Relative Bioavailability of 2 Fixed Dose Combinations of Linagliptin/Metformin Compared With Single Tablets

Relative Bioavailability of Two Newly Developed Extended Release FDC Tablet Strengths (5mg/1000mg and 2.5 mg/750 mg) of Linagliptin/Metformin Extended Release Compared With the Free Combination of Linagliptin and Metformin Extended Release in Healthy Subjects (an Open-label, Randomised, Single Dose, Two-way Crossover Study)

The purpose of the trial is to demonstrate the relative bioavailability of 2 newly developed fixed dose combination (FDC) tablets containing linagliptin & metformin and the single tablets of linagliptin and metformin when administered singularly.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: 2x500 mg Metformin (Glumetza); Drug: 5 mg Linagliptin (Tradjenta); Drug: 2 x 2.5 mg Linagliptin/750 mg Metformin FDC; Drug: 3x500 mg Metformin (Glumetza); Drug: 5 mg Linagliptin/1000mg Metformin FDC; Drug: 2 x 500 mg Metformin (Glumetza); Drug: 5 mg Linagliptin/1000 mg Metformin FDC

• Study Type: Interventional
• Enrollment (Actual): 72
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • Austin, Texas, United States
      • 1288.8.1 Boehringer Ingelheim Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion criteria:

1. Healthy males or females
2. Age 18 -50 years (incl)
3. Body Mass Index (BMI) 18.5 to 29.9 kg/m2 (incl.)
4. Subjects must be able to understand and comply with study requirements

Exclusion criteria:

Any deviation from healthy condition

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 5 mg Linagliptin/1000 mg Metformin, fed; 3 single tablets under fed conditions	Drug: 2x500 mg Metformin (Glumetza); 2 tablets; Drug: 5 mg Linagliptin (Tradjenta); 1 tablet
Experimental: 5 mg Linagliptin/1500 mg Metformin FDC; 2 FDC tablets under fasted conditions	Drug: 2 x 2.5 mg Linagliptin/750 mg Metformin FDC; 2 FDC tablets
Active Comparator: 5 mg Linagliptin/1500 mg Metformin; 4 single tablets under fasted conditions	Drug: 5 mg Linagliptin (Tradjenta); 1 tablet; Drug: 3x500 mg Metformin (Glumetza); 3 tablets
Experimental: 5 mg Linagliptin/1000 mg Metformin FDC; 1 fixed dose combination(FDC) tablet under fasted conditions	Drug: 5 mg Linagliptin/1000mg Metformin FDC; FDC Tablet
Active Comparator: 5 mg Linagliptin/1000 mg Metformin; 3 single tablets under fasted conditions	Drug: 5 mg Linagliptin (Tradjenta); 1 tablet; Drug: 2 x 500 mg Metformin (Glumetza); 2 tablets
Experimental: 5mg Linagliptin/1000mg Metformin, FDCfed; 1 FDC tablet under fed conditions	Drug: 5 mg Linagliptin/1000 mg Metformin FDC; FDC tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUC0-72 of Linagliptin	Area Under the Concentration-time Curve of Linagliptin in Plasma Over the Time Interval 0 to 72 Hours (AUC0-72). The shown geometric coefficients of variation (gCV) are the pooled intra-individual gCV - each over 2 treatment groups (FDC1000 fasted and L+M1000 fasted, FDC1000 fed and L+M1000 fed, FDC1500 fasted and L+M1500 fasted). The geometric means are actually adjusted geometric means.	1 hour (h) before drug administration and 20 minutes (min), 40 min, 1h, 1:30h, 2h, 3h, 4h, 5h, 6h, 8h, 10h, 12h, 16h, 24h, 36h, 48h and 72h after drug administration at Day 1 of each treatment period
Cmax of Linagliptin	Maximum Measured Concentration (Cmax) of Linagliptin in plasma. The shown geometric coefficients of variation (gCV) are the pooled intra-individual gCV - each over 2 treatment groups (FDC1000 fasted and L+M1000 fasted, FDC1000 fed and L+M1000 fed, FDC1500 fasted and L+M1500 fasted). The geometric means are actually adjusted geometric means.	1 hour (h) before drug administration and 20 minutes (min), 40 min, 1h, 1:30h, 2h, 3h, 4h, 5h, 6h, 8h, 10h, 12h, 16h, 24h, 36h, 48h and 72h after drug administration at Day 1 of each treatment period
AUC0-tz of Metformin	Area under the concentration-time curve of Metformin in plasma over the time interval from 0 to the last quantifiable data point (AUC0-tz). The shown geometric coefficients of variation (gCV) are the pooled intra-individual gCV - each over 2 treatment groups (FDC1000 fasted and L+M1000 fasted, FDC1000 fed and L+M1000 fed, FDC1500 fasted and L+M1500 fasted). The geometric means are actually adjusted geometric means.	1 hour (h) before drug administration and 20 minutes (min), 40 min, 1h, 1:30h, 2h, 3h, 4h, 5h, 6h, 8h, 10h, 12h, 16h, 24h, 36h, 48h and 72h after drug administration at Day 1 of each treatment period
Cmax of Metformin	Maximum Measured Concentration (Cmax) of Metformin in plasma. The shown geometric coefficients of variation (gCV) are the pooled intra-individual gCV - each over 2 treatment groups (FDC1000 fasted and L+M1000 fasted, FDC1000 fed and L+M1000 fed, FDC1500 fasted and L+M1500 fasted). The geometric means are actually adjusted geometric means.	1 hour (h) before drug administration and 20 minutes (min), 40 min, 1h, 1:30h, 2h, 3h, 4h, 5h, 6h, 8h, 10h, 12h, 16h, 24h, 36h, 48h and 72h after drug administration at Day 1 of each treatment period

