Gastrointestinal Drugs
Advisory Committee
Questions for NDA
21-597, Serostim for SBS
1.
The primary endpoint of this study was change in
Total IPN volume from week 2 to week 6.
Pairwise comparisons of results of the primary endpoint yielded
statistically significant differences between
the recombinant human growth hormone (rh-GH)-containing arms and the control
group. Are the findings in the table below clinically meaningful? In your response consider the definition of
the primary endpoint and the duration of study treatment.
Changes in
Total IPN Volume
|
Mean Change in
Total IPN Vol. |
Difference in
Total IPN Volume [L/wk] (p-value) |
|||
|
Group A rhGH (n=16) |
Group B rhGH + GLN (n=16) |
Group C GLN (n=9) |
Group B vs C |
Group A vs C |
|
-5.9 |
-7.7 |
-3.8 |
-3.9
(<0.001) |
-2.1 (0.043) |
Baseline IPN Requirements:
Group A: 10.3 L/wk
Group B: 10.5 L/wk
2.
Secondary endpoints were change in Total IPN
calories and change in IPN or lipid frequency. Pairwise comparisons of the
results of these secondary endpoints yielded statistically significant
differences between the
rh-GH-containing arms and the control group. Are the findings in the table
below clinically meaningful?
|
Treatment
Groups |
||||
|
Group A rhGH (n=16) |
Group B rhGH + GLN (n=16) |
Group C GLN (n=9) |
Group B vs C |
Group A vs C |
|
Change in Total IPN Calories [kcal/wk] /
(p-value) |
||||
|
-4338.3 |
-5751.2 |
-2633.3 |
-3117.9 (<0.001) |
-1705.0 (0.005) |
|
Change in IPN or Lipid frequency [d/wk] (p-value) |
||||
|
-3.0 |
-4.2 |
-2.0 |
-2.2 (<0.001) |
-1.0 (0.025) |
Gastrointestinal Drugs
Advisory Committee
Questions for NDA
21-597, Serostim for SBS
Continued
3.
The primary endpoint was change in Total IPN
volume. Only 1 of the 3 components (IPN
volume) was recorded between week 6 and 18.
Is the measurement of IPN volume adequate to demonstrate durability of
effect? If not, what do you recommend as a minimum follow up period?
4.
The data were primarily derived from a single,
nutritional support tertiary care center.
Are these data generalizable to the population of short bowel syndrome
patients?
5.
Are there specific safety concerns considering
the potential for long term use of
rh-GH in the treatment of short bowel syndrome patients?
6.
Do the data support the safety and effectiveness
of rh-GH alone or in co-therapy
with glutamine in patients with short bowel
syndrome? Are there any additional
studies that you would recommend, e.g., dose finding?