Diabetes Mellitus, Type 2
Conditions
Brief summary
The objective of the current study is to investigate the safety and tolerability of BI 1356 (5 mg / once daily) given for 78 weeks in different modalities of treatment. The treatment modalities are determined by the treatment in the blinded trial in which every patient was included previously as BI 1356 in monotherapy (patients in 1218.16 trial), BI 1356 in combination with pioglitazone (patients in 1218.15 trial), BI 1356 added to metformin background (patients in 1218.17 trial) or BI 1356 added to a background therapy of metformin in combination with a sulphonylurea (patients in 1218.18 study)
Interventions
DRUGlinagliptine 5 mg
safety and efficacy of linagliptine 5 mg open label
DRUGlinagliptine 5 mg and pioglitazone 30 mg
efficacy and safety of the combination linagliptine and pioglitazone
Sponsors
Boehringer Ingelheim
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 82 Years
Healthy volunteers
No
Inclusion criteria
1. Signed and dated written informed consent in accordance with the GCP and local legislation. 2. Patients completing the entire treatment period as a double blind trial whether or not they have been treated with rescue medication.
Exclusion criteria
1. Patients who meet one or more of the withdrawal criteria of the treatment period of the previous trial. 2. Pre-menopausal women (last menstruation =\< 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, true sexual abstinence (when this is in line with the preferred and usual lifestyle of the patient; periodic abstinence \[e.g. calendar, ovulation, symptothermal, post-ovulation methods\] and withdrawal are not acceptable methods of birth control) and vasectomised partners. No exception will be made. 3. Alcohol abuse within the 3 months prior to informed consent that would interfere with trial participation. 4. Drug abuse which, in the opinion of the investigator, would interfere with trial participation. 5. Any other clinical condition which, in the opinion of the investigator, would not allow safe completion of the protocol and safe administration of the trial medication.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With Abnormalities in Clinical Chemistry: Cholesterol | 78 weeks | For this laboratory parameter, a possibly clinically significant abnormality is defined as a value greater than 300 mg/dL. |
| Number of Patients With Abnormalities in Clinical Chemistry: Potassium | 78 weeks | For this laboratory parameter, a possibly clinically significant abnormality is defined as a value less than 3 mmol/L (decrease) or a value greater than 5.8 mmol/L (increase). |
| Number of Patients With Abnormalities in Clinical Chemistry: Uric Acid | 78 weeks | For this laboratory parameter, a possibly clinically significant abnormality is defined as a value greater than 11 mg/dL for male and as a value greater than 10 mg/dL for female patients. |
| Number of Patients With Abnormalities in Clinical Chemistry: Triglycerides | 78 weeks | For this laboratory parameter, a possibly clinically significant abnormality is defined as a value greater than 300 mg/dL. |
| Number of Patients With Abnormalities in Clinical Chemistry: Amylase | 78 weeks | For this laboratory parameter, a possibly clinically significant abnormality is defined as a value greater than 1.5 times the upper limit of normal (ULN). |
| Number of Patients With Abnormalities in Clinical Chemistry: γ-Glutamyl-transferase (GGT) | 78 weeks | For this laboratory parameter, a possibly clinically significant abnormality is defined as a value greater than or equal to 3 times the ULN. |
| Number of Patients With Abnormalities in Clinical Chemistry: Creatinine | 78 weeks | For this laboratory parameter, a possibly clinically significant abnormality is defined as a value greater than or equal to 1.5 mg/dL. |
| Number of Patients With Abnormalities in Clinical Chemistry: Creatinine Kinase | 78 weeks | For this laboratory parameter, a possibly clinically significant abnormality is defined as a value greater than or equal to 3 times the ULN. |
| Number of Patients With Abnormalities in Clinical Chemistry: Phosphate | 78 weeks | For this laboratory parameter, a possibly clinically significant abnormality is defined as a value less than 0.7 mmol/L (decrease) or a value greater than 1.7 mmol/L (increase). |
| Number of Patients With Abnormalities in Clinical Chemistry: Calcium | 78 weeks | For this laboratory parameter, a possibly clinically significant abnormality is defined as a value less than 1.8 mmol/L (decrease) or a value greater than 3 mmol/L (increase). |
| Number of Patients With Abnormalities in Clinical Chemistry: Sodium | 78 weeks | For this laboratory parameter, a possibly clinically significant abnormality is defined as a value less than 130 mmol/L (decrease) or a value greater than 160 mmol/L (increase). |
| Number of Patients With Abnormalities in Clinical Chemistry: Alanine Transaminase (ALT) | 78 weeks | For this laboratory parameter, a possibly clinically significant abnormality is defined as a value greater than or equal to 3 times the ULN. |
| Number of Patients With Abnormalities in Clinical Chemistry: Aspartate Transaminase (AST) | 78 weeks | For this laboratory parameter, a possibly clinically significant abnormality is defined as a value greater than or equal to 3 times the ULN. |
| Number of Patients With Abnormalities in Clinical Chemistry: Glucose | 78 weeks | For this laboratory parameter, a possibly clinically significant abnormality is defined as a value less than 54 mg/dL. |
| Number of Patients With Abnormalities in Clinical Chemistry: Bilirubin | 78 weeks | For this laboratory parameter, a possibly clinically significant abnormality is defined as a value greater than or equal to 2 mg/dL. |
| Number of Patients With Abnormalities in Clinical Chemistry: Alkaline Phosphatase (AP) | 78 weeks | For this laboratory parameter, a possibly clinically significant abnormality is defined as a value greater than or equal to 2 times the ULN. |
| Number of Patients With Abnormalities in Clinical Chemistry: Albumin | 78 weeks | For this laboratory parameter, a possibly clinically significant abnormality is defined as a value less than 2.5 g/dL. |
| Number of Patients With Abnormalities in Clinical Chemistry: Lactate Dehydrogenase (LDH) | 78 weeks | For this laboratory parameter, a possibly clinically significant abnormality is defined as a value greater than or equal to 3 times the ULN. |
| Frequency of Patients With Adverse Events (AEs) | 78 weeks | This includes any AEs detected during routine physical examination and electrocardiogram (ECG) procedures. |
| Frequency of Patients With Investigator-defined Hypoglycaemic Adverse Events | 78 weeks | — |
| Frequency of Patients With Significant Adverse Events Based on Standardised MedDRA Query (SMQ) | 78 weeks | As significant adverse events are considered: renal Aes (SMQ 'acute renal failure'), hypersensitivity reactions ('anaphylactic reactions' and 'angioedema'), hepatic Aes ('hepatitis, non-infectious', 'hepatic failure, fibrosis, cirrhosis and other liver damage-related conditions', 'liver-related investigations, signs and symptoms', 'cholestasis and jaundice of hepatic origin'), severe cutaneous adverse reactions ('severe cutaneous adverse reaction'), pancreatitis ('acute pancreatitis', 'chronic pancreatitis''). |
| Frequency of Patients With Adjudication of Cardiac and Cerebrovascular Events | 78 weeks | Patients reported with cardiac and cerebrovascular events qualified for adjudication by the Clinical Event Committee (CEC) |
| Number of Patients With Abnormalities in Vital Signs | 78 weeks | Vital sign abnormalities (any abnormalities found during PE or ECG are reported with adverse events) |
| Number of Patients With Abnormalities in Haematology: Eosinophils | 78 weeks | For this laboratory parameter, a possibly clinically significant abnormality is defined as a value greater than or equal to 10%. |
| Number of Patients With Abnormalities in Haematology: Haemoglobin | 78 weeks | For this laboratory parameter, a possibly clinically significant abnormality is defined as a value less than or equal to 11.5 g/dL for male and as a value less than or equal to 9.5 g/dL for female patients. |
| Number of Patients With Abnormalities in Haematology: Haematocrit | 78 weeks | For this laboratory parameter, a possibly clinically significant abnormality is defined as a value less than or equal to 32%. |
| Number of Patients With Abnormalities in Haematology: Red Blood Cell Count | 78 weeks | For this laboratory parameter, a possibly clinically significant abnormality is defined as a value less than 3 \* 10\^12/L. |
| Number of Patients With Abnormalities in Haematology: White Blood Cell Count | 78 weeks | For this laboratory parameter, a possibly clinically significant abnormality is defined as a value less than 3 \* 10\^9/L (decrease) or a value greater than 20.1 \* 10\^9/L (increase). |
| Number of Patients With Abnormalities in Haematology: Platelets | 78 weeks | For this laboratory parameter, a possibly clinically significant abnormality is defined as value less than or equal to 75 \* 10\^9/L (decrease) or a value greater than or equal to 700 \* 10\^9/L (increase). |
Secondary
| Measure | Time frame |
|---|---|
| Change in HbA1c From Baseline to Week 18 | Baseline and week 18 |
| Change in HbA1c From Baseline to Week 30 | Baseline and week 30 |
| Change in HbA1c From Baseline to Week 42 | Baseline and week 42 |
| Change in HbA1c From Baseline to Week 54 | Baseline and week 54 |
| Change in HbA1c From Baseline to Week 66 | Baseline and week 66 |
| Change in HbA1c From Baseline to Week 78 | Baseline and week 78 |
| Number of Patients With HbA1c<7.0% Over Time | 78 weeks |
| Number of Patients With HbA1c<6.5% Over Time | 78 weeks |
| Number of Patients With Lowered HbA1c by at Least 0.5% Over Time | 78 weeks |
| Change in FPG From Baseline to Week 6 | Baseline and week 6 |
| Change in FPG From Baseline to Week 18 | Baseline and week 18 |
