Clinical trial NCT03614455: Pharmacokinetics (PK) Drug Interaction Study of Milademetan and Itraconazole or Posaconazole in Healthy Participants
Official title: An Open-label, Randomized, 2-period, 2-sequence Study to Evaluate the Single-dose Pharmacokinetics of Milademetan When Administered Alone or Concomitantly With Itraconazole or Posaconazole in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Pharmacokinetics
Lead sponsor: Daiichi Sankyo
Sponsor class: INDUSTRY
First posted: 2018-08-03
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Prior to dosing on Day 1 of Treatment Period 1, subjects will be assigned to 1 of 2 sequences (sequences AB or AC), according to a pre-generated randomization scheme.
Primary purpose: BASIC_SCIENCE

Brief summary: 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.


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: pre-dose and then at 0.5, 1, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, and 168 hours postdose
measure: Area under the plasma concentration-time curve extrapolated to infinity (AUCinf) of milademetan
timeFrame: within 168 hours postdose
Secondary outcomes:
measure: Time to reach maximum plasma concentration (Tmax) of milademetan
timeFrame: pre-dose and then at 0.5, 1, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, and 168 hours postdose
measure: Area under the plasma concentration-time curve from time 0 to the time of last measurable concentration (AUC0-t) for milademetan
timeFrame: within 168 hours postdose
measure: Terminal elimination half-life (t½) of milademetan
timeFrame: within 168 hours postdose
measure: Apparent total body clearance (CL/F) of milademetan
timeFrame: within 168 hours postdose
measure: Apparent volume of distribution (Vz/F)
timeFrame: within 168 hours postdose
Other outcomes:
Locations:
city: Dallas
country: United States
facility: Covance Clinical Research Unit, Inc.
state: Texas
Study officials:
affiliation: Daiichi Sankyo
name: Global Clinical Leader
role: STUDY_DIRECTOR
References: