Pharmacokinetics (PK) Drug Interaction Study of Milademetan and Itraconazole or Posaconazole in Healthy Participants

Daiichi Sankyo

Status and phase: Completed; Early Phase 1

Conditions: Pharmacokinetics

Treatments: Drug: Itraconazole; Drug: Posaconazole; Drug: Milademetan

Study type: Interventional

Funder types: Industry

Identifiers

NCT03614455

DS3032-A-U107

Details and patient eligibility

About

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.

Enrollment: 36 patients

Sex: All

Ages: 18 to 55 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

---

36 participants in 3 patient groups

Milademetan alone (A)

Experimental group

Description:

During Period 1, participants receive a single 100 mg milademetan oral dose on Study Day 1, with PK sampling to 168 hours post-dose (during the following 7-day washout period)

Treatment:

Drug: Milademetan

Milademetan with itraconazole (AB)

Other group

Description:

During Period 2, participants receive itraconazole, 200 mg twice daily (BID) on Study day 8 and 200 mg once daily (QD) on Study Days 9 through 20, along with a single 100 mg milademetan dose on Day 14

Treatment:

Drug: Milademetan

Drug: Itraconazole

Milademetan with posaconazole (AC)

Other group

Description:

During Period 2, participants receive 200 mg posaconazole three times daily (TID) on Study Days 8 through 20, along with a single 100 mg milademetan dose on Day 14

Treatment:

Drug: Milademetan

Drug: Posaconazole