Journal of Rehabilitation Medicine 51-10 | Page 94

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P. J. McAllister et al.
We report here the results of a post hoc analysis of
data from a phase 3 study of aboBoNT-A (11). The
objective of this analysis was to evaluate walking speed
in patients with spastic hemiparesis who received abo-
BoNTA, comparing outcomes in those patients treated
solely in the LL with those receiving simultaneous
treatment in both the LL and UL.
METHODS
pregnancy; severe cognitive impairment that interfered with
consent provision.
Outcome measures
Duration of the walk in a 10-m walk test (10MWT) was recorded
using a stopwatch. Walking speed outcomes, assessed as change
in unassisted CBWS between baseline and week 4 of each TC,
were compared between patients who received simultaneous
injections in the LL+UL during TC3 and TC4 and patients
who received LL injections only throughout the study (Fig. 1).
Study design and treatment Statistical analysis
The phase 3, open-label (OL) extension study of aboBoNT-A
(NCT01251367) followed a double-blind (DB) study
(NCT01249404), as described previously (11). Briefly, the DB
phase was a multicentre, prospective, randomized, placebo-
controlled study in adults with chronic hemiparesis who
received a single injection of 1,000 U or 1,500 U aboBoNT-A
or placebo into both soleus and gastrocnemius muscles and ≥ 1
other (investigator-selected) LL muscle(s).
The OL extension was based on multiple injections of 1,000
U or 1,500 U aboBoNT-A for ≤4 treatment cycles (TCs), un-
dertaken at 52 centres across 11 countries. At TC1 of the OL
phase, patients received aboBoNT-A 1,500 U in the LL, except
those who experienced treatment-emergent adverse events
(AEs) during the DB phase that the investigator considered to
pose an unacceptable risk, who instead received 1,000 U. At
TC2, 1,000 U or 1,500 U could be administered in the LL (ac-
cording to the investigator’s clinical judgement). At TC3 and
TC4, either 1,000 U or 1,500 U was administered into the LL;
patients with co-existing disabling muscle overactivity in the
UL could receive simultaneous injections of up to 500 U in the
affected UL (as per investigator’s clinical judgement), with the
total aboBoNT-A dose not exceeding 1,500 U. The minimum
time between TCs was 12 weeks.
This study was conducted in accordance with the Declaration
of Helsinki, International Conference on Harmonisation Good
Clinical Practice Guidelines, and local regulatory requirements,
with approval from relevant independent ethics committee/insti-
tutional review boards. Written informed consent was obtained
from patients prior to study entry.
This post hoc analysis evaluates the subgroups of patients who
were injected with aboBoNT-A at both TC3 and TC4 of the OL
phase and received either simultaneous injections of aboBoNT-A
in the LL and UL, or injections in the LL only (Fig. 1). Due to the post hoc nature of these analyses, descriptive sta-
tistics only were performed. No hypothesis testing or p-values
are presented.
Patients
Inclusion criteria for the overall study population
are described elsewhere (11) and included the fol-
lowing requirements to enter the DB trial: adults
(18–80 years) with spastic hemiparesis causing
gait dysfunction; comfortable barefoot walking
speed (CBWS) 0.1–0.8 m/s without walking aids or
orthotics; at least 6 months after a stroke (ischaemic
or haemorrhagic) or traumatic brain injury (TBI).
To continue into the OL phase, patients had to have
completed follow-up visits in the DB trial without
any major protocol deviations and/or ongoing ad-
verse events. Key exclusion criteria were: major
limitation in passive range of motion at hip, knee or
ankle; known sensitivity to any form of botulinum
neurotoxin (BoNT) or aboBoNT-A excipients;
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RESULTS
Patient disposition and baseline characteristics
A total of 352 patients entered the OL study; 127 were
injected at both TC3 and TC4 and were thus included in
these analyses (n = 63 received co-injection in LL+UL;
n = 64 received injection in LL only, Fig. 1).
Baseline demographic characteristics were similar
between the LL+UL and LL only treatment groups,
including cause of spasticity (stroke or traumatic brain
injury (TBI)), time since causal event, and whether
naïve to any form of BoNT administered to the af-
fected LL (Table I).
Injection doses are shown in Table II. Mean (stan-
dard deviation; SD) doses in LL at TC3 and TC4
were lower in patients injected in LL+UL vs LL only
(1,006.7 U (SD 57.2), 1,001.1 U (SD 58.3) vs 1,381.8
U (SD 215.4), 1,367.2 U (SD 222.6)). Mean doses
in the UL at TC3 and TC4 were 486.9 U (SD 56.1)
and 491.0 U (SD 44.5), respectively. Overall LL dose
ranges received at TC3 and TC4, respectively, were
937.5–1,500 U and 1,000–1,500 U in LL only and
1,300–1,500 U and 1,000–1,500 U in LL+UL. The
most frequently injected UL muscles in TC3 and TC4,
respectively, were the flexor digitorum superficialis
Minimum of 12 weeks between treatment cycles
AboBoNT-A 1,000 U
or 1,500 U in LL only
Double-blind study
(N=388)
Received aboBoNT-A
(N=253)
Open-label
study
(N=352)
TC1
(N=345)
TC2
(N=297)
AboBoNT-A 1,000 U or 1,500 U
(500 U permitted in UL,
total dose ≤1,500 U)
TC3
(N=224)
LL only: n=117
LL+UL: n=107
TC4
(N=139)
LL only: n=64
LL+UL: n=75
TC3/TC4
LL only: n=64
LL+UL: n=63
Fig. 1. Design of the post hoc analysis. Patient numbers decreased across cycles
due to injection intervals of >12 weeks, with a maximum treatment duration of 1
year per patient. AboBoNT-A: abobotulinumtoxinA; LL: lower limb; TC: treatment
cycle; U: units; UL: upper limb.