Leukemia
Conditions
Brief summary
The purpose of this study is to determine the safety and effectiveness of ulocuplumab in combination with low dose cytarabine in the treatment of Newly Diagnosed Acute Myeloid Leukemia (AML).
Interventions
DRUGBMS-936564
DRUGCytarabine
Sponsors
Bristol-Myers Squibb
Study design
Allocation
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: * Newly Diagnosed Acute Myeloid Leukemia (AML) * Considered inappropriate for intensive remission induction therapy by an investigator * Not eligible for stem cell transplantation
Exclusion criteria
* Acute promyelocytic leukemia * Current Myelodysplastic syndrome only subjects * Unstable angina or uncontrolled congestive heart failure * Any other malignancy, excluding basal or squamous cell carcinoma of the skin, in situ melanoma, cervical carcinoma in situ, localized prostate cancer, or superficial bladder cancer stage 0, from which the subject has not been disease-free for at least 3 years * Respiratory disease requiring continuous supplemental oxygen Other protocol defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Dose-Limiting Toxicities (DLTs) in Treatment Cycle 1 - Phase 1 | From first dose to end of cycle 1 (28 days) | Safety data evaluated for DLTs. DLTs and all other toxicities were defined and evaluated using the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03 (NCI CTCAE v4.03). DLTs were defined based upon events that were considered to be related to ulocuplumab in combination with LDAC and that occurred during the first cycle of drug administration (28 days). |
| Number of Participants With Adverse Events (AEs) - Phase 1 | From first dose to 30 days post last dose | The number of participants with an on-study adverse event (AE). Safety data are evaluated for AEs, defined and evaluated using the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03 (NCI CTCAE v4.03). |
| Number of Participants With >= Grade 3 AEs - Phase 1 | From first dose to 30 days post last dose | The number of participants with an on-study adverse event \>= Grade level 3. Safety data are evaluated for \>= Grade 3 AEs, defined and evaluated using the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03 (NCI CTCAE v4.03). |
| Number of Participants With AEs Leading to Discontinuation - Phase 1 | From first dose to 30 days post last dose | The number of participants with an on-study adverse event (AE) leading to discontinuation. Safety data are evaluated for AEs leading to discontinuation, defined and evaluated using the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03 (NCI CTCAE v4.03). |
| Number of Participants With Serious Adverse Events (SAEs) - Phase 1 | From first dose to 30 days post last dose | The number of participants with an on-study serious adverse event (SAE). Safety data are evaluated for SAEs, defined and evaluated using the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03 (NCI CTCAE v4.03). |
| Number of Deaths - Phase 1 | From first dose to 30 days post last dose | The number of participants who died. |
| Number of Participants With Laboratory Abnormalities - Phase 1 | From first dose to 30 days post last dose | The number of participants with an on-study laboratory abnormality. Safety data are evaluated for laboratory abnormalities, defined and evaluated using the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03 (NCI CTCAE v4.03). grades 1, 2, 3, 4, 5, unknown, with 5 being the worst outcome |
| Best Overall Response (BOR) - Phase 2 | From first dose until a minimum follow-up of up to 2 months | The phase 2 primary endpoint was based on the rate of Complete Remission (CR/CRi) prior to the initiation of any alternative therapy (including any subsequent ulocuplumab 800 mg for participants in the LDAC alone arm). The phase 2 primary analysis was conducted after all participants had an opportunity for 6 months of follow-up. Complete remission rate: CR + CRi, confidence interval based on the Clopper and Pearson method. CR = complete response CRi = complete response, incomplete blood count |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Trough Observed Serum Concentration (Ctrough) - Phases 1 and 2 | Days 1, 8, 15 for cycle 1; Days 8, 15 for cycle 2; Days 1, 8 for cycles 3-5; Day 1 every 4th cycle thereafter; EOT; 30 days post last dose (follow-up) | The Pharmacokinetic (PK) parameters are assessed for ulocuplumab following study drug administration. EOT = end of treatment Measure type and method of dispersion are Geometric mean and %CV, respectively |
| Time of Maximum Observed Ulocuplumab Serum Concentration (Tmax) - Phases 1 and 2 | Cycle 1 Day 1 | The Pharmacokinetic (PK) parameters are assessed for ulocuplumab following study drug administration. EOT = end of treatment |
