Study to Compare the Efficacy and Safety of Administratio... | NCT01708902 | Trialant
NCT01708902
Sponsor
Boehringer Ingelheim
Status
Completed
Last Update Posted
Apr 24, 2015Estimated
Enrollment
876Actual
Phase
Phase 3
Conditions
Diabetes Mellitus, Type 2
Interventions
linagliptin2.5mg/metformin1000mg
linagliptin2.5mg/metformin1000mg
linagliptin 5mg
Metformin 500mg
linagliptin2.5mg/metformin500mg
linagliptin2.5mg/metformin500mg
linagliptin 5mg
Metformin 1000mg
Countries
China
Malaysia
Philippines
Vietnam
Protocol Section
Identification Module
NCT ID
NCT01708902
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
1288.18
Secondary IDs
Not provided
Brief Title
Study to Compare the Efficacy and Safety of Administration of the Fix Dose Combination of Linagliptin Plus Metformin in Drug naïve Type 2 Patients
Official Title
A Phase III Randomised, Double-blind, Double-dummy, Parallel Group Study to Compare the Efficacy and Safety of Twice Daily Administration of the Fix Dose Combination of Linagliptin 2.5 mg + Metformin 500 mg, or of Linagliptin 2.5 mg + Metformin 1000 mg, With the Individual Components of Metformin (500 mg or 1000 mg, Twice Daily), and Linagliptin (5.0 mg, Once Daily) Over 24 Weeks in Treatment naïve Type 2 Diabetic Patients With Insufficient Glycaemic Control
Acronym
Not provided
Organization
Boehringer IngelheimINDUSTRY
Status Module
Record Verification Date
Apr 2015
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
Oct 2012
Primary Completion Date
Apr 2014Actual
Completion Date
Apr 2014Actual
First Submitted Date
Oct 16, 2012
First Submission Date that Met QC Criteria
Oct 16, 2012
First Posted Date
Oct 17, 2012Estimated
Results Waived
Not provided
Results First Submitted Date
Apr 8, 2015
Results First Submitted that Met QC Criteria
Apr 8, 2015
Results First Posted Date
Apr 24, 2015Estimated
Certification/Extension (aka Delayed Results) First Submitted Date
Not provided
Certification/Extension First Submitted that Passed QC Review
Not provided
Certification/Extension First Posted Date
Not provided
Last Update Submitted Date
Apr 8, 2015
Last Update Posted Date
Apr 24, 2015Estimated
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
Boehringer IngelheimINDUSTRY
Collaborators
Name
Class
Eli Lilly and Company
INDUSTRY
Oversight Module
No data available
No data is available for this block.
Description Module
Brief Summary
Reduced factorial design study with 24 week randomized treatment of initial combination therapy with linagliptin and metformin in T2DM patients
Detailed Description
Not provided
Conditions Module
Conditions
Diabetes Mellitus, Type 2
Keywords
Not provided
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 3
Interventional Study Design
Allocation
Biospecimen
No data available
No data is available for this block.
Enrollment
876Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
linagliptin2.5mg / metformin500mg BID
Experimental
patient to receive a tablet containing linagliptin 2.5mg and metformin 500mg BID
Drug: linagliptin 5mg
Drug: Metformin 500mg
linagliptin2.5mg / metformin1000mg BID
Experimental
patient to receive a tablet containing linagliptin 2.5mg and metformin 1000mg BID
Drug: linagliptin 5mg
Drug: Metformin 1000mg
metformin 500mg BID
Active Comparator
patient to receive a tablet containing metformin 500mg BID
Drug: linagliptin2.5mg/metformin500mg
metformin 1000mg BID
Active Comparator
patient to receive a tablet containing metformin 1000mg BID
Drug: linagliptin2.5mg/metformin1000mg
linagliptin 5 mg QD
Active Comparator
patient to receive a tablet containing linagliptin 5mg once daily
Drug: linagliptin2.5mg/metformin1000mg
Drug: linagliptin2.5mg/metformin500mg
Interventions
Name
Type
Description
Arm Group Labels
Other Names
linagliptin2.5mg/metformin1000mg
Drug
linagliptin2.5mg/metformin1000mg BID
metformin 1000mg BID
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
The Change From Baseline in HbA1c After 24 Weeks of Treatment in Main Group
The change from baseline in HbA1c after 24 weeks of treatment in main group.
The mean was adjusted by baseline HbA1c and treatment group.
Baseline and week 24
The Change From Baseline in HbA1c After 24 Weeks of Treatment in Main Group - FAS (OC)
The change from baseline in HbA1c after 24 weeks of treatment in main group. Only subjects from the FAS with measured HbA1c values (observed cases [OC]) were considered.
The mean was adjusted by treatment, baseline HbA1c, week and treatment*week.
The sensitivity analysis was added as the primary analysis failed with borderline results.
Baseline and week 24
The Change From Baseline in HbA1c After 12 Weeks of Treatment in APG
The change from baseline in HbA1c after 12 weeks of treatment in additional parallel group (APG)
The mean was adjusted by baseline HbA1c and treatment group.
Baseline and week 12
Secondary Outcomes
Measure
Description
Time Frame
The Occurrence of Treat to Target Efficacy Response in Terms of HbA1c < 7.0 % After 24 Weeks of Treatment in Main Group
The occurrence of treat to target efficacy response in terms of HbA1c < 7.0 % after 24 weeks of treatment in main group.
Week 24 (after first drug administration)
The Occurrence of Treat to Target Efficacy Response in Terms of HbA1c < 7.0 % After 12 Weeks of Treatment in APG
Other Outcomes
Not provided
Eligibility Module
Eligibility Criteria
Inclusion criteria:
Diagnosis of Type 2 diabetes mellitus(T2DM) prior to informed consent
Male and female patients on diet and exercise regimen who are drug-naïve
Glycosylated haemoglobin A1c (HbA1c) at V1a >/=7.5 %<11% for main group and HbA1c >/= 11.0 % for the additional parallel group
Age >/= 18 and </= 80 years at Visit 1a (Screening)
Body Mass Index(BMI)</ = 40 kg/m2 at Visit 1a (Screening)
Signed and dated written informed consent by date of Visit 1a in accordance with good clinical practice(GCP) and local legislation
Exclusion criteria:
Uncontrolled hyperglycaemia required for rescue medication during placebo run-in phase
In main group, the patients with investigational medicinal product(IMP) compliance < 80 % or >120 % during 2 weeks placebo run in period
Acute coronary syndrome stroke or Transient ischaemic attack (TIA) within 3 months prior to randomisation
Impaired hepatic function, defined by serum levels of either Alanine aminotransferase(ALT) ,Aspartate aminotransferase(AST), or alkaline phosphatase (AP) above 3 x upper limit of normal (ULN) ,or total bilirubin above 1.5 x ULN as determined at Visit 1a
Known hypersensitivity or allergy to linagliptin or its excipients or metformin or placebo
Treatment with anti-obesity drugs 3 months prior to informed consent or any other treatment at the time of screening
Alcohol or drug abuse within the 3 months prior to informed consent that would interfere with trial participation or any ongoing condition leading to a decreased compliance to study procedures or study drug intake in the opinion of the investigator.
