Linagliptin as Add on Therapy to Empagliflozin 10 mg or 2... | NCT02489968 | Trialant
NCT02489968
Sponsor
Boehringer Ingelheim
Status
Completed
Last Update Posted
Sep 6, 2018Actual
Enrollment
880Actual
Phase
Phase 3
Conditions
Diabetes Mellitus, Type 2
Interventions
empagliflozin 10 mg + linagliptin 5 mg
empagliflozin 10 mg
empagliflozin 25 mg + linagliptin 5 mg
empagliflozin 25 mg
Placebo
Countries
Japan
Protocol Section
Identification Module
NCT ID
NCT02489968
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
1275.13
Secondary IDs
Not provided
Brief Title
Linagliptin as Add on Therapy to Empagliflozin 10 mg or 25 mg With Japanese Patients With Type 2 Diabetes Mellitus
Official Title
A Phase III, Randomised, Double-blind, Parallel Group, 24-week Study to Evaluate Efficacy and Safety of Once Daily Empagliflozin 10 mg and Linagliptin 5 mg Fixed Dose Combination Compared With Empagliflozin 10 mg Plus Placebo and a 52-week Study to Evaluate Efficacy and Safety of Once Daily Empagliflozin 25 mg and Linagliptin 5 mg Fixed Dose Combination Compared With Empagliflozin 25 mg Plus Placebo in Patients With Type 2 Diabetes Mellitus and Insufficient Glycaemic Control After 16-week Treatment With Empagliflozin (10 mg or 25 mg) Alone Once Daily.
Acronym
Not provided
Organization
Boehringer IngelheimINDUSTRY
Status Module
Record Verification Date
Sep 2018
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 12, 2015Actual
Primary Completion Date
Nov 18, 2016Actual
Completion Date
Jun 16, 2017Actual
First Submitted Date
May 27, 2015
First Submission Date that Met QC Criteria
Jul 1, 2015
First Posted Date
Jul 3, 2015Estimated
Results Waived
Not provided
Results First Submitted Date
Nov 16, 2017
Results First Submitted that Met QC Criteria
Sep 3, 2018
Results First Posted Date
Sep 6, 2018Actual
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
Sep 3, 2018
Last Update Posted Date
Sep 6, 2018Actual
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
Two independent study parts (i.e. Part A and Part B) are included in this trial. Part A will evaluate empagliflozin 10 mg + linagliptin and Part B will evaluate empagliflozin 25 mg + linagliptin. All analyses will be carried out separately for these study parts. The objective of Part A is to investigate the efficacy, safety and tolerability of the fixed dose combination (FDC) of empagliflozin 10 mg / linagliptin 5 mg compared with empagliflozin 10 mg plus FDC matching placebo administered orally once daily for 24 weeks in Japanese patients with T2DM (Type 2 Diabetes Mellitus) who have insufficient glycaemic control after 16 weeks of treatment with empagliflozin 10 mg alone once daily. The study is designed to show superiority of the FDC of empagliflozin 10 mg / linagliptin 5 mg over empagliflozin 10 mg plus FDC matching placebo after 24 weeks of treatment. The objective of Part B is to investigate the efficacy, safety and tolerability of the FDC of empagliflozin 25 mg / linagliptin 5 mg compared with empagliflozin 25 mg plus FDC matching placebo administered orally once daily for 24 weeks in Japanese patients with T2DM who have insufficient glycaemic control after 16 weeks of treatment with empagliflozin 25 mg alone once daily. The study is designed to show superiority of the FDC of empagliflozin 25 mg / linagliptin 5 mg over empagliflozin 25 mg plus FDC matching placebo after 24 weeks of treatment. The 24 week treatment period will be followed by a 28 week extension treatment period to evaluate further efficacy and safety up to 52 weeks.
