Trial Outcomes & Findings for A Study of Itacitinib in Combination With Low-Dose Ruxolitinib or Itacitinib Alone Following Ruxolitinib in Participants With Myelofibrosis (NCT NCT03144687)
NCT ID: NCT03144687
Last Updated: 2022-06-16
Results Overview
Spleen volume was measured using magnetic resonance imaging (MRI) or CT scan in participants who were not candidates for MRI or when MRI was not readily available. The MRIs or CTs were read in the central imaging laboratory. Spleen volume was obtained by outlining the circumference of the organ and determining the volume using the technique of least squares. The same method (MRI or CT) was used for a given participant unless a new contraindication to the use of MRI (eg, pacemaker insertion) occurred. A positive value indicates an increase in spleen volume and a negative value indicates a decrease in spleen volume.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
23 participants
Primary outcome timeframe
Baseline and Week 24
Results posted on
2022-06-16
Participant Flow
The study was conducted at 9 study centers in the United States, 1 study center in Austria, and 1 study center in the Netherlands.
A total of 23 participants with Myelofibrosis (MF) were enrolled in the study and received itacitinib + ruxolitinib (Cohort A) or itacitinib monotherapy (Cohort B).
Participant milestones
| Measure |
Cohort A
Participants with MF who were tolerating a ruxolitinib dose of less than 20 milligrams (mg) daily with no dose increase or no dose modification in the 8 weeks before screening visit received a combination of itacitinib at the dose of 200 mg, orally, once daily (QD) and ruxolitinib, orally, twice daily (BID) at their previous stable dose (must had been \< 20 mg daily). Participants continued study treatment until disease progression, unacceptable toxicity, withdrawal of consent, or other Protocol-specified criteria to stop treatment were met.
|
Cohort B
Participants with MF who progressed after initial reduction in spleen with ruxolitinib treatment, progressed or discontinued for hematologic toxicities received treatment with itacitinib alone at the dose of 600 mg QD. Participants continued study treatment until disease progression, unacceptable toxicity, withdrawal of consent, or other Protocol-specified criteria to stop treatment were met.
|
|---|---|---|
|
Overall Study
STARTED
|
13
|
10
|
|
Overall Study
COMPLETED
|
10
|
3
|
|
Overall Study
NOT COMPLETED
|
3
|
7
|
Reasons for withdrawal
| Measure |
Cohort A
Participants with MF who were tolerating a ruxolitinib dose of less than 20 milligrams (mg) daily with no dose increase or no dose modification in the 8 weeks before screening visit received a combination of itacitinib at the dose of 200 mg, orally, once daily (QD) and ruxolitinib, orally, twice daily (BID) at their previous stable dose (must had been \< 20 mg daily). Participants continued study treatment until disease progression, unacceptable toxicity, withdrawal of consent, or other Protocol-specified criteria to stop treatment were met.
|
Cohort B
Participants with MF who progressed after initial reduction in spleen with ruxolitinib treatment, progressed or discontinued for hematologic toxicities received treatment with itacitinib alone at the dose of 600 mg QD. Participants continued study treatment until disease progression, unacceptable toxicity, withdrawal of consent, or other Protocol-specified criteria to stop treatment were met.
|
|---|---|---|
|
Overall Study
Death
|
0
|
2
|
|
Overall Study
Lost to Follow-up
|
0
|
1
|
|
Overall Study
Physician Decision
|
0
|
1
|
|
Overall Study
Withdrawal by Subject
|
1
|
3
|
|
Overall Study
Not Reported
|
2
|
0
|
Baseline Characteristics
A Study of Itacitinib in Combination With Low-Dose Ruxolitinib or Itacitinib Alone Following Ruxolitinib in Participants With Myelofibrosis
Baseline characteristics by cohort
| Measure |
Cohort A
n=13 Participants
Participants with MF who were tolerating a ruxolitinib dose of less than 20 milligrams (mg) daily with no dose increase or no dose modification in the 8 weeks before screening visit received a combination of itacitinib at the dose of 200 mg, orally, once daily (QD) and ruxolitinib, orally, twice daily (BID) at their previous stable dose (must had been \< 20 mg daily). Participants continued study treatment until disease progression, unacceptable toxicity, withdrawal of consent, or other Protocol-specified criteria to stop treatment were met.
|
Cohort B
n=10 Participants
Participants with MF who progressed after initial reduction in spleen with ruxolitinib treatment, progressed or discontinued for hematologic toxicities received treatment with itacitinib alone at the dose of 600 mg QD. Participants continued study treatment until disease progression, unacceptable toxicity, withdrawal of consent, or other Protocol-specified criteria to stop treatment were met.
|
Total
n=23 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
69.8 years
STANDARD_DEVIATION 6.20 • n=5 Participants
|
72.0 years
STANDARD_DEVIATION 7.33 • n=7 Participants
|
70.8 years
STANDARD_DEVIATION 6.65 • n=5 Participants
|
|
Sex: Female, Male
Female
|
6 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
13 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
7 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
10 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
12 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
21 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White/Caucasian
|
13 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
21 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Other
|
0 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline and Week 24Population: Full Analysis Set included all enrolled participants who received at least 1 dose of itacitinib. Here, Overall Number of participants analyzed ("N") signifies participants who were evaluable for this outcome measure.
Spleen volume was measured using magnetic resonance imaging (MRI) or CT scan in participants who were not candidates for MRI or when MRI was not readily available. The MRIs or CTs were read in the central imaging laboratory. Spleen volume was obtained by outlining the circumference of the organ and determining the volume using the technique of least squares. The same method (MRI or CT) was used for a given participant unless a new contraindication to the use of MRI (eg, pacemaker insertion) occurred. A positive value indicates an increase in spleen volume and a negative value indicates a decrease in spleen volume.
Outcome measures
| Measure |
Cohort A
n=9 Participants
Participants with MF who were tolerating a ruxolitinib dose of less than 20 milligrams (mg) daily with no dose increase or no dose modification in the 8 weeks before screening visit received a combination of itacitinib at the dose of 200 mg, orally, once daily (QD) and ruxolitinib, orally, twice daily (BID) at their previous stable dose (must had been \< 20 mg daily). Participants continued study treatment until disease progression, unacceptable toxicity, withdrawal of consent, or other Protocol-specified criteria to stop treatment were met.
|
Cohort B
n=5 Participants
Participants with MF who progressed after initial reduction in spleen with ruxolitinib treatment, progressed or discontinued for hematologic toxicities received treatment with itacitinib alone at the dose of 600 mg QD. Participants continued study treatment until disease progression, unacceptable toxicity, withdrawal of consent, or other Protocol-specified criteria to stop treatment were met.
|
|---|---|---|
|
Change in Spleen Volume at Week 24 Compared to Baseline
|
88.7 cubic centimeter (cm^3)
Standard Deviation 563.5
|
-207 cubic centimeter (cm^3)
Standard Deviation 571.3
|
PRIMARY outcome
Timeframe: Baseline and Week 24Population: Full Analysis Set included all enrolled participants who received at least 1 dose of itacitinib. Here, "N" signifies participants who were evaluable for this outcome measure.
Spleen volume was measured using MRI or CT scan in participants who were not candidates for MRI or when MRI was not readily available. The MRIs or CTs were read in the central imaging laboratory. Spleen volume was obtained by outlining the circumference of the organ and determining the volume using the technique of least squares. The same method (MRI or CT) was used for a given participant unless a new contraindication to the use of MRI (eg, pacemaker insertion) occurred. A positive value indicates an increase in spleen volume and a negative value indicates a decrease in spleen volume.
Outcome measures
| Measure |
Cohort A
n=9 Participants
Participants with MF who were tolerating a ruxolitinib dose of less than 20 milligrams (mg) daily with no dose increase or no dose modification in the 8 weeks before screening visit received a combination of itacitinib at the dose of 200 mg, orally, once daily (QD) and ruxolitinib, orally, twice daily (BID) at their previous stable dose (must had been \< 20 mg daily). Participants continued study treatment until disease progression, unacceptable toxicity, withdrawal of consent, or other Protocol-specified criteria to stop treatment were met.
|
Cohort B
n=5 Participants
Participants with MF who progressed after initial reduction in spleen with ruxolitinib treatment, progressed or discontinued for hematologic toxicities received treatment with itacitinib alone at the dose of 600 mg QD. Participants continued study treatment until disease progression, unacceptable toxicity, withdrawal of consent, or other Protocol-specified criteria to stop treatment were met.
|
|---|---|---|
|
Percentage Change in Spleen Volume at Week 24 Compared to Baseline
|
6.9 percentage change
Standard Deviation 27.49
|
-3.0 percentage change
Standard Deviation 34.67
|
SECONDARY outcome
Timeframe: up to approximately 40 months (3.3 years)Population: Safety Population included all enrolled participants who received at least 1 dose of itacitinib.
An AE is defined as any untoward medical occurrence associated with the use of a drug in humans, whether considered drug related, that occurs after a participant provides informed consent. A TEAE is any AE either reported for the first time or worsening of a pre-existing event after first dose of study drug. An SAE is an AE resulting in: death; initial/prolonged inpatient hospitalization; life-threatening; persistent or significant disability/incapacity; congenital anomaly.
Outcome measures
| Measure |
Cohort A
n=13 Participants
Participants with MF who were tolerating a ruxolitinib dose of less than 20 milligrams (mg) daily with no dose increase or no dose modification in the 8 weeks before screening visit received a combination of itacitinib at the dose of 200 mg, orally, once daily (QD) and ruxolitinib, orally, twice daily (BID) at their previous stable dose (must had been \< 20 mg daily). Participants continued study treatment until disease progression, unacceptable toxicity, withdrawal of consent, or other Protocol-specified criteria to stop treatment were met.
|
Cohort B
n=10 Participants
Participants with MF who progressed after initial reduction in spleen with ruxolitinib treatment, progressed or discontinued for hematologic toxicities received treatment with itacitinib alone at the dose of 600 mg QD. Participants continued study treatment until disease progression, unacceptable toxicity, withdrawal of consent, or other Protocol-specified criteria to stop treatment were met.
|
|---|---|---|
|
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
TEAE
|
13 Participants
|
10 Participants
|
|
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
SAE
|
3 Participants
|
5 Participants
|
SECONDARY outcome
Timeframe: up to approximately 40 months (3.3 years)Population: Safety Population included all enrolled participants who received at least 1 dose of itacitinib.
Laboratory investigation included hematology, clinical chemistry, coagulation and urinalysis. Clinical significance was determined by the investigator. The number of participants with clinically significant changes from baseline in laboratory parameters were reported.
Outcome measures
| Measure |
Cohort A
n=13 Participants
Participants with MF who were tolerating a ruxolitinib dose of less than 20 milligrams (mg) daily with no dose increase or no dose modification in the 8 weeks before screening visit received a combination of itacitinib at the dose of 200 mg, orally, once daily (QD) and ruxolitinib, orally, twice daily (BID) at their previous stable dose (must had been \< 20 mg daily). Participants continued study treatment until disease progression, unacceptable toxicity, withdrawal of consent, or other Protocol-specified criteria to stop treatment were met.
|
Cohort B
n=10 Participants
Participants with MF who progressed after initial reduction in spleen with ruxolitinib treatment, progressed or discontinued for hematologic toxicities received treatment with itacitinib alone at the dose of 600 mg QD. Participants continued study treatment until disease progression, unacceptable toxicity, withdrawal of consent, or other Protocol-specified criteria to stop treatment were met.
|
|---|---|---|
|
Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameters
Hemoglobin: High Direction
|
0 Participants
|
0 Participants
|
|
Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameters
Hemoglobin: Low Direction
|
4 Participants
|
4 Participants
|
|
Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameters
Leukocytes: High Direction
|
0 Participants
|
1 Participants
|
|
Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameters
Leukocytes: Low Direction
|
0 Participants
|
0 Participants
|
|
Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameters
Lymphocytes: High Direction
|
0 Participants
|
0 Participants
|
|
Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameters
Lymphocytes: Low Direction
|
3 Participants
|
1 Participants
|
|
Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameters
Neutrophils
|
0 Participants
|
1 Participants
|
|
Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameters
Platelets
|
3 Participants
|
4 Participants
|
|
Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameters
Alanine Aminotransferase
|
0 Participants
|
0 Participants
|
|
Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameters
Albumin
|
0 Participants
|
0 Participants
|
|
Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameters
Alkaline Phosphatase
|
0 Participants
|
0 Participants
|
|
Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameters
Aspartate Aminotransferase
|
0 Participants
|
0 Participants
|
|
Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameters
Bilirubin
|
1 Participants
|
0 Participants
|
|
Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameters
Calcium: High Direction
|
0 Participants
|
0 Participants
|
|
Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameters
Calcium: Low Direction
|
0 Participants
|
0 Participants
|
|
Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameters
Cholesterol
|
0 Participants
|
0 Participants
|
|
Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameters
Creatinine
|
0 Participants
|
0 Participants
|
|
Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameters
Glucose: High Direction
|
0 Participants
|
0 Participants
|
|
Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameters
Glucose: Low Direction
|
0 Participants
|
0 Participants
|
|
Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameters
Phosphate
|
0 Participants
|
1 Participants
|
|
Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameters
Potassium: High Direction
|
0 Participants
|
0 Participants
|
|
Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameters
Potassium: Low Direction
|
0 Participants
|
0 Participants
|
|
Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameters
Sodium: High Direction
|
0 Participants
|
0 Participants
|
|
Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameters
Sodium: Low Direction
|
0 Participants
|
0 Participants
|
|
Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameters
Triglycerides
|
0 Participants
|
1 Participants
|
|
Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameters
Urate
|
1 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: up to approximately 40 months (3.3 years)Population: Safety Population included all enrolled participants who received at least 1 dose of itacitinib.
Vital signs included body temperature, systolic and diastolic blood pressure, pulse rate, respiratory rate, weight and height. Clinical significance was determined by the investigator. The number of participants with clinically significant changes from baseline in vital signs were reported.