Concurrent participation in another clinical trial or any investigational therapy within thirty days prior to signing the consent form or during the trial.
Pre-menopausal women (last menstruation \
Accepts Healthy Volunteers
No
Sex
All
Sex/Gender Based
Not provided
Sex/Gender Description
Not provided
Minimum Age
18 Years
Maximum Age
80 Years
Standard Ages
AdultOlder Adult
Study Population
Not provided
Sampling Method
Not provided
Contacts/Locations Module
Central Contacts
Not provided
Overall Officials
Name
Affiliation
Role
Boehringer Ingelheim
Boehringer Ingelheim
Study Chair
Locations
Facility
Status
City
State
ZIP
Country
Contacts
1288.18.86001 Boehringer Ingelheim Investigational Site
Beijing
China
1288.18.86002 Boehringer Ingelheim Investigational Site
Lv Q, Shen J, Miao L, Ye B, Schepers C, Plat A, Shi Y. Early Combination Therapy with Linagliptin and Metformin in People with Type 2 Diabetes Improves Glycemic Control to HbA1c </= 6.5% without Increasing Hypoglycemia: Pooled Analysis of Two Randomized Clinical Trials. Diabetes Ther. 2020 Jun;11(6):1317-1330. doi: 10.1007/s13300-020-00819-9. Epub 2020 Apr 23.
See Also Links
Not provided
Available IPD Information
Not provided
IPD Sharing Statement Module
No data available
No data is available for this block.
Results Section
Participant Flow Module
Pre-assignment Details
After 2-weeks placebo run-in in the main group, 730 of 733 randomised patients were treated in a double-blind fashion for 24 weeks. In the additional parallel group (APG), all of 143 randomised patients with HbA1c >=11% were treated for 24 weeks (the first 12 weeks were double-blind). There was a 1-week follow-up period after treatment.
Recruitment Details
Not provided
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
FG000
Main: Linagliptin 5mg QD
Main Group: Patients received linagliptin 5mg once daily (QD), administered oral as tablet.
FG001
Main: Metformin 500mg BID
Main Group: Patients received metformin 500mg twice daily (BID), administered oral as tablet.
Periods
Title
Milestones
Reasons Not Completed
Overall Study
Type
Comment
Milestone Data
STARTED
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
No data available
No data is available for this block.
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
Factorial Assignment
Intervention Model Description
Not provided
Primary Purpose
Treatment
Observational Model
Not provided
Time Perspective
Not provided
Masking Info
Masking
Double
Masking Description
Not provided
Who Masked
Not provided
linagliptin2.5mg/metformin1000mg
Drug
linagliptin2.5mg/metformin1000mg BID
linagliptin 5 mg QD
linagliptin 5mg
Drug
linagliptin 5mg once daily
linagliptin2.5mg / metformin500mg BID
Metformin 500mg
Drug
Metformin 500mg BID
linagliptin2.5mg / metformin500mg BID
linagliptin2.5mg/metformin500mg
Drug
linagliptin2.5mg/metformin500mg BID
metformin 500mg BID
linagliptin2.5mg/metformin500mg
Drug
linagliptin2.5mg/metformin500mg BID
linagliptin 5 mg QD
linagliptin 5mg
Drug
linagliptin 5mg once daily
linagliptin2.5mg / metformin1000mg BID
Metformin 1000mg
Drug
Metformin 1000mg BID
linagliptin2.5mg / metformin1000mg BID
The occurrence of treat to target efficacy response in terms of HbA1c < 7.0 % after 12 weeks of treatment in APG.
Week 12 (after first drug administration)
The Occurrence of Treat to Target Efficacy Response in Terms of HbA1c < 6.5% After 24 Weeks of Treatment in Main Group
The occurrence of treat to target efficacy response in terms of HbA1c < 6.5% after 24 weeks of treatment in main group.
Week 24 (after first drug administration)
The Occurrence of Treat to Target Efficacy Response in Terms of HbA1c < 6.5% After 12 Weeks of Treatment in APG
The occurrence of treat to target efficacy response in terms of HbA1c < 6.5% after 12 weeks of treatment in APG.
Week 12 (after first drug administration)
The Occurrence of Relative Efficacy Response in Main Group
The occurrence of relative efficacy response (HbA1c lowering by at least 0.5% after 24 weeks of treatment) in main group
From baseline until week 24
The Occurrence of Relative Efficacy Response in APG
The Occurrence of Relative Efficacy Response (HbA1c Lowering by at Least 0.5% After 12 Weeks of Treatment) in APG
From baseline until week 12
The Change in Fasting Plasma Glucose (FPG) From Baseline After 24 Weeks of Treatment in Main Group
The change in fasting plasma glucose (FPG) from baseline after 24 weeks of treatment in main group.
Adjusted mean: The model includes continuous baseline HbA1c, continuous baseline FPG and treatment group.
Baseline and week 24
The Change in Fasting Plasma Glucose (FPG) From Baseline After 12 Weeks of Treatment in APG
The Change in Fasting Plasma Glucose (FPG) From Baseline After 12 Weeks of Treatment in APG.
Adjusted mean: The model includes continuous baseline HbA1c, continuous baseline FPG and treatment group.
Baseline and week 12
The Frequency of Patients With Use of Rescue Therapy During 24 Week Treatment Period in Main Group
The frequency of patients with use of rescue therapy during 24 week treatment period in main group.
For this analysis the main group contrast 'Metformin 1000mg BID, Linagliptin 2.5mg / Metformin 1000mg BID' could not be analysed due to lack of events in the Metformin 1000mg BID group.
From baseline until week 24
The Frequency of Patients With Use of Rescue Therapy During 12 Week Treatment Period in APG
The Frequency of Patients With Use of Rescue Therapy During 12 Week Treatment Period in APG.
