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Mechanism of Action
GH binds to dimeric GH receptors located within the cell membranes of target tissue cells. This interaction results in intracellular signal transduction and subsequent induction of transcription and translation of GH-dependent proteins including IGF-I, IGF BP-3 and acid-labile subunit. GH has direct tissue and metabolic effects, including stimulation of chondrocyte differentiation, stimulation of lipolysis and stimulation of hepatic glucose output. In addition, some effects of somatropin are mediated indirectly by IGF-I, including stimulation of protein synthesis and chondrocyte proliferation.
In vitro, preclinical, and clinical testing have demonstrated that Humatrope (somatropin rdna origin) is therapeutically equivalent to human GH of pituitary origin and achieves equivalent pharmacokinetic profiles in healthy adults. The following effects have been reported for human GH of pituitary origin, and/or somatropin.
Total numbers of muscle cells are reduced in GH deficient children. Somatropin increases the number and size of muscle cells in such children.
Somatropin stimulates skeletal growth in children with GH deficiency as a result of effects on the growth plates (epiphyses) of long bones. Concentrations of IGF-I, which play a role in skeletal growth, are low in the serum of GH deficient children but increase during somatropin treatment in most patients. The stimulation of skeletal growth increases linear growth rate (height velocity) in most somatropin-treated children.
Linear growth is facilitated in part by increased cellular protein synthesis as reflected by nitrogen retention, which can be demonstrated by decreased urinary nitrogen excretion and serum urea nitrogen.
Connective Tissue Metabolism
GH has a physiological role in the maintenance of normoglycemia during times of substrate restriction (e.g., fasting), via mechanisms such as stimulation of hepatic gluconeogenesis and suppression of insulin-stimulated glucose uptake by peripheral tissues. Because of these actions GH is considered an insulin antagonist with respect to carbohydrate metabolism. Consequently, the fasting hypoglycemia that may occur in some children with hypopituitarism may be improved by somatropin treatment. As an extension of its physiological actions, supraphysiological GH concentrations may increase glucose production sufficiently to stimulate insulin secretion to maintain normoglycemia. Large doses of somatropin may impair glucose tolerance if compensatory insulin secretion is inadequate. Administration of somatropin to healthy adults and patients with Turner syndrome resulted in increases in mean serum fasting and postprandial insulin concentrations, although mean values remained in the normal range. In addition, mean HbA1c concentrations and mean fasting and postprandial glucose concentrations remained in the normal range.
Somatropin stimulates intracellular lipolysis, and administration of somatropin leads to an increase in plasma free fatty acids and triglycerides. Untreated GH deficiency is associated with increased body fat stores, including increased abdominal visceral and subcutaneous adipose tissue. Treatment of GH deficient patients with somatropin results in a general reduction of fat stores, and decreased serum concentrations of low density lipoprotein (LDL) cholesterol.
Administration of somatropin results in an increase in total body potassium and phosphorus and to a lesser extent sodium, probably as the result of cell growth. Serum concentrations of inorganic phosphate increase in somatropin-treated GH deficient children because of the metabolic activities associated with bone growth. Although urinary calcium excretion is increased, there is a simultaneous increase in calcium absorption from the intestine. Consequently, serum calcium concentrations generally are not altered, although negative calcium balance may occur occasionally during somatropin treatment. Associated with the changes in mineral metabolism, parathyroid hormone may increase during somatropin treatment.
Humatrope (somatropin rdna origin) has been studied following intramuscular, subcutaneous, and intravenous administration in adult volunteers (see Figure 1). The absolute bioavailability of somatropin is 75% and 63% after subcutaneous and intramuscular administration, respectively.
The volume of distribution of somatropin after intravenous injection is about 0.07 L/kg (Table 6).
Extensive metabolism studies have not been conducted. The metabolic fate of somatropin involves classical protein catabolism in both the liver and kidneys. In renal cells, at least a portion of the breakdown products of somatropin is returned to the systemic circulation. In healthy volunteers, mean somatropin clearance is 0.14 L/hr/kg. The mean half-life of intravenous somatropin is 0.36 hours, whereas subcutaneously and intramuscularly administered somatropin have mean half-lives of 3.8 and 4.9 hours, respectively. The longer half-life observed after subcutaneous or intramuscular administration is due to slow absorption from the injection site.