Outcome measures
| Measure |
Cohort A
n=13 Participants
Participants with MF who were tolerating a ruxolitinib dose of less than 20 milligrams (mg) daily with no dose increase or no dose modification in the 8 weeks before screening visit received a combination of itacitinib at the dose of 200 mg, orally, once daily (QD) and ruxolitinib, orally, twice daily (BID) at their previous stable dose (must had been \< 20 mg daily). Participants continued study treatment until disease progression, unacceptable toxicity, withdrawal of consent, or other Protocol-specified criteria to stop treatment were met.
|
Cohort B
n=10 Participants
Participants with MF who progressed after initial reduction in spleen with ruxolitinib treatment, progressed or discontinued for hematologic toxicities received treatment with itacitinib alone at the dose of 600 mg QD. Participants continued study treatment until disease progression, unacceptable toxicity, withdrawal of consent, or other Protocol-specified criteria to stop treatment were met.
|
|---|---|---|
|
Number of Participants With Clinically Significant Changes From Baseline in Vital Signs
Systolic blood pressure, Week 12
|
1 Participants
|
1 Participants
|
|
Number of Participants With Clinically Significant Changes From Baseline in Vital Signs
Systolic blood pressure, Week 24
|
0 Participants
|
1 Participants
|
|
Number of Participants With Clinically Significant Changes From Baseline in Vital Signs
Systolic blood pressure, Week 36
|
0 Participants
|
1 Participants
|
|
Number of Participants With Clinically Significant Changes From Baseline in Vital Signs
Systolic blood pressure, End of Treatment
|
1 Participants
|
0 Participants
|
|
Number of Participants With Clinically Significant Changes From Baseline in Vital Signs
Diastolic blood pressure, Week 12
|
0 Participants
|
1 Participants
|
|
Number of Participants With Clinically Significant Changes From Baseline in Vital Signs
Pulse, Week 84
|
1 Participants
|
0 Participants
|
|
Number of Participants With Clinically Significant Changes From Baseline in Vital Signs
Pulse, Follow-up
|
1 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Baseline through Week 12Population: Full Analysis Set included all enrolled participants who received at least 1 dose of itacitinib. Here, "N" signifies participants who were evaluable for this outcome measure.
Spleen volume was measured using magnetic resonance imaging (or CT scan in applicable participants). MRI of the upper and lower abdomen and pelvis was performed, to assess spleen volumes. MRI was performed with a body coil. The MRIs were read in the central imaging laboratory. Spleen volume was obtained by outlining the circumference of the organ and determining the volume using the technique of least squares. MRI was the preferred method for obtaining spleen volume data. The CT scans were processed by the same central laboratory used for MRIs. The same method (MRI or CT) was used for a given participant unless a new contraindication to the use of MRI (eg, pacemaker insertion) occurred.
Outcome measures
| Measure |
Cohort A
n=11 Participants
Participants with MF who were tolerating a ruxolitinib dose of less than 20 milligrams (mg) daily with no dose increase or no dose modification in the 8 weeks before screening visit received a combination of itacitinib at the dose of 200 mg, orally, once daily (QD) and ruxolitinib, orally, twice daily (BID) at their previous stable dose (must had been \< 20 mg daily). Participants continued study treatment until disease progression, unacceptable toxicity, withdrawal of consent, or other Protocol-specified criteria to stop treatment were met.
|
Cohort B
n=8 Participants
Participants with MF who progressed after initial reduction in spleen with ruxolitinib treatment, progressed or discontinued for hematologic toxicities received treatment with itacitinib alone at the dose of 600 mg QD. Participants continued study treatment until disease progression, unacceptable toxicity, withdrawal of consent, or other Protocol-specified criteria to stop treatment were met.
|
|---|---|---|
|
Change From Baseline Through Week 12 in SVR as Measured by MRI (or CT Scan in Applicable Participants)
|
-29.2 cm^3
Standard Deviation 349.3
|
-608 cm^3
Standard Deviation 669.6
|
SECONDARY outcome
Timeframe: Baseline through Week 12Population: Full Analysis Set included all enrolled participants who received at least 1 dose of itacitinib. Here, "N" signifies participants who were evaluable for this outcome measure.
Spleen volume was measured using magnetic resonance imaging (or CT scan in applicable participants). MRI of the upper and lower abdomen and pelvis was performed, to assess spleen volumes. MRI was performed with a body coil. The MRIs were read in the central imaging laboratory. Spleen volume was obtained by outlining the circumference of the organ and determining the volume using the technique of least squares. MRI was the preferred method for obtaining spleen volume data. The CT scans were processed by the same central laboratory used for MRIs. The same method (MRI or CT) was used for a given participant unless a new contraindication to the use of MRI (eg, pacemaker insertion) occurred.
Outcome measures
| Measure |
Cohort A
n=11 Participants
Participants with MF who were tolerating a ruxolitinib dose of less than 20 milligrams (mg) daily with no dose increase or no dose modification in the 8 weeks before screening visit received a combination of itacitinib at the dose of 200 mg, orally, once daily (QD) and ruxolitinib, orally, twice daily (BID) at their previous stable dose (must had been \< 20 mg daily). Participants continued study treatment until disease progression, unacceptable toxicity, withdrawal of consent, or other Protocol-specified criteria to stop treatment were met.
|
Cohort B
n=8 Participants
Participants with MF who progressed after initial reduction in spleen with ruxolitinib treatment, progressed or discontinued for hematologic toxicities received treatment with itacitinib alone at the dose of 600 mg QD. Participants continued study treatment until disease progression, unacceptable toxicity, withdrawal of consent, or other Protocol-specified criteria to stop treatment were met.
|
|---|---|---|
|
Percentage Change From Baseline Through Week 12 in SVR as Measured by MRI (or CT Scan in Applicable Participants)
|
-1.6 percentage change
Standard Deviation 14.69
|
-24.6 percentage change
Standard Deviation 21.72
|
SECONDARY outcome
Timeframe: Baseline through Weeks 12 and 24Population: Full Analysis Set included all enrolled participants who received at least 1 dose of itacitinib. Here, "N "signifies number of participants analyzed for this outcome measure and "n" signifies number of participants with data available at a particular time point.
Measurement of spleen length below the left costal margin was measured by palpation. Spleen size was determined at every physical examination with the participant in the recumbent (not left decubitus) position. The edge of the spleen was determined by palpation, and measured in centimeters, using a soft ruler, from the costal margin to the point of greatest splenic protrusion. The measurements should be noted and the site at which it was determined listed (eg, anterior axillary line, midclavicular line, and/or subxiphoid). A positive value indicates an increase in spleen volume and a negative value indicates a decrease in spleen volume.
Outcome measures
| Measure |
Cohort A
n=12 Participants
Participants with MF who were tolerating a ruxolitinib dose of less than 20 milligrams (mg) daily with no dose increase or no dose modification in the 8 weeks before screening visit received a combination of itacitinib at the dose of 200 mg, orally, once daily (QD) and ruxolitinib, orally, twice daily (BID) at their previous stable dose (must had been \< 20 mg daily). Participants continued study treatment until disease progression, unacceptable toxicity, withdrawal of consent, or other Protocol-specified criteria to stop treatment were met.
|
Cohort B
n=7 Participants
Participants with MF who progressed after initial reduction in spleen with ruxolitinib treatment, progressed or discontinued for hematologic toxicities received treatment with itacitinib alone at the dose of 600 mg QD. Participants continued study treatment until disease progression, unacceptable toxicity, withdrawal of consent, or other Protocol-specified criteria to stop treatment were met.
|
|---|---|---|
|
Change From Baseline Through Week 12 and Week 24 on Spleen Length as Measured by Palpation
Week 12
|
-0.2 cm
Standard Deviation 2.17
|
-3.6 cm
Standard Deviation 6.73
|
|
Change From Baseline Through Week 12 and Week 24 on Spleen Length as Measured by Palpation
Week 24
|
-0.4 cm
Standard Deviation 5.41
|
-2.6 cm
Standard Deviation 3.44
|
SECONDARY outcome
Timeframe: Baseline through Weeks 12 and 24Population: Full Analysis Set included all enrolled participants who received at least 1 dose of itacitinib. Here, "N" signifies number of participants analyzed for this outcome measure and "n" signifies number of participants with data available at a particular time point.
Measurement of spleen length below the left costal margin was measured by palpation. Spleen size was determined at every physical examination with the participant in the recumbent (not left decubitus) position. The edge of the spleen was determined by palpation, and measured in centimeters, using a soft ruler, from the costal margin to the point of greatest splenic protrusion. The measurements should be noted and the site at which it was determined listed (eg, anterior axillary line, midclavicular line, and/or subxiphoid). A positive value indicates an increase in spleen volume and a negative value indicates a decrease in spleen volume.
Outcome measures
| Measure |
Cohort A
n=12 Participants
Participants with MF who were tolerating a ruxolitinib dose of less than 20 milligrams (mg) daily with no dose increase or no dose modification in the 8 weeks before screening visit received a combination of itacitinib at the dose of 200 mg, orally, once daily (QD) and ruxolitinib, orally, twice daily (BID) at their previous stable dose (must had been \< 20 mg daily). Participants continued study treatment until disease progression, unacceptable toxicity, withdrawal of consent, or other Protocol-specified criteria to stop treatment were met.
|
Cohort B
n=7 Participants
Participants with MF who progressed after initial reduction in spleen with ruxolitinib treatment, progressed or discontinued for hematologic toxicities received treatment with itacitinib alone at the dose of 600 mg QD. Participants continued study treatment until disease progression, unacceptable toxicity, withdrawal of consent, or other Protocol-specified criteria to stop treatment were met.
|
|---|---|---|
|
Percentage Change From Baseline Through Week 12 and Week 24 on Spleen Length as Measured by Palpation
Week 12
|
8.8 percentage change
Standard Deviation 40.83
|
-14.4 percentage change
Standard Deviation 49.89
|
|
Percentage Change From Baseline Through Week 12 and Week 24 on Spleen Length as Measured by Palpation
Week 24
|
2.5 percentage change
Standard Deviation 50.72
|
-21.3 percentage change
Standard Deviation 27.94
|
SECONDARY outcome
Timeframe: Baseline through Weeks 12 and 24Population: Full Analysis Set included all enrolled participants who received at least 1 dose of itacitinib. Here, "N" signifies number of participants analyzed for this outcome measure and "n" signifies number of participants with data available at a particular time point.
Symptoms of myelofibrosis were assessed using a modified MFSAF Version 2.0 diary. Using the diary, participants rated the following symptoms on a scale from 0 (absent/as good as it can be) to 10 (worst imaginable/as bad as it can be): itching, night sweats, abdominal discomfort/bloating, early satiety, pain under the ribs on left side and bone/muscle pain. The total symptom score ranged from 0-60 and was calculated as the sum of the 6 symptom scores. A higher score indicates worse symptoms.
Outcome measures
| Measure |
Cohort A
n=12 Participants
Participants with MF who were tolerating a ruxolitinib dose of less than 20 milligrams (mg) daily with no dose increase or no dose modification in the 8 weeks before screening visit received a combination of itacitinib at the dose of 200 mg, orally, once daily (QD) and ruxolitinib, orally, twice daily (BID) at their previous stable dose (must had been \< 20 mg daily). Participants continued study treatment until disease progression, unacceptable toxicity, withdrawal of consent, or other Protocol-specified criteria to stop treatment were met.
|
Cohort B
n=7 Participants
Participants with MF who progressed after initial reduction in spleen with ruxolitinib treatment, progressed or discontinued for hematologic toxicities received treatment with itacitinib alone at the dose of 600 mg QD. Participants continued study treatment until disease progression, unacceptable toxicity, withdrawal of consent, or other Protocol-specified criteria to stop treatment were met.
|
|---|---|---|
|
Change From Baseline Through Week 12 and Week 24 in Total Symptom Score as Measured by the Myelofibrosis Symptom Assessment Form (MFSAF) v2.0 Symptom Diary
Change at Week 12
|
1.4 score on scale
Standard Deviation 6.06
|
-4.7 score on scale
Standard Deviation 12.50
|
|
Change From Baseline Through Week 12 and Week 24 in Total Symptom Score as Measured by the Myelofibrosis Symptom Assessment Form (MFSAF) v2.0 Symptom Diary
Change at Week 24
|
-1.0 score on scale
Standard Deviation 9.88
|
-0.3 score on scale
Standard Deviation 10.14
|
SECONDARY outcome
Timeframe: Baseline through Weeks 12 and 24Population: Full Analysis Set included all enrolled participants who received at least 1 dose of itacitinib. Here, "N" signifies number of participants analyzed for this outcome measure and "n" signifies number of participants with data available at a particular time point.
Symptoms of myelofibrosis were assessed using a modified MFSAF Version 2.0 diary. Using the diary, participants rated the following symptoms on a scale from 0 (absent/as good as it can be) to 10 (worst imaginable/as bad as it can be): itching, night sweats, abdominal discomfort/bloating, early satiety, pain under the ribs on left side and bone/muscle pain. The total symptom score ranged from 0-60 and was calculated as the sum of the 6 symptom scores. A higher score indicates worse symptoms.
Outcome measures
| Measure |
Cohort A
n=12 Participants
Participants with MF who were tolerating a ruxolitinib dose of less than 20 milligrams (mg) daily with no dose increase or no dose modification in the 8 weeks before screening visit received a combination of itacitinib at the dose of 200 mg, orally, once daily (QD) and ruxolitinib, orally, twice daily (BID) at their previous stable dose (must had been \< 20 mg daily). Participants continued study treatment until disease progression, unacceptable toxicity, withdrawal of consent, or other Protocol-specified criteria to stop treatment were met.
|
Cohort B
n=6 Participants
Participants with MF who progressed after initial reduction in spleen with ruxolitinib treatment, progressed or discontinued for hematologic toxicities received treatment with itacitinib alone at the dose of 600 mg QD. Participants continued study treatment until disease progression, unacceptable toxicity, withdrawal of consent, or other Protocol-specified criteria to stop treatment were met.
|
|---|---|---|
|
Percentage Change From Baseline Through Week 12 and Week 24 in Total Symptom Score as Measured by the MFSAF v2.0 Symptom Diary
Percentage Change at Week 12
|
0.7 percentage change
Standard Deviation 69.57
|
-1.8 percentage change
Standard Deviation 116.6
|
|
Percentage Change From Baseline Through Week 12 and Week 24 in Total Symptom Score as Measured by the MFSAF v2.0 Symptom Diary
Percentage Change at Week 24
|
-5.6 percentage change
Standard Deviation 95.56
|
33.7 percentage change
Standard Deviation 142.3
|
SECONDARY outcome
Timeframe: Baseline through Week 12 and Week 24Population: Full Analysis Set included all enrolled participants who received at least 1 dose of itacitinib. . Here, "N" signifies number of participants analyzed for this outcome measure and "n" signifies number of participants with data available at a particular time point.