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
880Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
empagliflozin 10 mg + linagliptin 5 mg
Experimental
patient to receive a tablet containing low dose empagliflozin and linagliptin once daily
Drug: empagliflozin 10 mg + linagliptin 5 mg
empagliflozin 10 mg
Experimental
patient to receive a tablet containing low dose empagliflozin once daily
Drug: empagliflozin 10 mg
Drug: Placebo
empagliflozin 25 mg + linagliptin 5 mg
Experimental
patient to receive a tablet containing high dose empagliflozin and linagliptin once daily
Drug: empagliflozin 25 mg + linagliptin 5 mg
empagliflozin 25 mg
Experimental
patients to receive a tablet containing high dose empagliflozin once daily
Drug: empagliflozin 25 mg
Drug: Placebo
Interventions
Name
Type
Description
Arm Group Labels
Other Names
empagliflozin 10 mg + linagliptin 5 mg
Drug
empagliflozin low dose + linagliptin once daily
empagliflozin 10 mg + linagliptin 5 mg
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
Change in Glycated Haemoglobin A1c (HbA1c) (%) From Baseline After 24 Weeks of Treatment
Change from baseline in HbA1c (%) after 24 weeks of treatment with double-blind trial medication. Change was calculated as: HbA1c value at 24-week - HbA1c value at baseline, for each patient. Baseline was defined as the last observation before the first intake of double-blind randomised trial medication. Statistical analysis presented is based on a restricted maximum likelihood (REML)-based mixed model repeated measures (MMRM) approach. Full Analysis Set (Observed Cases) [FAS (OC)]: This analysis set consisted of all patients who were randomised and treated with at least 1 dose of trial drug during the double-blind part of the trial and who had a baseline HbA1c assessment and at least 1 on-treatment HbA1c assessment during the 24-week double-blind part of the trial. Observed cases analysis included only the available data that were observed while patients were on treatment, i.e., excluding the missing data.
Baseline and 24 week
Secondary Outcomes
Not provided
Other Outcomes
Not provided
Eligibility Module
Eligibility Criteria
Inclusion criteria:
Diagnosis of type 2 diabetes prior to informed consent
Male and female patients on diet and exercise regimen for at least 12 weeks prior to informed consent who are:
drug-naïve, defined as no antidiabetic drugs for at least 12 weeks prior to informed consent or,
pre-treated with one oral antidiabetic drug (for sulfonylurea, with up to half of the maximum approved dose) on stable dosage for at least 12 weeks prior to the informed consent (for thiazolidinedione, therapy has to be unchanged for at least 18 weeks prior to the informed consent). Individual antidiabetic drug will have to be discontinued at Visit 1.
haemoglobin A1c (HbA1c) at Visit 1 (screening)
for patients without antidiabetic therapy : HbA1c >=8.0 to =<10.5%
for patients with one oral antidiabetic drug : HbA1c >=7.5 to =<10.5%
HbA1c >=7.5 to =<10.0% at Visit 4 for randomisation into the double blind treatment period
Exclusion criteria:
Uncontrolled hyperglycaemia with a glucose level >270 mg/dL (>15.0 mmol/L) during the open label stabilisation period and placebo run in period
Impaired renal function, defined as estimated glomerular filtration rate (eGFR) <45 mL/min/1.73m2 (modification of diet in renal disease (MDRD) formula)
Acute coronary syndrome, stroke or transient ischemic attack (TIA) within 12 weeks prior to informed consent
Indication of liver disease, defined by serum levels of either alanine transaminase (ALT), aspartate transaminase (AST), or alkaline phosphatase (ALP) above 3 x upper limit of normal (ULN)
Accepts Healthy Volunteers
No
Sex
All
Sex/Gender Based
Not provided
Sex/Gender Description
Not provided
Minimum Age
20 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
Boehringer Ingelheim
Boehringer Ingelheim
Study Chair
Locations
Facility
Status
City
State
ZIP
Country
Contacts
Tokai Memorial Hospital
Aichi, Kasugai
487-0031
Japan
Japan Organization of Occupational Health and Safety Chubu Rosai Hospital
Kaku K, Haneda M, Tanaka Y, Lee G, Shiki K, Miyamoto Y, Solimando F, Lee J, Lee C, George J. Linagliptin as add-on to empagliflozin in a fixed-dose combination in Japanese patients with type 2 diabetes: Glycaemic efficacy and safety profile in a two-part, randomized, placebo-controlled trial. Diabetes Obes Metab. 2019 Jan;21(1):136-145. doi: 10.1111/dom.13496. Epub 2018 Sep 6.
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
880 subjects started the open label period
Recruitment Details
Not provided
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
FG000
Empagliflozin 10 mg OL
Patients were administered empagliflozin 10 milligram (mg) tablets, orally with water, once daily for 16-weeks of open-label stabilisation period.
