Study of Management of Pasireotide-induced Hyperglycemia... | NCT02060383 | Trialant
NCT02060383
Sponsor
Novartis Pharmaceuticals
Status
Completed
Last Update Posted
May 29, 2019Actual
Enrollment
249Actual
Phase
Phase 4
Conditions
Cushing's Disease
Acromegaly
Interventions
Pasireotide s.c.
Sitagliptin
Liraglutide
Insulin
Pasireotide LAR
Metformin
Countries
United States
Belgium
Brazil
China
Denmark
Germany
India
Peru
Poland
Russia
Thailand
Turkey (Türkiye)
Protocol Section
Identification Module
NCT ID
NCT02060383
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
CSOM230B2219
Secondary IDs
ID
Type
Description
Link
2012-002916-16
EudraCT Number
Brief Title
Study of Management of Pasireotide-induced Hyperglycemia in Adult Patients With Cushing's Disease or Acromegaly
Official Title
A Multi-center, Randomized, Open-label, Phase IV Study to Investigate the Management of Pasireotide-induced Hyperglycemia With Incretin Based Therapy or Insulin in Adult Patients With Cushing's Disease or Acromegaly
Acronym
Not provided
Organization
NovartisINDUSTRY
Status Module
Record Verification Date
May 2019
Overall Recruitment Status or Expanded Access Status
Completed
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
Not provided
Expanded Access Info
No
Start Date
May 23, 2014Actual
Primary Completion Date
Feb 5, 2018Actual
Completion Date
Mar 26, 2018Actual
First Submitted Date
Feb 10, 2014
First Submission Date that Met QC Criteria
Feb 11, 2014
First Posted Date
Feb 12, 2014Estimated
Results Waived
Not provided
Results First Submitted Date
Feb 28, 2019
Results First Submitted that Met QC Criteria
May 7, 2019
Results First Posted Date
May 29, 2019Actual
Certification/Extension (aka Delayed Results) First Submitted Date
Oct 12, 2018
Certification/Extension First Submitted that Passed QC Review
Oct 19, 2018
Certification/Extension First Posted Date
Oct 23, 2018Actual
Last Update Submitted Date
May 7, 2019
Last Update Posted Date
May 29, 2019Actual
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
Novartis PharmaceuticalsINDUSTRY
Collaborators
Not provided
Oversight Module
Has Data Monitoring Committee (DMC)
No
Is FDA Regulated Drug
Yes
Is FDA Regulated Device
No
Is Unapproved Device
Not provided
Pediatric Postmarket Surveillance of a Device Product
Not provided
Product Exported from US
Not provided
FDAAA801 Violation
Not provided
Description Module
Brief Summary
The study was designed to investigate the optimal management of hyperglycemia developed during pasireotide treatment in participants with Cushing's disease or Acromegaly, which was not manageable with metformin.
This was a Phase IV, multi-center, randomized, open-label study. Eligible patients started pasireotide subcutaneously (s.c.) for Cushing's disease and pasireotide LAR (long-acting release) for Acromegaly.
Participants being treated with pasireotide s.c or LAR at screening were eligible as long as they met protocol criteria during the screening period. If previously normo-glycemic participants experienced an increase in their fasting blood glucose and met the criteria for diabetes while on pasireotide, they started anti-diabetic treatment using metformin. If they continued to have elevated blood glucose above target on metformin within the first 16 weeks, they were randomized in a 1:1 ratio to receive treatment with incretin based therapy or insulin for approximately 16 weeks.
Participants who continued to receive clinical benefit after completing the Core Phase could enter an optional Extension Phase if pasireotide was not commercially available in their country or a local access program was not available to provide drug. Patients continued in the Extension Phase until the last participant randomized in the Core Phase completed 16 weeks of treatment post-randomization.
Detailed Description
Not provided
Conditions Module
Conditions
Cushing's Disease
Acromegaly
Keywords
Cushing's disease
acromegaly
pasireotide
hyperglycemia
Design Module
Study Type
Interventional
Number of References to an Expanded Access Study
Not provided
Expanded Access Types
Not provided
Patient Registry
Not provided
Target Follow-Up Duration
Not provided
Phases
Phase 4
Interventional Study Design
Allocation
Biospecimen
No data available
No data is available for this block.
Enrollment
249Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
Incretin based therapy (randomized group)
Experimental
Participants randomized to the incretin based arm started with sitagliptin once daily. If sitagliptin did not control the participant's hyperglycemia, sitagliptin was stopped and participants switched to liraglutide once daily. If despite treatment with liraglutide, hyperglycemia was not controlled then the participant was eligible for rescue therapy with addition of insulin.
Drug: Pasireotide s.c.
Drug: Sitagliptin
Drug: Liraglutide
Drug: Insulin
Drug: Pasireotide LAR
Drug: Metformin
Insulin (randomized group)
Experimental
Participants randomized to the insulin arm started with once daily dose of basal insulin. The dose was up or down titrated at the discretion of the investigator. If blood glucose levels remained uncontrolled on basal insulin, participant switched to basal insulin plus prandial insulin.
Drug: Pasireotide s.c.
Drug: Insulin
Drug: Pasireotide LAR
Drug: Metformin
Non-Randomized Arm
Other
This arm represents the non-randomized participants: Cushing's Disease (CD) or Acromegaly participants, who received pasireotide s.c. or LAR (long-acting release) respectively, but who were not randomized to the Incretin or Insulin arms.
For the purpose of analysis, this non-randomized arm is further split into 3 groups:
Baseline insulin group (BL insulin) includes participants who were receiving insulin at study entry
Oral antidiabetic drugs (OAD) group includes participants who developed hyperglycemia that was controlled by metformin and/or other background anti-diabetic treatment
No OAD group includes participants who did not receive any anti-diabetic medication during the core phase of the trial
Interventions
Name
Type
Description
Arm Group Labels
Other Names
Pasireotide s.c.
Drug
Administered to Cushing's disease participants.
Incretin based therapy (randomized group)
Insulin (randomized group)
Non-Randomized Arm
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
Change in HbA1c From Randomization to Approximately 16 Weeks
Absolute change in HbA1c from randomization to end of core phase (16 weeks) in incretin based therapy arm and insulin arm, and mean difference of change in HbA1c between the two treatment groups based on an ANOVA model using treatment (Incretin, Insulin) and the two randomization stratification factors (Disease: Cushing's disease vs Acromegaly; Baseline glycemic status: HbA1c <7% vs HbA1c ≥ 7%) as fixed effects. For Participants who discontinued the study or required rescue treatment before the time of assessing the primary endpoint, the last HbA1c assessment collected 8 weeks (56 days) after randomization (and prior to or on the date of start of rescue treatment) was carried forward. If the participant discontinued the study or used rescue treatment within 8 weeks after randomization, it was considered missing.
Randomization, 16 weeks
Secondary Outcomes
Measure
Description
Time Frame
Change in HbA1c From Randomization (R) Over Time Per Randomized Arm
Absolute change in HbA1c overtime from randomization (i.e. start of randomized antidiabetic treatment) to end of core phase per randomized arm
Randomization (R), Week (W) 4 post R, W 8 post R, W 16 post R, end of Core phase (up to week 16 post R)
Other Outcomes
Not provided
Eligibility Module
Eligibility Criteria
Inclusion Criteria:
Patients greater than or equal to 18 years old
Confirmed diagnosis of Cushing's disease or acromegaly
Exclusion Criteria:
Patients who require surgical intervention
Patients receiving DPP-4 inhibitors or GLP-1 receptor agonists within 4 weeks prior to study entry
HbA1c > 10 % at screening
Known hypersensitivity to somatostatin analogues Other protocol-defined inclusion/exclusion criteria may apply.