| Change in FPG From Baseline to Week 30 | Baseline and week 30 |
| Change in FPG From Baseline to Week 42 | Baseline and week 42 |
| Change in FPG From Baseline to Week 54 | Baseline and week 54 |
| Change in FPG From Baseline to Week 66 | Baseline and week 66 |
| Change in FPG From Baseline to Week 78 | Baseline and week 78 |
| Change in HbA1c From Baseline to Week 6 | Baseline and week 6 |
Countries
Argentina, Austria, Belgium, Canada, China, Croatia, Czechia, Finland, Germany, Greece, Hungary, India, Israel, Italy, Japan, Malaysia, Mexico, Netherlands, New Zealand, Philippines, Poland, Romania, Russia, Slovakia, South Korea, Spain, Sweden, Taiwan, Thailand, Ukraine, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Old Lina Patients pre-treated with linagliptin | 1,532 |
| New Lina Patients pre-treated with placebo | 589 |
| Total | 2,121 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 61 | 18 |
| Overall Study | Lack of Efficacy | 15 | 8 |
| Overall Study | Lost to Follow-up | 12 | 5 |
| Overall Study | Other reason | 43 | 10 |
| Overall Study | Protocol Violation | 10 | 4 |
| Overall Study | Withdrawal by Subject | 42 | 13 |
Baseline characteristics
| Characteristic | New Lina | Old Lina | Total |
|---|---|---|---|
| Age, Continuous | 56.7 years STANDARD_DEVIATION 10 | 57.8 years STANDARD_DEVIATION 9.8 | 57.5 years STANDARD_DEVIATION 9.9 |
| Baseline Glycosylated haemoglobin (HbA1c) at baseline | 7.87 percent STANDARD_DEVIATION 1.04 | 7.38 percent STANDARD_DEVIATION 0.9 | 7.51 percent STANDARD_DEVIATION 0.97 |
| Baseline weight | 80.1 kg STANDARD_DEVIATION 16.9 | 78.7 kg STANDARD_DEVIATION 16.9 | 79.1 kg STANDARD_DEVIATION 16.9 |
| Body mass index (BMI) continuous | 29.18 kg/m^2 STANDARD_DEVIATION 4.91 | 28.86 kg/m^2 STANDARD_DEVIATION 4.82 | 28.95 kg/m^2 STANDARD_DEVIATION 4.85 |
| Fasting plasma glucose (FPG) at baseline | 164.31 mg/dL STANDARD_DEVIATION 37.36 | 151.59 mg/dL STANDARD_DEVIATION 35.32 | 155.12 mg/dL STANDARD_DEVIATION 36.34 |
| Sex: Female, Male Female | 279 Participants | 743 Participants | 1022 Participants |
| Sex: Female, Male Male | 310 Participants | 789 Participants | 1099 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 784 / 1,532 | 285 / 589 |
| serious Total, serious adverse events | 158 / 1,532 | 52 / 589 |
Outcome results
Primary
Frequency of Patients With Adjudication of Cardiac and Cerebrovascular Events
Patients reported with cardiac and cerebrovascular events qualified for adjudication by the Clinical Event Committee (CEC)
Time frame: 78 weeks
Population: Treated Set: all screened patients who were documented to have taken at least 1 dose of study drug
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Old Lina | Frequency of Patients With Adjudication of Cardiac and Cerebrovascular Events | 82 participants |
| New Lina | Frequency of Patients With Adjudication of Cardiac and Cerebrovascular Events | 37 participants |
Primary
Frequency of Patients With Adverse Events (AEs)
This includes any AEs detected during routine physical examination and electrocardiogram (ECG) procedures.
Time frame: 78 weeks
Population: Treated Set: all screened patients who were documented to have taken at lease 1 dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Old Lina | Frequency of Patients With Adverse Events (AEs) | Patients with any AEs | 1253 Participants |
| Old Lina | Frequency of Patients With Adverse Events (AEs) | Patients with severe AEs | 57 Participants |
| Old Lina | Frequency of Patients With Adverse Events (AEs) | Patients with withdrawal due to AEs (from AE page) | 57 Participants |
| New Lina | Frequency of Patients With Adverse Events (AEs) | Patients with any AEs | 465 Participants |
| New Lina | Frequency of Patients With Adverse Events (AEs) | Patients with severe AEs | 23 Participants |
| New Lina | Frequency of Patients With Adverse Events (AEs) | Patients with withdrawal due to AEs (from AE page) | 16 Participants |
Primary
Frequency of Patients With Investigator-defined Hypoglycaemic Adverse Events
Time frame: 78 weeks
Population: Treated Set: all screened patients who were documented to have taken at lease 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Old Lina | Frequency of Patients With Investigator-defined Hypoglycaemic Adverse Events | 209 Participants |
| New Lina | Frequency of Patients With Investigator-defined Hypoglycaemic Adverse Events | 86 Participants |
Primary
Frequency of Patients With Significant Adverse Events Based on Standardised MedDRA Query (SMQ)
As significant adverse events are considered: renal Aes (SMQ 'acute renal failure'), hypersensitivity reactions ('anaphylactic reactions' and 'angioedema'), hepatic Aes ('hepatitis, non-infectious', 'hepatic failure, fibrosis, cirrhosis and other liver damage-related conditions', 'liver-related investigations, signs and symptoms', 'cholestasis and jaundice of hepatic origin'), severe cutaneous adverse reactions ('severe cutaneous adverse reaction'), pancreatitis ('acute pancreatitis', 'chronic pancreatitis'').