FG001
Empagliflozin 25 mg OL
Periods
Title
Milestones
Reasons Not Completed
Open-label Treatment Period
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
Parallel 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
ParticipantInvestigator
empagliflozin 10 mg
Drug
empagliflozin low dose once daily
empagliflozin 10 mg
empagliflozin 25 mg + linagliptin 5 mg
Drug
empagliflozin high dose + linagliptin once daily
empagliflozin 25 mg + linagliptin 5 mg
empagliflozin 25 mg
Drug
empagliflozin high dose once daily
empagliflozin 25 mg
Placebo
Drug
empagliflozin 10 mg
empagliflozin 25 mg
Aichi, Nagoya
455-8530
Japan
Tokuyama Clinic
Chiba, Chiba
261-0004
Japan
Matsuyama Shimin Hospital
Ehime, Matsuyama
790-0067
Japan
Tanaka Int. Clinic, Ehime, DIA Med.,CV Med.
Ehime, Niihama
792-0045
Japan
Murakami Memorial Hp., Ehime, I.M.
Ehime, Saijo
793-0030
Japan
Kunisaki Makoto Clinic, Fukuoka, I.M./CV Med.
Fukuoka, Fukuoka
819-0168
Japan
Fukuoka Shin Mizumaki Hospital
Fukuoka, Onga
807-0051
Japan
Shin Yukuhashi Hospital
Fukuoka, Yukuhashi
824-0026
Japan
Hashimoto I.M., Gifu, I.M.
Gifu, Gifu
500-8225
Japan
Kikuchi Naika Clinic, Gunma, I.M.
Gunma, Maebashi
370-3573
Japan
Hasegawa Internal Medicine Clinic
Hokkaido, Chitose
066-0032
Japan
Ebetsu Internal Medicine Clinic
Hokkaido, Ebetsu
067-0041
Japan
Hakodate Koseiin Hakodate Central General Hospital
Hokkaido, Hakodate
040-8585
Japan
Iida Medical Clinic
Hokkaido, Hakodate
042-0942
Japan
Kurihara Clinic
Hokkaido, Sapporo
004-0053
Japan
Uehara Clinic
Hokkaido, Sapporo
006-0031
Japan
Manda Memorial Hospital
Hokkaido, Sapporo
060-0062
Japan
Sapporo Diabetes, Thyroid Clinic
Hokkaido, Sapporo
060-0807
Japan
Japan Community Health Care Organization Hokkaido Hospital
Hokkaido, Sapporo
062-8618
Japan
Ashiya Municipal Hospital
Hyogo, Ashiya
659-8502
Japan
Itabashi DIA Med. and DERM Clinic, Ibaraki, I.M.
Ibaraki, Koga
306-0232
Japan
Namegata District General Hospital
Ibaraki, Namegata
311-3516
Japan
Hokuriku Hp., Ishikawa, I.M.
Ishikawa, Kanazawa
921-8035
Japan
Oikawa Clinic
Iwate, Morioka
020-0066
Japan
Hirano Medical Clinic
Iwate, Morioka
020-0132
Japan
Iwamoto Clinic, Kagawa, DIAB I.M.
Kagawa, Zentsuji
765-0071
Japan
Tenpozan Clinic of I.M., Kagoshima, I.M.
Kagoshima, Kagoshima
890-0061
Japan
Hayashi DIA Clinic, Kanagawa, DIA Tract Med.·I.M.
Medical Corporation Toujinkai Sakado Central Hospital
Saitama, Sakado
350-0233
Japan
SAINO Clinic,
Saitama, Tokorozawa
359-1141
Japan
Hamamatsu Rosai Hospital
Shizuoka, Hamamatsu
430-8525
Japan
Plumeria Clinic, Shizuoka, I.M.
Shizuoka, Shizuoka
422-8006
Japan
Wakakusa Clinic, Tochigi, I.M.
Tochigi, Shimotsuke
329-0433
Japan
Kanda Clinic, Tokyo, I.M.
