Rapid and sustained reduction of serum growth hormone and insulin-like growth factor-1 in patients with acromegaly receiving lanreotide Autogel therapy: a randomized, placebo-controlled, multicenter study with a 52 week open extension

Shlomo Melmed, David Cook, Jochen Schopohl, Miklos I Goth, Karen S L Lam, Josef Marek, Shlomo Melmed, David Cook, Jochen Schopohl, Miklos I Goth, Karen S L Lam, Josef Marek

Abstract

The study was designed to evaluate the long-term efficacy and safety of the 28-day prolonged-release Autogel formulation of the somatostatin analogue lanreotide (Lan-Autogel) in unselected patients with acromegaly. The study comprised four phases: washout; a double-blind comparison with placebo, at a single randomized dose (60, 90 or 120 mg) of Lan-Autogel; a single-blind, fixed-dose phase for four injections (placebo group was re-allocated to active treatment); and eight injections with doses tailored according to biochemical response. Serum samples were assessed for growth hormone (GH) and insulin-like growth factor-1 (IGF-1) levels, at weeks 4, 13, 14, 15, 16, 32 and 52. 108 patients were enrolled and 99 completed 52 weeks' treatment. Four weeks after the first injection, serum GH levels decreased by >50% from baseline in 63% of patients receiving Lan-Autogel compared with 0% receiving placebo (P < 0.001). After four injections, 72% of patients had a >50% reduction in GH levels; 49% patients achieved GH levels < or = 2.5 ng/ml; 54% had normalized IGF-1; and 38% achieved the combined criterion of GH level < or = 2.5 ng/ml and normalized IGF-1. The corresponding proportions by week 52 were 82, 54, 59 and 43%, respectively. In patients not requiring dose escalation to 120 mg, 85% achieved biochemical control (combined criterion). Treatment was well tolerated by all patients. In conclusion, Lan-Autogel was effective in controlling GH and IGF-1 hypersecretion in patients with acromegaly and showed a rapid onset of action.

Figures

Fig. 1
Fig. 1
Study design showing the dose-titration schema. Dose-titration was based on serum levels of growth hormone (GH; ng/ml) and whether insulin-like growth factor-1 (IGF-1) levels were in the age-adjusted normalized range (N); A = GH > 2.5 or GH ≤ 2.5 + IGF-1 > N; B = GH ≤ 2.5 + IGF-1 ≤ N; C = 1 < GH ≤ 2.5 + IGF-1 ≤ N; D = GH ≤ 1 + IGF-1 ≤ N; E = GH > 1 or GH ≤ 1 + IGF-1 > N. *Only if 60 mg originally
Fig. 2
Fig. 2
Patient flow through the study
Fig. 3
Fig. 3
Proportion of patients with control of growth hormone (GH) and insulin-like growth factor-1 (IGF-1) A at weeks 4 and 16 by dose at randomization, and B at week 52, by last-dose administered
Fig. 4
Fig. 4
Mean serum A growth hormone (GH) and B insulin-like growth factor-1 (IGF-1) levels over time on study by last-dose administered. LVA last value available

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