Clarus Therapeutics, Inc.: testosterone undecanoate

Please refer to your New Drug Application (NDA) dated and received, January 3, 2014, and your amendments, submitted under section 505(b) of the Federal Food, Drug, and Cosmetic Act for testosterone undecanoate (TU) (oral).

We acknowledge receipt of your major amendments dated September 20 and 25, 2017, which extended the goal date by three months.

1. Jatenzo causes clinically meaningful increases in blood pressure.

Further, in the Jatenzo group, 7.2% of subjects in the Safety Population started antihypertensive medications after baseline or required an antihypertensive dose increase, compared to 1.8% of subjects in the Topical Axiron group.

Boxed Warning, Indication, Contraindication, and Warnings and Precautions) and strategies beyond labeling, such as a Risk Evaluation and Mitigation Strategy (REMS) with elements to assure safe use, together with an ssment of how your proposal will mitigate the risks and ensure a favorable benefit/risk profile.

Ensure you have adequately addressed these issues with FDA prior to NDA resubmission.

Carcinogenicity Studies (2008), the maximally tolerated dose (MTD), maximum feasible dose or limit dose was not identified in your 28-day dose range finding study or in your 6-month carcinogenicity study.

Your amendment dated August 6, 2014, contained bioanalytical study reports for all clinical trials as well as bioanalytical method validation data that were missing at the time of NDA submission.

The complete analytical validation section of your NDA will need to undergo further review in a future resubmission in the context of new trials that are conducted to support your NDA.

However, based on the food effect study, there are considerable increases in testosterone undecanoate (TU), testosterone, and dihydrotestosterone (DHT) as the fat content in the meal increases.

None of the key secondary efficacy endpoints for testosterone Cmax outliers met the prespecified success targets for the three Cmax outlier categories.

Nearly onefourth of subjects had a T-Cavg <300 ng/dL at the primary efficacy endpoint subsequent to all titration.

4. Clinically meaningful increases in systolic and diastolic blood pressure were observed with your product in Study CLAR-09007, with a larger blood pressure increase compared to Androgel 1%.

Almost 10% of subjects treated with your product in Study CLAR-09007 had at least one hematocrit value >54%, a clinically meaningful level.

In addition, this new trial would need to be adequately designed to avoid other deficiencies involving the completed phase 3 trial that were described above, such as the large extent of missing data for the primary efficacy endpoint.

8. Provide English translations of current approved foreign labeling not previously submitted.

Based on physicochemical properties, it is possible that alcohol will solubilize your product, leading to increased absorption via the portal vein, a high first pass effect, and reduced TU bioavailability.

However, it is also possible that alcohol could instead enhance absorption via the lymphatics, leading to increased bioavailability of TU.