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Bioequivalence of a Fixed Dose Combination Tablet Linagliptin/Pioglitazone Compared With Its Mono-components

Bioequivalence of a Fixed Dose Combination Tablet of Linagliptin 5 mg / Pioglitazone 30 mg Compared With Its Mono-components in Healthy Male and Female Subjects (an Open-label, Randomised, Single-dose, Replicate Design Study With Two Treatments in Four Crossover Periods)

Status
Completed
Phases
Phase 1
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT01276327
Enrollment
64
Registered
2011-01-13
Start date
2011-01-31
Completion date
Unknown
Last updated
2014-06-09

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Healthy

Brief summary

The objective of the current study is to establish the bioequivalence of linagliptin/ pioglitazone fixed dose combination tablet compared to single tablets of linagliptin and pioglitazone administered together.

Interventions

DRUGLinagliptin + Pioglitazone

Medium doses, oral administration

DRUGLinagliptin/Pioglitazone

Medium dose oral administration

Sponsors

Boehringer Ingelheim
Lead SponsorINDUSTRY

Study design

Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE

Eligibility

Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes

Inclusion criteria

Healthy male and female subjects

Exclusion criteria

Any relevant deviation from healthy conditions

Design outcomes

Primary

MeasureTime frameDescription
AUC0-72 of Linagliptin0-72 hours (measurements at baseline, 0.33, 0.67, 1, 1.5, 2, 3, 4, 6, 8, 11, 12, 24, 48 and 72 hours)Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to 72 hours
Cmax of Linagliptin0-72 hours (measurements at baseline, 0.33, 0.67, 1, 1.5, 2, 3, 4, 6, 8, 11, 12, 24, 48 and 72 hours)Maximum measured concentration of the analyte in plasma was measured. Adjusted by-treatment geometric mean and CV were reported.
AUC0-tz of Pioglitazone0-72 hours (measurements at baseline, 0.33, 0.67, 1, 1.5, 2, 3, 4, 6, 8, 11, 12, 24, 48 and 72 hours)Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the time of the last quantifiable data point
Cmax of Pioglitazone0-72 hours (measurements at baseline, 0.33, 0.67, 1, 1.5, 2, 3, 4, 6, 8, 11, 12, 24, 48 and 72 hours)Maximum concentration of the analyte in plasma was measured. Adjusted by-treatment geometric mean and CV were calculated.

Secondary

MeasureTime frameDescription
AUC0-tz for Linagliptin0-72 hours (measurements at baseline, 0.33, 0.67, 1, 1.5, 2, 3, 4, 6, 8, 11, 12, 24, 48 and 72 hours)Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the time of the last quantifiable data point for Linagliptin
Tmax for Pioglitazone0-72 hours (measurements at baseline, 0.33, 0.67, 1, 1.5, 2, 3, 4, 6, 8, 11, 12, 24, 48 and 72 hours)Time from dosing to the maximum measured concentration of the analyte in plasma for pioglitazone
AUC0-∞ of Linagliptin0-72 hours (measurements at baseline, 0.33, 0.67, 1, 1.5, 2, 3, 4, 6, 8, 11, 12, 24, 48 and 72 hours)Area under the concentration-time curve of the analyte in plasma over the time interval from 0 hours extrapolated to infinity (inf) for linagliptin
AUC0-∞ of Pioglitazone0-72 hours (measurements at baseline, 0.33, 0.67, 1, 1.5, 2, 3, 4, 6, 8, 11, 12, 24, 48 and 72 hours)Area under the concentration-time curve of the analyte in plasma over the time interval from 0 hours extrapolated to inf for pioglitazone
Tmax for Linagliptin0-72 hours (measurements at baseline, 0.33, 0.67, 1, 1.5, 2, 3, 4, 6, 8, 11, 12, 24, 48 and 72 hours)Time from dosing to the maximum measured concentration of the analyte in plasma for Linagliptin

Countries

Germany

Participant flow

Participants by arm

ArmCount
Sequence TRTR
Subjects received 2 single doses of the test treatment (T; Fixed-Dose-Combination-Tablet of linagliptin 5 mg and pioglitazone 30 mg) and 2 single doses of the reference treatment (R; Individual linagliptin 5mg tablet and pioglitazone 30 mg tablet) in the sequence of TRTR.
32
Sequence RTRT
Subjects received 2 single doses of the test treatment (T; Fixed-Dose-Combination-Tablet of linagliptin 5 mg and pioglitazone 30 mg) and 2 single doses of the reference treatment (R; Individual linagliptin 5mg tablet and pioglitazone 30 mg tablet) in the sequence of RTRT.
32
Total64

Withdrawals & dropouts

PeriodReasonFG000FG001
Overall StudyAdverse Event13
Overall StudyWithdrawal by Subject10

Baseline characteristics

CharacteristicSequence TRTRSequence RTRTTotal
Age, Continuous37.8 years
STANDARD_DEVIATION 8.8
38.0 years
STANDARD_DEVIATION 9.3
37.9 years
STANDARD_DEVIATION 9
Sex: Female, Male
Female
13 Participants13 Participants26 Participants
Sex: Female, Male
Male
19 Participants19 Participants38 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
deaths
Total, all-cause mortality
— / —— / —
other
Total, other adverse events
13 / 627 / 63
serious
Total, serious adverse events
0 / 621 / 63

Outcome results

Primary

AUC0-72 of Linagliptin

Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to 72 hours

Time frame: 0-72 hours (measurements at baseline, 0.33, 0.67, 1, 1.5, 2, 3, 4, 6, 8, 11, 12, 24, 48 and 72 hours)

Population: PKS - The PKS included all evaluable subjects in the treated set who had no important PV relevant to the evaluation of bioequivalence and provided at least 1 evaluable observation for a pharmacokinetic endpoint in at least 1 treatment period.

ArmMeasureValue (GEOMETRIC_MEAN)Dispersion
FDC L5P30 (Test)AUC0-72 of Linagliptin278 nmol*h/LGeometric Coefficient of Variation 20.6
L5+P30 (Ref)AUC0-72 of Linagliptin279 nmol*h/LGeometric Coefficient of Variation 20.6
90% CI: [97.11, 102.81]Unscaled average Bioequivalence
Primary

AUC0-tz of Pioglitazone

Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the time of the last quantifiable data point

Time frame: 0-72 hours (measurements at baseline, 0.33, 0.67, 1, 1.5, 2, 3, 4, 6, 8, 11, 12, 24, 48 and 72 hours)

Population: PKS - The PKS included all evaluable subjects in the treated set who had no important PV relevant to the evaluation of bioequivalence and provided at least 1 evaluable observation for a pharmacokinetic endpoint in at least 1 treatment period.

ArmMeasureValue (GEOMETRIC_MEAN)Dispersion
FDC L5P30 (Test)AUC0-tz of Pioglitazone6370 ng*h/mLGeometric Coefficient of Variation 49.3
L5+P30 (Ref)AUC0-tz of Pioglitazone8100 ng*h/mLGeometric Coefficient of Variation 41.2
90% CI: [74.65, 85.72]Scaled average bioequivalence (SABE)
Primary

Cmax of Linagliptin

Maximum measured concentration of the analyte in plasma was measured. Adjusted by-treatment geometric mean and CV were reported.

Time frame: 0-72 hours (measurements at baseline, 0.33, 0.67, 1, 1.5, 2, 3, 4, 6, 8, 11, 12, 24, 48 and 72 hours)

Population: PKS - The PKS included all evaluable subjects in the treated set who had no important PV relevant to the evaluation of bioequivalence and provided at least 1 evaluable observation for a pharmacokinetic endpoint in at least 1 treatment period.

ArmMeasureValue (GEOMETRIC_MEAN)Dispersion
FDC L5P30 (Test)Cmax of Linagliptin8.65 nmol/LGeometric Coefficient of Variation 33.3
L5+P30 (Ref)Cmax of Linagliptin9.09 nmol/LGeometric Coefficient of Variation 31.2
90% CI: [89.08, 99.55]Unscaled average Bioequivalence
Primary

Cmax of Pioglitazone

Maximum concentration of the analyte in plasma was measured. Adjusted by-treatment geometric mean and CV were calculated.

Time frame: 0-72 hours (measurements at baseline, 0.33, 0.67, 1, 1.5, 2, 3, 4, 6, 8, 11, 12, 24, 48 and 72 hours)

Population: PKS - The PKS included all evaluable subjects in the treated set who had no important PV relevant to the evaluation of bioequivalence and provided at least 1 evaluable observation for a pharmacokinetic endpoint in at least 1 treatment period.