Symptoms are evaluated by the MPN-SAF TSS. The MPN-SAF TSS assessed by the participants themselves and this includes fatigue, concentration, early satiety, inactivity, night sweats, itching, bone pain, abdominal discomfort, weight loss, and fevers. Scoring is from 0 (absent/as good as it can be) to 10 (worst imaginable/as bad as it can be) for each item. The MPN-SAF TSS is the summation of all the individual scores (0-100 scale). A higher score indicates worse symptoms.
Outcome measures
| Measure |
Cohort A
n=11 Participants
Participants with MF who were tolerating a ruxolitinib dose of less than 20 milligrams (mg) daily with no dose increase or no dose modification in the 8 weeks before screening visit received a combination of itacitinib at the dose of 200 mg, orally, once daily (QD) and ruxolitinib, orally, twice daily (BID) at their previous stable dose (must had been \< 20 mg daily). Participants continued study treatment until disease progression, unacceptable toxicity, withdrawal of consent, or other Protocol-specified criteria to stop treatment were met.
|
Cohort B
n=7 Participants
Participants with MF who progressed after initial reduction in spleen with ruxolitinib treatment, progressed or discontinued for hematologic toxicities received treatment with itacitinib alone at the dose of 600 mg QD. Participants continued study treatment until disease progression, unacceptable toxicity, withdrawal of consent, or other Protocol-specified criteria to stop treatment were met.
|
|---|---|---|
|
Change From Baseline Through Week 12 and Week 24 in Total Symptom Score as Measured by the Myeloproliferative Neoplasm-Symptom Assessment Form (MPN-SAF)
Change at Week 12
|
2.0 score on scale
Standard Deviation 9.76
|
-3.7 score on scale
Standard Deviation 12.91
|
|
Change From Baseline Through Week 12 and Week 24 in Total Symptom Score as Measured by the Myeloproliferative Neoplasm-Symptom Assessment Form (MPN-SAF)
Change at Week 24
|
-1.6 score on scale
Standard Deviation 11.11
|
-6.0 score on scale
Standard Deviation 8.76
|
SECONDARY outcome
Timeframe: Baseline through Week 12 and Week 24Population: Full Analysis Set included all enrolled participants who received at least 1 dose of itacitinib. Here, "N" signifies number of participants analyzed for this outcome measure and "n" signifies number of participants with data available at a particular time point.
Symptoms are evaluated by the MPN-SAF TSS. The MPN-SAF TSS assessed by the participants themselves and this includes fatigue, concentration, early satiety, inactivity, night sweats, itching, bone pain, abdominal discomfort, weight loss, and fevers. Scoring is from 0 (absent/as good as it can be) to 10 (worst imaginable/as bad as it can be) for each item. The MPN-SAF TSS is the summation of all the individual scores (0-100 scale). A higher score indicates worse symptoms. Note that the mean percentage change can vary in direction from the mean absolute change because percent increases (but not decreases) can exceed 100%.
Outcome measures
| Measure |
Cohort A
n=11 Participants
Participants with MF who were tolerating a ruxolitinib dose of less than 20 milligrams (mg) daily with no dose increase or no dose modification in the 8 weeks before screening visit received a combination of itacitinib at the dose of 200 mg, orally, once daily (QD) and ruxolitinib, orally, twice daily (BID) at their previous stable dose (must had been \< 20 mg daily). Participants continued study treatment until disease progression, unacceptable toxicity, withdrawal of consent, or other Protocol-specified criteria to stop treatment were met.
|
Cohort B
n=7 Participants
Participants with MF who progressed after initial reduction in spleen with ruxolitinib treatment, progressed or discontinued for hematologic toxicities received treatment with itacitinib alone at the dose of 600 mg QD. Participants continued study treatment until disease progression, unacceptable toxicity, withdrawal of consent, or other Protocol-specified criteria to stop treatment were met.
|
|---|---|---|
|
Percentage Change From Baseline Through Week 12 and Week 24 in Total Symptom Score as Measured by the MPN-SAF
Percentage Change at Week 12
|
3.8 percentage change
Standard Deviation 47.25
|
-6.1 percentage change
Standard Deviation 51.24
|
|
Percentage Change From Baseline Through Week 12 and Week 24 in Total Symptom Score as Measured by the MPN-SAF
Percentage Change at Week 24
|
5.8 percentage change
Standard Deviation 46.85
|
-22.7 percentage change
Standard Deviation 29.62
|
SECONDARY outcome
Timeframe: Weeks 4, 8, 12, 16, 20, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, and 168Population: Full Analysis Set included all enrolled participants who received at least 1 dose of itacitinib. Here, "N" signifies number of participants analyzed for this outcome measure and "n" signifies number of participants with data available at a particular time point.
Symptoms of myelofibrosis were assessed using the PGIC questionnaire. Using the questionnaire, participants rated the overall sense of treatment effect on their symptoms on a scale of 1 (very much improved)- 7(very much worse). The specific wording was: Since the start of the treatment you have received in this study, your myelofibrosis symptoms are: 1) Very much improved, 2) Much improved, 3) Minimally improved, 4) No change, 5) Minimally worse, 6) Much worse, 7) Very much worse. A higher score indicates worse symptoms.
Outcome measures
| Measure |
Cohort A
n=11 Participants
Participants with MF who were tolerating a ruxolitinib dose of less than 20 milligrams (mg) daily with no dose increase or no dose modification in the 8 weeks before screening visit received a combination of itacitinib at the dose of 200 mg, orally, once daily (QD) and ruxolitinib, orally, twice daily (BID) at their previous stable dose (must had been \< 20 mg daily). Participants continued study treatment until disease progression, unacceptable toxicity, withdrawal of consent, or other Protocol-specified criteria to stop treatment were met.
|
Cohort B
n=9 Participants
Participants with MF who progressed after initial reduction in spleen with ruxolitinib treatment, progressed or discontinued for hematologic toxicities received treatment with itacitinib alone at the dose of 600 mg QD. Participants continued study treatment until disease progression, unacceptable toxicity, withdrawal of consent, or other Protocol-specified criteria to stop treatment were met.
|
|---|---|---|
|
Patient Global Impression of Change (PGIC) Score at Each Visit
Week 4
|
3.6 score on scale
Standard Deviation 0.81
|
3.5 score on scale
Standard Deviation 0.93
|
|
Patient Global Impression of Change (PGIC) Score at Each Visit
Weeks 8
|
3.3 score on scale
Standard Deviation 0.90
|
3.3 score on scale
Standard Deviation 1.22
|
|
Patient Global Impression of Change (PGIC) Score at Each Visit
Weeks 12
|
3.2 score on scale
Standard Deviation 0.98
|
3.6 score on scale
Standard Deviation 0.98
|
|
Patient Global Impression of Change (PGIC) Score at Each Visit
Weeks 16
|
3.0 score on scale
Standard Deviation 1.00
|
4.2 score on scale
Standard Deviation 1.47
|
|
Patient Global Impression of Change (PGIC) Score at Each Visit
Weeks 20
|
3.3 score on scale
Standard Deviation 0.71
|
3.2 score on scale
Standard Deviation 0.75
|
|
Patient Global Impression of Change (PGIC) Score at Each Visit
Weeks 24
|
3.2 score on scale
Standard Deviation 1.09
|
2.8 score on scale
Standard Deviation 0.96
|
|
Patient Global Impression of Change (PGIC) Score at Each Visit
Weeks 36
|
3.2 score on scale
Standard Deviation 0.98
|
3.0 score on scale
Standard Deviation 1.00
|
|
Patient Global Impression of Change (PGIC) Score at Each Visit
Weeks 48
|
2.5 score on scale
Standard Deviation 1.00
|
2.0 score on scale
Standard Deviation NA
Standard deviation was not estimable since only 1 participant was evaluable.
|
|
Patient Global Impression of Change (PGIC) Score at Each Visit
Weeks 60
|
3.0 score on scale
Standard Deviation 1.73
|
3.0 score on scale
Standard Deviation NA
Standard deviation was not estimable since only 1 participant was evaluable.
|
|
Patient Global Impression of Change (PGIC) Score at Each Visit
Weeks 72
|
3.3 score on scale
Standard Deviation 1.50
|
3.0 score on scale
Standard Deviation NA
Standard deviation was not estimable since only 1 participant was evaluable.
|
|
Patient Global Impression of Change (PGIC) Score at Each Visit
Weeks 84
|
2.0 score on scale
Standard Deviation NA
Standard deviation was not estimable since only 1 participant was evaluable.
|
3.0 score on scale
Standard Deviation NA
Standard deviation was not estimable since only 1 participant was evaluable.
|
|
Patient Global Impression of Change (PGIC) Score at Each Visit
Weeks 96
|
—
|
2.0 score on scale
Standard Deviation NA
Standard deviation was not estimable since only 1 participant was evaluable.
|
|
Patient Global Impression of Change (PGIC) Score at Each Visit
Weeks 108
|
—
|
4.0 score on scale
Standard Deviation NA
Standard deviation was not estimable since only 1 participant was evaluable.
|
|
Patient Global Impression of Change (PGIC) Score at Each Visit
Week 120
|
—
|
3.0 score on scale
Standard Deviation NA
Standard deviation was not estimable since only 1 participant was evaluable.
|
|
Patient Global Impression of Change (PGIC) Score at Each Visit
Week 132
|
—
|
3.0 score on scale
Standard Deviation NA
Standard deviation was not estimable since only 1 participant was evaluable.
|
|
Patient Global Impression of Change (PGIC) Score at Each Visit
Week 168
|
—
|
3.0 score on scale
Standard Deviation NA
Standard deviation was not estimable since only 1 participant was evaluable.
|
SECONDARY outcome
Timeframe: up to approximately 40 months (3.3 years)Population: Full Analysis Set included all enrolled participants who received at least 1 dose of itacitinib.
Treatment response (complete remission \[CR\] or partial remission \[PR\]) graded per IWG-MRT. CR: Bone marrow (BM): \< 5% blasts; ≤ Grade 1 MF, Peripheral blood: Hemoglobin (Hb) ≥ 100 grams per liter (g/L), \< upper normal limit (UNL); neutrophil count ≥ 1 × 10\^9/L and \< UNL; Platelet count ≥ 100 × 10\^9/L and \< UNL; \< 2% immature myeloid cells (IMCs) and Clinical: Resolution of disease symptoms; spleen, liver not palpable; no evidence of extramedullary hematopoeisis (EMH). PR: Peripheral blood: Hb ≥ 100 g/L and \< UNL; neutrophil count ≥ 1 × 10\^9/L and \< UNL; platelet count ≥ 100 × 10\^9/L and \< UNL; \< 2% IMCs and Clinical: Resolution of symptoms; spleen and liver not palpable; no evidence of EMH or BM: \< 5% blasts; ≤ Grade 1 MF; and peripheral blood: Hb≥ 85 g/L but \< 100 g/L and \< UNL; neutrophil count ≥ 1 × 10\^9/L and \< UNL; platelet count ≥ 50 × 10\^9/L but \< 100 × 10\^9/L and \< UNL; \< 2% IMCs and Clinical: Resolution of symptoms; spleen, liver not palpable; no evidence of EMH.
Outcome measures
| Measure |
Cohort A
n=13 Participants
Participants with MF who were tolerating a ruxolitinib dose of less than 20 milligrams (mg) daily with no dose increase or no dose modification in the 8 weeks before screening visit received a combination of itacitinib at the dose of 200 mg, orally, once daily (QD) and ruxolitinib, orally, twice daily (BID) at their previous stable dose (must had been \< 20 mg daily). Participants continued study treatment until disease progression, unacceptable toxicity, withdrawal of consent, or other Protocol-specified criteria to stop treatment were met.
|
Cohort B
n=10 Participants
Participants with MF who progressed after initial reduction in spleen with ruxolitinib treatment, progressed or discontinued for hematologic toxicities received treatment with itacitinib alone at the dose of 600 mg QD. Participants continued study treatment until disease progression, unacceptable toxicity, withdrawal of consent, or other Protocol-specified criteria to stop treatment were met.
|
|---|---|---|
|
Number of Participants With Responses According to the 2013 International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) Consensus Criteria for Treatment Response
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: 0 (pre-dose), 1, 2, 5 and 8 hours post-dose on Week 2 and Week 4Population: Pharmacokinetic evaluable population included all participants who received at least 1 dose of itacitinib and provided at least 1 post-dose plasma sample for PK. Here, "N " signifies number of participants analyzed for this outcome measure.
AUCtau defined as area under the concentration-time curve over a dosing interval for Itacitinib. The concentrations of itacitinib in plasma were determined using a validated Liquid Chromatography with tandem mass spectrometry (LC/MS/MS) method with an assay range of 5 to 5000 nM. The PK parameters were calculated using standard noncompartmental analysis in Phoenix WinNonlin® v8.2 (Certara USA Inc., Princeton, NJ). Itacitinib PK data for Cohort A on Week 2 were not available as itacitinib was to be held until the completion of PK sample collection.
Outcome measures
| Measure |
Cohort A
n=12 Participants
Participants with MF who were tolerating a ruxolitinib dose of less than 20 milligrams (mg) daily with no dose increase or no dose modification in the 8 weeks before screening visit received a combination of itacitinib at the dose of 200 mg, orally, once daily (QD) and ruxolitinib, orally, twice daily (BID) at their previous stable dose (must had been \< 20 mg daily). Participants continued study treatment until disease progression, unacceptable toxicity, withdrawal of consent, or other Protocol-specified criteria to stop treatment were met.
|
Cohort B
n=8 Participants
Participants with MF who progressed after initial reduction in spleen with ruxolitinib treatment, progressed or discontinued for hematologic toxicities received treatment with itacitinib alone at the dose of 600 mg QD. Participants continued study treatment until disease progression, unacceptable toxicity, withdrawal of consent, or other Protocol-specified criteria to stop treatment were met.
|
|---|---|---|
|
Area Under the Concentration-time Curve Over a Dosing Interval (AUCtau) for Itacitinib
Week 2
|
—
|
24100 nanomolar* hour (nM*h)
Standard Deviation 6600
|
|
Area Under the Concentration-time Curve Over a Dosing Interval (AUCtau) for Itacitinib
Week 4
|
2540 nanomolar* hour (nM*h)
Standard Deviation 2020
|
28900 nanomolar* hour (nM*h)
Standard Deviation 11200
|
SECONDARY outcome
Timeframe: 0 (pre-dose), 1, 2, 5 and 8 hours post-dose on Week 2 and Week 4Population: Pharmacokinetic evaluable population included all participants who received at least 1 dose of ruxolitinib and provided at least 1 post-dose plasma sample for PK. Here, "N " signifies number of participants analyzed for this outcome measure. Only the data from 15mg QD is shown as it is the only dose level with at least three participants at both week 2 and week 4.
