Somatostatin Analogue SOM230 (Pasireotide) in Healthy Male Volunteers
Condition: Hyperglycemia
MeSH terms: Hyperglycemia
Study type: Interventional
Phase: Phase 2

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): pasireotide
Intervention type(s): Drug
Intervention description(s): Pasireotide 600 μg (batch number Y050DE) or 900 μg bid (batch number Y1270908) for subcutaneous injection. Placebo (batch number Y069HC) for subcutaneous injection.
Other intervention name(s): SOM230
Intervention MeSH terms: Pasireotide
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Outcomes Assessor)
Primary purpose: Treatment