could build two autoinjectors with two different speeds

TOO COMPLEX!

Manual injection was the only option

Flange to assist with injection force

Spacer to set the needle depth and angle

Foot to mimic contact of autoinjector

Timing reference to control the injection speed

3D printed devices were manufactured for the study

An example of the delivery method

Pain is measured on a 100 mm scale, anchored by word descriptors

22 mm

The patient marks on the line the point that they feel represents their perception of their current state. The VAS score is determined by measuring in millimeters from the left hand end of the line to the point that the patient marks.

D. Gould et al. Visual Analogue Scale (VAS). Journal of Clinical Nursing 2001; 10:697-706

Preliminary statistical analysis showed that a 15 second injection time is less painful

…but was unable to conclude that there is a difference due to injection site or content

11 5 19 4 4 2

The pain is within the range observed with marketed drugs

Median pain for 15 second injection into the abdomen

Median pain for 5 second injection into the abdomen

X

First Quartile Third Quartile

Median Mean

PK profiles were considered equivalent for both injection speeds and with or without a 5 second hold after injection

Time (hrs)

Pla

sma

Co

nce

ntr

atio

ns

15 secw/ holdw/o hold

5 secw/ holdw/o hold

Site leakage was evaluated using two different measurements

Visual AssessmentFluid Measurement

Fluid measurement showed very small amount of leakage (less than 0.01 ml) for most subjects

Visual assessments could not show statistical differences in the percentage of subjects with injection site leakage or blood

2D ultrasound showed exclusive SC localization and equivalent size for both speeds

• Simple low cost solution was developed to meet the needs of

the study

• SC injection of 2 mL into the abdomen is well tolerated with

less pain associated with 15 second injection compared to 5

second injection.

• The pain following 5 or 15 second administration is within the

range observed with marketed drugs.

Conclusions

Roche Team

Agnes Portron

Carsten Hofmann

Neil Cammish

Jörg Sielemann

With Support From

Technical Development Team

Isabelle Bauer Dauphin

Pierre Goldbach

Christelle Laroche

pRED Lab Technologies and Robotics

Thomas Zumstein

Tom Kissling

Product Development Global Operations

Emma Lindley

Jenny Tovey

Kristy Draper

PRA Lenexa, Kansas

Brandi Cadue

Daniel Dickerson

Jeffrey Hinchey

Amanda Barber

Acknowledgements

Questions?