Tokyo
101-0047
Japan
Nihonbashi Sakura Clinic
Tokyo, Chuo-ku
103-0025
Japan
Fukuwa Clinic
Tokyo, Chuo-ku
103-0027
Japan
Nihonbashi Enomoto Internal Medicine
Tokyo, Chuo-ku
103-0027
Japan
Tokyo-Eki Center-building Clinic
Tokyo, Chuo-ku
103-0027
Japan
Tokyo Center Clinic
Tokyo, Chuo-ku
103-0028
Japan
Hosono Clinic
Tokyo, Chuo-ku
104-0031
Japan
AGE Makita Medical Clinic
Tokyo, Chuo-ku
104-0061
Japan
Kasai Diabetes Clinic
Tokyo, Edogawa-ku
134-0084
Japan
New Medical Research System Clinic
Tokyo, Hachioji
192-0046
Japan
Medical Corporation Keikokai P1-Clinic
Tokyo, Hachioji
192-0071
Japan
Minamino Heart Clinic
Tokyo, Hachioji
192-0918
Japan
Shinkoiwa Ekimae Sougou Clinic
Tokyo, Katushika-ku
124-0024
Japan
Musashino Polyclinic
Tokyo, Kiyose
204-0021
Japan
Pedi Shiodome Clinic
Tokyo, Minato-ku
105-7390
Japan
Shinagawa East one Medical Clinic
Tokyo, Minato-ku
108-0075
Japan
Shimamura Kinen Hospital
Tokyo, Nerima-ku
177-0051
Japan
Kenkoukan Suzuki Clinic
Tokyo, Ota-ku
143-0015
Japan
Honda Hidehiko Clinic
Tokyo, Ota-ku
143-0023
Japan
Sakayori Clinic
Tokyo, Shinagawa-ku
140-0011
Japan
Miho Clinic
Tokyo, Shinagawa-ku
141-0032
Japan
ToCROM Clinic
Tokyo, Shinjuku-ku
160-0022
Japan
Ikebukuro Metropolitan Clinic
Tokyo, Toshima-ku
171-0021
Japan
Fujikoshi Hp., Toyama, I.M.
Toyama, Toyama
930-0964
Japan
Clinic Sugiyama, Yamagata, I.M.
Yamagata, Yamagata
990-0885
Japan
Patients were administered empagliflozin 25 mg tablets, orally with water, once daily for 16-weeks of open-label stabilisation period.
FG002
Empagliflozin 10 mg + Linagliptin 5 mg
Patients who received empagliflozin 10 mg during open-label stabilisation period were randomized to receive a fixed dose combination (FDC) tablet of empagliflozin 10 mg and linagliptin 5 mg along with a matching placebo of empagliflozin 10 mg, orally with water, once daily for 24-weeks of double-blind treatment period.
FG003
Empagliflozin 10 mg + Placebo
Patients who received empagliflozin 10 mg during open-label stabilisation period were randomized to receive empagliflozin 10 mg along with a matching placebo of the FDC tablet of empagliflozin 10 mg and linagliptin 5 mg, orally with water, once daily for 24-weeks of double-blind treatment period.
FG004
Empagliflozin 25 mg + Linagliptin 5 mg
Patients who received empagliflozin 25 mg during open-label stabilisation period were randomized to receive a FDC tablet of empagliflozin 25 mg and linagliptin 5 mg along with a matching placebo of empagliflozin 25 mg, orally with water, once daily for 52-weeks of double-blind treatment period.
FG005
Empagliflozin 25 mg + Placebo
Patients who received empagliflozin 25 mg during open-label stabilisation period were randomized to receive empagliflozin 25 mg along with a matching placebo of the FDC tablet of empagliflozin 25 mg and linagliptin 5 mg, orally with water, once daily for 52-weeks of double-blind treatment period.
FG000439 subjects
FG001440 subjects1 subject did not receive treatment and hence excluded. Started represents treated numbers.
FG0020 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
COMPLETED
FG000215 subjects
FG001232 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
NOT COMPLETED
FG000224 subjects
FG001208 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
Type
Comment
Reasons
Adverse Event
FG00014 subjects
FG0017 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
Protocol Violation
FG0002 subjects
FG0012 subjects
FG0020 subjects
FG0030 subjects
FG004
Lost to Follow-up
FG0000 subjects
FG0013 subjects
FG0020 subjects
FG0030 subjects
FG004
Withdrawal by Subject
FG0004 subjects
FG0017 subjects
FG0020 subjects
FG0030 subjects
FG004
Other than specified above
FG000204 subjects
FG001189 subjects
FG0020 subjects
FG0030 subjects
FG004
Double-blind Treatment Period
Type
Comment
Milestone Data
STARTED
FG0000 subjects
FG0010 subjects
FG002107 subjects
FG003108 subjects
FG004116 subjects
FG005116 subjects
COMPLETED
FG0000 subjects
FG0010 subjects
FG002105 subjects
FG003100 subjects
FG004
NOT COMPLETED
FG0000 subjects
FG0010 subjects
FG0022 subjects
FG0038 subjects
FG004
Type
Comment
Reasons
Adverse Event
FG0000 subjects
FG0010 subjects
FG0022 subjects
FG003
Open-label full analysis set (OLFAS) consisted of all patients in the open-label period who received at least 1 dose of open-label study drug during the trial and had a pre-treatment Glycated haemoglobin A1c (HbA1c) assessment and at least 1 on-treatment HbA1c assessment during the open-label part of the trial.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
Empagliflozin 10 mg OL
Patients were administered empagliflozin 10 milligram (mg) tablets, orally with water, once daily for 16-weeks of open-label stabilisation period.
