Acromegaly; lanreotide prolonged-release formulation; maximum tolerated dose; pharmacodynamics; pharmacokinetics; somatostatin analogues; Peptides, Cyclic; lanreotide; Human Growth Hormone; Somatostatin; Humans; Peptides, Cyclic/adverse effects; Somatostatin/adverse effects; Somatostatin/analogs & derivatives; Acromegaly/drug therapy; Human Growth Hormone/adverse effects; Pharmacology, Toxicology and Pharmaceutics (all); Pharmacology (medical); General Pharmacology, Toxicology and Pharmaceutics; General Medicine
Abstract :
[en] BACKGROUND: Patients with acromegaly require lifelong medication; a longer dosing interval would reduce treatment burden. This study investigated the pharmacokinetics, pharmacodynamics and safety profile of a new prolonged-release formulation (PRF) of lanreotide every 12 weeks.
RESEARCH DESIGN AND METHODS: In this multicenter, open-label, dose-ascending study, cohorts of nine patients with acromegaly received single doses of lanreotide PRF according to a 3 + 3 + 3 scheme in order to determine the maximum tolerated dose (MTD). Following a 12-week treatment period, patients were followed up for a further 12 weeks. Serum lanreotide, insulin-like growth factor-1 and growth hormone concentrations were analyzed. Adverse events were monitored throughout the study.
RESULTS: The MTD was not reached. Peak lanreotide serum concentration values were similar in all cohorts, whereas area under the curve values from time zero to 85 days increased but were not dose-proportional. The apparent elimination half-life of lanreotide PRF was approximately 54-63 days, in line with the expected prolonged-release characteristics. Growth hormone and insulin-like growth factor-1 levels were generally stable.
CONCLUSIONS: The safety and tolerability profile was in-line with the known safety profile of lanreotide autogel. Lanreotide PRF was well tolerated and the pharmacokinetic profile suggests that a dosing interval of 12 weeks could be achievable.
CLINICAL TRIAL REGISTRATION: www.clinicaltrials.gov identifier is NCT02396953; EudraCT 2014-002389-62.
Disciplines :
Endocrinology, metabolism & nutrition
Author, co-author :
Neggers, Sebastian; Medicine and Endocrinology, Erasmus University Medical Center, Erasmus University Rotterdam, Rotterdam, Netherlands
Badiu, Corin; Department of Endocrinology National Institute of Endocrinology, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
Biagetti, Betina ; Department of Endocrinology, Hospital Universitari Vall d'Hebron, Barcelona, Spain
Durand-Gasselin, Lucie; Clinical Pharmacokinetics & Pharmacometrics, Ipsen Innovation, Les Ulis, France
Petit, Anne; Drug Product Development & Industrialization, Ipsen PharmSciences, Dreux, France
Petrossians, Patrick ; Centre Hospitalier Universitaire de Liège - CHU > > Service d'endocrinologie clinique
Regnault, Benjamin; Ipsen, Boulogne-Billancourt, France
Rich, David; Global Development, Rare Diseases, Ipsen BioInnovation, Abingdon, UK
Shafigullina, Zulfiya; Department of Endocrinology, North-Western State Medical University Named after I.I Mechnikov, St. Petersburg, Russia
Shustov, Sergey; Department of Endocrinology, North-Western State Medical University Named after I.I Mechnikov, St. Petersburg, Russia
Vydrych, Anna; Department of Endocrinology, North-Western State Medical University Named after I.I Mechnikov, St. Petersburg, Russia
Language :
English
Title :
Pharmacological and safety profile of a prolonged-release lanreotide formulation in acromegaly.
S Neggers has received grants from Pfizer, Novartis and Ipsen and speaker fees from Pfizer and Ipsen. C Badiu has received speaker fees from Pfizer and Ipsen. B Biagetti has received grants from Pfizer and speaker fees from Pfizer, Novartis and Ipsen. L Durand-Gasselin, A Petit, B Regnault and D Rich are employees of Ipsen. P Petrossians has received grants from Ipsen and speaker and consultation fees from Ipsen, Pfizer, and Novartis. ZS, SS and AV have nothing to declare. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
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