Somatostatin Analogue SOM230 (Pasireotide) in Healthy Male Volunteers

• Sponsor: Robert R. Henry, MD (Other)
• Overall Status: Completed
• CT.gov ID: NCT01128192
• Collaborator: Veterans Medical Research Foundation (Other)
• Enrollment: 45
• Location: 1
• Arms: 3
• Duration (Months): 8
• Patients Per Site Per Month: 5.6

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Hyperglycemia	Drug: pasireotide	Phase 2

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 Design

• Study Type: Interventional
• Actual Enrollment: 45 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, 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
• Study Start Date: Aug 1, 2009
• Actual Primary Completion Date: Apr 1, 2010
• Actual Study Completion Date: Apr 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
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 Names: 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 Names: 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 Names: SOM230

Outcome Measures

Primary Outcome Measures

1. Change in Insulin Basal Level [-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)

2. Change in Area Under the Curve (AUC) of Plasma Insulin Level 0-10mins, 10-180mins, 0-180mins During Hyperglycemic Clamp [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.

3. Change in Basal Endogenous Glucose Production (EGP) [Day 3 and Day 10]

   Change from Day 3 and Day 10 of Basal EGP (Hyperinsulinemic-Euglycemic Clamp)

4. Change in Low Dose % Endogenous Glucose Production (EGP) Inhibition [Day 3 and Day 10]

   Change from Day 3 and Day 10 of low dose % EGP Inhibition (Hyperinsulinemic-Euglycemic Clamp)

5. Change in High Dose % Endogenous Glucose Production (EGP) Inhibition [Day 3 and Day 10]

   Change from Day 3 and Day 10 of high dose % EGP Inhibition (Hyperinsulinemic-Euglycemic Clamp)

6. Change in Low-Dose Glucose Disposal Rate (GDR) [Day 3 and Day 10]

   Change from Day 3 and Day 10 in Low-Dose Glucose Disposal Rate (GDR) during Hyperinsulinemic-Euglycemic Clamp.

7. Change in High-Dose Glucose Disposal Rate (GDR) [Day 3 and Day 10]

   Change from Day 3 and Day 10 in High-Dose Glucose Disposal Rate (GDR) during Hyperinsulinemic-Euglycemic Clamp.

Secondary Outcome Measures

1. Change in Fasting Plasma Glucose Level [-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.

2. Change in Area Under the Curve (AUC) of Plasma Glucose 0-30mins, 30-180mins, 0-180mins During Oral Glucose Tolerance Test (OGTT) [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.

3. Change Fasting Plasma Insulin Level [-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.

4. Change in Area Under the Curve (AUC) of Plasma Insulin 0-30mins, 30-180mins, 0-180mins During Oral Glucose Tolerance Test (OGTT) [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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 50 Years
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Lean, healthy, non-diabetic male.

Exclusion Criteria:

• Family history of diabetes, BMI over 25.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	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

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Study site Web site

Publications

None provided.

• Responsible Party: Robert R. Henry, MD, Study Principal Investigator, Veterans Medical Research Foundation
• ClinicalTrials.gov Identifier: NCT01128192
• Other Study ID Numbers: SOM230Novartis/VMRF
• First Posted: May 21, 2010
• Last Update Posted: Dec 25, 2014
• Last Verified: Dec 1, 2014

• Additional relevant MeSH terms: Hyperglycemia; Pasireotide

Study Results

Participant Flow

Recruitment Details	Participants were healthy men aged 18-50 years with a body mass index (BMI) ≤25 kg/m2 who came to the VA San Diego Healthcare System Metabolic Research medical clinic. Recruitment occurred between August of 2009 until March 2010.
Pre-assignment Detail	Participants were excluded if they had a family history of diabetes or a baseline diagnosis of impaired glucose tolerance.

