Regulatory Decision Summary for Trajenta
Review decision
The Regulatory Decision Summary explains Health Canada’s decision for the product seeking market authorization. The Regulatory Decision Summary includes the purpose of the submission and the reason for the decision.
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What was the purpose of this submission?
This Supplemental New Drug Submission (SNDS) was filed to obtain a new therapeutic indication for Trajenta (linagliptin) to improve glycemic control in patients with type 2 diabetes mellitus (T2DM) when used in combination with metformin and empagliflozin when diet and exercise plus metformin and empagliflozin do not provide adequate glycemic control.
Why was the decision issued?
The new proposed indication for Trajenta (linagliptin) is based on the efficacy and safety data from Study 1275.10. This Study was a phase III, randomised, double-blind, parallel group study to evaluate the efficacy and safety of linagliptin 5 mg compared to placebo, administered as oral fixed dose combinations with empagliflozin 10 mg or 25 mg for 24 weeks, in patients with T2DM and insufficient glycemic control after 16 week treatment with empagliflozin 10 mg or 25 mg once daily on metformin background therapy.
This study was designed to support the new fixed dose combination (FDC) of empagliflozin + linagliptin (Glyxambi), but it is provided within this submission with the intention of extending its results to its individual components (Trajenta). In order for the results of Study 1275.10 to support the indications sought for the individual components (empagliflozin and linagliptin), the data demonstrating comparable bioavailability of the FDCs used in Study 1275.10 and the commercial formulations of the individual mono-components, empagliflozin and linagliptin, are required. The applicant has provided data supporting the bioavailability of the higher dose of the FDC (linagliptin 5 mg/empagliflozin 25 mg) compared to its mono-components, but no data was provided supporting the bioavailability of the lower dose of the FDC (linagliptin 5 mg/empagliflozin 10 mg) in comparison to its mono-components. As there are two commercially available doses of empagliflozin and two corresponding doses of the FDC used in Study 1275.10, the standards for comparative bioavailability should be met for all doses of empagliflozin marketed in Canada. This is because the formulations of the FDC tablet used in 1275.10 are not considered to be proportional (as per the Health Canada Policy Bioequivalence of Proportional Formulations: Solid Oral Dosage Forms). A Notice of Deficiency (NOD) was issued.
In response to the NOD, the applicant has provided a new study (1275.21) demonstrating the relative bioavailability of Glyxambi 10 mg/5 mg to empagliflozin 10 mg and linagliptin 5 mg; however, some important supporting information for the submitted bioavailability study was incomplete. A Notice of Non-Compliance (NON) was issued.
In response to the NON, the applicant has provided the requested information. Study 1275.21 compared the proposed FDC Glyxambi tablet (10 mg/5 mg) with the coadministered individual components (10 mg empagliflozin and 5 mg linagliptin). The results demonstrated that the Glyxambi tablet met the standards for comparative bioavailability in comparison to the co-administration of the individual tablets. Bridging the data is possible since the 2 strengths of Glyxambi FDC (25 mg/5 mg and 10 mg/5 mg) demonstrated comparative bioavailability with their mono-components and data derived from Study 1275.10 supports the proposed indication.
The benefit-harm-uncertainty assessment for the proposed indication for Trajenta is favorable. A Notice of Compliance (NOC) is recommended.
Decision issued
Approved; issued a Notice of Compliance in accordance with the Food and Drug Regulations.