Somatostatin Analogue SOM230 (Pasireotide) in Healthy Male Volunteers

NCT ID: NCT01128192

Last Updated: 2014-12-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 45 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-08-31
• Study Completion Date: 2010-04-30

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.

Conditions

Hyperglycemia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Pasireotide 600 µg sc bid

n=19. Pasireotide 600 µg sc bid

Group Type: EXPERIMENTAL

pasireotide

Intervention Type: DRUG

Pasireotide 600 μg (batch number Y050DE) or 900 μg bid (batch number Y1270908) for subcutaneous injection. Placebo (batch number Y069HC) for subcutaneous injection.

Pasireotide 900 µg sc bid

n=19. Pasireotide 900 µg sc bid

Group Type: EXPERIMENTAL

pasireotide

Intervention Type: DRUG

Pasireotide 600 μg (batch number Y050DE) or 900 μg bid (batch number Y1270908) for subcutaneous injection. Placebo (batch number Y069HC) for subcutaneous injection.

Pasireotide 1200 µg sc bid

n=7. Due to increased severity of gastro-intestinal side effects, this arm was discontinued. These participants were only included in the safety analysis.

Group Type: EXPERIMENTAL

pasireotide

Intervention Type: DRUG

Pasireotide 600 μg (batch number Y050DE) or 900 μg bid (batch number Y1270908) for subcutaneous injection. Placebo (batch number Y069HC) for subcutaneous injection.

Interventions

pasireotide

Pasireotide 600 μg (batch number Y050DE) or 900 μg bid (batch number Y1270908) for subcutaneous injection. Placebo (batch number Y069HC) for subcutaneous injection.

Intervention Type: DRUG

Other Intervention Names

SOM230

Eligibility Criteria

Inclusion Criteria

• Lean, healthy, non-diabetic male.

Exclusion Criteria

• Family history of diabetes, BMI over 25.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

Veterans Medical Research Foundation

OTHER

Sponsor Role: collaborator

Robert R. Henry, MD

OTHER

Sponsor Role: lead

Responsible Party

Robert R. Henry, MD

Study Principal Investigator

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Robert R Henry, MD

Role: PRINCIPAL_INVESTIGATOR

Veterans Medical Research Foundation

Locations

CMR Center for Metabolic Research VASDHS

San Diego, California, United States

Countries

United States

References

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.

Reference Type: RESULT

PMID: 23733372 (View on PubMed)

Related Links

http://www.vacmr.org

Study site Web site

Other Identifiers

SOM230Novartis/VMRF

Identifier Type: -

Identifier Source: org_study_id