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Phase 3 Study of Pexidartinib for Pigmented Villonodular Synovitis (PVNS) or Giant Cell Tumor of the Tendon Sheath (GCT-TS) (ENLIVEN)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02371369
Recruitment Status : Completed
First Posted : February 25, 2015
Results First Posted : January 10, 2020
Last Update Posted : May 11, 2022
Sponsor:
Information provided by (Responsible Party):
Daiichi Sankyo

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Conditions Pigmented Villonodular Synovitis
Giant Cell Tumors of the Tendon Sheath
Tenosynovial Giant Cell Tumor
Interventions Drug: Pexidartinib
Drug: Placebo
Enrollment 120
Recruitment Details Part 1 was a double-blind, randomized, Pexidartinib or placebo in participants with symptomatic TGCT for whom surgical resection would be associated with potentially worsening functional limitation or severe morbidity. Part 2 is a long-term treatment phase in which all eligible participants received open-label Pexidartinib.
Pre-assignment Details Participants were screened for inclusion and exclusion criteria. Screening procedures were performed after consent was obtained and within the 42 days before the first dose of study drug, unless otherwise noted.
Arm/Group Title Pexidartinib Part 1, Then Pexidartinib Part 2 Placebo Part 1, Then Pexidartinib Part 2
Hide Arm/Group Description

Participants received Pexidartinib,1000 mg (5 capsules per day ) for 2 weeks, then 800 mg (4 capsules per day) for 22 weeks in Part 1 of study. Eligible participants from this group also received Pexidartinib in Part 2 at their prescribed dose.

Pexidartinib: Each capsule contains 200 mg of pexidartinib for oral administration.

Participants received treatment of matching placebo (5 capsules per day) for 2 weeks, then matching placebo (4 capsules per day) for 22 weeks in Part 1 of study. Eligible participants from this group also received Pexidartinib in Part 2 at their prescribed dose.

Placebo: Placebo capsule matching Pexidartinib capsule for oral administration. Pexidartinib: Each capsule contains 200 mg of Pexidartinib for oral administration (Part 2).
Period Title: Part 1
Started 61 59
Completed 52 48
Not Completed 9 11
Reason Not Completed
Physician Decision             0             3
Adverse Event             8             0
Withdrawal by Subject             1             6
Disease progression             0             1
Protocol Violation             0             1
Period Title: Part 2
Started 48 [1] 30 [2]
Completed 0 0
Not Completed 48 30
Reason Not Completed
Adverse Event             6             5
Withdrawal by Subject             16             6
Investigator decision             1             2
Death             0             1
Disease progression             1             0
Subject Noncompliance             1             0
Lost to Follow-up             1             1
Subject transitioned to commercial supply             6             4
Subject transitioned to another DS pexidartinib protocol             15             9
Surgical resection of tumor             1             1
Other             0             1
[1]
N=48; Only participants who were eligible to receive treatment in Part 2.
[2]
N=30; Only participants who were eligible to receive treatment in Part 2.
Arm/Group Title Pexidartinib Part 1, Then Pexidartinib Part 2 Placebo Part 1, Then Pexidartinib Part 2 Total
Hide Arm/Group Description

Participants received Pexidartinib,1000 mg (5 capsules per day ) for 2 weeks, then 800 mg (4 capsules per day) for 22 weeks in Part 1 of study. Eligible participants from this group also received Pexidartinib in Part 2 at their prescribed dose.

Pexidartinib: Each capsule contains 200 mg of pexidartinib for oral administration

Participants received treatment of matching placebo (5 capsules per day) for 2 weeks, then matching placebo (4 capsules per day) for 22 weeks in Part 1 of study. Eligible participants from this group also received Pexidartinib in Part 2 at their prescribed dose.

Placebo: Placebo capsule matching pexidartinib capsule for oral administration. Pexidartinib: Each capsule contains 200 mg of pexidartinib for oral administration (Part 2).

