Diabetes Mellitus, Type 2
Conditions
Brief summary
A phase III randomised, double-blind parallel group extension study to investigate the efficacy and safety of twice daily administration of the free combination of linagliptin 2.5 mg + metformin 500 mg or of linagliptin 2.5 mg + metformin 1000 mg versus monotherapy with metformin 1000 mg twice daily over 54 weeks in type 2 diabetic patients previously completing the double-blind part of study 1218.46
Interventions
Linagliptin tablet low dose + metformin tablet 500 mg bid
DRUGLinagliptin+metformin
Linagliptin low dose tablet + metformin 1000 mg tablet bid
DRUGMetformin
Metformin 1000 mg tablet bid
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
DOUBLE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Signed and dated written informed consent, at the latest by the date of Visit 1 * Patients completing the entire treatment period of the double-blind study 1218.46, who are not treated with rescue medication (Visit 7)
Exclusion criteria
* Patients who meet one or more of the withdrawal criteria of the treatment period of the previous study 1218.46 * Pre-menopausal women (last menstruation equal or less than 1 year prior to signing informed consent) who: * are nursing or pregnant, * 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, intra uterine devices/systems (IUDs/IUSs), oral, implantable or injectable contraceptives, sexual abstinence and vasectomised partner and in addition for male partners a barrier method, such as the use of condom with spermicide. No exception will be made. * Alcohol abuse within the 3 months prior to informed consent that would interfere with study participation * Drug abuse that in the opinion of the investigator would interfere with trial participation * Any other clinical condition which, in the opinion of the investigator, would not allow safe completion of the protocol and safe administration of the study medication
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Relevant Drug-related Abnormal Findings in Physical Examination and ECG as Reported as AE | Baseline and drug stop (up to 54 weeks) + 7 days | Frequency of patients with adverse events by treatment, primary system organ class and preferred term |
| Frequency of Patients With Adverse Events (AEs) | 54 weeks | This includes any AEs detected during routine physical examination and electrocardiogram (ECG) procedures. |
| Change From Baseline at Week 54 in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | 54 weeks | Baseline is defined as Visit 1 of 1218.52. |
| Change From Baseline at Week 54 in Pulse Rate | 54 weeks | Baseline is defined as Visit 1 of 1218.52. |
| Frequency of Patients With Possibly Clinically Significant Abnormal Laboratory Parameters: Haematology | 54 weeks | — |
| Possibly Clinically Significant Abnormal Laboratory Parameters: Clinical Chemistry | 54 weeks | ULN means upper limit of normal |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in HbA1c From Baseline Over Time | 54 weeks | HbA1c is measured as a percentage. Thus, this change from baseline reflects the visit HbA1c percent minus the baseline HbA1c percent. Baseline is defined as visit 1 of 1218.52. |
| Number of Patients With HbA1c <7.0% After 54 Weeks | 54 weeks | — |
| Number of Patients With HbA1c <6.5% Over Time | 54 weeks | — |
| Number of Patients With HbA1c of at Least <0.5% Over Time | 54 weeks | — |
| Change in FPG From Baseline Over Time | 54 weeks | Baseline is defined as visit 1 of 1218.52. |
| Number of Patients With Rescue Therapy | 54 weeks | — |
Countries
Canada, Croatia, Estonia, France, Germany, India, Lithuania, Mexico, Netherlands, Romania, Russia, Sweden, Tunisia, Ukraine
Participant flow
Pre-assignment details
In this study, 567 patients were entered and randomised, but only 566 were treated. Therefore the treated set (TS) comprises 566 patients.
Participants by arm
| Arm | Count |
|---|---|
| M1000 Metformin 1000mg monotherapy twice daily | 170 |
| L2.5+M500 Linagliptin 2.5mg and metformin 500mg twice daily | 225 |
| L2.5+M1000 Linagliptin 2.5mg and metformin 1000mg twice daily | 171 |
| Total | 566 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 12 | 13 | 11 |
| Overall Study | Any other reason | 4 | 7 | 7 |
| Overall Study | Lack of Efficacy | 9 | 15 | 3 |
| Overall Study | Lost to Follow-up | 1 | 2 | 2 |
| Overall Study | Protocol Violation | 4 | 1 | 2 |
| Overall Study | Refused to continue trial medication | 6 | 8 | 4 |
Baseline characteristics
| Characteristic | L2.5+M500 | L2.5+M1000 | M1000 | Total |
|---|---|---|---|---|
| Age, Continuous | 56.0 Years STANDARD_DEVIATION 10.7 | 55.7 Years STANDARD_DEVIATION 10.8 | 55.6 Years STANDARD_DEVIATION 10.7 | 55.8 Years STANDARD_DEVIATION 10.7 |
| Baseline Glycosylated haemoglobin (HbA1c) at baseline | 7.64 percent STANDARD_DEVIATION 1.04 | 7.35 percent STANDARD_DEVIATION 1.12 | 7.48 percent STANDARD_DEVIATION 0.99 | 7.50 percent STANDARD_DEVIATION 1.06 |
| Baseline weight | 79.17 kg STANDARD_DEVIATION 18.75 | 78.62 kg STANDARD_DEVIATION 16.86 | 81.09 kg STANDARD_DEVIATION 18.92 | 79.58 kg STANDARD_DEVIATION 18.25 |
| Body Mass Index (BMI) continuous | 29.06 kg/m2 STANDARD_DEVIATION 4.95 | 28.64 kg/m2 STANDARD_DEVIATION 4.79 | 29.33 kg/m2 STANDARD_DEVIATION 5.22 | 29.01 kg/m2 STANDARD_DEVIATION 4.98 |
| Fasting plasma glucose (FPG) at baseline | 167.088 mg/dL STANDARD_DEVIATION 44.633 | 153.721 mg/dL STANDARD_DEVIATION 37.128 | 156.585 mg/dL STANDARD_DEVIATION 39.194 | 159.868 mg/dL STANDARD_DEVIATION 41.206 |
| Sex: Female, Male Female | 105 Participants | 74 Participants | 77 Participants | 256 Participants |
| Sex: Female, Male Male | 120 Participants | 97 Participants | 93 Participants | 310 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 63 / 170 | 87 / 225 | 77 / 171 |
| serious Total, serious adverse events | 7 / 170 | 12 / 225 | 14 / 171 |
Outcome results
Primary
Change From Baseline at Week 54 in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)
Baseline is defined as Visit 1 of 1218.52.
