Trial Outcomes & Findings for Efficacy and Safety of Linagliptin in Elderly Patients With Type 2 Diabetes (NCT NCT01084005)

NCT ID: NCT01084005

Last Updated: 2014-01-29

Results Overview

HbA1c is measured as a percentage. Thus, this change from baseline reflects the Week 24 HbA1c percent minus the baseline HbA1c percent. Means are treatment adjusted for baseline HbA1c and prior use of insulin.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 241 participants
• Primary outcome timeframe: Baseline and week 24
• Results posted on: 2014-01-29

Participant Flow

A total of 241 patients were randomised in a 2:1 ratio to receive treatment with linagliptin 5mg (n=162) or placebo (n=79). All randomised patients were treated.

Participant milestones

Measure	Placebo Patients randomized to receive treatment with matching placebo	Linagliptin 5 mg Patients randomized to receive treatment with Linagliptin 5mg
Overall Study STARTED	79	162
Overall Study COMPLETED	74	146
Overall Study NOT COMPLETED	5	16

Reasons for withdrawal

Measure	Placebo Patients randomized to receive treatment with matching placebo	Linagliptin 5 mg Patients randomized to receive treatment with Linagliptin 5mg
Overall Study Adverse Event	1	8
Overall Study Protocol Violation	3	7
Overall Study Withdrawal by Subject	1	1

Baseline Characteristics

Efficacy and Safety of Linagliptin in Elderly Patients With Type 2 Diabetes

Baseline characteristics by cohort

Measure	Placebo n=79 Participants Patients randomized to receive treatment with matching placebo	Linagliptin 5 mg n=162 Participants Patients randomized to receive treatment with Linagliptin 5mg	Total n=241 Participants Total of all reporting groups
Age, Continuous	74.9 Years STANDARD_DEVIATION 4.2 • n=5 Participants	74.9 Years STANDARD_DEVIATION 4.4 • n=7 Participants	74.9 Years STANDARD_DEVIATION 4.3 • n=5 Participants
Sex: Female, Male Female	30 Participants n=5 Participants	46 Participants n=7 Participants	76 Participants n=5 Participants
Sex: Female, Male Male	49 Participants n=5 Participants	116 Participants n=7 Participants	165 Participants n=5 Participants
Body mass index (BMI) continuous	29.80 kg/m^2 STANDARD_DEVIATION 4.54 • n=5 Participants	29.60 kg/m^2 STANDARD_DEVIATION 4.74 • n=7 Participants	29.67 kg/m^2 STANDARD_DEVIATION 4.67 • n=5 Participants
Glycosylated Hemoglobin A1 (HbA1c)	7.70 Percent STANDARD_DEVIATION 0.70 • n=5 Participants	7.82 Percent STANDARD_DEVIATION 0.78 • n=7 Participants	7.78 Percent STANDARD_DEVIATION 0.76 • n=5 Participants
Fasting Plasma Glucose (FPG)	144.1 mg/dL STANDARD_DEVIATION 29.6 • n=5 Participants	152.7 mg/dL STANDARD_DEVIATION 28.7 • n=7 Participants	149.9 mg/dL STANDARD_DEVIATION 29.2 • n=5 Participants

PRIMARY outcome

Timeframe: Baseline and week 24

Population: FAS consisting of all randomised patients who were treated with at least one dose of study drug, had a baseline, and at least 1 on-treatment HbA1c measurement. Last observation carried forward (LOCF) was used as the imputation rule.

HbA1c is measured as a percentage. Thus, this change from baseline reflects the Week 24 HbA1c percent minus the baseline HbA1c percent. Means are treatment adjusted for baseline HbA1c and prior use of insulin.

Outcome measures

Measure	Placebo n=78 Participants Patients randomized to receive treatment with matching placebo	Linagliptin 5 mg n=160 Participants Patients randomized to receive treatment with Linagliptin 5mg
HbA1c Change From Baseline to Week 24	0.04 Percent Standard Error 0.07	-0.61 Percent Standard Error 0.06

SECONDARY outcome

Timeframe: Baseline and week 6

Population: FAS (LOCF)

HbA1c is measured as a percentage. Thus, this change from baseline reflects the Week 6 HbA1c percent minus the baseline HbA1c percent. Means are treatment adjusted for baseline HbA1c and prior use of insulin.