From baseline until week 12
Beijing
China
1288.18.86003 Boehringer Ingelheim Investigational Site
Beijing
China
1288.18.86004 Boehringer Ingelheim Investigational Site
Beijing
China
1288.18.86046 Boehringer Ingelheim Investigational Site
Beijing
China
1288.18.86019 Boehringer Ingelheim Investigational Site
Changchun
China
1288.18.86020 Boehringer Ingelheim Investigational Site
Changchun
China
1288.18.86028 Boehringer Ingelheim Investigational Site
Changsha
China
1288.18.86029 Boehringer Ingelheim Investigational Site
Changsha
China
1288.18.86050 Boehringer Ingelheim Investigational Site
Changsha
China
1288.18.86045 Boehringer Ingelheim Investigational Site
Chengdu
China
1288.18.86042 Boehringer Ingelheim Investigational Site
Chongqing
China
1288.18.86023 Boehringer Ingelheim Investigational Site
Dalian
China
1288.18.86009 Boehringer Ingelheim Investigational Site
Guangzhou
China
1288.18.86010 Boehringer Ingelheim Investigational Site
Guangzhou
China
1288.18.86012 Boehringer Ingelheim Investigational Site
Guangzhou
China
1288.18.86047 Boehringer Ingelheim Investigational Site
Haerbin
China
1288.18.86032 Boehringer Ingelheim Investigational Site
Hefei
China
1288.18.86016 Boehringer Ingelheim Investigational Site
Hengshui
China
1288.18.86017 Boehringer Ingelheim Investigational Site
Jinan
China
1288.18.86026 Boehringer Ingelheim Investigational Site
Lanzhou
China
1288.18.86039 Boehringer Ingelheim Investigational Site
Nanchang
China
1288.18.86035 Boehringer Ingelheim Investigational Site
Nanjing
China
1288.18.86036 Boehringer Ingelheim Investigational Site
Nanjing
China
1288.18.86034 Boehringer Ingelheim Investigational Site
Nanning
China
1288.18.86006 Boehringer Ingelheim Investigational Site
Shanghai
China
1288.18.86007 Boehringer Ingelheim Investigational Site
Shanghai
China
1288.18.86008 Boehringer Ingelheim Investigational Site
Shanghai
China
1288.18.86013 Boehringer Ingelheim Investigational Site
Shantou
China
1288.18.86022 Boehringer Ingelheim Investigational Site
Shenyang
China
1288.18.86014 Boehringer Ingelheim Investigational Site
Shijiazhuang
China
1288.18.86015 Boehringer Ingelheim Investigational Site
Shijiazhuang
China
1288.18.86038 Boehringer Ingelheim Investigational Site
Suzhou
China
1288.18.86049 Boehringer Ingelheim Investigational Site
Wuhan
China
1288.18.86033 Boehringer Ingelheim Investigational Site
Wuhu
China
1288.18.86024 Boehringer Ingelheim Investigational Site
Xi'an
China
1288.18.86025 Boehringer Ingelheim Investigational Site
Xi'an
China
1288.18.86030 Boehringer Ingelheim Investigational Site
Yueyang
China
1288.18.60004 Boehringer Ingelheim Investigational Site
Kelantan
Malaysia
1288.18.60003 Boehringer Ingelheim Investigational Site
Kuala Selangor
Malaysia
1288.18.60002 Boehringer Ingelheim Investigational Site
Malacca
Malaysia
1288.18.60005 Boehringer Ingelheim Investigational Site
Negeri Sembilan
Malaysia
1288.18.60007 Boehringer Ingelheim Investigational Site
Negeri Sembilan
Malaysia
1288.18.60001 Boehringer Ingelheim Investigational Site
Perak
Malaysia
1288.18.60006 Boehringer Ingelheim Investigational Site
Perak
Malaysia
1288.18.60008 Boehringer Ingelheim Investigational Site
Putrajaya
Malaysia
1288.18.63007 Boehringer Ingelheim Investigational Site
Cebu
Philippines
1288.18.63003 Boehringer Ingelheim Investigational Site
Cebu City
Philippines
1288.18.63002 Boehringer Ingelheim Investigational Site
Makati City
Philippines
1288.18.63001 Boehringer Ingelheim Investigational Site
Manila
Philippines
1288.18.63008 Boehringer Ingelheim Investigational Site
Quezon City
Philippines
1288.18.63006 Boehringer Ingelheim Investigational Site
Surigao City
Philippines
1288.18.63005 Boehringer Ingelheim Investigational Site
Tagum
Philippines
1288.18.84003 Boehringer Ingelheim Investigational Site
Hanoi
Vietnam
1288.18.84001 Boehringer Ingelheim Investigational Site
Ho Chi Minh City
Vietnam
1288.18.84002 Boehringer Ingelheim Investigational Site
Ho Chi Minh City
Vietnam
FG002
Main: Metformin 1000mg BID
Main Group: Patients received metformin 1000mg twice daily (BID), administered oral as tablet.
FG003
Main: Linagliptin 2.5mg / Metformin 500mg BID
Main Group: Patients received linagliptin 2.5mg and metformin 500mg twice daily (BID), administered oral as fixed dose combination (FDC) tablet.
FG004
Main: Linagliptin 2.5mg / Metformin 1000mg BID
Main Group: Patients received linagliptin 2.5mg and metformin 1000mg twice daily (BID), administered oral as fixed dose combination (FDC) tablet.
FG005
APG: Linagliptin 5mg QD
Additional parallel group (APG): Patients received linagliptin 5mg once daily (QD), administered oral as tablet.
(Data up to week 12)
FG006
APG: Linagliptin 2.5mg / Metformin 1000mg BID
Additional parallel group (APG): Patients received linagliptin 2.5mg and metformin 1000mg twice daily (BID), administered oral as fixed dose combination (FDC) tablet.
(Data up to week 12)
FG000147 subjects
FG001145 subjects
FG002144 subjects
FG003147 subjects
FG004147 subjects
FG00571 subjects
FG00672 subjects
COMPLETED
FG000130 subjects
FG001137 subjects
FG002127 subjects
FG003137 subjects
FG004131 subjects
FG00564 subjects
FG00665 subjects
NOT COMPLETED
FG00017 subjects
FG0018 subjects
FG00217 subjects
FG00310 subjects
FG00416 subjects
FG0057 subjects
FG0067 subjects
Type
Comment
Reasons
Adverse Event
FG0003 subjects
FG0014 subjects
FG0029 subjects
FG0032 subjects
FG0047 subjects
FG0053 subjects
FG0065 subjects
Lack of Efficacy
FG0003 subjects
FG0011 subjects
FG0020 subjects
FG0030 subjects
FG004
Non compliance with protocol
FG0000 subjects
FG0012 subjects
FG0021 subjects
FG0033 subjects
FG004
Lost to Follow-up
FG0002 subjects
FG0011 subjects
FG0022 subjects
FG0032 subjects
FG004
Refused to continue trial medication
FG0008 subjects
FG0010 subjects
FG0024 subjects
FG0032 subjects
FG004
Other Reason
FG0001 subjects
FG0010 subjects
FG0021 subjects
FG0031 subjects
FG004
Treated set (TS): all patients treated with at least 1 dose of study medication
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
Main: Linagliptin 5mg QD
Main Group: Patients received linagliptin 5mg QD, administered oral as tablet.
BG001
Main: Metformin 500mg BID
Main Group: Patients received metformin 500mg BID, administered oral as tablet.
BG002
Main: Metformin 1000mg BID
Main Group: Patients received metformin 1000mg BID, administered oral as tablet.
BG003
Main: Linagliptin 2.5mg / Metformin 500mg BID
Main Group: Patients received linagliptin 2.5mg and metformin 500mg BID, administered oral as fixed dose combination (FDC) tablet.
