Somatostatin Analogue SOM230 (Pasireotide) in Healthy Male Volunteers

This study has been completed.
Sponsor:
Collaborator:
Veterans Medical Research Foundation
Information provided by (Responsible Party):
Robert R. Henry, MD, Veterans Medical Research Foundation
ClinicalTrials.gov Identifier:
NCT01128192
First received: September 15, 2009
Last updated: December 23, 2014
Last verified: December 2014
  Purpose

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.


Condition Intervention Phase
Hyperglycemia
Drug: pasireotide
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Outcomes Assessor)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Veterans Medical Research Foundation:

Primary Outcome Measures:
  • Change in Insulin Basal Level [ Time Frame: -30 min and -15 min on Day 2 and Day 9 ] [ Designated as safety issue: No ]
    Change from Day 2 and Day 9 of insulin basal levels (2-step hyperglycemic clamp test with arginine stimulation)

  • Change in Area Under the Curve (AUC) of Plasma Insulin Level 0-10mins, 10-180mins, 0-180mins During Hyperglycemic Clamp [ Time Frame: 0-10 mins, 10-180 mins, 0-180 mins (Day 2 and Day 9) ] [ Designated as safety issue: No ]
    Blood samples were taken at -30 min, -15 min, 0 min, 15 min, 30 min, 45 min, 60 min, 75 min, 90 min, 105 min, 120 min, 135 min, 150 min, 165 min, 180 min to assess the plasma insulin levels during Hyperglycemic Clamp (2-step hyperglycemic clamp test with arginine stimulation). The mean change in plasma insulin levels from Day 2 to Day 9 were calculated as Values on Day 9 - Values on Day 2.

  • Change in Basal Endogenous Glucose Production (EGP) [ Time Frame: Day 3 and Day 10 ] [ Designated as safety issue: No ]
    Change from Day 3 and Day 10 of Basal EGP (Hyperinsulinemic-Euglycemic Clamp)

  • Change in Low Dose % Endogenous Glucose Production (EGP) Inhibition [ Time Frame: Day 3 and Day 10 ] [ Designated as safety issue: No ]
    Change from Day 3 and Day 10 of low dose % EGP Inhibition (Hyperinsulinemic-Euglycemic Clamp)

  • Change in High Dose % Endogenous Glucose Production (EGP) Inhibition [ Time Frame: Day 3 and Day 10 ] [ Designated as safety issue: No ]
    Change from Day 3 and Day 10 of high dose % EGP Inhibition (Hyperinsulinemic-Euglycemic Clamp)

  • Change in Low-Dose Glucose Disposal Rate (GDR) [ Time Frame: Day 3 and Day 10 ] [ Designated as safety issue: No ]
    Change from Day 3 and Day 10 in Low-Dose Glucose Disposal Rate (GDR) during Hyperinsulinemic-Euglycemic Clamp.

  • Change in High-Dose Glucose Disposal Rate (GDR) [ Time Frame: Day 3 and Day 10 ] [ Designated as safety issue: No ]
    Change from Day 3 and Day 10 in High-Dose Glucose Disposal Rate (GDR) during Hyperinsulinemic-Euglycemic Clamp.


Secondary Outcome Measures:
  • Change in Fasting Plasma Glucose Level [ Time Frame: -30 minutes on Day 1 and -30 minutes on Day 8 ] [ Designated as safety issue: No ]

    An Oral Glucose Tolerance Test was performed at Day 1 (baseline) and Day 8 (post-treatment). Samples were taken at

    -30 min to assess the fasting plasma glucose level. The mean change in fasting plasma glucose level from Day 1 to Day 8 was assessed.


  • Change in Area Under the Curve (AUC) of Plasma Glucose 0-30mins, 30-180mins, 0-180mins During Oral Glucose Tolerance Test (OGTT) [ Time Frame: 0-30 mins, 30-180 mins, 0-180 mins (Day 1 and Day 8) ] [ Designated as safety issue: No ]
    Blood samples were taken at -30 min, 0 min, 30 min, 60 min, 90 min, 120 min, 150 min, 180 min to assess the plasma glucose level. The mean change in plasma glucose level from Day 1 to Day 8 were calculated as Values on Day 8 - Values on Day 1.

  • Change Fasting Plasma Insulin Level [ Time Frame: -30 minutes on Day 1 and -30 minutes on Day 8 ] [ Designated as safety issue: No ]
    An Oral Glucose Tolerance Test was performed at Day 1 (baseline) and Day 8 (post-treatment). Samples were taken at -30 min to assess the fasting plasma insulin level. The mean change in fasting plasma insulin level from Day 1 to Day 8 was assessed.

  • Change in Area Under the Curve (AUC) of Plasma Insulin 0-30mins, 30-180mins, 0-180mins During Oral Glucose Tolerance Test (OGTT) [ Time Frame: 0-30 mins, 30-180 mins, 0-180 mins (Day 1 and Day 8) ] [ Designated as safety issue: No ]
    Blood samples were taken at -30 min, 0 min, 30 min, 60 min, 90 min, 120 min, 150 min, 180 min to assess the plasma insulin level. The mean change in plasma insulin level from Day 1 to Day 8 were calculated as Values on Day 8 - Values on Day 1


Enrollment: 45
Study Start Date: August 2009
Study Completion Date: April 2010
Primary Completion Date: April 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Pasireotide 600 µg sc bid
n=19. Pasireotide 600 µg sc bid
Drug: pasireotide
Pasireotide 600 μg (batch number Y050DE) or 900 μg bid (batch number Y1270908) for subcutaneous injection. Placebo (batch number Y069HC) for subcutaneous injection.
Other Name: SOM230
Experimental: Pasireotide 900 µg sc bid
n=19. Pasireotide 900 µg sc bid
Drug: pasireotide
Pasireotide 600 μg (batch number Y050DE) or 900 μg bid (batch number Y1270908) for subcutaneous injection. Placebo (batch number Y069HC) for subcutaneous injection.
Other Name: SOM230
Experimental: 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.
Drug: pasireotide
Pasireotide 600 μg (batch number Y050DE) or 900 μg bid (batch number Y1270908) for subcutaneous injection. Placebo (batch number Y069HC) for subcutaneous injection.
Other Name: SOM230

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

Ages Eligible for Study:   18 Years to 50 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Lean, healthy, non-diabetic male.

Exclusion Criteria:

  • Family history of diabetes, BMI over 25.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01128192

Locations
United States, California
CMR Center for Metabolic Research VASDHS
San Diego, California, United States, 92161
Sponsors and Collaborators
Robert R. Henry, MD
Veterans Medical Research Foundation
Investigators
Principal Investigator: Robert R Henry, MD Veterans Medical Research Foundation
  More Information

Additional Information:
Publications:
Responsible Party: Robert R. Henry, MD, Study Principal Investigator, Veterans Medical Research Foundation
ClinicalTrials.gov Identifier: NCT01128192     History of Changes
Other Study ID Numbers: SOM230Novartis/VMRF
Study First Received: September 15, 2009
Results First Received: July 26, 2013
Last Updated: December 23, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Hyperglycemia
Glucose Metabolism Disorders
Metabolic Diseases
Somatostatin
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 05, 2015