Time frame: 54 weeks
Population: TS and observed cases (OC)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| M1000 | Change From Baseline at Week 54 in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | DBP change from baseline | -0.3 mmHg | Standard Deviation 8.5 |
| M1000 | Change From Baseline at Week 54 in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | SBP change from baseline | 0.6 mmHg | Standard Deviation 12.2 |
| L2.5+M500 | Change From Baseline at Week 54 in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | DBP change from baseline | -0.1 mmHg | Standard Deviation 7.4 |
| L2.5+M500 | Change From Baseline at Week 54 in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | SBP change from baseline | -0.2 mmHg | Standard Deviation 13.2 |
| L2.5+M1000 | Change From Baseline at Week 54 in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | DBP change from baseline | 0.3 mmHg | Standard Deviation 8.8 |
| L2.5+M1000 | Change From Baseline at Week 54 in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | SBP change from baseline | 2.2 mmHg | Standard Deviation 13.6 |
Primary
Change From Baseline at Week 54 in Pulse Rate
Baseline is defined as Visit 1 of 1218.52.
Time frame: 54 weeks
Population: TS and observed cases (OC)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| M1000 | Change From Baseline at Week 54 in Pulse Rate | 0.0 beats per minute (bpm) | Standard Deviation 7.7 |
| L2.5+M500 | Change From Baseline at Week 54 in Pulse Rate | 0.6 beats per minute (bpm) | Standard Deviation 8.3 |
| L2.5+M1000 | Change From Baseline at Week 54 in Pulse Rate | 0.1 beats per minute (bpm) | Standard Deviation 8.3 |
Primary
Clinical Relevant Drug-related Abnormal Findings in Physical Examination and ECG as Reported as AE
Frequency of patients with adverse events by treatment, primary system organ class and preferred term
Time frame: Baseline and drug stop (up to 54 weeks) + 7 days
Population: Treated Set (TS)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| M1000 | Clinical Relevant Drug-related Abnormal Findings in Physical Examination and ECG as Reported as AE | Cardiogenic shock | 0 participants |
| M1000 | Clinical Relevant Drug-related Abnormal Findings in Physical Examination and ECG as Reported as AE | Supraventricular tachycardia | 0 participants |
| L2.5+M500 | Clinical Relevant Drug-related Abnormal Findings in Physical Examination and ECG as Reported as AE | Supraventricular tachycardia | 0 participants |
| L2.5+M500 | Clinical Relevant Drug-related Abnormal Findings in Physical Examination and ECG as Reported as AE | Cardiogenic shock | 0 participants |
| L2.5+M1000 | Clinical Relevant Drug-related Abnormal Findings in Physical Examination and ECG as Reported as AE | Cardiogenic shock | 1 participants |
| L2.5+M1000 | Clinical Relevant Drug-related Abnormal Findings in Physical Examination and ECG as Reported as AE | Supraventricular tachycardia | 1 participants |
| Post-treat | Clinical Relevant Drug-related Abnormal Findings in Physical Examination and ECG as Reported as AE | Cardiogenic shock | 0 participants |
| Post-treat | Clinical Relevant Drug-related Abnormal Findings in Physical Examination and ECG as Reported as AE | Supraventricular tachycardia | 0 participants |
Primary
Frequency of Patients With Adverse Events (AEs)
This includes any AEs detected during routine physical examination and electrocardiogram (ECG) procedures.
