MD Conference Express - ENDO 2015 - (Page 9)
Figure 1. Pasireotide Trough Concentration Increases
A
B
Probability of GH response
Probability of IGF-1 Response
Probability of GH Response
1.0
95% CI
0.8
0.6
0.4
0.2
0.0
0
10
20
30
40
Probability of IGF-1 response
1.0
0.8
0.6
0.4
0.2
0.0
50
0
Pasireotide Trough Concentration, ng/mL
10
20
30
40
50
Pasireotide Trough Concentration, ng/mL
C
D
Probability of overall response
1.0
95% CI
0.8
0.6
0.4
0.2
0.0
0
10
20
30
40
Probability of hyperglycemia
1.0
Probability of Hyperglycemia
Probability of Overall Response
95% CI
50
Pasireotide Trough Concentration, ng/mL
95% CI
0.8
0.6
0.4
0.2
0.0
0
10
20
30
40
50
Pasireotide Trough Concentration, ng/mL
GH, growth hormone; IGF-1, insulinlike growth factor.
Reprinted with permission from G Shen, PhD.
Pasireotide, a multireceptor-targeted SSA, was recently
approved for use in patients with acromegaly. Earlier
results from the PAOLA study found that pasireotide was
able to produce biochemical disease control in patients
who were not responsive to other agents, with an efficacy of
15.4% with pasireotide LAR 40 mg and 20.0% at 60 mg vs 0%
with octreotide LAR 30 mg or lanreotide Autogel 120 mg
[Gadelha MR et al. Lancet Diabetes Endocrinol. 2014].
Patients in the 2 treatment arms received doubleblind pasireotide LAR 40 or 60 mg every 28 days (n = 65
in each group). Patients in the open-label, active-control
treatment arm (n = 68) received either octreotide LAR
30 mg or lanreotide Autogel 120 mg every 28 days.
Within the dose range of pasireotide LAR 40 to 60 mg
that was evaluated, the dose-exposure relationship of
pasireotide LAR was approximately dose proportional.
The concentration of pasireotide reached steady state
after 3 consecutive monthly injections. Interpatient PK
variability was moderate to high.
The PK covariate of sex suggested that female patients
would have approximately 51% higher steady-state
trough concentration of pasireotide than male patients
with the same age and equal baseline bilirubin. However,
since efficacy and safety profiles were similar between
female and male patients, this PK difference was not
considered clinically meaningful.
Levels of both GH and IGF-1 had a clear exposureresponse relationship to pasireotide LAR concentration.
The estimated maximum suppression of GH was 83.0%,
which was relatively higher than the estimated maximum suppression of IGF-1 of 67.1%.
Increasing pasireotide trough concentration by 1.5fold corresponds to dose increases from 40 to 60 mg.
This 1.5-fold increase resulted in increased odds of GH
responses by 44%, of IGF-1 responses by 51%, and of
GH + IGF-1 responses by 54% (Figure 1). Also, a 1.5-fold
increase in pasireotide concentration increased the odds
of having hyperglycemia by 36%.
The change from baseline for both QTcF and QTcB had
a relatively flat relationship with pasireotide concentrations based on data up to week 24, suggesting no clinically
significant effect. Also, pasireotide exposure up to week
Official Peer-Reviewed Highlights From ENDO 2015
9
Table of Contents for the Digital Edition of MD Conference Express - ENDO 2015
Contents
MD Conference Express - ENDO 2015
MD Conference Express - ENDO 2015 - (Page Cover1)
MD Conference Express - ENDO 2015 - (Page Cover2)
MD Conference Express - ENDO 2015 - (Page i)
MD Conference Express - ENDO 2015 - (Page ii)
MD Conference Express - ENDO 2015 - Contents (Page 1)
MD Conference Express - ENDO 2015 - Contents (Page 2)
MD Conference Express - ENDO 2015 - Contents (Page 3)
MD Conference Express - ENDO 2015 - Contents (Page 4)
MD Conference Express - ENDO 2015 - Contents (Page 5)
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MD Conference Express - ENDO 2015 - Contents (Page 8)
MD Conference Express - ENDO 2015 - Contents (Page 9)
MD Conference Express - ENDO 2015 - Contents (Page 10)
MD Conference Express - ENDO 2015 - Contents (Page 11)
MD Conference Express - ENDO 2015 - Contents (Page 12)
MD Conference Express - ENDO 2015 - Contents (Page 13)
MD Conference Express - ENDO 2015 - Contents (Page 14)
MD Conference Express - ENDO 2015 - Contents (Page 15)
MD Conference Express - ENDO 2015 - Contents (Page 16)
MD Conference Express - ENDO 2015 - Contents (Page 17)
MD Conference Express - ENDO 2015 - Contents (Page 18)
MD Conference Express - ENDO 2015 - Contents (Page 19)
MD Conference Express - ENDO 2015 - Contents (Page 20)
MD Conference Express - ENDO 2015 - Contents (Page 21)
MD Conference Express - ENDO 2015 - Contents (Page 22)
MD Conference Express - ENDO 2015 - Contents (Page 23)
MD Conference Express - ENDO 2015 - Contents (Page 24)
MD Conference Express - ENDO 2015 - Contents (Page 25)
MD Conference Express - ENDO 2015 - Contents (Page 26)
MD Conference Express - ENDO 2015 - Contents (Page Cover3)
MD Conference Express - ENDO 2015 - Contents (Page Cover4)
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