 Total of all reporting groups
Overall Number of Baseline Participants 61 59 120
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 61 participants 59 participants 120 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
57
  93.4%
56
  94.9%
113
  94.2%
>=65 years
4
   6.6%
3
   5.1%
7
   5.8%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 61 participants 59 participants 120 participants
44.6  (13.2) 44.3  (13.6) 44.5  (13.4)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 61 participants 59 participants 120 participants
Female
35
  57.4%
36
  61.0%
71
  59.2%
Male
26
  42.6%
23
  39.0%
49
  40.8%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 61 participants 59 participants 120 participants
American Indian or Alaska Native
2
   3.3%
0
   0.0%
2
   1.7%
Asian
1
   1.6%
2
   3.4%
3
   2.5%
Native Hawaiian or Other Pacific Islander
2
   3.3%
2
   3.4%
4
   3.3%
Black or African American
3
   4.9%
1
   1.7%
4
   3.3%
White
52
  85.2%
54
  91.5%
106
  88.3%
More than one race
1
   1.6%
0
   0.0%
1
   0.8%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
 Number Analyzed 61 participants 59 participants 120 participants
Canada 2 3 5
Netherlands 7 4 11
Hungary 2 1 3
United States 23 22 45
Denmark 1 2 3
Poland 2 0 2
Italy 8 9 17
United Kingdom 0 1 1
Australia 5 7 12
France 2 5 7
Germany 4 2 6
Spain 5 3 8
1.Primary Outcome
Title Percentage of Participants With Symptomatic, Locally Advanced Tenosynovial Giant Cell Tumor (TGCT) Achieving Complete or Partial Response to Pexidartinib Compared With That of Placebo Per Response Evaluation Criteria in Solid Tumors Version 1.1 at Week 25
Hide Description Complete response (CR) and partial responses (PR) were assessed based on centrally-read magnetic resonance imaging (MRI) scans and Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1). A CR was defined as disappearance of all tumors and a PR was defined as at least a 30% decrease in the sum of diameters of target tumors using the baseline sum diameters as the reference.
Time Frame Week 25
Hide Outcome Measure Data
Hide Analysis Population Description
Best overall response was assessed in the Intent-to-Treat (ITT) population.
Arm/Group Title Pexidartinib Part 1 Placebo Part 1
Hide Arm/Group Description:
Participants received treatment of Pexidartinib,1000 mg (5 capsules per day ) for 2 weeks, then 800 mg (4 capsules per day) for 22 weeks Pexidartinib: Each capsule contains 200 mg of Pexidartinib for oral administration.
Participants received treatment of matching placebo (5 capsules per day) for 2 weeks, then matching placebo (4 capsules per day) for 22 weeks Placebo: Placebo capsule matching Pexidartinib capsule for oral administration.
Overall Number of Participants Analyzed 61 59
Measure Type: Number
Unit of Measure: Percentage of participants
Complete Response (CR) 14.8 0
Partial Response (PR) 24.6 0
Response (CR or PR) 39.3 0
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pexidartinib Part 1, Placebo Part 1
Comments Treatment comparison between the pexidartinib and placebo groups at Week 25
Type of Statistical Test Other
Comments Treatment comparison analysis
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Fisher's Exact Test
Comments [Not Specified]
2.Secondary Outcome
Title Mean Change From Baseline For Range of Motion (ROM) Score in Participants Receiving Pexidartinib Compared With Those on Placebo Up to Week 25
Hide Description Range of motion (ROM) of the joint was assessed by a qualified, independent, and blinded or third-party assessors at the clinical site. Measurements were recorded in degrees. At baseline, the plane of movement with the smallest relative value (worst) was identified and this plane was used for evaluating the relative change of motion subsequently. Only the plane with the worst impaired ROM at baseline was selected for subsequent analyses.
Time Frame Baseline, Week 13, and Week 25
Hide Outcome Measure Data
Hide Analysis Population Description
Range of motion was assessed in the ITT population in participants where data were available.
Arm/Group Title Pexidartinib Part 1 Placebo Part 1
Hide Arm/Group Description:
Participants received treatment of Pexidartinib,1000 mg (5 capsules per day ) for 2 weeks, then 800 mg (4 capsules per day) for 22 weeks Pexidartinib: Each capsule contains 200 mg of Pexidartinib for oral administration.
Participants received treatment of matching placebo (5 capsules per day) for 2 weeks, then matching placebo (4 capsules per day) for 22 weeks Placebo: Placebo capsule matching Pexidartinib capsule for oral administration.
Overall Number of Participants Analyzed 61 59
Least Squares Mean (Standard Error)
Unit of Measure: degrees
Baseline Number Analyzed 61 participants 58 participants
62.5  (3.2) 62.9  (2.9)
Week 13 Number Analyzed 52 participants 53 participants
13.0  (2.3) 4.8  (2.6)
Week 25 Number Analyzed 45 participants 43 participants
15.1  (2.1) 6.2  (2.4)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pexidartinib Part 1, Placebo Part 1
Comments Treatment comparison between the pexidartinib and placebo groups at Week 25
Type of Statistical Test Other
Comments Treatment comparison analysis
Statistical Test of Hypothesis P-Value 0.0043
Comments [Not Specified]
Method Fisher's Exact Test
Comments [Not Specified]
3.Secondary Outcome
Title Percentage of Participants With Symptomatic, Locally Advanced Tenosynovial Giant Cell Tumor (TGCT) Achieving Complete or Partial Response Based on Tumor Volume Score (TVS) After Receiving Pexidartinib Compared With Those on Placebo at Week 25
Hide Description Complete response (CR) and partial response (PR) were assessed using tumor volume score (TVS). A CR was defined as disappearance of all tumors and a PR was defined as at least a 30% decrease in the sum of diameters of target tumors using the baseline sum diameters as the reference. TVS is a semi-quantitative MRI scoring system that describes tumor mass and is based on 10% increments of the estimated volume of the maximally distended synovial cavity or tendon sheath involved. A tumor that is equal in volume to that of a maximally distended synovial cavity or tendon sheath was scored 10; a score of 0 indicated no evidence of tumor.
Time Frame Week 25
Hide Outcome Measure Data
Hide Analysis Population Description
Best overall response was assessed in the ITT population.
Arm/Group Title Pexidartinib Part 1 Placebo Part 1
Hide Arm/Group Description:
Participants received treatment of Pexidartinib,1000 mg (5 capsules per day ) for 2 weeks, then 800 mg (4 capsules per day) for 22 weeks Pexidartinib: Each capsule contains 200 mg of Pexidartinib for oral administration.
Participants received treatment of matching placebo (5 capsules per day) for 2 weeks, then matching placebo (4 capsules per day) for 22 weeks Placebo: Placebo capsule matching Pexidartinib capsule for oral administration.
Overall Number of Participants Analyzed 61 59
Measure Type: Number
Unit of Measure: Percentage of participants
Complete Response (CR) 4.9 0
Partial Response (PR) 50.8 0
Response (CR or PR) 55.7 0
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pexidartinib Part 1, Placebo Part 1
Comments Treatment comparison between the pexidartinib and placebo groups at Week 25
Type of Statistical Test Other
Comments Treatment comparison analysis
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Fisher's Exact Test
Comments [Not Specified]
4.Secondary Outcome
Title Mean Change From Baseline in the Patient-reported Outcomes Measurement Information System (PROMIS) Physical Function Score in Participants Receiving Pexidartinib Compared With Those on Placebo Up to Week 25
Hide Description The Patient-reported Outcomes Measurement Information System (PROMIS) physical function scale was used to assess physical function of the upper and lower limbs. The scale ranged from 1 defined as 'unable to do' or 'cannot do' to 5 defined as 'without any difficulty' or 'not at all', where higher scores represent better outcomes.
Time Frame at Week 9 , Week 17, and Week 25
Hide Outcome Measure Data
Hide Analysis Population Description
Physical function was assessed in the ITT population in participants where data were available.
Arm/Group Title Pexidartinib Part 1 Placebo Part 1
Hide Arm/Group Description:
Participants received treatment of Pexidartinib,1000 mg (5 capsules per day ) for 2 weeks, then 800 mg (4 capsules per day) for 22 weeks Pexidartinib: Each capsule contains 200 mg of Pexidartinib for oral administration.
Participants received treatment of matching placebo (5 capsules per day) for 2 weeks, then matching placebo (4 capsules per day) for 22 weeks Placebo: Placebo capsule matching Pexidartinib capsule for oral administration.
Overall Number of Participants Analyzed 61 59
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
Week 9 Number Analyzed 38 participants 41 participants
2.8  (1.0) -0.4  (0.8)
Week 17 Number Analyzed 39 participants 40 participants
3.2  (1.1) 0.2  (1.0)
Week 25 Number Analyzed 38 participants 31 participants
4.1  (1.1) -0.9  (1.0)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pexidartinib Part 1, Placebo Part 1
Comments Treatment comparison between pexidartinib and placebo groups at Week 25
Type of Statistical Test Other
Comments Treatment comparison analysis
Statistical Test of Hypothesis P-Value 0.0019
Comments [Not Specified]
Method Mixed effects model for repeated measure
Comments [Not Specified]
5.Secondary Outcome
Title Mean Change From Baseline for Worst Stiffness Numeric Rating Scale Score (NRS) in Participants Receiving Pexidartinib Compared With Those on Placebo Up to Week 25
Hide Description The Worst Stiffness Numeric Rating Scale (NRS) was a 1-item, self-administered questionnaire assessing the "worst" stiffness in the last 24 hours. The NRS for this item ranged from 0 (no stiffness) to 10 (stiffness as bad as you can imagine).
Time Frame Baseline, Week 9, Week 17, and Week 25
Hide Outcome Measure Data
Hide Analysis Population Description
Worst stiffness was assessed in the ITT population.
Arm/Group Title Pexidartinib Part 1 Placebo Part 1
Hide Arm/Group Description:
Participants received treatment of Pexidartinib,1000 mg (5 capsules per day ) for 2 weeks, then 800 mg (4 capsules per day) for 22 weeks Pexidartinib: Each capsule contains 200 mg of Pexidartinib for oral administration.
Participants received treatment of matching placebo (5 capsules per day) for 2 weeks, then matching placebo (4 capsules per day) for 22 weeks Placebo: Placebo capsule matching Pexidartinib capsule for oral administration.
Overall Number of Participants Analyzed 61 59
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
Baseline Number Analyzed 59 participants 58 participants
5.6  (0.2) 5.9  (0.3)
Week 9 Number Analyzed 30 participants 38 participants
-1.5  (0.3) -0.5  (0.3)
Week 17 Number Analyzed 37 participants 30 participants
-2.4  (0.3) -0.4  (0.3)
Week 25 Number Analyzed 33 participants 35 participants
-2.5  (0.3) -0.3  (0.3)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pexidartinib Part 1, Placebo Part 1
Comments Treatment comparison between the pexidartinib and placebo groups at Week 25
Type of Statistical Test Other
Comments Treatment comparison analysis
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed effects model for repeated measure
Comments [Not Specified]
6.Secondary Outcome
Title Percentage of Participants Who Responded With a Decrease of at Least 30% in the Mean Brief Pain Inventory Worst Pain Numeric Rating Scale Score Among Participants Receiving Pexidartinib Compared With Those on Placebo at Week 25
Hide Description The Brief Pain Inventory (BPI) Worst Pain Numeric Rating Scale Score (NRS) was a 1-item, self-administered questionnaire assessing the "worst" pain in the last 24 hours. The NRS for this item ranged from 0 (no pain) to 10 (pain as bad as you can imagine).
Time Frame Week 25
Hide Outcome Measure Data
Hide Analysis Population Description
Worst pain was assessed in the ITT population.
Arm/Group Title Pexidartinib Part 1 Placebo Part 1
Hide Arm/Group Description:

Participants received treatment of Pexidartinib,1000 mg (5 capsules per day ) for 2 weeks, then 800 mg (4 capsules per day) for 22 weeks

Pexidartinib: Each capsule contains 200 mg of Pexidartinib for oral administration.

Participants received treatment of matching placebo (5 capsules per day) for 2 weeks, then matching placebo (4 capsules per day) for 22 weeks

Placebo: Placebo capsule matching Pexidartinib capsule for oral administration.
Overall Number of Participants Analyzed 61 59
Measure Type: Number
Unit of Measure: percentage of participants
31.1 15.3
7.Secondary Outcome
Title Number of Responders to Pexidartinib With and Without Disease Progression
Hide Description Duration of response (DOR) based on RECIST 1.1 is defined as the date of the first recorded response to the first date of documented disease progression. The overall number of responses and the number of participants with and without disease progression was assessed.
Time Frame By Week 96
Hide Outcome Measure Data
Hide Analysis Population Description
The overall number of responses and the number of participants with and without disease progression were assessed in the ITT population, specifically among the Pexidartinib Part 1, Pexidartinib Part 2; Pexidartinib Part 2 only, All Pexidartinib Treated participants, . Participants randomized to Placebo Part 1 only were not analyzed.
Arm/Group Title Pexidartinib Part 1 and Part 2 Placebo Part 1, Pexidartinib Part 2 All Pexidartinib Treated
Hide Arm/Group Description:

Part 1: Participants received treatment of pexidartinib,1000 mg (5 capsules per day ) for 2 weeks, then 800 mg (4 capsules per day) for 22 weeks

Part 2: Participants also received pexidartinib at their prescribed dose.

Pexidartinib: Each capsule contains 200 mg of pexidartinib for oral administration

Participants that received placebo in part 1 and received Pexidartinib in Part 2 at their prescribed dose.