Time frame: 54 weeks
Population: Treated Set (TS): all screened patients who were documented to have taken at lease 1 dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| M1000 | Frequency of Patients With Adverse Events (AEs) | Patients with severe AEs | 4 participant |
| M1000 | Frequency of Patients With Adverse Events (AEs) | Patients with any AEs | 124 participant |
| M1000 | Frequency of Patients With Adverse Events (AEs) | Patients with withdrawal due to AEs (from AE page) | 10 participant |
| L2.5+M500 | Frequency of Patients With Adverse Events (AEs) | Patients with severe AEs | 7 participant |
| L2.5+M500 | Frequency of Patients With Adverse Events (AEs) | Patients with any AEs | 149 participant |
| L2.5+M500 | Frequency of Patients With Adverse Events (AEs) | Patients with withdrawal due to AEs (from AE page) | 11 participant |
| L2.5+M1000 | Frequency of Patients With Adverse Events (AEs) | Patients with any AEs | 132 participant |
| L2.5+M1000 | Frequency of Patients With Adverse Events (AEs) | Patients with withdrawal due to AEs (from AE page) | 9 participant |
| L2.5+M1000 | Frequency of Patients With Adverse Events (AEs) | Patients with severe AEs | 5 participant |
Primary
Frequency of Patients With Possibly Clinically Significant Abnormal Laboratory Parameters: Haematology
Time frame: 54 weeks
Population: TS and observed cases (OC)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| M1000 | Frequency of Patients With Possibly Clinically Significant Abnormal Laboratory Parameters: Haematology | Haemoglobin abnormality:Female ≤9.5;Male ≤11.5g/dL | 7 participants |
| M1000 | Frequency of Patients With Possibly Clinically Significant Abnormal Laboratory Parameters: Haematology | White Blood Cells abnormal increase: <20.1*10^9/L | 0 participants |
| M1000 | Frequency of Patients With Possibly Clinically Significant Abnormal Laboratory Parameters: Haematology | White Blood Cells abnormal decrease: < 3 * 10^9/L | 0 participants |
| M1000 | Frequency of Patients With Possibly Clinically Significant Abnormal Laboratory Parameters: Haematology | Haematocrit abnormality: <=32% | 2 participants |
| M1000 | Frequency of Patients With Possibly Clinically Significant Abnormal Laboratory Parameters: Haematology | Platelets abnormal increase: >= 700* 10^9/L | 0 participants |
| M1000 | Frequency of Patients With Possibly Clinically Significant Abnormal Laboratory Parameters: Haematology | Platelets abnormal decrease: <= 75* 10^9/L | 0 participants |
| M1000 | Frequency of Patients With Possibly Clinically Significant Abnormal Laboratory Parameters: Haematology | Red Blood Cells abnormality: < 3* 10^12/L | 0 participants |
| L2.5+M500 | Frequency of Patients With Possibly Clinically Significant Abnormal Laboratory Parameters: Haematology | White Blood Cells abnormal decrease: < 3 * 10^9/L | 3 participants |
| L2.5+M500 | Frequency of Patients With Possibly Clinically Significant Abnormal Laboratory Parameters: Haematology | Haematocrit abnormality: <=32% | 2 participants |
| L2.5+M500 | Frequency of Patients With Possibly Clinically Significant Abnormal Laboratory Parameters: Haematology | Haemoglobin abnormality:Female ≤9.5;Male ≤11.5g/dL | 4 participants |
| L2.5+M500 | Frequency of Patients With Possibly Clinically Significant Abnormal Laboratory Parameters: Haematology | Red Blood Cells abnormality: < 3* 10^12/L | 0 participants |
| L2.5+M500 | Frequency of Patients With Possibly Clinically Significant Abnormal Laboratory Parameters: Haematology | White Blood Cells abnormal increase: <20.1*10^9/L | 1 participants |
| L2.5+M500 | Frequency of Patients With Possibly Clinically Significant Abnormal Laboratory Parameters: Haematology | Platelets abnormal decrease: <= 75* 10^9/L | 0 participants |
| L2.5+M500 | Frequency of Patients With Possibly Clinically Significant Abnormal Laboratory Parameters: Haematology | Platelets abnormal increase: >= 700* 10^9/L | 0 participants |
| L2.5+M1000 | Frequency of Patients With Possibly Clinically Significant Abnormal Laboratory Parameters: Haematology | White Blood Cells abnormal increase: <20.1*10^9/L | 0 participants |
| L2.5+M1000 | Frequency of Patients With Possibly Clinically Significant Abnormal Laboratory Parameters: Haematology | Haemoglobin abnormality:Female ≤9.5;Male ≤11.5g/dL | 2 participants |
| L2.5+M1000 | Frequency of Patients With Possibly Clinically Significant Abnormal Laboratory Parameters: Haematology | Platelets abnormal increase: >= 700* 10^9/L | 0 participants |
| L2.5+M1000 | Frequency of Patients With Possibly Clinically Significant Abnormal Laboratory Parameters: Haematology | Platelets abnormal decrease: <= 75* 10^9/L | 1 participants |
| L2.5+M1000 | Frequency of Patients With Possibly Clinically Significant Abnormal Laboratory Parameters: Haematology | White Blood Cells abnormal decrease: < 3 * 10^9/L | 1 participants |