| Area Under the Ulocuplumab Concentration-time Curve From Time Zero to the Last Quantifiable Concentration [AUC(0-T)] - Phases 1 and 2 | Cycle 1 Day 1 | The Pharmacokinetic (PK) parameters are assessed for ulocuplumab following study drug administration. EOT = end of treatment AUC(0-T) calculated by log- and linear-trapezoidal summation Measure type and method of dispersion are Geometric mean and %CV, respectively |
| Area Under the Ulocuplumab Concentration-time Curve in One Dosing Interval [AUC(TAU)] - Phases 1 and 2 | Cycle 1 Day 1 | The Pharmacokinetic (PK) parameters are assessed for ulocuplumab following study drug administration. EOT = end of treatment Measure type and method of dispersion are Geometric mean and %CV, respectively |
| Area Under the Ulocuplumab Concentration-time Curve From Time Zero to Infinity [AUC(INF)] - Phases 1 and 2 | Days 1, 8, 15 for cycles 1 and 2; Days 1, 8 for cycles 3-5; Day 1 every 4th cycle thereafter; EOT; 30 days post last dose (follow-up) | The Pharmacokinetic (PK) parameters are assessed for ulocuplumab following study drug administration. EOT = end of treatment AUC(INF) calculated by summing AUC(0-T) and the extrapolated area, computed by the quotient Clast/λz Measure type and method of dispersion are Geometric mean and %CV, respectively |
| Elimination Half-life (T-HALF) - Phases 1 and 2 | Days 1, 8, 15 for cycles 1 and 2; Days 1, 8 for cycles 3-5; Day 1 every 4th cycle thereafter; EOT; 30 days post last dose (follow-up) | The Pharmacokinetic (PK) parameters are assessed for ulocuplumab following study drug administration. EOT = end of treatment T-HALF determined as 0.693/λz |
| Total Body Clearance of Ulocuplumab (CLT) - Phases 1 and 2 | Days 1, 8, 15 for cycles 1 and 2; Days 1, 8 for cycles 3-5; Day 1 every 4th cycle thereafter; EOT; 30 days post last dose (follow-up) | The Pharmacokinetic (PK) parameters are assessed for ulocuplumab following study drug administration. EOT = end of treatment CLT calculated by dividing the total dose of ulocuplumab by its corresponding AUC(INF) value Measure type and method of dispersion are Geometric mean and %CV, respectively |
| Volume of Distribution at Steady State (Vss) - Phases 1 and 2 | Days 1, 8, 15 for cycles 1 and 2; Days 1, 8 for cycles 3-5; Day 1 every 4th cycle thereafter; EOT; 30 days post last dose (follow-up) | The Pharmacokinetic (PK) parameters are assessed for ulocuplumab following study drug administration. EOT = end of treatment Measure type and method of dispersion are Geometric mean and %CV, respectively |
| Best Overall Response (BOR) - Phase 1 | From first dose until a minimum follow-up of up to 2 months | Investigator assessed best overall response prior to the initiation of any alternative therapy for Phase 1 participants. |
| Duration of Response in Participants With CR/CRi Treated With Ulocuplumab at Two Different Dose Levels 800 mg and 1000 mg in Combination With LDAC - Phase 2 | From first dose until a minimum follow-up of up to 2 months | This phase 2 secondary endpoint was based on the duration of complete remission prior to the initiation of any alternative therapy (including any subsequent ulocuplumab 800 mg for participants in the LDAC alone arm). The phase 2 analysis was conducted after all participants had an opportunity for 6 months of follow-up. |
| Rate of Complete Remission (CR/CRi) and Overall Rate of Remission in Participants Treated With LDAC Only - Phase 2 | From first dose until a minimum follow-up of up to 2 months | This phase 2 secondary endpoint was based on the rate of Complete Remission (CR/CRi) and rate of Overall Remission (OR=PR+CR +CRi) prior to the initiation of any alternative therapy (including any subsequent ulocuplumab 800 mg for participants in the LDAC alone arm). The phase 2 analysis was conducted after all participants had an opportunity for 6 months of follow-up. Overall remission rate: CR + CRi, + PR confidence interval based on the Clopper and Pearson method. CR = complete response CRi = complete response, incomplete blood count PR = partial remission |
| Duration of Response in Participants With CR/CRi Treated With LDAC Only - Phase 2 | From first dose until a minimum follow-up of up to 2 months | This phase 2 secondary endpoint was based on the duration of complete remission prior to the initiation of any alternative therapy (including any subsequent ulocuplumab 800 mg for participants in the LDAC alone arm). The phase 2 analysis was conducted after all participants had an opportunity for 6 months of follow-up. |
