Clinical trial NCT03647202: Food Effects on Milademetan Pharmacokinetics in Healthy Participants
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Food Effects on Pharmacokinetics
Lead sponsor: Daiichi Sankyo
Sponsor class: INDUSTRY
First posted: 2018-08-27
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Participants will be assigned to 1 of 6 treatment sequences (Sequences ABC, ACB, BAC, BCA, CAB, or CBA), according to a pre-generated randomization scheme.
Primary purpose: BASIC_SCIENCE

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.


Eligibility 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

Primary outcomes:
measure: Maximum plasma concentration (Cmax) of milademetan
timeFrame: 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
measure: Area under the plasma concentration-time curve (AUC) extrapolated to infinity (AUCinf) for milademetan
timeFrame: within 120 hours postdose in each treatment period
Secondary outcomes:
measure: Time to teach maximum plasma concentration (Tmax) of milademetan
timeFrame: within 120 hours postdose in each treatment period
measure: AUC from time 0 to the time of last measurable concentration (AUClast) for milademetan
timeFrame: within 120 hours postdose in each treatment period
measure: Lag time (tlag) for milademetan
timeFrame: within 120 hours postdose in each treatment period
measure: Terminal elimination half-life (t½) of milademetan
timeFrame: within 120 hours postdose in each treatment period
measure: Apparent total body clearance (CL/F) of milademetan clearance (CL/F),
timeFrame: within 120 hours postdose in each treatment period
measure: Apparent volume of distribution (Vz/F) of milademetan
timeFrame: within 120 hours postdose in each treatment period
Other outcomes:
Locations:
city: Dallas
country: United States
facility: Covance Clinical Research Unit, Inc.
state: Texas
Study officials:
affiliation: Daiichi Sankyo
name: Clinical Study Leader
role: STUDY_DIRECTOR
References: