Drug Interaction PotentialPhase 1NCT03291288

Effect of Pexidartinib on the Way the Body Processes CYP3A4 and CYP2C9 Substrates (Pharmacokinetics)

A Phase 1 study testing Tolbutamide, Midazolam and Pexidartinib in people with Drug Interaction Potential, run by Daiichi Sankyo at 11 sites in 4 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial summary

This study has two parts. Part 1 will evaluate how pexidartinib affects the way the body processes CYP3A4 and CYP2C9 substrates using midazolam and tolbutamide, respectively, as probe agents. Part 2 will test the efficacy and safety of pexidartinib treatment in various tumor types. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Drug Interaction Potential
What is being tested?: Tolbutamide, Midazolam and Pexidartinib
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 32 participants
Where: 11 sitesin 4 countries
Study dates: 26 Feb 2018to 16 Apr 2021
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

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 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Is the age of majority in country of residence
Has a diagnosis of:
tenosynovial giant cell tumor (TGCT), which is associated with severe morbidity or functional limitations and for whom surgery is not an option (prior pexidartinib is permitted for TGCT patients unless ineffective or not tolerated and there has been a washout period of at least 4 weeks)
KIT-mutant tumor, including melanoma or gastrointestinal stromal tumor (GIST), for which there is no standard systemic therapy, or
other solid tumors (all comers) for which there is no standard systemic therapy and there is a rationale for use of pexidartinib at the Investigator's discretion
If a female of childbearing potential, had a negative serum pregnancy test within 14 days before enrollment, or within 72 hours before enrollment where required

Show all 14Show fewer

Is a non-sterile male or female willing to use of one of the protocol-defined highly effective contraception methods:
intra-uterine device (nonhormonal or hormonal)
sexual abstinence (only if this is in line with the patient's current lifestyle)
barrier methods (eg, condom, diaphragm) used in combination with hormonal methods associated with inhibition of ovulation
Is a surgically sterile male or female, or is postmenopausal for at least 1 year, at least 50 years of age, with a follicle-stimulating hormone level > 40 milli-International units per mL (mIU/mL)
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 pregnant or breastfeeding
Is unable to swallow oral medication
Is unable to follow study procedures
Is taking or has taken any medications or therapies outside of protocol-defined parameters
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
analysis of results

Trial locations and contacts

11 sites in 4 countries.

Country

City, postcode or hospital

11 sites in 4 countries

United States8 sites

Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
Mary Crowley Cancer Research
Dallas, Texas, 75230
Karmanos Cancer Center
Detroit, Michigan, 48201
Northwell Health
Lake Success, New York, 10042
Stanford University
Palo Alto, California, 94304
HonorHealth
Scottsdale, Arizona, 85258
University of Arizona
Tucson, Arizona, 85719
University of Kansas Cancer Center
Westwood, Kansas, 66205

Other trials in United States

Netherlands1 site

Leids Universitair Medisch Centrum
Leiden, 2333 ZA

Other trials in Netherlands

New Zealand1 site

Christchurch Hospital NZ
Christchurch, 8011

Other trials in New Zealand

Taiwan1 site

National Taiwan University Hospital
Taipei, 10002

Other trials in Taiwan

About this study

Official title: An Open-label, Single Sequence, Crossover Drug-drug Interaction Study Assessing the Effect of Pexidartinib on the Pharmacokinetics of CYP3A4 and CYP2C9 Substrates in Patients

This study has two parts.

Part 1 will evaluate how pexidartinib affects the way the body processes CYP3A4 and CYP2C9 substrates using midazolam and tolbutamide, respectively, as probe agents.

Part 2 will test the efficacy and safety of pexidartinib treatment in various tumor types.

In Part 2, the same participants will continue to receive pexidartinib twice daily.

Participants will be allowed to continue using pexidartinib as long as the participant derives benefit.