| L2.5+M1000 | Frequency of Patients With Possibly Clinically Significant Abnormal Laboratory Parameters: Haematology | Red Blood Cells abnormality: < 3* 10^12/L | 0 participants |
| L2.5+M1000 | Frequency of Patients With Possibly Clinically Significant Abnormal Laboratory Parameters: Haematology | Haematocrit abnormality: <=32% | 0 participants |
Primary
Possibly Clinically Significant Abnormal Laboratory Parameters: Clinical Chemistry
ULN means upper limit of normal
Time frame: 54 weeks
Population: TS and observed cases (OC). In treatment group L2.5+M500, the number of patients analysed was 224 for lactate dehydrogenase abnormality and total bilirubin abnormality due to anailable data.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| M1000 | Possibly Clinically Significant Abnormal Laboratory Parameters: Clinical Chemistry | Bicarbonate abnormal decrease: <21 mmol/L | 0 participants |
| M1000 | Possibly Clinically Significant Abnormal Laboratory Parameters: Clinical Chemistry | Creatine kinase abnormality: >= 3 x ULN | 3 participants |
| M1000 | Possibly Clinically Significant Abnormal Laboratory Parameters: Clinical Chemistry | Phosphate abnormal increase: > 1.7 mmol/L | 0 participants |
| M1000 | Possibly Clinically Significant Abnormal Laboratory Parameters: Clinical Chemistry | Albumin abnormality: <2.5 g/dL | 0 participants |
| M1000 | Possibly Clinically Significant Abnormal Laboratory Parameters: Clinical Chemistry | Lactate dehydrogenase abnormality: >= 3 x ULN | 0 participants |
| M1000 | Possibly Clinically Significant Abnormal Laboratory Parameters: Clinical Chemistry | Aspartate Transaminase abnormality: ≥3xULN | 3 participants |
| M1000 | Possibly Clinically Significant Abnormal Laboratory Parameters: Clinical Chemistry | Triglyceride abnormality: >300 mg/dL | 14 participants |
| M1000 | Possibly Clinically Significant Abnormal Laboratory Parameters: Clinical Chemistry | γ-glutamyl transpeptidase (GGT) increase:≥3ULN | 8 participants |
| M1000 | Possibly Clinically Significant Abnormal Laboratory Parameters: Clinical Chemistry | Alanine Transaminase (ALT) abnormality: >= 3 x ULN | 4 participants |
| M1000 | Possibly Clinically Significant Abnormal Laboratory Parameters: Clinical Chemistry | Potassium abnormal decrease: < 3 mmol/L | 0 participants |
| M1000 | Possibly Clinically Significant Abnormal Laboratory Parameters: Clinical Chemistry | Alkaline phosphatase abnormality: >= 2 x ULN | 1 participants |
| M1000 | Possibly Clinically Significant Abnormal Laboratory Parameters: Clinical Chemistry | Sodium abnormal decrease: < 130 mmol/L | 0 participants |
| M1000 | Possibly Clinically Significant Abnormal Laboratory Parameters: Clinical Chemistry | Total bilirubin abnormality: >= 2 mg/dL | 0 participants |
| M1000 | Possibly Clinically Significant Abnormal Laboratory Parameters: Clinical Chemistry | Potassium abnormal increase: > 5.8 mmol/L | 2 participants |
| M1000 | Possibly Clinically Significant Abnormal Laboratory Parameters: Clinical Chemistry | Eosinophils abnormality : ≥ 10% | 2 participants |
| M1000 | Possibly Clinically Significant Abnormal Laboratory Parameters: Clinical Chemistry | Creatinine abnormality: >= 1.5 mg/dL | 0 participants |
| M1000 | Possibly Clinically Significant Abnormal Laboratory Parameters: Clinical Chemistry | Calcium abnormal decrease: < 1.8 mmol/L | 2 participants |
| M1000 | Possibly Clinically Significant Abnormal Laboratory Parameters: Clinical Chemistry | Uric acid abnormality:Female: >10;Male: >11 mg/dL | 4 participants |
| M1000 | Possibly Clinically Significant Abnormal Laboratory Parameters: Clinical Chemistry | Total cholesterol abnormality: > 300 mg/dL | 0 participants |
| M1000 | Possibly Clinically Significant Abnormal Laboratory Parameters: Clinical Chemistry | Calcium abnormal increase: > 3 mmol/L | 0 participants |
| M1000 | Possibly Clinically Significant Abnormal Laboratory Parameters: Clinical Chemistry | Sodium abnormal increase: > 160 mmol/L | 1 participants |
| M1000 | Possibly Clinically Significant Abnormal Laboratory Parameters: Clinical Chemistry | Amylase: > 1.5 x ULN | 2 participants |
| M1000 | Possibly Clinically Significant Abnormal Laboratory Parameters: Clinical Chemistry | Phosphate abnormal decrease: < 0.7 mmol/L | 1 participants |
| L2.5+M500 | Possibly Clinically Significant Abnormal Laboratory Parameters: Clinical Chemistry | Phosphate abnormal increase: > 1.7 mmol/L | 2 participants |
| L2.5+M500 | Possibly Clinically Significant Abnormal Laboratory Parameters: Clinical Chemistry | Eosinophils abnormality : ≥ 10% | 4 participants |
| L2.5+M500 | Possibly Clinically Significant Abnormal Laboratory Parameters: Clinical Chemistry | Sodium abnormal decrease: < 130 mmol/L | 1 participants |
| L2.5+M500 | Possibly Clinically Significant Abnormal Laboratory Parameters: Clinical Chemistry | Sodium abnormal increase: > 160 mmol/L | 0 participants |