Urinary excretion of intact Humatrope (somatropin rdna origin) has not been measured. Small amounts of somatropin have been detected in the urine of pediatric patients following replacement therapy.
The pharmacokinetics of Humatrope (somatropin rdna origin) have not been studied in patients greater than 65 years of age.
The pharmacokinetics of Humatrope (somatropin rdna origin) in pediatric patients are similar to those of adults.
No gender-specific pharmacokinetic studies have been performed with Humatrope (somatropin rdna origin) . The available literature indicates that the pharmacokinetics of somatropin are similar in men and women.
No data are available.
Renal, hepatic insufficiency
No studies have been performed with Humatrope (somatropin rdna origin) .
Table 6: Summary of Somatropin Parameters in Healthy Adult
|0.02 mg (0.05 IUb)/kg, iv Mean (SD)||415 (75)||0.363 (0.053)||156 (33)||0.135 (0.029)||0.0703 (0.0173)|
|0.1 mg (0.27 IUb)/kg, im Mean (SD)||53.2 (25.9)||4.93 (2.66)||495 (106)||0.215 (0.047)||1.55 (0.91)|
|0.1 mg (0.27 IUb)/kg, sc Mean (SD)||63.3 (18.2)||3.81 (1.40)||585 (90)||0.179 (0.028)||0.957 (0.301)|
|a Abbreviations: Cmax=maximum
concentration; t½=half-life; AUC0-∞=area under the curve;
Cls=systemic clearance; Vβ=volume distribution; iv=intravenous; SD=standard
deviation; im=intramuscular; sc=subcutaneous.
b Based on previous International Standard of 2.7 IU=1 mg. 13
Adult Patients with Growth Hormone Deficiency
Two multicenter trials in patients with adult-onset GH deficiency (n=98) and two studies in patients with childhood-onset GH deficiency (n=67) were designed to assess the effects of replacement therapy with Humatrope (somatropin rdna origin) . These four studies each included a 6-month randomized, blinded, placebo-controlled phase, during which approximately half of the patients received placebo injections, while the other half received Humatrope (somatropin rdna origin) injections. The Humatrope (somatropin rdna origin) dosages for all studies were identical: 1 month of treatment at 0.00625 mg/kg/day (6.25μg/kg/day) followed by 0.0125 mg/kg/day (12.5 μg/kg/day) for the next 5 months. The 6-month, double-blind phase was followed by 12 months of open-label Humatrope (somatropin rdna origin) treatment for all patients. The primary efficacy measures were body composition (lean body mass and fat mass), lipid parameters, and quality of life, as measured by the Nottingham Health Profile (a general health-related quality of life questionnaire). Lean body mass was determined by bioelectrical impedance analysis (BIA), validated with potassium 40. Body fat was assessed by BIA and sum of skinfold thickness. Lipid subfractions were analyzed by standard assay methods in a central laboratory. Adult-onset patients and childhood-onset patients differed by diagnosis (organic vs. idiopathic pituitary disease), body size (average vs. small [mean height and weight]), and age (mean 44 vs. 29 years).
In patients with adult-onset GH deficiency, Humatrope (somatropin rdna origin) treatment (vs. placebo) resulted in an increase in mean lean body mass (2.59 vs. -0.22 kg, p < 0.001) and a decrease in body fat (-3.27 vs. 0.56 kg, p < 0.001). Similar changes were seen in childhood-onset GH deficient patients. These significant changes in lean body mass persisted throughout the 18-month period for both the adult-onset and childhood-onset groups; the changes in fat mass persisted in the childhood-onset group. Serum concentrations of high-density lipoprotein (HDL) cholesterol which were low at baseline (mean, 30.1 mg/mL and 33.9 mg/mL in adult-onset and childhood-onset patients, respectively) had normalized by the end of 18 months of Humatrope (somatropin rdna origin) treatment (mean change of 13.7 and 11.1 mg/dL for the adult-onset and childhood-onset groups, respectively p < 0.001). After 6 months, the physical mobility and social isolation domains on the Nottingham Health Profile were significantly improved in Humatrope (somatropin rdna origin) -treated vs. placebo-treated patients with adult-onset GH deficiency (p < 0.01) (Table 7). There were no significant between-group differences (Humatrope (somatropin rdna origin) vs. placebo) for the other Nottingham Health Profile domains (energy level, emotional reactions, sleep, pain) in patients with adult-onset GH deficiency, and no significant between-group differences in any of the domains were demonstrated for patients with childhood-onset GH deficiency.
