PMID- 22383336
OWN - NLM
STAT- MEDLINE
DCOM- 20120625
LR  - 20220309
IS  - 1479-683X (Electronic)
IS  - 0804-4643 (Linking)
VI  - 166
IP  - 5
DP  - 2012 May
TI  - Safety, tolerability, and pharmacokinetics of a single dose of pasireotide 
      long-acting release in healthy volunteers: a single-center Phase I study.
PG  - 821-8
LID - 10.1530/EJE-11-0773 [doi]
AB  - OBJECTIVE: This study was conducted to evaluate the safety, tolerability, and 
      pharmacokinetics (PKs) of different doses of a long-acting release (LAR) 
      formulation of pasireotide in healthy subjects. DESIGN: Single-center, 
      open-label, randomized Phase I study. METHODS: Twelve healthy male subjects 
      received a single s.c. dose of pasireotide 300 mug followed by a washout period of 
      7 days (or at least 5 days), before receiving an i.m. injection of pasireotide 
      -LAR 40 mg (n=5) or 60 mg (n=7). Assessments included adverse events (AEs), PKs, 
      and glucose, insulin, glucagon, and HbA1c levels. RESULTS: Pasireotide LAR showed 
      an extended-release profile over 1 month with two concentration peaks observed 1 
      and around 20 days after injection. The area under curve exposure of pasireotide 
      LAR was dose proportional when the dose levels were compared, and the 
      bioavailability of the LAR relative to the s.c. formulation was complete. 
      Administration of pasireotide LAR resulted in an increase in fasting and 
      postprandial glucose levels; however, an attenuation of the hyperglycemic effect 
      was observed after 15 days. The most frequently reported AEs were 
      mild-to-moderate diarrhea, abdominal pain, and flatulence. Only gastrointestinal 
      AEs and injection site reactions were suspected to be drug related. CONCLUSIONS: 
      Pasireotide LAR was generally well tolerated with mostly mild AEs at doses up to 
      60 mg and showed a dose-proportional, extended-release profile in healthy 
      subjects. Based on the favorable results of this study, further clinical 
      development of pasireotide LAR is under way, which will give insight into the 
      PKs, efficacy, and safety of pasireotide LAR in patient populations.
FAU - Dietrich, Hartmut
AU  - Dietrich H
AD  - ClinPharmCologne, Neurather Ring 1, D-51063 Koln, Germany. 
      hartmut.dietrich@clinpharmcologne.de
FAU - Hu, Ke
AU  - Hu K
FAU - Ruffin, Matthieu
AU  - Ruffin M
FAU - Song, Dongweon
AU  - Song D
FAU - Bouillaud, Emmanuel
AU  - Bouillaud E
FAU - Wang, Yanfeng
AU  - Wang Y
FAU - Hasskarl, Jens
AU  - Hasskarl J
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Comparative Study
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20120301
PL  - England
TA  - Eur J Endocrinol
JT  - European journal of endocrinology
JID - 9423848
RN  - 0 (Delayed-Action Preparations)
RN  - 51110-01-1 (Somatostatin)
RN  - 98H1T17066 (pasireotide)
SB  - IM
MH  - Abdominal Pain/blood/chemically induced
MH  - Adolescent
MH  - Adult
MH  - Delayed-Action Preparations/administration & dosage/adverse 
      effects/pharmacokinetics
MH  - Diarrhea/blood/chemically induced
MH  - Humans
MH  - Male
MH  - Somatostatin/administration & dosage/adverse effects/*analogs & 
      derivatives/pharmacokinetics
MH  - Young Adult
EDAT- 2012/03/03 06:00
MHDA- 2012/06/26 06:00
CRDT- 2012/03/03 06:00
PHST- 2012/03/03 06:00 [entrez]
PHST- 2012/03/03 06:00 [pubmed]
PHST- 2012/06/26 06:00 [medline]
AID - EJE-11-0773 [pii]
AID - 10.1530/EJE-11-0773 [doi]
PST - ppublish
SO  - Eur J Endocrinol. 2012 May;166(5):821-8. doi: 10.1530/EJE-11-0773. Epub 2012 Mar 
      1.