Time frame: 78 weeks
Population: Treated Set: all screened patients who were documented to have taken at lease 1 dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Old Lina | Frequency of Patients With Significant Adverse Events Based on Standardised MedDRA Query (SMQ) | Hypersensitivity reactions | 7 Participants |
| Old Lina | Frequency of Patients With Significant Adverse Events Based on Standardised MedDRA Query (SMQ) | Severe cutaneous adverse reactions | 0 Participants |
| Old Lina | Frequency of Patients With Significant Adverse Events Based on Standardised MedDRA Query (SMQ) | Hepatic AEs | 21 Participants |
| Old Lina | Frequency of Patients With Significant Adverse Events Based on Standardised MedDRA Query (SMQ) | Pancreatitis | 4 Participants |
| Old Lina | Frequency of Patients With Significant Adverse Events Based on Standardised MedDRA Query (SMQ) | Renal AEs | 20 Participants |
| New Lina | Frequency of Patients With Significant Adverse Events Based on Standardised MedDRA Query (SMQ) | Pancreatitis | 0 Participants |
| New Lina | Frequency of Patients With Significant Adverse Events Based on Standardised MedDRA Query (SMQ) | Renal AEs | 10 Participants |
| New Lina | Frequency of Patients With Significant Adverse Events Based on Standardised MedDRA Query (SMQ) | Hypersensitivity reactions | 3 Participants |
| New Lina | Frequency of Patients With Significant Adverse Events Based on Standardised MedDRA Query (SMQ) | Hepatic AEs | 5 Participants |
| New Lina | Frequency of Patients With Significant Adverse Events Based on Standardised MedDRA Query (SMQ) | Severe cutaneous adverse reactions | 0 Participants |
Primary
Number of Patients With Abnormalities in Clinical Chemistry: Alanine Transaminase (ALT)
For this laboratory parameter, a possibly clinically significant abnormality is defined as a value greater than or equal to 3 times the ULN.
Time frame: 78 weeks
Population: Treated Set with values for ALT
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Old Lina | Number of Patients With Abnormalities in Clinical Chemistry: Alanine Transaminase (ALT) | 22 participants |
| New Lina | Number of Patients With Abnormalities in Clinical Chemistry: Alanine Transaminase (ALT) | 5 participants |
Primary
Number of Patients With Abnormalities in Clinical Chemistry: Albumin
For this laboratory parameter, a possibly clinically significant abnormality is defined as a value less than 2.5 g/dL.
Time frame: 78 weeks
Population: Treated Set with values for Albumin
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Old Lina | Number of Patients With Abnormalities in Clinical Chemistry: Albumin | 3 participants |
| New Lina | Number of Patients With Abnormalities in Clinical Chemistry: Albumin | 1 participants |
Primary
Number of Patients With Abnormalities in Clinical Chemistry: Alkaline Phosphatase (AP)
For this laboratory parameter, a possibly clinically significant abnormality is defined as a value greater than or equal to 2 times the ULN.
Time frame: 78 weeks
Population: Treated Set with values for AP
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Old Lina | Number of Patients With Abnormalities in Clinical Chemistry: Alkaline Phosphatase (AP) | 7 participants |
| New Lina | Number of Patients With Abnormalities in Clinical Chemistry: Alkaline Phosphatase (AP) | 0 participants |
Primary
Number of Patients With Abnormalities in Clinical Chemistry: Amylase
For this laboratory parameter, a possibly clinically significant abnormality is defined as a value greater than 1.5 times the upper limit of normal (ULN).
Time frame: 78 weeks
Population: Treated Set with values for Amylase
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Old Lina | Number of Patients With Abnormalities in Clinical Chemistry: Amylase | 92 Participants |
| New Lina | Number of Patients With Abnormalities in Clinical Chemistry: Amylase | 35 Participants |
Primary
Number of Patients With Abnormalities in Clinical Chemistry: Aspartate Transaminase (AST)
For this laboratory parameter, a possibly clinically significant abnormality is defined as a value greater than or equal to 3 times the ULN.