Two additional studies on the effect of Humatrope (somatropin rdna origin) on exercise capacity were conducted. Improved physical function was documented by increased exercise capacity (VO2 max, p < 0.005) and work performance (Watts, p < 0.01).
Table 7: Changesa in Nottingham Health Profile
Scoresb in Adult-Onset Growth Hormone-Deficient Patients
|Physical mobility||-3.1||-10.5||p < 0.01|
|Social isolation||0.5||-4.7||p < 0.01|
|a An improvement in score is indicated
by a more negative change in the score.
b To account for multiple analyses, appropriate statistical methods were applied and the required level of significance is 0.01.
c NS=not significant.
Two studies evaluating the effect of Humatrope (somatropin rdna origin) on bone mineralization were conducted subsequently. In a 2-year, randomized, double-blind, placebo-controlled trial, 67 patients with previously untreated adult-onset GH deficiency received placebo or Humatrope (somatropin rdna origin) injections titrated to maintain serum IGF-I within the age-adjusted normal range. In men, but not women, lumbar spine bone mineral density (BMD) increased with Humatrope (somatropin rdna origin) treatment compared to placebo, with a treatment difference of approximately 4% (p=0.001). There was no significant change in hip BMD with Humatrope (somatropin rdna origin) treatment in men or women, when compared to placebo.
In a 2-year, open-label, randomized trial, 149 patients with childhood-onset GH deficiency who had completed pediatric somatropin therapy, had attained final height (height velocity < 1 cm/yr) and were confirmed to be GH-deficient as young adults (commonly referred to as transition patients), were randomized to receive Humatrope (somatropin rdna origin) 0.0125 mg/kg/day (12.5 μg/kg/day), Humatrope (somatropin rdna origin) 0.025 mg/kg/day (25 μg/kg/day), or no injections (control). Patients who were randomized to treatment with Humatrope (somatropin rdna origin) at 12.5 μg/kg/day achieved a 2.9% greater increase from baseline than control patients in total body bone mineral content (BMC) (8.1 ± 9.0% vs. 5.2 ± 8.2%, p=0.02), whereas patients treated with Humatrope (somatropin rdna origin) at 25 μg/kg/day had no significant change in BMC. These results include data from patients who received less than 2 years of treatment. A greater treatment effect was observed for patients who completed 2 years of treatment. Increases in lumbar spine BMD and BMC were also statistically significant compared to control with the 12.5 μg/kg/day dose but not the 25 μg/kg/day dose. Hip BMD and BMC did not change significantly compared to control with either dose. The effect of GH treatment on BMC and BMD in transition patients at doses lower than12.5 μg/kg/day was not studied. The effect of Humatrope (somatropin rdna origin) on the occurrence of osteoporotic fractures has not been studied.
Pediatric Patients with Turner Syndrome
One long-term, randomized, open-label, Canadian multicenter, concurrently controlled study, two long-term, open-label multicenter, historically controlled US studies and one long-term, randomized, US dose-response study were conducted to evaluate the efficacy of somatropin treatment of short stature due to Turner syndrome.
