GENOTROPIN® somatropin [rDNA origin] for injection Clinical Studies

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Prescribing Information

GENOTROPIN^® (somatropin [rDNA origin] for injection)
Clinical Studies


	Return to the GENOTROPIN Product Center

Adult Growth Hormone Deficiency (GHD)
GENOTROPIN lyophilized powder was compared with placebo in six randomized clinical trials involving a total of 172 adult GHD patients. These trials included a 6-month double-blind treatment period, during which 85 patients received GENOTROPIN and 87 patients received placebo, followed by an open-label treatment period in which participating patients received GENOTROPIN for up to a total of 24 months. GENOTROPIN was administered as a daily SC injection at a dose of 0.04 mg/kg/week for the first month of treatment and 0.08 mg/kg/week for subsequent months.

Beneficial changes in body composition were observed at the end of the 6-month treatment period for the patients receiving GENOTROPIN as compared with the placebo patients. Lean body mass, total body water, and lean/fat ratio increased while total body fat mass and waist circumference decreased. These effects on body composition were maintained when treatment was continued beyond 6 months. Bone mineral density declined after 6 months of treatment but returned to baseline values after 12 months of treatment.

Prader-Willi Syndrome (PWS)
The safety and efficacy of GENOTROPIN in the treatment of pediatric patients with Prader-Willi syndrome (PWS) were evaluated in two randomized, open-label, controlled clinical trials. Patients received either GENOTROPIN or no treatment for the first year of the studies, while all patients received GENOTROPIN during the second year. GENOTROPIN was administered as a daily SC injection, and the dose was calculated for each patient every 3 months. In Study 1, the treatment group received GENOTROPIN at a dose of 0.24 mg/kg/week during the entire study. During the second year, the control group received GENOTROPIN at a dose of 0.48 mg/kg/week. In Study 2, the treatment group received GENOTROPIN at a dose of 0.36 mg/kg/week during the entire study. During the second year, the control group received GENOTROPIN at a dose of 0.36 mg/kg/week.

Patients who received GENOTROPIN showed significant increases in linear growth during the first year of study, compared with patients who received no treatment (see Table 3). Linear growth continued to increase in the second year, when both groups received treatment with GENOTROPIN.

Table 3 Efficacy of GENOTROPIN in Pediatric Patients with Prader-Willi Syndrome (Mean ± SD)

Changes in body composition were also observed in the patients receiving GENOTROPIN (see Table 4). These changes included a decrease in the amount of fat mass, and increases in the amount of lean body mass and the ratio of lean-to-fat tissue, while changes in body weight were similar to those seen in patients who received no treatment. Treatment with GENOTROPIN did not accelerate bone age, compared with patients who received no treatment.

Table 4 Effect of GENOTROPIN on Body Composition in Pediatric Patients with Prader-Willi Syndrome (Mean ± SD)

SGA

Pediatric Patients Born Small for Gestational Age (SGA) Who Fail to Manifest Catch-up Growth by Age 2
The safety and efficacy of GENOTROPIN in the treatment of children born small for gestational age (SGA) were evaluated in 4 randomized, open-label, controlled clinical trials. Patients (age range of 2 to 8 years) were observed for 12 months before being randomized to receive either GENOTROPIN (two doses per study, most often 0.24 and 0.48 mg/kg/week) as a daily SC injection or no treatment for the first 24 months of the studies. After 24 months in the studies, all patients received GENOTROPIN.

Patients who received any dose of GENOTROPIN showed significant increases in growth during the first 24 months of study, compared with patients who received no treatment (see Table 5). Children receiving 0.48 mg/kg/week demonstrated a significant improvement in height standard deviation score (SDS) compared with children treated with 0.24 mg/kg/week. Both of these doses resulted in a slower but constant increase in growth between months 24 to 72 (data not shown).