Time frame: 78 weeks
Population: Treated Set with values for AST
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Old Lina | Number of Patients With Abnormalities in Clinical Chemistry: Aspartate Transaminase (AST) | 19 participants |
| New Lina | Number of Patients With Abnormalities in Clinical Chemistry: Aspartate Transaminase (AST) | 3 participants |
Primary
Number of Patients With Abnormalities in Clinical Chemistry: Bilirubin
For this laboratory parameter, a possibly clinically significant abnormality is defined as a value greater than or equal to 2 mg/dL.
Time frame: 78 weeks
Population: Treated Set with values for Bilirubin
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Old Lina | Number of Patients With Abnormalities in Clinical Chemistry: Bilirubin | 6 participants |
| New Lina | Number of Patients With Abnormalities in Clinical Chemistry: Bilirubin | 3 participants |
Primary
Number of Patients With Abnormalities in Clinical Chemistry: Calcium
For this laboratory parameter, a possibly clinically significant abnormality is defined as a value less than 1.8 mmol/L (decrease) or a value greater than 3 mmol/L (increase).
Time frame: 78 weeks
Population: Treated Set with values for Calcium
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Old Lina | Number of Patients With Abnormalities in Clinical Chemistry: Calcium | Decrease | 36 participants |
| Old Lina | Number of Patients With Abnormalities in Clinical Chemistry: Calcium | Increase | 4 participants |
| New Lina | Number of Patients With Abnormalities in Clinical Chemistry: Calcium | Decrease | 12 participants |
| New Lina | Number of Patients With Abnormalities in Clinical Chemistry: Calcium | Increase | 0 participants |
Primary
Number of Patients With Abnormalities in Clinical Chemistry: Cholesterol
For this laboratory parameter, a possibly clinically significant abnormality is defined as a value greater than 300 mg/dL.
Time frame: 78 weeks
Population: Treated Set with values for Cholesterol
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Old Lina | Number of Patients With Abnormalities in Clinical Chemistry: Cholesterol | 1 participants |
| New Lina | Number of Patients With Abnormalities in Clinical Chemistry: Cholesterol | 1 participants |
Primary
Number of Patients With Abnormalities in Clinical Chemistry: Creatinine
For this laboratory parameter, a possibly clinically significant abnormality is defined as a value greater than or equal to 1.5 mg/dL.
Time frame: 78 weeks
Population: Treated Set with values for Creatinine
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Old Lina | Number of Patients With Abnormalities in Clinical Chemistry: Creatinine | 52 Participants |
| New Lina | Number of Patients With Abnormalities in Clinical Chemistry: Creatinine | 18 Participants |
Primary
Number of Patients With Abnormalities in Clinical Chemistry: Creatinine Kinase
For this laboratory parameter, a possibly clinically significant abnormality is defined as a value greater than or equal to 3 times the ULN.
Time frame: 78 weeks
Population: Treated Set with values for Creatinine kinase
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Old Lina | Number of Patients With Abnormalities in Clinical Chemistry: Creatinine Kinase | 49 participants |
| New Lina | Number of Patients With Abnormalities in Clinical Chemistry: Creatinine Kinase | 6 participants |
Primary
Number of Patients With Abnormalities in Clinical Chemistry: Glucose
For this laboratory parameter, a possibly clinically significant abnormality is defined as a value less than 54 mg/dL.
Time frame: 78 weeks
Population: Treated Set with values for Glucose
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Old Lina | Number of Patients With Abnormalities in Clinical Chemistry: Glucose | 7 participants |
| New Lina | Number of Patients With Abnormalities in Clinical Chemistry: Glucose | 1 participants |
Primary
Number of Patients With Abnormalities in Clinical Chemistry: Lactate Dehydrogenase (LDH)
For this laboratory parameter, a possibly clinically significant abnormality is defined as a value greater than or equal to 3 times the ULN.
Time frame: 78 weeks
Population: Treated Set with values for LDH
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Old Lina | Number of Patients With Abnormalities in Clinical Chemistry: Lactate Dehydrogenase (LDH) | 1 participants |
| New Lina | Number of Patients With Abnormalities in Clinical Chemistry: Lactate Dehydrogenase (LDH) | 0 participants |
Primary
Number of Patients With Abnormalities in Clinical Chemistry: Phosphate
For this laboratory parameter, a possibly clinically significant abnormality is defined as a value less than 0.7 mmol/L (decrease) or a value greater than 1.7 mmol/L (increase).
Time frame: 78 weeks
Population: Treated Set with values for Phosphate
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Old Lina | Number of Patients With Abnormalities in Clinical Chemistry: Phosphate | Decrease | 11 participants |
| Old Lina | Number of Patients With Abnormalities in Clinical Chemistry: Phosphate | Increase | 38 participants |
| New Lina | Number of Patients With Abnormalities in Clinical Chemistry: Phosphate | Decrease | 8 participants |
| New Lina | Number of Patients With Abnormalities in Clinical Chemistry: Phosphate | Increase | 11 participants |
Primary
Number of Patients With Abnormalities in Clinical Chemistry: Potassium
For this laboratory parameter, a possibly clinically significant abnormality is defined as a value less than 3 mmol/L (decrease) or a value greater than 5.8 mmol/L (increase).
