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

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ClinicalTrials.gov Identifier: NCT03614455
Recruitment Status : Completed
First Posted : August 3, 2018
Last Update Posted : February 12, 2019
Sponsor:
Information provided by (Responsible Party):
Daiichi Sankyo, Inc.

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.


Condition or disease Intervention/treatment Phase
Pharmacokinetics Drug: Milademetan Drug: Itraconazole Drug: Posaconazole Early Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 36 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
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.
Masking: None (Open Label)
Primary Purpose: Basic Science
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
Actual Study Start Date : July 13, 2018
Actual Primary Completion Date : October 1, 2018
Actual Study Completion Date : October 1, 2018

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Milademetan alone (A)
During Period 1, participants receive a single 100 mg milademetan oral dose on Study Day 1, with PK sampling to 168 hours post-dose (during the following 7-day washout period)
Drug: Milademetan
Milademetan 100 mg capsule for oral administration
Other Names:
  • Experimental product
  • DS-3032
  • CYP3A4 Substrate

Milademetan with itraconazole (AB)
During Period 2, participants receive itraconazole, 200 mg twice daily (BID) on Study day 8 and 200 mg once daily (QD) on Study Days 9 through 20, along with a single 100 mg milademetan dose on Day 14
Drug: Milademetan
Milademetan 100 mg capsule for oral administration
Other Names:
  • Experimental product
  • DS-3032
  • CYP3A4 Substrate

Drug: Itraconazole
Itraconazole (200 mg) oral solution (20 mL of 10 mg/mL)
Other Name: CYP3A4 Inhibitor

Milademetan with posaconazole (AC)
During Period 2, participants receive 200 mg posaconazole three times daily (TID) on Study Days 8 through 20, along with a single 100 mg milademetan dose on Day 14
Drug: Milademetan
Milademetan 100 mg capsule for oral administration
Other Names:
  • Experimental product
  • DS-3032
  • CYP3A4 Substrate

Drug: Posaconazole
Posaconazole (200 mg) oral suspension (5 mL of 40 mg/mL)
Other Name: CYP3A4 Inhibitor




Primary Outcome Measures :
  1. Maximum plasma concentration (Cmax) of milademetan [ Time Frame: 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 ]
    Categories: alone (A), in sequence AB, in sequence AC

  2. Area under the plasma concentration-time curve extrapolated to infinity (AUCinf) of milademetan [ Time Frame: within 168 hours postdose ]
    Categories: alone (A), in sequence AB, in sequence AC


Secondary Outcome Measures :
  1. Time to reach maximum plasma concentration (Tmax) of milademetan [ Time Frame: 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 ]
    Categories: alone (A), in sequence AB, in sequence AC

  2. Area under the plasma concentration-time curve from time 0 to the time of last measurable concentration (AUC0-t) for milademetan [ Time Frame: within 168 hours postdose ]
    Categories: alone (A), in sequence AB, in sequence AC

  3. Terminal elimination half-life (t½) of milademetan [ Time Frame: within 168 hours postdose ]
    Categories: alone (A), in sequence AB, in sequence AC

  4. Apparent total body clearance (CL/F) of milademetan [ Time Frame: within 168 hours postdose ]
    Categories: alone (A), in sequence AB, in sequence AC

  5. Apparent volume of distribution (Vz/F) [ Time Frame: within 168 hours postdose ]
    Categories: alone (A), in sequence AB, in sequence AC



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03614455


Locations
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United States, Texas
Covance Clinical Research Unit, Inc.
Dallas, Texas, United States, 75247
Sponsors and Collaborators
Daiichi Sankyo, Inc.
Investigators
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Study Director: Global Clinical Leader Daiichi Sankyo, Inc.

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Responsible Party: Daiichi Sankyo, Inc.
ClinicalTrials.gov Identifier: NCT03614455     History of Changes
Other Study ID Numbers: DS3032-A-U107
First Posted: August 3, 2018    Key Record Dates
Last Update Posted: February 12, 2019
Last Verified: November 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Clinical Study Report (CSR)
Time Frame: Studies for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.
Access Criteria: Formal request from qualified scientific and medical researchers on IPD and clinical study documents from clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.
URL: https://vivli.org/ourmember/daiichi-sankyo/

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Itraconazole
Hydroxyitraconazole
Posaconazole
Cytochrome P-450 CYP3A Inhibitors
Antifungal Agents
Anti-Infective Agents
14-alpha Demethylase Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Steroid Synthesis Inhibitors
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Trypanocidal Agents
Antiprotozoal Agents
Antiparasitic Agents