BG001
Empagliflozin 25 mg OL
Patients were administered empagliflozin 25 mg tablets, orally with water, once daily for 16-weeks of open-label stabilisation period.
BG002
Total
Total of all reporting groups
Denominators
Units
Counts
Participants
BG000435
BG001433
BG002868
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
BG00056.8± 10.2
BG00157.5± 10.0
BG00257.2± 10.1
Sex: Female, Male
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Female
BG000111
BG001124
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 Glycated Haemoglobin A1c (HbA1c) (%) From Baseline After 24 Weeks of Treatment
Change from baseline in HbA1c (%) after 24 weeks of treatment with double-blind trial medication. Change was calculated as: HbA1c value at 24-week - HbA1c value at baseline, for each patient. Baseline was defined as the last observation before the first intake of double-blind randomised trial medication. Statistical analysis presented is based on a restricted maximum likelihood (REML)-based mixed model repeated measures (MMRM) approach. Full Analysis Set (Observed Cases) [FAS (OC)]: This analysis set consisted of all patients who were randomised and treated with at least 1 dose of trial drug during the double-blind part of the trial and who had a baseline HbA1c assessment and at least 1 on-treatment HbA1c assessment during the 24-week double-blind part of the trial. Observed cases analysis included only the available data that were observed while patients were on treatment, i.e., excluding the missing data.
FAS (OC)
Posted
Least Squares Mean
Standard Error
Percentage (%)
Baseline and 24 week
ID
Title
Description
OG000
Empagliflozin 10 mg + Linagliptin 5 mg
Patients who received empagliflozin 10 mg during open-label stabilisation period were randomized to receive a fixed dose combination (FDC) tablet of empagliflozin 10 mg and linagliptin 5 mg along with a matching placebo of empagliflozin 10 mg, orally with water, once daily for 24-weeks of double-blind treatment period.
OG001
Empagliflozin 10 mg + Placebo
Patients who received empagliflozin 10 mg during open-label stabilisation period were randomized to receive empagliflozin 10 mg along with a matching placebo of the FDC tablet of empagliflozin 10 mg and linagliptin 5 mg, orally with water, once daily for 24-weeks of double-blind treatment period.
OG002
Empagliflozin 25 mg + Linagliptin 5 mg
Patients who received empagliflozin 25 mg during open-label stabilisation period were randomized to receive a FDC tablet of empagliflozin 25 mg and linagliptin 5 mg along with a matching placebo of empagliflozin 25 mg, orally with water, once daily for 52-weeks of double-blind treatment period.
OG003
Empagliflozin 25 mg + Placebo
Patients who received empagliflozin 25 mg during open-label stabilisation period were randomized to receive empagliflozin 25 mg along with a matching placebo of the FDC tablet of empagliflozin 25 mg and linagliptin 5 mg, orally with water, once daily for 52-weeks of double-blind treatment period.
Units
Counts
Participants
OG000103
OG00196
OG002111
OG003
Title
Denominators
Categories
Title
Measurements
OG000-0.94± 0.05
OG001-0.12± 0.06
OG002-0.91± 0.05
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
OG000
OG001
REML based MMRM
Model including baseline HbA1c, treatment, baseline renal function, prior use of antidiabetic drug, visit, and visit by treatment interaction.
<0.0001
Adjusted mean difference
-0.82
Standard Error of the Mean
0.08
2-Sided
95
-0.97
-0.67
Adjusted mean difference: Change in HbA1c in (empagliflozin 10 mg + linagliptin 5 mg) - change in HbA1c in (empagliflozin 10 mg + placebo)
Superiority or Other
Time Frame
From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period).
Description
All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).
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
Empagliflozin 25 mg + Linagliptin 5 mg
Patients who received empagliflozin 25 mg during open-label stabilisation period were randomized to receive a FDC tablet of empagliflozin 25 mg and linagliptin 5 mg along with a matching placebo of empagliflozin 25 mg, orally with water, once daily for 52-weeks of double-blind treatment period.
