PMID- 31883703
OWN - NLM
STAT- MEDLINE
DCOM- 20200918
LR  - 20200918
IS  - 1879-114X (Electronic)
IS  - 0149-2918 (Linking)
VI  - 42
IP  - 1
DP  - 2020 Jan
TI  - A Phase I Study to Assess the Effect of Speed of Injection on Pain, Tolerability, 
      and Pharmacokinetics After High-volume Subcutaneous Administration of 
      Gantenerumab in Healthy Volunteers.
PG  - 108-120.e1
LID - S0149-2918(19)30577-6 [pii]
LID - 10.1016/j.clinthera.2019.11.015 [doi]
AB  - PURPOSE: Gantenerumab, a fully human anti-amyloid-beta IgG1 monoclonal antibody that 
      binds to aggregated forms of amyloid-beta, is being investigated as a potential 
      disease-modifying treatment for early (prodromal to mild) Alzheimer disease (AD). 
      Our study compared the pain associated with 5- and 15-s subcutaneous injections 
      of gantenerumab and evaluated the tolerability and pharmacokinetic properties of 
      subcutaneous gantenerumab. METHODS: This randomized, open-label, 
      single-active-dose, placebo-controlled crossover study was conducted in 50 
      healthy volunteers aged 40-80 years with no history of clinically significant 
      disorders, drug or alcohol abuse, familial history of early-onset AD, or prior 
      gantenerumab exposure. Eligible participants were randomized to a sequence of one 
      300-mg SC gantenerumab injection into the abdomen and 2 SC placebo injections (1 
      into the abdomen and 1 into the thigh) during 5 or 15 s. All injections were 
      administered at least 90 min apart. Participants were assessed for local pain by 
      visual analog scale (VAS) and verbal rating scale; safety profiles were assessed 
      by recording adverse events (AEs), and plasma pharmacokinetic properties were 
      also evaluated. FINDINGS: Immediately after the subcutaneous gantenerumab 
      injection, the pain VAS score was numerically higher without reaching statistical 
      significance in the 5-s versus 15-s injection group (VAS least-squares mean 
      difference, 7.492 mm; 95% CI, -4.439-19.423 mm). In both injection speed groups, 
      the mean pain VAS score was comparable after subcutaneous gantenerumab and 
      placebo injections into the abdomen. Pain was reported after needle insertion and 
      immediately after dosing, subsiding within 5 min after the dose. The pain VAS 
      score was numerically higher after SC placebo injection into the thigh versus 
      abdomen (5-s injection group: mean [SD] VAS score, 26.68 [27.83] vs 19.20 [25.60] 
      mm; 15-s injection group: mean [SD] VAS score, 14.16 [20.62] vs 9.48 [12.04] mm). 
      No serious AEs were reported; no participants withdrew because of an AE. All AEs 
      were of mild intensity, were transient, and had resolved without sequelae at 
      follow-up. The most common AEs were injection site reactions; redness was the 
      most frequently observed skin reactivity event after subcutaneous gantenerumab 
      administration (5-s injection group: 36%; 15-s injection group: 32%). After 
      subcutaneous administration, gantenerumab reached a peak plasma concentration at 
      a median time of 119 h (approximately 5 days); plasma concentrations declined in 
      a monoexponential manner. Comparable pharmacokinetic profiles were observed 
      between the injection speed groups. IMPLICATIONS: Subcutaneous gantenerumab 
      injections at speeds of 5 and 15 s were well tolerated in healthy volunteers and 
      could enable at-home administration by patients with AD or their caregivers. 
      ClinicalTrials.gov identifier: NCT02882009.
CI  - Copyright (c) 2019 The Author(s). Published by Elsevier Inc. All rights reserved.
FAU - Portron, Agnes
AU  - Portron A
AD  - F. Hoffmann-La Roche Ltd, Basel, Switzerland.
FAU - Jordan, Paul
AU  - Jordan P
AD  - F. Hoffmann-La Roche Ltd, Basel, Switzerland.
FAU - Draper, Kristy
AU  - Draper K
AD  - Roche Products Ltd, Welwyn Garden City, United Kingdom.
FAU - Muenzer, Christopher
AU  - Muenzer C
AD  - F. Hoffmann-La Roche Ltd, Basel, Switzerland.
FAU - Dickerson, Daniel
AU  - Dickerson D
AD  - PRA Health Sciences, Lenexa, KS, USA.
FAU - van Iersel, Thijs
AU  - van Iersel T
AD  - PRA Health Sciences, Groningen, the Netherlands.
FAU - Hofmann, Carsten
AU  - Hofmann C
AD  - F. Hoffmann-La Roche Ltd, Basel, Switzerland. Electronic address: 
      carsten.hofmann@roche.com.
LA  - eng
SI  - ClinicalTrials.gov/NCT02882009
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20191226
PL  - United States
TA  - Clin Ther
JT  - Clinical therapeutics
JID - 7706726
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Neuroprotective Agents)
RN  - 4DF060P933 (gantenerumab)
SB  - IM
MH  - Abdomen
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Antibodies, Monoclonal, Humanized/*administration & dosage/adverse 
      effects/blood/pharmacokinetics
MH  - Cross-Over Studies
MH  - Female
MH  - Healthy Volunteers
MH  - Humans
MH  - Injections, Subcutaneous
MH  - Male
MH  - Middle Aged
MH  - Neuroprotective Agents/*administration & dosage/adverse 
      effects/blood/pharmacokinetics
MH  - Pain/etiology
MH  - Pain Measurement
OTO - NOTNLM
OT  - amyloid-beta
OT  - gantenerumab
OT  - monoclonal antibody
OT  - safety
OT  - subcutaneous
OT  - tolerability
EDAT- 2019/12/31 06:00
MHDA- 2020/09/20 06:00
CRDT- 2019/12/30 06:00
PHST- 2019/09/18 00:00 [received]
PHST- 2019/11/15 00:00 [revised]
PHST- 2019/11/20 00:00 [accepted]
PHST- 2019/12/31 06:00 [pubmed]
PHST- 2020/09/20 06:00 [medline]
PHST- 2019/12/30 06:00 [entrez]
AID - S0149-2918(19)30577-6 [pii]
AID - 10.1016/j.clinthera.2019.11.015 [doi]
PST - ppublish
SO  - Clin Ther. 2020 Jan;42(1):108-120.e1. doi: 10.1016/j.clinthera.2019.11.015. Epub 
      2019 Dec 26.