Arm/Group Title	Pasireotide 600 μg sc Bid	Pasireotide 900 μg sc Bid	Pasireotide 1200 μg sc Bid
Arm/Group Description	19 healthy male volunteers were randomized to receive Pasireotide 600 μg (n=19). All participants completed the study.	19 healthy male volunteers were randomized to receive Pasireotide 900 μg (n=19). All participants completed the study.	7 healthy male volunteers were randomized to receive Pasireotide 1200 μg (n=7). This arm was used in safety analysis only.
Period Title: Overall Study
STARTED	19	19	7
COMPLETED	19	19	7
NOT COMPLETED	0	0	0

Baseline Characteristics

Arm/Group Title	Pasireotide 600 μg sc Bid	Pasireotide 900 μg sc Bid	Total
Arm/Group Description	Pasireotide 600 μg sc bid n=19	Pasireotide 900 μg sc bid n=19	Total of all reporting groups
Overall Participants	19	19	38
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	24.3 (4.6)	24.6 (6.1)	24.45 (5.4)
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%
Male	19 100%	19 100%	38 100%
Body Mass Index BMI (kg/m2) (kg/m2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m2]	23.30 (1.61)	23.68 (2.04)	23.49 (1.85)
Weight (kg) (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	75.67 (8.11)	74.49 (8.41)	75.08 (8.26)

Outcome Measures

1. Secondary Outcome

Title	Change in Fasting Plasma Glucose Level
Description	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.
Time Frame	-30 minutes on Day 1 and -30 minutes on Day 8

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pasireotide 600 µg sc Bid	Pasireotide 900 µg sc Bid
Arm/Group Description	Pasireotide 600 µg was injected subcutaneously twice daily from Day 3-10. Baseline OGTT was conducted on Day 1 (pre-treatment) and a post-treatment OGTT was conducted on Day 8.	Pasireotide 900 µg was injected subcutaneously twice daily from Day 3-10. Baseline OGTT was conducted on Day 1 (pre-treatment) and a post-treatment OGTT was conducted on Day 8.
Measure Participants	19	18
Mean (Standard Deviation) [mmol/L]	-0.10 (0.36)	0.12 (0.50)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pasireotide 600 µg sc Bid
	Comments	Change in fasting plasma glucose level
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.240
	Comments	Two sided P value
	Method	ANOVA
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Pasireotide 900 µg sc Bid
	Comments	Change in fasting plasma glucose level
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.339
	Comments	Two sided P value.
	Method	ANOVA
	Comments

2. Secondary Outcome

Title	Change in Area Under the Curve (AUC) of Plasma Glucose 0-30mins, 30-180mins, 0-180mins During Oral Glucose Tolerance Test (OGTT)
Description	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.
Time Frame	0-30 mins, 30-180 mins, 0-180 mins (Day 1 and Day 8)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pasireotide 600 µg sc Bid	Pasireotide 900 µg sc Bid
Arm/Group Description	Pasireotide 600 µg was injected subcutaneously twice daily from Day 3-10. Baseline OGTT was conducted on Day 1 (pre-treatment) and a post-treatment OGTT was conducted on Day 8.	Pasireotide 900 µg was injected subcutaneously twice daily from Day 3-10. Baseline OGTT was conducted on Day 1 (pre-treatment) and a post-treatment OGTT was conducted on Day 8.
Measure Participants	19	18
AUC 0-30 min	-0.43 (0.43)	-0.86 (0.45)
AUC 30-180 min	14.72 (4.23)	12.35 (4.25)
AUC 0-180 min	14.29 (4.02)	11.49 (4.49)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pasireotide 600 µg sc Bid
	Comments	Pre and Post treatment Area Under the Curve (AUC) 0-30 minutes
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	Two sided P value.
	Method	ANOVA
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Pasireotide 600 µg sc Bid
	Comments	Pre and Post treatment Area Under the Curve (AUC) 30-180 minutes
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	Two sided P Value.
	Method	ANOVA
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Pasireotide 600 µg sc Bid
	Comments	Pre and Post treatment Area Under the Curve (AUC) 0-180 minutes
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	Two sided P Value
	Method	ANOVA
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Pasireotide 900 µg sc Bid
	Comments	Pre and Post treatment Area Under the Curve (AUC) 0-30 minutes
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	Two sided P value.
	Method	ANOVA
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Pasireotide 900 µg sc Bid
	Comments	Pre and Post treatment Area Under the Curve (AUC) 30-180 minutes
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	Two sided P value.
	Method	ANOVA
	Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Pasireotide 900 µg sc Bid
	Comments	Pre and Post treatment Area Under the Curve (AUC) 0-180 minutes
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	Two sided P value.
	Method	ANOVA
	Comments