AUCtau defined as area under the concentration-time curve over a dosing interval for ruxolitinib. The concentrations of ruxolitinib in plasma were determined using a validated LC/MS/MS method with an assay range of 1 to 1000 nM. The PK parameters were calculated using standard noncompartmental analysis in Phoenix WinNonlin® v8.2 (Certara USA Inc., Princeton, NJ).
Outcome measures
| Measure |
Cohort A
n=4 Participants
Participants with MF who were tolerating a ruxolitinib dose of less than 20 milligrams (mg) daily with no dose increase or no dose modification in the 8 weeks before screening visit received a combination of itacitinib at the dose of 200 mg, orally, once daily (QD) and ruxolitinib, orally, twice daily (BID) at their previous stable dose (must had been \< 20 mg daily). Participants continued study treatment until disease progression, unacceptable toxicity, withdrawal of consent, or other Protocol-specified criteria to stop treatment were met.
|
Cohort B
Participants with MF who progressed after initial reduction in spleen with ruxolitinib treatment, progressed or discontinued for hematologic toxicities received treatment with itacitinib alone at the dose of 600 mg QD. Participants continued study treatment until disease progression, unacceptable toxicity, withdrawal of consent, or other Protocol-specified criteria to stop treatment were met.
|
|---|---|---|
|
Area Under the Concentration-time Curve Over a Dosing Interval (AUCtau) for Ruxolitinib
Week 2
|
2930 nM*h
Standard Deviation 486
|
—
|
|
Area Under the Concentration-time Curve Over a Dosing Interval (AUCtau) for Ruxolitinib
Week 4
|
2350 nM*h
Standard Deviation 635
|
—
|
SECONDARY outcome
Timeframe: 0 (pre-dose), 1, 2, 5 and 8 hours post-dose on Week 2 and Week 4Population: Pharmacokinetic evaluable population included all participants who received at least 1 dose of itacitinib and provided at least 1 post-dose plasma sample for PK. Here, "N " signifies number of participants analyzed for this outcome measure.
Clearance of a drug was measure of the rate at which a drug is metabolized or eliminated by normal biological processes. The concentrations of itacitinib in plasma were determined using a validated LC/MS/MS method with an assay range of 5 to 5000 nM. The PK parameters were calculated using standard noncompartmental analysis in Phoenix WinNonlin® v8.2 (Certara USA Inc., Princeton, NJ). Data for Cohort A (Itacitinib) on Week 2 was not available as Cohort A, itacitinib was to be held on Week 2 until the completion of the PK sample collection.
Outcome measures
| Measure |
Cohort A
n=12 Participants
Participants with MF who were tolerating a ruxolitinib dose of less than 20 milligrams (mg) daily with no dose increase or no dose modification in the 8 weeks before screening visit received a combination of itacitinib at the dose of 200 mg, orally, once daily (QD) and ruxolitinib, orally, twice daily (BID) at their previous stable dose (must had been \< 20 mg daily). Participants continued study treatment until disease progression, unacceptable toxicity, withdrawal of consent, or other Protocol-specified criteria to stop treatment were met.
|
Cohort B
n=8 Participants
Participants with MF who progressed after initial reduction in spleen with ruxolitinib treatment, progressed or discontinued for hematologic toxicities received treatment with itacitinib alone at the dose of 600 mg QD. Participants continued study treatment until disease progression, unacceptable toxicity, withdrawal of consent, or other Protocol-specified criteria to stop treatment were met.
|
|---|---|---|
|
Apparent Oral Dose Clearance (CL/F) of Itacitinib
Week 2
|
—
|
48.5 liters per hour (L/h)
Standard Deviation 14.9
|
|
Apparent Oral Dose Clearance (CL/F) of Itacitinib
Week 4
|
203 liters per hour (L/h)
Standard Deviation 97.4
|
42.4 liters per hour (L/h)
Standard Deviation 15.8
|
SECONDARY outcome
Timeframe: 0 (pre-dose), 1, 2, 5 and 8 hours post-dose on Week 2 and Week 4Population: Pharmacokinetic evaluable population included all participants who received at least 1 dose of ruxolitinib and provided at least 1 post-dose plasma sample for PK. Here, "N " signifies number of participants analyzed for this outcome measure. Only the data from 15mg QD is shown as it is the only dose level with at least three participants at both week 2 and week 4.
Clearance of a drug was measure of the rate at which a drug is metabolized or eliminated by normal biological processes. The concentrations of ruxolitinib in plasma were determined using a validated LC/MS/MS method with an assay range of 1 to 1000 nM. The PK parameters were calculated using standard noncompartmental analysis in Phoenix WinNonlin® v8.2 (Certara USA Inc., Princeton, NJ).
Outcome measures
| Measure |
Cohort A
n=4 Participants
Participants with MF who were tolerating a ruxolitinib dose of less than 20 milligrams (mg) daily with no dose increase or no dose modification in the 8 weeks before screening visit received a combination of itacitinib at the dose of 200 mg, orally, once daily (QD) and ruxolitinib, orally, twice daily (BID) at their previous stable dose (must had been \< 20 mg daily). Participants continued study treatment until disease progression, unacceptable toxicity, withdrawal of consent, or other Protocol-specified criteria to stop treatment were met.
|
Cohort B
Participants with MF who progressed after initial reduction in spleen with ruxolitinib treatment, progressed or discontinued for hematologic toxicities received treatment with itacitinib alone at the dose of 600 mg QD. Participants continued study treatment until disease progression, unacceptable toxicity, withdrawal of consent, or other Protocol-specified criteria to stop treatment were met.
|
|---|---|---|
|
Apparent Oral Dose Clearance (CL/F) of Ruxolitinib
Week 2
|
17.0 L/h
Standard Deviation 3.12
|
—
|
|
Apparent Oral Dose Clearance (CL/F) of Ruxolitinib
Week 4
|
22.2 L/h
Standard Deviation 6.82
|
—
|
SECONDARY outcome
Timeframe: 0 (pre-dose), 1, 2, 5 and 8 hours post-dose on Week 2 and Week 4Population: Pharmacokinetic evaluable population included all participants who received at least 1 dose of itacitinib and provided at least 1 post-dose plasma sample for PK. Here, "N " signifies number of participants analyzed for this outcome measure.
The concentrations of itacitinib in plasma were determined using a validated LC/MS/MS method with an assay range of 5 to 5000 nM. The PK parameters were calculated using standard noncompartmental analysis in Phoenix WinNonlin® v8.2 (Certara USA Inc., Princeton, NJ). Data for Cohort A (Itacitinib) on Week 2 was not available as Cohort A, itacitinib was to be held on Week 2 until the completion of the PK sample collection.
Outcome measures
| Measure |
Cohort A
n=12 Participants
Participants with MF who were tolerating a ruxolitinib dose of less than 20 milligrams (mg) daily with no dose increase or no dose modification in the 8 weeks before screening visit received a combination of itacitinib at the dose of 200 mg, orally, once daily (QD) and ruxolitinib, orally, twice daily (BID) at their previous stable dose (must had been \< 20 mg daily). Participants continued study treatment until disease progression, unacceptable toxicity, withdrawal of consent, or other Protocol-specified criteria to stop treatment were met.
|
Cohort B
n=8 Participants
Participants with MF who progressed after initial reduction in spleen with ruxolitinib treatment, progressed or discontinued for hematologic toxicities received treatment with itacitinib alone at the dose of 600 mg QD. Participants continued study treatment until disease progression, unacceptable toxicity, withdrawal of consent, or other Protocol-specified criteria to stop treatment were met.
|
|---|---|---|
|
Maximum Observed Plasma Concentration (Cmax) of Itacitinib
Week 2
|
—
|
3570 nanometer (nM)
Standard Deviation 1280
|
|
Maximum Observed Plasma Concentration (Cmax) of Itacitinib
Week 4
|
559 nanometer (nM)
Standard Deviation 518
|
4460 nanometer (nM)
Standard Deviation 2470
|
SECONDARY outcome
Timeframe: 0 (pre-dose), 1, 2, 5 and 8 hours post-dose on Week 2 and Week 4Population: Pharmacokinetic evaluable population included all participants who received at least 1 dose of ruxolitinib and provided at least 1 post-dose plasma sample for PK. Here, "N " signifies number of participants analyzed for this outcome measure. Only the data from 15mg QD is shown as it is the only dose level with at least three participants at both week 2 and week 4.
The concentrations of ruxolitinib in plasma were determined using a validated LC/MS/MS method with an assay range of 1 to 1000 nM. The PK parameters were calculated using standard noncompartmental analysis in Phoenix WinNonlin® v8.2 (Certara USA Inc., Princeton, NJ).
Outcome measures
| Measure |
Cohort A
n=4 Participants
Participants with MF who were tolerating a ruxolitinib dose of less than 20 milligrams (mg) daily with no dose increase or no dose modification in the 8 weeks before screening visit received a combination of itacitinib at the dose of 200 mg, orally, once daily (QD) and ruxolitinib, orally, twice daily (BID) at their previous stable dose (must had been \< 20 mg daily). Participants continued study treatment until disease progression, unacceptable toxicity, withdrawal of consent, or other Protocol-specified criteria to stop treatment were met.
|
Cohort B
Participants with MF who progressed after initial reduction in spleen with ruxolitinib treatment, progressed or discontinued for hematologic toxicities received treatment with itacitinib alone at the dose of 600 mg QD. Participants continued study treatment until disease progression, unacceptable toxicity, withdrawal of consent, or other Protocol-specified criteria to stop treatment were met.
|
|---|---|---|
|
Maximum Observed Plasma Concentration (Cmax) of Ruxolitinib
Week 2
|
695 nM
Standard Deviation 111
|
—
|
|
Maximum Observed Plasma Concentration (Cmax) of Ruxolitinib
Week 4
|
677 nM
Standard Deviation 118
|
—
|
SECONDARY outcome
Timeframe: 0 (pre-dose), 1, 2, 5 and 8 hours post-dose on Week 2 and Week 4Population: Pharmacokinetic evaluable population included all participants who received at least 1 dose of itacitinib and provided at least 1 post-dose plasma sample for PK. Here, "N " signifies number of participants analyzed for this outcome measure.
The concentrations of itacitinib in plasma were determined using a validated LC/MS/MS method with an assay range of 5 to 5000 nM. The PK parameters were calculated using standard noncompartmental analysis in Phoenix WinNonlin® v8.2 (Certara USA Inc., Princeton, NJ). Data for Cohort A (Itacitinib) on Week 2 was not available as Cohort A, itacitinib was to be held on Week 2 until the completion of the PK sample collection.
Outcome measures
| Measure |
Cohort A
n=12 Participants
Participants with MF who were tolerating a ruxolitinib dose of less than 20 milligrams (mg) daily with no dose increase or no dose modification in the 8 weeks before screening visit received a combination of itacitinib at the dose of 200 mg, orally, once daily (QD) and ruxolitinib, orally, twice daily (BID) at their previous stable dose (must had been \< 20 mg daily). Participants continued study treatment until disease progression, unacceptable toxicity, withdrawal of consent, or other Protocol-specified criteria to stop treatment were met.
|
Cohort B
n=8 Participants
Participants with MF who progressed after initial reduction in spleen with ruxolitinib treatment, progressed or discontinued for hematologic toxicities received treatment with itacitinib alone at the dose of 600 mg QD. Participants continued study treatment until disease progression, unacceptable toxicity, withdrawal of consent, or other Protocol-specified criteria to stop treatment were met.
|
|---|---|---|
|
Time to Maximum Concentration (Tmax) of Itacitinib
Week 2
|
—
|
2.0 hour (hr)
Interval 1.0 to 5.0
|
|
Time to Maximum Concentration (Tmax) of Itacitinib
Week 4
|
2.0 hour (hr)
Interval 1.0 to 2.3
|
2.0 hour (hr)
Interval 2.0 to 4.6
|
SECONDARY outcome
Timeframe: 0 (pre-dose), 1, 2, 5 and 8 hours post-dose on Week 2 and Week 4Population: Pharmacokinetic evaluable population included all participants who received at least 1 dose of ruxolitinib and provided at least 1 post-dose plasma sample for PK. Here, "N " signifies number of participants analyzed for this outcome measure. Only the data from 15mg QD is shown as it is the only dose level with at least three participants at both week 2 and week 4.
The concentrations of ruxolitinib in plasma were determined using a validated LC/MS/MS method with an assay range of 1 to 1000 nM. The PK parameters were calculated using standard noncompartmental analysis in Phoenix WinNonlin® v8.2 (Certara USA Inc., Princeton, NJ).
Outcome measures
| Measure |
Cohort A
n=4 Participants
Participants with MF who were tolerating a ruxolitinib dose of less than 20 milligrams (mg) daily with no dose increase or no dose modification in the 8 weeks before screening visit received a combination of itacitinib at the dose of 200 mg, orally, once daily (QD) and ruxolitinib, orally, twice daily (BID) at their previous stable dose (must had been \< 20 mg daily). Participants continued study treatment until disease progression, unacceptable toxicity, withdrawal of consent, or other Protocol-specified criteria to stop treatment were met.
|
Cohort B
Participants with MF who progressed after initial reduction in spleen with ruxolitinib treatment, progressed or discontinued for hematologic toxicities received treatment with itacitinib alone at the dose of 600 mg QD. Participants continued study treatment until disease progression, unacceptable toxicity, withdrawal of consent, or other Protocol-specified criteria to stop treatment were met.
|
|---|---|---|
|
Time to Maximum Concentration (Tmax) of Ruxolitinib
Week 2
|
1.0 hr
Interval 1.0 to 1.1
|
—
|
|
Time to Maximum Concentration (Tmax) of Ruxolitinib
Week 4
|
1.0 hr
Interval 1.0 to 1.1
|
—
|
SECONDARY outcome
Timeframe: 0 (pre-dose), 1, 2, 5 and 8 hours post-dose on Week 2 and Week 4Population: Pharmacokinetic evaluable population included all participants who received at least 1 dose of itacitinib and provided at least 1 post-dose plasma sample for PK. Here, "N " signifies number of participants analyzed for this outcome measure.