Accepts Healthy Volunteers
No
Sex
All
Sex/Gender Based
Not provided
Sex/Gender Description
Not provided
Minimum Age
18 Years
Maximum Age
Not provided
Standard Ages
AdultOlder Adult
Study Population
Not provided
Sampling Method
Not provided
Contacts/Locations Module
Central Contacts
Not provided
Overall Officials
Name
Affiliation
Role
Novartis Pharmaceuticals
Novartis Pharmaceuticals
Study Director
Locations
Facility
Status
City
State
ZIP
Country
Contacts
Diabetes and Endocrine Associates La Mesa Location
Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.
249 participants were included in study & treated with pasireotide s.c. (59 with Cushing's disease) or pasireotide LAR (190 with acromegaly). Following pre-randomization period (up to 16 weeks), 81 participants were randomized to either incretin-based therapy or insulin (72 evaluable for the primary analysis) & 168 not qualified for randomization.
Recruitment Details
A total of 68 randomized evaluable participants with at least 8 weeks of randomized treatment without any rescue anti-diabetic medication was required. Approximately 79 participants were planned to be randomized.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
FG000
Incretin Based Therapy (Randomized Group)
Participants randomized to the incretin based arm started with sitagliptin once daily. If sitagliptin did not control the participant's hyperglycemia, sitagliptin was stopped and participants switched to liraglutide once daily. If despite treatment with liraglutide, hyperglycemia was not controlled then the participant was eligible for rescue therapy with addition of insulin
Periods
Title
Milestones
Reasons Not Completed
Core Phase
Type
Comment
Milestone Data
STARTED
Entered Core Phase of Study
Baseline Characteristics Module
Baseline Analysis Population Description
Outcome Measures Module
Outcome Measures
Adverse Events Module
Frequency Threshold
5
More Info Module
Limitations and Caveats
Not provided
Annotation Section
No data available
No data is available for this block.
Document Section
Large Document Module
Document Has No Statistical Analysis Plan (SAP)
Not provided
Uploaded Document Information
Type
Includes Protocol
Includes SAP
Includes ICF
Document Label
Document Date
Document Uploaded Date
Document File Name
Prot
Yes
No
No
Study Protocol
Mar 17, 2017
Feb 28, 2019
Derived Section
Miscellaneous Info Module
Version Holder
Jul 10, 2026
Removed Countries
Not provided
Submission Tracking
No data available
No data is available for this block.
Condition Browse Module
MeSH Terms
Intervention Browse Module
MeSH Terms
Randomized
Intervention Model
Parallel Assignment
Intervention Model Description
Not provided
Primary Purpose
Supportive Care
Observational Model
Not provided
Time Perspective
Not provided
Masking Info
Masking
None (Open Label)
Masking Description
Not provided
Who Masked
Not provided
Drug: Pasireotide s.c.
Drug: Insulin
Drug: Pasireotide LAR
Drug: Metformin
SOM230
Sitagliptin
Drug
Taken for approximately 16 weeks during the core study phase or until the drug was found not to be effective
Incretin based therapy (randomized group)
Liraglutide
Drug
Participant switched to liraglutide if sitagliptin was found not to be effective.
Incretin based therapy (randomized group)
Insulin
Drug
Participant took insulin for 16 weeks. Insulin was also administered as rescue therapy in the incretin-based therapy arm if required.
Insulin was administered to the BL-insulin group at the discretion of the Principal Investigator.
Note: OAD and No OAD groups within the non-randomized arm did not take Insulin.
Incretin based therapy (randomized group)
Insulin (randomized group)
Non-Randomized Arm
Pasireotide LAR
Drug
Administered to Acromegaly participants.
Incretin based therapy (randomized group)
Insulin (randomized group)
Non-Randomized Arm
SOM230
Metformin
Drug
If previously normo-glycemic participants experienced increase in their fasting blood glucose and meeting the criteria for diabetes while on pasireotide, they started anti-diabetic treatment using metformin. If they continued to experience increase in their fasting blood glucose within the first 16 weeks, they were randomized in a 1:1 ratio to receive treatment with incretin based therapy or insulin for approximately 16 weeks. Metformin treatment was not required for the BL Insulin and OAD groups, within the non-randomized arm, but may have been prescribed at the discretion of the investigator.
Note: No OAD group within the non-randomized arm did not take metformin.
Incretin based therapy (randomized group)
Insulin (randomized group)
Non-Randomized Arm
Change in FPG (Fasting Plasma Glucose) From Randomization Until End of Core Phase
Absolute change in fasting glucose overtime from randomization (i.e. start of randomized antidiabetic treatment) to end of core phase per randomized arm
Percentage of Participants in the Incretin-based Arm Who Required Anti-diabetic Rescue Therapy With Insulin
The percentage of participants who received anti-diabetic rescue therapy in incretin based therapy is summarized.
Randomization to up to 16 weeks
Absolute Change in HbA1c From Baseline to End of Core Phase
Absolute change in HbA1c from baseline to end of core phase in the incretin based therapy arm and the insulin arm
Baseline, up to 32 weeks (end of Core phase)
Absolute Change in FPG From Baseline to End of Core Phase
Absolute change in FPG from baseline to end of core phase in the incretin based therapy arm and the insulin arm.
Baseline, Up to 32 weeks (end of Core Phase)
Percentage of Participants With ≤ 0.3% HbA1c Increase to End of Core Phase
Percentage of participants with ≤ 0.3% HbA1c increase in the incretin based therapy arm and the insulin arm.
Randomization, up to 16 weeks
LA Biomedical Research at Harbor UCLA Medical Center SC - SOM230B2219
Torrance
California
90502
United States
Coastal Metabolic Research Centre SC
Ventura
California
93003
United States
East Coast Institute for Research East Coast Inst. for Res(ECIR)
Jacksonville
Florida
32223
United States
Washington University SC - SOM230B2411
St Louis
Missouri
63110
United States
Great Falls Clinic
Great Falls
Montana
59405
United States
Robert Wood Johnson Medical School - Rutgers SC
New Brunswick
New Jersey
08901
United States
The Mount Sinai Hospital SC
New York
New York
10029
United States
Columbia University Medical Center New York Presbyterian Neuroendocrine Unit
New York
New York
10032
United States
Lenox Hill Hospital/Manhattan Eye, Ear and Throat Hospital SC
New York
New York
10075
United States
Allegheny Endocrinology Associates SC
Pittsburgh
Pennsylvania
15212
United States
Vanderbilt Clinical Trials Center SOM230B2219
Nashville
Tennessee
37212-8210
United States
Baylor College of Medicine Ben Taub General Hosp.