| Change From Baseline of Electrocardiogram (ECG) Endpoints: Heart Rate - Phases 1 and 2 | From first dose until a minimum follow-up of up to 2 months | Change from baseline of ECG endpoints Heart rate measured in beats per minute (bpm) |
| Change From Baseline of Electrocardiogram (ECG) Endpoints: PR Interval - Phases 1 and 2 | From first dose until a minimum follow-up of up to 2 months | Change from baseline of ECG endpoints PR interval measured in milliseconds (msec) |
| Change From Baseline of Electrocardiogram (ECG) Endpoints: QRS Interval - Phases 1 and 2 | From first dose until a minimum follow-up of up to 2 months | Change from baseline of ECG endpoints QRS interval measured in milliseconds (msec) |
| Change From Baseline of Electrocardiogram (ECG) Endpoints: QT Interval - Phases 1 and 2 | From first dose until a minimum follow-up of up to 2 months | Change from baseline of ECG endpoints QT interval measured in milliseconds (msec) |
| Overall Survival (OS) - Phases 1 and 2 | From first dose until a minimum follow-up of up to 2 months | OS is defined as the time between the first date of treatment and the date of death due to any cause. A participant who has not died was be censored at the last known alive date. |
| Overall Rate of Remission in Participants Treated With Ulocuplumab at Two Different Dose Levels 800 mg and 1000 mg in Combination With LDAC - Phase 2 | From first dose until a minimum follow-up of up to 2 months | This phase 2 secondary endpoint was based on the rate of Overall Remission (OR=PR+CR +CRi) prior to the initiation of any alternative therapy (including any subsequent ulocuplumab 800 mg for participants in the LDAC alone arm). The phase 2 analysis was conducted after all participants had an opportunity for 6 months of follow-up. Overall remission rate: CR + CRi, + PR confidence interval based on the Clopper and Pearson method. CR = complete response CRi = complete response, incomplete blood count PR = partial remission |
| Number of Participants With AEs - Phase 2 | From first dose until a minimum follow-up of up to 2 months | The number of participants with an on-study adverse event (AE). Safety data are evaluated for AEs, defined and evaluated using the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03 (NCI CTCAE v4.03). |
| Number of Participants With AEs Leading to Discontinuation - Phase 2 | From first dose until a minimum follow-up of up to 2 months | The number of participants with an on-study adverse event (AE) leading to discontinuation. Safety data are evaluated for AEs leading to discontinuation, defined and evaluated using the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03 (NCI CTCAE v4.03). |
| Number of Participants With SAEs - Phase 2 | From first dose until a minimum follow-up of up to 2 months | The number of participants with an on-study serious adverse event (SAE). Safety data are evaluated for SAEs, defined and evaluated using the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03 (NCI CTCAE v4.03). |
| Number of Deaths- Phase 2 | From first dose until a minimum follow-up of up to 2 months | The number of participants who died. Safety data are evaluated for deaths, defined and evaluated using the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03 (NCI CTCAE v4.03). |
| Number of Participants With Laboratory Abnormalities - Phase 2 | From first dose until a minimum follow-up of up to 2 months | The number of participants with an on-study laboratory abnormality, assessed from Grade 1-4 Serum Chemistry, Electrolytes, and Hematology Laboratory Test results, with grade 4 being the worst. Safety data are evaluated for laboratory abnormalities, defined and evaluated using the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03 (NCI CTCAE v4.03). |
| Number of Participants With Anti-drug Antibodies (ADA) Positive for Ulocuplumab - Phases 1 and 2 | From first dose until a minimum follow-up of up to 2 months | Serum samples from ulocuplumab treated participants were evaluated for the presence of anti-ulocuplumab antibodies |
| Maximum Observed Serum Concentration (Cmax) - Phases 1 and 2 | Cycle 1 Day 1 | The Pharmacokinetic (PK) parameters are assessed for ulocuplumab following study drug administration EOT = end of treatment Measure type and method of dispersion are Geometric mean and %CV, respectively |
Countries
Brazil, Canada, China, Israel, Italy, Japan, Romania, South Korea, Taiwan, United States
Participant flow
Pre-assignment details
6 participants in Phase 1 and 64 participants in Phase 2 (70 in total) were assigned to treatment. 2 participants randomized to the LDAC-only arm in Phase 2 did not receive treatment. 68 participants in total (phases 1 and 2) were treated.
