Diabetes Mellitus, Type 2
Conditions
Brief summary
Study of linagliptin vs. placebo in Black/African American patients with T2DM with a MTT sub-study
Interventions
DRUGLinagliptin
Active drug 1 tablet PO QD
DRUGPlacebo
1 Tablet PO QD
Sponsors
Eli Lilly and Company
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Dated written informed consent that is in accordance with GCP and local legislation. 2. Male and female Black / African American patients 3. Diagnosis of type 2 diabetes at least 3 months prior to the informed consent. 4. HbA1c more than or equal to 7.5% and less than or equal to 11% at Visit 1. 5. Patients are currently treatment-naive or being treated with up to one oral antidiabetic medication. Antidiabetic medication is to be unchanged for at least 10 weeks prior to the informed consent. 6. Age more than 18 and less than 80 years at Visit 1 (Screening). 7. BMI (Body Mass Index) less than 45 kg/m2 at Visit 1.
Exclusion criteria
1. Myocardial infarction (MI), stroke or transient ischemic attack (TIA) within 3 months of informed consent. 2. Type 1 diabetes. 3. Impaired hepatic function, defined by serum levels of either alanine aminotransferase (ALT, SGPT), aspartate aminotransferase (AST, SGOT), or alkaline phosphatase above 3 x upper limit of normal (ULN) as determined at Visit 1. 4. Known prior hypersensitivity or allergy to the investigational product or its excipients. 5. Treatment with insulin within 3 months prior to informed consent. 6. Treatment with anti-obesity drugs (e.g., sibutramine, orlistat, rimonabant) within three months prior to informed consent or initiating therapy during the study. 7. Any prior use of dipeptidyl peptidase-4 (DPP-4) inhibitors. 8. Glucagon-like peptide-1 (GLP-1) agonists are excluded 3 months prior to informed consent. 9. History of alcohol or drug abuse within 3 months prior to informed consent that would interfere with trial participation as assessed by the Investigator. 10. Participation in another trial with an investigational drug within 3 months prior to informed consent or during the study. 11. Pre-menopausal women (last menstruation less than 1 year prior to informed consent) who: * are nursing or pregnant * are not surgically sterile * or are of child-bearing potential and are not practicing an acceptable method of birth control or do not plan to continue using this method throughout the study and do not agree to submit to periodic pregnancy testing during participation in the trial. Acceptable methods of birth control include transdermal patch, intrauterine devices/systems (IUDs / IUSs), oral, implantable or injectable contraceptives, and vasectomised partners. No exceptions will be made. Hormonal birth control should have been in use for at least three months prior to signing informed consent and continue at least until the next menstrual period after completing the study. 12. Current treatment with chronic use of systemic steroids at time of informed consent or change in dosage of thyroid hormones within 6 weeks prior to informed consent. 13. History of bariatric surgery. 14. Patients who have demonstrated an inability to be compliant (80-120%) with the dosing regimen during the placebo run-in period.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in HbA1c (Glycosylated Hemoglobin) After 24 Weeks | baseline, 24 weeks | Glycosylated hemoglobin is reported as a percentage of the total hemoglobin |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in HbA1c (Glycosylated Hemoglobin) After 12 Weeks | baseline, 12 weeks | Glycosylated hemoglobin is reported as a percentage of the total hemoglobin |
| Change From Baseline in HbA1c (Glycosylated Hemoglobin) After 18 Weeks | baseline, 18 weeks | Glycosylated hemoglobin is reported as a percentage of the total hemoglobin |
| Occurrence of Absolute Efficacy Response (HbA1c < 7%) After 24 Weeks | 24 weeks | Glycosylated hemoglobin is reported as a percentage of the total hemoglobin |