BG004
Main: Linagliptin 2.5mg / Metformin 1000mg BID
Main Group: Patients received linagliptin 2.5mg and metformin 1000mg BID, administered oral as fixed dose combination (FDC) tablet.
BG005
APG: Linagliptin 5mg QD
Additional parallel group (APG): Patients received linagliptin 5mg QD, administered oral as tablet.
(Data up to week 12)
BG006
APG: Linagliptin 2.5mg / Metformin 1000mg BID
Additional parallel group (APG): Patients received linagliptin 2.5mg and metformin 1000mg BID, administered oral as fixed dose combination (FDC) tablet.
(Data up to week 12)
BG007
Total
Total of all reporting groups
Denominators
Units
Counts
Participants
BG000147
BG001145
BG002144
BG003147
BG004147
BG00571
BG00672
BG007873
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
BG00050.8± 10.5
BG00152.1± 9.6
BG00251.4± 10.4
BG003
Sex: Female, Male
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Female
BG00071
BG00154
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
The Change From Baseline in HbA1c After 24 Weeks of Treatment in Main Group
The change from baseline in HbA1c after 24 weeks of treatment in main group.
The mean was adjusted by baseline HbA1c and treatment group.
Full analysis set (FAS): all randomised and treated patients who had a baseline and at least 1 on-treatment HbA1c value As the imputation rule for missing data the last observation carried forward (LOCF) was used.
Posted
Mean
Standard Error
percentage
Baseline and week 24
ID
Title
Description
OG000
Main: Linagliptin 5mg QD
Main Group: Patients received linagliptin 5mg QD, administered oral as tablet.
OG001
Main: Metformin 500mg BID
Main Group: Patients received metformin 500mg BID, administered oral as tablet.
OG002
Main: Metformin 1000mg BID
Main Group: Patients received metformin 1000mg BID, administered oral as tablet.
OG003
Main: Linagliptin 2.5mg / Metformin 500mg BID
Main Group: Patients received linagliptin 2.5mg and metformin 500mg BID, administered oral as fixed dose combination (FDC) tablet.
OG004
Main: Linagliptin 2.5mg / Metformin 1000mg BID
Main Group: Patients received linagliptin 2.5mg and metformin 1000mg BID, administered oral as fixed dose combination (FDC) tablet.
Units
Counts
Participants
OG000141
OG001144
OG002133
OG003
Title
Denominators
Categories
Title
Measurements
OG000-1.29± 0.08
OG001-1.64± 0.08
OG002-2.07± 0.08
OG003
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
OG002
OG004
The model includes treatment as a fixed effect and baseline HbA1c as a linear covariate.
The null and alternative hypotheses were tested in a hierarchical sequence. The next null hypothesis was tested in a confirmatory way only if all prior null-hypotheses were rejected. 'Greater effect' refers to a greater reduction in HbA1c.
ANCOVA
0.0587
Mean Difference (Final Values)
-0.22
Standard Error of the Mean
0.12
2-Sided
95
-0.45
0.01
The adjusted mean difference was calculated as the adjusted mean of 'Main: Linagliptin 2.5mg / Metformin 1000mg BID' minus 'Main: Metformin 1000mg BID'.
No
Secondary
The Occurrence of Treat to Target Efficacy Response in Terms of HbA1c < 7.0 % After 24 Weeks of Treatment in Main Group
The occurrence of treat to target efficacy response in terms of HbA1c < 7.0 % after 24 weeks of treatment in main group.
FAS - non-completers were considered as nonresponders (NCF)
Posted
Number
95% Confidence Interval
percentage of participants
Week 24 (after first drug administration)
ID
Title
Description
OG000
Main: Linagliptin 5mg QD
Main Group: Patients received linagliptin 5mg QD, administered oral as tablet.
OG001
Main: Metformin 500mg BID
Main Group: Patients received metformin 500mg BID, administered oral as tablet.
OG002
Main: Metformin 1000mg BID
Main Group: Patients received metformin 1000mg BID, administered oral as tablet.
OG003
Main: Linagliptin 2.5mg / Metformin 500mg BID
Main Group: Patients received linagliptin 2.5mg and metformin 500mg BID, administered oral as fixed dose combination (FDC) tablet.
Secondary
The Occurrence of Treat to Target Efficacy Response in Terms of HbA1c < 7.0 % After 12 Weeks of Treatment in APG
The occurrence of treat to target efficacy response in terms of HbA1c < 7.0 % after 12 weeks of treatment in APG.
FAS (NCF)
Posted
Number
95% Confidence Interval
percentage of participants
Week 12 (after first drug administration)
ID
Title
Description
OG000
APG: Linagliptin 5mg QD
Additional parallel group (APG): Patients received linagliptin 5mg QD, administered oral as tablet.
(Data up to week 12)
OG001
APG: Linagliptin 2.5mg / Metformin 1000mg BID
Additional parallel group (APG): Patients received linagliptin 2.5mg and metformin 1000mg BID, administered oral as fixed dose combination (FDC) tablet.
(Data up to week 12)
Units
Counts
Participants
OG000
Secondary
The Occurrence of Treat to Target Efficacy Response in Terms of HbA1c < 6.5% After 24 Weeks of Treatment in Main Group
The occurrence of treat to target efficacy response in terms of HbA1c < 6.5% after 24 weeks of treatment in main group.
FAS (NCF)
Posted
Number
95% Confidence Interval
percentage of participants
Week 24 (after first drug administration)
ID
Title
Description
OG000
Main: Linagliptin 5mg QD
Main Group: Patients received linagliptin 5mg QD, administered oral as tablet.
OG001
Main: Metformin 500mg BID
Main Group: Patients received metformin 500mg BID, administered oral as tablet.
OG002
Main: Metformin 1000mg BID
Main Group: Patients received metformin 1000mg BID, administered oral as tablet.
OG003
Main: Linagliptin 2.5mg / Metformin 500mg BID
Main Group: Patients received linagliptin 2.5mg and metformin 500mg BID, administered oral as fixed dose combination (FDC) tablet.
Secondary
The Occurrence of Treat to Target Efficacy Response in Terms of HbA1c < 6.5% After 12 Weeks of Treatment in APG
The occurrence of treat to target efficacy response in terms of HbA1c < 6.5% after 12 weeks of treatment in APG.
FAS (NCF)
Posted
Number
95% Confidence Interval
percentage of participants
Week 12 (after first drug administration)
ID
Title
Description
OG000
APG: Linagliptin 5mg QD
Additional parallel group (APG): Patients received linagliptin 5mg QD, administered oral as tablet.
(Data up to week 12)
OG001
APG: Linagliptin 2.5mg / Metformin 1000mg BID
Additional parallel group (APG): Patients received linagliptin 2.5mg and metformin 1000mg BID, administered oral as fixed dose combination (FDC) tablet.
(Data up to week 12)
Units
Counts
Participants
OG000
Primary
The Change From Baseline in HbA1c After 24 Weeks of Treatment in Main Group - FAS (OC)
The change from baseline in HbA1c after 24 weeks of treatment in main group. Only subjects from the FAS with measured HbA1c values (observed cases [OC]) were considered.