Conditions: Drug Interaction Potential
Being tested: Tolbutamide, Midazolam, Pexidartinib
Keywords: Tenosynovial Giant Cell Tumors (TGCT), Kit-mutant melanoma, Kit-mutant gastrointestinal stromal tumor (GIST), Cocktail drug-drug interaction (DDI)
Medical subject headings: Synovitis, Pigmented Villonodular

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

TolbutamideDrug
Also called Orinase
Commercially available tolbutamide
MidazolamDrug
Also called Dormicum, Hypnovel, Versed, Others
Commercially available midazolam
PexidartinibDrug
Also called PLX-3397
Pexidartinib is formulated as opaque, white, 200-mg capsules

Study groups in NCT03291288
Study group	Role	What they receive
Pexidartinib	Experimental	Part 1 (Drug-drug Interaction Phase): On Day 1, all participants will receive a single oral dose each of midazolam (2 mg) and tolbutamide (500 mg). On Day 3, pexidartinib (800 mg/d) in twice daily (400 mg BID) dosing will be initiated and continue throughout the remainder of Part 1 and into Part 2. On the first day of pexidartinib treatment (Day 3), a single dose of midazolam (2 mg) and tolbutamide (500 mg) will be co-administered with the morning pexidartinib dose (400 mg). On Day 13, a single dose of midazolam (2 mg) and tolbutamide (500 mg) will be co-administered with the morning dose of pexidartinib (400 mg). Part 2 (Efficacy and Safety Phase): All participants will continue to receive pexidartinib 400 mg BID. Receives: Drug: Tolbutamide; Drug: Midazolam; Drug: Pexidartinib

What is being measured

The primary outcome is the main question the study is designed to answer.

Pharmacokinetic Analysis: Maximum Concentration (Cmax) for Midazolam
Plasma samples for midazolam were collected at predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 24, and 48 hours (h) (±10 minutes up to 1 h, ±10% thereafter) on Days 1 to 3, and also when co-administered with pexidartinib on Days 3 (to 5) and Days 13 (to 15).
Measured: Baseline to 15 days post treatment
Pharmacokinetic Analysis: Maximum Concentration (Cmax) for Tolbutamide
Plasma samples for tolbutamide were collected at predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 24, and 48 h (±10 min up to 1 h, ±10% thereafter) on Days 1 to 3, and also when co-administered with pexidartinib on Days 3 (to 5) and Days 13 (to 15).
Measured: Baseline to 15 days post treatment
Pharmacokinetic Analysis: Time to Maximum Concentration (Tmax) for Midazolam
Plasma samples for midazolam were collected at predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 24, and 48 hours (h) (±10 minutes up to 1 h, ±10% thereafter) on Days 1 to 3, and also when co-administered with pexidartinib on Days 3 (to 5) and Days 13 (to 15).
Measured: Baseline to 15 days post treatment
Pharmacokinetic Analysis: Time to Maximum Concentration (Tmax) for Tolbutamide
Plasma samples for tolbutamide were collected at predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 24, and 48 h (±10 min up to 1 h, ±10% thereafter) on Days 1 to 3, and also when co-administered with pexidartinib on Days 3 (to 5) and Days 13 (to 15).
Measured: Baseline to 15 days post treatment
Pharmacokinetic Analysis: Area Under the Curve to the Last Observable Concentration (AUClast) for Midazolam
Plasma samples for midazolam were collected at predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 24, and 48 hours (h) (±10 minutes up to 1 h, ±10% thereafter) on Days 1 to 3, and also when co-administered with pexidartinib on Days 3 (to 5) and Days 13 (to 15).
Measured: Baseline to 15 days post treatment
Pharmacokinetic Analysis: Area Under the Curve to the Last Observable Concentration (AUClast) for Tolbutamide
Plasma samples for tolbutamide were collected at predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 24, and 48 h (±10 min up to 1 h, ±10% thereafter) on Days 1 to 3, and also when co-administered with pexidartinib on Days 3 (to 5) and Days 13 (to 15).
Measured: Baseline to 15 days post treatment
Overall Summary of Treatment-emergent Adverse Events
Adverse events that emerge during treatment, having been absent pre-treatment, or worsens relative to the pre-treatment state.
Measured: Baseline to 1 year post treatment

Secondary outcomes (7)

