PMID- 33409604
OWN - NLM
STAT- MEDLINE
DCOM- 20210310
LR  - 20210310
IS  - 1530-9932 (Electronic)
IS  - 1530-9932 (Linking)
VI  - 22
IP  - 1
DP  - 2021 Jan 6
TI  - Subcutaneous Injection Performance in Yucatan Miniature Pigs with and without 
      Human Hyaluronidase and Auto-injector Tolerability in Humans.
PG  - 39
LID - 10.1208/s12249-020-01880-0 [doi]
LID - 39
AB  - Recombinant human hyaluronidase PH20 (rHuPH20) facilitates subcutaneous (SC) 
      delivery of co-administered therapeutic agents by locally and transiently 
      degrading hyaluronan in the SC space, and can be administered with therapeutics 
      using a variety of devices. Two SC delivery studies were carried out to assess 
      auto-injector (AI) performance, each in 18 Yucatan miniature pigs. Abdominal 
      injections were administered using three auto-injectors of 1 mL (AI1) and 2 mL 
      (AI2 and sAI2) with different injection speeds and depths (5.5-7.5 mm) and two 
      pre-filled syringe (PFS) devices of 1 and 2 mL. The injection included a placebo 
      buffer with and without rHuPH20 to evaluate the effect of rHuPH20 on SC injection 
      performance. The feasibility of using similar devices to deliver a placebo buffer 
      in humans was investigated. rHuPH20 was not studied in humans. In miniature pigs, 
      postinjection swelling was evident for most PFS/AI injections, particularly 2 mL. 
      Swelling heights and back leakage were typically lower with rHuPH20 
      co-administration versus placebo for most device configurations (1 or 2 mL PFS or 
      AI). Auto-injections with versus without rHuPH20 also resulted in reduced 
      swelling firmness and faster swelling resolution over time. Slow injections with 
      rHuPH20 had shorter and more consistent injection time versus placebo. In humans, 
      minimal injection site swelling and negligible back leakage were observed for 
      2-mL injections of placebo, while more erythema was observed in humans versus 
      miniature pigs. Even at high delivery rates with PFS or AI, the addition of 
      rHuPH20 resulted in improved SC injection performance versus placebo in miniature 
      pigs.
FAU - Shi, Galen H
AU  - Shi GH
AD  - Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana, USA.
FAU - Connor, Robert J
AU  - Connor RJ
AD  - Halozyme Therapeutics, Inc., 11388 Sorrento Valley Road, San Diego, California, 
      92121, USA.
FAU - Collins, David S
AU  - Collins DS
AD  - Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana, USA.
FAU - Kang, David W
AU  - Kang DW
AD  - Halozyme Therapeutics, Inc., 11388 Sorrento Valley Road, San Diego, California, 
      92121, USA. publications@halozyme.com.
LA  - eng
PT  - Journal Article
DEP - 20210106
PL  - United States
TA  - AAPS PharmSciTech
JT  - AAPS PharmSciTech
JID - 100960111
RN  - 0 (Recombinant Proteins)
RN  - EC 3.2.1.35 (Hyaluronoglucosaminidase)
SB  - IM
MH  - Animals
MH  - Humans
MH  - Hyaluronoglucosaminidase/*administration & dosage
MH  - Injections, Subcutaneous
MH  - Male
MH  - Recombinant Proteins/administration & dosage
MH  - Swine
MH  - Swine, Miniature
PMC - PMC7788039
OTO - NOTNLM
OT  - auto-injector
OT  - miniature pigs
OT  - pre-filled syringe
OT  - rHuPH20
OT  - subcutaneous injection
EDAT- 2021/01/08 06:00
MHDA- 2021/03/11 06:00
PMCR- 2021/01/06
CRDT- 2021/01/07 06:10
PHST- 2020/09/25 00:00 [received]
PHST- 2020/11/13 00:00 [accepted]
PHST- 2021/01/07 06:10 [entrez]
PHST- 2021/01/08 06:00 [pubmed]
PHST- 2021/03/11 06:00 [medline]
PHST- 2021/01/06 00:00 [pmc-release]
AID - 10.1208/s12249-020-01880-0 [pii]
AID - 1880 [pii]
AID - 10.1208/s12249-020-01880-0 [doi]
PST - epublish
SO  - AAPS PharmSciTech. 2021 Jan 6;22(1):39. doi: 10.1208/s12249-020-01880-0.