Ctau is defined as concentration at the end of the dosing interval of ruxolitinib.The concentrations of itacitinib in plasma were determined using a validated LC/MS/MS method with an assay range of 5 to 5000 nM. The PK parameters were calculated using standard noncompartmental analysis in Phoenix WinNonlin® v8.2 (Certara USA Inc., Princeton, NJ). Data for Cohort A (Itacitinib) on Week 2 was not available as Cohort A, itacitinib was to be held on Week 2 until the completion of the PK sample collection.
Outcome measures
| Measure |
Cohort A
n=12 Participants
Participants with MF who were tolerating a ruxolitinib dose of less than 20 milligrams (mg) daily with no dose increase or no dose modification in the 8 weeks before screening visit received a combination of itacitinib at the dose of 200 mg, orally, once daily (QD) and ruxolitinib, orally, twice daily (BID) at their previous stable dose (must had been \< 20 mg daily). Participants continued study treatment until disease progression, unacceptable toxicity, withdrawal of consent, or other Protocol-specified criteria to stop treatment were met.
|
Cohort B
n=9 Participants
Participants with MF who progressed after initial reduction in spleen with ruxolitinib treatment, progressed or discontinued for hematologic toxicities received treatment with itacitinib alone at the dose of 600 mg QD. Participants continued study treatment until disease progression, unacceptable toxicity, withdrawal of consent, or other Protocol-specified criteria to stop treatment were met.
|
|---|---|---|
|
Concentration at the End of the Dosing Interval (Ctau) of Itacitinib
Week 2
|
—
|
102 nM
Standard Deviation 120
|
|
Concentration at the End of the Dosing Interval (Ctau) of Itacitinib
Week 4
|
10.2 nM
Standard Deviation 8.67
|
108 nM
Standard Deviation 85.4
|
SECONDARY outcome
Timeframe: 0 (pre-dose), 1, 2, 5 and 8 hours post-dose Week 2 and Week 4Population: Pharmacokinetic evaluable population included all participants who received at least 1 dose of ruxolitinib and provided at least 1 post-dose plasma sample for PK. Here, "N " signifies number of participants analyzed for this outcome measure. Only the data from 15mg QD is shown as it is the only dose level with at least three participants at both week 2 and week 4.
Ctau is defined as concentration at the end of the dosing interval of ruxolitinib. The concentrations of ruxolitinib in plasma were determined using a validated LC/MS/MS method with an assay range of 1 to 1000 nM. The PK parameters were calculated using standard noncompartmental analysis in Phoenix WinNonlin® v8.2 (Certara USA Inc., Princeton, NJ).
Outcome measures
| Measure |
Cohort A
n=4 Participants
Participants with MF who were tolerating a ruxolitinib dose of less than 20 milligrams (mg) daily with no dose increase or no dose modification in the 8 weeks before screening visit received a combination of itacitinib at the dose of 200 mg, orally, once daily (QD) and ruxolitinib, orally, twice daily (BID) at their previous stable dose (must had been \< 20 mg daily). Participants continued study treatment until disease progression, unacceptable toxicity, withdrawal of consent, or other Protocol-specified criteria to stop treatment were met.
|
Cohort B
Participants with MF who progressed after initial reduction in spleen with ruxolitinib treatment, progressed or discontinued for hematologic toxicities received treatment with itacitinib alone at the dose of 600 mg QD. Participants continued study treatment until disease progression, unacceptable toxicity, withdrawal of consent, or other Protocol-specified criteria to stop treatment were met.
|
|---|---|---|
|
Concentration at the End of the Dosing Interval (Ctau) of Ruxolitinib
Week 2
|
16.6 nM
Standard Deviation 14.5
|
—
|
|
Concentration at the End of the Dosing Interval (Ctau) of Ruxolitinib
Week 4
|
19.7 nM
Standard Deviation 28.6
|
—
|
Adverse Events
Cohort A
Serious events: 3 serious events
Other events: 13 other events
Deaths: 0 deaths
Cohort B
Serious events: 5 serious events
Other events: 10 other events
Deaths: 2 deaths
Total
Serious events: 8 serious events
Other events: 23 other events
Deaths: 2 deaths
Serious adverse events
| Measure |
Cohort A
n=13 participants at risk
Participants with MF who were tolerating a ruxolitinib dose of less than 20 milligrams (mg) daily with no dose increase or no dose modification in the 8 weeks before screening visit received a combination of itacitinib at the dose of 200 mg, orally, once daily (QD) and ruxolitinib, orally, twice daily (BID) at their previous stable dose (must had been \< 20 mg daily). Participants continued study treatment until disease progression, unacceptable toxicity, withdrawal of consent, or other Protocol-specified criteria to stop treatment were met.
|
Cohort B
n=10 participants at risk
Participants with MF who progressed after initial reduction in spleen with ruxolitinib treatment, progressed or discontinued for hematologic toxicities received treatment with itacitinib alone at the dose of 600 mg QD. Participants continued study treatment until disease progression, unacceptable toxicity, withdrawal of consent, or other Protocol-specified criteria to stop treatment were met.
|
Total
n=23 participants at risk
Total
|
|---|---|---|---|
|
Cardiac disorders
Atrial fibrillation
|
0.00%
0/13 • up to approximately 40 months (3.3 years)
|
10.0%
1/10 • Number of events 1 • up to approximately 40 months (3.3 years)
|
4.3%
1/23 • Number of events 1 • up to approximately 40 months (3.3 years)
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
7.7%
1/13 • Number of events 1 • up to approximately 40 months (3.3 years)
|
0.00%
0/10 • up to approximately 40 months (3.3 years)
|
4.3%
1/23 • Number of events 1 • up to approximately 40 months (3.3 years)
|
|
Investigations
Blood creatinine increased
|
7.7%
1/13 • Number of events 1 • up to approximately 40 months (3.3 years)
|
0.00%
0/10 • up to approximately 40 months (3.3 years)
|
4.3%
1/23 • Number of events 1 • up to approximately 40 months (3.3 years)
|
|
Infections and infestations
Bronchitis
|
0.00%
0/13 • up to approximately 40 months (3.3 years)
|
10.0%
1/10 • Number of events 1 • up to approximately 40 months (3.3 years)
|
4.3%
1/23 • Number of events 1 • up to approximately 40 months (3.3 years)
|
|
Infections and infestations
Campylobacter gastroenteritis
|
7.7%
1/13 • Number of events 1 • up to approximately 40 months (3.3 years)
|
0.00%
0/10 • up to approximately 40 months (3.3 years)
|
4.3%
1/23 • Number of events 1 • up to approximately 40 months (3.3 years)
|
|
Cardiac disorders
Cardiac failure congestive
|
7.7%
1/13 • Number of events 2 • up to approximately 40 months (3.3 years)
|
0.00%
0/10 • up to approximately 40 months (3.3 years)
|
4.3%
1/23 • Number of events 2 • up to approximately 40 months (3.3 years)
|
|
Infections and infestations
Cellulitis
|
0.00%
0/13 • up to approximately 40 months (3.3 years)
|
10.0%
1/10 • Number of events 1 • up to approximately 40 months (3.3 years)
|
4.3%
1/23 • Number of events 1 • up to approximately 40 months (3.3 years)
|
|
Infections and infestations
Clostridium difficile infection
|
0.00%
0/13 • up to approximately 40 months (3.3 years)
|
10.0%
1/10 • Number of events 1 • up to approximately 40 months (3.3 years)
|
4.3%
1/23 • Number of events 1 • up to approximately 40 months (3.3 years)
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/13 • up to approximately 40 months (3.3 years)
|
10.0%
1/10 • Number of events 1 • up to approximately 40 months (3.3 years)
|
4.3%
1/23 • Number of events 1 • up to approximately 40 months (3.3 years)
|
|
Gastrointestinal disorders
Diarrhoea
|
7.7%
1/13 • Number of events 2 • up to approximately 40 months (3.3 years)
|
0.00%
0/10 • up to approximately 40 months (3.3 years)
|
4.3%
1/23 • Number of events 2 • up to approximately 40 months (3.3 years)
|
|
Blood and lymphatic system disorders
Disseminated intravascular coagulation
|
0.00%
0/13 • up to approximately 40 months (3.3 years)
|
10.0%
1/10 • Number of events 1 • up to approximately 40 months (3.3 years)
|
4.3%
1/23 • Number of events 1 • up to approximately 40 months (3.3 years)
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.00%
0/13 • up to approximately 40 months (3.3 years)
|
10.0%
1/10 • Number of events 1 • up to approximately 40 months (3.3 years)
|
4.3%
1/23 • Number of events 1 • up to approximately 40 months (3.3 years)
|
|
General disorders
Fatigue
|
7.7%
1/13 • Number of events 1 • up to approximately 40 months (3.3 years)
|
0.00%
0/10 • up to approximately 40 months (3.3 years)
|
4.3%
1/23 • Number of events 1 • up to approximately 40 months (3.3 years)
|
|
Musculoskeletal and connective tissue disorders
Haematoma muscle
|
0.00%
0/13 • up to approximately 40 months (3.3 years)
|
10.0%
1/10 • Number of events 2 • up to approximately 40 months (3.3 years)
|
4.3%
1/23 • Number of events 2 • up to approximately 40 months (3.3 years)
|
|
Hepatobiliary disorders
Hepatic lesion
|
7.7%
1/13 • Number of events 1 • up to approximately 40 months (3.3 years)
|
0.00%
0/10 • up to approximately 40 months (3.3 years)
|
4.3%
1/23 • Number of events 1 • up to approximately 40 months (3.3 years)
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
0.00%
0/13 • up to approximately 40 months (3.3 years)
|
10.0%
1/10 • Number of events 1 • up to approximately 40 months (3.3 years)
|
4.3%
1/23 • Number of events 1 • up to approximately 40 months (3.3 years)
|
|
Renal and urinary disorders
Nephrolithiasis
|
0.00%
0/13 • up to approximately 40 months (3.3 years)
|
10.0%
1/10 • Number of events 1 • up to approximately 40 months (3.3 years)
|
4.3%
1/23 • Number of events 1 • up to approximately 40 months (3.3 years)
|
|
General disorders
Non-cardiac chest pain
|
7.7%
1/13 • Number of events 1 • up to approximately 40 months (3.3 years)
|
0.00%
0/10 • up to approximately 40 months (3.3 years)
|
4.3%
1/23 • Number of events 1 • up to approximately 40 months (3.3 years)
|
|
Gastrointestinal disorders
Pancreatic cyst
|
7.7%
1/13 • Number of events 1 • up to approximately 40 months (3.3 years)
|
0.00%
0/10 • up to approximately 40 months (3.3 years)
|
4.3%
1/23 • Number of events 1 • up to approximately 40 months (3.3 years)
|
|
Infections and infestations
Pneumonia
|
0.00%
0/13 • up to approximately 40 months (3.3 years)
|
10.0%
1/10 • Number of events 1 • up to approximately 40 months (3.3 years)
|
4.3%
1/23 • Number of events 1 • up to approximately 40 months (3.3 years)
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary oedema
|
0.00%
0/13 • up to approximately 40 months (3.3 years)
|
10.0%
1/10 • Number of events 1 • up to approximately 40 months (3.3 years)
|
4.3%
1/23 • Number of events 1 • up to approximately 40 months (3.3 years)
|
|
Investigations
Pulse absent
|
0.00%
0/13 • up to approximately 40 months (3.3 years)
|
10.0%
1/10 • Number of events 1 • up to approximately 40 months (3.3 years)
|
4.3%
1/23 • Number of events 1 • up to approximately 40 months (3.3 years)
|
|
General disorders
Pyrexia
|
0.00%
0/13 • up to approximately 40 months (3.3 years)
|
10.0%
1/10 • Number of events 1 • up to approximately 40 months (3.3 years)
|
4.3%
1/23 • Number of events 1 • up to approximately 40 months (3.3 years)
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
0.00%
0/13 • up to approximately 40 months (3.3 years)
|
10.0%
1/10 • Number of events 1 • up to approximately 40 months (3.3 years)
|
4.3%
1/23 • Number of events 1 • up to approximately 40 months (3.3 years)
|
|
Infections and infestations
Sepsis
|
0.00%
0/13 • up to approximately 40 months (3.3 years)
|
10.0%
1/10 • Number of events 1 • up to approximately 40 months (3.3 years)
|
4.3%
1/23 • Number of events 1 • up to approximately 40 months (3.3 years)
|
|
Surgical and medical procedures
Stent removal
|
0.00%
0/13 • up to approximately 40 months (3.3 years)
|
10.0%
1/10 • Number of events 1 • up to approximately 40 months (3.3 years)
|
4.3%
1/23 • Number of events 1 • up to approximately 40 months (3.3 years)
|
|
Injury, poisoning and procedural complications
Subdural haematoma
|
0.00%
0/13 • up to approximately 40 months (3.3 years)
|
10.0%
1/10 • Number of events 1 • up to approximately 40 months (3.3 years)
|
4.3%
1/23 • Number of events 1 • up to approximately 40 months (3.3 years)
|
|
Cardiac disorders
Tachycardia
|
0.00%
0/13 • up to approximately 40 months (3.3 years)
|
10.0%
1/10 • Number of events 1 • up to approximately 40 months (3.3 years)
|
4.3%
1/23 • Number of events 1 • up to approximately 40 months (3.3 years)
|
|
Respiratory, thoracic and mediastinal disorders
Wheezing
|
0.00%
0/13 • up to approximately 40 months (3.3 years)
|
10.0%
1/10 • Number of events 1 • up to approximately 40 months (3.3 years)
|
4.3%
1/23 • Number of events 1 • up to approximately 40 months (3.3 years)
|
Other adverse events
| Measure |
Cohort A
n=13 participants at risk
Participants with MF who were tolerating a ruxolitinib dose of less than 20 milligrams (mg) daily with no dose increase or no dose modification in the 8 weeks before screening visit received a combination of itacitinib at the dose of 200 mg, orally, once daily (QD) and ruxolitinib, orally, twice daily (BID) at their previous stable dose (must had been \< 20 mg daily). Participants continued study treatment until disease progression, unacceptable toxicity, withdrawal of consent, or other Protocol-specified criteria to stop treatment were met.
|
Cohort B
n=10 participants at risk
Participants with MF who progressed after initial reduction in spleen with ruxolitinib treatment, progressed or discontinued for hematologic toxicities received treatment with itacitinib alone at the dose of 600 mg QD. Participants continued study treatment until disease progression, unacceptable toxicity, withdrawal of consent, or other Protocol-specified criteria to stop treatment were met.