ArmMeasureValue (GEOMETRIC_MEAN)Dispersion
FDC L5P30 (Test)Cmax of Pioglitazone806 ng/mLGeometric Coefficient of Variation 58.5
L5+P30 (Ref)Cmax of Pioglitazone843 ng/mLGeometric Coefficient of Variation 42.7
90% CI: [88.9, 106.51]Scaled average bioequivalence (SABE)
Secondary

AUC0-∞ of Linagliptin

Area under the concentration-time curve of the analyte in plasma over the time interval from 0 hours extrapolated to infinity (inf) for linagliptin

Time frame: 0-72 hours (measurements at baseline, 0.33, 0.67, 1, 1.5, 2, 3, 4, 6, 8, 11, 12, 24, 48 and 72 hours)

Population: PKS - The PKS included all evaluable subjects in the treated set who had no important PV relevant to the evaluation of bioequivalence and provided at least 1 evaluable observation for a pharmacokinetic endpoint in at least 1 treatment period.

ArmMeasureValue (GEOMETRIC_MEAN)Dispersion
FDC L5P30 (Test)AUC0-∞ of Linagliptin455 nmol*h/LGeometric Coefficient of Variation 27.4
L5+P30 (Ref)AUC0-∞ of Linagliptin447 nmol*h/LGeometric Coefficient of Variation 24.5
90% CI: [98.18, 105.67]Unscaled average bioequivalence
Secondary

AUC0-∞ of Pioglitazone

Area under the concentration-time curve of the analyte in plasma over the time interval from 0 hours extrapolated to inf for pioglitazone

Time frame: 0-72 hours (measurements at baseline, 0.33, 0.67, 1, 1.5, 2, 3, 4, 6, 8, 11, 12, 24, 48 and 72 hours)

Population: PKS - The PKS included all evaluable subjects in the treated set who had no important PV relevant to the evaluation of bioequivalence and provided at least 1 evaluable observation for a pharmacokinetic endpoint in at least 1 treatment period.

ArmMeasureValue (GEOMETRIC_MEAN)Dispersion
FDC L5P30 (Test)AUC0-∞ of Pioglitazone6580 ng*h/mLGeometric Coefficient of Variation 47.5
L5+P30 (Ref)AUC0-∞ of Pioglitazone8300 ng*h/mLGeometric Coefficient of Variation 40.4
90% CI: [75.6, 86.34]Scaled average bioequivalence (SABE)
Secondary

AUC0-tz for Linagliptin

Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the time of the last quantifiable data point for Linagliptin

Time frame: 0-72 hours (measurements at baseline, 0.33, 0.67, 1, 1.5, 2, 3, 4, 6, 8, 11, 12, 24, 48 and 72 hours)

Population: PKS - The PKS included all evaluable subjects in the treated set who had no important PV relevant to the evaluation of bioequivalence and provided at least 1 evaluable observation for a pharmacokinetic endpoint in at least 1 treatment period.

ArmMeasureValue (GEOMETRIC_MEAN)Dispersion
FDC L5P30 (Test)AUC0-tz for Linagliptin278 nmol*h/LGeometric Coefficient of Variation 20.6
L5+P30 (Ref)AUC0-tz for Linagliptin279 nmol*h/LGeometric Coefficient of Variation 20.6
90% CI: [97.1, 102.81]Unscaled average bioequivalence
Secondary

Tmax for Linagliptin

Time from dosing to the maximum measured concentration of the analyte in plasma for Linagliptin

Time frame: 0-72 hours (measurements at baseline, 0.33, 0.67, 1, 1.5, 2, 3, 4, 6, 8, 11, 12, 24, 48 and 72 hours)

Population: PKS - The PKS included all evaluable subjects in the treated set who had no important PV relevant to the evaluation of bioequivalence and provided at least 1 evaluable observation for a pharmacokinetic endpoint in at least 1 treatment period.

ArmMeasureValue (MEDIAN)
FDC L5P30 (Test)Tmax for Linagliptin1.73 hours
L5+P30 (Ref)Tmax for Linagliptin1.50 hours
Secondary

Tmax for Pioglitazone

Time from dosing to the maximum measured concentration of the analyte in plasma for pioglitazone

Time frame: 0-72 hours (measurements at baseline, 0.33, 0.67, 1, 1.5, 2, 3, 4, 6, 8, 11, 12, 24, 48 and 72 hours)

Population: PKS - The PKS included all evaluable subjects in the treated set who had no important PV relevant to the evaluation of bioequivalence and provided at least 1 evaluable observation for a pharmacokinetic endpoint in at least 1 treatment period.

ArmMeasureValue (MEDIAN)
FDC L5P30 (Test)Tmax for Pioglitazone1.00 hours
L5+P30 (Ref)Tmax for Pioglitazone1.50 hours

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026