Trial Outcomes & Findings for Randomized, Double-blind (db), Placebo-controlled 18 Week Study of Linagliptin (BI 1356) in Type 2 Diabetic Patients With Insufficient Glycaemic Control on a Sulfonylurea Drug (NCT NCT00819091)

NCT ID: NCT00819091

Last Updated: 2014-06-27

Results Overview

HbA1c is measured as a percent. The change from baseline reflects the Week 18 HbA1c percent minus the Week 0 HbA1c percent. Means are adjusted for baseline HbA1c and previous anti-diabetic medication.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 245 participants
• Primary outcome timeframe: Baseline, week 18
• Results posted on: 2014-06-27

Participant Flow

Participant milestones

Measure	Placebo Matching placebo tablet taken orally once daily	Linagliptin (BI 1356) 5.0 mg Linagliptin 5.0 mg tablet taken orally once daily
Overall Study STARTED	84	161
Overall Study COMPLETED	77	151
Overall Study NOT COMPLETED	7	10

Reasons for withdrawal

Measure	Placebo Matching placebo tablet taken orally once daily	Linagliptin (BI 1356) 5.0 mg Linagliptin 5.0 mg tablet taken orally once daily
Overall Study Adverse Event	3	5
Overall Study Protocol Violation	0	1
Overall Study Lost to Follow-up	2	0
Overall Study Withdrawal by Subject	1	2
Overall Study Other	1	2

Baseline Characteristics

Randomized, Double-blind (db), Placebo-controlled 18 Week Study of Linagliptin (BI 1356) in Type 2 Diabetic Patients With Insufficient Glycaemic Control on a Sulfonylurea Drug

Baseline characteristics by cohort

Measure	Placebo n=84 Participants Matching placebo tablet taken orally once daily	Linagliptin 5.0 mg n=161 Participants Linagliptin 5.0 mg tablet taken orally once daily	Total n=245 Participants Total of all reporting groups
Age, Continuous	56.2 years STANDARD_DEVIATION 10.2 • n=5 Participants	57.2 years STANDARD_DEVIATION 9.8 • n=7 Participants	56.9 years STANDARD_DEVIATION 9.9 • n=5 Participants
Sex: Female, Male Female	32 Participants n=5 Participants	84 Participants n=7 Participants	116 Participants n=5 Participants
Sex: Female, Male Male	52 Participants n=5 Participants	77 Participants n=7 Participants	129 Participants n=5 Participants
Race/Ethnicity, Customized White	34 participants n=5 Participants	73 participants n=7 Participants	107 participants n=5 Participants
Race/Ethnicity, Customized Black	6 participants n=5 Participants	11 participants n=7 Participants	17 participants n=5 Participants
Race/Ethnicity, Customized Asian	43 participants n=5 Participants	76 participants n=7 Participants	119 participants n=5 Participants
Race/Ethnicity, Customized American Indian/Alaskan Native	1 participants n=5 Participants	1 participants n=7 Participants	2 participants n=5 Participants
Race/Ethnicity, Customized Not Hispanic	70 participants n=5 Participants	133 participants n=7 Participants	203 participants n=5 Participants
Race/Ethnicity, Customized Hispanic	14 participants n=5 Participants	28 participants n=7 Participants	42 participants n=5 Participants
Body Mass Index (BMI)	28.21 kilogram/square meter STANDARD_DEVIATION 5.12 • n=5 Participants	28.40 kilogram/square meter STANDARD_DEVIATION 5.02 • n=7 Participants	28.33 kilogram/square meter STANDARD_DEVIATION 5.04 • n=5 Participants
Baseline glycosylated hemoglobin (HbA1c)	8.6 percentage STANDARD_DEVIATION 0.72 • n=5 Participants	8.61 percentage STANDARD_DEVIATION 0.85 • n=7 Participants	8.61 percentage STANDARD_DEVIATION 0.81 • n=5 Participants
Fasting blood plasma glucose (FPG)	174.9 milligram/deciliter (mg/dL) STANDARD_DEVIATION 49.0 • n=5 Participants	182.0 milligram/deciliter (mg/dL) STANDARD_DEVIATION 51.8 • n=7 Participants	179.6 milligram/deciliter (mg/dL) STANDARD_DEVIATION 50.9 • n=5 Participants

PRIMARY outcome

Timeframe: Baseline, week 18

Population: Full Analysis Set includes all randomized patients with baseline and on-treatment value of HbA1c. Last observation carried forward (LOCF) was used as the imputation rule.

HbA1c is measured as a percent. The change from baseline reflects the Week 18 HbA1c percent minus the Week 0 HbA1c percent. Means are adjusted for baseline HbA1c and previous anti-diabetic medication.

