Food Effects on Milademetan Pharmacokinetics in Healthy Participants
Study Details
Study Description
Brief Summary
The primary objectives of this trial are:
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To evaluate the effect of a high-calorie, high-fat meal on the single-dose pharmacokinetics (PK) of milademetan
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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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Early Phase 1 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 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. |
Drug: Milademetan Treatment A
Treatment A: Single oral dose of milademetan 160 mg capsules under fasted conditions
Other Names:
Drug: Milademetan Treatment B
Treatment B: Single oral dose of milademetan 160 mg capsules with a high-calorie, high-fat meal
Other Names:
Drug: Milademetan Treatment C
Treatment C: Single oral dose of milademetan 160 mg capsules with a standard meal.
|
| Experimental: 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. |
Drug: Milademetan Treatment A
Treatment A: Single oral dose of milademetan 160 mg capsules under fasted conditions
Other Names:
Drug: Milademetan Treatment B
Treatment B: Single oral dose of milademetan 160 mg capsules with a high-calorie, high-fat meal
Other Names:
Drug: Milademetan Treatment C
Treatment C: Single oral dose of milademetan 160 mg capsules with a standard meal.
|
| Experimental: 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. |
Drug: Milademetan Treatment A
Treatment A: Single oral dose of milademetan 160 mg capsules under fasted conditions
Other Names:
Drug: Milademetan Treatment B
Treatment B: Single oral dose of milademetan 160 mg capsules with a high-calorie, high-fat meal
Other Names:
Drug: Milademetan Treatment C
Treatment C: Single oral dose of milademetan 160 mg capsules with a standard meal.
|
| Experimental: 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. |
Drug: Milademetan Treatment A
Treatment A: Single oral dose of milademetan 160 mg capsules under fasted conditions
Other Names:
Drug: Milademetan Treatment B
Treatment B: Single oral dose of milademetan 160 mg capsules with a high-calorie, high-fat meal
Other Names:
Drug: Milademetan Treatment C
Treatment C: Single oral dose of milademetan 160 mg capsules with a standard meal.
|
| Experimental: 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. |
Drug: Milademetan Treatment A
Treatment A: Single oral dose of milademetan 160 mg capsules under fasted conditions
Other Names:
Drug: Milademetan Treatment B
Treatment B: Single oral dose of milademetan 160 mg capsules with a high-calorie, high-fat meal
Other Names:
Drug: Milademetan Treatment C
Treatment C: Single oral dose of milademetan 160 mg capsules with a standard meal.
|
| Experimental: 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. |
Drug: Milademetan Treatment A
Treatment A: Single oral dose of milademetan 160 mg capsules under fasted conditions
Other Names:
Drug: Milademetan Treatment B
Treatment B: Single oral dose of milademetan 160 mg capsules with a high-calorie, high-fat meal
Other Names:
Drug: Milademetan Treatment C
Treatment C: Single oral dose of milademetan 160 mg capsules with a standard meal.
|
Outcome Measures
Primary Outcome Measures
- Maximum plasma concentration (Cmax) of milademetan [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 [within 120 hours postdose in each treatment period]
Secondary Outcome Measures
- Time to teach maximum plasma concentration (Tmax) 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]
- Lag time (tlag) for milademetan [within 120 hours postdose in each treatment period]
Tlag is used to characterize the delay in absorption of orally administered drugs
- Terminal elimination half-life (t½) of 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]
- Apparent volume of distribution (Vz/F) of milademetan [within 120 hours postdose in each treatment period]
Eligibility Criteria
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:
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Has negative urine test for drugs of abuse, alcohol and tobacco
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If female, is surgically sterile or postmenopausal
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If male, agrees to protocol-defined contraceptive methods
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Has adequate hematologic, hepatic, and renal function as defined by the protocol
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Is able and willing to follow all study procedures
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Has provided a signed informed consent
Exclusion Criteria:
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Is female who is pregnant or breastfeeding
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Is unable to swallow oral medication
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Is unable to follow study procedures
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Has creatinine clearance < 90 mL/min at screening
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Is taking or has taken any medications or therapies outside of protocol-defined parameters
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Has history of or a known allergic reaction to azole antifungal agents
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Has any disease or condition that, per protocol or in the opinion of the investigator, might affect:
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safety and well-being of the participant or offspring
-
safety of study staff
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Covance Clinical Research Unit, Inc. | Dallas | Texas | United States | 75247 |
Sponsors and Collaborators
- Daiichi Sankyo, Inc.
Investigators
- Study Director: Clinical Study Leader, Daiichi Sankyo, Inc.
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- DS3032-A-U115