The mean was adjusted by treatment, baseline HbA1c, week and treatment*week.
The sensitivity analysis was added as the primary analysis failed with borderline results.
FAS (OC): subjects from the FAS with measured HbA1c values (observed cases [OC]) were considered
Posted
Mean
Standard Error
percentage
Baseline and week 24
ID
Title
Description
OG000
Main: Linagliptin 5mg QD
Main Group: Patients received linagliptin 5mg QD, administered oral as tablet.
OG001
Main: Metformin 500mg BID
Main Group: Patients received metformin 500mg BID, administered oral as tablet.
OG002
Main: Metformin 1000mg BID
Main Group: Patients received metformin 1000mg BID, administered oral as tablet.
OG003
Main: Linagliptin 2.5mg / Metformin 500mg BID
Primary
The Change From Baseline in HbA1c After 12 Weeks of Treatment in APG
The change from baseline in HbA1c after 12 weeks of treatment in additional parallel group (APG)
The mean was adjusted by baseline HbA1c and treatment group.
FAS (LOCF)
Posted
Mean
Standard Error
percentage
Baseline and week 12
ID
Title
Description
OG000
APG: Linagliptin 5mg QD
Additional parallel group (APG): Patients received linagliptin 5mg QD, administered oral as tablet.
(Data up to week 12)
OG001
APG: Linagliptin 2.5mg / Metformin 1000mg BID
Additional parallel group (APG): Patients received linagliptin 2.5mg and metformin 1000mg BID, administered oral as fixed dose combination (FDC) tablet.
(Data up to week 12)
Units
Counts
Participants
OG000
Secondary
The Occurrence of Relative Efficacy Response in Main Group
The occurrence of relative efficacy response (HbA1c lowering by at least 0.5% after 24 weeks of treatment) in main group
FAS (NCF)
Posted
Number
95% Confidence Interval
percentage of participants
From baseline until week 24
ID
Title
Description
OG000
Main: Linagliptin 5mg QD
Main Group: Patients received linagliptin 5mg QD, administered oral as tablet.
OG001
Main: Metformin 500mg BID
Main Group: Patients received metformin 500mg BID, administered oral as tablet.
OG002
Main: Metformin 1000mg BID
Main Group: Patients received metformin 1000mg BID, administered oral as tablet.
OG003
Main: Linagliptin 2.5mg / Metformin 500mg BID
Main Group: Patients received linagliptin 2.5mg and metformin 500mg BID, administered oral as fixed dose combination (FDC) tablet.
OG004
Secondary
The Occurrence of Relative Efficacy Response in APG
The Occurrence of Relative Efficacy Response (HbA1c Lowering by at Least 0.5% After 12 Weeks of Treatment) in APG
FAS (NCF)
Posted
Number
95% Confidence Interval
percentage of participants
From baseline until week 12
ID
Title
Description
OG000
APG: Linagliptin 5mg QD
Additional parallel group (APG): Patients received linagliptin 5mg QD, administered oral as tablet.
(Data up to week 12)
OG001
APG: Linagliptin 2.5mg / Metformin 1000mg BID
Additional parallel group (APG): Patients received linagliptin 2.5mg and metformin 1000mg BID, administered oral as fixed dose combination (FDC) tablet.
(Data up to week 12)
Units
Counts
Participants
OG000
Secondary
The Change in Fasting Plasma Glucose (FPG) From Baseline After 24 Weeks of Treatment in Main Group
The change in fasting plasma glucose (FPG) from baseline after 24 weeks of treatment in main group.
Adjusted mean: The model includes continuous baseline HbA1c, continuous baseline FPG and treatment group.
FAS (LOCF)
Posted
Mean
Standard Error
mg/dL
Baseline and week 24
ID
Title
Description
OG000
Main: Linagliptin 5mg QD
Main Group: Patients received linagliptin 5mg QD, administered oral as tablet.
OG001
Main: Metformin 500mg BID
Main Group: Patients received metformin 500mg BID, administered oral as tablet.
OG002
Main: Metformin 1000mg BID
Main Group: Patients received metformin 1000mg BID, administered oral as tablet.
OG003
Main: Linagliptin 2.5mg / Metformin 500mg BID
Main Group: Patients received linagliptin 2.5mg and metformin 500mg BID, administered oral as fixed dose combination (FDC) tablet.
Secondary
The Change in Fasting Plasma Glucose (FPG) From Baseline After 12 Weeks of Treatment in APG
The Change in Fasting Plasma Glucose (FPG) From Baseline After 12 Weeks of Treatment in APG.
Adjusted mean: The model includes continuous baseline HbA1c, continuous baseline FPG and treatment group.
FAS (LOCF)
Posted
Mean
Standard Error
mg/dL
Baseline and week 12
ID
Title
Description
OG000
APG: Linagliptin 5mg QD
Additional parallel group (APG): Patients received linagliptin 5mg QD, administered oral as tablet.
(Data up to week 12)
OG001
APG: Linagliptin 2.5mg / Metformin 1000mg BID
Additional parallel group (APG): Patients received linagliptin 2.5mg and metformin 1000mg BID, administered oral as fixed dose combination (FDC) tablet.
(Data up to week 12)
Units
Counts
Participants
OG000
Secondary
The Frequency of Patients With Use of Rescue Therapy During 24 Week Treatment Period in Main Group
The frequency of patients with use of rescue therapy during 24 week treatment period in main group.
For this analysis the main group contrast 'Metformin 1000mg BID, Linagliptin 2.5mg / Metformin 1000mg BID' could not be analysed due to lack of events in the Metformin 1000mg BID group.
FAS
Posted
Number
95% Confidence Interval
percentage of participants
From baseline until week 24
ID
Title
Description
OG000
Main: Linagliptin 5mg QD
Main Group: Patients received linagliptin 5mg QD, administered oral as tablet.
OG001
Main: Metformin 500mg BID
Main Group: Patients received metformin 500mg BID, administered oral as tablet.
OG002
Main: Metformin 1000mg BID
Main Group: Patients received metformin 1000mg BID, administered oral as tablet.
OG003
Main: Linagliptin 2.5mg / Metformin 500mg BID
Main Group: Patients received linagliptin 2.5mg and metformin 500mg BID, administered oral as fixed dose combination (FDC) tablet.
Secondary
The Frequency of Patients With Use of Rescue Therapy During 12 Week Treatment Period in APG
The Frequency of Patients With Use of Rescue Therapy During 12 Week Treatment Period in APG.
FAS
Posted
Number
95% Confidence Interval
percentage of participants
From baseline until week 12
ID
Title
Description
OG000
APG: Linagliptin 5mg QD
Additional parallel group (APG): Patients received linagliptin 5mg QD, administered oral as tablet.