Pexidartinib: Each capsule contains 200 mg of pexidartinib for oral administration
All participants who received Pexidartinib in Part 1 and Part 2 as well as those who only received Pexidartinib in Part 2.
Overall Number of Participants Analyzed 61 30 91
Measure Type: Number
Unit of Measure: participants
Number of responses 23 12 35
Week 12 (Day 84); Without disease progression 23 12 35
Week 12 (Day 84); With disease progression 0 0 0
Week 24 (Day 168); Without disease progression 23 12 35
Week 24 (Day 168); With disease progression 0 0 0
Week 48 (Day 336); Without disease progression 15 9 24
Week 48 (Day 336); With disease progression 1 0 1
Week 72 (Day 504); Without disease progression 9 3 12
Week 72 (Day 504); With disease progression 1 0 1
Week 96 (Day 672); Without disease progression 2 1 3
Week 96 (Day 672); With disease progression 1 0 1
8.Secondary Outcome
Title Number of Responders to Pexidartinib With and Without Disease Progression Based on Tumor Volume Score
Hide Description Tumor Volume Score (TVS) is a semi-quantitative MRI scoring system that describes tumor mass and is based on 10% increments of the estimated volume of the maximally distended synovial cavity or tendon sheath involved. A tumor that is equal in volume to that of a maximally distended synovial cavity or tendon sheath was scored 10; a score of 0 indicated no evidence of tumor. The overall number of responses and the number of participants with and without disease progression was assessed.
Time Frame By Week 120
Hide Outcome Measure Data
Hide Analysis Population Description
The overall number of responses and the number of participants with and without disease progression was assessed in the ITT population, specifically among the Pexidartinib Part 1, Pexidartinib Part 2; Pexidartinib Part 2 only; and All Pexidartinib Treated participants. Participants who received Placebo Part 1 only were not analyzed.
Arm/Group Title Pexidartinib in Part 1 and Part 2 Placebo Part 1, Pexidartinib Part 2 All Pexidartinib Treated
Hide Arm/Group Description:

Participants received treatment of Pexidartinib,1000 mg (5 capsules per day ) for 2 weeks, then 800 mg (4 capsules per day) for 22 weeks in Part 1 and also received Pexidartinib in Part 2 at their prescribed dose.

Pexidartinib: Each capsule contains 200 mg of pexidartinib for oral administration

Participants received treatment of matching placebo (5 capsules per day) for 2 weeks, then matching placebo (4 capsules per day) for 22 weeks in Part 1 and also received Pexidartinib in Part 2 at their prescribed dose.

Placebo: Placebo capsule matching Pexidartinib capsule for oral administration Pexidartinib: Each capsule contains 200 mg of Pexidartinib for oral administration.
All participants who received pexidartinib in Part 1 and Part 2 as well as those who received pexidartinib in Part 2 only.
Overall Number of Participants Analyzed 61 30 91
Measure Type: Number
Unit of Measure: participants
Number of responders 34 18 52
Week 12 (Day 84); Without disease progression 33 18 51
Week 12 (Day 84); With disease progression 0 0 0
Week 24 (Day 168); Without disease progression 32 18 50
Week 24 (Day 168); With disease progression 0 0 0
Week 48 (Day 336); Without disease progression 22 13 35
Week 48 (Day 336); With disease progression 3 1 4
Week 72 (Day 504); Without disease progression 13 3 16
Week 72 (Day 504); With disease progression 3 1 4
Week 96 (Day 672); Without disease progression 3 1 4
Week 96 (Day 672); With disease progression 3 1 4
Week 120 (Day 840); Without disease progression 1 0 1
Week 120 (Day 840); With disease progression 3 1 4
9.Secondary Outcome
Title Duration of Response (DOR) Based on RECIST 1.1
Hide Description Duration of response (DOR) based on RECIST 1.1 is defined from the date of the first recorded evidence of response to the first date of documented disease progression.
Time Frame Date of first documentation of objective response up to date of first documentation of progressive disease, assessed up to end of study (approximately 71 months)
Hide Outcome Measure Data
Hide Analysis Population Description
DOR was assessed in the ITT population, specifically among the Pexidartinib Part 1, Pexidartinib Part 2; Pexidartinib Part 2 only. Participants randomized to Placebo Part 1 only were not analyzed. DOR was based on numbers of responders only.
Arm/Group Title Pexidartinib Part 1 and Part 2 Placebo Part 1, Pexidartinib Part 2
Hide Arm/Group Description:

Part 1: Participants received treatment of pexidartinib,1000 mg (5 capsules per day ) for 2 weeks, then 800 mg (4 capsules per day) for 22 weeks Part 2: Participants also received pexidartinib at their prescribed dose.

Pexidartinib: Each capsule contains 200 mg of pexidartinib for oral administration

Participants that received placebo in part 1 and received Pexidartinib in Part 2 at their prescribed dose.

Pexidartinib: Each capsule contains 200 mg of pexidartinib for oral administration
Overall Number of Participants Analyzed 37 18
Median (95% Confidence Interval)
Unit of Measure: months
NA [1] 
(31.01 to NA)
NA [1] 
(39.0 to NA)
[1]
Median and upper limit 95% CI was not estimable due to insufficient number of events.
10.Secondary Outcome
Title Duration of Response (DOR) Based on Tumor Volume Score (TVS)
Hide Description Duration of response (DOR) based on TVS is defined from the date of the first recorded evidence of response to the first date of documented disease progression.
Time Frame Date of first documentation of objective response up to date of first documentation of progressive disease, assessed up to end of study (approximately 71 months)
Hide Outcome Measure Data
Hide Analysis Population Description
DOR was assessed in the ITT population, specifically among the Pexidartinib Part 1, Pexidartinib Part 2; Pexidartinib Part 2 only. Participants randomized to Placebo Part 1 only were not analyzed. DOR was based on numbers of responders only.
Arm/Group Title Pexidartinib Part 1 and Part 2 Placebo Part 1, Pexidartinib Part 2
Hide Arm/Group Description:

Part 1: Participants received treatment of pexidartinib,1000 mg (5 capsules per day ) for 2 weeks, then 800 mg (4 capsules per day) for 22 weeks Part 2: Participants also received pexidartinib at their prescribed dose.

Pexidartinib: Each capsule contains 200 mg of pexidartinib for oral administration

Participants that received placebo in part 1 and received Pexidartinib in Part 2 at their prescribed dose.

Pexidartinib: Each capsule contains 200 mg of pexidartinib for oral administration
Overall Number of Participants Analyzed 41 21
Median (95% Confidence Interval)
Unit of Measure: months
52.70 [1] 
(38.60 to NA)
NA [2] 
(NA to NA)
[1]
Upper limit 95% CI was not estimable due to insufficient number of events.
[2]
Median and 95% CIs was not estimable due to insufficient number of events.
11.Secondary Outcome
Title Percentage of Participants Reporting Frequent (≥10%) Treatment-Emergent Adverse Events by Preferred Term
Hide Description Treatment-emergent adverse events (TEAEs) were defined as adverse events that started or worsened after the first dose of treatment and within 28 days after the last dose. The National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0 was used to grade adverse events. Any Grade and Grade ≥3 (severe) TEAEs are reported. TEAEs were coded using MedDRA version 17.1.
Time Frame After the first dose of treatment up to 28 days after the last dose
Hide Outcome Measure Data
Hide Analysis Population Description
All safety events were assessed in the Safety Analysis Set.
Arm/Group Title Pexidartinib Part 1 Placebo Part 1 Pexidartinib Part 1 and Part 2 Placebo Part 1, Pexidartinib Part 2 All Pexidartinib Treated
Hide Arm/Group Description:
Participants received treatment of Pexidartinib,1000 mg (5 capsules per day ) for 2 weeks, then 800 mg (4 capsules per day) for 22 weeks Pexidartinib: Each capsule contains 200 mg of Pexidartinib for oral administration.
Participants received treatment of matching placebo (5 capsules per day) for 2 weeks, then matching placebo (4 capsules per day) for 22 weeks Placebo: Placebo capsule matching Pexidartinib capsule for oral administration.

Participants received treatment of Pexidartinib,1000 mg (5 capsules per day) for 2 weeks, then 800 mg (4 capsules per day) for 22 weeks and also received Pexidartinib in Part 2 at their prescribed dose.

Pexidartinib: Each capsule contains 200 mg of Pexidartinib for oral administration.

Participants received treatment of matching placebo (5 capsules per day) for 2 weeks, then matching placebo (4 capsules per day) for 22 weeks in Part 1 and also received Pexidartinib in Part 2 at their prescribed dose.

