Clinical trial NCT01128192: Somatostatin Analogue SOM230 (Pasireotide) in Healthy Male Volunteers
Official title: Phase 2, Double-Blind, Randomized, Single Center Trial to Assess the Mechanism(s) Responsible for the Effect of the Somatostatin Analogue SOM230 (Pasireotide) in Healthy Male Volunteers. Version #2 05/09/2009
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hyperglycemia
Lead sponsor: Veterans Medical Research Foundation
Sponsor class: OTHER
Collaborators: name: Veterans Medical Research Foundation
First posted: 2010-05-21
Enrollment: 45
Sex: MALE
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Eligibility criteria: Inclusion Criteria:

* Lean, healthy, non-diabetic male.

Exclusion Criteria:

* Family history of diabetes, BMI over 25.

Primary outcomes:
measure: Change in Insulin Basal Level
timeFrame: -30 min and -15 min on Day 2 and Day 9
measure: Change in Area Under the Curve (AUC) of Plasma Insulin Level 0-10mins, 10-180mins, 0-180mins During Hyperglycemic Clamp
timeFrame: 0-10 mins, 10-180 mins, 0-180 mins (Day 2 and Day 9)
measure: Change in Basal Endogenous Glucose Production (EGP)
timeFrame: Day 3 and Day 10
measure: Change in Low Dose % Endogenous Glucose Production (EGP) Inhibition
timeFrame: Day 3 and Day 10
measure: Change in High Dose % Endogenous Glucose Production (EGP) Inhibition
timeFrame: Day 3 and Day 10
measure: Change in Low-Dose Glucose Disposal Rate (GDR)
timeFrame: Day 3 and Day 10
measure: Change in High-Dose Glucose Disposal Rate (GDR)
timeFrame: Day 3 and Day 10
Secondary outcomes:
measure: Change in Fasting Plasma Glucose Level
timeFrame: -30 minutes on Day 1 and -30 minutes on Day 8
measure: Change in Area Under the Curve (AUC) of Plasma Glucose 0-30mins, 30-180mins, 0-180mins During Oral Glucose Tolerance Test (OGTT)
timeFrame: 0-30 mins, 30-180 mins, 0-180 mins (Day 1 and Day 8)
measure: Change Fasting Plasma Insulin Level
timeFrame: -30 minutes on Day 1 and -30 minutes on Day 8
measure: Change in Area Under the Curve (AUC) of Plasma Insulin 0-30mins, 30-180mins, 0-180mins During Oral Glucose Tolerance Test (OGTT)
timeFrame: 0-30 mins, 30-180 mins, 0-180 mins (Day 1 and Day 8)
Other outcomes:
Locations:
city: San Diego
country: United States
facility: CMR Center for Metabolic Research VASDHS
state: California
Study officials:
affiliation: Veterans Medical Research Foundation
name: Robert R Henry, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Henry RR, Ciaraldi TP, Armstrong D, Burke P, Ligueros-Saylan M, Mudaliar S. Hyperglycemia associated with pasireotide: results from a mechanistic study in healthy volunteers. J Clin Endocrinol Metab. 2013 Aug;98(8):3446-53. doi: 10.1210/jc.2013-1771. Epub 2013 Jun 3.