Immune Thrombocytopenic Purpura
Conditions
Brief summary
The purpose of this study is to assess the safety and tolerability of BMS-986004 when administered in subjects with ITP.
Interventions
DRUGBMS-986004 75 mg IV
BMS-986004 (75 mg) infusion (50 ml) administered in 120 minutes
DRUGBMS-986004 225 mg IV
BMS-986004 (225 mg) infusion (100 ml) administered in 120 minutes
DRUGBMS-986004 675 mg IV
BMS-986004 (675 mg) infusion (100 ml) administered in 120 minutes
DRUGBMS-986004 1500 mg IV
BMS-986004 (1500 mg) infusion (100 ml) administered in 120 minutes
Sponsors
Bristol-Myers Squibb
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com Inclusion Criteria: * ≥18 years old, diagnosed with persistent or chronic ITP
Exclusion criteria
* Secondary immune thrombocytopenia * Drug induced thrombocytopenia
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs): Short Term and Long Term | Day 1 to Day 141 (Short term) and Day 1 to Day 398 (Long term) | The primary objective to establish safety was measured by the primary endpoints of AEs and SAEs for both Short term and Long term periods |
| Number of ECG Abnormalities | Day 1 to Day 141 (Short term) and Day 1 to Day 398 (Long term) | The primary objective to establish safety was measured by investigator identified Electrocardiogram Abnormalities for both Short term and Long term periods. ECG parameters included heart rate, PR interval, QRS interval, and QTcF interval (QT interval corrected for heart rate) |
| Number of Laboratory Abnormalities of Safety Biomarkers: d-Dimer and Thrombin Anti-Thrombin (TAT) | Day 1 to Day 141 (Short term) and Day 1 to Day 398 (Long Term) | D-dimer and thrombin antithrombin (TAT) in plasma were quantified as measures of thromboembolism risk. D-dimer was evaluated by Enzyme linked immune sorbent assay (ELISA) method (D-dimer reference range 0-0.63 micrograms/milliliters fibrinogen equivalent units \[mcg/ml FEU\]). TAT reference range 0-4.1 ng/ml. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Trough Observed Serum Concentration (Ctrough) of BMS-986004 | Day 1 (0 hour [h], 2h, 24h, 72h, 168h), Day 15 (0h), Day 29 (0h), Day 43 (0h, 168h), Day 57 (0h, 2h), Day 71 (0h, 2h, 24h, 96h, 168h), Day 85 (0h, 336h, 672h, 1008h, 1344h) | Pharmacokinetics of BMS-986004 were derived from serum concentration versus time data. Ctrough = Trough observed serum concentration. On study Day 57, non-responders in each treatment group other than the 1500 mg group were dose escalated to the starting dose of the next higher treatment group. |
| Response Rate (RR) of BMS-986004: Short Term and Long Term | Day 1 to Day 141 (Short term) and Day 1 to Day 398 (Long term) | Overall Response Rate (ORR) was defined as the proportion of participants who achieved a complete response (CR) or response (R). CR was defined as platelet count ≥ 100,000/mm3 and absence of bleeding. R was defined as platelet count ≥ 30,000/mm3 and at least 2-fold increase from the baseline count and absence of bleeding. |
| AUC Accumulation Index (AI_AUC) of BMS-986004 | Day 1 (0 hour [h], 2h, 24h, 72h, 168h), Day 15 (0h), Day 29 (0h), Day 43 (0h, 168h), Day 57 (0h, 2h), Day 71 (0h, 2h, 24h, 96h, 168h), Day 85 (0h, 336h, 672h, 1008h, 1344h) | AUC accumulation index (AI\_AUC) = ratio of AUC(TAU) at steady state to AUC(TAU) after the first dose of BMS-986004. On study Day 57, non-responders in each treatment group other than the 1500 mg group were dose escalated to the starting dose of the next higher treatment group. |