Placebo: Placebo capsule matching Pexidartinib capsule for oral administration Pexidartinib: Each capsule contains 200 mg of Pexidartinib for oral administration.
All participants who received Pexidartinib in Part 1 and Part 2 as well as those who only received Pexidartinib in Part 2.
Overall Number of Participants Analyzed 61 59 61 30 91
Measure Type: Number
Unit of Measure: Percentage of participants
Any Hair color changes 67.2 3.4 73.8 83.3 76.9
Grade ≥3 Hair color changes 0 0 0 0 0
Any Pruritis 9.8 3.4 16.4 20.0 17.6
Grade ≥3 Pruritis 0 0 1.6 0 1.1
Any Rash maculopapular 9.8 1.7 14.8 10.0 13.2
Grade ≥3 Rash maculopapular 0 0 1.6 0 1.1
Any Pruritis generalized 8.2 0 8.2 10.0 8.8
Grade ≥3 Pruritis generalized 0 0 0 0 0
Any Erythema 1.6 0 3.3 20.0 8.8
Grade ≥3 Erythema 0 0 0 0 0
Any Dry skin 3.3 3.4 6.6 10.0 7.7
Grade ≥3 Dry skin 0 0 0 3.3 1.1
Any Photosensitivity reaction 0 0 1.6 10.0 4.4
Grade ≥3 Photosensitivity reaction 0 0 0 0 0
Any Nausea 37.7 40.7 44.3 20.0 36.3
Grade ≥3 Nausea 0 0 0 0 0
Any Diarrhea 19.7 25.4 26.2 30.0 27.5
Grade ≥3 Diarrhea 0 0 0 0 0
Any Vomiting 19.7 5.1 23.0 6.7 17.6
Grade ≥3 Vomiting 1.6 0 1.6 0 1.1
Any Abdominal Pain 16.4 10.2 21.3 6.7 16.5
Grade ≥3 Abdominal Pain 0 0 0 0 0
Any Dry mouth 9.8 3.4 13.1 13.3 13.2
Grade ≥3 Dry mouth 0 0 0 0 0
Any Constipation 11.5 5.1 14.8 10.0 13.2
Grade ≥3 Constipation 0 0 0 0 0
Any Stomatitis 6.6 1.7 8.2 10.0 8.8
Grade ≥3 Stomatitis 0 0 0 0 0
Any Fatigue 54.1 35.6 55.7 26.7 46.2
Grade ≥3 Fatigue 0 0 0 0 0
Any Edema peripheral 13.1 3.4 16.4 20.0 17.6
Grade ≥3 Edema peripheral 0 0 0 0 0
Any Face edema 13.1 1.7 14.8 20.0 16.5
Grade ≥3 Face edema 0 0 1.6 3.3 2.2
Any Asthenia 9.8 5.1 11.5 20.0 14.3
Grade ≥3 Asthenia 0 0 0 0 0
Any Pyrexia 6.6 1.7 8.2 13.3 9.9
Grade ≥ Pyrexia 0 0 0 0 0
Any AST increased 39.3 0 44.3 16.7 35.2
Grade ≥3 AST increased 9.8 0 9.8 6.7 8.8
Any ALT increased 27.9 1.7 31.1 23.3 28.6
Grade ≥3 ALT increased 9.8 0 9.8 10.0 9.9
Any ALP increased 14.8 0 14.8 3.3 11.0
Grade ≥3 ALP increased 6.6 0 6.6 3.3 5.5
Any LDH increased 11.5 0 11.5 10.0 11.0
Grade ≥3 LDH increased 1.6 0 1.6 0 1.1
Any Weight increased 3.3 0 4.9 10.0 6.6
Grade ≥3 Weight increased 0 0 0 0 0
Any Dysgeusia 24.6 1.7 27.9 23.3 26.4
Grade ≥3 Dysgeusia 0 0 0 0 0
Any Headache 19.7 18.6 23.0 20.0 22.0
Grade ≥3 Headache 0 0 1.6 0 1.1
Any Dizziness 9.8 15.3 13.1 13.3 13.2
Grade ≥3 Dizziness 1.6 0 1.6 0 1.1
Any Paresthesia 1.6 1.7 8.2 10.0 8.8
Grade ≥3 Paresthesia 0 0 0 0 0
Any Memory impairment 0 1.7 1.6 10.0 4.4
Grade ≥3 Memory impairment 0 0 0 0 0
Any Arthralgia 23.0 25.4 27.9 30.0 28.6
Grade ≥3 Arthralgia 3.3 1.7 3.3 0 2.2
Any Pain in extremity 6.6 6.8 9.8 13.3 11.0
Grade ≥3 Pain in extremity 0 1.7 0 0 0
Any Periorbital edema 18.0 1.7 24.6 13.3 20.0
Grade ≥3 Periorbital edema 1.6 0 1.6 0 1.1
Any Eyelid edema 3.3 0 4.9 10.0 6.6
Grade ≥3 Eyelid edema 0 0 0 0 0
Any Decreased appetite 16.4 10.2 18.0 10.0 15.4
Grade ≥3 Decreased appetite 0 0 0 0 0
Any Hypertension 14.8 10.2 19.7 30.0 13.1
Grade ≥3 Hypertension 4.9 0 4.9 6.7 5.5
Any Upper respiratory tract infection 1.6 0 11.5 3.3 8.8
Grade ≥3 Upper respiratory tract infection 0 0 0 0 0
Any Cough 4.9 5.1 6.6 10.0 7.7
Grade ≥3 Cough 0 0 0 0 0
Any Dyspnea 1.6 0 4.9 10.0 7.7
Grade ≥3 Dyspnea 0 0 0 0 0
Any Insomnia 4.9 3.4 4.9 10.0 6.6
Grade ≥3 Insomnia 0 0 0 0 0
Any Rash 14.8 5.1 27.9 23.3 26.4
Grade ≥3 Rash 1.6 0 1.6 0 1.1
12.Other Pre-specified Outcome
Title Percentage of Participants With Symptomatic, Locally Advanced Tenosynovial Giant Cell Tumor (TGCT) Achieving Complete or Partial Response to Pexidartinib Compared With That of Placebo Per Response Evaluation Criteria in Solid Tumors Version 1.1 by Week 49
Hide Description Complete (CR) and partial responses (PR) were assessed based on centrally-read magnetic resonance imaging (MRI) scans and Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1). A CR was defined as disappearance of all tumors and a PR was defined as at least a 30% decrease in the sum of diameters of target tumors using the baseline sum diameters as the reference.
Time Frame By Week 49
Hide Outcome Measure Data
Hide Analysis Population Description
Best overall response was assessed in the ITT population.
Arm/Group Title Pexidartinib Part 1 and Part 2 Placebo Part 1, Pexidartinib Part 2 All Pexidartinib Treated
Hide Arm/Group Description:

Participants received treatment of Pexidartinib,1000 mg (5 capsules per day) for 2 weeks, then 800 mg (4 capsules per day) for 22 weeks and also received Pexidartinib in Part 2 at their prescribed dose.

Pexidartinib: Each capsule contains 200 mg of Pexidartinib for oral administration.

Participants received treatment of matching placebo (5 capsules per day) for 2 weeks, then matching placebo (4 capsules per day) for 22 weeks in Part 1 and also received Pexidartinib in Part 2 at their prescribed dose.

Placebo: Placebo capsule matching Pexidartinib capsule for oral administration Pexidartinib: Each capsule contains 200 mg of Pexidartinib for oral administration.
All participants who received Pexidartinib in Part 1 and Part 2 as well as those who only received Pexidartinib in Part 2.
Overall Number of Participants Analyzed 61 30 91
Measure Type: Number
Unit of Measure: Percentage of participants
Complete Response (CR) 24.6 23.3 24.2
Partial Response (PR) 29.5 30.0 29.7
Response (CR or PR) 54.1 53.3 53.8
13.Other Pre-specified Outcome
Title Mean Change From Baseline For Range of Motion (ROM) Score in Participants Receiving Pexidartinib Compared With Those on Placebo by Week 49
Hide Description Range of motion (ROM) of the joint was assessed by a qualified, independent, and blinded or third-party assessors at the clinical site. Measurements were recorded in degrees. At baseline, the plane of movement with the smallest relative value (worst) was identified and this plane was used for evaluating the relative change of motion subsequently. Only the plane with the worst impaired ROM at baseline was selected for subsequent analyses.
Time Frame By Week 49
Hide Outcome Measure Data
Hide Analysis Population Description
Range of Motion (ROM) was assessed in the ITT population.
Arm/Group Title Pexidartinib Part 1 and Part 2 Placebo Part 1, Pexidartinib Part 2 All Pexidartinib Treated
Hide Arm/Group Description:

Participants received treatment of Pexidartinib,1000 mg (5 capsules per day) for 2 weeks, then 800 mg (4 capsules per day) for 22 weeks and also received Pexidartinib in Part 2 at their prescribed dose.

Pexidartinib: Each capsule contains 200 mg of Pexidartinib for oral administration.

Participants received treatment of matching placebo (5 capsules per day) for 2 weeks, then matching placebo (4 capsules per day) for 22 weeks in Part 1 and also received Pexidartinib in Part 2 at their prescribed dose.

