HyperglycemiaPhase 2PasireotideNCT01128192
Somatostatin Analogue SOM230 (Pasireotide) in Healthy Male Volunteers
A Phase 2 study testing pasireotide in people with Hyperglycemia, run by Robert R. Henry, MD at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 50 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Hyperglycemia
- What is being tested?
- pasireotide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 45 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2009to Apr 2010
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 50 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Lean, healthy, non-diabetic male.
Who cannot join
- Family history of diabetes, BMI over 25.
Trial locations and contacts
1 site in 1 country.
United States1 site
CMR Center for Metabolic Research VASDHS
San Diego, California, 92161
About this study
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
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.
Read the 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
- Being tested
- pasireotide
- Medical subject headings
- Hyperglycemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
pasireotideDrug
Also called SOM230
Pasireotide 600 μg (batch number Y050DE) or 900 μg bid (batch number Y1270908) for subcutaneous injection. Placebo (batch number Y069HC) for subcutaneous injection.
| Study group | Role | What they receive |
|---|---|---|
| Pasireotide 600 µg sc bid | Experimental | n=19. Pasireotide 600 µg sc bid Receives: Drug: pasireotide |
| Pasireotide 900 µg sc bid | Experimental | n=19. Pasireotide 900 µg sc bid Receives: Drug: pasireotide |
| Pasireotide 1200 µg sc bid | Experimental | n=7. Due to increased severity of gastro-intestinal side effects, this arm was discontinued. These participants were only included in the safety analysis. Receives: Drug: pasireotide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Insulin Basal Level
Change from Day 2 and Day 9 of insulin basal levels (2-step hyperglycemic clamp test with arginine stimulation)
Measured: -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
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.
Measured: 0-10 mins, 10-180 mins, 0-180 mins (Day 2 and Day 9)
Change in Basal Endogenous Glucose Production (EGP)
Change from Day 3 and Day 10 of Basal EGP (Hyperinsulinemic-Euglycemic Clamp)
Measured: Day 3 and Day 10
Change in Low Dose % Endogenous Glucose Production (EGP) Inhibition
Change from Day 3 and Day 10 of low dose % EGP Inhibition (Hyperinsulinemic-Euglycemic Clamp)
Measured: Day 3 and Day 10
Change in High Dose % Endogenous Glucose Production (EGP) Inhibition
Change from Day 3 and Day 10 of high dose % EGP Inhibition (Hyperinsulinemic-Euglycemic Clamp)
Measured: Day 3 and Day 10
Change in Low-Dose Glucose Disposal Rate (GDR)
Change from Day 3 and Day 10 in Low-Dose Glucose Disposal Rate (GDR) during Hyperinsulinemic-Euglycemic Clamp.
Measured: Day 3 and Day 10
Change in High-Dose Glucose Disposal Rate (GDR)
Change from Day 3 and Day 10 in High-Dose Glucose Disposal Rate (GDR) during Hyperinsulinemic-Euglycemic Clamp.
Measured: Day 3 and Day 10
Secondary outcomes (4)
Change in Fasting Plasma Glucose Level
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.
Measured: -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)
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.
Measured: 0-30 mins, 30-180 mins, 0-180 mins (Day 1 and Day 8)
Change Fasting Plasma Insulin Level
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.
Measured: -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)
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
Measured: 0-30 mins, 30-180 mins, 0-180 mins (Day 1 and Day 8)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 May 2010 (estimated)
- Study startAug 2009
- Primary completionApr 2010
- Study completionApr 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HyperglycemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 45 participants (actual)
Sponsor and investigators
- Lead sponsor
- Robert R. Henry, MD
- Sponsor type
- University, hospital or other
- Collaborators
- Veterans Medical Research Foundation
- Responsible party
- Sponsor-investigator, Robert R. Henry, MD, Veterans Medical Research Foundation
- Investigators
- Robert R Henry, MD, Principal investigator, Veterans Medical Research Foundation
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01128192
- Sponsor's protocol ID
- SOM230Novartis/VMRF
- Acronym
- Pasireotide
- Status last verified
- Dec 2014
- First submitted
- 15 Sep 2009
- Last updated
- 25 Dec 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
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.
PubMed 23733372
Study at a glance
From the registry record, last updated by the sponsor on 25 Dec 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01128192
- Acronym / sponsor ID
- Pasireotide / SOM230Novartis/VMRF
- Conditions
- Hyperglycemia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 45 participants (actual)
- Lead sponsor
- Robert R. Henry, MDUniversity, hospital or other
- Collaborators
- Veterans Medical Research Foundation
- Study start
- Aug 2009
- Primary completion
- Apr 2010 (actual)
- Study completion
- Apr 2010 (actual)
- First posted
- 21 May 2010 (estimated)
- Results
- Posted 25 Dec 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Pasireotide 600 µg sc bid | Experimental | Drug: pasireotiden=19. Pasireotide 600 µg sc bid |
| Pasireotide 900 µg sc bid | Experimental | Drug: pasireotiden=19. Pasireotide 900 µg sc bid |
| Pasireotide 1200 µg sc bid | Experimental | Drug: pasireotiden=7. Due to increased severity of gastro-intestinal side effects, this arm was discontinued. These participants were only included in the safety analysis. |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (1 listed)
- Lean, healthy, non-diabetic male.
Key exclusion criteria (1 listed)
- Family history of diabetes, BMI over 25.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| pasireotideAlso: SOM230Pasireotide 600 μg (batch number Y050DE) or 900 μg bid (batch number Y1270908) for subcutaneous injection. Placebo (batch number Y069HC) for subcutaneous injection. | Drug | Pasireotide 1200 µg sc bid, Pasireotide 600 µg sc bid, Pasireotide 900 µg sc bid |
Primary outcome
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)
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.
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)
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)
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)
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.
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.
4 secondary outcomes
Change in Fasting Plasma Glucose Level
Time frame: -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)
Change Fasting Plasma Insulin Level
Time frame: -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)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Dec 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 23733372Henry 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.
- Study site Web siteLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Robert R Henry, MD principal investigator
Veterans Medical Research Foundation
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing pasireotide in people with Hyperglycemia, run by Robert R. Henry, MD at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 Dec 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 25 Dec 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Insulin Basal Level (time frame: -30 min and -15 min on Day 2 and Day 9). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01128192, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Dec 2014.