| L2.5+M500 | Possibly Clinically Significant Abnormal Laboratory Parameters: Clinical Chemistry | Potassium abnormal decrease: < 3 mmol/L | 0 participants |
| L2.5+M500 | Possibly Clinically Significant Abnormal Laboratory Parameters: Clinical Chemistry | Potassium abnormal increase: > 5.8 mmol/L | 2 participants |
| L2.5+M500 | Possibly Clinically Significant Abnormal Laboratory Parameters: Clinical Chemistry | Calcium abnormal decrease: < 1.8 mmol/L | 1 participants |
| L2.5+M500 | Possibly Clinically Significant Abnormal Laboratory Parameters: Clinical Chemistry | Calcium abnormal increase: > 3 mmol/L | 1 participants |
| L2.5+M500 | Possibly Clinically Significant Abnormal Laboratory Parameters: Clinical Chemistry | Phosphate abnormal decrease: < 0.7 mmol/L | 0 participants |
| L2.5+M500 | Possibly Clinically Significant Abnormal Laboratory Parameters: Clinical Chemistry | Aspartate Transaminase abnormality: ≥3xULN | 2 participants |
| L2.5+M500 | Possibly Clinically Significant Abnormal Laboratory Parameters: Clinical Chemistry | Alanine Transaminase (ALT) abnormality: >= 3 x ULN | 3 participants |
| L2.5+M500 | Possibly Clinically Significant Abnormal Laboratory Parameters: Clinical Chemistry | Alkaline phosphatase abnormality: >= 2 x ULN | 0 participants |
| L2.5+M500 | Possibly Clinically Significant Abnormal Laboratory Parameters: Clinical Chemistry | γ-glutamyl transpeptidase (GGT) increase:≥3ULN | 5 participants |
| L2.5+M500 | Possibly Clinically Significant Abnormal Laboratory Parameters: Clinical Chemistry | Lactate dehydrogenase abnormality: >= 3 x ULN | 0 participants |
| L2.5+M500 | Possibly Clinically Significant Abnormal Laboratory Parameters: Clinical Chemistry | Creatine kinase abnormality: >= 3 x ULN | 1 participants |
| L2.5+M500 | Possibly Clinically Significant Abnormal Laboratory Parameters: Clinical Chemistry | Amylase: > 1.5 x ULN | 5 participants |
| L2.5+M500 | Possibly Clinically Significant Abnormal Laboratory Parameters: Clinical Chemistry | Total cholesterol abnormality: > 300 mg/dL | 0 participants |
| L2.5+M500 | Possibly Clinically Significant Abnormal Laboratory Parameters: Clinical Chemistry | Creatinine abnormality: >= 1.5 mg/dL | 1 participants |
| L2.5+M500 | Possibly Clinically Significant Abnormal Laboratory Parameters: Clinical Chemistry | Total bilirubin abnormality: >= 2 mg/dL | 1 participants |
| L2.5+M500 | Possibly Clinically Significant Abnormal Laboratory Parameters: Clinical Chemistry | Triglyceride abnormality: >300 mg/dL | 14 participants |
| L2.5+M500 | Possibly Clinically Significant Abnormal Laboratory Parameters: Clinical Chemistry | Uric acid abnormality:Female: >10;Male: >11 mg/dL | 3 participants |
| L2.5+M500 | Possibly Clinically Significant Abnormal Laboratory Parameters: Clinical Chemistry | Albumin abnormality: <2.5 g/dL | 1 participants |
| L2.5+M500 | Possibly Clinically Significant Abnormal Laboratory Parameters: Clinical Chemistry | Bicarbonate abnormal decrease: <21 mmol/L | 0 participants |
| L2.5+M1000 | Possibly Clinically Significant Abnormal Laboratory Parameters: Clinical Chemistry | Calcium abnormal increase: > 3 mmol/L | 0 participants |
| L2.5+M1000 | Possibly Clinically Significant Abnormal Laboratory Parameters: Clinical Chemistry | Sodium abnormal decrease: < 130 mmol/L | 2 participants |
| L2.5+M1000 | Possibly Clinically Significant Abnormal Laboratory Parameters: Clinical Chemistry | Amylase: > 1.5 x ULN | 4 participants |
| L2.5+M1000 | Possibly Clinically Significant Abnormal Laboratory Parameters: Clinical Chemistry | Calcium abnormal decrease: < 1.8 mmol/L | 0 participants |
| L2.5+M1000 | Possibly Clinically Significant Abnormal Laboratory Parameters: Clinical Chemistry | Eosinophils abnormality : ≥ 10% | 6 participants |
| L2.5+M1000 | Possibly Clinically Significant Abnormal Laboratory Parameters: Clinical Chemistry | Total cholesterol abnormality: > 300 mg/dL | 1 participants |
| L2.5+M1000 | Possibly Clinically Significant Abnormal Laboratory Parameters: Clinical Chemistry | Potassium abnormal increase: > 5.8 mmol/L | 4 participants |
| L2.5+M1000 | Possibly Clinically Significant Abnormal Laboratory Parameters: Clinical Chemistry | Uric acid abnormality:Female: >10;Male: >11 mg/dL | 6 participants |
| L2.5+M1000 | Possibly Clinically Significant Abnormal Laboratory Parameters: Clinical Chemistry | Creatinine abnormality: >= 1.5 mg/dL | 0 participants |
| L2.5+M1000 | Possibly Clinically Significant Abnormal Laboratory Parameters: Clinical Chemistry | Potassium abnormal decrease: < 3 mmol/L | 0 participants |
| L2.5+M1000 | Possibly Clinically Significant Abnormal Laboratory Parameters: Clinical Chemistry | Bicarbonate abnormal decrease: <21 mmol/L | 2 participants |