Houston
Texas
77030
United States
Virginia Endocrinology Research SC-2
Chesapeake
Virginia
23321
United States
Swedish Medical Center Dept.ofSeattle Neuroscience(2)
Seattle
Washington
98122-4379
United States
Novartis Investigative Site
Leuven
3000
Belgium
Novartis Investigative Site
Wilrijk
2610
Belgium
Novartis Investigative Site
Rio de Janeiro
Rio de Janeiro
21941-590
Brazil
Novartis Investigative Site
Porto Alegre
Rio Grande do Sul
90560-030
Brazil
Novartis Investigative Site
Joinville
Santa Catarina
89201260
Brazil
Novartis Investigative Site
São Paulo
São Paulo
05403 000
Brazil
Novartis Investigative Site
Beijing
Beijing Municipality
100730
China
Novartis Investigative Site
Guangzhou
Guangdong
510000
China
Novartis Investigative Site
Chengdu
Sichuan
610041
China
Novartis Investigative Site
Aalborg
9000
Denmark
Novartis Investigative Site
Aarhus
DK-8000
Denmark
Novartis Investigative Site
Herlev
DK-2730
Denmark
Novartis Investigative Site
Odense C
DK-5000
Denmark
Novartis Investigative Site
Erlangen
91054
Germany
Novartis Investigative Site
Freiburg im Breisgau
79106
Germany
Novartis Investigative Site
Oldenburg
26122
Germany
Novartis Investigative Site
Bangalore
Karnataka
560054
India
Novartis Investigative Site
Vellore
Tamil Nadu
632004
India
Novartis Investigative Site
San Isidro
Lima region
27
Peru
Novartis Investigative Site
Warsaw
00-909
Poland
Novartis Investigative Site
Wroclaw
50 367
Poland
Novartis Investigative Site
Saint Petersburg
197341
Russia
Novartis Investigative Site
Bangkok
10400
Thailand
Novartis Investigative Site
Bangkok
10700
Thailand
Novartis Investigative Site
Songkhla
90110
Thailand
Novartis Investigative Site
Altunizade
34662
Turkey (Türkiye)
Novartis Investigative Site
Ankara
06500
Turkey (Türkiye)
Novartis Investigative Site
Antalya
07070
Turkey (Türkiye)
Silverstein JM. Hyperglycemia induced by pasireotide in patients with Cushing's disease or acromegaly. Pituitary. 2016 Oct;19(5):536-43. doi: 10.1007/s11102-016-0734-1.
FG001
Insulin (Randomized Group)
Participants randomized to the insulin arm started with once daily dose of basal insulin. The dose was up or down titrated at the discretion of the investigator. If blood glucose levels remained uncontrolled on basal insulin, participant switched to basal insulin plus prandial insulin.
FG002
Baseline Insulin (BL) (Non-randomized Group)
This group included participants who were receiving insulin at study entry.
This group included participants who developed hyperglycemia that was controlled by metformin and/or other background anti-diabetic treatment. Patients in this group did not require additional treatment with either incretin or insulin.
FG004
No OAD (Non-randomized Group)
This group included participants who did not receive any anti-diabetic medication during the Core Phase of the study as they did not develop hyperglycemia.
FG00038 subjects
FG00143 subjects
FG00219 subjects
FG00346 subjects
FG004103 subjects
Completed Core/Entered Extension
FG00017 subjects
FG00117 subjects
FG00210 subjects
FG00321 subjects
FG00453 subjects
Completed Core/Did Not Enter Extension
FG00018 subjects
FG00120 subjects
FG0029 subjects
FG00318 subjects
FG00442 subjects
COMPLETED
FG00035 subjects
FG00137 subjects
FG00219 subjects
FG00339 subjects
FG00495 subjects
NOT COMPLETED
FG0003 subjects
FG0016 subjects
FG0020 subjects
FG0037 subjects
FG0048 subjects
Type
Comment
Reasons
Unsatisfactory therapeutic effect
FG0001 subjects
FG0015 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
Adverse Event
FG0002 subjects
FG0010 subjects
FG0020 subjects
FG0032 subjects
FG004
Administrative problems
FG0000 subjects
FG0011 subjects
FG0020 subjects
FG0030 subjects
FG004
Protocol Violation
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0031 subjects
FG004
Withdrawal by Subject
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0034 subjects
FG004
Extension Phase
Type
Comment
Milestone Data
STARTED
Entered the Extension phase from the Core phase
FG00017 subjects
FG00117 subjects
FG00210 subjects
FG00321 subjects
FG00453 subjects
COMPLETED
Completed the Extension phase
FG00014 subjects
FG00114 subjects
FG0027 subjects
FG00319 subjects
NOT COMPLETED
FG0003 subjects
FG0013 subjects
FG0023 subjects
FG0032 subjects
FG004
Type
Comment
Reasons
Unsatisfactory therapeutic effect
FG0001 subjects
FG0011 subjects
FG0020 subjects
FG003
Full Analysis Set (FAS): all participants who received at least one dose of pasireotide.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
Incretin Based Therapy (Randomized Group)
Participants randomized to the incretin based arm started with sitagliptin once daily. If sitagliptin did not control the participant's hyperglycemia, sitagliptin was stopped and participants switched to liraglutide once daily. If despite treatment with liraglutide, hyperglycemia was not controlled then the participant was eligible for rescue therapy with addition of insulin
BG001
Insulin (Randomized Group)
Participants randomized to the insulin arm started with once daily dose of basal insulin. The dose was up or down titrated at the discretion of the investigator. If blood glucose levels remained uncontrolled on basal insulin, participant switched to basal insulin plus prandial insulin.
BG002
Baseline Insulin (BL) (Non-randomized Group)
This group included participants who were receiving insulin at study entry.
This group included participants who developed hyperglycemia that was controlled by metformin and/or other background anti-diabetic treatment. Patients in this group did not require additional treatment with either incretin or insulin.
BG004
No OAD (Non-randomized Group)
This group included participants who did not receive any anti-diabetic medication during the Core Phase of the study as they did not develop hyperglycemia.
BG005
Total
Total of all reporting groups
Denominators
Units
Counts
Participants
BG00038
BG00143
BG00219
BG00346
BG004103
BG005249
Baseline Measures
Title
Description
Population Description
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Denominator Units Selected
Denominators
Classes
Age, Continuous
Mean
Standard Deviation
Years
Title
Denominators
Categories
Title
Measurements
BG00050.6± 11.76
BG00146.4± 12.90
BG00246.7± 12.54
BG003
Sex: Female, Male
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Female
BG00022
BG00127
BG002
Race/Ethnicity, Customized
Number
Participants
Title
Denominators
Categories
Other
Title
Measurements
BG00022
BG00124
BG002
Type
Title
Description
Population Description
Reporting Status
Anticipated Posting Date
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Time Frame
Units Analyzed
Denominator Units Selected
Arm/Group Information
Denominators
Classes
Analyses
Primary
Change in HbA1c From Randomization to Approximately 16 Weeks
Absolute change in HbA1c from randomization to end of core phase (16 weeks) in incretin based therapy arm and insulin arm, and mean difference of change in HbA1c between the two treatment groups based on an ANOVA model using treatment (Incretin, Insulin) and the two randomization stratification factors (Disease: Cushing's disease vs Acromegaly; Baseline glycemic status: HbA1c <7% vs HbA1c ≥ 7%) as fixed effects. For Participants who discontinued the study or required rescue treatment before the time of assessing the primary endpoint, the last HbA1c assessment collected 8 weeks (56 days) after randomization (and prior to or on the date of start of rescue treatment) was carried forward. If the participant discontinued the study or used rescue treatment within 8 weeks after randomization, it was considered missing.
Randomized Analysis Set (RAS): all patients who received at least one dose of pasireotide and were assigned to either incretin based therapy or insulin by randomization.
If the patient discontinued the study or used rescue treatment within 8 weeks after randomization, it was considered missing.
Posted
Mean
95% Confidence Interval
Hba1c percentage
Randomization, 16 weeks
ID
Title
Description
OG000
Incretin Based Therapy (Randomized Group)
Participants randomized to the incretin based arm started with sitagliptin once daily. If sitagliptin did not control the participant's hyperglycemia, sitagliptin was stopped and participants switched to liraglutide once daily. If despite treatment with liraglutide, hyperglycemia was not controlled then the participant was eligible for rescue therapy with addition of insulin
OG001
Insulin (Randomized Group)
Participants randomized to the insulin arm started with once daily dose of basal insulin. The dose was up or down titrated at the discretion of the investigator. If blood glucose levels remained uncontrolled on basal insulin, participant switched to basal insulin plus prandial insulin.
