An Open-label, Randomized, 3-period, 3-treatment Crossover Study to Evaluate the Effect of High-fat, High-calorie Food and Standard Food on the Single-dose Pharmacokinetics of Milademetan in Healthy Subjects
Overview
- Phase
- Early Phase 1
- Intervention
- Milademetan Treatment C
- Conditions
- Food Effects on Pharmacokinetics
- Sponsor
- Daiichi Sankyo
- Enrollment
- 18
- Locations
- 1
- Primary Endpoint
- Maximum plasma concentration (Cmax) of milademetan
- Status
- Completed
- Last Updated
- 7 years ago
Overview
Brief Summary
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.
Investigators
Eligibility Criteria
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:
- •safety and well-being of the participant or offspring
- •safety of study staff
Arms & Interventions
Sequence BAC
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.
Intervention: Milademetan Treatment C
Sequence ABC
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.
Intervention: Milademetan Treatment A
Sequence ABC
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.
Intervention: Milademetan Treatment B
Sequence ABC
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.
Intervention: Milademetan Treatment C
Sequence ACB
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.
Intervention: Milademetan Treatment A
Sequence ACB
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.
Intervention: Milademetan Treatment B
Sequence ACB
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.
Intervention: Milademetan Treatment C
Sequence BAC
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.
Intervention: Milademetan Treatment A
Sequence BAC
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.
Intervention: Milademetan Treatment B
Sequence BCA
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.
Intervention: Milademetan Treatment A
Sequence BCA
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.
Intervention: Milademetan Treatment B
Sequence BCA
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.
Intervention: Milademetan Treatment C
Sequence CAB
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.
Intervention: Milademetan Treatment A
Sequence CAB
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.
Intervention: Milademetan Treatment B
Sequence CAB
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.
Intervention: Milademetan Treatment C
Sequence CBA
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.
Intervention: Milademetan Treatment A
Sequence CBA
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.
Intervention: Milademetan Treatment B
Sequence CBA
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.
Intervention: Milademetan Treatment C
Outcomes
Primary Outcomes
Maximum plasma concentration (Cmax) of milademetan
Time Frame: predose and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36, 48, 72, 96, and 120 hours postdose in each treatment period
Area under the plasma concentration-time curve (AUC) extrapolated to infinity (AUCinf) for milademetan
Time Frame: within 120 hours postdose in each treatment period
Secondary Outcomes
- Terminal elimination half-life (t½) of milademetan(within 120 hours postdose in each treatment period)
- AUC from time 0 to the time of last measurable concentration (AUClast) for milademetan(within 120 hours postdose in each treatment period)
- Apparent volume of distribution (Vz/F) of milademetan(within 120 hours postdose in each treatment period)
- Time to teach maximum plasma concentration (Tmax) of milademetan(within 120 hours postdose in each treatment period)
- Lag time (tlag) for milademetan(within 120 hours postdose in each treatment period)
- Apparent total body clearance (CL/F) of milademetan clearance (CL/F),(within 120 hours postdose in each treatment period)