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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03291288




Registration number
NCT03291288
Ethics application status
Date submitted
19/09/2017
Date registered
25/09/2017

Titles & IDs
Public title
Effect of Pexidartinib on the Way the Body Processes CYP3A4 and CYP2C9 Substrates (Pharmacokinetics)
Scientific 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
Secondary ID [1] 0 0
PL3397-A-U126
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Drug Interaction Potential 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Tolbutamide
Treatment: Drugs - Midazolam
Treatment: Drugs - Pexidartinib

Experimental: Pexidartinib - 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.


Treatment: Drugs: Tolbutamide
Commercially available tolbutamide

Treatment: Drugs: Midazolam
Commercially available midazolam

Treatment: Drugs: Pexidartinib
Pexidartinib is formulated as opaque, white, 200-mg capsules
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Pharmacokinetic Analysis: Maximum Concentration (Cmax) for Midazolam
Timepoint [1] 0 0
Baseline to 15 days post treatment
Primary outcome [2] 0 0
Pharmacokinetic Analysis: Maximum Concentration (Cmax) for Tolbutamide
Timepoint [2] 0 0
Baseline to 15 days post treatment
Primary outcome [3] 0 0
Pharmacokinetic Analysis: Time to Maximum Concentration (Tmax) for Midazolam
Timepoint [3] 0 0
Baseline to 15 days post treatment
Primary outcome [4] 0 0
Pharmacokinetic Analysis: Time to Maximum Concentration (Tmax) for Tolbutamide
Timepoint [4] 0 0
Baseline to 15 days post treatment
Primary outcome [5] 0 0
Pharmacokinetic Analysis: Area Under the Curve to the Last Observable Concentration (AUClast) for Midazolam
Timepoint [5] 0 0
Baseline to 15 days post treatment
Primary outcome [6] 0 0
Pharmacokinetic Analysis: Area Under the Curve to the Last Observable Concentration (AUClast) for Tolbutamide
Timepoint [6] 0 0
Baseline to 15 days post treatment
Primary outcome [7] 0 0
Overall Summary of Treatment-emergent Adverse Events
Timepoint [7] 0 0
Baseline to 1 year post treatment
Secondary outcome [1] 0 0
Pharmacokinetic Analysis: Maximum Concentration (Cmax) for Pexidartinib and ZAAD-1006a Metabolite
Timepoint [1] 0 0
Baseline to 13 days post treatment
Secondary outcome [2] 0 0
Pharmacokinetic Analysis: Time to Maximum Concentration (Tmax) for Pexidartinib and ZAAD-1006a Metabolite
Timepoint [2] 0 0
Baseline to 13 days post treatment
Secondary outcome [3] 0 0
Pharmacokinetic Analysis: Area Under the Curve to the Last Observable Concentration (AUClast) for Pexidartinib and ZAAD-1006a Metabolite
Timepoint [3] 0 0
Baseline to 13 days post treatment
Secondary outcome [4] 0 0
Pharmacokinetic Analysis: Maximum Concentration (Cmax) for Midazolam Metabolite, 1-Hydroxy Midazolam
Timepoint [4] 0 0
Baseline to 13 days post treatment
Secondary outcome [5] 0 0
Pharmacokinetic Analysis: Time to Maximum Concentration (Tmax) for Midazolam Metabolite, 1-Hydroxy Midazolam
Timepoint [5] 0 0
Baseline to 13 days post treatment
Secondary outcome [6] 0 0
Pharmacokinetic Analysis: Area Under the Curve to the Last Observable Concentration (AUClast) for Midazolam Metabolite, 1-Hydroxy Midazolam
Timepoint [6] 0 0
Baseline to 13 days post treatment
Secondary outcome [7] 0 0
Pharmacokinetic Analysis: Metabolite to Parent Ratio (MPR) for Midazolam
Timepoint [7] 0 0
Baseline to 13 days post treatment

Eligibility
Key inclusion criteria
* Is the age of majority in country of residence
* Has a diagnosis of:

1. 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)
2. KIT-mutant tumor, including melanoma or gastrointestinal stromal tumor (GIST), for which there is no standard systemic therapy, or
3. 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
* Is a non-sterile male or female willing to use of one of the protocol-defined highly effective contraception methods:

1. intra-uterine device (nonhormonal or hormonal)
2. sexual abstinence (only if this is in line with the patient's current lifestyle)
3. 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* 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:

1. safety and well-being of the participant or offspring
2. safety of study staff
3. analysis of results

Study design
Purpose of the study
Treatment
Allocation to intervention
Not applicable
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
26/02/2018
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
16/04/2021
Sample size
Target
Accrual to date
Final
32
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Kansas
Country [4] 0 0
United States of America
State/province [4] 0 0
Massachusetts
Country [5] 0 0
United States of America
State/province [5] 0 0
Michigan
Country [6] 0 0
United States of America
State/province [6] 0 0
New York
Country [7] 0 0
United States of America
State/province [7] 0 0
Texas
Country [8] 0 0
Netherlands
State/province [8] 0 0
Leiden
Country [9] 0 0
New Zealand
State/province [9] 0 0
Christchurch
Country [10] 0 0
Taiwan
State/province [10] 0 0
Taipei

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Daiichi Sankyo
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Global Clinical Leader
Address 0 0
Daiichi Sankyo
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
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 document/s available: Study protocol, Statistical analysis plan (SAP), Clinical study report (CSR)
When will data be available (start and end dates)?
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.
Available to whom?
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.
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://vivli.org/ourmember/daiichi-sankyo/


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results are available at https://clinicaltrials.gov/study/NCT03291288