Geref Pharmacology, Pharmacokinetics, Studies, Metabolism - Sermorelin

Geref Pharmacology, Pharmacokinetics, Studies, Metabolism - Sermorelin

CLINICAL PHARMACOLOGY

Geref® (sermorelin acetate for injection) increases plasma growth hormone (GH) concentration by stimulating the pituitary gland to release GH. Geref® is similar to the native hormone (GRF [1-44]-NH ₂ ) in its ability to stimulate GH secretion in humans.

Pharmacokinetics

Absorption

In subcutaneous administration of 2 mg sermorelin to 12 normal volunteers, peak concentrations of sermorelin were reached in 5-20 minutes. The mean absolute bioavailability after SC administration is about 6%.

Distribution

After intravenous administration of 0.25-1.0 mg Geref® to 12 normal volunteers, the mean volume of distribution ranged between 23.7-25.8 liters.

Metabolism

No metabolism studies have been performed in humans.

Elimination

Sermorelin is rapidly cleared from the circulation, with clearance values in adults ranging between 2.4-2.8 L/min. The halflife of Geref® is short, 11-12 minutes after either intravenous or subcutaneous administration.

Special Populations

Gender/Age:  No gender data are available in pediatric patients. In normal adults, the clearance of sermorelin in men and women is similar. No age data are available.

Renal/Hepatic Insufficiency:  No data are available.

CLINICAL STUDIES

In one multicenter, open-label clinical study in prepubertal children with idiopathic growth hormone deficiency, 110 children were administered Geref® 0.03 mg (30 mcg) per kg per day by subcutaneous injection. Fifty-six patients were evaluable for efficacy at 12 months. Fifty-four patients were considered unevaluable: 24 for eligibility criteria violations; 10 for protocol discontinuation criteria and 20 for failing to satisfy the efficacy criteria at 6 months for continuing in the study. Fifty-six of all 110 patients and 47 of 56 patients in the evaluable patient subset who initiated and continued with Geref® therapy up to 12 months demonstrated an increase of 2 cm/year or more over the baseline height velocity (HV). For the 56 patients in the evaluable patient subset, mean height velocity (± SD) increased from 4.1 ± 1.0 cm/year at baseline to 8.0 ± 1.5 cm/year at 6 months and 7.2 ± 1.3 cm/year at 12 months, an increase of 3.1 ± 1.4 cm/year (p = 0.0001). Mean height standard deviation score (± SD) increased from -3.71 ± 0.92 at baseline to -3.21 ± 0.91 at 12 months, an increase of 0.50 ± 0.23 over the 12 month period (p = 0.0001). Mean changes in bone age at 12 months were proportional to gains in height (1.04 ± 0.58, (DELTA)BA/(DELTA)HA, n=42).