Participants by arm
| Arm | Count |
|---|---|
| ULO 600mg + LDAC - Ph1 Ulocuplumab (ULO) at 600mg + low dose cytarabine (LDAC) - Phase 1 (Ph1) | 3 |
| ULO 800mg + LDAC - Ph1 Ulocuplumab (ULO) at 800mg + low dose cytarabine (LDAC) - Phase 1 (Ph1) | 3 |
| ULO 800mg + LDAC - Ph2 Ulocuplumab (ULO) at 800mg + low dose cytarabine (LDAC) - Phase 2 (Ph2) | 26 |
| ULO 1000mg + LDAC - Ph2 Ulocuplumab (ULO) at 1000mg + low dose cytarabine (LDAC) - Phase 2 (Ph2) | 14 |
| LDAC - Ph2 Low dose cytarabine (LDAC) - Phase 2 (Ph2) Participants in the LDAC only arm were permitted to add ulocuplumab 800 mg into their treatment regimen if they did not achieve complete remission (CR or complete remission with incomplete blood count recovery \[CRi\]) confirmed by blast count reduction after 4 treatment cycles or if they relapsed after achieving complete remission | 24 |
| Total | 70 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Follow-up Period | Death | 0 | 0 | 5 | 4 | 7 |
| Follow-up Period | Followup no longer required per protocol | 3 | 3 | 4 | 1 | 4 |
| Follow-up Period | other reason | 0 | 0 | 0 | 0 | 1 |
| Follow-up Period | Participant withdrew consent | 0 | 0 | 2 | 1 | 0 |
| Treatment Period | added ULO, then disease progression | 0 | 0 | 0 | 0 | 4 |
| Treatment Period | added ULO; then other reason | 0 | 0 | 0 | 0 | 1 |
| Treatment Period | added ULO, then request to stop | 0 | 0 | 0 | 0 | 1 |
| Treatment Period | Administrative reason by Sponsor | 0 | 0 | 0 | 0 | 1 |
| Treatment Period | Adverse Event (AE) unrelated to drug | 0 | 0 | 7 | 1 | 2 |
| Treatment Period | Death | 0 | 0 | 1 | 2 | 1 |
| Treatment Period | Disease progression | 0 | 0 | 15 | 6 | 6 |
| Treatment Period | Maximum clinical benefit | 0 | 0 | 0 | 0 | 1 |
| Treatment Period | other reason | 2 | 0 | 2 | 2 | 1 |
| Treatment Period | Participant request to stop therapy | 0 | 2 | 0 | 1 | 0 |
| Treatment Period | Participant withdrew consent | 0 | 0 | 1 | 1 | 1 |
| Treatment Period | Poor/non-compliance | 0 | 0 | 0 | 0 | 1 |
| Treatment Period | Randomized but not treated | 0 | 0 | 0 | 0 | 2 |
| Treatment Period | Study drug toxicity | 0 | 0 | 0 | 1 | 2 |
Baseline characteristics
| Characteristic | LDAC - Ph2 | ULO 600mg + LDAC - Ph1 | Total | ULO 800mg + LDAC - Ph1 | ULO 800mg + LDAC - Ph2 | ULO 1000mg + LDAC - Ph2 |
|---|---|---|---|---|---|---|
| Age, Continuous | 75.9 Years STANDARD_DEVIATION 5.7 | 73.7 Years STANDARD_DEVIATION 8.02 | 74.9 Years STANDARD_DEVIATION 5.21 | 77.3 Years STANDARD_DEVIATION 1.53 | 74.9 Years STANDARD_DEVIATION 5.4 | 73.1 Years STANDARD_DEVIATION 3.7 |
| Age, Customized <70 | 3 Participants | 1 Participants | 11 Participants | 0 Participants | 4 Participants | 3 Participants |
| Age, Customized >=70 | 21 Participants | 2 Participants | 59 Participants | 3 Participants | 22 Participants | 11 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | — | — | 0 Participants | — | — | — |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | — | — | 0 Participants | — | — | — |
| Ethnicity (NIH/OMB) Unknown or Not Reported | — | — | 0 Participants | — | — | — |
| Race/Ethnicity, Customized American Indian/Alaskan Native | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian Indian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian Other | 2 Participants | 0 Participants | 5 Participants | 0 Participants | 3 Participants | 0 Participants |
| Race/Ethnicity, Customized Black/African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Chinese | 3 Participants | 0 Participants | 7 Participants | 0 Participants | 2 Participants | 2 Participants |
| Race/Ethnicity, Customized Japanese | 4 Participants | 3 Participants | 22 Participants | 3 Participants | 6 Participants | 6 Participants |