The Canadian randomized study compared near-adult height outcomes for Humatrope (somatropin rdna origin) -treated patients to those of a concurrent control group who received no injections. The Humatrope (somatropin rdna origin) -treated patients received a dosage of 0.3 mg/kg/week given in divided doses 6 times per week from a mean age of 11.7 years for a mean duration of 4.7 years. Puberty was induced with a standardized estrogen regimen initiated at 13 years of age for both treatment groups. The Humatrope (somatropin rdna origin) -treated group (n=27) attained a mean (± SD) near-final height of 146.0 ± 6.2 cm; the untreated control group (n=19) attained a near-final height of 142.1 ± 4.8 cm. By analysis of covariance (with adjustments for baseline height and mid-parental height), the effect of somatropin treatment was a mean height increase of 5.4 cm (p=0.001).
In two of the US studies, the effect of long-term somatropin treatment (0.375 mg/kg/week given in divided doses either 3 times per week or daily) on adult height was determined by comparing adult heights in the treated patients with those of age-matched historical controls with Turner syndrome who received no growth-promoting therapy. Puberty was induced with a standardized estrogen regimen initiated after 14 years of age in one study; in the second study patients treated with early somatropin (before 11 years of age) were randomized to begin pubertal induction at either age 12 (n=26) or 15 (n=29) years (conjugated estrogens, 0.3 mg escalating to 0.625 mg daily); those whose somatropin was initiated after 11 years of age began estrogen replacement after 1 year of somatropin. Mean height gains from baseline to adult (or near-adult) height ranged from 5.0 to 8.3 cm, depending on age at initiation of somatropin treatment and estrogen replacement (Table 8).
In the third US study, a randomized, blinded dose-response study, patients were treated from a mean age of 11.1 years for a mean duration of 5.3 years with a weekly Humatrope (somatropin rdna origin) dosage of either 0.27 mg/kg or 0.36 mg/kg administered in divided doses 3 or 6 times weekly. The mean near-final height of Humatrope (somatropin rdna origin) -treated patients was 148.7 ± 6.5 cm (n=31). When compared to historical control data, the mean gain in adult height was approximately 5 cm.
In summary, patients with Turner syndrome (total n=181 from the 4 studies above) treated to adult height achieved statistically significant average height gains ranging from 5.0 to 8.3 cm.
Table 8: Summary Table of Efficacy Resultsa
|Study||Group||Study Designb||Number at Adult Height||GH Age (yr)||Estrogen Age (yr)||GH Duration (yr)||Adult Height
| a Data shown are mean values.
b RCT: randomized controlled trial; MHT: matched historical controlled trial; RDT: randomized dose-response trial.
c Analysis of covariance vs. controls.
d Compared with historical data.
e GH age < 11 yr, estrogen age 15 yr.
f GH age < 11 yr, estrogen age 12 yr. g GH age > 11 yr, estrogen at month 12.
Pediatric Patients with Idiopathic Short Stature
Two randomized, multicenter trials, 1 placebo-controlled and 1 dose-response, were conducted in pediatric patients with idiopathic short stature, also called non-GH-deficient short stature. The diagnosis of idiopathic short stature was made after excluding other known causes of short stature, as well as GH deficiency. Limited safety and efficacy data are available below the age of 7 years. No specific studies have been conducted in pediatric patients with familial short stature. The placebo-controlled study enrolled 71 pediatric patients (55 males, 16 females) 9 to 15 years old (mean age 12.4 ± 1.5 years), with short stature, 68 of whom received Humatrope (somatropin rdna origin) . Patients were predominately prepubertal (Tanner I, 45%) or in early puberty (Tanner II, 47%) at baseline. In this double-blind trial, patients received subcutaneous injections of either Humatrope (somatropin rdna origin) 0.222 mg/kg/week (equivalent to 32 μg/kg/day), or placebo given in divided doses 3 times per week until height velocity decreased to ≤ 1.5 cm/year (“final height”). Final height measurements were available for 33 subjects (22 Humatrope (somatropin rdna origin) , 11 placebo) after a mean treatment duration of 4.4 years (range 0.1-9.1 years).