Placebo: Placebo capsule matching Pexidartinib capsule for oral administration Pexidartinib: Each capsule contains 200 mg of Pexidartinib for oral administration.
All participants who received Pexidartinib in Part 1 and Part 2 as well as those who only received Pexidartinib in Part 2.
Overall Number of Participants Analyzed 61 30 91
Mean (Standard Deviation)
Unit of Measure: degrees
Baseline Number Analyzed 61 participants 30 participants 91 participants
62.5  (24.8) 66.5  (22.9) 63.8  (24.2)
Week 25 Number Analyzed 45 participants 24 participants 69 participants
15.6  (14.9) 13.1  (12.9) 14.8  (14.2)
Week 49 Number Analyzed 33 participants 22 participants 55 participants
14.4  (19.5) 12.0  (13.4) 13.4  (17.3)
14.Other Pre-specified Outcome
Title Mean Change From Baseline in the Patient-reported Outcomes Measurement Information System (PROMIS) Physical Function Score in Participants Receiving Pexidartinib Compared With Those on Placebo by Week 49
Hide Description The Patient-reported Outcomes Measurement Information System (PROMIS) physical function scale was used to assess physical function of the upper and lower limbs. The scale ranged from 1 defined as 'unable to do' or 'cannot do' to 5 defined as 'without any difficulty' or 'not at all', where higher scores represent better outcomes.
Time Frame By Week 49
Hide Outcome Measure Data
Hide Analysis Population Description
Physical function was assessed in the ITT population.
Arm/Group Title Pexidartinib Part 1 and Part 2 Placebo Part 1, Pexidartinib Part 2 All Pexidartinib Treated
Hide Arm/Group Description:

Participants received treatment of Pexidartinib,1000 mg (5 capsules per day) for 2 weeks, then 800 mg (4 capsules per day) for 22 weeks and also received Pexidartinib in Part 2 at their prescribed dose.

Pexidartinib: Each capsule contains 200 mg of Pexidartinib for oral administration.

Participants received treatment of matching placebo (5 capsules per day) for 2 weeks, then matching placebo (4 capsules per day) for 22 weeks in Part 1 and also received Pexidartinib in Part 2 at their prescribed dose.

Placebo: Placebo capsule matching Pexidartinib capsule for oral administration Pexidartinib: Each capsule contains 200 mg of Pexidartinib for oral administration.
All participants who received Pexidartinib in Part 1 and Part 2 as well as those who only received Pexidartinib in Part 2.
Overall Number of Participants Analyzed 61 30 91
Mean (Standard Deviation)
Unit of Measure: units on a scale
Week 25 Number Analyzed 38 participants 16 participants 54 participants
3.6  (4.9) 4.9  (6.3) 4.0  (5.4)
Week 49 Number Analyzed 25 participants 14 participants 39 participants
4.7  (4.4) 7.6  (6.3) 5.8  (5.2)
15.Other Pre-specified Outcome
Title Mean Change From Baseline for Worst Stiffness Numeric Rating Scale Score (NRS) in Participants Receiving Pexidartinib Compared With Those on Placebo by Week 49
Hide Description The Worst Stiffness Numeric Rating Scale (NRS) was a 1-item, self-administered questionnaire assessing the "worst" stiffness in the last 24 hours. The NRS for this item ranged from 0 (no stiffness) to 10 (stiffness as bad as you can imagine).
Time Frame Baseline, Week 25, and Week 49
Hide Outcome Measure Data
Hide Analysis Population Description
Worst stiffness was assessed in the ITT population, specifically among the Pexidartinib Part 1, Pexidartinib Part 2; Placebo Part 1, Pexidartinib Part 2; and All Pexidartinib Treated participants. Participants who received Placebo Part 1 only or Pexidartinib Part 2 only were not analyzed.
Arm/Group Title Pexidartinib Part 1 and Part 2 Placebo Part 1, Pexidartinib Part 2 All Pexidartinib Treated
Hide Arm/Group Description:

Participants received treatment of Pexidartinib,1000 mg (5 capsules per day) for 2 weeks, then 800 mg (4 capsules per day) for 22 weeks and also received Pexidartinib in Part 2 at their prescribed dose.

Pexidartinib: Each capsule contains 200 mg of Pexidartinib for oral administration.

Participants received treatment of matching placebo (5 capsules per day) for 2 weeks, then matching placebo (4 capsules per day) for 22 weeks in Part 1 and also received Pexidartinib in Part 2 at their prescribed dose.

Placebo: Placebo capsule matching Pexidartinib capsule for oral administration Pexidartinib: Each capsule contains 200 mg of Pexidartinib for oral administration.
All participants who received Pexidartinib in Part 1 and Part 2 as well as those who only received Pexidartinib in Part 2.
Overall Number of Participants Analyzed 61 30 91
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline Number Analyzed 59 participants 26 participants 85 participants
5.6  (1.7) 5.7  (2.3) 5.6  (1.9)
Week 25 Number Analyzed 33 participants 18 participants 51 participants
-2.7  (2.2) -3.0  (3.1) -2.8  (2.5)
Week 49 Number Analyzed 22 participants 10 participants 32 participants
-3.5  (1.9) -2.2  (2.8) -3.1  (2.3)
16.Other Pre-specified Outcome
Title Mean Change From Baseline for Worst Pain Numeric Rating Scale Score (NRS) in Participants Receiving Pexidartinib Compared With Those on Placebo by Week 49
Hide Description The Brief Pain Inventory (BPI) Worst Pain NRS was a 1-item, self-administered questionnaire assessing the "worst" pain in the last 24 hours. The NRS for this item ranged from 0 (no pain) to 10 (pain as bad as you can imagine).
Time Frame By Week 49
Hide Outcome Measure Data
Hide Analysis Population Description
Worst pain was assessed in the ITT population, specifically among the Pexidartinib Part 1, Pexidartinib Part 2; Placebo Part 1, Pexidartinib Part 2; and All Pexidartinib Treated participants. Participants who received Placebo Part 1 only or Pexidartinib Part 2 only were not analyzed.
Arm/Group Title Pexidartinib Part 1 and Part 2 Placebo Part 1, Pexidartinib Part 2 All Pexidartinib Treated
Hide Arm/Group Description:

Participants received treatment of Pexidartinib,1000 mg (5 capsules per day) for 2 weeks, then 800 mg (4 capsules per day) for 22 weeks and also received Pexidartinib in Part 2 at their prescribed dose.

Pexidartinib: Each capsule contains 200 mg of Pexidartinib for oral administration.

Participants received treatment of matching placebo (5 capsules per day) for 2 weeks, then matching placebo (4 capsules per day) for 22 weeks in Part 1 and also received Pexidartinib in Part 2 at their prescribed dose.

Placebo: Placebo capsule matching Pexidartinib capsule for oral administration Pexidartinib: Each capsule contains 200 mg of Pexidartinib for oral administration.
All participants who received Pexidartinib in Part 1 and Part 2 as well as those who only received Pexidartinib in Part 2.
Overall Number of Participants Analyzed 61 30 91
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline Number Analyzed 59 participants 26 participants 85 participants
5.6  (1.6) 5.2  (2.5) 5.5  (1.9)
Week 25 Number Analyzed 33 participants 18 participants 51 participants
-2.7  (2.2) -2.6  (3.1) -2.7  (2.5)
Week 49 Number Analyzed 22 participants 10 participants 32 participants
-3.3  (1.7) -2.8  (3.4) -3.2  (2.3)
17.Other Pre-specified Outcome
Title Percentage of Participants With Symptomatic, Locally Advanced Tenosynovial Giant Cell Tumor (TGCT) Achieving Complete or Partial Response Based on Tumor Volume Score (TVS) After Receiving Pexidartinib Compared With Those on Placebo by Week 49
Hide Description Best overall response (CR or PR) was assessed using tumor volume score (TVS) in the ITT population. Tumor Volume Score is a semi-quantitative MRI scoring system that describes tumor mass and is based on 10% increments of the estimated volume of the maximally distended synovial cavity or tendon sheath involved. A tumor that is equal in volume to that of a maximally distended synovial cavity or tendon sheath was scored 10; a score of 0 indicated no evidence of tumor.
Time Frame By Week 49
Hide Outcome Measure Data
Hide Analysis Population Description
Best overall response on Tumor Volume Score was assessed in the ITT population, specifically among the Pexidartinib Part 1, Pexidartinib Part 2; Placebo Part 1, Pexidartinib Part 2; and All Pexidartinib Treated participants. Participants who received Placebo Part 1 only or Pexidartinib Part 2 only were not analyzed..
Arm/Group Title Pexidartinib Part 1 and Part 2 Placebo Part 1, Pexidartinib Part 2 All Pexidartinib Treated
Hide Arm/Group Description:

Participants received treatment of Pexidartinib,1000 mg (5 capsules per day) for 2 weeks, then 800 mg (4 capsules per day) for 22 weeks and also received Pexidartinib in Part 2 at their prescribed dose.

Pexidartinib: Each capsule contains 200 mg of Pexidartinib for oral administration.

Participants received treatment of matching placebo (5 capsules per day) for 2 weeks, then matching placebo (4 capsules per day) for 22 weeks in Part 1 and also received Pexidartinib in Part 2 at their prescribed dose.