Units
Counts
Participants
OG00031
OG00141
Title
Denominators
Categories
All Patients
ParticipantsOG00031
ParticipantsOG00141
Title
Measurements
OG000-0.12(-0.36 to 0.13)
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
All Patients
Mean Difference (Net)
-0.28
Standard Error of the Mean
0.18
2-Sided
95
-0.63
0.08
Difference of adjusted mean change in HbA1c between the two arms based on an ANOVA model with treatment (Incretin, Insulin) and randomization stratification factors (Cushing's vs. Acromegaly; baseline HbA1c <7% vs ≥7%) as fixed effects.
Other
There was no formal hypothesis testing planned in this study.
Secondary
Change in HbA1c From Randomization (R) Over Time Per Randomized Arm
Absolute change in HbA1c overtime from randomization (i.e. start of randomized antidiabetic treatment) to end of core phase per randomized arm
Randomized Analysis Set (RAS): all patients who received at least one dose of pasireotide and were assigned to either incretin based therapy or insulin by randomization.
Posted
Mean
Standard Deviation
HbA1c percentage
Randomization (R), Week (W) 4 post R, W 8 post R, W 16 post R, end of Core phase (up to week 16 post R)
ID
Title
Description
OG000
Incretin Based Therapy (Randomized Group)
Participants randomized to the incretin based arm started with sitagliptin once daily. If sitagliptin did not control the participant's hyperglycemia, sitagliptin was stopped and participants switched to liraglutide once daily. If despite treatment with liraglutide, hyperglycemia was not controlled then the participant was eligible for rescue therapy with addition of insulin
OG001
Insulin (Randomized Group)
Participants randomized to the insulin arm started with once daily dose of basal insulin. The dose was up or down titrated at the discretion of the investigator. If blood glucose levels remained uncontrolled on basal insulin, participant switched to basal insulin plus prandial insulin.
Secondary
Change in FPG (Fasting Plasma Glucose) From Randomization Until End of Core Phase
Absolute change in fasting glucose overtime from randomization (i.e. start of randomized antidiabetic treatment) to end of core phase per randomized arm
Randomized Analysis Set (RAS): all patients who received at least one dose of pasireotide and were assigned to either incretin based therapy or insulin by randomization.
Participants randomized to the incretin based arm started with sitagliptin once daily. If sitagliptin did not control the participant's hyperglycemia, sitagliptin was stopped and participants switched to liraglutide once daily. If despite treatment with liraglutide, hyperglycemia was not controlled then the participant was eligible for rescue therapy with addition of insulin
OG001
Insulin (Randomized Group)
Participants randomized to the insulin arm started with once daily dose of basal insulin. The dose was up or down titrated at the discretion of the investigator. If blood glucose levels remained uncontrolled on basal insulin, participant switched to basal insulin plus prandial insulin.
Secondary
Percentage of Participants in the Incretin-based Arm Who Required Anti-diabetic Rescue Therapy With Insulin
The percentage of participants who received anti-diabetic rescue therapy in incretin based therapy is summarized.
Safety set - All participants randomized to the incretin-based therapy who received at least one dose of pasireotide and had at least one post-baseline safety assessment. Randomized participants within the safety set were analyzed according to the anti-diabetic study treatment first received.
Posted
Number
95% Confidence Interval
Percentage of participants
Randomization to up to 16 weeks
ID
Title
Description
OG000
Incretin Based Therapy (Randomized Group)
Participants randomized to the incretin based arm started with sitagliptin once daily. If sitagliptin did not control the participant's hyperglycemia, sitagliptin was stopped and participants switched to liraglutide once daily. If despite treatment with liraglutide, hyperglycemia was not controlled then the participant was eligible for rescue therapy with addition of insulin
Units
Counts
Participants
OG000
Secondary
Absolute Change in HbA1c From Baseline to End of Core Phase
Absolute change in HbA1c from baseline to end of core phase in the incretin based therapy arm and the insulin arm
Full Analysis Set (FAS): Participants who received at least 1 dose of pasireotide. Randomized participants were analyzed according to the anti-diabetic treatment assigned to at randomization. Non-randomized participants were analyzed by the anti-diabetic treatment received during the core phase (insulin at baseline, oral antidiabetics (OAD), none).
Posted
Mean
Standard Deviation
HbA1c percentage
Baseline, up to 32 weeks (end of Core phase)
ID
Title
Description
OG000
Incretin Based Therapy (Randomized Group)
Participants randomized to the incretin based arm started with sitagliptin once daily. If sitagliptin did not control the participant's hyperglycemia, sitagliptin was stopped and participants switched to liraglutide once daily. If despite treatment with liraglutide, hyperglycemia was not controlled then the participant was eligible for rescue therapy with addition of insulin
OG001
Insulin (Randomized Group)
Participants randomized to the insulin arm started with once daily dose of basal insulin. The dose was up or down titrated at the discretion of the investigator. If blood glucose levels remained uncontrolled on basal insulin, participant switched to basal insulin plus prandial insulin.
Secondary
Absolute Change in FPG From Baseline to End of Core Phase
Absolute change in FPG from baseline to end of core phase in the incretin based therapy arm and the insulin arm.
Full Analysis Set (FAS): All participants who received at least one dose of pasireotide. Randomized patients were analyzed according to the anti-diabetic treatment assigned to at randomization. Non-randomized patients were analyzed by the anti-diabetic treatment received during the core phase (insulin at baseline, oral antidiabetics (OAD), none).
Posted
Mean
Standard Deviation
mg/dL
Baseline, Up to 32 weeks (end of Core Phase)
ID
Title
Description
OG000
Incretin Based Therapy (Randomized Group)
Participants randomized to the incretin based arm started with sitagliptin once daily. If sitagliptin did not control the participant's hyperglycemia, sitagliptin was stopped and participants switched to liraglutide once daily. If despite treatment with liraglutide, hyperglycemia was not controlled then the participant was eligible for rescue therapy with addition of insulin
OG001
Insulin (Randomized Group)
Participants randomized to the insulin arm started with once daily dose of basal insulin. The dose was up or down titrated at the discretion of the investigator. If blood glucose levels remained uncontrolled on basal insulin, participant switched to basal insulin plus prandial insulin.
Secondary
Percentage of Participants With ≤ 0.3% HbA1c Increase to End of Core Phase
Percentage of participants with ≤ 0.3% HbA1c increase in the incretin based therapy arm and the insulin arm.
Randomized Analysis Set (RAS): all participants who received at least one dose of pasireotide and were assigned to either incretin based therapy or insulin by randomization.
Posted
Number
95% Confidence Interval
Percentage of participants
Randomization, up to 16 weeks
ID
Title
Description
OG000
Incretin Based Therapy (Randomized Group)
Participants randomized to the incretin based arm started with sitagliptin once daily. If sitagliptin did not control the participant's hyperglycemia, sitagliptin was stopped and participants switched to liraglutide once daily. If despite treatment with liraglutide, hyperglycemia was not controlled then the participant was eligible for rescue therapy with addition of insulin
OG001
Insulin (Randomized Group)
Participants randomized to the insulin arm started with once daily dose of basal insulin. The dose was up or down titrated at the discretion of the investigator. If blood glucose levels remained uncontrolled on basal insulin, participant switched to basal insulin plus prandial insulin.
Time Frame
Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 46 months.