Outcome measures

Measure	Placebo n=82 Participants Matching placebo tablet taken orally once daily	Linagliptin 5.0 mg n=158 Participants Linagliptin 5.0 mg tablet taken orally once daily
Change From Baseline in HbA1c (Glycosylated Hemoglobin) at Week 18	-0.07 percent Standard Error 0.10	-0.54 percent Standard Error 0.07

SECONDARY outcome

Timeframe: Baseline, week 18

Population: Full Analysis Set includes all randomized patients with baseline and on-treatment value of FPG. Last observation carried forward (LOCF) was used as the imputation rule.

Change from baseline reflects the Week 18 FPG minus the Week 0 FPG. Means are adjusted for baseline FPG and previous anti-diabetic medication.

Outcome measures

Measure	Placebo n=78 Participants Matching placebo tablet taken orally once daily	Linagliptin 5.0 mg n=155 Participants Linagliptin 5.0 mg tablet taken orally once daily
Change From Baseline in Fasting Plasma Glucose at Week 18	-1.8 mg/dL Standard Error 4.5	-8.2 mg/dL Standard Error 3.3

SECONDARY outcome

Timeframe: week 18

Population: FAS patients with baseline HbA1c \>= 7.0%. Non-completers were considered as failure imputation (NCF).

An absolute efficacy response is defined as HbA1c < 7.0% at 18 weeks. A non-response is defined as HbA1c >= 7.0% at 18 weeks.

Outcome measures

Measure	Placebo n=82 Participants Matching placebo tablet taken orally once daily	Linagliptin 5.0 mg n=158 Participants Linagliptin 5.0 mg tablet taken orally once daily
Percentage of Patients With Absolute Efficacy Response (HbA1c < 7%) at Week 18 HbA1c < 7%	3.7 Percentage of Patients	15.2 Percentage of Patients
Percentage of Patients With Absolute Efficacy Response (HbA1c < 7%) at Week 18 HbA1c >= 7%	96.3 Percentage of Patients	84.8 Percentage of Patients

SECONDARY outcome

Timeframe: week 18

Population: FAS patients with baseline HbA1c \>= 6.5%. Non-completers were considered as failure imputation (NCF).

An absolute efficacy response is defined as HbA1c < 6.5% at 18 weeks. A non-response is defined as HbA1c >= 6.5% at 18 weeks.

Outcome measures

Measure	Placebo n=82 Participants Matching placebo tablet taken orally once daily	Linagliptin 5.0 mg n=158 Participants Linagliptin 5.0 mg tablet taken orally once daily
Percentage of Patients With Absolute Efficacy Response (HbA1c < 6.5%) at Week 18 HbA1c < 6.5%	2.4 percentage of participants	5.7 percentage of participants
Percentage of Patients With Absolute Efficacy Response (HbA1c < 6.5%) at Week 18 HbA1c >= 6.5%	97.6 percentage of participants	94.3 percentage of participants

SECONDARY outcome

Timeframe: Baseline, week 18

Population: FAS patients. Non-completers were considered as failure imputation (NCF).

An efficacy response is defined as HbA1c lowered by 0.5% or more at 18 weeks. A non-response is defined as HbA1c not lowered by 0.5% or more at 18 weeks.

Outcome measures

Measure	Placebo n=82 Participants Matching placebo tablet taken orally once daily	Linagliptin 5.0 mg n=158 Participants Linagliptin 5.0 mg tablet taken orally once daily
Percentage of Patients With HbA1c Lowering by at Least 0.5% From Baseline at Week 18 HbA1c lower by at least 0.5%	22 percentage of participants	57.6 percentage of participants
Percentage of Patients With HbA1c Lowering by at Least 0.5% From Baseline at Week 18 HbA1c not lower by at least 0.5%	78.0 percentage of participants	42.4 percentage of participants

SECONDARY outcome

Timeframe: Baseline, week 6

Population: FAS patients. Mixed Model Repeated Measurements (MMRM) analysis of Observed Cases (OC).

HbA1c is measured as a percent. The change from baseline reflects the Week 6 HbA1c percent minus the Week 0 HbA1c percent. Means are adjusted for baseline HbA1c and previous anti-diabetic medication.

Outcome measures

Measure	Placebo n=82 Participants Matching placebo tablet taken orally once daily	Linagliptin 5.0 mg n=158 Participants Linagliptin 5.0 mg tablet taken orally once daily
Mixed Model Repeated Measurements Analysis of Change From Baseline in HbA1c at Week 6	-0.02 percent Standard Error 0.07	-0.43 percent Standard Error 0.05

SECONDARY outcome

Timeframe: Baseline, week 12

Population: FAS patients. Mixed Model Repeated Measurements (MMRM) analysis of Observed Cases (OC).

HbA1c is measured as a percent. The change from baseline reflects the Week 12 HbA1c percent minus the Week 0 HbA1c percent. Means are adjusted for baseline HbA1c and previous anti-diabetic medication.

