Trial Outcomes & Findings for Efficacy vs Placebo as Initial Combination Therapy With Pioglitazone (NCT NCT00641043)

NCT ID: NCT00641043

Last Updated: 2014-02-17

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 previous anti-diabetic medication.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 389 participants
• Primary outcome timeframe: Baseline and week 24
• Results posted on: 2014-02-17

Participant Flow

Participant milestones

Measure	Placebo + Pioglitazone Patients randomized to receive treatment with matching placebo (to Linagliptin 5 mg) and Pioglitazone 30 mg	Linagliptin + Pioglitazone Patients randomized to receive treatment with Linagliptin 5 mg and Pioglitazone 30 mg
Overall Study STARTED	130	259
Overall Study COMPLETED	111	244
Overall Study NOT COMPLETED	19	15

Reasons for withdrawal

Measure	Placebo + Pioglitazone Patients randomized to receive treatment with matching placebo (to Linagliptin 5 mg) and Pioglitazone 30 mg	Linagliptin + Pioglitazone Patients randomized to receive treatment with Linagliptin 5 mg and Pioglitazone 30 mg
Overall Study Adverse Event	6	4
Overall Study Protocol Violation	2	3
Overall Study Lost to Follow-up	3	2
Overall Study Withdrawal by Subject	4	4
Overall Study Other incl. lack of efficacy	4	2

Baseline Characteristics

Efficacy vs Placebo as Initial Combination Therapy With Pioglitazone

Baseline characteristics by cohort

Measure	Placebo + Pioglitazone n=130 Participants Patients randomized to receive treatment with matching placebo (to Linagliptin 5 mg) and Pioglitazone 30 mg	Linagliptin + Pioglitazone n=259 Participants Patients randomized to receive treatment with Linagliptin 5 mg and Pioglitazone 30 mg	Total n=389 Participants Total of all reporting groups
Age, Continuous	57.1 Years STANDARD_DEVIATION 10.1 • n=93 Participants	57.7 Years STANDARD_DEVIATION 9.6 • n=4 Participants	57.5 Years STANDARD_DEVIATION 9.8 • n=27 Participants
Sex: Female, Male Female	45 Participants n=93 Participants	107 Participants n=4 Participants	152 Participants n=27 Participants
Sex: Female, Male Male	85 Participants n=93 Participants	152 Participants n=4 Participants	237 Participants n=27 Participants
Body mass index continuous	29.72 kg/m^2 STANDARD_DEVIATION 4.84 • n=93 Participants	28.68 kg/m^2 STANDARD_DEVIATION 4.82 • n=4 Participants	29.02 kg/m^2 STANDARD_DEVIATION 4.85 • n=27 Participants
Glycosylated haemoglobin A1 (HbA1c)	8.58 Percent STANDARD_DEVIATION 0.87 • n=93 Participants	8.60 Percent STANDARD_DEVIATION 0.79 • n=4 Participants	8.59 Percent STANDARD_DEVIATION 0.82 • n=27 Participants
Fasting Plasma Glucose (FPG)	190.3 mg/dL STANDARD_DEVIATION 43.8 • n=93 Participants	189.8 mg/dL STANDARD_DEVIATION 42.7 • n=4 Participants	189.9 mg/dL STANDARD_DEVIATION 43.0 • n=27 Participants

PRIMARY outcome

Timeframe: Baseline and week 24

Population: The Full Analysis Set (FAS) included all treated and randomised patients with a baseline and at least one on treatment HbA1c measurement available. 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 previous anti-diabetic medication.

Outcome measures

Measure	Placebo + Pioglitazone n=128 Participants Patients randomized to receive treatment with matching placebo (to Linagliptin 5 mg) and Pioglitazone 30 mg	Linagliptin + Pioglitazone n=252 Participants Patients randomized to receive treatment with Linagliptin 5 mg and Pioglitazone 30 mg
HbA1c Change From Baseline to Week 24	-0.56 Percent Standard Error 0.09	-1.06 Percent Standard Error 0.06

SECONDARY outcome

Timeframe: Baseline and week 6

Population: The Full Analysis Set (FAS) included all randomised and treated patients with a baseline and at least one on treatment HbA1c measurement available. 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 6 HbA1c percent minus the baseline HbA1c percent. Means are treatment adjusted for baseline HbA1c and previous anti-diabetic medication.