| Total Body Clearance (CLT) of BMS-986004 | Day 1 (0 hour [h], 2h, 24h, 72h, 168h), Day 15 (0h), Day 29 (0h), Day 43 (0h, 168h), Day 57 (0h, 2h), Day 71 (0h, 2h, 24h, 96h, 168h), Day 85 (0h, 336h, 672h, 1008h, 1344h) | Pharmacokinetics of BMS-986004 were derived from serum concentration versus time data. On study Day 57, non-responders in each treatment group other than the 1500 mg group were dose escalated to the starting dose of the next higher treatment group. |
| Maximum Observed Serum Concentration (Cmax) of BMS-986004 | Day 1 (0 hour [h], 2h, 24h, 72h, 168h), Day 15 (0h), Day 29 (0h), Day 43 (0h, 168h), Day 57 (0h, 2h), Day 71 (0h, 2h, 24h, 96h, 168h), Day 85 (0h, 336h, 672h, 1008h, 1344h) | Pharmacokinetic parameter (Cmax) of BMS-986004, derived from serum concentration versus time. who have adequate PK profiles. On study Day 57, non-responders in each treatment group other than the 1500 mg group were dose escalated to the starting dose of the next higher treatment group. |
| Area Under the Concentration-time Curve in One Dosing Interval [AUC(TAU)] of BMS-986004 | Day 1 (0 hour [h], 2h, 24h, 72h, 168h), Day 15 (0h), Day 29 (0h), Day 43 (0h, 168h), Day 57 (0h, 2h), Day 71 (0h, 2h, 24h, 96h, 168h), Day 85 (0h, 336h, 672h, 1008h, 1344h) | Pharmacokinetics of BMS-986004 were derived from serum concentration versus time data. AUC(TAU) = Area under the concentration-time curve in one dosing interval. On study Day 57, non-responders in each treatment group other than the 1500 mg group were dose escalated to the starting dose of the next higher treatment group. |
Countries
Australia, Canada, Georgia, Moldova, Poland, Russia, United Kingdom, United States
Participant flow
Pre-assignment details
46 participants were enrolled in the study and 26 participants entered the treatment period. Of the 20 who did not enter the treatment period, 19 did not meet study criteria and 1 experienced an adverse event.
Participants by arm
| Arm | Count |
|---|---|
| BMS 75 mg BMS-986004 dose level 75 mg | 5 |
| BMS-986004 225mg IV BMS-986004 dose level 225 mg | 6 |
| BMS 675mg BMS-986004 dose level 675 mg | 5 |
| BMS 1500mg BMS-986004 dose level 1500 mg | 10 |
| Total | 26 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Long Term Extension | Death | 0 | 0 | 0 | 1 |
| Short Term Period | Lack of Efficacy | 0 | 0 | 0 | 1 |
| Short Term Period | Lost to Follow-up | 1 | 0 | 0 | 0 |
| Short Term Period | ST complete, not entering LTE | 4 | 6 | 4 | 5 |
Baseline characteristics
| Characteristic | BMS 75 mg | BMS-986004 225mg IV | BMS 675mg | BMS 1500mg | Total |
|---|---|---|---|---|---|
| Age, Continuous | 52.8 Years STANDARD_DEVIATION 20.58 | 43.2 Years STANDARD_DEVIATION 16.33 | 34.2 Years STANDARD_DEVIATION 16.93 | 55.3 Years STANDARD_DEVIATION 16.09 | 48.0 Years STANDARD_DEVIATION 18.16 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1 Participants | 4 Participants | 4 Participants | 8 Participants | 17 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 4 Participants | 2 Participants | 1 Participants | 2 Participants | 9 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) White | 4 Participants | 5 Participants | 5 Participants | 7 Participants | 21 Participants |
| Sex: Female, Male Female | 2 Participants | 2 Participants | 4 Participants | 4 Participants | 12 Participants |