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUC0-infinity of Linagliptin	Area under the concentration-time curve of Linagliptin in plasma over the time interval from 0 extrapolated to infinity based on predicted last concentration values. The shown geometric coefficients of variation (gCV) are the pooled intra-individual gCV - each over 2 treatment groups (FDC1000 fasted and L+M1000 fasted, FDC1000 fed and L+M1000 fed, FDC1500 fasted and L+M1500 fasted). The geometric means are actually adjusted geometric means.	1 hour (h) before drug administration and 20 minutes (min), 40 min, 1h, 1:30h, 2h, 3h, 4h, 5h, 6h, 8h, 10h, 12h, 16h, 24h, 36h, 48h and 72h after drug administration at Day 1 of each treatment period
AUC0-infinity of Metformin	Area under the concentration-time curve of Metformin in plasma over the time interval from 0 extrapolated to infinity based on predicted last concentration values. The shown geometric coefficients of variation (gCV) are the pooled intra-individual gCV - each over 2 treatment groups (FDC1000 fasted and L+M1000 fasted, FDC1000 fed and L+M1000 fed, FDC1500 fasted and L+M1500 fasted). The geometric means are actually adjusted geometric means.	1 hour (h) before drug administration and 20 minutes (min), 40 min, 1h, 1:30h, 2h, 3h, 4h, 5h, 6h, 8h, 10h, 12h, 16h, 24h, 36h, 48h and 72h after drug administration at Day 1 of each treatment period

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim
• Collaborators: Eli Lilly and Company

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: May 1, 2013
• Primary Completion (Actual): August 1, 2013
• Study Completion (Actual): August 1, 2013

Study Registration Dates

• First Submitted: April 30, 2013
• First Submitted That Met QC Criteria: May 1, 2013
• First Posted (Estimate): May 3, 2013

Study Record Updates

• Last Update Posted (Estimate): August 19, 2014
• Last Update Submitted That Met QC Criteria: July 29, 2014
• Last Verified: July 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Protease Inhibitors; Incretins; Dipeptidyl-Peptidase IV Inhibitors; Metformin; Linagliptin
• Other Study ID Numbers: 1288.8