| Change From Baseline in HbA1c (Glycosylated Hemoglobin) After 6 Weeks | baseline, 6 weeks | Glycosylated hemoglobin is reported as a percentage of the total hemoglobin |
| Occurrence of Relative Efficacy Response (Reduction in HbA1c >= 0.5%) After 24 Weeks | 24 weeks | Glycosylated hemoglobin is reported as a percentage of the total hemoglobin |
| Change From Baseline in Fasting Plasma Glucose (FPG) After 24 Weeks | baseline, 24 weeks | — |
| Change From Baseline in 2-hour Post-prandial Glucose (PPG) After 24 Weeks | baseline, 24 weeks | — |
| Occurrence of Absolute Efficacy Response (HbA1c < 6.5%) After 24 Weeks | 24 weeks | Glycosylated hemoglobin is reported as a percentage of the total hemoglobin |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Tablet Placebo matching linagliptin 5 mg tablet | 120 |
| Linagliptin 5 mg Tablet Linagliptin 5 mg (milligrams) tablet given by mouth once daily | 106 |
| Total | 226 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 3 | 2 |
| Overall Study | Lack of Efficacy | 1 | 1 |
| Overall Study | Lost to Follow-up | 9 | 7 |
| Overall Study | Non-compliance issues | 4 | 4 |
| Overall Study | Other Reason | 12 | 8 |
| Overall Study | Protocol Violation | 5 | 4 |
| Overall Study | Withdrawal by Subject | 2 | 1 |
Baseline characteristics
| Characteristic | Total | Placebo Tablet | Linagliptin 5 mg Tablet |
|---|---|---|---|
| Age, Continuous | 53.9 years STANDARD_DEVIATION 9.9 | 54.1 years STANDARD_DEVIATION 9.9 | 53.7 years STANDARD_DEVIATION 10.1 |
| Age, Customized 65 to 74 years | 26 Number of participants | 12 Number of participants | 14 Number of participants |
| Age, Customized < 65 years | 193 Number of participants | 104 Number of participants | 89 Number of participants |
| Age, Customized >= 75 years | 7 Number of participants | 4 Number of participants | 3 Number of participants |
| Alcohol status Drinks - no interference with study | 95 Number of participants | 50 Number of participants | 45 Number of participants |
| Alcohol status Drinks - possible interference with study | 0 Number of participants | 0 Number of participants | 0 Number of participants |
| Alcohol status Non drinker | 131 Number of participants | 70 Number of participants | 61 Number of participants |
| Body Mass Index (BMI) | 32.74 kilograms per square meter STANDARD_DEVIATION 5.74 | 33.35 kilograms per square meter STANDARD_DEVIATION 5.36 | 32.04 kilograms per square meter STANDARD_DEVIATION 6.1 |
| Body Mass Index (BMI) categories < 30 kilograms/square meter | 78 Number of participants | 33 Number of participants | 45 Number of participants |
| Body Mass Index (BMI) categories >= 30 kilograms/square meter | 148 Number of participants | 87 Number of participants | 61 Number of participants |
| Height | 172.4 centimeters STANDARD_DEVIATION 10.6 | 172.1 centimeters STANDARD_DEVIATION 10.9 | 172.8 centimeters STANDARD_DEVIATION 10.3 |
| Sex: Female, Male Female | 105 Participants | 59 Participants | 46 Participants |
| Sex: Female, Male Male | 121 Participants | 61 Participants | 60 Participants |
| Smoking status Currently smokes | 45 Number of participants | 16 Number of participants | 29 Number of participants |
| Smoking status Ex-smoker | 43 Number of participants | 22 Number of participants | 21 Number of participants |
| Smoking status Never smoked | 138 Number of participants | 82 Number of participants | 56 Number of participants |
| Waist circumference | 107.7 centimeters STANDARD_DEVIATION 18.8 | 111.5 centimeters STANDARD_DEVIATION 16.7 | 103.5 centimeters STANDARD_DEVIATION 20.2 |
| Weight | 97.52 kilograms STANDARD_DEVIATION 20.55 | 99.02 kilograms STANDARD_DEVIATION 20.16 | 95.83 kilograms STANDARD_DEVIATION 20.96 |
| Weight categories <= 70 kilograms | 10 Number of participants | 2 Number of participants | 8 Number of participants |
| Weight categories > 70 to 80 kilograms | 39 Number of participants | 21 Number of participants | 18 Number of participants |