The Humatrope (somatropin rdna origin) -treated group achieved a mean final height SDS of -1.8 (Table 9), whereas placebo-treated patients had a mean final height SDS of -2.3 (mean treatment difference, 0.51 SDS, p=0.017). Height gain across the duration of the study and final height SDS minus baseline predicted height SDS were also significantly greater in Humatrope (somatropin rdna origin) -treated patients than in placebo-treated patients (Tables 9 and 10). In addition, the number of patients whose final height was above the 5th percentile of the general population height standard for age and sex was significantly greater in the Humatrope (somatropin rdna origin) group than the placebo group (41% vs. 0%, p < 0.05), as was the number of patients who gained at least 1 SDS unit in height across the duration of the study (50% vs. 0%, p < 0.05).
Table 9: Baseline Height Characteristics and Effect of Humatrope (somatropin rdna origin)
on Final Height in Placebo-Controlled Studya,b
|Humatrope (somatropin rdna origin)
|Baseline height SDS||-2.75 (0.6)||-2.7 (0.6)||NA||0.77|
|BPH SDS||-2.3 (0.8)||-2.1 (0.7)||NA||0.53|
|Final height SDSc||-2.3 (0.6)||-1.8 (0.8)||0.51 (0.10, 0.92)||0.017|
|FH SDS -baseline height SDS||0.4 (0.2)||0.9 (0.7)||0.51 (0.04, 0.97)||0.034|
|FH SDS - BPH SDS||-0.1 (0.6)||0.3 (0.6)||0.46 (0.02, 0.89)||0.043|
|a Abbreviations: BPH=baseline
predicted height; CI=confidence interval; FH=final height; NA=not applicable;
SDS=standard deviation score.
b For final height population.
c Between-group comparison was performed using analysis of covariance with baseline predicted height SDS as the covariate.Treatment effect is expressed as least squares mean (95% CI).
The dose-response study included 239 pediatric patients (158 males, 81 females), 5 to 15 years old, (mean age 9.8 ± 2.3 years). Mean ± SD baseline characteristics included: height SDS -3.21 ± 0.70, predicted adult height SDS -2.63 ± 1.08, and height velocity SDS -1.09 ± 1.15. All but 3 patients were prepubertal. Patients were randomized to one of three Humatrope (somatropin rdna origin) treatment groups: 0.24 mg/kg/week (equivalent to 34 μg/kg/day); 0.24 mg/kg/week for 1 year, followed by 0.37 mg/kg/week (equivalent to 53 μg/kg/day); and 0.37 mg/kg/week. The primary hypothesis of this study was that treatment with Humatrope (somatropin rdna origin) would increase height velocity during the first 2 years of therapy in a dose-dependent manner. Additionally, after completing the initial 2-year dose-response phase of the study, 50 patients were followed to final height.
Patients who received the Humatrope (somatropin rdna origin) dosage of 0.37 mg/kg/week had a significantly greater increase in mean height velocity after 2 years of treatment than patients who received 0.24 mg/kg/week (4.04 vs. 3.27 cm/year, p=0.003). The mean difference between final height and baseline predicted height was 7.2 cm for patients who received Humatrope (somatropin rdna origin) 0.37 mg/kg/week and 5.4 cm for patients who received 0.24 mg/kg/week (Table 10). While no patient had height above the 5th percentile in any dosage group at baseline, 82% of the patients who received 0.37 mg/kg/week and 47% of the patients who received 0.24 mg/kg/week achieved final heights above the 5th percentile of the general population height standards (p=NS).
Table 10: Idiopathic Short Stature Trials: Final Height Minus
Baseline Predicted Heighta
|Placebo-controlled Trial 3x per week dosing||Dose Response Trial 6x per week dosing|
|Humatrope (somatropin rdna origin)
| Humatrope (somatropin rdna origin)
|Humatrope (somatropin rdna origin)
|Humatrope (somatropin rdna origin)
|FH - Baseline PH Mean (95% CI), cm||-0.7 (-3.6, 2.3)||+2.2 (0.4, 3.9)||+5.4 (2.8, 7.9)||+6.7 (4.1, 9.2)||+7.2 (4.6, 9.8)|
|a Abbreviations: FH=final height; PH=predicted height; CI=confidence interval; cm=centimeters.|
Pediatric Patients with SHOX Deficiency
SHOX deficiency may result either from a deletion of one copy of the short stature homeobox-containing (SHOX) gene or from a mutation within or outside one copy of the SHOX gene that impairs the production or function of SHOX protein.