Placebo: Placebo capsule matching Pexidartinib capsule for oral administration Pexidartinib: Each capsule contains 200 mg of Pexidartinib for oral administration.
All participants who received Pexidartinib in Part 1 and Part 2 as well as those who only received Pexidartinib in Part 2.
Overall Number of Participants Analyzed 61 30 91
Measure Type: Number
Unit of Measure: Percentage of participants
63.9 66.7 64.8
Time Frame Adverse events were monitored throughout the study from the time the participant signed the informed consent form to 28 days after the final treatment dose, up to 71 months.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Pexidartinib (Part 1) Placebo (Part 1) Pexidartinib (Parts 1 and 2) Placebo (Part 1), Crossover Pexidartinib (Part 2) All Pexidartinib Treated
Hide Arm/Group Description

Participants received blinded treatment of pexidartinib,1000 mg (5 capsules per day ) for 2 weeks, then 800 mg (4 capsules per day) for 22 weeks

Pexidartinib: Each capsule contains 200 mg of pexidartinib for oral administration

Participants received blinded treatment of matching placebo (5 capsules per day) for 2 weeks, then matching placebo (4 capsules per day) for 22 weeks

Placebo: Placebo capsule matching pexidartinib capsule for oral administration

Participants received pexidartinib in Part 1 and in Part 2 at their prescribed dose

Pexidartinib: Each capsule contains 200 mg of pexidartinib for oral administration

Participants received placebo in Part 1 and pexidartinib in Part 2 at their prescribed dose

Pexidartinib: Each capsule contains 200 mg of pexidartinib for oral administration