Outcome measures

Measure	Placebo n=78 Participants Patients randomized to receive treatment with matching placebo	Linagliptin 5 mg n=160 Participants Patients randomized to receive treatment with Linagliptin 5mg
HbA1c Change From Baseline to Week 6	-0.07 Percent Standard Error 0.05	-0.42 Percent Standard Error 0.03

SECONDARY outcome

Timeframe: Baseline and week 12

Population: FAS (LOCF)

HbA1c is measured as a percentage. Thus, this change from baseline reflects the Week 12 HbA1c percent minus the baseline HbA1c percent. Means are treatment adjusted for baseline HbA1c and prior use of insulin.

Outcome measures

Measure	Placebo n=78 Participants Patients randomized to receive treatment with matching placebo	Linagliptin 5 mg n=160 Participants Patients randomized to receive treatment with Linagliptin 5mg
HbA1c Change From Baseline to Week 12	-0.03 Percent Standard Error 0.06	-0.60 Percent Standard Error 0.05

SECONDARY outcome

Timeframe: Baseline and week 18

Population: FAS (LOCF)

HbA1c is measured as a percentage. Thus, this change from baseline reflects the Week 18 HbA1c percent minus the baseline HbA1c percent. Means are treatment adjusted for baseline HbA1c and prior use of insulin.

Outcome measures

Measure	Placebo n=78 Participants Patients randomized to receive treatment with matching placebo	Linagliptin 5 mg n=160 Participants Patients randomized to receive treatment with Linagliptin 5mg
HbA1c Change From Baseline to Week 18	0.04 Percent Standard Error 0.07	-0.58 Percent Standard Error 0.05

SECONDARY outcome

Timeframe: Baseline and week 24

Population: FAS (LOCF)

This change from baseline reflects the Week 24 FPG minus the baseline FPG. Means are treatment-adjusted for baseline HbA1c, baseline FPG and prior use of insulin.

Outcome measures

Measure	Placebo n=78 Participants Patients randomized to receive treatment with matching placebo	Linagliptin 5 mg n=156 Participants Patients randomized to receive treatment with Linagliptin 5mg
FPG Change From Baseline to Week 24	10.1 mg/dL Standard Error 4.3	-10.6 mg/dL Standard Error 3.2

SECONDARY outcome

Timeframe: Baseline and week 6

Population: FAS Observed cases (OC)

This change from baseline reflects the Week 6 FPG minus the baseline FPG. Means are treatment-adjusted for baseline HbA1c, baseline FPG and prior use of insulin, week repeated within patient and week by treatment interaction.

Outcome measures

Measure	Placebo n=77 Participants Patients randomized to receive treatment with matching placebo	Linagliptin 5 mg n=153 Participants Patients randomized to receive treatment with Linagliptin 5mg
FPG Change From Baseline to Week 6	4.6 mg/dL Standard Error 2.7	-14.1 mg/dL Standard Error 2.0

SECONDARY outcome

Timeframe: Baseline and week 12

Population: FAS (OC)

This change from baseline reflects the Week 12 FPG minus the baseline FPG. Means are treatment-adjusted for baseline HbA1c, baseline FPG and prior use of insulin, week repeated within patient and week by treatment interaction.

Outcome measures

Measure	Placebo n=75 Participants Patients randomized to receive treatment with matching placebo	Linagliptin 5 mg n=148 Participants Patients randomized to receive treatment with Linagliptin 5mg
FPG Change From Baseline to Week 12	6.8 mg/dL Standard Error 2.9	-14.7 mg/dL Standard Error 2.1

SECONDARY outcome

Timeframe: Baseline and week 18

Population: FAS (OC)

This change from baseline reflects the Week 18 FPG minus the baseline FPG. Means are treatment-adjusted for baseline HbA1c, baseline FPG and prior use of insulin, week repeated within patient and week by treatment interaction.