3. Secondary Outcome

Title	Change Fasting Plasma Insulin Level
Description	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.
Time Frame	-30 minutes on Day 1 and -30 minutes on Day 8

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pasireotide 600 µg sc Bid	Pasireotide 900 µg sc Bid
Arm/Group Description	Pasireotide 600 µg was injected subcutaneously twice daily from Day 3-10. Baseline OGTT was conducted on Day 1 (pre-treatment) and a post-treatment OGTT was conducted on Day 8.	Pasireotide 900 µg was injected subcutaneously twice daily from Day 3-10. Baseline OGTT was conducted on Day 1 (pre-treatment) and a post-treatment OGTT was conducted on Day 8.
Measure Participants	19	18
Mean (Standard Deviation) [pmol/L]	-6.62 (11.17)	-11.69 (10.96)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pasireotide 600 µg sc Bid
	Comments	Change in fasting plasma insulin level
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.019
	Comments	Two sided P value.
	Method	ANOVA
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Pasireotide 900 µg sc Bid
	Comments	Change in fasting plasma insulin level
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	Two sided P value.
	Method	ANOVA
	Comments

4. Secondary Outcome

Title	Change in Area Under the Curve (AUC) of Plasma Insulin 0-30mins, 30-180mins, 0-180mins During Oral Glucose Tolerance Test (OGTT)
Description	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
Time Frame	0-30 mins, 30-180 mins, 0-180 mins (Day 1 and Day 8)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pasireotide 600 µg sc Bid	Pasireotide 900 µg sc Bid
Arm/Group Description	Pasireotide 600 µg was injected subcutaneously twice daily from Day 3-10. Baseline OGTT was conducted on Day 1 (pre-treatment) and a post-treatment OGTT was conducted on Day 8.	Pasireotide 900 µg was injected subcutaneously twice daily from Day 3-10. Baseline OGTT was conducted on Day 1 (pre-treatment) and a post-treatment OGTT was conducted on Day 8.
Measure Participants	19	18
AUC 0-30 min	-104.18 (90.60)	-100.90 (68.99)
AUC 30-180 min	-184.96 (126.57)	-262.15 (158.58)
AUC 0-180 min	-289.14 (162.54)	-363.06 (191.58)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pasireotide 600 µg sc Bid
	Comments	Pre and Post treatment Area Under the Curve (AUC) 0-30 minutes
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	Two sided P value.
	Method	ANOVA
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Pasireotide 600 µg sc Bid
	Comments	Pre and Post treatment Area Under the Curve (AUC) 30-180 minutes
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	Two sided P value
	Method	ANOVA
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Pasireotide 600 µg sc Bid
	Comments	Pre and Post treatment Area Under the Curve (AUC) 0-180 minutes
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	Two sided P value.
	Method	ANOVA
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Pasireotide 900 µg sc Bid
	Comments	Pre and Post treatment Area Under the Curve (AUC) 0-30 minutes
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	Two sided P value.
	Method	ANOVA
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Pasireotide 900 µg sc Bid
	Comments	Pre and Post treatment Area Under the Curve (AUC) 30-180 minutes
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	Two sided P value.
	Method	ANOVA
	Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Pasireotide 900 µg sc Bid
	Comments	Pre and Post treatment Area Under the Curve (AUC) 0-180 minutes
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	Two sided P value.
	Method	ANOVA
	Comments