6
116
54
116
EG001
Empagliflozin 10 mg + Linagliptin 5 mg
Patients who received empagliflozin 10 mg during open-label stabilisation period were randomized to receive a fixed dose combination (FDC) tablet of empagliflozin 10 mg and linagliptin 5 mg along with a matching placebo of empagliflozin 10 mg, orally with water, once daily for 24-weeks of double-blind treatment period.
1
107
24
107
EG002
Empagliflozin 25 mg + Placebo
Patients who received empagliflozin 25 mg during open-label stabilisation period were randomized to receive empagliflozin 25 mg along with a matching placebo of the FDC tablet of empagliflozin 25 mg and linagliptin 5 mg, orally with water, once daily for 52-weeks of double-blind treatment period.
8
116
51
116
EG003
Empagliflozin 10 mg + Placebo
Patients who received empagliflozin 10 mg during open-label stabilisation period were randomized to receive empagliflozin 10 mg along with a matching placebo of the FDC tablet of empagliflozin 10 mg and linagliptin 5 mg, orally with water, once daily for 24-weeks of double-blind treatment period.
4
108
36
108
EG004
Empagliflozin 25 mg OL
Patients were administered empagliflozin 25 mg tablets, orally with water, once daily for 16-weeks of open-label stabilisation period.
11
440
131
440
EG005
Empagliflozin 10 mg OL
Patients were administered empagliflozin 10 milligram (mg) tablets, orally with water, once daily for 16-weeks of open-label stabilisation period.
9
439
120
439
Serious Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Sepsis
Infections and infestations
MedDRA 20.0
Systematic Assessment
EG0000 affected116 at risk
EG0010 affected107 at risk
EG0020 affected116 at risk
EG0031 affected108 at risk
EG0040 affected440 at risk
EG0050 affected439 at risk
Appendicitis
Infections and infestations
MedDRA 20.0
Systematic Assessment
EG0000 affected116 at risk
EG0010 affected107 at risk
EG0020 affected116 at risk
EG003
Diabetic gangrene
Infections and infestations
MedDRA 20.0
Systematic Assessment
EG0000 affected116 at risk
EG0010 affected107 at risk
EG0020 affected116 at risk
EG003
Diverticulitis
Infections and infestations
MedDRA 20.0
Systematic Assessment
EG0000 affected116 at risk
EG0010 affected107 at risk
EG0020 affected116 at risk
EG003
Viral infection
Infections and infestations
MedDRA 20.0
Systematic Assessment
EG0000 affected116 at risk
EG0010 affected107 at risk
EG0020 affected116 at risk
EG003
Metastases to bone
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 20.0
Systematic Assessment
EG0000 affected116 at risk
EG0010 affected107 at risk
EG0021 affected116 at risk
EG003
Metastases to lymph nodes
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 20.0
Systematic Assessment
EG0000 affected116 at risk
EG0010 affected107 at risk
EG0021 affected116 at risk
EG003
Prostate cancer
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 20.0
Systematic Assessment
EG0000 affected116 at risk
EG0011 affected107 at risk
EG0021 affected116 at risk
EG003
Gastric cancer
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 20.0
Systematic Assessment
EG0000 affected116 at risk
EG0010 affected107 at risk
EG0020 affected116 at risk
EG003
Lymphangioma
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 20.0
Systematic Assessment
EG0000 affected116 at risk
EG0010 affected107 at risk
EG0020 affected116 at risk
EG003
Rectal cancer
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 20.0
Systematic Assessment
EG0000 affected116 at risk
EG0010 affected107 at risk
EG0020 affected116 at risk
EG003
Transitional cell carcinoma
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 20.0
Systematic Assessment
EG0000 affected116 at risk
EG0010 affected107 at risk
EG0020 affected116 at risk
EG003
Disseminated intravascular coagulation
Blood and lymphatic system disorders
MedDRA 20.0
Systematic Assessment
EG0000 affected116 at risk
EG0010 affected107 at risk
EG0020 affected116 at risk
EG003
Immune thrombocytopenic purpura
Blood and lymphatic system disorders
MedDRA 20.0
Systematic Assessment
EG0000 affected116 at risk