|
Total
n=23 participants at risk
Total
|
|---|---|---|---|
|
Gastrointestinal disorders
Abdominal discomfort
|
0.00%
0/13 • up to approximately 40 months (3.3 years)
|
10.0%
1/10 • Number of events 1 • up to approximately 40 months (3.3 years)
|
4.3%
1/23 • Number of events 1 • up to approximately 40 months (3.3 years)
|
|
Gastrointestinal disorders
Abdominal distension
|
15.4%
2/13 • Number of events 2 • up to approximately 40 months (3.3 years)
|
0.00%
0/10 • up to approximately 40 months (3.3 years)
|
8.7%
2/23 • Number of events 2 • up to approximately 40 months (3.3 years)
|
|
Gastrointestinal disorders
Abdominal pain
|
30.8%
4/13 • Number of events 4 • up to approximately 40 months (3.3 years)
|
30.0%
3/10 • Number of events 3 • up to approximately 40 months (3.3 years)
|
30.4%
7/23 • Number of events 7 • up to approximately 40 months (3.3 years)
|
|
Gastrointestinal disorders
Abdominal pain upper
|
7.7%
1/13 • Number of events 1 • up to approximately 40 months (3.3 years)
|
20.0%
2/10 • Number of events 4 • up to approximately 40 months (3.3 years)
|
13.0%
3/23 • Number of events 5 • up to approximately 40 months (3.3 years)
|
|
Renal and urinary disorders
Acute kidney injury
|
0.00%
0/13 • up to approximately 40 months (3.3 years)
|
20.0%
2/10 • Number of events 2 • up to approximately 40 months (3.3 years)
|
8.7%
2/23 • Number of events 2 • up to approximately 40 months (3.3 years)
|
|
Blood and lymphatic system disorders
Anaemia
|
30.8%
4/13 • Number of events 4 • up to approximately 40 months (3.3 years)
|
40.0%
4/10 • Number of events 10 • up to approximately 40 months (3.3 years)
|
34.8%
8/23 • Number of events 14 • up to approximately 40 months (3.3 years)
|
|
Cardiac disorders
Arrhythmia
|
0.00%
0/13 • up to approximately 40 months (3.3 years)
|
10.0%
1/10 • Number of events 1 • up to approximately 40 months (3.3 years)
|
4.3%
1/23 • Number of events 1 • up to approximately 40 months (3.3 years)
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
7.7%
1/13 • Number of events 2 • up to approximately 40 months (3.3 years)
|
10.0%
1/10 • Number of events 1 • up to approximately 40 months (3.3 years)
|
8.7%
2/23 • Number of events 3 • up to approximately 40 months (3.3 years)
|
|
Investigations
Aspartate aminotransferase increased
|
7.7%
1/13 • Number of events 2 • up to approximately 40 months (3.3 years)
|
0.00%
0/10 • up to approximately 40 months (3.3 years)
|
4.3%
1/23 • Number of events 2 • up to approximately 40 months (3.3 years)
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
7.7%
1/13 • Number of events 1 • up to approximately 40 months (3.3 years)
|
10.0%
1/10 • Number of events 1 • up to approximately 40 months (3.3 years)
|
8.7%
2/23 • Number of events 2 • up to approximately 40 months (3.3 years)
|
|
Nervous system disorders
Balance disorder
|
0.00%
0/13 • up to approximately 40 months (3.3 years)
|
10.0%
1/10 • Number of events 1 • up to approximately 40 months (3.3 years)
|
4.3%
1/23 • Number of events 1 • up to approximately 40 months (3.3 years)
|
|
Investigations
Blood bilirubin increased
|
15.4%
2/13 • Number of events 3 • up to approximately 40 months (3.3 years)
|
10.0%
1/10 • Number of events 1 • up to approximately 40 months (3.3 years)
|
13.0%
3/23 • Number of events 4 • up to approximately 40 months (3.3 years)
|
|
Investigations
Blood chloride increased
|
7.7%
1/13 • Number of events 1 • up to approximately 40 months (3.3 years)
|
0.00%
0/10 • up to approximately 40 months (3.3 years)
|
4.3%
1/23 • Number of events 1 • up to approximately 40 months (3.3 years)
|
|
Investigations
Blood creatinine increased
|
7.7%
1/13 • Number of events 2 • up to approximately 40 months (3.3 years)
|
10.0%
1/10 • Number of events 2 • up to approximately 40 months (3.3 years)
|
8.7%
2/23 • Number of events 4 • up to approximately 40 months (3.3 years)
|
|
Investigations
Blood lactate dehydrogenase increased
|
0.00%
0/13 • up to approximately 40 months (3.3 years)
|
10.0%
1/10 • Number of events 1 • up to approximately 40 months (3.3 years)
|
4.3%
1/23 • Number of events 1 • up to approximately 40 months (3.3 years)
|
|
Investigations
Blood triglycerides increased
|
7.7%
1/13 • Number of events 1 • up to approximately 40 months (3.3 years)
|
0.00%
0/10 • up to approximately 40 months (3.3 years)
|
4.3%
1/23 • Number of events 1 • up to approximately 40 months (3.3 years)
|
|
Investigations
Blood uric acid increased
|
15.4%
2/13 • Number of events 2 • up to approximately 40 months (3.3 years)
|
0.00%
0/10 • up to approximately 40 months (3.3 years)
|
8.7%
2/23 • Number of events 2 • up to approximately 40 months (3.3 years)
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
15.4%
2/13 • Number of events 2 • up to approximately 40 months (3.3 years)
|
10.0%
1/10 • Number of events 1 • up to approximately 40 months (3.3 years)
|
13.0%
3/23 • Number of events 3 • up to approximately 40 months (3.3 years)
|
|
Investigations
C-reactive protein increased
|
0.00%
0/13 • up to approximately 40 months (3.3 years)
|
10.0%
1/10 • Number of events 1 • up to approximately 40 months (3.3 years)
|
4.3%
1/23 • Number of events 1 • up to approximately 40 months (3.3 years)
|
|
General disorders
Calcinosis
|
0.00%
0/13 • up to approximately 40 months (3.3 years)
|
10.0%
1/10 • Number of events 1 • up to approximately 40 months (3.3 years)
|
4.3%
1/23 • Number of events 1 • up to approximately 40 months (3.3 years)
|
|
Cardiac disorders
Cardiac failure
|
0.00%
0/13 • up to approximately 40 months (3.3 years)
|
10.0%
1/10 • Number of events 1 • up to approximately 40 months (3.3 years)
|
4.3%
1/23 • Number of events 1 • up to approximately 40 months (3.3 years)
|
|
Infections and infestations
Cellulitis
|
0.00%
0/13 • up to approximately 40 months (3.3 years)
|
10.0%
1/10 • Number of events 1 • up to approximately 40 months (3.3 years)
|
4.3%
1/23 • Number of events 1 • up to approximately 40 months (3.3 years)
|
|
General disorders
Chest discomfort
|
7.7%
1/13 • Number of events 1 • up to approximately 40 months (3.3 years)
|
0.00%
0/10 • up to approximately 40 months (3.3 years)
|
4.3%
1/23 • Number of events 1 • up to approximately 40 months (3.3 years)
|
|
General disorders
Chills
|
7.7%
1/13 • Number of events 1 • up to approximately 40 months (3.3 years)
|
10.0%
1/10 • Number of events 1 • up to approximately 40 months (3.3 years)
|
8.7%
2/23 • Number of events 2 • up to approximately 40 months (3.3 years)
|
|
Musculoskeletal and connective tissue disorders
Chondrocalcinosis pyrophosphate
|
7.7%
1/13 • Number of events 2 • up to approximately 40 months (3.3 years)
|
0.00%
0/10 • up to approximately 40 months (3.3 years)
|
4.3%
1/23 • Number of events 2 • up to approximately 40 months (3.3 years)
|
|
Renal and urinary disorders
Chronic kidney disease
|
0.00%
0/13 • up to approximately 40 months (3.3 years)
|
10.0%
1/10 • Number of events 1 • up to approximately 40 months (3.3 years)
|
4.3%
1/23 • Number of events 1 • up to approximately 40 months (3.3 years)
|
|
Infections and infestations
Clostridium difficile colitis
|
0.00%
0/13 • up to approximately 40 months (3.3 years)
|
10.0%
1/10 • Number of events 1 • up to approximately 40 months (3.3 years)
|
4.3%
1/23 • Number of events 1 • up to approximately 40 months (3.3 years)
|
|
Infections and infestations
Conjunctivitis
|
7.7%
1/13 • Number of events 1 • up to approximately 40 months (3.3 years)
|
0.00%
0/10 • up to approximately 40 months (3.3 years)
|
4.3%
1/23 • Number of events 1 • up to approximately 40 months (3.3 years)
|
|
Gastrointestinal disorders
Constipation
|
7.7%
1/13 • Number of events 1 • up to approximately 40 months (3.3 years)
|
20.0%
2/10 • Number of events 3 • up to approximately 40 months (3.3 years)
|
13.0%
3/23 • Number of events 4 • up to approximately 40 months (3.3 years)
|
|
Injury, poisoning and procedural complications
Contusion
|
15.4%
2/13 • Number of events 2 • up to approximately 40 months (3.3 years)
|
20.0%
2/10 • Number of events 3 • up to approximately 40 months (3.3 years)
|
17.4%
4/23 • Number of events 5 • up to approximately 40 months (3.3 years)
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
7.7%
1/13 • Number of events 2 • up to approximately 40 months (3.3 years)
|
10.0%
1/10 • Number of events 2 • up to approximately 40 months (3.3 years)
|
8.7%
2/23 • Number of events 4 • up to approximately 40 months (3.3 years)
|
|
Metabolism and nutrition disorders
Decreased appetite
|
15.4%
2/13 • Number of events 2 • up to approximately 40 months (3.3 years)
|
20.0%
2/10 • Number of events 2 • up to approximately 40 months (3.3 years)
|
17.4%
4/23 • Number of events 4 • up to approximately 40 months (3.3 years)
|
|
Skin and subcutaneous tissue disorders
Decubitus ulcer
|
0.00%
0/13 • up to approximately 40 months (3.3 years)
|
10.0%
1/10 • Number of events 1 • up to approximately 40 months (3.3 years)
|
4.3%
1/23 • Number of events 1 • up to approximately 40 months (3.3 years)
|
|
Metabolism and nutrition disorders
Dehydration
|
15.4%
2/13 • Number of events 2 • up to approximately 40 months (3.3 years)
|
0.00%
0/10 • up to approximately 40 months (3.3 years)
|
8.7%
2/23 • Number of events 2 • up to approximately 40 months (3.3 years)
|
|
Psychiatric disorders
Depressive symptom
|
0.00%
0/13 • up to approximately 40 months (3.3 years)
|
10.0%
1/10 • Number of events 1 • up to approximately 40 months (3.3 years)
|
4.3%
1/23 • Number of events 1 • up to approximately 40 months (3.3 years)
|
|
Skin and subcutaneous tissue disorders
Dermatitis
|
0.00%
0/13 • up to approximately 40 months (3.3 years)
|
10.0%
1/10 • Number of events 1 • up to approximately 40 months (3.3 years)
|
4.3%
1/23 • Number of events 1 • up to approximately 40 months (3.3 years)
|
|
Skin and subcutaneous tissue disorders
Dermatitis acneiform
|
0.00%
0/13 • up to approximately 40 months (3.3 years)
|
10.0%
1/10 • Number of events 1 • up to approximately 40 months (3.3 years)
|
4.3%
1/23 • Number of events 1 • up to approximately 40 months (3.3 years)
|
|
Nervous system disorders
Diabetic neuropathy
|
0.00%
0/13 • up to approximately 40 months (3.3 years)
|
10.0%
1/10 • Number of events 1 • up to approximately 40 months (3.3 years)
|
4.3%
1/23 • Number of events 1 • up to approximately 40 months (3.3 years)
|
|
Gastrointestinal disorders
Diarrhoea
|
30.8%
4/13 • Number of events 4 • up to approximately 40 months (3.3 years)
|
40.0%
4/10 • Number of events 8 • up to approximately 40 months (3.3 years)
|
34.8%
8/23 • Number of events 12 • up to approximately 40 months (3.3 years)
|
|
Nervous system disorders
Dizziness
|
30.8%
4/13 • Number of events 4 • up to approximately 40 months (3.3 years)
|
20.0%
2/10 • Number of events 2 • up to approximately 40 months (3.3 years)
|
26.1%
6/23 • Number of events 6 • up to approximately 40 months (3.3 years)
|
|
Gastrointestinal disorders
Dry mouth
|
0.00%
0/13 • up to approximately 40 months (3.3 years)
|
10.0%
1/10 • Number of events 1 • up to approximately 40 months (3.3 years)
|
4.3%
1/23 • Number of events 1 • up to approximately 40 months (3.3 years)
|
|
Nervous system disorders
Dysarthria
|
0.00%
0/13 • up to approximately 40 months (3.3 years)
|
10.0%
1/10 • Number of events 1 • up to approximately 40 months (3.3 years)
|
4.3%
1/23 • Number of events 1 • up to approximately 40 months (3.3 years)
|
|
Psychiatric disorders
Dysphoria
|
7.7%
1/13 • Number of events 1 • up to approximately 40 months (3.3 years)
|
0.00%
0/10 • up to approximately 40 months (3.3 years)
|
4.3%
1/23 • Number of events 1 • up to approximately 40 months (3.3 years)
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
15.4%
2/13 • Number of events 2 • up to approximately 40 months (3.3 years)
|
30.0%
3/10 • Number of events 3 • up to approximately 40 months (3.3 years)
|
21.7%
5/23 • Number of events 5 • up to approximately 40 months (3.3 years)
|
|
Renal and urinary disorders
Dysuria
|
0.00%
0/13 • up to approximately 40 months (3.3 years)
|
10.0%
1/10 • Number of events 1 • up to approximately 40 months (3.3 years)
|
4.3%
1/23 • Number of events 1 • up to approximately 40 months (3.3 years)
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
0.00%
0/13 • up to approximately 40 months (3.3 years)
|
20.0%
2/10 • Number of events 2 • up to approximately 40 months (3.3 years)
|
8.7%
2/23 • Number of events 2 • up to approximately 40 months (3.3 years)
|
|
General disorders
Exercise tolerance decreased
|
0.00%
0/13 • up to approximately 40 months (3.3 years)
|
10.0%
1/10 • Number of events 1 • up to approximately 40 months (3.3 years)
|
4.3%
1/23 • Number of events 1 • up to approximately 40 months (3.3 years)
