Regulatory Decision Summary for Jentadueto

Decision issued

A Notice of Deficiency was issued by Health Canada. The company cancelled its submission before a final decision was issued.

Date of cancellation

2017-05-02

What was the purpose of this submission?

The primary purpose of this Supplemental New Drug Submission (SNDS) was to obtain a new therapeutic indication for Jentadueto in combination with a sodium-glucose co-transporter 2 (SGLT-2) inhibitor as an adjunct to diet and exercise to improve glycemic control in adult patients with type 2 diabetes mellitus (T2DM) inadequately controlled on metformin and a SGLT-2 inhibitor.

What did the company submit to support its submission?

The submission included a clinical package containing two phase III trials. Study 1275.10 was provided in support of the newly proposed indication. This 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 (FDCs) with empagliflozin 10 mg or 25 mg for 24 weeks, in patients with T2DM and insufficient glycaemic control after 16 weeks of treatment with empagliflozin 10 mg or 25 mg once daily on metformin background therapy. Study 1275.01 was also provided as part of the submission. This was a Phase III study designed to evaluate the efficacy and safety of once daily administration of empagliflozin 25 mg/linagliptin 5 mg and empagliflozin 10 mg/linagliptin 5 mg fixed dose combinations vs. the individual components (empagliflozin 25 mg, empagliflozin 10 mg, linagliptin 5 mg) for 52 weeks in both treatment naïve and metformin-treated T2DM patients. This study was not considered pivotal to the proposed indication. It investigated the combination of linagliptin and empagliflozin as a FDC, did not investigate linagliptin as an add-on medication, and did not investigate linagliptin with SGLT-2 inhibitors other than empagliflozin.

Due to major deficiencies identified with the submission which resulted in a Notice of Deficiency, a review of in the clinical studies provided in support of the proposed changes was not initiated.

What was the status of the submission when it was cancelled? What was Health Canadas assessment of the submission at the time of cancellation?

At the time of the cancellation, the review of the submission was not complete; however Health Canada had identified major deficiencies in the information provided that precluded continuation of the review. Specifically, study 1275.10 did not adequately support the new therapeutic indication. No evidence was provided in this submission for the clinical efficacy and safety of Jentadueto in combination with SGLT-2 inhibitors other than empagliflozin, in the proposed target population. No evidence was provided in this submission to demonstrate the link between the proposed use of the FDC of linagliptin/metformin with empagliflozin and the FDC of empagliflozin/linagliptin in combination with metformin used in Study 1275.10. In the study, both the target population and tested doses of metformin did not correspond to the proposed indication. As a result, Health Canada issued a Notice of Deficiency outlining its concerns.

Following issuance of the Notice of Deficiency, Boehringer Ingelheim (Canada) Ltd/Ltée withdrew the submission for Jentadueto in combination with a sodium-glucose co-transporter 2 (SGLT-2) inhibitor as an adjunct to diet and exercise to improve glycemic control in adult patients with type 2 diabetes mellitus (T2DM) inadequately controlled on metformin and a SGLT-2 inhibitor. This withdrawal was without prejudice to a resubmission when data from new studies will be available.

What consequences does the cancellation have for patients accessing the drug under the Special Access Programme (SAP), or via clinical trials?

There is no expected impact for patients using SAP or in clinical trials.

Additional information

*Proposed Brand Name
JENTADUETO