| Sex: Female, Male Male | 3 Participants | 4 Participants | 1 Participants | 6 Participants | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 5 | 0 / 6 | 0 / 5 | 1 / 10 |
| other Total, other adverse events | 1 / 5 | 5 / 6 | 5 / 5 | 9 / 10 |
| serious Total, serious adverse events | 0 / 5 | 0 / 6 | 2 / 5 | 1 / 10 |
Outcome results
Primary
Number of ECG Abnormalities
The primary objective to establish safety was measured by investigator identified Electrocardiogram Abnormalities for both Short term and Long term periods. ECG parameters included heart rate, PR interval, QRS interval, and QTcF interval (QT interval corrected for heart rate)
Time frame: Day 1 to Day 141 (Short term) and Day 1 to Day 398 (Long term)
Population: All participants who had received at least 1 dose of study treatment
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| BMS 75 mg | Number of ECG Abnormalities | Screening | 1 Events |
| BMS 75 mg | Number of ECG Abnormalities | End of Treatment | 1 Events |
| BMS 75 mg | Number of ECG Abnormalities | End of LTE | 0 Events |
| BMS 75 mg | Number of ECG Abnormalities | Day 1 | 1 Events |
| BMS 75 mg | Number of ECG Abnormalities | LTE Day 1 | 0 Events |
| BMS 75 mg | Number of ECG Abnormalities | Day 71 | 0 Events |
| BMS 75 mg | Number of ECG Abnormalities | Day 72 | 1 Events |
| BMS 75 mg | Number of ECG Abnormalities | LTE Day 71 | 0 Events |
| BMS 225 mg | Number of ECG Abnormalities | Screening | 3 Events |
| BMS 225 mg | Number of ECG Abnormalities | Day 72 | 0 Events |
| BMS 225 mg | Number of ECG Abnormalities | End of Treatment | 3 Events |
| BMS 225 mg | Number of ECG Abnormalities | Day 71 | 2 Events |
| BMS 225 mg | Number of ECG Abnormalities | LTE Day 71 | 0 Events |
| BMS 225 mg | Number of ECG Abnormalities | End of LTE | 0 Events |
| BMS 225 mg | Number of ECG Abnormalities | LTE Day 1 | 0 Events |
| BMS 225 mg | Number of ECG Abnormalities | Day 1 | 2 Events |
| BMS-986004 675 mg IV | Number of ECG Abnormalities | LTE Day 1 | 0 Events |
| BMS-986004 675 mg IV | Number of ECG Abnormalities | LTE Day 71 | 0 Events |
| BMS-986004 675 mg IV | Number of ECG Abnormalities | Day 1 | 2 Events |
| BMS-986004 675 mg IV | Number of ECG Abnormalities | End of LTE | 0 Events |
| BMS-986004 675 mg IV | Number of ECG Abnormalities | Day 71 | 0 Events |
| BMS-986004 675 mg IV | Number of ECG Abnormalities | Screening | 2 Events |
| BMS-986004 675 mg IV | Number of ECG Abnormalities | Day 72 | 1 Events |
| BMS-986004 675 mg IV | Number of ECG Abnormalities | End of Treatment | 2 Events |
| BMS 1500mg | Number of ECG Abnormalities | End of LTE | 1 Events |
| BMS 1500mg | Number of ECG Abnormalities | Screening | 3 Events |
| BMS 1500mg | Number of ECG Abnormalities | Day 1 | 3 Events |
| BMS 1500mg | Number of ECG Abnormalities | Day 71 | 0 Events |
| BMS 1500mg | Number of ECG Abnormalities | Day 72 | 1 Events |
| BMS 1500mg | Number of ECG Abnormalities | End of Treatment | 1 Events |
| BMS 1500mg | Number of ECG Abnormalities | LTE Day 1 | 2 Events |
| BMS 1500mg | Number of ECG Abnormalities | LTE Day 71 | 2 Events |
Primary
Number of Laboratory Abnormalities of Safety Biomarkers: d-Dimer and Thrombin Anti-Thrombin (TAT)
D-dimer and thrombin antithrombin (TAT) in plasma were quantified as measures of thromboembolism risk. D-dimer was evaluated by Enzyme linked immune sorbent assay (ELISA) method (D-dimer reference range 0-0.63 micrograms/milliliters fibrinogen equivalent units \[mcg/ml FEU\]). TAT reference range 0-4.1 ng/ml.