|
|
Injury, poisoning and procedural complications
Fall
|
7.7%
1/13 • Number of events 1 • up to approximately 40 months (3.3 years)
|
30.0%
3/10 • Number of events 3 • up to approximately 40 months (3.3 years)
|
17.4%
4/23 • Number of events 4 • up to approximately 40 months (3.3 years)
|
|
General disorders
Fatigue
|
23.1%
3/13 • Number of events 3 • up to approximately 40 months (3.3 years)
|
50.0%
5/10 • Number of events 6 • up to approximately 40 months (3.3 years)
|
34.8%
8/23 • Number of events 9 • up to approximately 40 months (3.3 years)
|
|
Gastrointestinal disorders
Flatulence
|
7.7%
1/13 • Number of events 1 • up to approximately 40 months (3.3 years)
|
0.00%
0/10 • up to approximately 40 months (3.3 years)
|
4.3%
1/23 • Number of events 1 • up to approximately 40 months (3.3 years)
|
|
Infections and infestations
Fungal skin infection
|
0.00%
0/13 • up to approximately 40 months (3.3 years)
|
10.0%
1/10 • Number of events 1 • up to approximately 40 months (3.3 years)
|
4.3%
1/23 • Number of events 1 • up to approximately 40 months (3.3 years)
|
|
Infections and infestations
Gastrointestinal viral infection
|
7.7%
1/13 • Number of events 1 • up to approximately 40 months (3.3 years)
|
0.00%
0/10 • up to approximately 40 months (3.3 years)
|
4.3%
1/23 • Number of events 1 • up to approximately 40 months (3.3 years)
|
|
Gastrointestinal disorders
Gingival bleeding
|
0.00%
0/13 • up to approximately 40 months (3.3 years)
|
10.0%
1/10 • Number of events 1 • up to approximately 40 months (3.3 years)
|
4.3%
1/23 • Number of events 1 • up to approximately 40 months (3.3 years)
|
|
Metabolism and nutrition disorders
Gout
|
0.00%
0/13 • up to approximately 40 months (3.3 years)
|
20.0%
2/10 • Number of events 2 • up to approximately 40 months (3.3 years)
|
8.7%
2/23 • Number of events 2 • up to approximately 40 months (3.3 years)
|
|
Vascular disorders
Haematoma
|
7.7%
1/13 • Number of events 1 • up to approximately 40 months (3.3 years)
|
10.0%
1/10 • Number of events 1 • up to approximately 40 months (3.3 years)
|
8.7%
2/23 • Number of events 2 • up to approximately 40 months (3.3 years)
|
|
Respiratory, thoracic and mediastinal disorders
Haemoptysis
|
0.00%
0/13 • up to approximately 40 months (3.3 years)
|
10.0%
1/10 • Number of events 1 • up to approximately 40 months (3.3 years)
|
4.3%
1/23 • Number of events 1 • up to approximately 40 months (3.3 years)
|
|
Gastrointestinal disorders
Haemorrhoidal haemorrhage
|
7.7%
1/13 • Number of events 1 • up to approximately 40 months (3.3 years)
|
0.00%
0/10 • up to approximately 40 months (3.3 years)
|
4.3%
1/23 • Number of events 1 • up to approximately 40 months (3.3 years)
|
|
Nervous system disorders
Headache
|
15.4%
2/13 • Number of events 2 • up to approximately 40 months (3.3 years)
|
10.0%
1/10 • Number of events 1 • up to approximately 40 months (3.3 years)
|
13.0%
3/23 • Number of events 3 • up to approximately 40 months (3.3 years)
|
|
Hepatobiliary disorders
Hepatomegaly
|
7.7%
1/13 • Number of events 1 • up to approximately 40 months (3.3 years)
|
0.00%
0/10 • up to approximately 40 months (3.3 years)
|
4.3%
1/23 • Number of events 1 • up to approximately 40 months (3.3 years)
|
|
Infections and infestations
Herpes simplex
|
7.7%
1/13 • Number of events 1 • up to approximately 40 months (3.3 years)
|
0.00%
0/10 • up to approximately 40 months (3.3 years)
|
4.3%
1/23 • Number of events 1 • up to approximately 40 months (3.3 years)
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
0.00%
0/13 • up to approximately 40 months (3.3 years)
|
10.0%
1/10 • Number of events 1 • up to approximately 40 months (3.3 years)
|
4.3%
1/23 • Number of events 1 • up to approximately 40 months (3.3 years)
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
7.7%
1/13 • Number of events 1 • up to approximately 40 months (3.3 years)
|
0.00%
0/10 • up to approximately 40 months (3.3 years)
|
4.3%
1/23 • Number of events 1 • up to approximately 40 months (3.3 years)
|
|
Metabolism and nutrition disorders
Hyperkalaemia
|
7.7%
1/13 • Number of events 1 • up to approximately 40 months (3.3 years)
|
10.0%
1/10 • Number of events 1 • up to approximately 40 months (3.3 years)
|
8.7%
2/23 • Number of events 2 • up to approximately 40 months (3.3 years)
|
|
Immune system disorders
Hypersensitivity
|
0.00%
0/13 • up to approximately 40 months (3.3 years)
|
10.0%
1/10 • Number of events 1 • up to approximately 40 months (3.3 years)
|
4.3%
1/23 • Number of events 1 • up to approximately 40 months (3.3 years)
|
|
Metabolism and nutrition disorders
Hyperuricaemia
|
7.7%
1/13 • Number of events 1 • up to approximately 40 months (3.3 years)
|
10.0%
1/10 • Number of events 1 • up to approximately 40 months (3.3 years)
|
8.7%
2/23 • Number of events 2 • up to approximately 40 months (3.3 years)
|
|
Nervous system disorders
Hypoaesthesia
|
7.7%
1/13 • Number of events 1 • up to approximately 40 months (3.3 years)
|
0.00%
0/10 • up to approximately 40 months (3.3 years)
|
4.3%
1/23 • Number of events 1 • up to approximately 40 months (3.3 years)
|
|
Metabolism and nutrition disorders
Hypoalbuminaemia
|
0.00%
0/13 • up to approximately 40 months (3.3 years)
|
10.0%
1/10 • Number of events 1 • up to approximately 40 months (3.3 years)
|
4.3%
1/23 • Number of events 1 • up to approximately 40 months (3.3 years)
|
|
Metabolism and nutrition disorders
Hypocalcaemia
|
7.7%
1/13 • Number of events 2 • up to approximately 40 months (3.3 years)
|
20.0%
2/10 • Number of events 3 • up to approximately 40 months (3.3 years)
|
13.0%
3/23 • Number of events 5 • up to approximately 40 months (3.3 years)
|
|
Blood and lymphatic system disorders
Hypofibrinogenaemia
|
0.00%
0/13 • up to approximately 40 months (3.3 years)
|
10.0%
1/10 • Number of events 1 • up to approximately 40 months (3.3 years)
|
4.3%
1/23 • Number of events 1 • up to approximately 40 months (3.3 years)
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
7.7%
1/13 • Number of events 1 • up to approximately 40 months (3.3 years)
|
20.0%
2/10 • Number of events 2 • up to approximately 40 months (3.3 years)
|
13.0%
3/23 • Number of events 3 • up to approximately 40 months (3.3 years)
|
|
Metabolism and nutrition disorders
Hypomagnesaemia
|
0.00%
0/13 • up to approximately 40 months (3.3 years)
|
10.0%
1/10 • Number of events 1 • up to approximately 40 months (3.3 years)
|
4.3%
1/23 • Number of events 1 • up to approximately 40 months (3.3 years)
|
|
Metabolism and nutrition disorders
Hypophosphataemia
|
0.00%
0/13 • up to approximately 40 months (3.3 years)
|
10.0%
1/10 • Number of events 1 • up to approximately 40 months (3.3 years)
|
4.3%
1/23 • Number of events 1 • up to approximately 40 months (3.3 years)
|
|
Vascular disorders
Hypotension
|
15.4%
2/13 • Number of events 2 • up to approximately 40 months (3.3 years)
|
20.0%
2/10 • Number of events 2 • up to approximately 40 months (3.3 years)
|
17.4%
4/23 • Number of events 4 • up to approximately 40 months (3.3 years)
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
7.7%
1/13 • Number of events 1 • up to approximately 40 months (3.3 years)
|
10.0%
1/10 • Number of events 1 • up to approximately 40 months (3.3 years)
|
8.7%
2/23 • Number of events 2 • up to approximately 40 months (3.3 years)
|
|
Blood and lymphatic system disorders
Increased tendency to bruise
|
7.7%
1/13 • Number of events 1 • up to approximately 40 months (3.3 years)
|
0.00%
0/10 • up to approximately 40 months (3.3 years)
|
4.3%
1/23 • Number of events 1 • up to approximately 40 months (3.3 years)
|
|
General disorders
Influenza like illness
|
0.00%
0/13 • up to approximately 40 months (3.3 years)
|
10.0%
1/10 • Number of events 1 • up to approximately 40 months (3.3 years)
|
4.3%
1/23 • Number of events 1 • up to approximately 40 months (3.3 years)
|
|
Metabolism and nutrition disorders
Iron deficiency
|
7.7%
1/13 • Number of events 1 • up to approximately 40 months (3.3 years)
|
10.0%
1/10 • Number of events 1 • up to approximately 40 months (3.3 years)
|
8.7%
2/23 • Number of events 2 • up to approximately 40 months (3.3 years)
|
|
Metabolism and nutrition disorders
Lactic acidosis
|
7.7%
1/13 • Number of events 1 • up to approximately 40 months (3.3 years)
|
0.00%
0/10 • up to approximately 40 months (3.3 years)
|
4.3%
1/23 • Number of events 1 • up to approximately 40 months (3.3 years)
|
|
Cardiac disorders
Left ventricular hypertrophy
|
0.00%
0/13 • up to approximately 40 months (3.3 years)
|
10.0%
1/10 • Number of events 1 • up to approximately 40 months (3.3 years)
|
4.3%
1/23 • Number of events 1 • up to approximately 40 months (3.3 years)
|
|
Nervous system disorders
Lethargy
|
7.7%
1/13 • Number of events 1 • up to approximately 40 months (3.3 years)
|
0.00%
0/10 • up to approximately 40 months (3.3 years)
|
4.3%
1/23 • Number of events 1 • up to approximately 40 months (3.3 years)
|
|
Blood and lymphatic system disorders
Leukocytosis
|
0.00%
0/13 • up to approximately 40 months (3.3 years)
|
10.0%
1/10 • Number of events 1 • up to approximately 40 months (3.3 years)
|
4.3%
1/23 • Number of events 1 • up to approximately 40 months (3.3 years)
|
|
General disorders
Malaise
|
0.00%
0/13 • up to approximately 40 months (3.3 years)
|
10.0%
1/10 • Number of events 1 • up to approximately 40 months (3.3 years)
|
4.3%
1/23 • Number of events 1 • up to approximately 40 months (3.3 years)
|
|
Renal and urinary disorders
Micturition urgency
|
0.00%
0/13 • up to approximately 40 months (3.3 years)
|
10.0%
1/10 • Number of events 1 • up to approximately 40 months (3.3 years)
|
4.3%
1/23 • Number of events 1 • up to approximately 40 months (3.3 years)
|
|
Gastrointestinal disorders
Mouth ulceration
|
7.7%
1/13 • Number of events 1 • up to approximately 40 months (3.3 years)
|
0.00%
0/10 • up to approximately 40 months (3.3 years)
|
4.3%
1/23 • Number of events 1 • up to approximately 40 months (3.3 years)
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
23.1%
3/13 • Number of events 3 • up to approximately 40 months (3.3 years)
|
0.00%
0/10 • up to approximately 40 months (3.3 years)
|
13.0%
3/23 • Number of events 3 • up to approximately 40 months (3.3 years)
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
7.7%
1/13 • Number of events 1 • up to approximately 40 months (3.3 years)
|
10.0%
1/10 • Number of events 1 • up to approximately 40 months (3.3 years)
|
8.7%
2/23 • Number of events 2 • up to approximately 40 months (3.3 years)
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
|
7.7%
1/13 • Number of events 1 • up to approximately 40 months (3.3 years)
|
0.00%
0/10 • up to approximately 40 months (3.3 years)
|
4.3%
1/23 • Number of events 1 • up to approximately 40 months (3.3 years)
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
7.7%
1/13 • Number of events 1 • up to approximately 40 months (3.3 years)
|
0.00%
0/10 • up to approximately 40 months (3.3 years)
|
4.3%
1/23 • Number of events 1 • up to approximately 40 months (3.3 years)
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
0.00%
0/13 • up to approximately 40 months (3.3 years)
|
10.0%
1/10 • Number of events 1 • up to approximately 40 months (3.3 years)
|
4.3%
1/23 • Number of events 1 • up to approximately 40 months (3.3 years)
|
|
Gastrointestinal disorders
Nausea
|
15.4%
2/13 • Number of events 2 • up to approximately 40 months (3.3 years)
|
30.0%
3/10 • Number of events 5 • up to approximately 40 months (3.3 years)
|
21.7%
5/23 • Number of events 7 • up to approximately 40 months (3.3 years)
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasm malignant
|
7.7%
1/13 • Number of events 1 • up to approximately 40 months (3.3 years)
|
0.00%
0/10 • up to approximately 40 months (3.3 years)
|
4.3%
1/23 • Number of events 1 • up to approximately 40 months (3.3 years)
|
|
Renal and urinary disorders
Nephrolithiasis
|
0.00%
0/13 • up to approximately 40 months (3.3 years)
|
10.0%
1/10 • Number of events 1 • up to approximately 40 months (3.3 years)
|
4.3%
1/23 • Number of events 1 • up to approximately 40 months (3.3 years)
|
|
Investigations
Neutrophil count decreased
|
0.00%
0/13 • up to approximately 40 months (3.3 years)
|
10.0%
1/10 • Number of events 1 • up to approximately 40 months (3.3 years)
|
4.3%
1/23 • Number of events 1 • up to approximately 40 months (3.3 years)
|
|
Skin and subcutaneous tissue disorders
Night sweats
|
7.7%
1/13 • Number of events 1 • up to approximately 40 months (3.3 years)
|
0.00%
0/10 • up to approximately 40 months (3.3 years)
|
4.3%
1/23 • Number of events 1 • up to approximately 40 months (3.3 years)
|
|
General disorders
Oedema
|