Time frame: 78 weeks
Population: Treated Set with values for Potassium
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Old Lina | Number of Patients With Abnormalities in Clinical Chemistry: Potassium | Decrease | 3 participants |
| Old Lina | Number of Patients With Abnormalities in Clinical Chemistry: Potassium | Increase | 135 participants |
| New Lina | Number of Patients With Abnormalities in Clinical Chemistry: Potassium | Decrease | 0 participants |
| New Lina | Number of Patients With Abnormalities in Clinical Chemistry: Potassium | Increase | 50 participants |
Primary
Number of Patients With Abnormalities in Clinical Chemistry: Sodium
For this laboratory parameter, a possibly clinically significant abnormality is defined as a value less than 130 mmol/L (decrease) or a value greater than 160 mmol/L (increase).
Time frame: 78 weeks
Population: Treated Set with values for Sodium
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Old Lina | Number of Patients With Abnormalities in Clinical Chemistry: Sodium | Decrease | 16 participants |
| Old Lina | Number of Patients With Abnormalities in Clinical Chemistry: Sodium | Increase | 13 participants |
| New Lina | Number of Patients With Abnormalities in Clinical Chemistry: Sodium | Decrease | 3 participants |
| New Lina | Number of Patients With Abnormalities in Clinical Chemistry: Sodium | Increase | 8 participants |
Primary
Number of Patients With Abnormalities in Clinical Chemistry: Triglycerides
For this laboratory parameter, a possibly clinically significant abnormality is defined as a value greater than 300 mg/dL.
Time frame: 78 weeks
Population: Treated Set with values for Triglycerides
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Old Lina | Number of Patients With Abnormalities in Clinical Chemistry: Triglycerides | 329 Participants |
| New Lina | Number of Patients With Abnormalities in Clinical Chemistry: Triglycerides | 101 Participants |
Primary
Number of Patients With Abnormalities in Clinical Chemistry: Uric Acid
For this laboratory parameter, a possibly clinically significant abnormality is defined as a value greater than 11 mg/dL for male and as a value greater than 10 mg/dL for female patients.
Time frame: 78 weeks
Population: Treated Set with values for Uric acid
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Old Lina | Number of Patients With Abnormalities in Clinical Chemistry: Uric Acid | 124 Participants |
| New Lina | Number of Patients With Abnormalities in Clinical Chemistry: Uric Acid | 48 Participants |
Primary
Number of Patients With Abnormalities in Clinical Chemistry: γ-Glutamyl-transferase (GGT)
For this laboratory parameter, a possibly clinically significant abnormality is defined as a value greater than or equal to 3 times the ULN.
Time frame: 78 weeks
Population: Treated Set with values for GGT
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Old Lina | Number of Patients With Abnormalities in Clinical Chemistry: γ-Glutamyl-transferase (GGT) | 54 Participants |
| New Lina | Number of Patients With Abnormalities in Clinical Chemistry: γ-Glutamyl-transferase (GGT) | 14 Participants |
Primary
Number of Patients With Abnormalities in Haematology: Eosinophils
For this laboratory parameter, a possibly clinically significant abnormality is defined as a value greater than or equal to 10%.
Time frame: 78 weeks
Population: Treated Set with values for Eosinophils
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Old Lina | Number of Patients With Abnormalities in Haematology: Eosinophils | 91 participants |
| New Lina | Number of Patients With Abnormalities in Haematology: Eosinophils | 33 participants |
Primary
Number of Patients With Abnormalities in Haematology: Haematocrit
For this laboratory parameter, a possibly clinically significant abnormality is defined as a value less than or equal to 32%.
Time frame: 78 weeks
Population: Treated Set with values for Haematocrit
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Old Lina | Number of Patients With Abnormalities in Haematology: Haematocrit | 48 Participants |
| New Lina | Number of Patients With Abnormalities in Haematology: Haematocrit | 22 Participants |
Primary
Number of Patients With Abnormalities in Haematology: Haemoglobin
For this laboratory parameter, a possibly clinically significant abnormality is defined as a value less than or equal to 11.5 g/dL for male and as a value less than or equal to 9.5 g/dL for female patients.
Time frame: 78 weeks
Population: Treated Set with values for Haemoglobin
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Old Lina | Number of Patients With Abnormalities in Haematology: Haemoglobin | 63 Participants |
| New Lina | Number of Patients With Abnormalities in Haematology: Haemoglobin | 31 Participants |
Primary
Number of Patients With Abnormalities in Haematology: Platelets
For this laboratory parameter, a possibly clinically significant abnormality is defined as value less than or equal to 75 \* 10\^9/L (decrease) or a value greater than or equal to 700 \* 10\^9/L (increase).