Outcome measures

Measure	Placebo + Pioglitazone n=128 Participants Patients randomized to receive treatment with matching placebo (to Linagliptin 5 mg) and Pioglitazone 30 mg	Linagliptin + Pioglitazone n=252 Participants Patients randomized to receive treatment with Linagliptin 5 mg and Pioglitazone 30 mg
HbA1c Change From Baseline to Week 6	-0.03 Percent Standard Error 0.06	-0.41 Percent Standard Error 0.04

SECONDARY outcome

Timeframe: Baseline and week 12

Population: The Full Analysis Set (FAS) included all randomised and treated patients with a baseline and at least one on treatment HbA1c measurement available. 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 12 HbA1c percent minus the baseline HbA1c percent. Means are treatment adjusted for baseline HbA1c and previous anti-diabetic medication.

Outcome measures

Measure	Placebo + Pioglitazone n=128 Participants Patients randomized to receive treatment with matching placebo (to Linagliptin 5 mg) and Pioglitazone 30 mg	Linagliptin + Pioglitazone n=252 Participants Patients randomized to receive treatment with Linagliptin 5 mg and Pioglitazone 30 mg
HbA1c Change From Baseline to Week 12	-0.35 Percent Standard Error 0.07	-0.85 Percent Standard Error 0.05

SECONDARY outcome

Timeframe: Baseline and week 18

Population: The Full Analysis Set (FAS) included all treated and randomised patients with a baseline and at least one on treatment HbA1c measurement available. 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 18 HbA1c percent minus the baseline HbA1c percent. Means are treatment adjusted for baseline HbA1c and previous anti-diabetic medication.

Outcome measures

Measure	Placebo + Pioglitazone n=128 Participants Patients randomized to receive treatment with matching placebo (to Linagliptin 5 mg) and Pioglitazone 30 mg	Linagliptin + Pioglitazone n=252 Participants Patients randomized to receive treatment with Linagliptin 5 mg and Pioglitazone 30 mg
HbA1c Change From Baseline to Week 18	-0.55 Percent Standard Error 0.08	-1.06 Percent Standard Error 0.06

SECONDARY outcome

Timeframe: Baseline and week 24

Population: This population includes the FAS using the LOCF imputation, with the further restriction of patients with a baseline and post-baseline FPG value.

This change from baseline reflects the Week 24 FPG minus the baseline FPG. Means are treatment adjusted for baseline HbA1c, baseline FPG and previous anti-diabetic medication.

Outcome measures

Measure	Placebo + Pioglitazone n=122 Participants Patients randomized to receive treatment with matching placebo (to Linagliptin 5 mg) and Pioglitazone 30 mg	Linagliptin + Pioglitazone n=243 Participants Patients randomized to receive treatment with Linagliptin 5 mg and Pioglitazone 30 mg
FPG Change From Baseline to Week 24	-18.4 mg/dL Standard Error 3.0	-32.6 mg/dL Standard Error 2.2

SECONDARY outcome

Timeframe: Baseline and week 6

Population: This population includes the FAS using the LOCF imputation, with the further restriction of patients with a baseline and post-baseline FPG value.

This change from baseline reflects the Week 6 FPG minus the baseline FPG. Means are treatment adjusted for baseline HbA1c, baseline FPG and previous anti-diabetic medication.

Outcome measures

Measure	Placebo + Pioglitazone n=122 Participants Patients randomized to receive treatment with matching placebo (to Linagliptin 5 mg) and Pioglitazone 30 mg	Linagliptin + Pioglitazone n=243 Participants Patients randomized to receive treatment with Linagliptin 5 mg and Pioglitazone 30 mg
FPG Change From Baseline to Week 6	-17.0 mg/dL Standard Error 2.5	-33.3 mg/dL Standard Error 1.9

SECONDARY outcome

Timeframe: Baseline and week 12

Population: This population includes the FAS using the LOCF imputation, with the further restriction of patients with a baseline and post-baseline FPG value.

This change from baseline reflects the Week 12 FPG minus the baseline FPG. Means are treatment adjusted for baseline HbA1c, baseline FPG and previous anti-diabetic medication.

