Experience
Because clinical trials are conducted under widely varying conditions, the adverse reaction rates observed cannot be directly compared to rates in other clinical trials and may not reflect the rates observed in clinical practice.
Across all clinical studies, 566 subjects were exposed to at least one dose of GATTEX (190 patient-years of exposure; mean duration of exposure was 17 weeks). Of the 566 subjects, 173 subjects were treated in Phase 3 SBS studies (134/173 [77%] at the dose of 0.05 mg/kg/day and 39/173 [23%] at the dose of 0.10 mg/kg/day).
The most commonly reported (≥ 10%) adverse reactions in patients treated with GATTEX across all clinical studies (n = 566) were: abdominal pain (30.0%); injection site reactions (22.4%); nausea (18.2%); headaches (15.9%); abdominal distension (13.8%); upper respiratory tract infection (11.8%).
The rates of adverse reactions in subjects with SBS participating in two randomized, placebo-controlled, 24-week, double-blind clinical studies (Study 1 and Study 3) are summarized in Table 1. Only those reactions with a rate of at least 5% in the GATTEX group, and greater than placebo group, are summarized in Table 1. The majority of these reactions were mild or moderate. Of subjects receiving GATTEX at the recommended dose of 0.05 mg/kg/day, 88.3% (N=68/77) experienced an adverse reaction, as compared to 83.1% (49/59) for placebo. Many of these adverse reactions have been reported in association with the underlying disease and/or parenteral nutrition.
Table 1: Adverse reactions in ≥5% of GATTEX-treated SBS subjects and more frequent than placebo: Studies 1 and 3 Adverse Reaction Placebo
(N=59)
n (%) GATTEX
0.05mg/kg/day
(N=77)
n (%)
*
Percentage based on 53 subjects with a stoma (N = 22 placebo; N = 31 GATTEX 0.05 mg/kg/day)
Abdominal Pain 16 ( 27.1) 29 ( 37.7)
Upper Respiratory Tract Infection 8 ( 13.6) 20 ( 26.0)
Nausea 12 ( 20.3) 19 ( 24.7)
Abdominal Distension 1 ( 1.7) 15 ( 19.5)
Vomiting 6 ( 10.2) 9 ( 11.7)
Fluid Overload 4 ( 6.8) 9 ( 11.7)
Flatulence 4 ( 6.8) 7 ( 9.1)
Hypersensitivity 3 ( 5.1) 6 ( 7.8)
Appetite Disorders 2 ( 3.4) 5 ( 6.5)
Sleep Disturbances 0 4 ( 5.2)
Cough 0 4 ( 5.2)
Skin Hemorrhage 1 ( 1.7) 4 ( 5.2)
Subjects with Stoma
Gastrointestinal Stoma Complication 3 (13.6)* 13 (41.9)*
In placebo-controlled Studies 1 and 3, 12% of patients in each of the placebo and GATTEX study groups experienced an injection site reaction.
Adverse Reactions of Special Interest
Malignancy. Three subjects were diagnosed with malignancy in the clinical studies, all of whom were male and had received GATTEX 0.05 mg/kg/day in Study 2. One subject had a history of abdominal radiation for Hodgkin's disease two decades prior to receiving GATTEX and prior liver lesion on CT scan, and was diagnosed with metastatic adenocarcinoma of unconfirmed origin after 11 months of exposure to GATTEX. Two subjects had extensive smoking histories, and were diagnosed with lung cancers (squamous and non-small cell) after 12 months and 3 months of GATTEX exposure, respectively.
Colorectal Polyps. In the clinical studies, 6 subjects were diagnosed with polyps of the G.I. tract after initiation of study treatment. In the SBS placebo-controlled studies, 1/59 (1.7%) of subjects on placebo and 1/109 (0.9%) of subjects on GATTEX 0.05 mg/kg/day were diagnosed with intestinal polyps (inflammatory stomal and hyperplastic sigmoidal after 3 and 5 months, respectively). The remaining 4 |
