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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT03291288
Ethics application status
Date submitted
19/09/2017
Date registered
25/09/2017
Date last updated
22/04/2019

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

Active Comparator: Part 1 - Reference treatment - On Day 1 all participants will receive a single oral dose each of midazolam (2 mg) and tolbutamide (500 mg), followed by blood draws for pharmacokinetic (PK) analysis.

Experimental: Part 1 - Test Treatment 1 - On Day 3 all participants will receive a single oral dose each of midazolam (2 mg) and tolbutamide (500 mg) with morning dose of pexidartinib (400 mg) followed by blood draws for PK analysis.

Experimental: Part 1 - Test Treatment 2 - All participants will receive only the 400 mg pm dose of pexidartinib on Day 3 and continue twice-daily (BID) dosing of pexidartinib (400 mg for the am dose, and 400 mg for the pm dose) until Day 13.
On Day 13, all participants will receive a single oral dose of midazolam (2 mg) and tolbutamide (500 mg) with the morning dose of pexidartinib (400 mg) followed by blood draws for PK analysis.

Experimental: Part 2 - Pexidartinib only - On Day 13, all participants will receive a pm dose of 400 mg pexidartinib only.
All participants will continue to receive pexidartinib BID dosing in 28-day cycles at the 400 mg/day dose for up to one year. The dose of pexidartinib may be further modified within that year, depending upon tolerance as defined in the protocol.


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
Maximum concentration (Cmax) for midazolam - Plasma samples for midazolam will be 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)
Timepoint [1] 0 0
within 15 days
Primary outcome [2] 0 0
Cmax for tolbutamide - Plasma samples for tolbutamide will be 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)
Timepoint [2] 0 0
within 15 days
Primary outcome [3] 0 0
Time to maximum concentration (Tmax) for midazolam
Timepoint [3] 0 0
within 15 days
Primary outcome [4] 0 0
Tmax for tolbutamide
Timepoint [4] 0 0
within 15 days
Primary outcome [5] 0 0
Area under the curve to the last observable concentration (AUClast) for midazolam
Timepoint [5] 0 0
within 15 days
Primary outcome [6] 0 0
AUClast for tolbutamide
Timepoint [6] 0 0
within 15 days
Primary outcome [7] 0 0
Number of participants with an adverse event by the end of Part 2
Timepoint [7] 0 0
1 year
Secondary outcome [1] 0 0
Overall response rate (ORR) by the end of Part 2 - ORR is defined as the percentage of participants who achieve a confirmed complete response (CR) or partial response (PR) based on locally read tumor assessments according to Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1 or other applicable assessment of treatment response based upon the applicable tumor.
Timepoint [1] 0 0
1 year
Secondary outcome [2] 0 0
Cmax for pexidartinib and its metabolites - Plasma samples for pexidartinib and its metabolite will be 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.
Timepoint [2] 0 0
within 13 days
Secondary outcome [3] 0 0
Tmax for pexidartinib and its metabolite
Timepoint [3] 0 0
within 13 days
Secondary outcome [4] 0 0
AUClast for pexidartinib and its metabolite
Timepoint [4] 0 0
within 13 days
Secondary outcome [5] 0 0
Cmax for midazolam metabolite
Timepoint [5] 0 0
within 13 days
Secondary outcome [6] 0 0
Tmax for midazolam metabolite
Timepoint [6] 0 0
within 13 days
Secondary outcome [7] 0 0
AUClast for midazolam metabolite
Timepoint [7] 0 0
within 13 days
Secondary outcome [8] 0 0
Metabolite to parent ratio (MPR) for midazolam
Timepoint [8] 0 0
within 13 days

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
Gender
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
Non-randomised trial
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
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
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, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
Brief 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.

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.
Trial website
https://clinicaltrials.gov/show/NCT03291288
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Global Clinical Leader
Address 0 0
Daiichi Sankyo, Inc.
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

Summary results
Other publications