Somatostatin Analogue SOM230 (Pasireotide) in Healthy Male Volunteers
Somatostatin Analogue SOM230 (Pasireotide) in Healthy Male Volunteers
This clinical study will attempt to find out why in early studies in healthy volunteers,
 injections under the skin of pasireotide were associated with temporary increases in both
 fasting and post-meal glucose levels, along with possible increases in insulin and glucagon
 levels. Glucose refers to the amount of sugar in your blood and insulin and glucagon levels
 are amounts of hormones that lower and raise blood sugar.

 The purpose of the study is to evaluate the effects of pasireotide on insulin resistance and
 secretion. Insulin is a natural hormone made by the pancreas (a gland inside the abdomen)
 that controls the level of sugar in the blood. Insulin permits cells to use sugar for energy.
 Insulin resistance is the condition in which higher than normal amounts of insulin are
 necessary to allow the sugar to enter the cells. Insulin secretion refers to the amount of
 insulin produced by the body and released in the blood. Glucagon is a hormone (chemical
 substance produced by the pancreas gland in the body) which increases blood glucose.
This was a Phase 2, double-blinded, single-center study to assess the effects of pasireotide
 on insulin secretion and glucose metabolism in healthy male volunteers. Subjects who had
 given written informed consent and had been shown to satisfy the inclusion and exclusion
 criteria underwent baseline tests. An oral glucose tolerance test (OGTT) was administered on
 Day 1. If the OGTT results confirmed normal glycemia, the subject continued with baseline
 testing on Day 2 (2-step hyperglycemic clamp test with arginine stimulation) and Day 3
 (2-step hyperinsulinemic euglycemic clamp (HEC) test with [3-3H]glucose). Each subject was
 then randomized into 1 of 3 dose groups: 600 µg twice daily (bid) delivered subcutaneously ,
 pasireotide 900 µg bid delivered subcutaneously, or pasireotide 1200 µg bid delivered
 subcutaneously. Subcutaneous injections of pasireotide were given twice daily from Days 3-10
 (for 8 consecutive days, starting from the evening of Day 3 and up to the morning injection
 on Day 10). On Study Days 8-10, the last 3 days of treatment with the pasireotide injections,
 the tests performed at Baseline (ie, the OGTT; the 2-step hyperglycemic clamp test with
 arginine stimulation; and the 2-step HEC test with [3-3H] glucose) were repeated. Subjects
 returned for a post-study safety follow-up visit 5 to 7 days after the last injection of the
 study drug and an H&P and safety labs (including a fasting glucose level) was performed. In
 addition, depending on subject convenience, a 3rd OGTT was either performed on this visit or
 was performed on another occasion convenient for subjects, in order to confirm that subjects'
 OGTT status had returned to baseline levels.

 This additional post-study OGTT was added in a protocol amendment. Those subjects who
 completed the clinical trial and the follow-up visit before the amendment was approved were
 contacted and asked to return for another follow-up visit. The optional post-study OGTT was
 voluntary and subjects could choose not to participate. In order to reduce the severity of
 gastrointestinal adverse events (AEs), the protocol was amended (while keeping the blind
 intact) on 08 December 2009 to discontinue the pasireotide 1200 µg bid arm. The randomization
 scheme was subsequently adjusted to assign subjects in a 1:1 ratio to the 2 remaining arms:
 pasireotide 600 µg bid and pasireotide 900 µg bid.
Inclusion Criteria:

 -  Lean, healthy, non-diabetic male.

 Exclusion Criteria:

 -  Family history of diabetes, BMI over 25.