Placebo: Placebo capsule matching pexidartinib capsule for oral administration

 All participants who received pexidartinib in Part 1 and Part 2 (placebo crossed over to pexidartinib)
All-Cause Mortality
Pexidartinib (Part 1) Placebo (Part 1) Pexidartinib (Parts 1 and 2) Placebo (Part 1), Crossover Pexidartinib (Part 2) All Pexidartinib Treated
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/61 (0.00%)      0/59 (0.00%)      0/61 (0.00%)      1/30 (3.33%)      1/91 (1.10%)    
Hide Serious Adverse Events
Pexidartinib (Part 1) Placebo (Part 1) Pexidartinib (Parts 1 and 2) Placebo (Part 1), Crossover Pexidartinib (Part 2) All Pexidartinib Treated
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   8/61 (13.11%)      1/59 (1.69%)      12/61 (19.67%)      9/30 (30.00%)      21/91 (23.08%)    
Cardiac disorders           
Cardiac arrest † 1  0/61 (0.00%)  0/59 (0.00%)  0/61 (0.00%)  1/30 (3.33%)  1/91 (1.10%) 
Gastrointestinal disorders           
Abdominal pain † 1  0/61 (0.00%)  0/59 (0.00%)  1/61 (1.64%)  0/30 (0.00%)  1/91 (1.10%) 
General disorders           
Local swelling † 1  0/61 (0.00%)  0/59 (0.00%)  0/61 (0.00%)  1/30 (3.33%)  1/91 (1.10%) 
Non-cardiac chest pain † 1  0/61 (0.00%)  0/59 (0.00%)  0/61 (0.00%)  1/30 (3.33%)  1/91 (1.10%) 
Hepatobiliary disorders           
Hepatoxicity † 1  1/61 (1.64%)  0/59 (0.00%)  1/61 (1.64%)  0/30 (0.00%)  1/91 (1.10%) 
Liver disorder † 1  1/61 (1.64%)  0/59 (0.00%)  1/61 (1.64%)  0/30 (0.00%)  1/91 (1.10%) 
Hepatotoxicity † 1  1/61 (1.64%)  0/59 (0.00%)  1/61 (1.64%)  0/30 (0.00%)  1/91 (1.10%) 
Infections and infestations           
Hepatitis A † 1  1/61 (1.64%)  0/59 (0.00%)  1/61 (1.64%)  0/30 (0.00%)  1/91 (1.10%) 
Hepatitis E † 1  1/61 (1.64%)  0/59 (0.00%)  1/61 (1.64%)  0/30 (0.00%)  1/91 (1.10%) 
Lymphangitis † 1  0/61 (0.00%)  0/59 (0.00%)  0/61 (0.00%)  1/30 (3.33%)  1/91 (1.10%) 
Bronchopneumonia † 1  0/61 (0.00%)  0/59 (0.00%)  1/61 (1.64%)  0/30 (0.00%)  1/91 (1.10%) 
Paronychia † 1  0/61 (0.00%)  0/59 (0.00%)  1/61 (1.64%)  0/30 (0.00%)  1/91 (1.10%) 
Injury, poisoning and procedural complications           
Joint injury † 1  0/61 (0.00%)  0/59 (0.00%)  0/61 (0.00%)  1/30 (3.33%)  1/91 (1.10%) 
Post procedural complication † 1  0/61 (0.00%)  0/59 (0.00%)  1/61 (1.64%)  0/30 (0.00%)  1/91 (1.10%) 
Rib fracture † 1  0/61 (0.00%)  0/59 (0.00%)  0/61 (0.00%)  1/30 (3.33%)  1/91 (1.10%) 
Spinal fracture † 1  0/61 (0.00%)  0/59 (0.00%)  0/61 (0.00%)  1/30 (3.33%)  1/91 (1.10%) 
Wound dehiscence † 1  0/61 (0.00%)  0/59 (0.00%)  0/61 (0.00%)  1/30 (3.33%)  1/91 (1.10%) 
Investigations           
Transaminases increased † 1  1/61 (1.64%)  0/59 (0.00%)  1/61 (1.64%)  0/30 (0.00%)  1/91 (1.10%) 
Liver function test abnormal † 1  1/61 (1.64%)  0/59 (0.00%)  1/61 (1.64%)  0/30 (0.00%)  1/91 (1.10%) 
Hepatic enzyme abnormal † 1  1/61 (1.64%)  0/59 (0.00%)  1/61 (1.64%)  0/30 (0.00%)  1/91 (1.10%) 
Blood bilirubin increased † 1  1/61 (1.64%)  0/59 (0.00%)  1/61 (1.64%)  0/30 (0.00%)  1/91 (1.10%) 
Musculoskeletal and connective tissue disorders           
Neck pain † 1  0/61 (0.00%)  0/59 (0.00%)  0/61 (0.00%)  1/30 (3.33%)  1/91 (1.10%) 
Osteoarthritis † 1  0/61 (0.00%)  0/59 (0.00%)  1/61 (1.64%)  0/30 (0.00%)  1/91 (1.10%) 
Spondylolisthesis † 1  0/61 (0.00%)  0/59 (0.00%)  0/61 (0.00%)  1/30 (3.33%)  1/91 (1.10%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)           
Adenosquamous carcinoma of the cervix † 1  0/61 (0.00%)  0/59 (0.00%)  0/61 (0.00%)  1/30 (3.33%)  1/91 (1.10%) 
Rectal adenocarcinoma † 1  0/61 (0.00%)  0/59 (0.00%)  0/61 (0.00%)  1/30 (3.33%)  1/91 (1.10%) 
Endometrial cancer † 1  0/61 (0.00%)  1/59 (1.69%)  0/61 (0.00%)  0/30 (0.00%)  0/91 (0.00%) 
Squamous cell carcinoma of skin † 1  0/61 (0.00%)  0/59 (0.00%)  0/61 (0.00%)  1/30 (3.33%)  1/91 (1.10%) 
Lipoma † 1  0/61 (0.00%)  0/59 (0.00%)  1/61 (1.64%)  0/30 (0.00%)  1/91 (1.10%) 
Rectal cancer stage II † 1  0/61 (0.00%)  0/59 (0.00%)  0/61 (0.00%)  1/30 (3.33%)  1/91 (1.10%) 
Squamous cell carcinoma † 1  0/61 (0.00%)  0/59 (0.00%)  1/61 (1.64%)  0/30 (0.00%)  1/91 (1.10%) 
Nervous system disorders           
Migraine † 1  1/61 (1.64%)  0/59 (0.00%)  1/61 (1.64%)  0/30 (0.00%)  1/91 (1.10%) 
Pregnancy, puerperium and perinatal conditions           
Abortion spontaneous † 1  0/61 (0.00%)  0/59 (0.00%)  0/61 (0.00%)  1/30 (3.33%)  1/91 (1.10%) 
Respiratory, thoracic and mediastinal disorders           
Asthma † 1  0/61 (0.00%)  0/59 (0.00%)  1/61 (1.64%)  0/30 (0.00%)  1/91 (1.10%) 
Skin and subcutaneous tissue disorders           
Rash papular † 1  0/61 (0.00%)  0/59 (0.00%)  1/61 (1.64%)  0/30 (0.00%)  1/91 (1.10%) 
Rash † 1  1/61 (1.64%)  0/59 (0.00%)  1/61 (1.64%)  0/30 (0.00%)  1/91 (1.10%) 
1
Term from vocabulary, MedDRA (17.1)
†
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Pexidartinib (Part 1) Placebo (Part 1) Pexidartinib (Parts 1 and 2) Placebo (Part 1), Crossover Pexidartinib (Part 2) All Pexidartinib Treated
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   60/61 (98.36%)      55/59 (93.22%)      61/61 (100.00%)      30/30 (100.00%)      91/91 (100.00%)    
Blood and lymphatic system disorders           
Anaemia † 1  3/61 (4.92%)  3 1/59 (1.69%)  2 7/61 (11.48%)  12 1/30 (3.33%)  1 8/91 (8.79%)  13
Neutropenia † 1  3/61 (4.92%)  3 0/59 (0.00%)  0 4/61 (6.56%)  13 2/30 (6.67%)  3 6/91 (6.59%)  16
Leukopenia † 1  2/61 (3.28%)  2 0/59 (0.00%)  0 4/61 (6.56%)  7 2/30 (6.67%)  10 6/91 (6.59%)  17
Thrombocytopenia † 1  2/61 (3.28%)  2 0/59 (0.00%)  0 2/61 (3.28%)  2 2/30 (6.67%)  5 4/91 (4.40%)  7
Cardiac disorders           
Bradycardia † 1  0/61 (0.00%)  0 0/59 (0.00%)  0 0/61 (0.00%)  0 2/30 (6.67%)  3 2/91 (2.20%)  3
Palpitations † 1  2/61 (3.28%)  2 0/59 (0.00%)  0 4/61 (6.56%)  5 0/30 (0.00%)  0 4/91 (4.40%)  5
Tachycardia † 1  0/61 (0.00%)  0 0/59 (0.00%)  0 1/61 (1.64%)  3 2/30 (6.67%)  2 3/91 (3.30%)  5
Ear and labyrinth disorders           
Tinnitus † 1  1/61 (1.64%)  1 0/59 (0.00%)  0 2/61 (3.28%)  2 3/30 (10.00%)  6 5/91 (5.49%)  8
Vertigo † 1  1/61 (1.64%)  1 0/59 (0.00%)  0 4/61 (6.56%)  4 4/30 (13.33%)  4 8/91 (8.79%)  8
Eye disorders           
Periorbital oedema † 1  11/61 (18.03%)  13 1/59 (1.69%)  1 17/61 (27.87%)  23 5/30 (16.67%)  6 22/91 (24.18%)  29
Eye oedema † 1  6/61 (9.84%)  6 2/59 (3.39%)  2 6/61 (9.84%)  6 0/30 (0.00%)  0 6/91 (6.59%)  6
Eyelid oedema † 1  0/61 (0.00%)  0 0/59 (0.00%)  0 3/61 (4.92%)  5 3/30 (10.00%)  4 6/91 (6.59%)  9
Vision blurred † 1  0/61 (0.00%)  0 0/59 (0.00%)  0 5/61 (8.20%)  5 2/30 (6.67%)  3 7/91 (7.69%)  8
Lacrimation increased † 1  3/61 (4.92%)  3 0/59 (0.00%)  0 4/61 (6.56%)  4 1/30 (3.33%)  1 5/91 (5.49%)  5
Gastrointestinal disorders           
Nausea † 1  23/61 (37.70%)  40 24/59 (40.68%)  27 28/61 (45.90%)  66 7/30 (23.33%)  10 35/91 (38.46%)  76
Diarrhea † 1  13/61 (21.31%)  17 15/59 (25.42%)  18 19/61 (31.15%)  34 10/30 (33.33%)  23 29/91 (31.87%)  57
Vomiting † 1  12/61 (19.67%)  16 3/59 (5.08%)  3 16/61 (26.23%)  23 3/30 (10.00%)  3 19/91 (20.88%)  26
Abdominal pain † 1  10/61 (16.39%)  12 6/59 (10.17%)  8 13/61 (21.31%)  15 3/30 (10.00%)  3 16/91 (17.58%)  18
Constipation † 1  7/61 (11.48%)  8 3/59 (5.08%)  3 10/61 (16.39%)  13 3/30 (10.00%)  5 13/91 (14.29%)  18
Dry mouth † 1  6/61 (9.84%)  6 2/59 (3.39%)  2 8/61 (13.11%)  10 4/30 (13.33%)  4 12/91 (13.19%)  14
Stomatitis † 1  4/61 (6.56%)  4 1/59 (1.69%)  2 5/61 (8.20%)  5 3/30 (10.00%)  5 8/91 (8.79%)  10
Abdominal pain upper † 1  0/61 (0.00%)  0 4/59 (6.78%)  4 3/61 (4.92%)  3 2/30 (6.67%)  2 5/91 (5.49%)  5
General disorders           
Fatigue † 1  33/61 (54.10%)  49 21/59 (35.59%)  26 35/61 (57.38%)  57 8/30 (26.67%)  13 43/91 (47.25%)  70
Face oedema † 1  8/61 (13.11%)  8 1/59 (1.69%)  1 9/61 (14.75%)  11 6/30 (20.00%)  13 15/91 (16.48%)  24
Oedema peripheral † 1  8/61 (13.11%)  9 2/59 (3.39%)  2 15/61 (24.59%)  18 9/30 (30.00%)  11 24/91 (26.37%)  29
Asthenia † 1  6/61 (9.84%)  7 3/59 (5.08%)  5 9/61 (14.75%)  16 7/30 (23.33%)  18 16/91 (17.58%)  34