| L2.5+M1000 | Possibly Clinically Significant Abnormal Laboratory Parameters: Clinical Chemistry | Alanine Transaminase (ALT) abnormality: >= 3 x ULN | 2 participants |
| L2.5+M1000 | Possibly Clinically Significant Abnormal Laboratory Parameters: Clinical Chemistry | Total bilirubin abnormality: >= 2 mg/dL | 0 participants |
| L2.5+M1000 | Possibly Clinically Significant Abnormal Laboratory Parameters: Clinical Chemistry | Alkaline phosphatase abnormality: >= 2 x ULN | 0 participants |
| L2.5+M1000 | Possibly Clinically Significant Abnormal Laboratory Parameters: Clinical Chemistry | Aspartate Transaminase abnormality: ≥3xULN | 2 participants |
| L2.5+M1000 | Possibly Clinically Significant Abnormal Laboratory Parameters: Clinical Chemistry | Sodium abnormal increase: > 160 mmol/L | 0 participants |
| L2.5+M1000 | Possibly Clinically Significant Abnormal Laboratory Parameters: Clinical Chemistry | γ-glutamyl transpeptidase (GGT) increase:≥3ULN | 7 participants |
| L2.5+M1000 | Possibly Clinically Significant Abnormal Laboratory Parameters: Clinical Chemistry | Phosphate abnormal increase: > 1.7 mmol/L | 1 participants |
| L2.5+M1000 | Possibly Clinically Significant Abnormal Laboratory Parameters: Clinical Chemistry | Albumin abnormality: <2.5 g/dL | 0 participants |
| L2.5+M1000 | Possibly Clinically Significant Abnormal Laboratory Parameters: Clinical Chemistry | Lactate dehydrogenase abnormality: >= 3 x ULN | 0 participants |
| L2.5+M1000 | Possibly Clinically Significant Abnormal Laboratory Parameters: Clinical Chemistry | Phosphate abnormal decrease: < 0.7 mmol/L | 0 participants |
| L2.5+M1000 | Possibly Clinically Significant Abnormal Laboratory Parameters: Clinical Chemistry | Triglyceride abnormality: >300 mg/dL | 10 participants |
| L2.5+M1000 | Possibly Clinically Significant Abnormal Laboratory Parameters: Clinical Chemistry | Creatine kinase abnormality: >= 3 x ULN | 2 participants |
Secondary
Change in FPG From Baseline Over Time
Baseline is defined as visit 1 of 1218.52.
Time frame: 54 weeks
Population: TS (OC) with non-missing data at visit
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| M1000 | Change in FPG From Baseline Over Time | Change in FPG to week 18 (n=133, 174 and 142) | -1.14 mg/dL | Standard Deviation 43.18 |
| M1000 | Change in FPG From Baseline Over Time | Change in FPG to week 2 (n=158, 200 and 158) | -4.36 mg/dL | Standard Deviation 27.86 |
| M1000 | Change in FPG From Baseline Over Time | Change in FPG to week 30 (n=116, 156 and 130) | -7.22 mg/dL | Standard Deviation 41.67 |
| M1000 | Change in FPG From Baseline Over Time | Change in FPG to week 54 (n=93, 132 and 115) | -6.02 mg/dL | Standard Deviation 29.25 |
| M1000 | Change in FPG From Baseline Over Time | Change in FPG to week 6 (n=152, 189 and 157) | -4.18 mg/dL | Standard Deviation 32.68 |
| M1000 | Change in FPG From Baseline Over Time | Change in FPG to week 42 (n=103, 149 and 124) | -7.43 mg/dL | Standard Deviation 30.48 |
| L2.5+M500 | Change in FPG From Baseline Over Time | Change in FPG to week 6 (n=152, 189 and 157) | -13.28 mg/dL | Standard Deviation 27.36 |
| L2.5+M500 | Change in FPG From Baseline Over Time | Change in FPG to week 2 (n=158, 200 and 158) | -12.22 mg/dL | Standard Deviation 28.7 |
| L2.5+M500 | Change in FPG From Baseline Over Time | Change in FPG to week 18 (n=133, 174 and 142) | -11.76 mg/dL | Standard Deviation 33.1 |
| L2.5+M500 | Change in FPG From Baseline Over Time | Change in FPG to week 30 (n=116, 156 and 130) | -13.49 mg/dL | Standard Deviation 33.68 |
| L2.5+M500 | Change in FPG From Baseline Over Time | Change in FPG to week 42 (n=103, 149 and 124) | -9.46 mg/dL | Standard Deviation 33.61 |
| L2.5+M500 | Change in FPG From Baseline Over Time | Change in FPG to week 54 (n=93, 132 and 115) | -7.24 mg/dL | Standard Deviation 36.27 |
| L2.5+M1000 | Change in FPG From Baseline Over Time | Change in FPG to week 6 (n=152, 189 and 157) | -13.46 mg/dL | Standard Deviation 32.97 |
| L2.5+M1000 | Change in FPG From Baseline Over Time | Change in FPG to week 54 (n=93, 132 and 115) | -9.82 mg/dL | Standard Deviation 31.83 |
| L2.5+M1000 | Change in FPG From Baseline Over Time | Change in FPG to week 42 (n=103, 149 and 124) | -13.10 mg/dL | Standard Deviation 34.96 |
| L2.5+M1000 | Change in FPG From Baseline Over Time | Change in FPG to week 18 (n=133, 174 and 142) | -12.88 mg/dL | Standard Deviation 33.74 |
| L2.5+M1000 | Change in FPG From Baseline Over Time | Change in FPG to week 2 (n=158, 200 and 158) | -10.57 mg/dL | Standard Deviation 28.15 |
| L2.5+M1000 | Change in FPG From Baseline Over Time | Change in FPG to week 30 (n=116, 156 and 130) | -13.90 mg/dL | Standard Deviation 32.07 |
Secondary
Change in HbA1c From Baseline Over Time
HbA1c is measured as a percentage. Thus, this change from baseline reflects the visit HbA1c percent minus the baseline HbA1c percent. Baseline is defined as visit 1 of 1218.52.