Table 5 Efficacy of GENOTROPIN in Children Born Small for Gestational Age (Mean ± SD)

Turner Syndrome
Two randomized, open-label, clinical trials were conducted that evaluated the efficacy and safety of GENOTROPIN in Turner syndrome patients with short stature. Turner syndrome patients were treated with GENOTROPIN alone or GENOTROPIN plus adjunctive hormonal therapy (ethinylestradiol or oxandrolone). A total of 38 patients were treated with GENOTROPIN alone in the two studies. In Study 055, 22 patients were treated for 12 months, and in Study 092, 16 patients were treated for 12 months. Patients received GENOTROPIN at a dose between 0.13 to 0.33 mg/kg/week.

SDS for height velocity and height are expressed using either the Tanner (Study 055) or Sempé (Study 092) standards for age-matched normal children as well as the Ranke standard (both studies) for age-matched, untreated Turner syndrome patients. As seen in Table 5, height velocity SDS and height SDS values were smaller at baseline and after treatment with GENOTROPIN when the normative standards were utilized as opposed to the Turner syndrome standard.

Both studies demonstrated statistically significant increases from baseline in all of the linear growth variables (i.e., mean height velocity, height velocity SDS, and height SDS) after treatment with GENOTROPIN (see Table 6). The linear growth response was greater in Study 055 wherein patients were treated with a larger dose of GENOTROPIN.

Table 6 Growth Parameters (mean ± SD) after 12 Months of Treatment with GENOTROPIN in Pediatric Patients with Turner Syndrome in Two Open Label Studies

Idiopathic Short Stature
The long-term efficacy and safety of GENOTROPIN in patients with idiopathic short stature (ISS) were evaluated in one randomized, open-label, clinical trial that enrolled 177 children. Patients were enrolled on the basis of short stature, stimulated GH secretion > 10 ng/mL, and prepubertal status (criteria for idiopathic short stature were retrospectively applied and included 126 patients). All patients were observed for height progression for 12 months and were subsequently randomized to Genotropin or observation only and followed to final height. Two Genotropin doses were evaluated in this trial: 0.23 mg/kg/week (0.033 mg/kg/day) and 0.47 mg/kg/week (0.067 mg/kg/day). Baseline patient characteristics for the ISS patients who remained prepubertal at randomization (n= 105) were: mean (± SD): chronological age 11.4 (1.3) years, height SDS -2.4 (0.4), height velocity SDS -1.1 (0.8), and height velocity 4.4 (0.9) cm/yr, IGF-1 SDS -0.8 (1.4). Patients were treated for a median duration of 5.7 years. Results for final height SDS are displayed by treatment arm in Table 7. GENOTROPIN therapy improved final height in ISS children relative to untreated controls. The observed mean gain in final height was 9.8 cm for females and 5.0 cm for males for both doses combined compared to untreated control subjects. A height gain of 1 SDS was observed in 10 % of untreated subjects, 50% of subjects receiving 0.23 mg/kg/week and 69% of subjects receiving 0.47 mg/kg/week

Table 7. Final height SDS results for pre-pubertal patients with ISS^*

PRINTER-FRIENDLY

GENOTROPIN Safety Information

Important Safety Information

Contraindications

Somatropin should not be used for growth promotion in pediatric patients with closed epiphyses.

Somatropin is contraindicated in patients with active proliferative or severe nonproliferative diabetic retinopathy.

Somatropin is contraindicated in patients with active malignancy. Because growth hormone deficiency may be a sign of pituitary or other brain tumors, the presence of such tumors should be ruled out before treatment is initiated. Somatropin should not be used in patients with any evidence of progression or recurrence of an underlying intracranial tumor.

Somatropin should not be used to treat patients with acute critical illness due to complications from surgery, trauma, or respiratory failure; the safety of continuing somatropin treatment for approved uses in patients who develop these illnesses has not been established.

Somatropin is contraindicated in patients with Prader-Willi syndrome who are severely obese or have respiratory impairment (see WARNINGS).

Additional Safety Information

Monitor patients with glucose intolerance closely; dosage of antihyperglycemic drug may need to be adjusted. Monitor carefully if somatropin is administered in combination with glucocorticoid therapy and/or other drugs metabolized by the CP450 pathway.