Pyrexia † 1  4/61 (6.56%)  4 1/59 (1.69%)  1 8/61 (13.11%)  8 6/30 (20.00%)  6 14/91 (15.38%)  14
Influenza like illness † 1  0/61 (0.00%)  0 0/59 (0.00%)  0 5/61 (8.20%)  6 1/30 (3.33%)  1 6/91 (6.59%)  7
Chest pain † 1  0/61 (0.00%)  0 0/59 (0.00%)  0 1/61 (1.64%)  1 2/30 (6.67%)  2 3/91 (3.30%)  3
Malaise † 1  0/61 (0.00%)  0 0/59 (0.00%)  0 1/61 (1.64%)  1 2/30 (6.67%)  3 3/91 (3.30%)  4
Peripheral swelling † 1  0/61 (0.00%)  0 1/59 (1.69%)  1 0/61 (0.00%)  0 2/30 (6.67%)  2 2/91 (2.20%)  2
Infections and infestations           
Nasopharyngitis † 1  4/61 (6.56%)  5 3/59 (5.08%)  3 5/61 (8.20%)  7 2/30 (6.67%)  2 7/91 (7.69%)  9
Upper respiratory tract infection † 1  0/61 (0.00%)  0 0/59 (0.00%)  0 8/61 (13.11%)  11 2/30 (6.67%)  2 10/91 (10.99%)  13
Sinusitis † 1  0/61 (0.00%)  0 0/59 (0.00%)  0 5/61 (8.20%)  9 1/30 (3.33%)  1 6/91 (6.59%)  10
Cellulitis † 1  0/61 (0.00%)  0 0/59 (0.00%)  0 1/61 (1.64%)  1 3/30 (10.00%)  3 4/91 (4.40%)  4
Cystitis † 1  0/61 (0.00%)  0 1/59 (1.69%)  1 0/61 (0.00%)  0 2/30 (6.67%)  3 2/91 (2.20%)  3
Influenza † 1  0/61 (0.00%)  0 2/59 (3.39%)  2 2/61 (3.28%)  3 4/30 (13.33%)  5 6/91 (6.59%)  8
Urinary tract infection † 1  0/61 (0.00%)  0 4/59 (6.78%)  5 2/61 (3.28%)  2 2/30 (6.67%)  6 4/91 (4.40%)  8
Herpes zoster † 1  0/61 (0.00%)  0 0/59 (0.00%)  0 0/61 (0.00%)  0 2/30 (6.67%)  2 2/91 (2.20%)  2
Investigations           
Aspartate aminotransferase increased † 1  24/61 (39.34%)  48 0/59 (0.00%)  0 28/61 (45.90%)  63 6/30 (20.00%)  11 34/91 (37.36%)  74
Alanine aminotransferase increased † 1  17/61 (27.87%)  44 1/59 (1.69%)  1 19/61 (31.15%)  53 7/30 (23.33%)  13 26/91 (28.57%)  66
Blood alkaline phosphatase increased † 1  9/61 (14.75%)  26 0/59 (0.00%)  0 9/61 (14.75%)  30 1/30 (3.33%)  1 10/91 (10.99%)  31
Blood lactate dehydrogenase increased † 1  7/61 (11.48%)  12 0/59 (0.00%)  0 7/61 (11.48%)  17 3/30 (10.00%)  6 10/91 (10.99%)  23
White blood cell count decreased † 1  0/61 (0.00%)  0 1/59 (1.69%)  1 6/61 (9.84%)  11 1/30 (3.33%)  2 7/91 (7.69%)  13
Weight increased † 1  0/61 (0.00%)  0 0/59 (0.00%)  0 3/61 (4.92%)  4 4/30 (13.33%)  4 7/91 (7.69%)  8
Blood bilirubin increased † 1  0/61 (0.00%)  0 1/59 (1.69%)  2 4/61 (6.56%)  8 1/30 (3.33%)  1 5/91 (5.49%)  9
Blood creatinine phosphokinase increased † 1  0/61 (0.00%)  0 0/59 (0.00%)  0 6/61 (9.84%)  16 4/30 (13.33%)  27 10/91 (10.99%)  43
Blood triglycerides increased † 1  1/61 (1.64%)  1 0/59 (0.00%)  0 1/61 (1.64%)  3 2/30 (6.67%)  2 3/91 (3.30%)  5
Metabolism and nutrition disorders           
Decreased appetite † 1  10/61 (16.39%)  13 6/59 (10.17%)  6 11/61 (18.03%)  15 3/30 (10.00%)  4 14/91 (15.38%)  19
Hypercholesterolemia † 1  5/61 (8.20%)  8 0/59 (0.00%)  0 7/61 (11.48%)  20 4/30 (13.33%)  7 11/91 (12.09%)  27
Fluid retention † 1  0/61 (0.00%)  0 0/59 (0.00%)  0 3/61 (4.92%)  6 2/30 (6.67%)  5 5/91 (5.49%)  11
Hyperglycemia † 1  0/61 (0.00%)  0 1/59 (1.69%)  1 1/61 (1.64%)  1 2/30 (6.67%)  2 3/91 (3.30%)  3
Hypophosphataemia † 1  3/61 (4.92%)  3 1/59 (1.69%)  1 3/61 (4.92%)  6 2/30 (6.67%)  3 5/91 (5.49%)  9
Hypertriglyceridaemia † 1  0/61 (0.00%)  0 4/59 (6.78%)  5 2/61 (3.28%)  4 2/30 (6.67%)  3 4/91 (4.40%)  7
Musculoskeletal and connective tissue disorders           
Arthralgia † 1  14/61 (22.95%)  17 15/59 (25.42%)  18 19/61 (31.15%)  29 15/30 (50.00%)  33 34/91 (37.36%)  62
Pain in extremity † 1  4/61 (6.56%)  6 3/59 (5.08%)  3 9/61 (14.75%)  11 6/30 (20.00%)  17 15/91 (16.48%)  28
Back pain † 1  0/61 (0.00%)  0 0/59 (0.00%)  0 6/61 (9.84%)  7 4/30 (13.33%)  8 10/91 (10.99%)  15
Myalgia † 1  1/61 (1.64%)  1 2/59 (3.39%)  2 2/61 (3.28%)  2 4/30 (13.33%)  7 6/91 (6.59%)  9
Muscle spasms † 1  2/61 (3.28%)  2 1/59 (1.69%)  1 4/61 (6.56%)  6 1/30 (3.33%)  1 5/91 (5.49%)  7
neck pain † 1  1/61 (1.64%)  1 1/59 (1.69%)  1 1/61 (1.64%)  1 4/30 (13.33%)  5 5/91 (5.49%)  6
Neoplasms benign, malignant and unspecified (incl cysts and polyps)           
Tumor pain † 1  4/61 (6.56%)  7 4/59 (6.78%)  6 4/61 (6.56%)  7 2/30 (6.67%)  2 6/91 (6.59%)  9
Nervous system disorders           
Dysgeusia † 1  15/61 (24.59%)  24 1/59 (1.69%)  1 18/61 (29.51%)  29 7/30 (23.33%)  10 25/91 (27.47%)  39
Headache † 1  11/61 (18.03%)  16 11/59 (18.64%)  15 15/61 (24.59%)  25 6/30 (20.00%)  8 21/91 (23.08%)  33
Dizziness † 1  6/61 (9.84%)  7 9/59 (15.25%)  12 10/61 (16.39%)  14 5/30 (16.67%)  5 15/91 (16.48%)  19
Paresthesia † 1  0/61 (0.00%)  0 1/59 (1.69%)  1 6/61 (9.84%)  7 3/30 (10.00%)  6 9/91 (9.89%)  13
Memory impairment † 1  0/61 (0.00%)  0 1/59 (1.69%)  1 2/61 (3.28%)  2 3/30 (10.00%)  7 5/91 (5.49%)  9
Neuropathy peripheral † 1  0/61 (0.00%)  0 0/59 (0.00%)  0 4/61 (6.56%)  5 1/30 (3.33%)  1 5/91 (5.49%)  6
Hypoaesthesia † 1  1/61 (1.64%)  1 2/59 (3.39%)  2 1/61 (1.64%)  1 3/30 (10.00%)  5 4/91 (4.40%)  6
Sciatica † 1  0/61 (0.00%)  0 1/59 (1.69%)  1 0/61 (0.00%)  0 2/30 (6.67%)  2 2/91 (2.20%)  2
Psychiatric disorders           
Insomnia † 1  0/61 (0.00%)  0 2/59 (3.39%)  2 4/61 (6.56%)  4 3/30 (10.00%)  4 7/91 (7.69%)  8
Anxiety † 1  0/61 (0.00%)  0 1/59 (1.69%)  1 1/61 (1.64%)  1 2/30 (6.67%)  2 3/91 (3.30%)  3
Renal and urinary disorders           
Haematuria † 1  0/61 (0.00%)  0 2/59 (3.39%)  2 0/61 (0.00%)  0 2/30 (6.67%)  2 2/91 (2.20%)  2
Respiratory, thoracic and mediastinal disorders           
Cough † 1  0/61 (0.00%)  0 3/59 (5.08%)  3 4/61 (6.56%)  6 5/30 (16.67%)  7 9/91 (9.89%)  13
Dyspnoea † 1  0/61 (0.00%)  0 0/59 (0.00%)  0 3/61 (4.92%)  4 4/30 (13.33%)  4 7/91 (7.69%)  8
Oropharyngeal pain † 1  0/61 (0.00%)  0 2/59 (3.39%)  3 4/61 (6.56%)  4 1/30 (3.33%)  1 5/91 (5.49%)  5
Skin and subcutaneous tissue disorders           
Hair color changes † 1  41/61 (67.21%)  46 2/59 (3.39%)  2 44/61 (72.13%)  53 25/30 (83.33%)  39 69/91 (75.82%)  92
Pruritis † 1  10/61 (16.39%)  11 2/59 (3.39%)  2 10/61 (16.39%)  10 9/30 (30.00%)  15 19/91 (20.88%)  25
Rash † 1  8/61 (13.11%)  9 3/59 (5.08%)  4 17/61 (27.87%)  28 8/30 (26.67%)  13 25/91 (27.47%)  41
Rash maculo-papular † 1  6/61 (9.84%)  8 1/59 (1.69%)  1 10/61 (16.39%)  17 4/30 (13.33%)  5 14/91 (15.38%)  22
Erythema † 1  0/61 (0.00%)  0 0/59 (0.00%)  0 2/61 (3.28%)  3 6/30 (20.00%)  10 8/91 (8.79%)  13
Pruritis generalized † 1  0/61 (0.00%)  0 0/59 (0.00%)  0 6/61 (9.84%)  7 5/30 (16.67%)  5 11/91 (12.09%)  12
Dry skin † 1  0/61 (0.00%)  0 2/59 (3.39%)  2 5/61 (8.20%)  6 3/30 (10.00%)  4 8/91 (8.79%)  10
Alopecia † 1  0/61 (0.00%)  0 0/59 (0.00%)  0 4/61 (6.56%)  4 2/30 (6.67%)  2 6/91 (6.59%)  6
Skin hypopigmentation † 1  0/61 (0.00%)  0 0/59 (0.00%)  0 5/61 (8.20%)  7 1/30 (3.33%)  1 6/91 (6.59%)  8
Photosensitivity reaction † 1  0/61 (0.00%)  0 0/59 (0.00%)  0 3/61 (4.92%)  3 3/30 (10.00%)  4 6/91 (6.59%)  7
Rash pruritic † 1  0/61 (0.00%)  0 1/59 (1.69%)  1 1/61 (1.64%)  1 2/30 (6.67%)  3 3/91 (3.30%)  4
Dermatitis † 1  0/61 (0.00%)  0 0/59 (0.00%)  0 0/61 (0.00%)  0 2/30 (6.67%)  3 2/91 (2.20%)  3
Vascular disorders           
Hypertension † 1  9/61 (14.75%)  15 6/59 (10.17%)  6 14/61 (22.95%)  24 12/30 (40.00%)  21 26/91 (28.57%)  45
Hypotension † 1  0/61 (0.00%)  0 0/59 (0.00%)  0 0/61 (0.00%)  0 2/30 (6.67%)  2 2/91 (2.20%)  2
1
Term from vocabulary, MedDRA (17.1)
†
Indicates events were collected by systematic assessment
Enrollment was stopped on 30 Sep 2016; no new participants received the study drug. After Part 1, those who wished to continue were un-blinded; those on placebo were discontinued.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Daiichi Sankyo
Organization: Contact for Clinical Trial Information
Phone: 1-908-992-6400
EMail: CTRinfo@dsi.com
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Daiichi Sankyo
ClinicalTrials.gov Identifier: NCT02371369    
Other Study ID Numbers: PLX108-10
2014-000148-14 ( EudraCT Number )
First Submitted: February 19, 2015
First Posted: February 25, 2015
Results First Submitted: August 26, 2019
Results First Posted: January 10, 2020
Last Update Posted: May 11, 2022