A randomized, controlled, two-year, three-arm, open-label study was conducted to evaluate the efficacy of Humatrope (somatropin rdna origin) treatment of short stature in pediatric patients with SHOX deficiency who were not GH–deficient. 52 patients (24 male, 28 female) with SHOX deficiency, 3.0 to 12.3 years of age, were randomized to either a Humatrope (somatropin rdna origin) -treated arm (27 patients; mean age 7.3 ± 2.1 years) or an untreated control arm (25 patients; mean age 7.5 ± 2.7 years). To determine the comparability of treatment effect between patients with SHOX deficiency and patients with Turner syndrome, the third study arm enrolled 26 patients with Turner syndrome, 4.5 to 11.8 years of age (mean age 7.5 ± 1.9 years), to Humatrope (somatropin rdna origin) treatment. All patients were prepubertal at study entry. Patients in the Humatrope (somatropin rdna origin) -treated group(s) received daily subcutaneous injections of 0.05 mg/kg (50 μg/kg) of Humatrope (somatropin rdna origin) , equivalent to 0.35 mg/kg/week. Patients in the untreated group received no injections.
Patients with SHOX deficiency who received Humatrope (somatropin rdna origin) had significantly greater first-year height velocity than untreated patients (8.7 cm/year vs. 5.2 cm/year, p < 0.001, primary efficacy analysis) and similar first-year height velocity to Humatrope (somatropin rdna origin) -treated patients with Turner syndrome (8.7 cm/year vs. 8.9 cm/year). In addition, patients who received Humatrope (somatropin rdna origin) had significantly greater second year height velocity, and first- and second-year height gain (cm and SDS) than untreated patients (Table 11).
Table 11: Summary of Efficacy Results in Patients with SHOX
deficiency and Turner Syndrome
|SHOX Deficiency||Turner Syndrome
Humatrope (somatropin rdna origin)
|Humatrope (somatropin rdna origin)
Mean (95% CI)
|Height Velocity (cm/yr)|
|1st Year||5.2 (1.1)||8.7 (1.6)b||+3.5 (2.8, 4.2)||8.9 (2.0)|
|2ndYear||5.4 (1.2)||7.3 (1.1)b||+2.0 (1.3, 2.6)||7.0 (1.1)|
|Height Gain (cm)|
|Baseline to 1 st Year||+5.4 (1.2)||+9.1 (1.5)b||+3.7 (2.9, 4.5)||+8.9 (1.9)|
|Baseline to 2 nd Year||+10.5 (1.9)||+16.4 (2.0)b||+5.8 (4.6, 7.1)||+15.7 (2.7)|
|Height SDS Gain|
|Baseline to 1 stYear||+0.1 (0.5)||+0.7 (0.5)b||+0.5 (0.3, 0.8)||+0.8 (0.5)|
|Baseline to 2 nd Year||+0.2 (0.5)||+1.2 (0.7)b||+1.0 (0.7, 1.3)||+1.2 (0.7)|
|Patients with height SDS > -2.0 at 2 years||1 (4%)||11 (41%) c||--||8 (31%)|
|a Positive values favor Humatrope (somatropin rdna origin)
b Statistically significantly different from untreated, p < 0.001.
c Statistically significantly different from untreated, p < 0.05.
Pediatric Patients Born Small for Gestational Age (SGA) Who Fail to Demonstrate Catch-up Growth by Age 2 4 Years
Data from 2 clinical trials demonstrate the effectiveness of Humatrope (somatropin rdna origin) in promoting linear growth in short children born SGA who fail to demonstrate catch-up growth.