Pharmacokinetic Analysis: Maximum Concentration (Cmax) for Pexidartinib and ZAAD-1006a Metabolite
Plasma samples for pexidartinib and its metabolite were collected at predose, 0.5, 1, 2, 2.5, 3, 4, 6, 8, and 10 (±1) h after the first dose on Day 3, and at steady state when co-administered with midazolam and tolbutamide on Day 13.
Measured: Baseline to 13 days post treatment
Pharmacokinetic Analysis: Time to Maximum Concentration (Tmax) for Pexidartinib and ZAAD-1006a Metabolite
Plasma samples for pexidartinib and its metabolite were collected at predose, 0.5, 1, 2, 2.5, 3, 4, 6, 8, and 10 (±1) h after the first dose on Day 3, and at steady state when co-administered with midazolam and tolbutamide on Day 13.
Measured: Baseline to 13 days post treatment
Pharmacokinetic Analysis: Area Under the Curve to the Last Observable Concentration (AUClast) for Pexidartinib and ZAAD-1006a Metabolite
Plasma samples for pexidartinib and its metabolite were collected at predose, 0.5, 1, 2, 2.5, 3, 4, 6, 8, and 10 (±1) h after the first dose on Day 3, and at steady state when co-administered with midazolam and tolbutamide on Day 13.
Measured: Baseline to 13 days post treatment
Pharmacokinetic Analysis: Maximum Concentration (Cmax) for Midazolam Metabolite, 1-Hydroxy Midazolam
Plasma samples for midazolam and 1-hydroxy midazolam were to be collected at predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8 (±10 min up to 8 h), 10 (±2), 24 (±2), and 48 (±2) hours on Days 1 to 3 and also when co-administered with pexidartinib on Days 3 to 5 and Days 13 to 15.
Measured: Baseline to 13 days post treatment
Pharmacokinetic Analysis: Time to Maximum Concentration (Tmax) for Midazolam Metabolite, 1-Hydroxy Midazolam
Plasma samples for midazolam and 1-hydroxy midazolam were to be collected at predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8 (±10 min up to 8 h), 10 (±2), 24 (±2), and 48 (±2) hours on Days 1 to 3 and also when co-administered with pexidartinib on Days 3 to 5 and Days 13 to 15.
Measured: Baseline to 13 days post treatment
Pharmacokinetic Analysis: Area Under the Curve to the Last Observable Concentration (AUClast) for Midazolam Metabolite, 1-Hydroxy Midazolam
Plasma samples for midazolam and 1-hydroxy midazolam were to be collected at predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8 (±10 min up to 8 h), 10 (±2), 24 (±2), and 48 (±2) hours on Days 1 to 3 and also when co-administered with pexidartinib on Days 3 to 5 and Days 13 to 15.
Measured: Baseline to 13 days post treatment
Pharmacokinetic Analysis: Metabolite to Parent Ratio (MPR) for Midazolam
Plasma samples for midazolam were collected at predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 24, and 48 hours (h) (±10 minutes up to 1 h, ±10% thereafter) on Days 1 to 3, and also when co-administered with pexidartinib on Days 3 (to 5) and Days 13 (to 15).
Plasma pharmacokinetic parameters calculated for Midazolam metabolite. 1-hydroxy midazolam and midazolam for the MPR value.
Measured: Baseline to 13 days post treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

26 Feb 201816 Apr 2021

First posted25 Sep 2017
Study start26 Feb 2018
Primary completion26 Sep 2018
Study completion16 Apr 2021

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Drug Interaction PotentialStudies 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: Phase 1
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Sequential
Model description: Open-label, single sequence study with 2 parts
Masking: None (open label)
Enrolment: 32 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03291288
Sponsor's protocol ID: PL3397-A-U126
Status last verified: Apr 2021
First submitted: 19 Sep 2017
Last updated: 14 May 2021
Results posted: Yes, on ClinicalTrials.gov
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/

