Debio 4126, a new 3-month octreotide formulation, provides sustained release of octreotide, as well as enhanced bioavailability and similar suppression of insulin-like growth factor 1 (IGF-1), compared to monthly Sandostatin LAR in healthy volunteers - interim results

A. Bellon*^a (Dr), J. Klein^b (Dr), D. Spaggiari^a (Dr), M. Marquardt^a (Mr), F. Frérart^c (Dr), D. Rechavi-Robinson^a (Dr), A. Marguerettaz^d (Dr), B. Plagès^d (Dr), L. Merinat^a (Ms), C. Beden^a (Dr), B. Ducrey^a (Dr), B. Gavillet^a (Dr), L. Tauchmanova^a (Dr)

^a Debiopharm International, Lausanne, SWITZERLAND ; ^b SGS Belgium - Health & Nutrition, Edegem, BELGIUM ; ^c SGS Belgium - Health & Nutrition, Mechelen, BELGIUM ; ^d Debiopharm Research & Manufacturing, Martigny, SWITZERLAND

* Anne.Bellon@debiopharm.com

INTRODUCTION

An open-label, active-controlled, parallel-group, single site Phase 1 study with adaptive design is ongoing to characterize the pharmacokinetics (PK), pharmacodynamics (PD), safety and tolerability of a single administration of a 3-month sustained-release octreotide formulation, Debio 4126, in healthy volunteers.

METHODS

After administration of 200µg octreotide immediate-release, subjects were enrolled in 1 of 7 cohorts to receive a single administration of 1 of 2 Debio 4126 formulations, either intramuscularly or subcutaneously, at 30 or 90mg, in 1 of 2 different solvents (aqueous, lipidic), or 3 monthly injections of 30mg Sandostatin LAR. The cohorts enrolled between 7 and 15 subjects.

RESULTS

Ninety subjects completed at least 12 weeks of follow-up. Interim results show that for the 6 Debio 4126 cohorts, octreotide levels were sustained over 12 weeks.

As with other octreotide-containing sustained-release products, a short drug burst was observed in all Debio 4126 cohorts, followed by a valley and a plateau phase, reached at around Day 28. After a 90mg Debio 4126 dose, octreotide levels stayed above the threshold of 1 ng/mL, considered therapeutic in patients, until the end of the dosing interval (12 weeks). Exposure over 12 weeks was higher with 90mg Debio 4126 than with 3 monthly injections of 30mg Sandostatin LAR.

A reduction in IGF-1 levels was seen in all cohorts over 12 weeks and was comparable between the 90mg Debio 4126 dose and 3 monthly 30mg Sandostatin LAR doses. PK of Debio 4126 was dose-proportional within the dosing range and the 90mg dose was associated with a higher IGF-1 reduction. No new safety information was reported compared to Sandostatin LAR regardless of Debio 4126 combination used. Most frequent adverse reactions were gastrointestinal disorders, biliary disorders and injection site reactions, these were transient and manageable.

DISCUSSION

Debio 4126 administered in healthy volunteers had a safety profile consistent with that of Sandostatin LAR and IGF-1 reduction was maintained over 12 weeks. Bioavailability appeared higher after Debio 4126 administration. Debio 4126 provides sustained release of octreotide over the dosing interval of 12 weeks at a level considered adequate for treatment of patients with acromegaly.

The author has declared the following conflict(s) of interest:

AB, DS, MM, DRR, AM, BP, LM, CB, BD, BG are employees of Debiopharm

LT was an employee of Debiopharm at the time of the study conduct

JK and FF received compensation from Debiopharm for the work performed on the study