Description
There are different safety follow-up period for Cushing's and for acromegaly patients: On-treatment period: from day of first dose of study medication to 28 days after last dose of pasireotide s.c. and 84 days after last dose of pasireotide long acting, or the follow-up visit, whichever comes later.
All-Cause Mortality Comment
Not provided
Arm/Groups
ID
Title
Description
Deaths (Affected)
Deaths (At Risk)
Serious Events (Affected)
Serious Events (At Risk)
Other Events (Affected)
Other Events (At Risk)
EG000
Incretin Based Therapy (Randomized Group)
Participants randomized to the incretin based arm started with sitagliptin once daily. If sitagliptin did not control the participant's hyperglycemia, sitagliptin was stopped and participants switched to liraglutide once daily. If despite treatment with liraglutide, hyperglycemia was not controlled then the participant was eligible for rescue therapy with addition of insulin
0
38
6
38
37
38
EG001
Insulin (Randomized Group)
Participants randomized to the insulin arm started with once daily dose of basal insulin. The dose was up or down titrated at the discretion of the investigator. If blood glucose levels remained uncontrolled on basal insulin, participant switched to basal insulin plus prandial insulin.
0
43
3
43
40
43
EG002
Baseline Insulin (BL) (Non-randomized Group)
This group included participants who were receiving insulin at study entry.
This group included participants who developed hyperglycemia that was controlled by metformin and/or other background anti-diabetic treatment. Patients in this group did not require additional treatment with either incretin or insulin.
0
46
2
46
38
46
EG004
No OAD (Non-randomized Group)
This group included participants who did not receive any anti-diabetic medication during the Core Phase of the study as they did not develop hyperglycemia.
1
103
7
103
87
103
Serious Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Febrile neutropenia
Blood and lymphatic system disorders
MedDRA (21.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected43 at risk
EG0021 affected19 at risk
EG0030 affected46 at risk
EG004
Coronary artery stenosis
Cardiac disorders
MedDRA (21.0)
Systematic Assessment
EG0000 affected38 at risk
EG0011 affected43 at risk
EG0020 affected19 at risk
EG003
Cushing's syndrome
Endocrine disorders
MedDRA (21.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected43 at risk
EG0020 affected19 at risk
EG003
Diarrhoea
Gastrointestinal disorders
MedDRA (21.0)
Systematic Assessment
EG0001 affected38 at risk
EG0011 affected43 at risk
EG0020 affected19 at risk
EG003
Pancreatitis acute
Gastrointestinal disorders
MedDRA (21.0)
Systematic Assessment
EG0000 affected38 at risk
EG0011 affected43 at risk
EG0020 affected19 at risk
EG003
Vomiting
Gastrointestinal disorders
MedDRA (21.0)
Systematic Assessment
EG0001 affected38 at risk
EG0010 affected43 at risk
EG0020 affected19 at risk
EG003
Fatigue
General disorders
MedDRA (21.0)
Systematic Assessment
EG0000 affected38 at risk
EG0011 affected43 at risk
EG0020 affected19 at risk
EG003
Cholecystitis acute
Hepatobiliary disorders
MedDRA (21.0)
Systematic Assessment
EG0001 affected38 at risk
EG0010 affected43 at risk
EG0020 affected19 at risk
EG003
Breast abscess
Infections and infestations
MedDRA (21.0)
Systematic Assessment
EG0000 affected38 at risk
EG0011 affected43 at risk
EG0020 affected19 at risk
EG003
Cellulitis
Infections and infestations
MedDRA (21.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected43 at risk
EG0021 affected19 at risk
EG003
Epiglottitis
Infections and infestations
MedDRA (21.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected43 at risk
EG0020 affected19 at risk
EG003
Infectious pleural effusion
Infections and infestations
MedDRA (21.0)
Systematic Assessment
EG0001 affected38 at risk
EG0010 affected43 at risk
EG0020 affected19 at risk
EG003
Paronychia
Infections and infestations
MedDRA (21.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected43 at risk
EG0020 affected19 at risk
EG003
Sepsis
Infections and infestations
MedDRA (21.0)
Systematic Assessment
EG0002 affected38 at risk
EG0010 affected43 at risk
EG0020 affected19 at risk
EG003
Upper respiratory tract infection
Infections and infestations
MedDRA (21.0)
Systematic Assessment
EG0001 affected38 at risk
EG0010 affected43 at risk
EG0020 affected19 at risk
EG003
Urinary tract infection
Infections and infestations
MedDRA (21.0)
Systematic Assessment
EG0001 affected38 at risk
EG0010 affected43 at risk
EG0020 affected19 at risk
EG003
Subdural haematoma
Injury, poisoning and procedural complications
MedDRA (21.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected43 at risk
EG0020 affected19 at risk
EG003
Wound
Injury, poisoning and procedural complications
MedDRA (21.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected43 at risk
EG0020 affected19 at risk
EG003
Glycosylated haemoglobin increased
Investigations
MedDRA (21.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected43 at risk
EG0021 affected19 at risk
EG003
Dehydration
Metabolism and nutrition disorders
MedDRA (21.0)
Systematic Assessment
EG0001 affected38 at risk
EG0010 affected43 at risk
EG0020 affected19 at risk
EG003
Diabetes mellitus inadequate control
Metabolism and nutrition disorders
MedDRA (21.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected43 at risk
EG0021 affected19 at risk
EG003
Hyperglycaemia
Metabolism and nutrition disorders
MedDRA (21.0)
Systematic Assessment
EG0001 affected38 at risk
EG0011 affected43 at risk
EG0021 affected19 at risk
EG003
Hypoglycaemia
Metabolism and nutrition disorders
MedDRA (21.0)
Systematic Assessment
EG0001 affected38 at risk
EG0010 affected43 at risk
EG0020 affected19 at risk
EG003
Hypovolaemia
Metabolism and nutrition disorders
MedDRA (21.0)
Systematic Assessment
EG0001 affected38 at risk
EG0010 affected43 at risk
EG0020 affected19 at risk
EG003
Lactic acidosis
Metabolism and nutrition disorders
MedDRA (21.0)
Systematic Assessment
EG0001 affected38 at risk
EG0010 affected43 at risk
EG0020 affected19 at risk
EG003
Papillary thyroid cancer
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA (21.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected43 at risk
EG0020 affected19 at risk
EG003
Pituitary tumour benign
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA (21.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected43 at risk
EG0020 affected19 at risk
EG003
Tubular breast carcinoma
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA (21.0)
Systematic Assessment
EG0001 affected38 at risk
EG0010 affected43 at risk
EG0020 affected19 at risk
EG003
Seizure
Nervous system disorders
MedDRA (21.0)
Systematic Assessment
EG0001 affected38 at risk
EG0010 affected43 at risk
EG0020 affected19 at risk
EG003
Abortion spontaneous
Pregnancy, puerperium and perinatal conditions
MedDRA (21.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected43 at risk
EG0020 affected19 at risk