Publications

Lewis JH, Gelderblom H, van de Sande M, Stacchiotti S, Healey JH, Tap WD, Wagner AJ, Pousa AL, Druta M, Lin CC, Baba HA, Choi Y, Wang Q, Shuster DE, Bauer S. Pexidartinib Long-Term Hepatic Safety Profile in Patients with Tenosynovial Giant Cell Tumors. Oncologist. 2021 May;26(5):e863-e873. doi: 10.1002/onco.13629. Epub 2020 Dec 24.
PubMed 33289960

Study at a glance

From the registry record, last updated by the sponsor on 14 May 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: An Open-label, Single Sequence, Crossover Drug-drug Interaction Study Assessing the Effect of Pexidartinib on the Pharmacokinetics of CYP3A4 and CYP2C9 Substrates in Patients
ClinicalTrials.gov ID: NCT03291288
Acronym / sponsor ID: PL3397-A-U126
Conditions: Drug Interaction Potential
Keywords: Tenosynovial Giant Cell Tumors (TGCT), Kit-mutant melanoma, Kit-mutant gastrointestinal stromal tumor (GIST), Cocktail drug-drug interaction (DDI)
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 32 participants (actual)
Lead sponsor: Daiichi SankyoIndustry (pharma, biotech, devices)
Study start: 26 Feb 2018 (actual)
Primary completion: 26 Sep 2018 (actual)
Study completion: 16 Apr 2021 (actual)
First posted: 25 Sep 2017 (actual)
Results: Posted 19 Mar 2020

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

This study has two parts.

Part 1 will evaluate how pexidartinib affects the way the body processes CYP3A4 and CYP2C9 substrates using midazolam and tolbutamide, respectively, as probe agents.

Part 2 will test the efficacy and safety of pexidartinib treatment in various tumor types.

In Part 2, the same participants will continue to receive pexidartinib twice daily.

Participants will be allowed to continue using pexidartinib as long as the participant derives benefit.

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Sequential
Masking: None (open label)
Number of arms: 1
Model description: Open-label, single sequence study with 2 parts

Arm	Type	Receives
Pexidartinib	Experimental	Drug: Tolbutamide, Drug: Midazolam, Drug: PexidartinibPart 1 (Drug-drug Interaction Phase): On Day 1, all participants will receive a single oral dose each of midazolam (2 mg) and tolbutamide (500 mg). On Day 3, pexidartinib (800 mg/d) in twice daily (400 mg BID) dosing will be initiated and continue throughout the remainder of Part 1 and into Part 2. On the first day of pexidartinib treatment (Day 3), a single dose of midazolam (2 mg) and tolbutamide (500 mg) will be co-administered with the morning pexidartinib dose (400 mg). On Day 13, a single dose of midazolam (2 mg) and tolbutamide (500 mg) will be co-administered with the morning dose of pexidartinib (400 mg). Part 2 (Efficacy and Safety Phase): All participants will continue to receive pexidartinib 400 mg BID.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (14 listed)

Is the age of majority in country of residence
Has a diagnosis of:
If a female of childbearing potential, had a negative serum pregnancy test within 14 days before enrollment, or within 72 hours before enrollment where required
Is a non-sterile male or female willing to use of one of the protocol-defined highly effective contraception methods:
Is a surgically sterile male or female, or is postmenopausal for at least 1 year, at least 50 years of age, with a follicle-stimulating hormone level > 40 milli-International units per mL (mIU/mL)

Key exclusion criteria (8 listed)

Is pregnant or breastfeeding
Is unable to swallow oral medication
Is unable to follow study procedures
Is taking or has taken any medications or therapies outside of protocol-defined parameters
Has any disease or condition that, per protocol or in the opinion of the investigator, might affect:

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
TolbutamideAlso: OrinaseCommercially available tolbutamide	Drug	Pexidartinib
MidazolamAlso: Dormicum, Hypnovel, Versed, OthersCommercially available midazolam	Drug	Pexidartinib
PexidartinibAlso: PLX-3397Pexidartinib is formulated as opaque, white, 200-mg capsules	Drug	Pexidartinib