Outcome measures

Measure	Placebo n=82 Participants Matching placebo tablet taken orally once daily	Linagliptin 5.0 mg n=158 Participants Linagliptin 5.0 mg tablet taken orally once daily
Mixed Model Repeated Measurements Analysis of Change From Baseline in HbA1c at Week 12	-0.11 percent Standard Error 0.09	-0.61 percent Standard Error 0.07

SECONDARY outcome

Timeframe: Baseline, week 18

Population: FAS patients. Mixed Model Repeated Measurements (MMRM) analysis of Observed Cases (OC).

HbA1c is measured as a percent. The change from baseline reflects the Week 18 HbA1c percent minus the Week 0 HbA1c percent. Means are adjusted for baseline HbA1c and previous anti-diabetic medication.

Outcome measures

Measure	Placebo n=82 Participants Matching placebo tablet taken orally once daily	Linagliptin 5.0 mg n=158 Participants Linagliptin 5.0 mg tablet taken orally once daily
Mixed Model Repeated Measurements Analysis of Change From Baseline in HbA1c at Week 18	-0.08 percent Standard Error 0.10	-0.55 percent Standard Error 0.07

SECONDARY outcome

Timeframe: Baseline, week 6

Population: Full Analysis Set includes all randomized patients with baseline and on-treatment value of FPG. Last observation carried forward (LOCF) was used as the imputation rule.

Change from baseline reflects the Week 6 FPG minus the Week 0 FPG. Means are adjusted for baseline FPG and previous anti-diabetic medication.

Outcome measures

Measure	Placebo n=78 Participants Matching placebo tablet taken orally once daily	Linagliptin 5.0 mg n=155 Participants Linagliptin 5.0 mg tablet taken orally once daily
Change From Baseline in Fasting Plasma Glucose at Week 6	-7.6 mg/dL Standard Error 3.8	-13.5 mg/dL Standard Error 2.7

SECONDARY outcome

Timeframe: Baseline, week 12

Population: Full Analysis Set includes all randomized patients with baseline and on-treatment value of FPG. Last observation carried forward (LOCF) was used as the imputation rule.

Change from baseline reflects the Week 12 FPG minus the Week 0 FPG. Means are adjusted for baseline FPG and previous anti-diabetic medication.

Outcome measures

Measure	Placebo n=78 Participants Matching placebo tablet taken orally once daily	Linagliptin 5.0 mg n=155 Participants Linagliptin 5.0 mg tablet taken orally once daily
Change From Baseline in Fasting Plasma Glucose at Week 12	4.1 mg/dL Standard Error 4.7	-10.3 mg/dL Standard Error 3.4

Adverse Events

Placebo

Serious events: 1 serious events

Other events: 14 other events

Deaths: 0 deaths

Linagliptin 5.0 mg

Serious events: 5 serious events

Other events: 14 other events

Deaths: 0 deaths

Serious adverse events

Measure	Placebo n=84 participants at risk Matching placebo tablet taken orally once daily	Linagliptin 5.0 mg n=161 participants at risk Linagliptin 5.0 mg tablet taken orally once daily
Cardiac disorders Cardio-respiratory arrest	0.00% 0/84 • From day of first dose until 7 days after last dose	0.62% 1/161 • From day of first dose until 7 days after last dose
Cardiac disorders Myocardial infarction	0.00% 0/84 • From day of first dose until 7 days after last dose	0.62% 1/161 • From day of first dose until 7 days after last dose
Cardiac disorders Supraventricular tachycardia	0.00% 0/84 • From day of first dose until 7 days after last dose	0.62% 1/161 • From day of first dose until 7 days after last dose
Eye disorders Vitreous haemorrhage	0.00% 0/84 • From day of first dose until 7 days after last dose	0.62% 1/161 • From day of first dose until 7 days after last dose
Hepatobiliary disorders Cholelithiasis	0.00% 0/84 • From day of first dose until 7 days after last dose	0.62% 1/161 • From day of first dose until 7 days after last dose
Infections and infestations Pyelonephritis	0.00% 0/84 • From day of first dose until 7 days after last dose	0.62% 1/161 • From day of first dose until 7 days after last dose
Infections and infestations Sepsis	0.00% 0/84 • From day of first dose until 7 days after last dose	0.62% 1/161 • From day of first dose until 7 days after last dose
Infections and infestations Septic shock	0.00% 0/84 • From day of first dose until 7 days after last dose	0.62% 1/161 • From day of first dose until 7 days after last dose
Nervous system disorders Epilepsy	1.2% 1/84 • From day of first dose until 7 days after last dose	0.00% 0/161 • From day of first dose until 7 days after last dose
Renal and urinary disorders Renal failure acute	0.00% 0/84 • From day of first dose until 7 days after last dose	0.62% 1/161 • From day of first dose until 7 days after last dose

Other adverse events

Measure	Placebo n=84 participants at risk Matching placebo tablet taken orally once daily	Linagliptin 5.0 mg n=161 participants at risk Linagliptin 5.0 mg tablet taken orally once daily
Metabolism and nutrition disorders Hyperglycaemia	16.7% 14/84 • From day of first dose until 7 days after last dose	8.7% 14/161 • From day of first dose until 7 days after last dose

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