| Race/Ethnicity, Customized Native Hawaiian/Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Other | 3 Participants | 0 Participants | 4 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 12 Participants | 0 Participants | 31 Participants | 0 Participants | 15 Participants | 4 Participants |
| Sex: Female, Male Female | 14 Participants | 3 Participants | 33 Participants | 0 Participants | 9 Participants | 7 Participants |
| Sex: Female, Male Male | 10 Participants | 0 Participants | 37 Participants | 3 Participants | 17 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 3 | 19 / 26 | 10 / 14 | 16 / 22 |
| other Total, other adverse events | 3 / 3 | 3 / 3 | 25 / 26 | 14 / 14 | 22 / 22 |
| serious Total, serious adverse events | 2 / 3 | 1 / 3 | 21 / 26 | 8 / 14 | 15 / 22 |
Outcome results
Primary
Best Overall Response (BOR) - Phase 2
The phase 2 primary endpoint was based on the rate of Complete Remission (CR/CRi) prior to the initiation of any alternative therapy (including any subsequent ulocuplumab 800 mg for participants in the LDAC alone arm). The phase 2 primary analysis was conducted after all participants had an opportunity for 6 months of follow-up. Complete remission rate: CR + CRi, confidence interval based on the Clopper and Pearson method. CR = complete response CRi = complete response, incomplete blood count
Time frame: From first dose until a minimum follow-up of up to 2 months
Population: All randomized participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ULO 600mg + LDAC - Ph1 | Best Overall Response (BOR) - Phase 2 | 15.4 Percentage of participants |
| ULO 800mg + LDAC - Ph1 | Best Overall Response (BOR) - Phase 2 | 7.1 Percentage of participants |
| LDAC - Ph2 | Best Overall Response (BOR) - Phase 2 | 25.0 Percentage of participants |
Primary
Number of Deaths - Phase 1
The number of participants who died.
Time frame: From first dose to 30 days post last dose
Population: All treated participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ULO 600mg + LDAC - Ph1 | Number of Deaths - Phase 1 | 0 Participants |
| ULO 800mg + LDAC - Ph1 | Number of Deaths - Phase 1 | 0 Participants |
Primary
Number of Participants With Adverse Events (AEs) - Phase 1
The number of participants with an on-study adverse event (AE). Safety data are evaluated for AEs, defined and evaluated using the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03 (NCI CTCAE v4.03).
Time frame: From first dose to 30 days post last dose
Population: All treated participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ULO 600mg + LDAC - Ph1 | Number of Participants With Adverse Events (AEs) - Phase 1 | 3 Participants |
| ULO 800mg + LDAC - Ph1 | Number of Participants With Adverse Events (AEs) - Phase 1 | 3 Participants |
Primary
Number of Participants With AEs Leading to Discontinuation - Phase 1
The number of participants with an on-study adverse event (AE) leading to discontinuation. Safety data are evaluated for AEs leading to discontinuation, defined and evaluated using the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03 (NCI CTCAE v4.03).
Time frame: From first dose to 30 days post last dose
Population: All treated participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ULO 600mg + LDAC - Ph1 | Number of Participants With AEs Leading to Discontinuation - Phase 1 | 0 Participants |
| ULO 800mg + LDAC - Ph1 | Number of Participants With AEs Leading to Discontinuation - Phase 1 | 0 Participants |
Primary
Number of Participants With Dose-Limiting Toxicities (DLTs) in Treatment Cycle 1 - Phase 1
Safety data evaluated for DLTs. DLTs and all other toxicities were defined and evaluated using the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03 (NCI CTCAE v4.03). DLTs were defined based upon events that were considered to be related to ulocuplumab in combination with LDAC and that occurred during the first cycle of drug administration (28 days).