The primary objective of Study 1 was to demonstrate that the increase from baseline in height SDS after 1 year of treatment would be similar when Humatrope (somatropin rdna origin) is administered according to an individually adjusted dose (IAD) regimen or a fixed high dose (FHD) regimen. The height increases would be considered similar if the lower bound of the 95% confidence interval (CI) for the mean difference between the groups (IAD – FHD) was greater than -0.5 height SDS. This 2-year, open-label, multicenter, European study enrolled 193 prepubertal, non-GH deficient children with mean chronological age 6.8 ± 2.4 years (range: 3.0 to 12.3). Additional study entry criteria included birth weight < 10th percentile and/or birth length SDS < -2 for gestational age, and height SDS for chronological age ≤ -3. Exclusion criteria included syndromal conditions (e.g., Turner syndrome), chronic disease (e.g., diabetes mellitus), and tumor activity. Children were randomized to either a FHD (0.067 mg/kg/day [0.47 mg/kg/week]; n=99) or an IAD treatment group (n=94). The initial Humatrope (somatropin rdna origin) dosage in the IAD treatment group was 0.035 mg/kg/day (0.25 mg/kg/week). The dosage was increased to 0.067 mg/kg/day in those patients in the IAD group whose 1-year height gain predicted at Month 3 was < 0.75 height SDS (n=40) or whose actual height gain measured at Year 1 was < 0.75 height SDS (n=11). Approximately 85% of the randomized patients completed 2 years of therapy.
At baseline, the FHD and IAD treatment groups had comparable height SDS (mean -3.9; Table 12). Although the mean 1-year height increase in the IAD group was statistically significantly lower than that observed in the FHD group, the study achieved its primary objective by demonstrating that the increase from baseline in height SDS in the IAD group was clinically similar (noninferior) to that in the FHD group (mean between-group difference = -0.3 SDS [95% CI: -0.4, -0.2 SDS]). The mean changes from baseline in height SDS at the end of the 2-year study were 1.4 and 1.6 SDS in the IAD and FHD groups, respectively. The results were similar when children who entered puberty during the study were removed from the analysis.
Table 12: Study 1 – Results for Height SDS and Change from
Baseline in Height SDS at Year 1 and Year 2 After Humatrope (somatropin rdna origin) Treatment of Short
Children Born SGA Who Fail to Demonstrate Catch-up Growtha
0.035 to 0.067 mg/kg/day
IAD – FHDb
|-3.9 (0.6)||-3.9 (0.7)||(-0.2, 0.2)|
|p-value = 0.95|
|Height SDS||-3.0 (0.7)||-2.7 (0.7)||(-0.4, -0.2)|
|Change from baseline||0.9 (0.4)||1.1 (0.4)||p-value < 0.001|
|Height SDS||-2.5 (0.8)||-2.2 (0.7)||(-0.4, -0.1)|
|Change from baseline||1.4 (0.5)||1.6 (0.5)||p-value = 0.003|
|a Abbreviations: IAD=individually
adjusted dose; FHD=fixed high dose; SD=standard deviation; SDS=standard
b Least squares mean difference ± standard error and 95% confidence interval based on ANCOVA model with treatment and gender as fixed effects, and baseline height SDS, baseline chronological age, baseline bone age, and mid-parental target height SDS as covariates.
c Only children with actual height measurements were included in the Year 1 and Year 2 analyses.
Study 2 was an open-label, multicenter, single arm study conducted in France, during which 35 prepubertal, non-GH deficient children were treated for 2 years with Humatrope (somatropin rdna origin) 0.067 mg/kg/day (0.47 mg/kg/week). Mean chronological age at baseline was 9.3 ± 0.9 years (range: 6.7 to 10.8). Additional study entry criteria included birth length SDS < -2 or < 3rd percentile for gestational age, and height SDS for chronological age < -2. Exclusion criteria included syndromal conditions (e.g., Turner syndrome), chronic disease (e.g., diabetes mellitus), and any active disease. All 35 patients completed the study. Mean height SDS increased from a baseline value of -2.7 (SD 0.5) to -1.5 (SD 0.6) after 2 years of Humatrope (somatropin rdna origin) treatment.
Last reviewed on RxList: 8/11/2010
This monograph has been modified to include the generic and brand name in many instances.
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