Time frame: Day 1 to Day 141 (Short term) and Day 1 to Day 398 (Long Term)
Population: All participants who had received at least 1 dose of study treatment
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| BMS 75 mg | Number of Laboratory Abnormalities of Safety Biomarkers: d-Dimer and Thrombin Anti-Thrombin (TAT) | # of events: d-Dimer, Normal | 56 Events |
| BMS 75 mg | Number of Laboratory Abnormalities of Safety Biomarkers: d-Dimer and Thrombin Anti-Thrombin (TAT) | # of events: d-Dimer, High | 12 Events |
| BMS 75 mg | Number of Laboratory Abnormalities of Safety Biomarkers: d-Dimer and Thrombin Anti-Thrombin (TAT) | # of events: TAT Complex, Normal | 52 Events |
| BMS 75 mg | Number of Laboratory Abnormalities of Safety Biomarkers: d-Dimer and Thrombin Anti-Thrombin (TAT) | # of events: TAT Complex, High | 21 Events |
| BMS 225 mg | Number of Laboratory Abnormalities of Safety Biomarkers: d-Dimer and Thrombin Anti-Thrombin (TAT) | # of events: d-Dimer, High | 14 Events |
| BMS 225 mg | Number of Laboratory Abnormalities of Safety Biomarkers: d-Dimer and Thrombin Anti-Thrombin (TAT) | # of events: TAT Complex, Normal | 71 Events |
| BMS 225 mg | Number of Laboratory Abnormalities of Safety Biomarkers: d-Dimer and Thrombin Anti-Thrombin (TAT) | # of events: TAT Complex, High | 30 Events |
| BMS 225 mg | Number of Laboratory Abnormalities of Safety Biomarkers: d-Dimer and Thrombin Anti-Thrombin (TAT) | # of events: d-Dimer, Normal | 81 Events |
| BMS-986004 675 mg IV | Number of Laboratory Abnormalities of Safety Biomarkers: d-Dimer and Thrombin Anti-Thrombin (TAT) | # of events: TAT Complex, Normal | 46 Events |
| BMS-986004 675 mg IV | Number of Laboratory Abnormalities of Safety Biomarkers: d-Dimer and Thrombin Anti-Thrombin (TAT) | # of events: d-Dimer, High | 15 Events |
| BMS-986004 675 mg IV | Number of Laboratory Abnormalities of Safety Biomarkers: d-Dimer and Thrombin Anti-Thrombin (TAT) | # of events: TAT Complex, High | 31 Events |
| BMS-986004 675 mg IV | Number of Laboratory Abnormalities of Safety Biomarkers: d-Dimer and Thrombin Anti-Thrombin (TAT) | # of events: d-Dimer, Normal | 60 Events |
| BMS 1500mg | Number of Laboratory Abnormalities of Safety Biomarkers: d-Dimer and Thrombin Anti-Thrombin (TAT) | # of events: TAT Complex, High | 28 Events |
| BMS 1500mg | Number of Laboratory Abnormalities of Safety Biomarkers: d-Dimer and Thrombin Anti-Thrombin (TAT) | # of events: d-Dimer, High | 17 Events |
| BMS 1500mg | Number of Laboratory Abnormalities of Safety Biomarkers: d-Dimer and Thrombin Anti-Thrombin (TAT) | # of events: d-Dimer, Normal | 106 Events |
| BMS 1500mg | Number of Laboratory Abnormalities of Safety Biomarkers: d-Dimer and Thrombin Anti-Thrombin (TAT) | # of events: TAT Complex, Normal | 112 Events |
Primary
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs): Short Term and Long Term
The primary objective to establish safety was measured by the primary endpoints of AEs and SAEs for both Short term and Long term periods
Time frame: Day 1 to Day 141 (Short term) and Day 1 to Day 398 (Long term)
Population: All participants who had received at least 1 dose of study treatment
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| BMS 75 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs): Short Term and Long Term | Number of participants with AEs | 1 Participants |