Time frame: From first dose to end of cycle 1 (28 days)
Population: All treated participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ULO 600mg + LDAC - Ph1 | Number of Participants With Dose-Limiting Toxicities (DLTs) in Treatment Cycle 1 - Phase 1 | 0 Participants |
| ULO 800mg + LDAC - Ph1 | Number of Participants With Dose-Limiting Toxicities (DLTs) in Treatment Cycle 1 - Phase 1 | 0 Participants |
Primary
Number of Participants With >= Grade 3 AEs - Phase 1
The number of participants with an on-study adverse event \>= Grade level 3. Safety data are evaluated for \>= Grade 3 AEs, defined and evaluated using the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03 (NCI CTCAE v4.03).
Time frame: From first dose to 30 days post last dose
Population: All treated participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ULO 600mg + LDAC - Ph1 | Number of Participants With >= Grade 3 AEs - Phase 1 | 3 Participants |
| ULO 800mg + LDAC - Ph1 | Number of Participants With >= Grade 3 AEs - Phase 1 | 3 Participants |
Primary
Number of Participants With Laboratory Abnormalities - Phase 1
The number of participants with an on-study laboratory abnormality. Safety data are evaluated for laboratory abnormalities, defined and evaluated using the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03 (NCI CTCAE v4.03). grades 1, 2, 3, 4, 5, unknown, with 5 being the worst outcome
Time frame: From first dose to 30 days post last dose
Population: All treated participants
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| ULO 600mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 1 | ALANINE AMINOTRANSFERASE - grade 0 | 2 Participants |
| ULO 600mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 1 | LEUKOCYTES - grade 0 | 0 Participants |
| ULO 600mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 1 | CALCIUM, TOTAL - grade 0 | 1 Participants |
| ULO 600mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 1 | LEUKOCYTES - grade 3 | 1 Participants |
| ULO 600mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 1 | ALKALINE PHOSPHATASE - grade 0 | 2 Participants |
| ULO 600mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 1 | LEUKOCYTES - grade 4 | 2 Participants |
| ULO 600mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 1 | CALCIUM, TOTAL - grade 1 | 0 Participants |
| ULO 600mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 1 | LIPASE, TOTAL (COLORIMETRIC ASSAY) - grade 0 | 2 Participants |
| ULO 600mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 1 | ALBUMIN - grade 0 | 1 Participants |
| ULO 600mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 1 | LIPASE, TOTAL (COLORIMETRIC ASSAY) - grade 1 | 1 Participants |
| ULO 600mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 1 | CALCIUM, TOTAL - grade 2 | 2 Participants |
| ULO 600mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 1 | LIPASE, TOTAL (COLORIMETRIC ASSAY) - grade 3 | 0 Participants |
| ULO 600mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 1 | ALKALINE PHOSPHATASE grade 1 | 1 Participants |
| ULO 600mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 1 | LYMPHOCYTES (ABSOLUTE) - grade 0 | 0 Participants |
| ULO 600mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 1 | CREATINE KINASE - grade 0 | 3 Participants |
| ULO 600mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 1 | LYMPHOCYTES (ABSOLUTE) - grade 1 | 0 Participants |
| ULO 600mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 1 | ABSOLUTE NEUTROPHIL COUNT - grade 4 | 3 Participants |
| ULO 600mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 1 | LYMPHOCYTES (ABSOLUTE) - grade 2 | 2 Participants |
| ULO 600mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 1 | CREATININE - grade 0 | 2 Participants |
| ULO 600mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 1 | LYMPHOCYTES (ABSOLUTE) - grade 3 | 1 Participants |
| ULO 600mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 1 | ASPARTATE AMINOTRANSFERASE - grade 0 | 3 Participants |
| ULO 600mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 1 | NEUTROPHILS (ABSOLUTE) - grade 3 | 0 Participants |
| ULO 600mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 1 | CREATININE - grade 1 | 1 Participants |
| ULO 600mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 1 | NEUTROPHILS (ABSOLUTE) - grade 4 | 3 Participants |
| ULO 600mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 1 | ALBUMIN - grade 1 | 0 Participants |
| ULO 600mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 1 | PHOSPHORUS, INORGANIC - grade 0 | 3 Participants |
| ULO 600mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 1 | FIBRINOGEN - grade 0 | 1 Participants |
| ULO 600mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 1 | PHOSPHORUS, INORGANIC - grade 3 | 0 Participants |
