Pharmacokinetics (PK) Drug Interaction Study of Milademetan and Itraconazole or Posaconazole in Healthy Participants

Pharmacokinetics Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03614455
• Other study ID #: DS3032-A-U107
• Status: Completed
• Phase: Early Phase 1
• Start date: July 13, 2018
• Est. completion date: October 1, 2018

Study information

• Verified date: November 2018
• Source: Daiichi Sankyo, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 36
• Est. completion date: October 1, 2018
• Est. primary completion date: October 1, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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

Related Conditions & MeSH terms

• Pharmacokinetics

Intervention

Drug:
• Milademetan
Milademetan 100 mg capsule for oral administration
• Itraconazole
Itraconazole (200 mg) oral solution (20 mL of 10 mg/mL)
• Posaconazole
Posaconazole (200 mg) oral suspension (5 mL of 40 mg/mL)

Locations

Country	Name	City	State
United States	Covance Clinical Research Unit, Inc.	Dallas	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Daiichi Sankyo, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum plasma concentration (Cmax) of milademetan	Categories: alone (A), in sequence AB, in sequence AC	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
Primary	Area under the plasma concentration-time curve extrapolated to infinity (AUCinf) of milademetan	Categories: alone (A), in sequence AB, in sequence AC	within 168 hours postdose
Secondary	Time to reach maximum plasma concentration (Tmax) of milademetan	Categories: alone (A), in sequence AB, in sequence AC	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
Secondary	Area under the plasma concentration-time curve from time 0 to the time of last measurable concentration (AUC0-t) for milademetan	Categories: alone (A), in sequence AB, in sequence AC	within 168 hours postdose
Secondary	Terminal elimination half-life (t½) of milademetan	Categories: alone (A), in sequence AB, in sequence AC	within 168 hours postdose
Secondary	Apparent total body clearance (CL/F) of milademetan	Categories: alone (A), in sequence AB, in sequence AC	within 168 hours postdose
Secondary	Apparent volume of distribution (Vz/F)	Categories: alone (A), in sequence AB, in sequence AC	within 168 hours postdose