OBJECTIVE: The relative bioavailability of two highly concentrated (12 IU/ml) formulations of biosynthetic human growth hormone (GH) administered subcutaneously was compared. DESIGN: A randomized, crossover study. Conventional GH therapy was withdrawn 72 hours before each study period. There was a washout period of at least four weeks between the study periods. SETTING:Participants were recruited from an outpatient clinic and were hospitalized during the two study periods. PATIENTS: Fourteen GH-deficient patients (mean age 25.2 y, range 14-54). One patient was excluded from data analysis because of signs of endogenous GH secretion. INTERVENTIONS: At the start of each study period, GH 3 IU/m2 was injected subcutaneously. The two formulations, PenFill and PenSet, differ in the buffers used and in the relative content of mannitol and glycine. Serum profiles of GH were monitored frequently for 24 hours. Samples were taken every 30 minutes for 6 hours and then hourly. MAIN OUTCOME MEASURES: Bioavailability (F) and absorption dynamics of human GH were measured. The relative absorption fractions estimated from the areas under the individual serum concentration curves from 0 to 24 hours, and the observed time (Tmax) to reach the maximum concentration (Cmax) were determined. Short-term metabolic effects of GH on insulin-like growth factor (IGF-I), glucose, and insulin were determined. RESULTS: The geometric mean (SD) of F was 0.910 (1,236). The 90 percent confidence interval was 0.819-1.010. Mean (+/- SD) of Cmax was 12.65 +/- 5.89 and 12.58 +/- 4.40 ng/mL for PenFill and PenSet, respectively. Corresponding values for Tmax were 5.49 +/- 1.55 and 5.89 +/- 1.79 hours for PenFill and PenSet, respectively. There was a considerable interindividual variation, but the relative absorption fraction did not significantly differ from 1 (p = 0.13). Neither Cmax (p = 0.74) nor Tmax (p = 0.58) of the two formulations was significantly different. Injection of the two formulations induced similar increments in serum IFG-I (p = 0.48). Serum insulin and blood glucose concentrations were not significantly different. CONCLUSIONS: There is no significant difference between the absorption kinetics and short-term metabolic effects of these two highly concentrated formulations of biosynthetic GH. The two formulations are bioequivalent.
RCT Entities:
OBJECTIVE: The relative bioavailability of two highly concentrated (12 IU/ml) formulations of biosynthetic humangrowth hormone (GH) administered subcutaneously was compared. DESIGN: A randomized, crossover study. Conventional GH therapy was withdrawn 72 hours before each study period. There was a washout period of at least four weeks between the study periods. SETTING:Participants were recruited from an outpatient clinic and were hospitalized during the two study periods. PATIENTS: Fourteen GH-deficientpatients (mean age 25.2 y, range 14-54). One patient was excluded from data analysis because of signs of endogenous GH secretion. INTERVENTIONS: At the start of each study period, GH 3 IU/m2 was injected subcutaneously. The two formulations, PenFill and PenSet, differ in the buffers used and in the relative content of mannitol and glycine. Serum profiles of GH were monitored frequently for 24 hours. Samples were taken every 30 minutes for 6 hours and then hourly. MAIN OUTCOME MEASURES: Bioavailability (F) and absorption dynamics of human GH were measured. The relative absorption fractions estimated from the areas under the individual serum concentration curves from 0 to 24 hours, and the observed time (Tmax) to reach the maximum concentration (Cmax) were determined. Short-term metabolic effects of GH on insulin-like growth factor (IGF-I), glucose, and insulin were determined. RESULTS: The geometric mean (SD) of F was 0.910 (1,236). The 90 percent confidence interval was 0.819-1.010. Mean (+/- SD) of Cmax was 12.65 +/- 5.89 and 12.58 +/- 4.40 ng/mL for PenFill and PenSet, respectively. Corresponding values for Tmax were 5.49 +/- 1.55 and 5.89 +/- 1.79 hours for PenFill and PenSet, respectively. There was a considerable interindividual variation, but the relative absorption fraction did not significantly differ from 1 (p = 0.13). Neither Cmax (p = 0.74) nor Tmax (p = 0.58) of the two formulations was significantly different. Injection of the two formulations induced similar increments in serum IFG-I (p = 0.48). Serum insulin and blood glucose concentrations were not significantly different. CONCLUSIONS: There is no significant difference between the absorption kinetics and short-term metabolic effects of these two highly concentrated formulations of biosynthetic GH. The two formulations are bioequivalent.