5. Primary Outcome

Title	Change in Insulin Basal Level
Description	Change from Day 2 and Day 9 of insulin basal levels (2-step hyperglycemic clamp test with arginine stimulation)
Time Frame	-30 min and -15 min on Day 2 and Day 9

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pasireotide 600 µg sc Bid	Pasireotide 900 µg sc Bid
Arm/Group Description	Pasireotide 600 µg was injected subcutaneously twice daily from Day 3-10. Baseline hyperglycemic clamp test was conducted on Day 2 (pre-treatment) and a post-treatment hyperglycemic clamp was conducted on Day 9.	Pasireotide 900 µg was injected subcutaneously twice daily from Day 3-10. Baseline hyperglycemic clamp test was conducted on Day 2 (pre-treatment) and a post-treatment hyperglycemic clamp was conducted on Day 9.
Measure Participants	19	19
Mean (Standard Deviation) [pmol/L]	-24.37 (10.42)	-29.60 (16.05)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pasireotide 600 µg sc Bid
	Comments	Change in Baseline Insulin Level
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	Two sided P value.
	Method	ANOVA
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Pasireotide 900 µg sc Bid
	Comments	Change in Baseline Insulin Level
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	Two sided P value
	Method	ANOVA
	Comments

6. Primary Outcome

Title	Change in Area Under the Curve (AUC) of Plasma Insulin Level 0-10mins, 10-180mins, 0-180mins During Hyperglycemic Clamp
Description	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.
Time Frame	0-10 mins, 10-180 mins, 0-180 mins (Day 2 and Day 9)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pasireotide 600 µg sc Bid	Pasireotide 900 µg sc Bid
Arm/Group Description	Pasireotide 600 µg was injected subcutaneously twice daily from Day 3-10. Baseline hyperglycemic clamp test was conducted on Day 2 (pre-treatment) and a post-treatment hyperglycemic clamp was conducted on Day 9.	Pasireotide 900 µg was injected subcutaneously twice daily from Day 3-10. Baseline hyperglycemic clamp test was conducted on Day 2 (pre-treatment) and a post-treatment hyperglycemic clamp was conducted on Day 9.
Measure Participants	19	19
AUC 0-10 min	-28.07 (19.15)	-27.95 (18.56)
AUC 10-180 min	-1450.59 (1237.44)	-1474.65 (1009.00)
AUC 0-180 min	-1478.65 (1254.66)	-1502.60 (1022.33)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pasireotide 600 µg sc Bid
	Comments	Pre and Post treatment Area Under the Curve (AUC) 0-10 minutes
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	Two sided P value.
	Method	ANOVA
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Pasireotide 600 µg sc Bid
	Comments	Pre and Post treatment Area Under the Curve (AUC) 10-180 minutes
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	Two sided P value
	Method	ANOVA
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Pasireotide 600 µg sc Bid
	Comments	Pre and Post treatment Area Under the Curve (AUC) 0-180 minutes
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	Two sided P value
	Method	ANOVA
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Pasireotide 900 µg sc Bid
	Comments	Pre and Post treatment Area Under the Curve (AUC) 0-10 minutes
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	Two sided P value
	Method	ANOVA
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Pasireotide 900 µg sc Bid
	Comments	Pre and Post treatment Area Under the Curve (AUC) 10-180 minutes
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	Two sided P value.
	Method	ANOVA
	Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Pasireotide 900 µg sc Bid
	Comments	Pre and Post treatment Area Under the Curve (AUC) 0-180 minutes
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	Two sided P value.
	Method	ANOVA
	Comments

7. Primary Outcome

Title	Change in Basal Endogenous Glucose Production (EGP)
Description	Change from Day 3 and Day 10 of Basal EGP (Hyperinsulinemic-Euglycemic Clamp)
Time Frame	Day 3 and Day 10