| ULO 600mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 1 | ASPARTATE AMINOTRANSFERASE - grade 1 | 0 Participants |
| ULO 600mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 1 | PLATELET COUNT - grade 3 | 0 Participants |
| ULO 600mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 1 | GLUCOSE, FASTING SERUM - grade 0 | 1 Participants |
| ULO 600mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 1 | PLATELET COUNT - grade 4 | 3 Participants |
| ULO 600mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 1 | ALANINE AMINOTRANSFERASE - grade 1 | 1 Participants |
| ULO 600mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 1 | POTASSIUM, SERUM - grade 0 | 1 Participants |
| ULO 600mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 1 | GLUCOSE, FASTING SERUM - grade 1 | 2 Participants |
| ULO 600mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 1 | POTASSIUM, SERUM - grade 1 | 0 Participants |
| ULO 600mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 1 | BILIRUBIN, TOTAL - grade 0 | 3 Participants |
| ULO 600mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 1 | POTASSIUM, SERUM - grade 3 | 2 Participants |
| ULO 600mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 1 | GLUCOSE, FASTING SERUM - grade 2 | 0 Participants |
| ULO 600mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 1 | SODIUM, SERUM - grade 0 | 2 Participants |
| ULO 600mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 1 | ALBUMIN - grade 2 | 2 Participants |
| ULO 600mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 1 | SODIUM, SERUM - grade 1 | 0 Participants |
| ULO 600mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 1 | HEMOGLOBIN - grade 2 | 1 Participants |
| ULO 600mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 1 | SODIUM, SERUM - grade 3 | 1 Participants |
| ULO 600mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 1 | BILIRUBIN, TOTAL - grade 2 | 0 Participants |
| ULO 600mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 1 | URIC ACID - grade 0 | 3 Participants |
| ULO 600mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 1 | HEMOGLOBIN - grade 3 | 2 Participants |
| ULO 600mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 1 | URIC ACID - grade 1 | 0 Participants |
| ULO 600mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 1 | ABSOLUTE NEUTROPHIL COUNT - grade 3 | 0 Participants |
| ULO 800mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 1 | URIC ACID - grade 1 | 1 Participants |
| ULO 800mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 1 | ABSOLUTE NEUTROPHIL COUNT - grade 3 | 1 Participants |
| ULO 800mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 1 | ABSOLUTE NEUTROPHIL COUNT - grade 4 | 2 Participants |
| ULO 800mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 1 | ALANINE AMINOTRANSFERASE - grade 0 | 2 Participants |
| ULO 800mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 1 | ALANINE AMINOTRANSFERASE - grade 1 | 1 Participants |
| ULO 800mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 1 | ALBUMIN - grade 0 | 0 Participants |
| ULO 800mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 1 | ALBUMIN - grade 1 | 2 Participants |
| ULO 800mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 1 | ALBUMIN - grade 2 | 1 Participants |
| ULO 800mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 1 | ALKALINE PHOSPHATASE - grade 0 | 2 Participants |
| ULO 800mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 1 | ALKALINE PHOSPHATASE grade 1 | 1 Participants |
| ULO 800mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 1 | ASPARTATE AMINOTRANSFERASE - grade 0 | 2 Participants |
| ULO 800mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 1 | ASPARTATE AMINOTRANSFERASE - grade 1 | 1 Participants |
| ULO 800mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 1 | BILIRUBIN, TOTAL - grade 0 | 2 Participants |
| ULO 800mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 1 | BILIRUBIN, TOTAL - grade 2 | 1 Participants |
| ULO 800mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 1 | CALCIUM, TOTAL - grade 0 | 1 Participants |
| ULO 800mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 1 | CALCIUM, TOTAL - grade 1 | 1 Participants |
| ULO 800mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 1 | CALCIUM, TOTAL - grade 2 | 1 Participants |
| ULO 800mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 1 | CREATINE KINASE - grade 0 | 3 Participants |
| ULO 800mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 1 | CREATININE - grade 0 | 3 Participants |
| ULO 800mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 1 | CREATININE - grade 1 | 0 Participants |
| ULO 800mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 1 | FIBRINOGEN - grade 0 | 0 Participants |