Time frame: 54 weeks
Population: TS (OC) with non-missing data at visit
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| M1000 | Change in HbA1c From Baseline Over Time | Change in HbA1c to week 42 (n=110, 152 and 127) | -0.14 Percentage | Standard Deviation 0.78 |
| M1000 | Change in HbA1c From Baseline Over Time | Change in HbA1c to week 30 (n=121, 165 and 134) | -0.10 Percentage | Standard Deviation 0.82 |
| M1000 | Change in HbA1c From Baseline Over Time | Change in HbA1c to week 6 (n=157, 207 and 166) | -0.06 Percentage | Standard Deviation 0.41 |
| M1000 | Change in HbA1c From Baseline Over Time | Change in HbA1c to week 18 (n=136, 184 and 147) | -0.08 Percentage | Standard Deviation 0.56 |
| M1000 | Change in HbA1c From Baseline Over Time | Change in HbA1c to week 54 (n=98, 132 and 117) | -0.06 Percentage | Standard Deviation 0.77 |
| L2.5+M500 | Change in HbA1c From Baseline Over Time | Change in HbA1c to week 30 (n=121, 165 and 134) | -0.41 Percentage | Standard Deviation 0.8 |
| L2.5+M500 | Change in HbA1c From Baseline Over Time | Change in HbA1c to week 6 (n=157, 207 and 166) | -0.24 Percentage | Standard Deviation 0.51 |
| L2.5+M500 | Change in HbA1c From Baseline Over Time | Change in HbA1c to week 18 (n=136, 184 and 147) | -0.29 Percentage | Standard Deviation 0.79 |
| L2.5+M500 | Change in HbA1c From Baseline Over Time | Change in HbA1c to week 42 (n=110, 152 and 127) | -0.35 Percentage | Standard Deviation 0.8 |
| L2.5+M500 | Change in HbA1c From Baseline Over Time | Change in HbA1c to week 54 (n=98, 132 and 117) | -0.28 Percentage | Standard Deviation 0.86 |
| L2.5+M1000 | Change in HbA1c From Baseline Over Time | Change in HbA1c to week 54 (n=98, 132 and 117) | -0.24 Percentage | Standard Deviation 0.91 |
| L2.5+M1000 | Change in HbA1c From Baseline Over Time | Change in HbA1c to week 42 (n=110, 152 and 127) | -0.28 Percentage | Standard Deviation 1 |
| L2.5+M1000 | Change in HbA1c From Baseline Over Time | Change in HbA1c to week 6 (n=157, 207 and 166) | -0.26 Percentage | Standard Deviation 0.59 |
| L2.5+M1000 | Change in HbA1c From Baseline Over Time | Change in HbA1c to week 30 (n=121, 165 and 134) | -0.36 Percentage | Standard Deviation 0.87 |
| L2.5+M1000 | Change in HbA1c From Baseline Over Time | Change in HbA1c to week 18 (n=136, 184 and 147) | -0.34 Percentage | Standard Deviation 0.93 |
Secondary
Change in HbA1c From Baseline Over Time
HbA1c is measured as a percentage. Thus, this change from baseline reflects the visit HbA1c percent minus the baseline HbA1c percent. Baseline is defined as visit 3 from study 1218.46 (NCT00915772).