Time frame: 78 weeks
Population: Treated Set with values for Platelets
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Old Lina | Number of Patients With Abnormalities in Haematology: Platelets | Decrease | 5 Participants |
| Old Lina | Number of Patients With Abnormalities in Haematology: Platelets | Increase | 0 Participants |
| New Lina | Number of Patients With Abnormalities in Haematology: Platelets | Decrease | 0 Participants |
| New Lina | Number of Patients With Abnormalities in Haematology: Platelets | Increase | 0 Participants |
Primary
Number of Patients With Abnormalities in Haematology: Red Blood Cell Count
For this laboratory parameter, a possibly clinically significant abnormality is defined as a value less than 3 \* 10\^12/L.
Time frame: 78 weeks
Population: Treated Set with values for Red blood cell count
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Old Lina | Number of Patients With Abnormalities in Haematology: Red Blood Cell Count | 31 Participants |
| New Lina | Number of Patients With Abnormalities in Haematology: Red Blood Cell Count | 13 Participants |
Primary
Number of Patients With Abnormalities in Haematology: White Blood Cell Count
For this laboratory parameter, a possibly clinically significant abnormality is defined as a value less than 3 \* 10\^9/L (decrease) or a value greater than 20.1 \* 10\^9/L (increase).
Time frame: 78 weeks
Population: Treated Set with values for White blood cell count
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Old Lina | Number of Patients With Abnormalities in Haematology: White Blood Cell Count | Decrease | 30 Participants |
| Old Lina | Number of Patients With Abnormalities in Haematology: White Blood Cell Count | Increase | 1 Participants |
| New Lina | Number of Patients With Abnormalities in Haematology: White Blood Cell Count | Decrease | 10 Participants |
| New Lina | Number of Patients With Abnormalities in Haematology: White Blood Cell Count | Increase | 1 Participants |
Primary
Number of Patients With Abnormalities in Vital Signs
Vital sign abnormalities (any abnormalities found during PE or ECG are reported with adverse events)
Time frame: 78 weeks
Population: Treated Set: all screened patients who were documented to have taken at lease 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Old Lina | Number of Patients With Abnormalities in Vital Signs | 0 Participants |
| New Lina | Number of Patients With Abnormalities in Vital Signs | 0 Participants |
Secondary
Change in FPG From Baseline to Week 18
Time frame: Baseline and week 18
Population: Treated Set with values for FPG at baseline and at week 18. Values after rescue therapy are set to missing.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Old Lina | Change in FPG From Baseline to Week 18 | 2.13 mg/dL | Standard Deviation 31.47 |
| New Lina | Change in FPG From Baseline to Week 18 | -13.92 mg/dL | Standard Deviation 33.54 |
Secondary
Change in FPG From Baseline to Week 30
Time frame: Baseline and week 30
Population: Treated Set with values for FPG at baseline and at week 30. Values after rescue therapy are set to missing.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Old Lina | Change in FPG From Baseline to Week 30 | 1.52 mg/dL | Standard Deviation 31.84 |
| New Lina | Change in FPG From Baseline to Week 30 | -16.17 mg/dL | Standard Deviation 33 |
Secondary
Change in FPG From Baseline to Week 42
Time frame: Baseline and week 42
Population: Treated Set with values for FPG at baseline and at week 42. Values after rescue therapy are set to missing.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Old Lina | Change in FPG From Baseline to Week 42 | 2.97 mg/dL | Standard Deviation 31.07 |
| New Lina | Change in FPG From Baseline to Week 42 | -11.87 mg/dL | Standard Deviation 31.27 |
Secondary
Change in FPG From Baseline to Week 54
Time frame: Baseline and week 54
Population: Treated Set with values for FPG at baseline and at week 54. Values after rescue therapy are set to missing.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Old Lina | Change in FPG From Baseline to Week 54 | 3.44 mg/dL | Standard Deviation 30.52 |
| New Lina | Change in FPG From Baseline to Week 54 | -12.62 mg/dL | Standard Deviation 30.96 |
Secondary
Change in FPG From Baseline to Week 6
Time frame: Baseline and week 6
Population: Treated Set with values for FPG at baseline and at week 6. Values after rescue therapy are set to missing.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Old Lina | Change in FPG From Baseline to Week 6 | 1.21 mg/dL | Standard Deviation 30.54 |
| New Lina | Change in FPG From Baseline to Week 6 | -15.17 mg/dL | Standard Deviation 30.84 |
Secondary
Change in FPG From Baseline to Week 66
Time frame: Baseline and week 66
Population: Treated Set with values for FPG at baseline and at week 66. Values after rescue therapy are set to missing.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Old Lina | Change in FPG From Baseline to Week 66 | 0.88 mg/dL | Standard Deviation 31.96 |
