Liters for placebo-treated subjects (from pre-treatment baseline of 13.2 Liters/week) (p<0.001).
Twenty-one subjects on GATTEX (53.8%) versus 9 on placebo (23.1%) achieved at least a one-day reduction in PN/I.V. support.
The mean changes from Baseline in PN/I.V. volume by visit are shown in Figure 2.
Figure 2: Change (±95% CI) in PN/I.V. volume (L/week)
Study 2
Study 2 was a 2-year open-label extension of Study 1 in which 88 subjects received GATTEX 0.05 mg/kg/day. Ninety-seven percent (76/78) of subjects who completed Study 1 elected to enroll in Study 2 (37 received GATTEX; 39 received Placebo). An additional 12 subjects entered Study 2, who had been optimized and stabilized but not randomized in Study 1 because of closed enrollment.
30 months exposure
Thirty GATTEX subjects completed a total duration of 30 months (Study 1 followed by Study 2 treatment). Of these, 28 subjects (93%) achieved a 20% or greater reduction of parenteral support. Of responders in Study 1 who had completed 2 additional years of continuous treatment with GATTEX, 96% (21/22) sustained their response to GATTEX. The mean reduction in PN/I.V. (n=30) was 7.55 L/week (a 65.6% reduction from baseline). Ten subjects were weaned off their PN/I.V. support while on GATTEX treatment for 30 months. Subjects were maintained on GATTEX even if no longer requiring PN/I.V. support. These 10 subjects had required PN/I.V. support for 1.2 to 15.5 years, and prior to GATTEX had required between 3.5 L/week and 13.4 L/week of PN/I.V. support. At the end of study, 21 (70%), 18 (60%) and 18 (60%) of the 30 completers achieved a reduction of 1, 2, or 3 days per week in PN/I.V. support, respectively.
24 month exposure
Of the 39 placebo subjects from Study 1 entering Study 2, 29 completed 24 months of treatment with GATTEX. The mean reduction in PN/I.V. was 3.11 L/week (an additional 28.3% reduction) from the start of Study 2. Sixteen (55.2%) of the 29 completers achieved a 20% or greater reduction of parenteral support. At the end of study, 14 (48.3%), 7 (24.1%) and 5 (17.2%) achieved a reduction of 1, 2, or 3 days per week in PN/I.V. support, respectively. Two subjects were weaned off their PN/I.V. support while on GATTEX. Of the 12 subjects entering Study 2 directly, 6 completed 24 months of treatment with GATTEX. Similar effects were seen. One of the six subjects was weaned off their PN/I.V. support while on GATTEX.
14.2 Study 3 (Placebo-controlled) and Study 4 (Blinded uncontrolled extension of Study 3)
Study 3
Study 3 was a randomized, double-blind, placebo-controlled, three parallel-group, multinational study in adults with Short Bowel Syndrome who were dependent on parenteral nutrition/intravenous (PN/I.V.) support for at least 12 months and required PN at least 3 times per week. After a period of optimization and stabilization similar to Study 1, subjects were randomized to receive 24 weeks of one of the following treatment regimens: GATTEX 0.05 mg/kg/day (n=35), GATTEX 0.10 mg/kg/day dose (n=33), or placebo (n=16). The treatment groups were compared using the intent-to-treat population of this study which was defined as all randomized patients who were administered at least one dose of study drug. This population contained one less patient in the 0.10 mg/kg/day dose group hence n=32 in this group for all analyses. The primary efficacy endpoint was a graded categorical score that did not achieve statistical significance for the high dose. Further eva luation of PN/I.V. volume reduction using the endpoint of response |