| BMS 75 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs): Short Term and Long Term | Number of participants with SAEs | 0 Participants |
| BMS 225 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs): Short Term and Long Term | Number of participants with SAEs | 0 Participants |
| BMS 225 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs): Short Term and Long Term | Number of participants with AEs | 5 Participants |
| BMS-986004 675 mg IV | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs): Short Term and Long Term | Number of participants with AEs | 5 Participants |
| BMS-986004 675 mg IV | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs): Short Term and Long Term | Number of participants with SAEs | 1 Participants |
| BMS 1500mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs): Short Term and Long Term | Number of participants with AEs | 9 Participants |
| BMS 1500mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs): Short Term and Long Term | Number of participants with SAEs | 1 Participants |
Secondary
Area Under the Concentration-time Curve in One Dosing Interval [AUC(TAU)] of BMS-986004
Pharmacokinetics of BMS-986004 were derived from serum concentration versus time data. AUC(TAU) = Area under the concentration-time curve in one dosing interval. On study Day 57, non-responders in each treatment group other than the 1500 mg group were dose escalated to the starting dose of the next higher treatment group.
Time frame: Day 1 (0 hour [h], 2h, 24h, 72h, 168h), Day 15 (0h), Day 29 (0h), Day 43 (0h, 168h), Day 57 (0h, 2h), Day 71 (0h, 2h, 24h, 96h, 168h), Day 85 (0h, 336h, 672h, 1008h, 1344h)
Population: Evaluable PK Population. The number of analyzed participants in each arm at specified time points represent the actual number of subjects evaluated after intra-participant dose escalation once the participant had completed the response phase of the study.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BMS 75 mg | Area Under the Concentration-time Curve in One Dosing Interval [AUC(TAU)] of BMS-986004 | AUC(TAU) Day 1 | 915500 h*ng/mL | Standard Deviation 196460 |
| BMS 225 mg | Area Under the Concentration-time Curve in One Dosing Interval [AUC(TAU)] of BMS-986004 | AUC(TAU) Day 1 | 3445000 h*ng/mL | Standard Deviation 708290 |
| BMS 225 mg | Area Under the Concentration-time Curve in One Dosing Interval [AUC(TAU)] of BMS-986004 | AUC(TAU) Day 71 | 4408000 h*ng/mL | Standard Deviation 3313000 |
| BMS-986004 675 mg IV | Area Under the Concentration-time Curve in One Dosing Interval [AUC(TAU)] of BMS-986004 | AUC(TAU) Day 71 | 11460000 h*ng/mL | Standard Deviation 2124900 |
| BMS-986004 675 mg IV | Area Under the Concentration-time Curve in One Dosing Interval [AUC(TAU)] of BMS-986004 | AUC(TAU) Day 1 | 11440000 h*ng/mL | Standard Deviation 3041300 |
| BMS 1500mg | Area Under the Concentration-time Curve in One Dosing Interval [AUC(TAU)] of BMS-986004 | AUC(TAU) Day 1 | 18370000 h*ng/mL | Standard Deviation 7351000 |
| BMS 1500mg | Area Under the Concentration-time Curve in One Dosing Interval [AUC(TAU)] of BMS-986004 | AUC(TAU) Day 71 | 26500000 h*ng/mL | Standard Deviation 9366800 |
Secondary
AUC Accumulation Index (AI_AUC) of BMS-986004
AUC accumulation index (AI\_AUC) = ratio of AUC(TAU) at steady state to AUC(TAU) after the first dose of BMS-986004. On study Day 57, non-responders in each treatment group other than the 1500 mg group were dose escalated to the starting dose of the next higher treatment group.