Outcome measures

Measure	Placebo + Pioglitazone n=122 Participants Patients randomized to receive treatment with matching placebo (to Linagliptin 5 mg) and Pioglitazone 30 mg	Linagliptin + Pioglitazone n=243 Participants Patients randomized to receive treatment with Linagliptin 5 mg and Pioglitazone 30 mg
FPG Change From Baseline to Week 12	-20.5 mg/dL Standard Error 2.7	-33.8 mg/dL Standard Error 2.0

SECONDARY outcome

Timeframe: Baseline and week 18

Population: This population includes the FAS using the LOCF imputation, with the further restriction of patients with a baseline and post-baseline FPG value.

This change from baseline reflects the Week 18 FPG minus the baseline FPG. Means are treatment adjusted for baseline HbA1c, baseline FPG and previous anti-diabetes medication.

Outcome measures

Measure	Placebo + Pioglitazone n=122 Participants Patients randomized to receive treatment with matching placebo (to Linagliptin 5 mg) and Pioglitazone 30 mg	Linagliptin + Pioglitazone n=243 Participants Patients randomized to receive treatment with Linagliptin 5 mg and Pioglitazone 30 mg
FPG Change From Baseline to Week 18	-19.3 mg/dL Standard Error 2.9	-33.2 mg/dL Standard Error 2.1

SECONDARY outcome

Timeframe: Baseline and Week 24

Population: This population includes the FAS with baseline HbA1c \>= 7.0%. Non-completers were 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 + Pioglitazone n=128 Participants Patients randomized to receive treatment with matching placebo (to Linagliptin 5 mg) and Pioglitazone 30 mg	Linagliptin + Pioglitazone n=252 Participants Patients randomized to receive treatment with Linagliptin 5 mg and Pioglitazone 30 mg
Percentage of Patients With HbA1c <7.0% at Week 24	30.5 percentage of patients 0	42.9 percentage of patients 0

SECONDARY outcome

Timeframe: Baseline and Week 24

Population: This population includes the Full Analysis Set (FAS). Non-completers were 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%.

Outcome measures

Measure	Placebo + Pioglitazone n=128 Participants Patients randomized to receive treatment with matching placebo (to Linagliptin 5 mg) and Pioglitazone 30 mg	Linagliptin + Pioglitazone n=252 Participants Patients randomized to receive treatment with Linagliptin 5 mg and Pioglitazone 30 mg
Percentage of Patients With HbA1c<7.0 at Week 24	30.5 percentage of patients	42.9 percentage of patients

SECONDARY outcome

Timeframe: Baseline and Week 24

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

The percentage of patients with an HbA1c value below 6.5% 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 6.5%. Only patients with baseline HbA1c >= 6.5%

Outcome measures

Measure	Placebo + Pioglitazone n=128 Participants Patients randomized to receive treatment with matching placebo (to Linagliptin 5 mg) and Pioglitazone 30 mg	Linagliptin + Pioglitazone n=252 Participants Patients randomized to receive treatment with Linagliptin 5 mg and Pioglitazone 30 mg
Percentage of Patients With HbA1c <6.5% at Week 24	14.1 percentage of patients 0	17.5 percentage of patients 0

SECONDARY outcome

Timeframe: Baseline and week 24

Population: This population includes the Full Analysis Set (FAS). Non-completers were considered as failure imputation (NCF).

The percentage of patients with an HbA1c value below 6.5% 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 6.5%

Outcome measures

Measure	Placebo + Pioglitazone n=128 Participants Patients randomized to receive treatment with matching placebo (to Linagliptin 5 mg) and Pioglitazone 30 mg	Linagliptin + Pioglitazone n=252 Participants Patients randomized to receive treatment with Linagliptin 5 mg and Pioglitazone 30 mg
Percentage of Patients With HbA1c<6.5% at Week 24	14.1 percentage of patients	17.5 percentage of patients

SECONDARY outcome

Timeframe: Baseline and Week 24

Population: The Full Analysis Set (FAS) included all patients with a baseline and at least one on treatment HbA1c measurement available. Non-completers were considered as failure imputation (NCF).

The percentage of patients with an HbA1c reduction from baseline greater than 0.5% 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 reduction less than 0.5%.