EG003
Pregnancy
Pregnancy, puerperium and perinatal conditions
MedDRA (21.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected43 at risk
EG0020 affected19 at risk
EG003
Mental status changes
Psychiatric disorders
MedDRA (21.0)
Systematic Assessment
EG0001 affected38 at risk
EG0010 affected43 at risk
EG0020 affected19 at risk
EG003
Acute kidney injury
Renal and urinary disorders
MedDRA (21.0)
Systematic Assessment
EG0001 affected38 at risk
EG0010 affected43 at risk
EG0020 affected19 at risk
EG003
Renal injury
Renal and urinary disorders
MedDRA (21.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected43 at risk
EG0020 affected19 at risk
EG003
Shock
Vascular disorders
MedDRA (21.0)
Systematic Assessment
EG0001 affected38 at risk
EG0010 affected43 at risk
EG0020 affected19 at risk
EG003
Other Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Anaemia
Blood and lymphatic system disorders
MedDRA (21.0)
Systematic Assessment
EG0000 affected38 at risk
EG0012 affected43 at risk
EG0021 affected19 at risk
EG0032 affected46 at risk
EG0043 affected103 at risk
Leukopenia
Blood and lymphatic system disorders
MedDRA (21.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected43 at risk
EG0021 affected19 at risk
EG003
Neutropenia
Blood and lymphatic system disorders
MedDRA (21.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected43 at risk
EG0022 affected19 at risk
EG003
Bradycardia
Cardiac disorders
MedDRA (21.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected43 at risk
EG0021 affected19 at risk
EG003
Sinus bradycardia
Cardiac disorders
MedDRA (21.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected43 at risk
EG0020 affected19 at risk
EG003
Vertigo
Ear and labyrinth disorders
MedDRA (21.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected43 at risk
EG0021 affected19 at risk
EG003
Adrenal insufficiency
Endocrine disorders
MedDRA (21.0)
Systematic Assessment
EG0002 affected38 at risk
EG0010 affected43 at risk
EG0020 affected19 at risk
EG003
Hypothyroidism
Endocrine disorders
MedDRA (21.0)
Systematic Assessment
EG0000 affected38 at risk
EG0011 affected43 at risk
EG0020 affected19 at risk
EG003
Abdominal discomfort
Gastrointestinal disorders
MedDRA (21.0)
Systematic Assessment
EG0002 affected38 at risk
EG0012 affected43 at risk
EG0020 affected19 at risk
EG003
Abdominal distension
Gastrointestinal disorders
MedDRA (21.0)
Systematic Assessment
EG0004 affected38 at risk
EG0010 affected43 at risk
EG0020 affected19 at risk
EG003
Abdominal pain
Gastrointestinal disorders
MedDRA (21.0)
Systematic Assessment
EG0002 affected38 at risk
EG0011 affected43 at risk
EG0020 affected19 at risk
EG003
Abdominal pain upper
Gastrointestinal disorders
MedDRA (21.0)
Systematic Assessment
EG0001 affected38 at risk
EG0012 affected43 at risk
EG0021 affected19 at risk
EG003
Constipation
Gastrointestinal disorders
MedDRA (21.0)
Systematic Assessment
EG0003 affected38 at risk
EG0010 affected43 at risk
EG0020 affected19 at risk
EG003
Diarrhoea
Gastrointestinal disorders
MedDRA (21.0)
Systematic Assessment
EG00011 affected38 at risk
EG00112 affected43 at risk
EG0022 affected19 at risk
EG003
Erosive duodenitis
Gastrointestinal disorders
MedDRA (21.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected43 at risk
EG0021 affected19 at risk
EG003
Gingival hypertrophy
Gastrointestinal disorders
MedDRA (21.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected43 at risk
EG0021 affected19 at risk
EG003
Nausea
Gastrointestinal disorders
MedDRA (21.0)
Systematic Assessment
EG00013 affected38 at risk
EG0017 affected43 at risk
EG0020 affected19 at risk
EG003
Vomiting
Gastrointestinal disorders
MedDRA (21.0)
Systematic Assessment
EG0005 affected38 at risk
EG0010 affected43 at risk
EG0020 affected19 at risk
EG003
Asthenia
General disorders
MedDRA (21.0)
Systematic Assessment
EG0002 affected38 at risk
EG0010 affected43 at risk
EG0020 affected19 at risk
EG003
Fatigue
General disorders
MedDRA (21.0)
Systematic Assessment
EG0004 affected38 at risk
EG0014 affected43 at risk
EG0020 affected19 at risk
EG003
Peripheral swelling
General disorders
MedDRA (21.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected43 at risk
EG0021 affected19 at risk
EG003
Pyrexia
General disorders
MedDRA (21.0)
Systematic Assessment
EG0001 affected38 at risk
EG0010 affected43 at risk
EG0021 affected19 at risk
EG003
Cholelithiasis
Hepatobiliary disorders
MedDRA (21.0)
Systematic Assessment
EG0005 affected38 at risk
EG0018 affected43 at risk
EG0020 affected19 at risk
EG003
Hepatic steatosis
Hepatobiliary disorders
MedDRA (21.0)
Systematic Assessment
EG0000 affected38 at risk
EG0011 affected43 at risk
EG0021 affected19 at risk
EG003
Bone abscess
Infections and infestations
MedDRA (21.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected43 at risk
EG0021 affected19 at risk
EG003
Nasopharyngitis
Infections and infestations
MedDRA (21.0)
Systematic Assessment
EG0003 affected38 at risk
EG0014 affected43 at risk
EG0020 affected19 at risk
EG003
Onychomycosis
Infections and infestations
MedDRA (21.0)
Systematic Assessment
EG0000 affected38 at risk
EG0011 affected43 at risk
EG0021 affected19 at risk
EG003
Pharyngitis
Infections and infestations
MedDRA (21.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected43 at risk
EG0021 affected19 at risk
EG003
Pneumonia
Infections and infestations
MedDRA (21.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected43 at risk
EG0021 affected19 at risk
EG003
Respiratory tract infection viral
Infections and infestations
MedDRA (21.0)
Systematic Assessment
EG0002 affected38 at risk
EG0010 affected43 at risk
EG0020 affected19 at risk
EG003
Subcutaneous abscess
Infections and infestations
MedDRA (21.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected43 at risk
EG0021 affected19 at risk
EG003
Upper respiratory tract infection
Infections and infestations
MedDRA (21.0)
Systematic Assessment
EG0002 affected38 at risk
EG0013 affected43 at risk
EG0023 affected19 at risk
EG003
Urinary tract infection
Infections and infestations
MedDRA (21.0)
Systematic Assessment
EG0003 affected38 at risk
EG0015 affected43 at risk
EG0021 affected19 at risk
EG003
Laceration
Injury, poisoning and procedural complications
MedDRA (21.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected43 at risk
EG0021 affected19 at risk
EG003
Alanine aminotransferase increased
Investigations
MedDRA (21.0)
Systematic Assessment
EG0003 affected38 at risk
EG0012 affected43 at risk
EG0021 affected19 at risk
EG003
Aspartate aminotransferase increased
Investigations
MedDRA (21.0)
Systematic Assessment
EG0002 affected38 at risk
EG0013 affected43 at risk
EG0021 affected19 at risk
EG003
Bacterial test positive
Investigations
MedDRA (21.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected43 at risk
EG0021 affected19 at risk
EG003
Blood creatine phosphokinase increased
Investigations
MedDRA (21.0)
Systematic Assessment
EG0002 affected38 at risk
EG0010 affected43 at risk