Primary outcome

Pharmacokinetic Analysis: Maximum Concentration (Cmax) for Midazolam
Time frame: Baseline to 15 days post treatment
Plasma samples for midazolam were collected at predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 24, and 48 hours (h) (±10 minutes up to 1 h, ±10% thereafter) on Days 1 to 3, and also when co-administered with pexidartinib on Days 3 (to 5) and Days 13 (to 15).
Pharmacokinetic Analysis: Maximum Concentration (Cmax) for Tolbutamide
Time frame: Baseline to 15 days post treatment
Plasma samples for tolbutamide were collected at predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 24, and 48 h (±10 min up to 1 h, ±10% thereafter) on Days 1 to 3, and also when co-administered with pexidartinib on Days 3 (to 5) and Days 13 (to 15).
Pharmacokinetic Analysis: Time to Maximum Concentration (Tmax) for Midazolam
Time frame: Baseline to 15 days post treatment
Plasma samples for midazolam were collected at predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 24, and 48 hours (h) (±10 minutes up to 1 h, ±10% thereafter) on Days 1 to 3, and also when co-administered with pexidartinib on Days 3 (to 5) and Days 13 (to 15).
Pharmacokinetic Analysis: Time to Maximum Concentration (Tmax) for Tolbutamide
Time frame: Baseline to 15 days post treatment
Plasma samples for tolbutamide were collected at predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 24, and 48 h (±10 min up to 1 h, ±10% thereafter) on Days 1 to 3, and also when co-administered with pexidartinib on Days 3 (to 5) and Days 13 (to 15).
Pharmacokinetic Analysis: Area Under the Curve to the Last Observable Concentration (AUClast) for Midazolam
Time frame: Baseline to 15 days post treatment
Plasma samples for midazolam were collected at predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 24, and 48 hours (h) (±10 minutes up to 1 h, ±10% thereafter) on Days 1 to 3, and also when co-administered with pexidartinib on Days 3 (to 5) and Days 13 (to 15).
Pharmacokinetic Analysis: Area Under the Curve to the Last Observable Concentration (AUClast) for Tolbutamide
Time frame: Baseline to 15 days post treatment
Plasma samples for tolbutamide were collected at predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 24, and 48 h (±10 min up to 1 h, ±10% thereafter) on Days 1 to 3, and also when co-administered with pexidartinib on Days 3 (to 5) and Days 13 (to 15).
Overall Summary of Treatment-emergent Adverse Events
Time frame: Baseline to 1 year post treatment
Adverse events that emerge during treatment, having been absent pre-treatment, or worsens relative to the pre-treatment state.

7 secondary outcomes

Pharmacokinetic Analysis: Maximum Concentration (Cmax) for Pexidartinib and ZAAD-1006a Metabolite
Time frame: Baseline to 13 days post treatment
Pharmacokinetic Analysis: Time to Maximum Concentration (Tmax) for Pexidartinib and ZAAD-1006a Metabolite
Time frame: Baseline to 13 days post treatment
Pharmacokinetic Analysis: Area Under the Curve to the Last Observable Concentration (AUClast) for Pexidartinib and ZAAD-1006a Metabolite
Time frame: Baseline to 13 days post treatment
Pharmacokinetic Analysis: Maximum Concentration (Cmax) for Midazolam Metabolite, 1-Hydroxy Midazolam
Time frame: Baseline to 13 days post treatment
Pharmacokinetic Analysis: Time to Maximum Concentration (Tmax) for Midazolam Metabolite, 1-Hydroxy Midazolam
Time frame: Baseline to 13 days post treatment
Pharmacokinetic Analysis: Area Under the Curve to the Last Observable Concentration (AUClast) for Midazolam Metabolite, 1-Hydroxy Midazolam
Time frame: Baseline to 13 days post treatment
Pharmacokinetic Analysis: Metabolite to Parent Ratio (MPR) for Midazolam
Time frame: Baseline to 13 days post treatment

Results and safety

Results posted to the registry on 19 Mar 2020, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Part 1: Drug-drug Interaction Phase	32	26
Part 2: Pexidartinib Only	0	0

Primary outcome: Pharmacokinetic Analysis: Maximum Concentration (Cmax) for Midazolam

Time frame: Baseline to 15 days post treatment. Mean (Standard Deviation). Unit: ng/mL

Measure	Part 1: Midazolam Only n = 32	Part 1: Pexidartinib + Midazolam (Cycle 1, Day 1) n = 30	Part 1: Pexidartinib + Midazolam (Cycle 1, Day 11) n = 25
Value	13.6 (6.8)	12.0 (4.9)	9.7 (4.1)

Population analysed: Pharmacokinetic parameters were assessed in the Pharmacokinetic Evaluable population.