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pasireotide 600 µg sc Bid	Pasireotide 900 µg sc Bid
Arm/Group Description	Pasireotide 600 µg was injected subcutaneously twice daily from Day 3-10. Baseline Hyperinsulinemic-Euglycemic Clamp was conducted on Day 3 (pre-treatment) and post-treatment on Day 10.	Pasireotide 900 µg was injected subcutaneously twice daily from Day 3-10. Baseline Hyperinsulinemic-Euglycemic Clamp was conducted on Day 3 (pre-treatment) and post-treatment on Day 10.
Measure Participants	19	19
Mean (Standard Deviation) [mg/kg/min]	-0.041 (0.342)	0.112 (0.308)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pasireotide 600 µg sc Bid
	Comments	Change in Basal EGP
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.608
	Comments	Two sided P value.
	Method	ANOVA
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Pasireotide 900 µg sc Bid
	Comments	Change in Basal EGP
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.132
	Comments	Two sided P value.
	Method	ANOVA
	Comments

8. Primary Outcome

Title	Change in Low Dose % Endogenous Glucose Production (EGP) Inhibition
Description	Change from Day 3 and Day 10 of low dose % EGP Inhibition (Hyperinsulinemic-Euglycemic Clamp)
Time Frame	Day 3 and Day 10

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pasireotide 600 µg sc Bid	Pasireotide 900 µg sc Bid
Arm/Group Description	Pasireotide 600 µg was injected subcutaneously twice daily from Day 3-10. Baseline Hyperinsulinemic-Euglycemic Clamp was conducted on Day 3 (pre-treatment) and post-treatment on Day 10.	Pasireotide 900 µg was injected subcutaneously twice daily from Day 3-10. Baseline Hyperinsulinemic-Euglycemic Clamp was conducted on Day 3 (pre-treatment) and post-treatment on Day 10.
Measure Participants	19	19
Mean (Standard Deviation) [percentage of EGP Inhibition]	-7.54 (23.47)	-6.28 (16.31)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pasireotide 600 µg sc Bid
	Comments	Change in Low-Dose % EGP Inhibition
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.178
	Comments	Two sided P value.
	Method	ANOVA
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Pasireotide 900 µg sc Bid
	Comments	Change in Low-Dose % EGP Inhibition
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.111
	Comments	Two sided P value.
	Method	ANOVA
	Comments

9. Primary Outcome

Title	Change in High Dose % Endogenous Glucose Production (EGP) Inhibition
Description	Change from Day 3 and Day 10 of high dose % EGP Inhibition (Hyperinsulinemic-Euglycemic Clamp)
Time Frame	Day 3 and Day 10

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pasireotide 600 µg sc Bid	Pasireotide 900 µg sc Bid
Arm/Group Description	Pasireotide 600 µg was injected subcutaneously twice daily from Day 3-10. Baseline Hyperinsulinemic-Euglycemic Clamp was conducted on Day 3 (pre-treatment) and post-treatment on Day 10.	Pasireotide 900 µg was injected subcutaneously twice daily from Day 3-10. Baseline Hyperinsulinemic-Euglycemic Clamp was conducted on Day 3 (pre-treatment) and post-treatment on Day 10.
Measure Participants	19	19
Mean (Standard Deviation) [percentage of EGP inhibition]	-2.06 (15.65)	0.00 (0.00)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pasireotide 600 µg sc Bid
	Comments	Change in high-dose % EGP Inhibition
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.573
	Comments	Two sided P value.
	Method	ANOVA
	Comments

10. Primary Outcome

Title	Change in Low-Dose Glucose Disposal Rate (GDR)
Description	Change from Day 3 and Day 10 in Low-Dose Glucose Disposal Rate (GDR) during Hyperinsulinemic-Euglycemic Clamp.
Time Frame	Day 3 and Day 10