EG0021 affected19 at risk
EG003
Blood creatinine increased
Investigations
MedDRA (21.0)
Systematic Assessment
EG0002 affected38 at risk
EG0010 affected43 at risk
EG0020 affected19 at risk
EG003
Blood glucose increased
Investigations
MedDRA (21.0)
Systematic Assessment
EG0002 affected38 at risk
EG0011 affected43 at risk
EG0020 affected19 at risk
EG003
Blood insulin increased
Investigations
MedDRA (21.0)
Systematic Assessment
EG0001 affected38 at risk
EG0010 affected43 at risk
EG0021 affected19 at risk
EG003
Blood urea increased
Investigations
MedDRA (21.0)
Systematic Assessment
EG0001 affected38 at risk
EG0010 affected43 at risk
EG0021 affected19 at risk
EG003
Blood uric acid increased
Investigations
MedDRA (21.0)
Systematic Assessment
EG0000 affected38 at risk
EG0012 affected43 at risk
EG0021 affected19 at risk
EG003
Carbon dioxide decreased
Investigations
MedDRA (21.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected43 at risk
EG0021 affected19 at risk
EG003
Gamma-glutamyltransferase increased
Investigations
MedDRA (21.0)
Systematic Assessment
EG0002 affected38 at risk
EG0014 affected43 at risk
EG0020 affected19 at risk
EG003
Glycosylated haemoglobin increased
Investigations
MedDRA (21.0)
Systematic Assessment
EG0003 affected38 at risk
EG0011 affected43 at risk
EG0020 affected19 at risk
EG003
Lipase increased
Investigations
MedDRA (21.0)
Systematic Assessment
EG0003 affected38 at risk
EG0012 affected43 at risk
EG0020 affected19 at risk
EG003
Weight decreased
Investigations
MedDRA (21.0)
Systematic Assessment
EG00010 affected38 at risk
EG0014 affected43 at risk
EG0020 affected19 at risk
EG003
Weight increased
Investigations
MedDRA (21.0)
Systematic Assessment
EG0000 affected38 at risk
EG0011 affected43 at risk
EG0021 affected19 at risk
EG003
Decreased appetite
Metabolism and nutrition disorders
MedDRA (21.0)
Systematic Assessment
EG0003 affected38 at risk
EG0013 affected43 at risk
EG0020 affected19 at risk
EG003
Diabetes mellitus
Metabolism and nutrition disorders
MedDRA (21.0)
Systematic Assessment
EG0005 affected38 at risk
EG0019 affected43 at risk
EG0022 affected19 at risk
EG003
Dyslipidaemia
Metabolism and nutrition disorders
MedDRA (21.0)
Systematic Assessment
EG0000 affected38 at risk
EG0011 affected43 at risk
EG0021 affected19 at risk
EG003
Hyperglycaemia
Metabolism and nutrition disorders
MedDRA (21.0)
Systematic Assessment
EG00014 affected38 at risk
EG00111 affected43 at risk
EG0026 affected19 at risk
EG003
Hypertriglyceridaemia
Metabolism and nutrition disorders
MedDRA (21.0)
Systematic Assessment
EG0003 affected38 at risk
EG0011 affected43 at risk
EG0020 affected19 at risk
EG003
Hypoglycaemia
Metabolism and nutrition disorders
MedDRA (21.0)
Systematic Assessment
EG0005 affected38 at risk
EG00110 affected43 at risk
EG0028 affected19 at risk
EG003
Hypokalaemia
Metabolism and nutrition disorders
MedDRA (21.0)
Systematic Assessment
EG0003 affected38 at risk
EG0010 affected43 at risk
EG0021 affected19 at risk
EG003
Impaired fasting glucose
Metabolism and nutrition disorders
MedDRA (21.0)
Systematic Assessment
EG0000 affected38 at risk
EG0012 affected43 at risk
EG0020 affected19 at risk
EG003
Type 2 diabetes mellitus
Metabolism and nutrition disorders
MedDRA (21.0)
Systematic Assessment
EG0002 affected38 at risk
EG0011 affected43 at risk
EG0020 affected19 at risk
EG003
Arthralgia
Musculoskeletal and connective tissue disorders
MedDRA (21.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected43 at risk
EG0020 affected19 at risk
EG003
Back pain
Musculoskeletal and connective tissue disorders
MedDRA (21.0)
Systematic Assessment
EG0000 affected38 at risk
EG0013 affected43 at risk
EG0020 affected19 at risk
EG003
Muscular weakness
Musculoskeletal and connective tissue disorders
MedDRA (21.0)
Systematic Assessment
EG0003 affected38 at risk
EG0012 affected43 at risk
EG0020 affected19 at risk
EG003
Myalgia
Musculoskeletal and connective tissue disorders
MedDRA (21.0)
Systematic Assessment
EG0001 affected38 at risk
EG0012 affected43 at risk
EG0021 affected19 at risk
EG003
Osteopenia
Musculoskeletal and connective tissue disorders
MedDRA (21.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected43 at risk
EG0021 affected19 at risk
EG003
Dizziness
Nervous system disorders
MedDRA (21.0)
Systematic Assessment
EG0005 affected38 at risk
EG0015 affected43 at risk
EG0020 affected19 at risk
EG003
Dysgeusia
Nervous system disorders
MedDRA (21.0)
Systematic Assessment
EG0002 affected38 at risk
EG0010 affected43 at risk
EG0020 affected19 at risk
EG003
Headache
Nervous system disorders
MedDRA (21.0)
Systematic Assessment
EG0004 affected38 at risk
EG0014 affected43 at risk
EG0020 affected19 at risk
EG003
Syncope
Nervous system disorders
MedDRA (21.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected43 at risk
EG0021 affected19 at risk
EG003
Glycosuria
Renal and urinary disorders
MedDRA (21.0)
Systematic Assessment
EG0000 affected38 at risk
EG0011 affected43 at risk
EG0021 affected19 at risk
EG003
Haematuria
Renal and urinary disorders
MedDRA (21.0)
Systematic Assessment
EG0003 affected38 at risk
EG0010 affected43 at risk
EG0020 affected19 at risk
EG003
Nephrolithiasis
Renal and urinary disorders
MedDRA (21.0)
Systematic Assessment
EG0000 affected38 at risk
EG0011 affected43 at risk
EG0021 affected19 at risk
EG003
Amenorrhoea
Reproductive system and breast disorders
MedDRA (21.0)
Systematic Assessment
EG0000 affected38 at risk
EG0011 affected43 at risk
EG0021 affected19 at risk
EG003
Polycystic ovaries
Reproductive system and breast disorders
MedDRA (21.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected43 at risk
EG0021 affected19 at risk
EG003
Rhinitis allergic
Respiratory, thoracic and mediastinal disorders
MedDRA (21.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected43 at risk
EG0021 affected19 at risk
EG003
Alopecia
Skin and subcutaneous tissue disorders
MedDRA (21.0)
Systematic Assessment
EG0002 affected38 at risk
EG0011 affected43 at risk
EG0020 affected19 at risk
EG003
Pruritus generalised
Skin and subcutaneous tissue disorders
MedDRA (21.0)
Systematic Assessment
EG0002 affected38 at risk
EG0011 affected43 at risk
EG0020 affected19 at risk
EG003
Rash
Skin and subcutaneous tissue disorders
MedDRA (21.0)
Systematic Assessment
EG0003 affected38 at risk
EG0012 affected43 at risk
EG0021 affected19 at risk
EG003
Rash generalised
Skin and subcutaneous tissue disorders
MedDRA (21.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected43 at risk
EG0021 affected19 at risk
EG003
Skin ulcer
Skin and subcutaneous tissue disorders
MedDRA (21.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected43 at risk
EG0021 affected19 at risk
EG003
Hypotension
Vascular disorders
MedDRA (21.0)
Systematic Assessment
EG0002 affected38 at risk
EG0010 affected43 at risk
EG0021 affected19 at risk
EG003
Certain Agreements
Are all PI(s) employees of the sponsor?
No
Restriction Type
OTHER
Results Disclosure Restriction on PI(s)?