In childhood cancer survivors, an increased risk of a second neoplasm, in particular meningiomas, has been reported in patients treated with somatropin after their first neoplasm, particularly those who were treated with cranial radiation.

Intracranial hypertension (IH) has been reported in a small number of patients treated with somatropin. If papilledema is observed during somatropin treatment, treatment should be stopped and reassessed. Patients with Turner syndrome and Prader-Willi syndrome may be at increased risk for the development of IH.

Patients treated with somatropin should have periodic thyroid function tests and thyroid hormone replacement therapy should be initiated or adjusted when indicated.

In patients with multiple hormone deficiencies, standard hormonal replacement therapy should be monitored closely when somatropin therapy is administered.

Progression of scoliosis can occur in patients who experience rapid growth. Patients with scoliosis should be monitored for manifestation or progression during GH therapy.

Slipped capital femoral epiphyses may occur more frequently in patients with endocrine disorders or in patients undergoing rapid growth.

Somatropin should be used during pregnancy only if clearly needed and with caution in nursing mothers because it is not known whether somatropin is excreted in human milk.

In clinical trials with GENOTROPIN in pediatric GHD patients, the following events were reported infrequently: injection site reactions, including pain or burning associated with the injection, fibrosis, nodules, rash, inflammation, pigmentation, or bleeding; lipoatrophy; headache; hematuria; hypothyroidism; and mild hyperglycemia.

In clinical studies of 273 pediatric patients born SGA treated with GENOTROPIN, the following clinically significant events were reported: mild transient hyperglycemia; 1 patient with benign intracranial hypertension; 2 patients with central precocious puberty; 2 patients with jaw prominence; and several patients with aggravation of preexisting scoliosis, injection site reactions, and self-limited progression of pigmented nevi. Anti-hGH antibodies were not detected in any of the patients treated with GENOTROPIN.

Deaths have been reported with the use of a growth hormone in pediatric PWS patients with severe obesity, history of upper airway obstruction or sleep apnea, and/or unidentified respiratory infection. Therefore, all patients with PWS should be evaluated and monitored for signs of upper airway obstruction, sleep apnea, and respiratory infections, and have effective weight control.

In clinical trials with GENOTROPIN in pediatric patients with PWS, the following drug-related events were reported: edema, aggressiveness, arthralgia, benign intracranial hypertension, hair loss, headache, and myalgia.

Somatropin may increase the occurrence of otitis media in Turner syndrome patients.

In 2 clinical studies with GENOTROPIN in pediatric patients with Turner syndrome, the most frequently reported adverse events were respiratory illnesses (influenza, tonsillitis, otitis, sinusitis), joint pain, and urinary tract infection. The only treatment-related adverse event that occurred in more than 1 patient was joint pain.

In 2 clinical studies with GENOTROPIN in pediatric patients with ISS, the most commonly encountered adverse events included upper respiratory tract infections, influenza, tonsillitis, nasopharyngitis, gastroenteritis, headaches, increased appetite, pyrexia, fracture, altered mood, and arthralgia.

In clinical trials with GENOTROPIN adults with GHD, the majority of side effects were symptoms of fluid retention, including peripheral swelling/edema, arthralgia, pain and stiffness of the extremities, myalgia, paresthesia, and hypoesthesia.

In women on oral estrogen replacement, a larger dose of somatropin may be required to achieve the defined treatment goal (see DOSAGE AND ADMINISTRATION).

Elderly patients may be more sensitive to the action of somatropin, and therefore may be more prone to develop adverse reactions.

The cartridges of GENOTROPIN contain m-Cresol and should not be used by patients with a known sensitivity to this preservative.

Subcutaneous injection of somatropin at the same site repeatedly may result in tissue atrophy. This can be avoided by rotating the injection site.

Health care providers should supervise the first injection and provide appropriate training and instruction for the proper use of all devices for GENOTROPIN.

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Please see full prescribing information.

GENOTROPIN ^®somatropin [rDNA origin] for injection

genotropin_safety_information.htm

Full Prescribing Information

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