| Weight categories > 80 to 90 kilograms | 51 Number of participants | 25 Number of participants | 26 Number of participants |
| Weight categories > 90 kilograms | 126 Number of participants | 72 Number of participants | 54 Number of participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 15 / 120 | 9 / 106 |
| serious Total, serious adverse events | 2 / 120 | 1 / 106 |
Outcome results
Primary
Change From Baseline in HbA1c (Glycosylated Hemoglobin) After 24 Weeks
Glycosylated hemoglobin is reported as a percentage of the total hemoglobin
Time frame: baseline, 24 weeks
Population: Full Analysis Set (FAS) includes all randomized patients who received study medication and had both a baseline HbA1c value and an on-treatment HbA1c value. Four subjects in each arm excluded for site non-compliance.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo Tablet | Change From Baseline in HbA1c (Glycosylated Hemoglobin) After 24 Weeks | -0.25 Percentage | Standard Error 0.16 |
| Linagliptin 5 mg Tablet | Change From Baseline in HbA1c (Glycosylated Hemoglobin) After 24 Weeks | -0.84 Percentage | Standard Error 0.15 |
p-value: 0.000595% CI: [-0.91, -0.26]ANCOVA
Secondary
Change From Baseline in 2-hour Post-prandial Glucose (PPG) After 24 Weeks
Time frame: baseline, 24 weeks
Population: Meal Tolerance Test, observed cases data set (MTT-OC) includes all randomized patients who participated in the MTT sub-study. Patients required to have both baseline and on-treatment results.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo Tablet | Change From Baseline in 2-hour Post-prandial Glucose (PPG) After 24 Weeks | -36.77 mg/dL (milligrams per deciliter) | Standard Error 23.76 |
| Linagliptin 5 mg Tablet | Change From Baseline in 2-hour Post-prandial Glucose (PPG) After 24 Weeks | -38.74 mg/dL (milligrams per deciliter) | Standard Error 22.77 |
p-value: 0.936895% CI: [-53.8, 49.86]ANCOVA
Secondary
Change From Baseline in Fasting Plasma Glucose (FPG) After 24 Weeks
Time frame: baseline, 24 weeks
Population: Full Analysis Set (FAS) includes all randomized patients who received study medication and had both a baseline FPG value and an on-treatment FPG value.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo Tablet | Change From Baseline in Fasting Plasma Glucose (FPG) After 24 Weeks | -11.0 mg/dL (milligrams per deciliter) | Standard Error 6.6 |
| Linagliptin 5 mg Tablet | Change From Baseline in Fasting Plasma Glucose (FPG) After 24 Weeks | -22.9 mg/dL (milligrams per deciliter) | Standard Error 6.4 |
p-value: 0.097295% CI: [-26.1, 2.2]ANCOVA
Secondary
Change From Baseline in HbA1c (Glycosylated Hemoglobin) After 12 Weeks
Glycosylated hemoglobin is reported as a percentage of the total hemoglobin
Time frame: baseline, 12 weeks
Population: Full Analysis Set (FAS) includes all randomized patients who received study medication and had both a baseline HbA1c value and an on-treatment HbA1c value. Four subjects in each arm excluded for site non-compliance.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo Tablet | Change From Baseline in HbA1c (Glycosylated Hemoglobin) After 12 Weeks | -0.17 Percentage | Standard Error 0.14 |
| Linagliptin 5 mg Tablet | Change From Baseline in HbA1c (Glycosylated Hemoglobin) After 12 Weeks | -0.72 Percentage | Standard Error 0.13 |
p-value: 0.000295% CI: [-0.84, -0.26]ANCOVA
Secondary
Change From Baseline in HbA1c (Glycosylated Hemoglobin) After 18 Weeks
Glycosylated hemoglobin is reported as a percentage of the total hemoglobin
Time frame: baseline, 18 weeks
Population: Full Analysis Set (FAS) includes all randomized patients who received study medication and had both a baseline HbA1c value and an on-treatment HbA1c value. Four subjects in each arm excluded for site non-compliance.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo Tablet | Change From Baseline in HbA1c (Glycosylated Hemoglobin) After 18 Weeks | -0.26 Percentage | Standard Error 0.14 |
