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In Vitro and In Vivo Performance of a Pre-Filled, Electrochemically-Actuated Infusion System

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Abstract

Purpose

A novel infusion system (PatchPump®) has been developed using an electrochemical actuator and a semi-flexible container to deliver liquid formulations through an infusion set. In vitro studies characterized pump performance, and clinical studies evaluated functionality and pharmacokinetic (PK) performance in humans.

Methods

Total delivered volume and flow rate accuracy were determined in vitro by real-time gravimetric analysis. Functionality was evaluated in vivo using prototype devices delivering saline for 18 h in a clinical study enrolling 10 healthy volunteers. A second clinical study examined the PK of delivering treprostinil at an average dose of 2.3 ng/kg/min to 5 healthy volunteers for 18 h.

Results

Relative to a design target of 0.042 mL/hr, the average flow rate of 23 PatchPumps operating for 48 continuous hours was 0.043 ± 0.007 mL/hr as tested in vitro. In vivo functionality was confirmed by complete infusion of saline for the entire duration with only mild and transient adverse effects. PK results with an infusion rate of 0.045 mL/hr of treprostinil resulted in mean Css of 297 pg/mL and T1/2 of 4.44 h, comparable to prior studies using conventional infusion pumps.

Conclusions

The results of these studies demonstrate a successful proof-of-concept for the PatchPump technology.

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Abbreviations

AE:

Adverse event

AUCinf :

Area under the plasma concentration-time curve from time zero to infinity

AUClast :

Area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration

Cmax :

Maximum (peak) plasma concentration

Css (ng/mL):

Steady-state plasma concentration

HV:

Healthy volunteer

IEC:

International Electrotechnical Commission

IV:

Intravenous

LED:

Light emitting diode

PCBA:

Printed Circuit Board Assembly

PK:

Pharmacokinetics

SC:

Subcutaneous

T1/2 :

Apparent terminal half-life

Tmax :

Time to reach Cmax (maximum plasma concentration)

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ACKNOWLEDGMENTS AND DISCLOSURES

The authors would like to express gratitude to Yasmin Noonoo, Lior Bat-Gat, Maya Gartenberg, Inna Nachkimova and Gal Shakked of SteadyMed Ltd. for their contributions towards device design, data generation and compilation and clinical trial readiness. The authors further acknowledge contributions from Stewart Fox and the staff at Team Consulting Ltd. to the device design and from Patricia Eliahu in the preparation of this manuscript.

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Authors and Affiliations

  1. SteadyMed Ltd., Rehovot, Israel

    Assaf Shaked

  2. Blue-Key Healthcare & Life Sciences Consulting, Ramat Hasharon, Israel

    Ella Tenenbaum-Koren

  3. Tel Aviv Sourasky Medical Center CRC, Affiliated to Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

    Jacob Atsmon

  4. SteadyMed Therapeutics Inc., 2603 Camino Ramon, Suite 350, San Ramon, California, 94583, USA

    Peter Noymer

Authors
  1. Assaf Shaked
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  2. Ella Tenenbaum-Koren
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  3. Jacob Atsmon
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  4. Peter Noymer
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Corresponding author

Correspondence to Peter Noymer.

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Shaked, A., Tenenbaum-Koren, E., Atsmon, J. et al. In Vitro and In Vivo Performance of a Pre-Filled, Electrochemically-Actuated Infusion System. Pharm Res 33, 83–91 (2016). https://doi.org/10.1007/s11095-015-1765-4

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  • DOI: https://doi.org/10.1007/s11095-015-1765-4

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