0.00%
0/13 • up to approximately 40 months (3.3 years)
|
10.0%
1/10 • Number of events 1 • up to approximately 40 months (3.3 years)
|
4.3%
1/23 • Number of events 1 • up to approximately 40 months (3.3 years)
|
|
General disorders
Oedema peripheral
|
15.4%
2/13 • Number of events 2 • up to approximately 40 months (3.3 years)
|
10.0%
1/10 • Number of events 1 • up to approximately 40 months (3.3 years)
|
13.0%
3/23 • Number of events 3 • up to approximately 40 months (3.3 years)
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
7.7%
1/13 • Number of events 1 • up to approximately 40 months (3.3 years)
|
10.0%
1/10 • Number of events 1 • up to approximately 40 months (3.3 years)
|
8.7%
2/23 • Number of events 2 • up to approximately 40 months (3.3 years)
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
7.7%
1/13 • Number of events 1 • up to approximately 40 months (3.3 years)
|
0.00%
0/10 • up to approximately 40 months (3.3 years)
|
4.3%
1/23 • Number of events 1 • up to approximately 40 months (3.3 years)
|
|
Nervous system disorders
Paraesthesia
|
7.7%
1/13 • Number of events 1 • up to approximately 40 months (3.3 years)
|
0.00%
0/10 • up to approximately 40 months (3.3 years)
|
4.3%
1/23 • Number of events 1 • up to approximately 40 months (3.3 years)
|
|
General disorders
Peripheral swelling
|
0.00%
0/13 • up to approximately 40 months (3.3 years)
|
10.0%
1/10 • Number of events 1 • up to approximately 40 months (3.3 years)
|
4.3%
1/23 • Number of events 1 • up to approximately 40 months (3.3 years)
|
|
Investigations
Platelet count decreased
|
7.7%
1/13 • Number of events 1 • up to approximately 40 months (3.3 years)
|
10.0%
1/10 • Number of events 2 • up to approximately 40 months (3.3 years)
|
8.7%
2/23 • Number of events 3 • up to approximately 40 months (3.3 years)
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
7.7%
1/13 • Number of events 1 • up to approximately 40 months (3.3 years)
|
0.00%
0/10 • up to approximately 40 months (3.3 years)
|
4.3%
1/23 • Number of events 1 • up to approximately 40 months (3.3 years)
|
|
Infections and infestations
Pneumonia
|
7.7%
1/13 • Number of events 1 • up to approximately 40 months (3.3 years)
|
10.0%
1/10 • Number of events 1 • up to approximately 40 months (3.3 years)
|
8.7%
2/23 • Number of events 2 • up to approximately 40 months (3.3 years)
|
|
Renal and urinary disorders
Pollakiuria
|
7.7%
1/13 • Number of events 2 • up to approximately 40 months (3.3 years)
|
0.00%
0/10 • up to approximately 40 months (3.3 years)
|
4.3%
1/23 • Number of events 2 • up to approximately 40 months (3.3 years)
|
|
Musculoskeletal and connective tissue disorders
Posterior tibial tendon dysfunction
|
0.00%
0/13 • up to approximately 40 months (3.3 years)
|
10.0%
1/10 • Number of events 1 • up to approximately 40 months (3.3 years)
|
4.3%
1/23 • Number of events 1 • up to approximately 40 months (3.3 years)
|
|
Nervous system disorders
Presyncope
|
0.00%
0/13 • up to approximately 40 months (3.3 years)
|
10.0%
1/10 • Number of events 1 • up to approximately 40 months (3.3 years)
|
4.3%
1/23 • Number of events 1 • up to approximately 40 months (3.3 years)
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
23.1%
3/13 • Number of events 4 • up to approximately 40 months (3.3 years)
|
0.00%
0/10 • up to approximately 40 months (3.3 years)
|
13.0%
3/23 • Number of events 4 • up to approximately 40 months (3.3 years)
|
|
General disorders
Pyrexia
|
7.7%
1/13 • Number of events 1 • up to approximately 40 months (3.3 years)
|
40.0%
4/10 • Number of events 6 • up to approximately 40 months (3.3 years)
|
21.7%
5/23 • Number of events 7 • up to approximately 40 months (3.3 years)
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.00%
0/13 • up to approximately 40 months (3.3 years)
|
10.0%
1/10 • Number of events 1 • up to approximately 40 months (3.3 years)
|
4.3%
1/23 • Number of events 1 • up to approximately 40 months (3.3 years)
|
|
Infections and infestations
Rash pustular
|
7.7%
1/13 • Number of events 1 • up to approximately 40 months (3.3 years)
|
0.00%
0/10 • up to approximately 40 months (3.3 years)
|
4.3%
1/23 • Number of events 1 • up to approximately 40 months (3.3 years)
|
|
Investigations
Reticulocyte count increased
|
0.00%
0/13 • up to approximately 40 months (3.3 years)
|
10.0%
1/10 • Number of events 1 • up to approximately 40 months (3.3 years)
|
4.3%
1/23 • Number of events 1 • up to approximately 40 months (3.3 years)
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
15.4%
2/13 • Number of events 2 • up to approximately 40 months (3.3 years)
|
0.00%
0/10 • up to approximately 40 months (3.3 years)
|
8.7%
2/23 • Number of events 2 • up to approximately 40 months (3.3 years)
|
|
Investigations
Serum ferritin increased
|
0.00%
0/13 • up to approximately 40 months (3.3 years)
|
10.0%
1/10 • Number of events 1 • up to approximately 40 months (3.3 years)
|
4.3%
1/23 • Number of events 1 • up to approximately 40 months (3.3 years)
|
|
Injury, poisoning and procedural complications
Skin abrasion
|
7.7%
1/13 • Number of events 1 • up to approximately 40 months (3.3 years)
|
0.00%
0/10 • up to approximately 40 months (3.3 years)
|
4.3%
1/23 • Number of events 1 • up to approximately 40 months (3.3 years)
|
|
Skin and subcutaneous tissue disorders
Skin exfoliation
|
7.7%
1/13 • Number of events 1 • up to approximately 40 months (3.3 years)
|
0.00%
0/10 • up to approximately 40 months (3.3 years)
|
4.3%
1/23 • Number of events 1 • up to approximately 40 months (3.3 years)
|
|
Injury, poisoning and procedural complications
Skin laceration
|
0.00%
0/13 • up to approximately 40 months (3.3 years)
|
10.0%
1/10 • Number of events 1 • up to approximately 40 months (3.3 years)
|
4.3%
1/23 • Number of events 1 • up to approximately 40 months (3.3 years)
|
|
Skin and subcutaneous tissue disorders
Skin lesion
|
7.7%
1/13 • Number of events 1 • up to approximately 40 months (3.3 years)
|
0.00%
0/10 • up to approximately 40 months (3.3 years)
|
4.3%
1/23 • Number of events 1 • up to approximately 40 months (3.3 years)
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Skin papilloma
|
7.7%
1/13 • Number of events 1 • up to approximately 40 months (3.3 years)
|
0.00%
0/10 • up to approximately 40 months (3.3 years)
|
4.3%
1/23 • Number of events 1 • up to approximately 40 months (3.3 years)
|
|
Blood and lymphatic system disorders
Splenic infarction
|
7.7%
1/13 • Number of events 1 • up to approximately 40 months (3.3 years)
|
10.0%
1/10 • Number of events 1 • up to approximately 40 months (3.3 years)
|
8.7%
2/23 • Number of events 2 • up to approximately 40 months (3.3 years)
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Squamous cell carcinoma of skin
|
0.00%
0/13 • up to approximately 40 months (3.3 years)
|
10.0%
1/10 • Number of events 1 • up to approximately 40 months (3.3 years)
|
4.3%
1/23 • Number of events 1 • up to approximately 40 months (3.3 years)
|
|
Gastrointestinal disorders
Stomatitis
|
7.7%
1/13 • Number of events 1 • up to approximately 40 months (3.3 years)
|
10.0%
1/10 • Number of events 1 • up to approximately 40 months (3.3 years)
|
8.7%
2/23 • Number of events 2 • up to approximately 40 months (3.3 years)
|
|
Cardiac disorders
Tachycardia
|
0.00%
0/13 • up to approximately 40 months (3.3 years)
|
10.0%
1/10 • Number of events 1 • up to approximately 40 months (3.3 years)
|
4.3%
1/23 • Number of events 1 • up to approximately 40 months (3.3 years)
|
|
General disorders
Thirst
|
0.00%
0/13 • up to approximately 40 months (3.3 years)
|
10.0%
1/10 • Number of events 1 • up to approximately 40 months (3.3 years)
|
4.3%
1/23 • Number of events 1 • up to approximately 40 months (3.3 years)
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
15.4%
2/13 • Number of events 5 • up to approximately 40 months (3.3 years)
|
20.0%
2/10 • Number of events 2 • up to approximately 40 months (3.3 years)
|
17.4%
4/23 • Number of events 7 • up to approximately 40 months (3.3 years)
|
|
Blood and lymphatic system disorders
Thrombocytosis
|
0.00%
0/13 • up to approximately 40 months (3.3 years)
|
10.0%
1/10 • Number of events 1 • up to approximately 40 months (3.3 years)
|
4.3%
1/23 • Number of events 1 • up to approximately 40 months (3.3 years)
|
|
Vascular disorders
Thrombophlebitis
|
0.00%
0/13 • up to approximately 40 months (3.3 years)
|
10.0%
1/10 • Number of events 1 • up to approximately 40 months (3.3 years)
|
4.3%
1/23 • Number of events 1 • up to approximately 40 months (3.3 years)
|
|
Infections and infestations
Tooth abscess
|
0.00%
0/13 • up to approximately 40 months (3.3 years)
|
10.0%
1/10 • Number of events 1 • up to approximately 40 months (3.3 years)
|
4.3%
1/23 • Number of events 1 • up to approximately 40 months (3.3 years)
|
|
Gastrointestinal disorders
Tooth disorder
|
7.7%
1/13 • Number of events 1 • up to approximately 40 months (3.3 years)
|
0.00%
0/10 • up to approximately 40 months (3.3 years)
|
4.3%
1/23 • Number of events 1 • up to approximately 40 months (3.3 years)
|
|
Infections and infestations
Upper respiratory tract infection
|
7.7%
1/13 • Number of events 3 • up to approximately 40 months (3.3 years)
|
0.00%
0/10 • up to approximately 40 months (3.3 years)
|
4.3%
1/23 • Number of events 3 • up to approximately 40 months (3.3 years)
|
|
Respiratory, thoracic and mediastinal disorders
Upper-airway cough syndrome
|
7.7%
1/13 • Number of events 1 • up to approximately 40 months (3.3 years)
|
0.00%
0/10 • up to approximately 40 months (3.3 years)
|
4.3%
1/23 • Number of events 1 • up to approximately 40 months (3.3 years)
|
|
Renal and urinary disorders
Urinary incontinence
|
0.00%
0/13 • up to approximately 40 months (3.3 years)
|
10.0%
1/10 • Number of events 1 • up to approximately 40 months (3.3 years)
|
4.3%
1/23 • Number of events 1 • up to approximately 40 months (3.3 years)
|
|
Renal and urinary disorders
Urinary retention
|
0.00%
0/13 • up to approximately 40 months (3.3 years)
|
10.0%
1/10 • Number of events 1 • up to approximately 40 months (3.3 years)
|
4.3%
1/23 • Number of events 1 • up to approximately 40 months (3.3 years)
|
|
Infections and infestations
Urinary tract infection
|
23.1%
3/13 • Number of events 6 • up to approximately 40 months (3.3 years)
|
20.0%
2/10 • Number of events 3 • up to approximately 40 months (3.3 years)
|
21.7%
5/23 • Number of events 9 • up to approximately 40 months (3.3 years)
|
|
Renal and urinary disorders
Urinary tract pain
|
7.7%
1/13 • Number of events 1 • up to approximately 40 months (3.3 years)
|
0.00%
0/10 • up to approximately 40 months (3.3 years)
|
4.3%
1/23 • Number of events 1 • up to approximately 40 months (3.3 years)
|
|
Infections and infestations
Vaginal infection
|
7.7%
1/13 • Number of events 1 • up to approximately 40 months (3.3 years)
|
0.00%
0/10 • up to approximately 40 months (3.3 years)
|
4.3%
1/23 • Number of events 1 • up to approximately 40 months (3.3 years)
|
|
Ear and labyrinth disorders
Vertigo
|
0.00%
0/13 • up to approximately 40 months (3.3 years)
|
10.0%
1/10 • Number of events 1 • up to approximately 40 months (3.3 years)
|
4.3%
1/23 • Number of events 1 • up to approximately 40 months (3.3 years)
|
|
Eye disorders
Visual impairment
|
7.7%
1/13 • Number of events 1 • up to approximately 40 months (3.3 years)
|
0.00%
0/10 • up to approximately 40 months (3.3 years)
|
4.3%
1/23 • Number of events 1 • up to approximately 40 months (3.3 years)
|
|
Metabolism and nutrition disorders
Vitamin D deficiency
|
7.7%
1/13 • Number of events 1 • up to approximately 40 months (3.3 years)
|
0.00%
0/10 • up to approximately 40 months (3.3 years)
|
4.3%
1/23 • Number of events 1 • up to approximately 40 months (3.3 years)
|
|
Gastrointestinal disorders
Vomiting
|
7.7%
1/13 • Number of events 1 • up to approximately 40 months (3.3 years)
|
20.0%
2/10 • Number of events 2 • up to approximately 40 months (3.3 years)
|
13.0%
3/23 • Number of events 3 • up to approximately 40 months (3.3 years)
|
|
Investigations
Weight decreased
|
7.7%
1/13 • Number of events 1 • up to approximately 40 months (3.3 years)
|
0.00%
0/10 • up to approximately 40 months (3.3 years)
|
4.3%
1/23 • Number of events 1 • up to approximately 40 months (3.3 years)
|
|
Investigations
White blood cell count decreased
|
0.00%
0/13 • up to approximately 40 months (3.3 years)
|
10.0%
1/10 • Number of events 2 • up to approximately 40 months (3.3 years)
|
4.3%
1/23 • Number of events 2 • up to approximately 40 months (3.3 years)
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Clinical Study Agreement
- Publication restrictions are in place
Restriction type: OTHER