This will be an open-label, randomized, 3-treatment, 2-period, 2-sequence study in healthy subjects to evaluate the single-dose PK of milademetan when given as monotherapy and when administered with steady-state levels of the strong CYP3A4 inhibitors itraconazole or posaconazole.

The duration of the study for each individual subject will be approximately 49 days from the start of Screening through Study Discharge. Subjects will remain in-house for up to 23 days, including 22 overnight stays.

Healthy participants with no clinically significant medical history or physical examination findings and who also meet all protocol-defined inclusion and exclusion criteria summarized as follows:

Inclusion Criteria:

• Has negative urine test for drugs of abuse, alcohol and tobacco
• If female, is surgically sterile or postmenopausal
• If male, agrees to protocol-defined contraceptive methods
• Has adequate hematologic, hepatic, and renal function as defined by the protocol
• Is able and willing to follow all study procedures
• Has provided a signed informed consent

Exclusion Criteria:

• Is female who is pregnant or breastfeeding

• Is unable to swallow oral medication

• Is unable to follow study procedures

• Has creatinine clearance < 90 mL/min at screening

• Is taking or has taken any medications or therapies outside of protocol-defined parameters

• Has history of or a known allergic reaction to azole antifungal agents

• Has any disease or condition that, per protocol or in the opinion of the investigator, might affect:

  1. safety and well-being of the participant or offspring
  2. safety of study staff

De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/

Studies for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.

Formal request from qualified scientific and medical researchers on IPD and clinical study documents from clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.