(Data up to week 12)
OG001
APG: Linagliptin 2.5mg / Metformin 1000mg BID
Additional parallel group (APG): Patients received linagliptin 2.5mg and metformin 1000mg BID, administered oral as fixed dose combination (FDC) tablet.
(Data up to week 12)
Units
Counts
Participants
OG000
Time Frame
From first drug administration (week 1) until end of treatment, up to 24 weeks
Description
Not provided
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
Main: Linagliptin 5mg QD
Main Group: Patients once daily received linagliptin 5mg QD, administered oral as tablet.
2
147
30
147
EG001
Main: Metformin 500mg BID
Main Group: Patients twice daily received metformin 500mg BID, administered oral as tablet.
1
145
31
145
EG002
Main: Metformin 1000mg BID
Main Group: Patients twice daily received metformin 1000mg BID, administered oral as tablet.
2
144
42
144
EG003
Main: Linagliptin 2.5mg / Metformin 500mg BID
Main Group: Patients twice daily received linagliptin 2.5mg and metformin 500mg BID, administered oral as fixed dose combination (FDC) tablet.
1
147
32
147
EG004
Main: Linagliptin 2.5mg / Metformin 1000mg BID
Main Group: Patients twice daily received linagliptin 2.5mg and metformin 1000mg BID, administered oral as fixed dose combination (FDC) tablet.
4
147
41
147
EG005
APG: Linagliptin 5mg QD up to Week 12
Additional parallel group (APG): Patients once daily received linagliptin 5mg QD, administered oral as tablet.
(Data up to week 12)
1
71
20
71
EG006
APG: Linagliptin 2.5mg / Metformin 1000mg BID up to Week 12
Additional parallel group (APG): Patients twice daily received linagliptin 2.5mg and metformin 1000mg BID, administered oral as fixed dose combination (FDC) tablet.
(Data up to week 12)
1
72
15
72
EG007
APG: Linagliptin 5mg After Week 12
Additional parallel group (APG): Patients once daily received linagliptin 5mg QD, administered oral as tablet. Data from week 12 to week 24
0
33
2
33
EG008
APG: Linagliptin 5mg - Linagliptin 2.5mg / Met After Week 12
Additional parallel group (APG): Patients who received linagliptin 5mg QD, administered oral as tablet during the first 12 weeks and switched to linagliptin 2.5mg and metformin 1000mg (met) BID, administered oral as fixed dose combination (FDC) tablet from week 12 to week 24. Data from week 12 to week 24.
1
31
9
31
EG009
APG: Linagliptin 2.5mg / Metformin 1000mg After Week 12
Additional parallel group (APG): Patients twice daily received linagliptin 2.5mg and metformin 1000mg BID, administered oral as fixed dose combination (FDC) tablet.
Data from week 12 to week 24.
1
65
9
65
Serious Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Anaemia
Blood and lymphatic system disorders
MEDDRA 17.0
Systematic Assessment
EG0000 affected147 at risk
EG0010 affected145 at risk
EG0020 affected144 at risk
EG0030 affected147 at risk
EG0041 affected147 at risk
EG0050 affected71 at risk
EG0060 affected72 at risk
EG0070 affected33 at risk
EG0080 affected31 at risk
EG0090 affected65 at risk
Acute coronary syndrome
Cardiac disorders
MEDDRA 17.0
Systematic Assessment
EG0000 affected147 at risk
EG0010 affected145 at risk
EG0021 affected144 at risk
EG003
Otosclerosis
Ear and labyrinth disorders
MEDDRA 17.0
Systematic Assessment
EG0000 affected147 at risk
EG0010 affected145 at risk
EG0021 affected144 at risk
EG003
Gastric ulcer
Gastrointestinal disorders
MEDDRA 17.0
Systematic Assessment
EG0000 affected147 at risk
EG0010 affected145 at risk
EG0020 affected144 at risk
EG003
Gastritis
Gastrointestinal disorders
MEDDRA 17.0
Systematic Assessment
EG0000 affected147 at risk
EG0010 affected145 at risk
EG0020 affected144 at risk
EG003
Paronychia
Infections and infestations
MEDDRA 17.0
Systematic Assessment
EG0000 affected147 at risk
EG0010 affected145 at risk
EG0020 affected144 at risk
EG003
Pharyngotonsillitis
Infections and infestations
MEDDRA 17.0
Systematic Assessment
EG0000 affected147 at risk
EG0010 affected145 at risk
EG0020 affected144 at risk
EG003
Pneumonia
Infections and infestations
MEDDRA 17.0
Systematic Assessment
EG0000 affected147 at risk
EG0010 affected145 at risk
EG0020 affected144 at risk
EG003
Septic shock
Infections and infestations
MEDDRA 17.0
Systematic Assessment
EG0000 affected147 at risk
EG0010 affected145 at risk
EG0020 affected144 at risk
EG003
Urinary tract infection
Infections and infestations
MEDDRA 17.0
Systematic Assessment
EG0000 affected147 at risk
EG0010 affected145 at risk
EG0020 affected144 at risk
EG003
Clavicle fracture
Injury, poisoning and procedural complications
MEDDRA 17.0
Systematic Assessment
EG0000 affected147 at risk
EG0010 affected145 at risk
EG0020 affected144 at risk
EG003
Contusion
Injury, poisoning and procedural complications
MEDDRA 17.0
Systematic Assessment
EG0001 affected147 at risk
EG0010 affected145 at risk
EG0020 affected144 at risk
EG003
Foot fracture
Injury, poisoning and procedural complications
MEDDRA 17.0
Systematic Assessment
EG0000 affected147 at risk
EG0010 affected145 at risk
EG0020 affected144 at risk
EG003
Dehydration
Metabolism and nutrition disorders
MEDDRA 17.0
Systematic Assessment
EG0000 affected147 at risk
EG0010 affected145 at risk
EG0020 affected144 at risk
EG003
Pituitary tumour
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MEDDRA 17.0
Systematic Assessment
EG0000 affected147 at risk
EG0010 affected145 at risk
EG0020 affected144 at risk
EG003
Cerebral infarction
Nervous system disorders
MEDDRA 17.0
Systematic Assessment
EG0000 affected147 at risk
EG0010 affected145 at risk
EG0020 affected144 at risk
EG003
Lacunar infarction
Nervous system disorders
MEDDRA 17.0
Systematic Assessment
EG0000 affected147 at risk
EG0011 affected145 at risk
EG0020 affected144 at risk
EG003
Renal failure acute
Renal and urinary disorders
MEDDRA 17.0
Systematic Assessment
EG0000 affected147 at risk
EG0010 affected145 at risk
EG0020 affected144 at risk
EG003
Breast disorder
Reproductive system and breast disorders
MEDDRA 17.0
Systematic Assessment
EG0001 affected147 at risk
EG0010 affected145 at risk
EG0020 affected144 at risk
EG003
Other Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Upper respiratory tract infection
Infections and infestations
MEDDRA 17.0
Systematic Assessment
EG0006 affected147 at risk
EG0016 affected145 at risk
EG00214 affected144 at risk
EG00312 affected147 at risk
EG00411 affected147 at risk
EG0052 affected71 at risk
EG0064 affected72 at risk
EG0070 affected33 at risk
EG0081 affected31 at risk
EG0091 affected65 at risk
Nasopharyngitis
Infections and infestations
MEDDRA 17.0
Systematic Assessment
EG0002 affected147 at risk
EG0012 affected145 at risk
EG0023 affected144 at risk
EG003
Hyperglycaemia
Metabolism and nutrition disorders
MEDDRA 17.0
Systematic Assessment
EG0007 affected147 at risk
EG0014 affected145 at risk
EG0020 affected144 at risk
EG003
Hyperuricaemia
Metabolism and nutrition disorders
MEDDRA 17.0
Systematic Assessment
EG00011 affected147 at risk
EG00113 affected145 at risk
EG00213 affected144 at risk
EG003
Dyslipidaemia
Metabolism and nutrition disorders
MEDDRA 17.0
Systematic Assessment
EG0002 affected147 at risk
EG0013 affected145 at risk
EG0024 affected144 at risk
EG003
Diarrhoea
Gastrointestinal disorders
MEDDRA 17.0
Systematic Assessment
EG0005 affected147 at risk
EG0018 affected145 at risk
EG00216 affected144 at risk
EG003
Dizziness
Nervous system disorders
MEDDRA 17.0
Systematic Assessment
EG0003 affected147 at risk
EG0012 affected145 at risk
EG0027 affected144 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
Other - Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights.