Yes
Other Details
The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of pooled data (i.e.,data from all sites) in clinical trial or disclosure of trial results in their entirety.
Hormones, Hormone Substitutes, and Hormone Antagonists
D011384
Proinsulin
D061385
Insulins
D010187
Pancreatic Hormones
D036361
Peptide Hormones
D010455
Peptides
D000602
Amino Acids, Peptides, and Proteins
D001645
Biguanides
D006146
Guanidines
D000578
Amidines
D009930
Organic Chemicals
Browse Leaves
Not provided
Browse Branches
Not provided
6 subjects
0 subjects
0 subjects
2 subjects
FG00446 subjects
7 subjects
2 subjects
FG0042 subjects
Adverse Event
FG0001 subjects
FG0011 subjects
FG0022 subjects
FG0030 subjects
FG0041 subjects
Withdrawal by Subject
FG0000 subjects
FG0011 subjects
FG0020 subjects
FG0030 subjects
FG0042 subjects
Administrative problems
FG0001 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
Death
FG0000 subjects
FG0010 subjects
FG0021 subjects
FG0030 subjects
FG0041 subjects
Protocol Violation
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0041 subjects
40.2
± 13.80
BG00437.8± 11.17
BG00542.4± 13.05
10
BG00331
BG00447
BG005137
Male
BG00016
BG00116
BG0029
BG00315
BG00456
BG005112
11
BG00325
BG00443
BG005125
Chinese
Title
Measurements
BG0005
BG0019
BG0021
BG00313
BG00433
BG00561
Hispanic/Latino
Title
Measurements
BG0007
BG0012
BG0025
BG0036
BG00419
BG00539
Indian (Indian subcontinent)
Title
Measurements
BG0004
BG0018
BG0022
BG0032
BG0047
BG00523
Japanese
Title
Measurements
BG0000
BG0010
BG0020
BG0030
BG0041
BG0051
OG0010.26(-0.01 to 0.53)
Cushing's Disease
ParticipantsOG0007
ParticipantsOG00111
Title
Measurements
OG0000.33(-0.41 to 1.07)
OG0010.45(-0.20 to 1.09)
Acromegaly
ParticipantsOG00024
ParticipantsOG00130
Title
Measurements
OG000-0.25(-0.49 to -0.00)
OG0010.19(-0.12 to 0.49)
OG000
OG001
Cushing's Disease
Mean Difference (Net)
-0.01
Standard Error of the Mean
0.45
2-Sided
95
-0.96
0.95
Difference of adjusted mean change in HbA1c between the two arms based on an ANOVA model with treatment (Incretin, Insulin) and randomization stratification factors (baseline HbA1c <7% vs ≥7%) as fixed effects.
Other
There was no formal hypothesis testing planned in this study.
OG000
OG001
Acromegaly
Mean Difference (Net)
-0.36
Standard Error of the Mean
0.19
2-Sided
95
-0.74
0.02
Difference of adjusted mean change in HbA1c between the two arms based on an ANOVA model with treatment (Incretin, Insulin) and randomization stratification factors (baseline HbA1c <7% vs ≥7%) as fixed effects.
Other
There was no formal hypothesis testing planned in this study.
Units
Counts
Participants
OG00038
OG00143
Title
Denominators
Categories
Randomization
ParticipantsOG00038
ParticipantsOG00143
Title
Measurements
OG0007.1± 1.00
OG0017.1± 0.75
Change at RW4 D29
ParticipantsOG00037
ParticipantsOG00143
Title
Measurements
OG0000.5± 0.73
OG001
Change at RW8 D57
ParticipantsOG00037
ParticipantsOG00143
Title
Measurements
OG0000.3± 0.98
OG001
Change at RW12 D85
ParticipantsOG00037
ParticipantsOG00140
Title
Measurements
OG0000.2± 1.03
OG001
Change at RW16 D113
ParticipantsOG00035
ParticipantsOG00137
Title
Measurements
OG0000.0± 0.93
OG001
End of Core Phase
ParticipantsOG00037
ParticipantsOG00142
Title
Measurements
OG0000.0± 0.92
OG001
Units
Counts
Participants
OG00038
OG00143
Title
Denominators
Categories
Randomization
ParticipantsOG00038
ParticipantsOG00143
Title
Measurements
OG000172.2± 60.78
OG001167.9± 40.77
Change at RW2 D15
ParticipantsOG00036
ParticipantsOG00142
Title
Measurements
OG0004.6± 51.01
OG001
Change at RW4 D29
ParticipantsOG00038
ParticipantsOG00143
Title
Measurements
OG000-15.0± 47.95
OG001
Change at RW6 D43
ParticipantsOG00036
ParticipantsOG00141
Title
Measurements
OG000-17.7± 57.97
OG001
Change at RW8 D57
ParticipantsOG00036
ParticipantsOG00142
Title
Measurements
OG000-25.7± 53.32
OG001
Change at RW10 D71
ParticipantsOG00037
ParticipantsOG00137
Title
Measurements
OG000-28.8± 61.14
OG001
Change at RW12 D85
ParticipantsOG00037
ParticipantsOG00140
Title
Measurements
OG000-33.4± 50.17
OG001
Change at RW14 D99
ParticipantsOG00036
ParticipantsOG00136
Title
Measurements
OG000-35.1± 55.83
OG001
Change at RW16 D113
ParticipantsOG00035
ParticipantsOG00134
Title
Measurements
OG000-38.8± 53.69
OG001
End of Core Phase
ParticipantsOG00037
ParticipantsOG00141
Title
Measurements
OG000-40.1± 56.35
OG001
38
Title
Denominators
Categories
Title
Measurements
OG00031.6(17.5 to 48.7)
OG002
Baseline Insulin (BL) (Non-randomized Group)
This group included participants who were receiving insulin at study entry.
This group included participants who developed hyperglycemia that was controlled by metformin and/or other background anti-diabetic treatment. Patients in this group did not require additional treatment with either incretin or insulin.
OG004
No OAD (Non-randomized Group)
This group included participants who did not receive any anti-diabetic medication during the Core Phase of the study as they did not develop hyperglycemia.
Units
Counts
Participants
OG00038
OG00143
OG00219
OG00346
OG004103
Title
Denominators
Categories
Baseline: All Patients
ParticipantsOG00038
ParticipantsOG00143
ParticipantsOG00219
ParticipantsOG00346
ParticipantsOG004102
Title
Measurements
OG0006.3± 0.80
OG0016.3± 0.63
OG0027.7± 1.51
OG003
Change at EOP: All Patients
ParticipantsOG00037
ParticipantsOG00142
ParticipantsOG00219
ParticipantsOG00345
Baseline: Cushing's
ParticipantsOG00012
ParticipantsOG00113
ParticipantsOG0026
ParticipantsOG00313
Change at EOP: Cushing's
ParticipantsOG00012
ParticipantsOG00113
ParticipantsOG0026
ParticipantsOG00313
Baseline: Acromegaly
ParticipantsOG00026
ParticipantsOG00130
ParticipantsOG00213
ParticipantsOG00333
Change at EOP: Acromegaly
ParticipantsOG00025
ParticipantsOG00129
ParticipantsOG00213
ParticipantsOG00332
OG002
Baseline Insulin (BL) (Non-randomized Group)
This group included participants who were receiving insulin at study entry.
This group included participants who developed hyperglycemia that was controlled by metformin and/or other background anti-diabetic treatment. Patients in this group did not require additional treatment with either incretin or insulin.
OG004
No OAD (Non-randomized Group)
This group included participants who did not receive any anti-diabetic medication during the Core Phase of the study as they did not develop hyperglycemia.