Octreotide s.c. depot provides sustained octreotide bioavailability and similar IGF-1 suppression to octreotide LAR in healthy volunteers

Br J Clin Pharmacol. 2015 Sep;80(3):460-72. doi: 10.1111/bcp.12698. Epub 2015 Aug 6.

Abstract

Aims: The aim was to assess the pharmacokinetics, pharmacodynamics, safety and tolerability of octreotide subcutaneous (s.c.) depot, a novel octreotide formulation.

Methods: This was a phase I, randomized, open label study. After a single dose of octreotide immediate release (IR) 200 µg, subjects were randomized to one of eight groups to receive three monthly injections of octreotide s.c. depot A 10, 20 or 30 mg, B 30 mg, C 10, 20 or 30 mg or long acting octreotide (octreotide LAR) 30 mg.

Results: One hundred and twenty-two subjects were randomized. For all depot variants, onset of octreotide release was rapid and sustained for up to 4 weeks. The relative octreotide bioavailability of depot variants vs. octreotide IR ranged from 0.68 (90% confidence interval [CI] 0.61, 0.76) to 0.91 (90% CI 0.81, 1.02) and, vs. octreotide LAR, was approximately four- to five-fold greater: 3.97 (90% CI 3.35, 4.71) to 5.27 ng ml(-1) h (90% CI 4.43, 6.27). All depot variants showed relatively rapid initial reductions of insulin-like growth factor 1 (IGF-1) compared with octreotide LAR. A trend of octreotide dose dependence was also indicated from the plasma concentrations and suppression of IGF-1. Maximum inhibition of IGF-1 at steady-state was highest for depot B and C. All depot treatments were well tolerated. The most frequent adverse events were gastrointestinal related.

Conclusions: Octreotide s.c. depot provides greater octreotide bioavailability with a more rapid onset and stronger suppression of IGF-1 than octreotide LAR in healthy volunteers.

Keywords: FluidCrystal®; depot; formulation; injection; octreotide; subcutaneous.

Publication types

  • Clinical Trial, Phase I
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antineoplastic Agents, Hormonal / administration & dosage
  • Antineoplastic Agents, Hormonal / adverse effects
  • Antineoplastic Agents, Hormonal / pharmacokinetics*
  • Antineoplastic Agents, Hormonal / pharmacology*
  • Biological Availability
  • Delayed-Action Preparations
  • Dose-Response Relationship, Drug
  • Drug Liberation
  • Female
  • Humans
  • Injections, Subcutaneous
  • Insulin-Like Growth Factor I / antagonists & inhibitors*
  • Male
  • Middle Aged
  • Octreotide / administration & dosage
  • Octreotide / adverse effects
  • Octreotide / pharmacokinetics*
  • Octreotide / pharmacology*
  • Young Adult

Substances

  • Antineoplastic Agents, Hormonal
  • Delayed-Action Preparations
  • Insulin-Like Growth Factor I
  • Octreotide