Point of Contact
Title
Organization
Phone
Extension
Email
Boehringer Ingelheim Call Center
Boehringer Ingelheim Pharmaceuticals
1-800-243-0127
clintriage.rdg@boehringer-ingelheim.com
ID
Term
D003924
Diabetes Mellitus, Type 2
Ancestor Terms
ID
Term
D003920
Diabetes Mellitus
D044882
Glucose Metabolism Disorders
D008659
Metabolic Diseases
D009750
Nutritional and Metabolic Diseases
D004700
Endocrine System Diseases
Browse Leaves
Not provided
Browse Branches
Not provided
ID
Term
D000069476
Linagliptin
D008687
Metformin
Ancestor Terms
ID
Term
D011687
Purines
D006574
Heterocyclic Compounds, 2-Ring
D000072471
Heterocyclic Compounds, Fused-Ring
D006571
Heterocyclic Compounds
D011799
Quinazolines
D001645
Biguanides
D006146
Guanidines
D000578
Amidines
D009930
Organic Chemicals
Browse Leaves
Not provided
Browse Branches
Not provided
0 subjects
FG0051 subjects
FG0060 subjects
0 subjects
FG0050 subjects
FG0060 subjects
0 subjects
FG0050 subjects
FG0061 subjects
8 subjects
FG0051 subjects
FG0061 subjects
1 subjects
FG0052 subjects
FG0060 subjects
51.4
± 10.2
BG00450.7± 9.4
BG00549.5± 11.6
BG00649.9± 11.7
BG00751.0± 10.3
53
BG00355
BG00460
BG00523
BG00632
BG007348
Male
BG00076
BG00191
BG00291
BG00392
BG00487
BG00548
BG00640
BG007525
142
OG004141
-2.15
± 0.08
OG004-2.29± 0.08
Superiority or Other
OG000
OG004
The model includes treatment as a fixed effect and baseline HbA1c as a linear covariate.
The null and alternative hypotheses were tested in a hierarchical sequence. The next null hypothesis was tested in a confirmatory way only if all prior null-hypotheses were rejected. 'Greater effect' refers to a greater reduction in HbA1c.
ANCOVA
<0.0001
Mean Difference (Final Values)
-1.00
Standard Error of the Mean
0.11
2-Sided
95
-1.23
-0.78
The adjusted mean difference was calculated as the adjusted mean of 'Main: Linagliptin 2.5mg / Metformin 1000mg BID' minus 'Main: Linagliptin 5mg QD'.
No
Superiority or Other
OG001
OG003
The model includes treatment as a fixed effect and baseline HbA1c as a linear covariate.
The null and alternative hypotheses were tested in a hierarchical sequence. The next null hypothesis was tested in a confirmatory way only if all prior null-hypotheses were rejected. 'Greater effect' refers to a greater reduction in HbA1c.
ANCOVA
<0.0001
Mean Difference (Final Values)
-0.51
Standard Error of the Mean
0.11
2-Sided
95
-0.73
-0.29
The adjusted mean difference was calculated as the adjusted mean of 'Main: Linagliptin 2.5mg / Metformin 500mg BID' minus 'Main: Metformin 500mg BID'.
No
Superiority or Other
OG000
OG003
The model includes treatment as a fixed effect and baseline HbA1c as a linear covariate.
The null and alternative hypotheses were tested in a hierarchical sequence. The next null hypothesis was tested in a confirmatory way only if all prior null-hypotheses were rejected. 'Greater effect' refers to a greater reduction in HbA1c.
ANCOVA
<0.0001
Mean Difference (Final Values)
-0.87
Standard Error of the Mean
0.11
2-Sided
95
-1.09
-0.64
The adjusted mean difference was calculated as the adjusted mean of 'Main: Linagliptin 2.5mg / Metformin 500mg BID' minus 'Main: Linagliptin 5mg QD'.
No
Superiority or Other
OG004
Main: Linagliptin 2.5mg / Metformin 1000mg BID
Main Group: Patients received linagliptin 2.5mg and metformin 1000mg BID, administered oral as fixed dose combination (FDC) tablet.
The logistic regression includes treatment and continuous baseline HbA1c.
Regression, Logistic
0.0062
Odds Ratio (OR)
3.135
Standard Error of the Mean
1.310
2-Sided
95
1.383
7.110
No
Superiority or Other
Main Group: Patients received linagliptin 2.5mg and metformin 500mg BID, administered oral as fixed dose combination (FDC) tablet.
OG004
Main: Linagliptin 2.5mg / Metformin 1000mg BID
Main Group: Patients received linagliptin 2.5mg and metformin 1000mg BID, administered oral as fixed dose combination (FDC) tablet.
Units
Counts
Participants
OG000125
OG001133
OG002127
OG003135
OG004128
Title
Denominators
Categories
Title
Measurements
OG000-1.34± 0.08
OG001-1.68± 0.08
OG002-2.08± 0.08
OG003-2.16± 0.08
OG004-2.38± 0.08
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
OG002
OG004
Sensitivity analysis: Mixed Model for repeated measurements
The model includes baseline HbA1c as a linear covariate; visit, treatment and visit by treatment interaction as fixed classification effects and patient as a random effect with unstructured covariance structure to model within-patients errors.
ANCOVA
0.0109
Mean Difference (Final Values)
-0.30
Standard Error of the Mean
0.12
2-Sided
95
-0.53
-0.07
The adjusted mean difference was calculated as the adjusted mean of 'Main: Linagliptin 2.5mg / Metformin 1000mg BID' minus 'Main: Metformin 1000mg BID'.
