PharmacokineticsEarly Phase 1NCT03614455
Pharmacokinetics (PK) Drug Interaction Study of Milademetan and Itraconazole or Posaconazole in Healthy Participants
A Early Phase 1 study testing Milademetan, Itraconazole and Posaconazole in people with Pharmacokinetics, run by Daiichi Sankyo at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Pharmacokinetics
- What is being tested?
- Milademetan, Itraconazole and Posaconazole
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 36 participants
- Where
- 1 siteUnited States
- Study dates
- 13 Jul 2018to 1 Oct 2018
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 9Show fewer
- Has any disease or condition that, per protocol or in the opinion of the investigator, might affect:
- safety and well-being of the participant or offspring
- safety of study staff
Trial locations and contacts
1 site in 1 country.
United States1 site
Covance Clinical Research Unit, Inc.
Dallas, Texas, 75247
About this study
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
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.
- Conditions
- Pharmacokinetics
- Being tested
- Milademetan, Itraconazole, Posaconazole
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MilademetanDrug
Also called Experimental product, DS-3032, CYP3A4 Substrate
Milademetan 100 mg capsule for oral administration
ItraconazoleDrug
Also called CYP3A4 Inhibitor
Itraconazole (200 mg) oral solution (20 mL of 10 mg/mL)
PosaconazoleDrug
Also called CYP3A4 Inhibitor
Posaconazole (200 mg) oral suspension (5 mL of 40 mg/mL)
| Study group | Role | What they receive |
|---|---|---|
| Milademetan alone (A) | Experimental | 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) Receives: Drug: Milademetan |
| Milademetan with itraconazole (AB) | Other | 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 Receives: Drug: Milademetan; Drug: Itraconazole |
| Milademetan with posaconazole (AC) | Other | 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 Receives: Drug: Milademetan; Drug: Posaconazole |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum plasma concentration (Cmax) of milademetan
Categories: alone (A), in sequence AB, in sequence AC
Measured: 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
Area under the plasma concentration-time curve extrapolated to infinity (AUCinf) of milademetan
Categories: alone (A), in sequence AB, in sequence AC
Measured: within 168 hours postdose
Secondary outcomes (5)
Time to reach maximum plasma concentration (Tmax) of milademetan
Categories: alone (A), in sequence AB, in sequence AC
Measured: 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
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
Measured: within 168 hours postdose
Terminal elimination half-life (t½) of milademetan
Categories: alone (A), in sequence AB, in sequence AC
Measured: within 168 hours postdose
Apparent total body clearance (CL/F) of milademetan
Categories: alone (A), in sequence AB, in sequence AC
Measured: within 168 hours postdose
Apparent volume of distribution (Vz/F)
Categories: alone (A), in sequence AB, in sequence AC
Measured: within 168 hours postdose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Aug 2018
- Study start13 Jul 2018
- Primary completion1 Oct 2018
- Study completion1 Oct 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for PharmacokineticsStudies of the same condition, open and under way.
- More trials run by Daiichi SankyoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Sequential
- 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)
- Enrolment
- 36 participants (actual)
Sponsor and investigators
- Lead sponsor
- Daiichi Sankyo
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Global Clinical Leader, Study director, Daiichi Sankyo
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03614455
- Sponsor's protocol ID
- DS3032-A-U107
- Status last verified
- Nov 2018
- First submitted
- 30 Jul 2018
- Last updated
- 12 Feb 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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/
Study at a glance
From the registry record, last updated by the sponsor on 12 Feb 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03614455
- Acronym / sponsor ID
- DS3032-A-U107
- Conditions
- Pharmacokinetics
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 36 participants (actual)
- Lead sponsor
- Daiichi SankyoIndustry (pharma, biotech, devices)
- Study start
- 13 Jul 2018 (actual)
- Primary completion
- 1 Oct 2018 (actual)
- Study completion
- 1 Oct 2018 (actual)
- First posted
- 3 Aug 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 3
- 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.
| Arm | Type | Receives |
|---|---|---|
| Milademetan alone (A) | Experimental | Drug: MilademetanDuring 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) |
| Milademetan with itraconazole (AB) | Other | Drug: Milademetan, Drug: ItraconazoleDuring 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 |
| Milademetan with posaconazole (AC) | Other | Drug: Milademetan, Drug: PosaconazoleDuring 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 |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (9 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MilademetanAlso: Experimental product, DS-3032, CYP3A4 SubstrateMilademetan 100 mg capsule for oral administration | Drug | Milademetan alone (A), Milademetan with itraconazole (AB), Milademetan with posaconazole (AC) |
| ItraconazoleAlso: CYP3A4 InhibitorItraconazole (200 mg) oral solution (20 mL of 10 mg/mL) | Drug | Milademetan with itraconazole (AB) |
| PosaconazoleAlso: CYP3A4 InhibitorPosaconazole (200 mg) oral suspension (5 mL of 40 mg/mL) | Drug | Milademetan with posaconazole (AC) |
Primary outcome
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
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
5 secondary outcomes
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
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
Terminal elimination half-life (t½) of milademetan
Time frame: within 168 hours postdose
Apparent total body clearance (CL/F) of milademetan
Time frame: within 168 hours postdose
Apparent volume of distribution (Vz/F)
Time frame: within 168 hours postdose
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Feb 2019.
- Individual participant dataSharing planned: Yes. 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/
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Global Clinical Leader study director
Daiichi Sankyo
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Milademetan, Itraconazole and Posaconazole in people with Pharmacokinetics, run by Daiichi Sankyo at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Feb 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Feb 2019.