Food Effects on Milademetan Pharmacokinetics in Healthy Participants

Daiichi Sankyo

Status and phase: Completed; Early Phase 1

Conditions: Food Effects on Pharmacokinetics

Treatments: Drug: Milademetan Treatment C; Drug: Milademetan Treatment A; Drug: Milademetan Treatment B

Study type: Interventional

Funder types: Industry

Identifiers

NCT03647202

DS3032-A-U115

Details and patient eligibility

About

The primary objectives of this trial are:

• To evaluate the effect of a high-calorie, high-fat meal on the single-dose pharmacokinetics (PK) of milademetan
• To evaluate the effect of a standard meal on the single-dose PK of milademetan

The key secondary objective is to evaluate the safety and tolerability of single-dose milademetan in all treatments.

The duration of the study for each individual participant will be approximately 8 weeks from the start of Screening (within 28 days prior to dosing of study drug on Day 1) through the final Follow-up visit or phone call. Participants will remain in the Clinical Research Unit (CRU) from Study Day -2 through Study Day 20 (a total of 22 days and 21 nights).

Participants will receive 3 single doses of study drug (at least 1 week apart) over the course of 15 days.

At the investigator's discretion, participants may be asked to return to the CRU 14 days (±2 days) after final dose of study drug for a follow-up visit.

The end of the study is defined as the date of final follow-up visit of the last subject undergoing the study.

Enrollment: 18 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: Crossover Assignment

Masking: None (Open label)

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18 participants in 6 patient groups

Sequence ABC

Experimental group

Description:

Participants receive milademetan in a fasted condition (A), then with a high-calorie, high-fat breakfast (B), then with a standard breakfast (C) - with a washout period between treatments.

Treatment:

Drug: Milademetan Treatment B

Drug: Milademetan Treatment A

Drug: Milademetan Treatment C

Sequence ACB

Experimental group

Description:

Participants receive milademetan in a fasted condition (A), then with a standard breakfast (C), then with a high-calorie, high-fat breakfast (B) - with a washout period between treatments.

Treatment:

Drug: Milademetan Treatment B

Drug: Milademetan Treatment A

Drug: Milademetan Treatment C

Sequence BAC

Experimental group

Description:

Participants receive milademetan with a high-calorie, high-fat breakfast (B), then in a fasted condition (A), then with a standard breakfast (C) - with a washout period between treatments.

Treatment:

Drug: Milademetan Treatment B

Drug: Milademetan Treatment A

Drug: Milademetan Treatment C

Sequence BCA

Experimental group

Description:

Participants receive milademetan with a high-calorie, high-fat breakfast (B), then with a standard breakfast (C), then in a fasted condition (A) - with a washout period between treatments.

Treatment:

Drug: Milademetan Treatment B

Drug: Milademetan Treatment A

Drug: Milademetan Treatment C

Sequence CAB

Experimental group

Description:

Participants receive milademetan with a standard breakfast (C), then in a fasted condition (A), then with a high-calorie, high-fat breakfast (B) - with a washout period between treatments.

Treatment:

Drug: Milademetan Treatment B

Drug: Milademetan Treatment A

Drug: Milademetan Treatment C

Sequence CBA

Experimental group

Description:

Participants receive milademetan with a standard breakfast (C), then with a high-calorie, high-fat breakfast (B), then in a fasted condition (A) - with a washout period between treatments.

Treatment:

Drug: Milademetan Treatment B

Drug: Milademetan Treatment A

Drug: Milademetan Treatment C