No
Superiority or Other
OG000
OG004
Sensitivity analysis: Mixed Model for repeated measurements
The model includes baseline HbA1c as a linear covariate; visit, treatment and visit by treatment interaction as fixed classification effects and patient as a random effect with unstructured covariance structure to model within-patients errors.
ANCOVA
<0.0001
Mean Difference (Final Values)
-1.04
Standard Error of the Mean
0.12
2-Sided
95
-1.27
-0.81
The adjusted mean difference was calculated as the adjusted mean of 'Main: Linagliptin 2.5mg / Metformin 1000mg BID' minus 'Main: Linagliptin 5mg QD'.
No
Superiority or Other
OG001
OG003
Sensitivity analysis: Mixed Model for repeated measurements
The model includes baseline HbA1c as a linear covariate; visit, treatment and visit by treatment interaction as fixed classification effects and patient as a random effect with unstructured covariance structure to model within-patients errors.
ANCOVA
<0.0001
Mean Difference (Final Values)
-0.47
Standard Error of the Mean
0.12
2-Sided
95
-0.70
-0.24
The adjusted mean difference was calculated as the adjusted mean of 'Main: Linagliptin 2.5mg / Metformin 500mg BID ' minus 'Main: Metformin 500mg BID' .
No
Superiority or Other
OG000
OG003
Sensitivity analysis: Mixed Model for repeated measurements
The model includes baseline HbA1c as a linear covariate; visit, treatment and visit by treatment interaction as fixed classification effects and patient as a random effect with unstructured covariance structure to model within-patients errors.
ANCOVA
<0.0001
Mean Difference (Final Values)
-0.81
Standard Error of the Mean
0.12
2-Sided
95
-1.04
-0.58
The adjusted mean difference was calculated as the adjusted mean of 'Main: Linagliptin 2.5mg / Metformin 500mg BID' minus 'Main: Linagliptin 5mg QD'.
No
Superiority or Other
70
OG00168
Title
Denominators
Categories
Title
Measurements
OG000-3.46± 0.22
OG001-4.71± 0.22
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
The treatment effect of the 'APG: Linagliptin 2.5mg / Metformin 1000mg BID' was compared with 'APG: Linagliptin 5mg QD'.
The model includes treatment as a fixed effect and baseline HbA1c as a linear covariate.
ANCOVA
0.0001
Mean Difference (Final Values)
-1.25
Standard Error of the Mean
0.32
2-Sided
95
-1.87
-0.63
The adjusted mean difference was calculated as the adjusted mean of 'APG: Linagliptin 2.5mg / Metformin 1000mg BID' minus 'APG: Linagliptin 5mg QD'.
No
Superiority or Other
Main: Linagliptin 2.5mg / Metformin 1000mg BID
Main Group: Patients received linagliptin 2.5mg and metformin 1000mg BID, administered oral as fixed dose combination (FDC) tablet.
The logistic regression includes treatment and continuous baseline HbA1c.
Regression, Logistic
0.2523
Odds Ratio (OR)
1.865
Standard Error of the Mean
1.015
2-Sided
95
0.642
5.420
No
Superiority or Other
OG004
Main: Linagliptin 2.5mg / Metformin 1000mg BID
Main Group: Patients received linagliptin 2.5mg and metformin 1000mg BID, administered oral as fixed dose combination (FDC) tablet.
Units
Counts
Participants
OG000140
OG001144
OG002133
OG003142
OG004140
Title
Denominators
Categories
Title
Measurements
OG000-15.03± 2.25
OG001-29.87± 2.23
OG002-42.07± 2.31
OG003-39.33± 2.24
OG004-47.44± 2.26
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
OG002
OG004
The model includes continuous baseline HbA1c, continuous baseline FPG and treatment group.
ANCOVA
0.0971
Mean Difference (Final Values)
-5.37
Standard Error of the Mean
3.23
2-Sided
95
-11.72
0.98
The adjusted mean difference was calculated as the adjusted mean of 'Main: Linagliptin 2.5mg / Metformin 1000mg BID' minus 'Main: Metformin 1000mg BID'.
No
Superiority or Other
OG000
OG004
The model includes continuous baseline HbA1c, continuous baseline FPG and treatment group.
ANCOVA
<0.0001
Mean Difference (Final Values)
-32.42
Standard Error of the Mean
3.19
2-Sided
95
-38.67
-26.16
The adjusted mean difference was calculated as the adjusted mean of 'Main: Linagliptin 2.5mg / Metformin 1000mg BID' minus 'Main: Linagliptin 5mg QD'.
No
Superiority or Other
OG001
OG003
The model includes continuous baseline HbA1c, continuous baseline FPG and treatment group.
ANCOVA
0.0028
Median Difference (Net)
-9.47
Standard Error of the Mean
3.16
2-Sided
95
-15.66
-3.27
The adjusted mean difference was calculated as the adjusted mean of 'Main: Linagliptin 2.5mg / Metformin 500mg BID' minus 'Main: Metformin 500mg BID'.
No
Superiority or Other
OG000
OG003
The model includes continuous baseline HbA1c, continuous baseline FPG and treatment group.
ANCOVA
<0.0001
Mean Difference (Final Values)
-24.31
Standard Error of the Mean
3.17
2-Sided
95
-30.54
-18.08
The adjusted mean difference was calculated as the adjusted mean of 'Main: Linagliptin 2.5mg / Metformin 500mg BID' minus 'Main: Linagliptin 5mg QD'.
No
Superiority or Other
66
OG00167
Title
Denominators
Categories
Title
Measurements
OG000-56.70± 6.53
OG001-91.92± 6.48
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
The model includes continuous baseline HbA1c, continuous baseline FPG and treatment group.
ANCOVA
0.0002
Mean Difference (Final Values)
-35.21
Standard Error of the Mean
9.23
2-Sided
95
-53.48
-16.95
The adjusted mean difference was calculated as the adjusted mean of 'APG: Linagliptin 2.5mg / Metformin 1000mg BID' minus 'APG: Linagliptin 5mg QD'.
No
Superiority or Other
OG004
Main: Linagliptin 2.5mg / Metformin 1000mg BID
Main Group: Patients received linagliptin 2.5mg and metformin 1000mg BID, administered oral as fixed dose combination (FDC) tablet.
The logistic regression includes treatment and continuous baseline HbA1c. The validity of the model is questionable as there is possibly a quasi-complete separation of data points, the results shown are based on the last maximum likelihood iteration.
The logistic regression includes treatment and continuous baseline HbA1c. The validity of the model is questionable as there is possibly a quasi-complete separation of data points, the results shown are based on the last maximum likelihood iteration.
The logistic regression includes treatment and continuous baseline HbA1c. The validity of the model is questionable as there is possibly a quasi-complete separation of data points, the results shown are based on the last maximum likelihood iteration.