- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01128192
Somatostatin Analogue SOM230 (Pasireotide) in Healthy Male Volunteers (Pasireotide)
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
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.
Study Overview
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.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
California
-
San Diego, California, United States, 92161
- CMR Center for Metabolic Research VASDHS
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Lean, healthy, non-diabetic male.
Exclusion Criteria:
- Family history of diabetes, BMI over 25.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Pasireotide 600 µg sc bid
n=19.
Pasireotide 600 µg sc bid
|
Pasireotide 600 μg (batch number Y050DE) or 900 μg bid (batch number Y1270908) for subcutaneous injection.
Placebo (batch number Y069HC) for subcutaneous injection.
Other Names:
|
Experimental: Pasireotide 900 µg sc bid
n=19.
Pasireotide 900 µg sc bid
|
Pasireotide 600 μg (batch number Y050DE) or 900 μg bid (batch number Y1270908) for subcutaneous injection.
Placebo (batch number Y069HC) for subcutaneous injection.
Other Names:
|
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.
|
Pasireotide 600 μg (batch number Y050DE) or 900 μg bid (batch number Y1270908) for subcutaneous injection.
Placebo (batch number Y069HC) for subcutaneous injection.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in Insulin Basal Level
Time Frame: -30 min and -15 min on Day 2 and Day 9
|
Change from Day 2 and Day 9 of insulin basal levels (2-step hyperglycemic clamp test with arginine stimulation)
|
-30 min and -15 min on Day 2 and Day 9
|
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)
|
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.
|
0-10 mins, 10-180 mins, 0-180 mins (Day 2 and Day 9)
|
Change in Basal Endogenous Glucose Production (EGP)
Time Frame: Day 3 and Day 10
|
Change from Day 3 and Day 10 of Basal EGP (Hyperinsulinemic-Euglycemic Clamp)
|
Day 3 and Day 10
|
Change in Low Dose % Endogenous Glucose Production (EGP) Inhibition
Time Frame: Day 3 and Day 10
|
Change from Day 3 and Day 10 of low dose % EGP Inhibition (Hyperinsulinemic-Euglycemic Clamp)
|
Day 3 and Day 10
|
Change in High Dose % Endogenous Glucose Production (EGP) Inhibition
Time Frame: Day 3 and Day 10
|
Change from Day 3 and Day 10 of high dose % EGP Inhibition (Hyperinsulinemic-Euglycemic Clamp)
|
Day 3 and Day 10
|
Change in Low-Dose Glucose Disposal Rate (GDR)
Time Frame: Day 3 and Day 10
|
Change from Day 3 and Day 10 in Low-Dose Glucose Disposal Rate (GDR) during Hyperinsulinemic-Euglycemic Clamp.
|
Day 3 and Day 10
|
Change in High-Dose Glucose Disposal Rate (GDR)
Time Frame: Day 3 and Day 10
|
Change from Day 3 and Day 10 in High-Dose Glucose Disposal Rate (GDR) during Hyperinsulinemic-Euglycemic Clamp.
|
Day 3 and Day 10
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in Fasting Plasma Glucose Level
Time Frame: -30 minutes on Day 1 and -30 minutes on Day 8
|
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. |
-30 minutes on Day 1 and -30 minutes on Day 8
|
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)
|
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.
|
0-30 mins, 30-180 mins, 0-180 mins (Day 1 and Day 8)
|
Change Fasting Plasma Insulin Level
Time Frame: -30 minutes on Day 1 and -30 minutes on Day 8
|
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.
|
-30 minutes on Day 1 and -30 minutes on Day 8
|
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)
|
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
|
0-30 mins, 30-180 mins, 0-180 mins (Day 1 and Day 8)
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Robert R Henry, MD, Veterans Medical Research Foundation
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- SOM230Novartis/VMRF
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Hyperglycemia
-
Mayo ClinicCompletedHospital Hyperglycemia | Post-transplant HyperglycemiaUnited States
-
Zealand University HospitalNot yet recruitingStress Hyperglycemia | Postoperative Hyperglycemia
-
University of CopenhagenUnknownSurgery--Complications | Hyperglycemia Stress | Hyperglycemia Steroid-inducedDenmark
-
University of LeedsCompletedEffect of Food on Postprandial HyperglycemiaUnited Kingdom
-
Emory UniversityNational Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); National...RecruitingHyperglycemia StressUnited States
-
Loughborough UniversityUniversity of BedfordshireCompletedPostprandial HyperglycemiaUnited Kingdom
-
Centre Hospitalier Universitaire de BesanconEli Lilly and Company; AstraZenecaCompleted
-
Medical University of ViennaCompleted
-
Addis Ababa UniversityCompletedHyperglycemia, Postprandial
-
University of Eastern FinlandFinnsugar LtdCompletedHyperglycemia, PostprandialFinland
Clinical Trials on pasireotide
-
Novartis PharmaceuticalsCompletedGastroenteropancreatic Neuroendocrine Tumor of the Pulmonary ot Gastroenteropancreatic SystemGermany
-
Novartis PharmaceuticalsCompletedMetastatic Melanoma and Merkel Cell CarcinomaGermany, Switzerland
-
RECORDATI GROUPRecruitingPost-Bariatric HypoglycemiaUnited States, Belgium, France, Italy, Spain, United Kingdom
-
Patrick Y. Wen, MDMemorial Sloan Kettering Cancer Center; Massachusetts General Hospital; Northwestern... and other collaboratorsCompleted
-
Milton S. Hershey Medical CenterWithdrawnMultiple MyelomaUnited States
-
Novartis PharmaceuticalsCompleted
-
Alliance Pour La Recherche en CancerologieCompleted
-
NYU Langone HealthUnited States Department of DefenseCompletedAtypical Ductal Breast Hyperplasia | Lobular Carcinoma in Situ (LCIS) | Atypical Lobular Hyperplasia (ALH) of BreastUnited States
-
Hospices Civils de LyonCompleted
-
Novartis PharmaceuticalsCompletedDose Escalation Study of Pasireotide (SOM230) in Patients With Advanced Neuroendocrine Tumors (NETs)Neuroendocrine TumorsUnited States