Primary outcome: Pharmacokinetic Analysis: Maximum Concentration (Cmax) for Tolbutamide

Time frame: Baseline to 15 days post treatment. Mean (Standard Deviation). Unit: ng/mL

Measure	Part 1: Tolbutamide Only n = 32	Part 1: Pexidartinib + Tolbutamide (Cycle 1, Day 1) n = 30	Part 1: Pexidartinib + Tolbutamide (Cycle 1, Day 11) n = 25
Value	44400 (13100)	46700 (16300)	44400 (12200)

Population analysed: Pharmacokinetic parameters were assessed in the Pharmacokinetic Evaluable population.

Primary outcome: Pharmacokinetic Analysis: Time to Maximum Concentration (Tmax) for Midazolam

Time frame: Baseline to 15 days post treatment. Median (Full Range). Unit: hours

Measure	Part 1: Midazolam Only n = 32	Part 1: Pexidartinib + Midazolam (Cycle 1, Day 1) n = 30	Part 1: Pexidartinib + Midazolam (Cycle 1, Day 11) n = 25
Value	0.525 (0.333 to 1.37)	0.5 (0.417 to 1.42)	0.5 (0.333 to 0.917)

Population analysed: Pharmacokinetic parameters were assessed in the Pharmacokinetic Evaluable population.

Primary outcome: Pharmacokinetic Analysis: Time to Maximum Concentration (Tmax) for Tolbutamide

Time frame: Baseline to 15 days post treatment. Median (Full Range). Unit: hours

Measure	Part 1: Tolbutamide Only n = 32	Part 1: Pexidartinib + Tolbutamide (Cycle 1, Day 1) n = 30	Part 1: Pexidartinib + Tolbutamide (Cycle 1, Day 11) n = 25
Value	2.90 (1 to 8.2)	2.94 (1.52 to 8.08)	3.17 (2.45 to 6.02)

Population analysed: Pharmacokinetic parameters were assessed in the Pharmacokinetic Evaluable population.

7 secondary outcomes are reported in the full results.

Adverse events

Time frame: Adverse events were collected after first dose up to 28 days after the last dose of study drug, up to 1 year.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Part 1: Drug-drug Interaction Phase	5 of 30 (16.7%)	24 of 30 (80%)	1 of 30
Part 2: Pexidartinib Only	5 of 25 (20%)	23 of 25 (92%)	0 of 25

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 14 May 2021.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 33289960Lewis JH, Gelderblom H, van de Sande M, Stacchiotti S, Healey JH, Tap WD, Wagner AJ, Pousa AL, Druta M, Lin CC, Baba HA, Choi Y, Wang Q, Shuster DE, Bauer S. Pexidartinib Long-Term Hepatic Safety Profile in Patients with Tenosynovial Giant Cell Tumors. Oncologist. 2021 May;26(5):e863-e873. doi: 10.1002/onco.13629. Epub 2020 Dec 24.
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/

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 chair

Daiichi Sankyo

11 sites in 4 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Tolbutamide, Midazolam and Pexidartinib in people with Drug Interaction Potential, run by Daiichi Sankyo at 11 sites in 4 countries.

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 14 inclusion and 8 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 14 May 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 11 sites in United States, Netherlands, New Zealand, Taiwan. 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?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 19 Mar 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Pharmacokinetic Analysis: Maximum Concentration (Cmax) for Midazolam (time frame: Baseline to 15 days post treatment). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03291288, which also lists 1 linked publication.

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 14 May 2021.