Time frame: Day 1 (0 hour [h], 2h, 24h, 72h, 168h), Day 15 (0h), Day 29 (0h), Day 43 (0h, 168h), Day 57 (0h, 2h), Day 71 (0h, 2h, 24h, 96h, 168h), Day 85 (0h, 336h, 672h, 1008h, 1344h)
Population: Evaluable PK Population. Only participants with adequate PK profiles were included in the summary statistics; 0 participants analyzed indicates no data were available for that cohort for this Summary Statistic
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BMS 1500mg | AUC Accumulation Index (AI_AUC) of BMS-986004 | 1.7996 Ratio | Standard Deviation 0.597881 |
Secondary
Maximum Observed Serum Concentration (Cmax) of BMS-986004
Pharmacokinetic parameter (Cmax) of BMS-986004, derived from serum concentration versus time. who have adequate PK profiles. On study Day 57, non-responders in each treatment group other than the 1500 mg group were dose escalated to the starting dose of the next higher treatment group.
Time frame: Day 1 (0 hour [h], 2h, 24h, 72h, 168h), Day 15 (0h), Day 29 (0h), Day 43 (0h, 168h), Day 57 (0h, 2h), Day 71 (0h, 2h, 24h, 96h, 168h), Day 85 (0h, 336h, 672h, 1008h, 1344h)
Population: Evaluable PK population defined as participants with adequate PK profiles. The number of analyzed participants in each arm at specified time points represent the actual number of subjects evaluated after intra-participant dose escalation once the participant had completed the response phase of the study.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BMS 75 mg | Maximum Observed Serum Concentration (Cmax) of BMS-986004 | Cmax Day 1 | 19353.5 ng/mL | Standard Deviation 6131.32 |
| BMS 225 mg | Maximum Observed Serum Concentration (Cmax) of BMS-986004 | Cmax Day 1 | 59478.8 ng/mL | Standard Deviation 10021.04 |
| BMS 225 mg | Maximum Observed Serum Concentration (Cmax) of BMS-986004 | Cmax Day 71 | 62469.8 ng/mL | Standard Deviation 27336.64 |
| BMS-986004 675 mg IV | Maximum Observed Serum Concentration (Cmax) of BMS-986004 | Cmax Day 71 | 186981.0 ng/mL | Standard Deviation 22216.82 |
| BMS-986004 675 mg IV | Maximum Observed Serum Concentration (Cmax) of BMS-986004 | Cmax Day 1 | 177706.3 ng/mL | Standard Deviation 37924.3 |
| BMS 1500mg | Maximum Observed Serum Concentration (Cmax) of BMS-986004 | Cmax Day 1 | 296561.9 ng/mL | Standard Deviation 119530.86 |
| BMS 1500mg | Maximum Observed Serum Concentration (Cmax) of BMS-986004 | Cmax Day 71 | 373588.9 ng/mL | Standard Deviation 89833.77 |
Secondary
Response Rate (RR) of BMS-986004: Short Term and Long Term
Overall Response Rate (ORR) was defined as the proportion of participants who achieved a complete response (CR) or response (R). CR was defined as platelet count ≥ 100,000/mm3 and absence of bleeding. R was defined as platelet count ≥ 30,000/mm3 and at least 2-fold increase from the baseline count and absence of bleeding.
