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

• ClinicalTrials.gov Identifier: NCT01845077
• Recruitment Status: Completed
• First Posted: May 3, 2013
• Results First Posted: August 19, 2014
• Last Update Posted: August 19, 2014
• Sponsor: Boehringer Ingelheim
• Collaborator: Eli Lilly and Company
• Information provided by (Responsible Party): Boehringer Ingelheim

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Healthy	Drug: 2x500 mg Metformin (Glumetza); Drug: 5 mg Linagliptin/1000 mg Metformin FDC; Drug: 5 mg Linagliptin (Tradjenta); Drug: 3x500 mg Metformin (Glumetza); Drug: 2 x 500 mg Metformin (Glumetza); Drug: 5 mg Linagliptin/1000mg Metformin FDC; Drug: 2 x 2.5 mg Linagliptin/750 mg Metformin FDC	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 72 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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)
• Study Start Date: May 2013
• Actual Primary Completion Date: August 2013
• Actual Study Completion Date: August 2013

Arms and Interventions

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: 3x500 mg Metformin (Glumetza); 3 tablets; Drug: 5 mg Linagliptin (Tradjenta); 1 tablet
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

Outcome Measures

Primary Outcome Measures :

1. AUC0-72 of Linagliptin [ Time Frame: 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 ]
   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.
2. Cmax of Linagliptin [ Time Frame: 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 ]
   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.
3. AUC0-tz of Metformin [ Time Frame: 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 ]
   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.
4. Cmax of Metformin [ Time Frame: 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 ]
   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.

Secondary Outcome Measures :

1. AUC0-infinity of Linagliptin [ Time Frame: 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 ]
   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.
2. AUC0-infinity of Metformin [ Time Frame: 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 ]
   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.

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

United States, Texas

1288.8.1 Boehringer Ingelheim Investigational Site

Austin, Texas, United States

Sponsors and Collaborators

Boehringer Ingelheim

Eli Lilly and Company

Investigators

• Study Chair: Boehringer Ingelheim; Boehringer Ingelheim

More Information

Additional Information:

Related Info 

• Responsible Party: Boehringer Ingelheim
• ClinicalTrials.gov Identifier: NCT01845077
• Other Study ID Numbers: 1288.8
• First Posted: May 3, 2013
• Results First Posted: August 19, 2014
• Last Update Posted: August 19, 2014
• Last Verified: July 2014

Additional relevant MeSH terms:

Metformin; Linagliptin; Hypoglycemic Agents; Physiological Effects of Drugs; Incretins; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Dipeptidyl-Peptidase IV Inhibitors; Protease Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action