EG0010 affected107 at risk
EG0020 affected116 at risk
EG003
Anaphylactic shock
Immune system disorders
MedDRA 20.0
Systematic Assessment
EG0001 affected116 at risk
EG0010 affected107 at risk
EG0020 affected116 at risk
EG003
Dehydration
Metabolism and nutrition disorders
MedDRA 20.0
Systematic Assessment
EG0000 affected116 at risk
EG0010 affected107 at risk
EG0020 affected116 at risk
EG003
Diabetic ketoacidosis
Metabolism and nutrition disorders
MedDRA 20.0
Systematic Assessment
EG0000 affected116 at risk
EG0010 affected107 at risk
EG0020 affected116 at risk
EG003
Cerebral infarction
Nervous system disorders
MedDRA 20.0
Systematic Assessment
EG0000 affected116 at risk
EG0010 affected107 at risk
EG0020 affected116 at risk
EG003
Lateral medullary syndrome
Nervous system disorders
MedDRA 20.0
Systematic Assessment
EG0000 affected116 at risk
EG0010 affected107 at risk
EG0020 affected116 at risk
EG003
Cataract
Eye disorders
MedDRA 20.0
Systematic Assessment
EG0000 affected116 at risk
EG0010 affected107 at risk
EG0020 affected116 at risk
EG003
Sudden hearing loss
Ear and labyrinth disorders
MedDRA 20.0
Systematic Assessment
EG0000 affected116 at risk
EG0010 affected107 at risk
EG0020 affected116 at risk
EG003
Acute myocardial infarction
Cardiac disorders
MedDRA 20.0
Systematic Assessment
EG0000 affected116 at risk
EG0010 affected107 at risk
EG0020 affected116 at risk
EG003
Atrial flutter
Cardiac disorders
MedDRA 20.0
Systematic Assessment
EG0000 affected116 at risk
EG0010 affected107 at risk
EG0020 affected116 at risk
EG003
Ventricular hypokinesia
Cardiac disorders
MedDRA 20.0
Systematic Assessment
EG0000 affected116 at risk
EG0010 affected107 at risk
EG0020 affected116 at risk
EG003
Pneumonia aspiration
Respiratory, thoracic and mediastinal disorders
MedDRA 20.0
Systematic Assessment
EG0000 affected116 at risk
EG0010 affected107 at risk
EG0020 affected116 at risk
EG003
Colitis ischaemic
Gastrointestinal disorders
MedDRA 20.0
Systematic Assessment
EG0000 affected116 at risk
EG0010 affected107 at risk
EG0021 affected116 at risk
EG003
Cholangitis
Hepatobiliary disorders
MedDRA 20.0
Systematic Assessment
EG0000 affected116 at risk
EG0010 affected107 at risk
EG0020 affected116 at risk
EG003
Drug-induced liver injury
Hepatobiliary disorders
MedDRA 20.0
Systematic Assessment
EG0001 affected116 at risk
EG0010 affected107 at risk
EG0020 affected116 at risk
EG003
Intervertebral disc protrusion
Musculoskeletal and connective tissue disorders
MedDRA 20.0
Systematic Assessment
EG0001 affected116 at risk
EG0010 affected107 at risk
EG0020 affected116 at risk
EG003
Ureterolithiasis
Renal and urinary disorders
MedDRA 20.0
Systematic Assessment
EG0000 affected116 at risk
EG0010 affected107 at risk
EG0021 affected116 at risk
EG003
Hydronephrosis
Renal and urinary disorders
MedDRA 20.0
Systematic Assessment
EG0000 affected116 at risk
EG0010 affected107 at risk
EG0020 affected116 at risk
EG003
Glycosylated haemoglobin increased
Investigations
MedDRA 20.0
Systematic Assessment
EG0000 affected116 at risk
EG0010 affected107 at risk
EG0021 affected116 at risk
EG003
Femur fracture
Injury, poisoning and procedural complications
MedDRA 20.0
Systematic Assessment
EG0000 affected116 at risk
EG0010 affected107 at risk
EG0020 affected116 at risk
EG003
Rib fracture
Injury, poisoning and procedural complications
MedDRA 20.0
Systematic Assessment
EG0000 affected116 at risk
EG0010 affected107 at risk
EG0020 affected116 at risk
EG003
Tibia fracture
Injury, poisoning and procedural complications
MedDRA 20.0
Systematic Assessment
EG0000 affected116 at risk
EG0010 affected107 at risk
EG0020 affected116 at risk
EG003
Torus fracture
Injury, poisoning and procedural complications
MedDRA 20.0
Systematic Assessment
EG0000 affected116 at risk
EG0010 affected107 at risk
EG0020 affected116 at risk
EG003
Hepatitis E
Infections and infestations
MedDRA 20.0
Systematic Assessment
EG0001 affected116 at risk
EG0010 affected107 at risk
EG0020 affected116 at risk
EG003
Lung adenocarcinoma
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 20.0