Outcome measures

Measure	Placebo n=68 Participants Patients randomized to receive treatment with matching placebo	Linagliptin 5 mg n=145 Participants Patients randomized to receive treatment with Linagliptin 5mg
FPG Change From Baseline to Week 18	9.6 mg/dL Standard Error 3.6	-12.0 mg/dL Standard Error 2.5

SECONDARY outcome

Timeframe: Baseline and week 24

Population: FAS with baseline HbA1c \>=7% and non-completers considered as failure imputation (NCF)

The percentage of patients with an HbA1c value below 7% at week 24 was calculated for each treatment arm. If a patient did not have an HbA1c value at week 24 they were considered a failure, so HbA1c above 7%. Only patients with baseline HbA1c >= 7%

Outcome measures

Measure	Placebo n=72 Participants Patients randomized to receive treatment with matching placebo	Linagliptin 5 mg n=149 Participants Patients randomized to receive treatment with Linagliptin 5mg
Percentage of Patients With HbA1c <7.0% at Week 24	8.3 percentage of patients	38.9 percentage of patients

SECONDARY outcome

Timeframe: Baseline and week 24

Population: FAS (NCF)

The percentage of patients with an HbA1c value below 7% at week 24 were calculated for each treatment arm. If a patient did not have an HbA1c value at week 24 they were considered a failure, so HbA1c above 7%.

Outcome measures

Measure	Placebo n=78 Participants Patients randomized to receive treatment with matching placebo	Linagliptin 5 mg n=160 Participants Patients randomized to receive treatment with Linagliptin 5mg
Percentage of Patients With HbA1c <7.0% at Week 24	11.5 percentage of patients	41.9 percentage of patients

SECONDARY outcome

Timeframe: Baseline and week 24

Population: FAS (NCF)

The percentage of patients with an HbA1c reduction of ≥0.5% at week 24 from baseline was calculated for each treatment arm. If a patient did not have an HbA1c value at week 24 they were considered a failure, so HbA1c reduction less than 0.5%

Outcome measures

Measure	Placebo n=78 Participants Patients randomized to receive treatment with matching placebo	Linagliptin 5 mg n=160 Participants Patients randomized to receive treatment with Linagliptin 5mg
Percentage of Patients Who Have a HbA1c Lowering by at Least 0.5% at Week 24	12.8 percentage of patients	54.4 percentage of patients

SECONDARY outcome

Timeframe: week 24

Population: FAS (OC)

The use of rescue therapy was planned for patients failing to achieve preset criteria based on glucose levels during the randomised treatment period of the trial

Outcome measures

Measure	Placebo n=78 Participants Patients randomized to receive treatment with matching placebo	Linagliptin 5 mg n=160 Participants Patients randomized to receive treatment with Linagliptin 5mg
Number of Patients With Rescue Therapy	11 Number of patients	7 Number of patients