Outcome measures

Measure	Placebo + Pioglitazone n=128 Participants Patients randomized to receive treatment with matching placebo (to Linagliptin 5 mg) and Pioglitazone 30 mg	Linagliptin + Pioglitazone n=252 Participants Patients randomized to receive treatment with Linagliptin 5 mg and Pioglitazone 30 mg
Percentage of Patients Who Have an HbA1c Lowering by 0.5% at Week 24	50.8 percentage of patients 0	75.0 percentage of patients 0

Adverse Events

Placebo + Pioglitazone

Serious events: 3 serious events

Other events: 21 other events

Deaths: 0 deaths

Linagliptin + Pioglitazone

Serious events: 8 serious events

Other events: 33 other events

Deaths: 0 deaths

Serious adverse events

Measure	Placebo + Pioglitazone n=130 participants at risk Patients randomized to receive treatment with matching placebo (to Linagliptin 5 mg) and Pioglitazone 30 mg	Linagliptin + Pioglitazone n=259 participants at risk Patients randomized to receive treatment with Linagliptin 5 mg and Pioglitazone 30 mg
Cardiac disorders Acute coronary syndrome	0.00% 0/130 • From day of first dose until 7 days after last dose, up to 202 days	0.39% 1/259 • From day of first dose until 7 days after last dose, up to 202 days
Eye disorders Glaucoma	0.77% 1/130 • From day of first dose until 7 days after last dose, up to 202 days	0.00% 0/259 • From day of first dose until 7 days after last dose, up to 202 days
Gastrointestinal disorders Abdominal pain upper	0.00% 0/130 • From day of first dose until 7 days after last dose, up to 202 days	0.39% 1/259 • From day of first dose until 7 days after last dose, up to 202 days
Gastrointestinal disorders Colonic polyp	0.00% 0/130 • From day of first dose until 7 days after last dose, up to 202 days	0.39% 1/259 • From day of first dose until 7 days after last dose, up to 202 days
Gastrointestinal disorders Vomiting	0.00% 0/130 • From day of first dose until 7 days after last dose, up to 202 days	0.39% 1/259 • From day of first dose until 7 days after last dose, up to 202 days
Hepatobiliary disorders Cholecystitis acute	0.77% 1/130 • From day of first dose until 7 days after last dose, up to 202 days	0.00% 0/259 • From day of first dose until 7 days after last dose, up to 202 days
Hepatobiliary disorders Cholelithiasis	0.77% 1/130 • From day of first dose until 7 days after last dose, up to 202 days	0.39% 1/259 • From day of first dose until 7 days after last dose, up to 202 days
Musculoskeletal and connective tissue disorders Tendonitis	0.77% 1/130 • From day of first dose until 7 days after last dose, up to 202 days	0.00% 0/259 • From day of first dose until 7 days after last dose, up to 202 days
Nervous system disorders Carotid artery stenosis	0.00% 0/130 • From day of first dose until 7 days after last dose, up to 202 days	0.39% 1/259 • From day of first dose until 7 days after last dose, up to 202 days
Nervous system disorders Hypoaesthesia	0.00% 0/130 • From day of first dose until 7 days after last dose, up to 202 days	0.39% 1/259 • From day of first dose until 7 days after last dose, up to 202 days
Surgical and medical procedures Meniscus removal	0.00% 0/130 • From day of first dose until 7 days after last dose, up to 202 days	0.39% 1/259 • From day of first dose until 7 days after last dose, up to 202 days
Vascular disorders Varicose vein	0.00% 0/130 • From day of first dose until 7 days after last dose, up to 202 days	0.39% 1/259 • From day of first dose until 7 days after last dose, up to 202 days

Other adverse events

Measure	Placebo + Pioglitazone n=130 participants at risk Patients randomized to receive treatment with matching placebo (to Linagliptin 5 mg) and Pioglitazone 30 mg	Linagliptin + Pioglitazone n=259 participants at risk Patients randomized to receive treatment with Linagliptin 5 mg and Pioglitazone 30 mg
Infections and infestations Nasopharyngitis	8.5% 11/130 • From day of first dose until 7 days after last dose, up to 202 days	9.3% 24/259 • From day of first dose until 7 days after last dose, up to 202 days
Infections and infestations Upper respiratory tract infection	7.7% 10/130 • From day of first dose until 7 days after last dose, up to 202 days	3.5% 9/259 • From day of first dose until 7 days after last dose, up to 202 days

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