Time frame: Day 1 to Day 141 (Short term) and Day 1 to Day 398 (Long term)
Population: All participants who had received at least 1 dose of study treatment
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| BMS 75 mg | Response Rate (RR) of BMS-986004: Short Term and Long Term | RR during ST | 0.2 Proportion of participants |
| BMS 225 mg | Response Rate (RR) of BMS-986004: Short Term and Long Term | RR during ST | 0.3 Proportion of participants |
| BMS-986004 675 mg IV | Response Rate (RR) of BMS-986004: Short Term and Long Term | RR during ST | 0.4 Proportion of participants |
| BMS-986004 675 mg IV | Response Rate (RR) of BMS-986004: Short Term and Long Term | RR during LTE | 0 Proportion of participants |
| BMS 1500mg | Response Rate (RR) of BMS-986004: Short Term and Long Term | RR during LTE | 0 Proportion of participants |
| BMS 1500mg | Response Rate (RR) of BMS-986004: Short Term and Long Term | RR during ST | 0.4 Proportion of participants |
Secondary
Total Body Clearance (CLT) of BMS-986004
Pharmacokinetics of BMS-986004 were derived from serum concentration versus time data. On study Day 57, non-responders in each treatment group other than the 1500 mg group were dose escalated to the starting dose of the next higher treatment group.
Time frame: Day 1 (0 hour [h], 2h, 24h, 72h, 168h), Day 15 (0h), Day 29 (0h), Day 43 (0h, 168h), Day 57 (0h, 2h), Day 71 (0h, 2h, 24h, 96h, 168h), Day 85 (0h, 336h, 672h, 1008h, 1344h)
Population: Evaluable PK Population. The number of analyzed participants in each arm at specified time points represent the actual number of subjects evaluated after intra-participant dose escalation once the participant had completed the response phase of the study.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BMS 75 mg | Total Body Clearance (CLT) of BMS-986004 | CLT Day 1 | 0.0789 L/H | Standard Deviation 0.01514 |
| BMS 225 mg | Total Body Clearance (CLT) of BMS-986004 | CLT Day 1 | 0.0618 L/H | Standard Deviation 0.01617 |
| BMS 225 mg | Total Body Clearance (CLT) of BMS-986004 | CLT Day 71 | 0.0716 L/H | Standard Deviation 0.04106 |
| BMS-986004 675 mg IV | Total Body Clearance (CLT) of BMS-986004 | CLT Day 71 | 0.0611 L/H | Standard Deviation 0.01449 |
| BMS-986004 675 mg IV | Total Body Clearance (CLT) of BMS-986004 | CLT Day 1 | 0.0561 L/H | Standard Deviation 0.01395 |
| BMS 1500mg | Total Body Clearance (CLT) of BMS-986004 | CLT Day 1 | 0.0860 L/H | Standard Deviation 0.03037 |
| BMS 1500mg | Total Body Clearance (CLT) of BMS-986004 | CLT Day 71 | 0.0628 L/H | Standard Deviation 0.02061 |
Secondary
Trough Observed Serum Concentration (Ctrough) of BMS-986004
Pharmacokinetics of BMS-986004 were derived from serum concentration versus time data. Ctrough = Trough observed serum concentration. On study Day 57, non-responders in each treatment group other than the 1500 mg group were dose escalated to the starting dose of the next higher treatment group.
