Hepatic Insufficiency - A reduction in r-hGH clearance has been noted in patients with hepatic dysfunction as compared with normal controls.

CLINICAL STUDIES
ADULT GROWTH HORMONE DEFICIENCY (GHD)

A multicenter, randomized, double-blind, placebo-controlled clinical trial was conducted in 115 adults with GHD comparing the effects of Saizen® [somatropin (rDNA origin) for injection] and placebo on body composition.  Patients in the active treatment arm were treated with Saizen ® at an initial dose of 0.005 mg/kg/day for one month which was increased to 0.01 mg/kg/day if tolerated for the remaining five months of the study.  The primary endpoint was the change from baseline in lean body mass (LBM) measured by dual energy X-ray absorptiometry (DXA) after 6 months.  Treatment with Saizen® produced significant (p<0.001) increases from baseline in LBM compared to placebo (Table 1).

Table 1 – Lean Body Mass (kg) by DXA  Saizen®
(n=52) Placebo
(n=51)
Baseline (mean) 47.7 54.0
Change from baseline at 6 months (mean) +1.9 -0.2
Treatment difference (mean)
95% confidence interval
p-value  2.1
(1.3, 2.9)
<0.001

Sixty-seven (58%) of the 115 randomized patients were male.  The adjusted mean treatment difference on the increase in LBM from baseline was significantly greater in males (2.9 kg) than females (0.8 kg).

Ninety-seven (84%) of the 115 randomized patients had adult onset (AO) GHD.  The adjusted mean treatment differences on the increase in LBM from baseline were not significantly different in AO GHD (2.1 kg) compared with childhood onset (CO) GHD (1.0 kg) patients.  However, there were relatively few patients with CO GHD (n=18) on which to base the comparison.

Analysis of the treatment difference on the change from baseline in total fat mass (by DXA) revealed a significant decrease (p<0.001) in the Saizen®-treated group compared to the placebo group.  Saizen® also produced beneficial effects on several bone turnover markers including bone specific alkaline phosphatase, c-terminal propeptide, osteocalcin, urine deoxypyridinoline and iPTH.

One hundred and eleven patients were enrolled in an open label follow up study and treated with Saizen® for an additional 6-30 months.  During this period, the beneficial effects on LBM and total fat mass achieved during the initial six months of treatment were maintained.

INDICATIONS AND USAGE
Pediatric Patients

Saizen® [somatropin (rDNA origin) for injection] is indicated for the treatment of children with growth failure due to inadequate secretion of endogenous growth hormone.

Adult Patients

Saizen® [somatropin (rDNA origin) for injection] is indicated for replacement of endogenous growth hormone in adults with growth hormone deficiency who meet either of the following two criteria:

Adult Onset:  Patients who have growth hormone deficiency, either alone or associated with multiple hormone deficiencies (hypopituitarism), as a result of pituitary disease, hypothalamic disease, surgery, radiation therapy, or trauma; or

Childhood Onset:  Patients who were growth hormone deficient during childhood as a result of congenital, genetic, acquired, or idiopathic causes.

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