Safety of Somatropin (Recombinant Human Growth Hormone), Including Effects on Glucose Metabolism, in Adult Patients with Growth Hormone Deficiency: Interim Analysis of an Open-Label, Phase 3b, Multicenter Trial

Presentation Number: SUN 422
Date of Presentation: April 2nd, 2017

Mohita Kumar*1, Bradley Scott Miller2, Alberto M. Pereira3 and Nitin Agarwal4
1Ferring Pharmaceuticals Inc., Parsipanny, NJ, 2University of Minnesota Masonic Children's Hospital, Minneapolis, MN, 3Leiden University Medical Center, Leiden, Netherlands, 4Minnesota Epilepsy Group, P.A.; Children’s Minnesota, St. Paul, MN

Abstract

Somatropin is approved for the treatment of pediatric growth hormone deficiency (GHD) in the US. A phase 3b, open-label, multicenter, observational, noncomparative study, with planned follow-up for 5 years, was conducted to evaluate long-term efficacy and safety of somatropin in adults with GHD. This interim analysis of data from up to 24 months of treatment assessed safety, including effects on glucose metabolism. Patients aged ≥18 years with GHD confirmed by insulin-like growth factor 1 (IGF-1; ≤2 standard deviations [SD] of normal range for age/gender) or blood glucose (<2 mmol [36.0 mg/dL] on insulin tolerance test) and peak GH concentration (<9 mE/L on insulin tolerance, arginine, clonidine, or GHRH test) were enrolled and stratified by treatment experience. Somatropin was administered daily using the Zoma-Jet™ needle-free injector. New patients (no somatropin treatment in previous 12 mo) were initiated on somatropin 0.17 mg/day, and this dose was titrated to the minimum dose required to achieve an IGF-1 level within normal range; switch patients (previously treated) continued their current somatropin dose. Safety assessments included measures of glucose metabolism (mean changes from baseline in glycosylated hemoglobin [HbA1c] and fasting blood glucose [FBG] levels) and adverse events (AEs). Of 98 patients enrolled, 42 were new (mean age: 46.1 y) and 56 were switch (mean age: 46.3 y) patients; 1 patient did not receive treatment and was excluded. Baseline mean HbA1c levels did not differ between new (5.51%) and switch patients (5.46%). New patients had no significant changes in mean HbA1c levels over 24 months; switch patients had a significant decrease at 12 months (−2.08%; P=0.0087) but at no other timepoint. Mean HbA1c level at 24 months was 5.51% (change: −3.8%; P=NS) in new and 5.46% (change: −0.51%; P=NS) in switch patients. Baseline mean FBG levels did not differ between new (4.68 mmol/L [84.3 mg/dL]) and switch (4.96 mmol/L [89.4 mg/dL]) patients. New patients had significant increases in FBG levels beginning at 6 months (P=0.017); at 24 months, the mean level was 5.52 mmol/L (99.5 mg/dL; change: 12.06%; P=0.0313). Switch patients had no significant changes in FBG levels at any timepoint (mean at 24 mo: 4.98 mmol/L [89.7 mg/dL; change: 1.41%; P=NS]. AEs occurred in 20 (48.8%) new and 31 (55.4%) switch patients; most were mild or moderate. Nine patients had serious AEs, including 1 with 2 occurrences of inadequate control of pre-existing type 2 diabetes. AEs possibly/probably related to somatropin occurred in 21 patients; most were musculoskeletal/connective tissue or nervous system disorders. Somatropin was not associated with significant changes in HbA1c levels. FBG levels increased significantly beginning at 6 months in new patients. Overall, the safety profile was consistent with previous studies.

 

Disclosure: MK: Employee, Ferring Pharmaceuticals. BSM: Consultant, Ferring Pharmaceuticals. Nothing to Disclose: AMP, NA