Systematic Assessment
EG0001 affected116 at risk
EG0010 affected107 at risk
EG0020 affected116 at risk
EG003
Deafness neurosensory
Ear and labyrinth disorders
MedDRA 20.0
Systematic Assessment
EG0000 affected116 at risk
EG0010 affected107 at risk
EG0021 affected116 at risk
EG003
Vertigo positional
Ear and labyrinth disorders
MedDRA 20.0
Systematic Assessment
EG0000 affected116 at risk
EG0010 affected107 at risk
EG0021 affected116 at risk
EG003
Angina pectoris
Cardiac disorders
MedDRA 20.0
Systematic Assessment
EG0001 affected116 at risk
EG0010 affected107 at risk
EG0020 affected116 at risk
EG003
Mediastinal cyst
Respiratory, thoracic and mediastinal disorders
MedDRA 20.0
Systematic Assessment
EG0000 affected116 at risk
EG0010 affected107 at risk
EG0021 affected116 at risk
EG003
Duodenitis
Gastrointestinal disorders
MedDRA 20.0
Systematic Assessment
EG0000 affected116 at risk
EG0010 affected107 at risk
EG0021 affected116 at risk
EG003
Gastrooesophageal reflux disease
Gastrointestinal disorders
MedDRA 20.0
Systematic Assessment
EG0000 affected116 at risk
EG0010 affected107 at risk
EG0021 affected116 at risk
EG003
Other Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Pollakiuria
Renal and urinary disorders
MedDRA 20.0
Systematic Assessment
EG0000 affected116 at risk
EG0010 affected107 at risk
EG0020 affected116 at risk
EG0031 affected108 at risk
EG00435 affected440 at risk
EG00530 affected439 at risk
Blood ketone body increased
Investigations
MedDRA 20.0
Systematic Assessment
EG00016 affected116 at risk
EG0012 affected107 at risk
EG0029 affected116 at risk
EG003
Weight decreased
Investigations
MedDRA 20.0
Systematic Assessment
EG0002 affected116 at risk
EG0010 affected107 at risk
EG0027 affected116 at risk
EG003
Viral upper respiratory tract infection
Infections and infestations
MedDRA 20.0
Systematic Assessment
EG00031 affected116 at risk
EG00116 affected107 at risk
EG00234 affected116 at risk
EG003
Periodontitis
Infections and infestations
MedDRA 20.0
Systematic Assessment
EG0003 affected116 at risk
EG0010 affected107 at risk
EG0026 affected116 at risk
EG003
Constipation
Gastrointestinal disorders
MedDRA 20.0
Systematic Assessment
EG0005 affected116 at risk
EG0012 affected107 at risk
EG0026 affected116 at risk
EG003
Back pain
Musculoskeletal and connective tissue disorders
MedDRA 20.0
Systematic Assessment
EG0007 affected116 at risk
EG0013 affected107 at risk
EG0022 affected116 at risk
EG003
Contusion
Injury, poisoning and procedural complications
MedDRA 20.0
Systematic Assessment
EG0004 affected116 at risk
EG0013 affected107 at risk
EG0026 affected116 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
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
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
C570240
empagliflozin
D000069476
Linagliptin
Ancestor Terms
ID
Term
D011687
Purines
D006574
Heterocyclic Compounds, 2-Ring
D000072471
Heterocyclic Compounds, Fused-Ring
D006571
Heterocyclic Compounds
D011799
Quinazolines
Browse Leaves
Not provided
Browse Branches
Not provided
0 subjects
FG0050 subjects
0 subjects
FG0050 subjects
0 subjects
FG0050 subjects
0 subjects
FG0050 subjects
110 subjects
FG005108 subjects
6 subjects
FG0058 subjects
6 subjects
FG0044 subjects
FG0055 subjects
Protocol Violation
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0041 subjects
FG0051 subjects
Withdrawal by Subject
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0032 subjects
FG0040 subjects
FG0052 subjects
Other than specified above
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0041 subjects
FG0050 subjects
235
Male
BG000324
BG001309
BG002633
108
-0.33
± 0.05
OG002
OG003
REML based MMRM
Model including baseline HbA1c, treatment, baseline renal function, prior use of antidiabetic drug, visit, and visit by treatment interaction.
<0.0001
Adjusted mean difference
-0.59
Standard Error of the Mean
0.07
2-Sided
95
-0.73
-0.45
Adjusted mean difference: Change in HbA1c in (empagliflozin 25 mg + linagliptin 5 mg) - change in HbA1c in (empagliflozin 25 mg + placebo)