| New Lina | Change in FPG From Baseline to Week 66 | -12.87 mg/dL | Standard Deviation 30.16 |
Secondary
Change in FPG From Baseline to Week 78
Time frame: Baseline and week 78
Population: Treated Set with values for FPG at baseline and at week 78. Values after rescue therapy are set to missing.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Old Lina | Change in FPG From Baseline to Week 78 | 1.90 mg/dL | Standard Deviation 34.11 |
| New Lina | Change in FPG From Baseline to Week 78 | -13.64 mg/dL | Standard Deviation 31.67 |
Secondary
Change in HbA1c From Baseline to Week 18
Time frame: Baseline and week 18
Population: Treated Set with values for HbA1c at baseline and week 18. Values after rescue therapy are set to missing.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Old Lina | Change in HbA1c From Baseline to Week 18 | 0.03 percent | Standard Deviation 0.63 |
| New Lina | Change in HbA1c From Baseline to Week 18 | -0.63 percent | Standard Deviation 0.72 |
Secondary
Change in HbA1c From Baseline to Week 30
Time frame: Baseline and week 30
Population: Treated Set with values for HbA1c at baseline and week 30. Values after rescue therapy are set to missing.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Old Lina | Change in HbA1c From Baseline to Week 30 | 0.06 percent | Standard Deviation 0.71 |
| New Lina | Change in HbA1c From Baseline to Week 30 | -0.60 percent | Standard Deviation 0.78 |
Secondary
Change in HbA1c From Baseline to Week 42
Time frame: Baseline and week 42
Population: Treated Set with values for HbA1c at baseline and week 42. Values after rescue therapy are set to missing.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Old Lina | Change in HbA1c From Baseline to Week 42 | 0.13 percent | Standard Deviation 0.65 |
| New Lina | Change in HbA1c From Baseline to Week 42 | -0.53 percent | Standard Deviation 0.78 |
Secondary
Change in HbA1c From Baseline to Week 54
Time frame: Baseline and week 54
Population: Treated Set with values for HbA1c at baseline and week 54. Values after rescue therapy are set to missing.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Old Lina | Change in HbA1c From Baseline to Week 54 | 0.19 percent | Standard Deviation 0.7 |
| New Lina | Change in HbA1c From Baseline to Week 54 | -0.45 percent | Standard Deviation 0.81 |
Secondary
Change in HbA1c From Baseline to Week 6
Time frame: Baseline and week 6
Population: Treated Set with values for HbA1c at baseline and week 6. Values after rescue therapy are set to missing.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Old Lina | Change in HbA1c From Baseline to Week 6 | -0.02 percent | Standard Deviation 0.47 |
| New Lina | Change in HbA1c From Baseline to Week 6 | -0.46 percent | Standard Deviation 0.51 |
Secondary
Change in HbA1c From Baseline to Week 66
Time frame: Baseline and week 66
Population: Treated Set with values for HbA1c at baseline and week 66. Values after rescue therapy are set to missing.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Old Lina | Change in HbA1c From Baseline to Week 66 | 0.14 percent | Standard Deviation 0.73 |
| New Lina | Change in HbA1c From Baseline to Week 66 | -0.44 percent | Standard Deviation 0.85 |
Secondary
Change in HbA1c From Baseline to Week 78
Time frame: Baseline and week 78
Population: Treated Set with values for HbA1c at baseline and week 78. Values after rescue therapy are set to missing.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Old Lina | Change in HbA1c From Baseline to Week 78 | 0.12 percent | Standard Deviation 0.76 |
| New Lina | Change in HbA1c From Baseline to Week 78 | -0.49 percent | Standard Deviation 0.85 |
Secondary
Number of Patients With HbA1c<6.5% Over Time
Time frame: 78 weeks
Population: Treated Set with values for HbA1c at baseline and week 78. Values after rescue therapy are set to missing.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Old Lina | Number of Patients With HbA1c<6.5% Over Time | 139 participants |
| New Lina | Number of Patients With HbA1c<6.5% Over Time | 74 participants |
Secondary
Number of Patients With HbA1c<7.0% Over Time
Time frame: 78 weeks
Population: Treated Set with values for HbA1c at baseline and week 78. Values after rescue therapy are set to missing.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Old Lina | Number of Patients With HbA1c<7.0% Over Time | 382 participants |
| New Lina | Number of Patients With HbA1c<7.0% Over Time | 172 participants |
Secondary
Number of Patients With Lowered HbA1c by at Least 0.5% Over Time
Time frame: 78 weeks
Population: Treated Set with values for HbA1c at baseline and week 78. Values after rescue therapy are set to missing.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Old Lina | Number of Patients With Lowered HbA1c by at Least 0.5% Over Time | 155 participants |
| New Lina | Number of Patients With Lowered HbA1c by at Least 0.5% Over Time | 175 participants |