| Linagliptin 5 mg Tablet | Change From Baseline in HbA1c (Glycosylated Hemoglobin) After 18 Weeks | -0.81 Percentage | Standard Error 0.14 |
p-value: 0.000395% CI: [-0.85, -0.26]ANCOVA
Secondary
Change From Baseline in HbA1c (Glycosylated Hemoglobin) After 6 Weeks
Glycosylated hemoglobin is reported as a percentage of the total hemoglobin
Time frame: baseline, 6 weeks
Population: Full Analysis Set (FAS) includes all randomized patients who received study medication and had both a baseline HbA1c value and an on-treatment HbA1c value. Four subjects in each arm excluded for site non-compliance.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo Tablet | Change From Baseline in HbA1c (Glycosylated Hemoglobin) After 6 Weeks | -0.22 Percentage | Standard Error 0.1 |
| Linagliptin 5 mg Tablet | Change From Baseline in HbA1c (Glycosylated Hemoglobin) After 6 Weeks | -0.64 Percentage | Standard Error 0.09 |
p-value: <0.000195% CI: [-0.62, -0.22]ANCOVA
Secondary
Occurrence of Absolute Efficacy Response (HbA1c < 6.5%) After 24 Weeks
Glycosylated hemoglobin is reported as a percentage of the total hemoglobin
Time frame: 24 weeks
Population: Full Analysis Set (FAS) includes all randomized patients who received study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo Tablet | Occurrence of Absolute Efficacy Response (HbA1c < 6.5%) After 24 Weeks | Responder (HbA1c < 6.5%) | 2 Participants |
| Placebo Tablet | Occurrence of Absolute Efficacy Response (HbA1c < 6.5%) After 24 Weeks | Non-responder (HbA1c >= 6.5%) | 108 Participants |
| Linagliptin 5 mg Tablet | Occurrence of Absolute Efficacy Response (HbA1c < 6.5%) After 24 Weeks | Responder (HbA1c < 6.5%) | 9 Participants |
| Linagliptin 5 mg Tablet | Occurrence of Absolute Efficacy Response (HbA1c < 6.5%) After 24 Weeks | Non-responder (HbA1c >= 6.5%) | 89 Participants |
p-value: 0.035295% CI: [1.124, 26.26]Regression, Logistic
Secondary
Occurrence of Absolute Efficacy Response (HbA1c < 7%) After 24 Weeks
Glycosylated hemoglobin is reported as a percentage of the total hemoglobin
Time frame: 24 weeks
Population: Full Analysis Set (FAS) includes all randomized patients who received study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo Tablet | Occurrence of Absolute Efficacy Response (HbA1c < 7%) After 24 Weeks | Responder (HbA1c < 7.0%) | 10 Participants |
| Placebo Tablet | Occurrence of Absolute Efficacy Response (HbA1c < 7%) After 24 Weeks | Non-responder (HbA1c >= 7.0%) | 100 Participants |
| Linagliptin 5 mg Tablet | Occurrence of Absolute Efficacy Response (HbA1c < 7%) After 24 Weeks | Responder (HbA1c < 7.0%) | 26 Participants |
| Linagliptin 5 mg Tablet | Occurrence of Absolute Efficacy Response (HbA1c < 7%) After 24 Weeks | Non-responder (HbA1c >= 7.0%) | 72 Participants |
p-value: 0.00195% CI: [1.764, 9.358]Regression, Logistic
Secondary
Occurrence of Relative Efficacy Response (Reduction in HbA1c >= 0.5%) After 24 Weeks
Glycosylated hemoglobin is reported as a percentage of the total hemoglobin
Time frame: 24 weeks
Population: Full Analysis Set (FAS) includes all randomized patients who received study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo Tablet | Occurrence of Relative Efficacy Response (Reduction in HbA1c >= 0.5%) After 24 Weeks | Responder (reduction in HbA1c >= 0.5%) | 33 Participants |
| Placebo Tablet | Occurrence of Relative Efficacy Response (Reduction in HbA1c >= 0.5%) After 24 Weeks | Non-responder (reduction in HbA1c < 0.5%) | 77 Participants |
| Linagliptin 5 mg Tablet | Occurrence of Relative Efficacy Response (Reduction in HbA1c >= 0.5%) After 24 Weeks | Responder (reduction in HbA1c >= 0.5%) | 53 Participants |
| Linagliptin 5 mg Tablet | Occurrence of Relative Efficacy Response (Reduction in HbA1c >= 0.5%) After 24 Weeks | Non-responder (reduction in HbA1c < 0.5%) | 45 Participants |
p-value: 0.000395% CI: [1.651, 5.274]Regression, Logistic