Time frame: 78 weeks
Population: Non-switcher set (OC) with non-missing data at visit. Only patients who continued on the same treatment in both studies are included
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| M1000 | Change in HbA1c From Baseline Over Time | Change in HbA1c to week 42 (n=90, 92 and 95) | -1.16 Percentage | Standard Deviation 0.98 |
| M1000 | Change in HbA1c From Baseline Over Time | Change in HbA1c to week 66 (n=74, 73 and 84) | -1.26 Percentage | Standard Deviation 1.02 |
| M1000 | Change in HbA1c From Baseline Over Time | Change in HbA1c to week 30 (n=102, 103 and 108) | -1.19 Percentage | Standard Deviation 0.98 |
| M1000 | Change in HbA1c From Baseline Over Time | Change in HbA1c to week 54 (n=81, 81 and 87) | -1.20 Percentage | Standard Deviation 1.14 |
| M1000 | Change in HbA1c From Baseline Over Time | Change in HbA1c to week 78 (n=66, 66 and 78) | -1.25 Percentage | Standard Deviation 0.91 |
| L2.5+M500 | Change in HbA1c From Baseline Over Time | Change in HbA1c to week 54 (n=81, 81 and 87) | -1.41 Percentage | Standard Deviation 1.03 |
| L2.5+M500 | Change in HbA1c From Baseline Over Time | Change in HbA1c to week 66 (n=74, 73 and 84) | -1.42 Percentage | Standard Deviation 0.93 |
| L2.5+M500 | Change in HbA1c From Baseline Over Time | Change in HbA1c to week 78 (n=66, 66 and 78) | -1.32 Percentage | Standard Deviation 1.06 |
| L2.5+M500 | Change in HbA1c From Baseline Over Time | Change in HbA1c to week 42 (n=90, 92 and 95) | -1.31 Percentage | Standard Deviation 0.99 |
| L2.5+M500 | Change in HbA1c From Baseline Over Time | Change in HbA1c to week 30 (n=102, 103 and 108) | -1.34 Percentage | Standard Deviation 0.91 |
| L2.5+M1000 | Change in HbA1c From Baseline Over Time | Change in HbA1c to week 78 (n=66, 66 and 78) | -1.63 Percentage | Standard Deviation 1.05 |
| L2.5+M1000 | Change in HbA1c From Baseline Over Time | Change in HbA1c to week 30 (n=102, 103 and 108) | -1.74 Percentage | Standard Deviation 0.98 |
| L2.5+M1000 | Change in HbA1c From Baseline Over Time | Change in HbA1c to week 42 (n=90, 92 and 95) | -1.62 Percentage | Standard Deviation 1.05 |
| L2.5+M1000 | Change in HbA1c From Baseline Over Time | Change in HbA1c to week 54 (n=81, 81 and 87) | -1.73 Percentage | Standard Deviation 0.99 |
| L2.5+M1000 | Change in HbA1c From Baseline Over Time | Change in HbA1c to week 66 (n=74, 73 and 84) | -1.65 Percentage | Standard Deviation 1.09 |
Secondary
Number of Patients With HbA1c <6.5% Over Time
Time frame: 54 weeks
Population: Treated Set with non completers considered as failures (NCF)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| M1000 | Number of Patients With HbA1c <6.5% Over Time | No | 148 participant |
| M1000 | Number of Patients With HbA1c <6.5% Over Time | Yes | 22 participant |
| L2.5+M500 | Number of Patients With HbA1c <6.5% Over Time | No | 196 participant |
| L2.5+M500 | Number of Patients With HbA1c <6.5% Over Time | Yes | 29 participant |
| L2.5+M1000 | Number of Patients With HbA1c <6.5% Over Time | No | 130 participant |
| L2.5+M1000 | Number of Patients With HbA1c <6.5% Over Time | Yes | 41 participant |
Secondary
Number of Patients With HbA1c <7.0% After 54 Weeks
Time frame: 54 weeks
Population: Treated Set with non completers considered as failures (NCF)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| M1000 | Number of Patients With HbA1c <7.0% After 54 Weeks | No | 119 participant |
| M1000 | Number of Patients With HbA1c <7.0% After 54 Weeks | Yes | 51 participant |
| L2.5+M500 | Number of Patients With HbA1c <7.0% After 54 Weeks | No | 168 participant |
| L2.5+M500 | Number of Patients With HbA1c <7.0% After 54 Weeks | Yes | 57 participant |
| L2.5+M1000 | Number of Patients With HbA1c <7.0% After 54 Weeks | Yes | 67 participant |
| L2.5+M1000 | Number of Patients With HbA1c <7.0% After 54 Weeks | No | 104 participant |
Secondary
Number of Patients With HbA1c of at Least <0.5% Over Time
Time frame: 54 weeks
Population: Treated Set with non completers considered as failures (NCF)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| M1000 | Number of Patients With HbA1c of at Least <0.5% Over Time | No | 143 participant |
| M1000 | Number of Patients With HbA1c of at Least <0.5% Over Time | Yes | 27 participant |
| L2.5+M500 | Number of Patients With HbA1c of at Least <0.5% Over Time | No | 176 participant |
| L2.5+M500 | Number of Patients With HbA1c of at Least <0.5% Over Time | Yes | 49 participant |
| L2.5+M1000 | Number of Patients With HbA1c of at Least <0.5% Over Time | No | 135 participant |
| L2.5+M1000 | Number of Patients With HbA1c of at Least <0.5% Over Time | Yes | 36 participant |
Secondary
Number of Patients With Rescue Therapy
Time frame: 54 weeks
Population: TS
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| M1000 | Number of Patients With Rescue Therapy | Yes | 42 Number of patients |
| M1000 | Number of Patients With Rescue Therapy | No | 128 Number of patients |
| L2.5+M500 | Number of Patients With Rescue Therapy | Yes | 62 Number of patients |
| L2.5+M500 | Number of Patients With Rescue Therapy | No | 163 Number of patients |
| L2.5+M1000 | Number of Patients With Rescue Therapy | Yes | 24 Number of patients |
| L2.5+M1000 | Number of Patients With Rescue Therapy | No | 147 Number of patients |