Time frame: Day 1 (0 hour [h], 2h, 24h, 72h, 168h), Day 15 (0h), Day 29 (0h), Day 43 (0h, 168h), Day 57 (0h, 2h), Day 71 (0h, 2h, 24h, 96h, 168h), Day 85 (0h, 336h, 672h, 1008h, 1344h)
Population: Evaluable PK Population. The number of analyzed participants in each arm at specified time points represent the actual number of subjects evaluated after intra-participant dose escalation once the participant had completed the response phase of the study.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BMS 75 mg | Trough Observed Serum Concentration (Ctrough) of BMS-986004 | Ctrough, Day 43 | 1207.0 ng/mL | Standard Deviation 852.88 |
| BMS 75 mg | Trough Observed Serum Concentration (Ctrough) of BMS-986004 | Ctrough, Day 15 | 978.0 ng/mL | Standard Deviation 1080.82 |
| BMS 75 mg | Trough Observed Serum Concentration (Ctrough) of BMS-986004 | Ctrough, Day 29 | 1011.4 ng/mL | Standard Deviation 999.13 |
| BMS 225 mg | Trough Observed Serum Concentration (Ctrough) of BMS-986004 | Ctrough, Day 85 | 4018.8 ng/mL | Standard Deviation 4099.35 |
| BMS 225 mg | Trough Observed Serum Concentration (Ctrough) of BMS-986004 | Ctrough, Day 43 | 3527.7 ng/mL | Standard Deviation 1576.34 |
| BMS 225 mg | Trough Observed Serum Concentration (Ctrough) of BMS-986004 | Ctrough, Day 29 | 3157.7 ng/mL | Standard Deviation 1458.85 |
| BMS 225 mg | Trough Observed Serum Concentration (Ctrough) of BMS-986004 | Ctrough, Day 15 | 2373.0 ng/mL | Standard Deviation 1182 |
| BMS 225 mg | Trough Observed Serum Concentration (Ctrough) of BMS-986004 | Ctrough, Day 71 | 3466.0 ng/mL | Standard Deviation 3209.75 |
| BMS 225 mg | Trough Observed Serum Concentration (Ctrough) of BMS-986004 | Ctrough, Day 57 | 25339.5 ng/mL | Standard Deviation 49053.16 |
| BMS-986004 675 mg IV | Trough Observed Serum Concentration (Ctrough) of BMS-986004 | Ctrough, Day 43 | 9416.2 ng/mL | Standard Deviation 4410.57 |
| BMS-986004 675 mg IV | Trough Observed Serum Concentration (Ctrough) of BMS-986004 | Ctrough, Day 15 | 7556.4 ng/mL | Standard Deviation 1952.53 |
| BMS-986004 675 mg IV | Trough Observed Serum Concentration (Ctrough) of BMS-986004 | Ctrough, Day 29 | 10236.0 ng/mL | Standard Deviation 3737.42 |
| BMS-986004 675 mg IV | Trough Observed Serum Concentration (Ctrough) of BMS-986004 | Ctrough, Day 57 | 3360.5 ng/mL | Standard Deviation 1082.75 |
| BMS-986004 675 mg IV | Trough Observed Serum Concentration (Ctrough) of BMS-986004 | Ctrough, Day 71 | 8347.7 ng/mL | Standard Deviation 3215.32 |
| BMS-986004 675 mg IV | Trough Observed Serum Concentration (Ctrough) of BMS-986004 | Ctrough, Day 85 | 9075.7 ng/mL | Standard Deviation 4268.76 |
| BMS 1500mg | Trough Observed Serum Concentration (Ctrough) of BMS-986004 | Ctrough, Day 29 | 21353.6 ng/mL | Standard Deviation 14144.9 |
| BMS 1500mg | Trough Observed Serum Concentration (Ctrough) of BMS-986004 | Ctrough, Day 85 | 24308.9 ng/mL | Standard Deviation 19213.61 |
| BMS 1500mg | Trough Observed Serum Concentration (Ctrough) of BMS-986004 | Ctrough, Day 71 | 25057.3 ng/mL | Standard Deviation 18007.59 |
| BMS 1500mg | Trough Observed Serum Concentration (Ctrough) of BMS-986004 | Ctrough, Day 43 | 19105.3 ng/mL | Standard Deviation 14980.5 |
| BMS 1500mg | Trough Observed Serum Concentration (Ctrough) of BMS-986004 | Ctrough, Day 15 | 15282.5 ng/mL | Standard Deviation 9710.77 |
| BMS 1500mg | Trough Observed Serum Concentration (Ctrough) of BMS-986004 | Ctrough, Day 57 | 20553.1 ng/mL | Standard Deviation 19099.39 |