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pasireotide 600 µg sc Bid	Pasireotide 900 µg sc Bid
Arm/Group Description	Pasireotide 600 µg was injected subcutaneously twice daily from Day 3-10. Baseline Hyperinsulinemic-Euglycemic Clamp was conducted on Day 3 (pre-treatment) and post-treatment on Day 10.	Pasireotide 900 µg was injected subcutaneously twice daily from Day 3-10. Baseline Hyperinsulinemic-Euglycemic Clamp was conducted on Day 3 (pre-treatment) and post-treatment on Day 10.
Measure Participants	19	19
Mean (Standard Deviation) [mg/kg/min]	-0.029 (2.230)	0.791 (2.144)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pasireotide 600 µg sc Bid
	Comments	Change in Low-Dose Glucose Disposal Rate (GDR)
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.956
	Comments	Two sided P value.
	Method	ANOVA
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Pasireotide 900 µg sc Bid
	Comments	Change in Low-Dose Glucose Disposal Rate (GDR)
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.125
	Comments	Two sided P value.
	Method	ANOVA
	Comments

11. Primary Outcome

Title	Change in High-Dose Glucose Disposal Rate (GDR)
Description	Change from Day 3 and Day 10 in High-Dose Glucose Disposal Rate (GDR) during Hyperinsulinemic-Euglycemic Clamp.
Time Frame	Day 3 and Day 10

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pasireotide 600 µg sc Bid	Pasireotide 900 µg sc Bid
Arm/Group Description	Pasireotide 600 µg was injected subcutaneously twice daily from Day 3-10. Baseline Hyperinsulinemic-Euglycemic Clamp was conducted on Day 3 (pre-treatment) and post-treatment on Day 10.	Pasireotide 900 µg was injected subcutaneously twice daily from Day 3-10. Baseline Hyperinsulinemic-Euglycemic Clamp was conducted on Day 3 (pre-treatment) and post-treatment on Day 10.
Measure Participants	19	19
Mean (Standard Deviation) [mg/kg/min]	0.004 (2.051)	-0.027 (2.099)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pasireotide 600 µg sc Bid
	Comments	Change in High-Dose Glucose Disposal Rate (GDR)
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.993
	Comments	Two sided P value.
	Method	ANOVA
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Pasireotide 900 µg sc Bid
	Comments	Change in High-Dose Glucose Disposal Rate (GDR)
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.956
	Comments	Two sided P value.
	Method	ANOVA
	Comments