Adverse Events

Placebo

Serious events: 5 serious events

Other events: 37 other events

Deaths: 0 deaths

Linagliptin 5 mg

Serious events: 14 serious events

Other events: 70 other events

Deaths: 0 deaths

Serious adverse events

Measure	Placebo n=79 participants at risk Patients randomized to receive treatment with matching placebo	Linagliptin 5 mg n=162 participants at risk Patients randomized to receive treatment with Linagliptin 5mg
Cardiac disorders Atrial fibrillation	0.00% 0/79 • 24 weeks + 7 days of follow-up	0.62% 1/162 • 24 weeks + 7 days of follow-up
Cardiac disorders Atrioventricular block complete	0.00% 0/79 • 24 weeks + 7 days of follow-up	0.62% 1/162 • 24 weeks + 7 days of follow-up
Cardiac disorders Bradycardia	0.00% 0/79 • 24 weeks + 7 days of follow-up	0.62% 1/162 • 24 weeks + 7 days of follow-up
Cardiac disorders Coronary artery disease	0.00% 0/79 • 24 weeks + 7 days of follow-up	0.62% 1/162 • 24 weeks + 7 days of follow-up
Gastrointestinal disorders Rectal haemorrhage	0.00% 0/79 • 24 weeks + 7 days of follow-up	0.62% 1/162 • 24 weeks + 7 days of follow-up
Infections and infestations Lower respiratory tract infection	1.3% 1/79 • 24 weeks + 7 days of follow-up	0.00% 0/162 • 24 weeks + 7 days of follow-up
Infections and infestations Pneumonia	0.00% 0/79 • 24 weeks + 7 days of follow-up	1.9% 3/162 • 24 weeks + 7 days of follow-up
Infections and infestations Vestibular neuronitis	0.00% 0/79 • 24 weeks + 7 days of follow-up	0.62% 1/162 • 24 weeks + 7 days of follow-up
Injury, poisoning and procedural complications Fall	0.00% 0/79 • 24 weeks + 7 days of follow-up	1.2% 2/162 • 24 weeks + 7 days of follow-up
Injury, poisoning and procedural complications Limb traumatic amputation	0.00% 0/79 • 24 weeks + 7 days of follow-up	0.62% 1/162 • 24 weeks + 7 days of follow-up
Injury, poisoning and procedural complications Lower limb fracture	0.00% 0/79 • 24 weeks + 7 days of follow-up	0.62% 1/162 • 24 weeks + 7 days of follow-up
Injury, poisoning and procedural complications Thoracic vertebral fracture	0.00% 0/79 • 24 weeks + 7 days of follow-up	0.62% 1/162 • 24 weeks + 7 days of follow-up
Metabolism and nutrition disorders Dehydration	0.00% 0/79 • 24 weeks + 7 days of follow-up	0.62% 1/162 • 24 weeks + 7 days of follow-up
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung adenocarcinoma	1.3% 1/79 • 24 weeks + 7 days of follow-up	0.00% 0/162 • 24 weeks + 7 days of follow-up
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant melanoma	1.3% 1/79 • 24 weeks + 7 days of follow-up	0.00% 0/162 • 24 weeks + 7 days of follow-up
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer	1.3% 1/79 • 24 weeks + 7 days of follow-up	0.00% 0/162 • 24 weeks + 7 days of follow-up
Nervous system disorders Cerebrovascular accident	0.00% 0/79 • 24 weeks + 7 days of follow-up	0.62% 1/162 • 24 weeks + 7 days of follow-up
Nervous system disorders Presyncope	0.00% 0/79 • 24 weeks + 7 days of follow-up	0.62% 1/162 • 24 weeks + 7 days of follow-up
Renal and urinary disorders Urinary bladder polyp	1.3% 1/79 • 24 weeks + 7 days of follow-up	0.00% 0/162 • 24 weeks + 7 days of follow-up

Other adverse events

Measure	Placebo n=79 participants at risk Patients randomized to receive treatment with matching placebo	Linagliptin 5 mg n=162 participants at risk Patients randomized to receive treatment with Linagliptin 5mg
Gastrointestinal disorders Diarrhoea	2.5% 2/79 • 24 weeks + 7 days of follow-up	5.6% 9/162 • 24 weeks + 7 days of follow-up
Infections and infestations Nasopharyngitis	8.9% 7/79 • 24 weeks + 7 days of follow-up	10.5% 17/162 • 24 weeks + 7 days of follow-up
Infections and infestations Upper respiratory tract infection	6.3% 5/79 • 24 weeks + 7 days of follow-up	3.7% 6/162 • 24 weeks + 7 days of follow-up
Infections and infestations Urinary tract infection	6.3% 5/79 • 24 weeks + 7 days of follow-up	4.3% 7/162 • 24 weeks + 7 days of follow-up
Metabolism and nutrition disorders Hyperglycaemia	10.1% 8/79 • 24 weeks + 7 days of follow-up	5.6% 9/162 • 24 weeks + 7 days of follow-up
Metabolism and nutrition disorders Hypoglycaemia	16.5% 13/79 • 24 weeks + 7 days of follow-up	22.8% 37/162 • 24 weeks + 7 days of follow-up
Nervous system disorders Dizziness	5.1% 4/79 • 24 weeks + 7 days of follow-up	3.7% 6/162 • 24 weeks + 7 days of follow-up

Additional Information

Boehringer Ingelheim Call Center

Boehringer Ingelheim Pharmaceuticals

Phone: 1-800-243-0127

Email: clintriage.rdg@boehringer-ingelheim.com

Results disclosure agreements

• Principal investigator is a sponsor employee Any publication of the result of this trial must be consistent with the Boehringer Ingelheim publication policy. The rights of the investigator and of the sponsor with regard to publication of the results of this trial are described in the investigator contract.
• Publication restrictions are in place

Restriction type: OTHER