Adverse Events

Time Frame	Adverse events (AE) were collected in real time as reported by each study subject. The study Investigators' reviewed and evaluated each individually reported Adverse Event within one week of reporting (if not immediately upon report).
Adverse Event Reporting Description	The investigator provided a listing of each subject's AEs. The individual AEs that occurred in each subject were then identified using the Investigator's term and AE frequency was summarized by dose group and adverse event.
Arm/Group Title	Pasireotide 600 μg sc Bid		Pasireotide 900 μg sc Bid		Pasireotide 1200 μg sc Bid
Arm/Group Description	Forty-five healthy male volunteers were randomized to receive pasireotide 600 μg (n=19), 900 μg (n=19) or 1200 μg (n=7) sc bid. All participants completed the study. Due to an increased severity of gastrointestinal AEs in the 1200 μg bid arm, randomization to this dose was discontinued after seven participants had completed the 7 days of treatment. These participants were included in the safety analyses only.		Forty-five healthy male volunteers were randomized to receive pasireotide 600 μg (n=19), 900 μg (n=19) or 1200 μg (n=7) sc bid. All participants completed the study. Due to an increased severity of gastrointestinal AEs in the 1200 μg bid arm, randomization to this dose was discontinued after seven participants had completed the 7 days of treatment. These participants were included in the safety analyses only.		Forty-five healthy male volunteers were randomized to receive pasireotide 600 μg (n=19), 900 μg (n=19) or 1200 μg (n=7) sc bid. All participants completed the study. Due to an increased severity of gastrointestinal AEs in the 1200 μg bid arm, randomization to this dose was discontinued after seven participants had completed the 7 days of treatment. These participants were included in the safety analyses only.
All Cause Mortality
	Pasireotide 600 μg sc Bid		Pasireotide 900 μg sc Bid		Pasireotide 1200 μg sc Bid
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Pasireotide 600 μg sc Bid		Pasireotide 900 μg sc Bid		Pasireotide 1200 μg sc Bid
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/19 (0%)		0/19 (0%)		0/7 (0%)
Other (Not Including Serious) Adverse Events
	Pasireotide 600 μg sc Bid		Pasireotide 900 μg sc Bid		Pasireotide 1200 μg sc Bid
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	18/19 (94.7%)		18/19 (94.7%)		7/7 (100%)
Gastrointestinal disorders
Nausea	10/19 (52.6%)	10	10/19 (52.6%)	10	5/7 (71.4%)	5
Abdominal Cramping	6/19 (31.6%)	6	9/19 (47.4%)	9	4/7 (57.1%)	4
Loose Stools (soft stools)	5/19 (26.3%)	5	13/19 (68.4%)	13	2/7 (28.6%)	2
Burning Sensation	4/19 (21.1%)	4	2/19 (10.5%)	2	0/7 (0%)	0
Diarrhea	3/19 (15.8%)	3	4/19 (21.1%)	4	1/7 (14.3%)	1
Vomiting/emesis	2/19 (10.5%)	2	3/19 (15.8%)	3	3/7 (42.9%)	3
Gas (Flatulence)	1/19 (5.3%)	1	4/19 (21.1%)	4	0/7 (0%)	0
Frequent Stools	1/19 (5.3%)	1	0/19 (0%)	0	0/7 (0%)	0
Light colored stool	1/19 (5.3%)	1	0/19 (0%)	0	0/7 (0%)	0
Pressure in gut	1/19 (5.3%)	1	0/19 (0%)	0	0/7 (0%)	0
Stomach ache	1/19 (5.3%)	1	0/19 (0%)	0	0/7 (0%)	0
Stomach cramps	0/19 (0%)	0	1/19 (5.3%)	1	0/7 (0%)	0
Stomach fullness	1/19 (5.3%)	1	0/19 (0%)	0	0/7 (0%)	0
Heartburn	0/19 (0%)	0	1/19 (5.3%)	1	0/7 (0%)	0
General disorders
Fatigue	3/19 (15.8%)	3	0/19 (0%)	0	1/7 (14.3%)	1
Impacted wisdom tooth	1/19 (5.3%)	1	0/19 (0%)	0	0/7 (0%)	0
Sleepiness	0/19 (0%)	0	1/19 (5.3%)	1	0/7 (0%)	0
Dizziness	0/19 (0%)	0	0/19 (0%)	0	1/7 (14.3%)	1
Histamine-like reaction	0/19 (0%)	0	0/19 (0%)	0	1/7 (14.3%)	1
Sweating	0/19 (0%)	0	0/19 (0%)	0	1/7 (14.3%)	1
Vasovagal reaction while voiding	0/19 (0%)	0	2/19 (10.5%)	2	0/7 (0%)	0
Injury, poisoning and procedural complications
Infiltration, left ACFf	0/19 (0%)	0	1/19 (5.3%)	1	0/7 (0%)	0
Respiratory, thoracic and mediastinal disorders
Upper respiratory infection (common cold)	1/19 (5.3%)	1	3/19 (15.8%)	3	0/7 (0%)	0
Skin and subcutaneous tissue disorders
Injection site redness	2/19 (10.5%)	2	2/19 (10.5%)	2	0/7 (0%)	0
Injection site stinging	2/19 (10.5%)	2	2/19 (10.5%)	2	0/7 (0%)	0
Injection site bruise	0/19 (0%)	0	1/19 (5.3%)	1	0/7 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.