| ULO 800mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 1 | GLUCOSE, FASTING SERUM - grade 0 | 1 Participants |
| ULO 800mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 1 | GLUCOSE, FASTING SERUM - grade 1 | 0 Participants |
| ULO 800mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 1 | GLUCOSE, FASTING SERUM - grade 2 | 2 Participants |
| ULO 800mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 1 | HEMOGLOBIN - grade 2 | 1 Participants |
| ULO 800mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 1 | HEMOGLOBIN - grade 3 | 2 Participants |
| ULO 800mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 1 | LEUKOCYTES - grade 0 | 1 Participants |
| ULO 800mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 1 | LEUKOCYTES - grade 3 | 1 Participants |
| ULO 800mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 1 | LEUKOCYTES - grade 4 | 1 Participants |
| ULO 800mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 1 | LIPASE, TOTAL (COLORIMETRIC ASSAY) - grade 0 | 1 Participants |
| ULO 800mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 1 | LIPASE, TOTAL (COLORIMETRIC ASSAY) - grade 1 | 0 Participants |
| ULO 800mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 1 | LIPASE, TOTAL (COLORIMETRIC ASSAY) - grade 3 | 2 Participants |
| ULO 800mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 1 | LYMPHOCYTES (ABSOLUTE) - grade 0 | 1 Participants |
| ULO 800mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 1 | LYMPHOCYTES (ABSOLUTE) - grade 1 | 1 Participants |
| ULO 800mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 1 | LYMPHOCYTES (ABSOLUTE) - grade 2 | 1 Participants |
| ULO 800mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 1 | LYMPHOCYTES (ABSOLUTE) - grade 3 | 0 Participants |
| ULO 800mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 1 | NEUTROPHILS (ABSOLUTE) - grade 3 | 1 Participants |
| ULO 800mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 1 | NEUTROPHILS (ABSOLUTE) - grade 4 | 2 Participants |
| ULO 800mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 1 | PHOSPHORUS, INORGANIC - grade 0 | 2 Participants |
| ULO 800mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 1 | PHOSPHORUS, INORGANIC - grade 3 | 1 Participants |
| ULO 800mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 1 | PLATELET COUNT - grade 3 | 1 Participants |
| ULO 800mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 1 | PLATELET COUNT - grade 4 | 2 Participants |
| ULO 800mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 1 | POTASSIUM, SERUM - grade 0 | 2 Participants |
| ULO 800mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 1 | POTASSIUM, SERUM - grade 1 | 1 Participants |
| ULO 800mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 1 | POTASSIUM, SERUM - grade 3 | 0 Participants |
| ULO 800mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 1 | SODIUM, SERUM - grade 0 | 1 Participants |
| ULO 800mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 1 | SODIUM, SERUM - grade 1 | 2 Participants |
| ULO 800mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 1 | SODIUM, SERUM - grade 3 | 0 Participants |
| ULO 800mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 1 | URIC ACID - grade 0 | 2 Participants |
Primary
Number of Participants With Serious Adverse Events (SAEs) - Phase 1
The number of participants with an on-study serious adverse event (SAE). Safety data are evaluated for SAEs, defined and evaluated using the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03 (NCI CTCAE v4.03).
Time frame: From first dose to 30 days post last dose
Population: All treated participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ULO 600mg + LDAC - Ph1 | Number of Participants With Serious Adverse Events (SAEs) - Phase 1 | 2 Participants |
| ULO 800mg + LDAC - Ph1 | Number of Participants With Serious Adverse Events (SAEs) - Phase 1 | 1 Participants |
Secondary
Area Under the Ulocuplumab Concentration-time Curve From Time Zero to Infinity [AUC(INF)] - Phases 1 and 2
The Pharmacokinetic (PK) parameters are assessed for ulocuplumab following study drug administration. EOT = end of treatment AUC(INF) calculated by summing AUC(0-T) and the extrapolated area, computed by the quotient Clast/λz Measure type and method of dispersion are Geometric mean and %CV, respectively
Time frame: Days 1, 8, 15 for cycles 1 and 2; Days 1, 8 for cycles 3-5; Day 1 every 4th cycle thereafter; EOT; 30 days post last dose (follow-up)
Population: Based on the PK sample collections, PK parameters depended on terminal phase time points including AUC(INF), T-HALF; or at steady-state, including CLT, Vss are not reportable
Secondary
Area Under the Ulocuplumab Concentration-time Curve From Time Zero to the Last Quantifiable Concentration [AUC(0-T)] - Phases 1 and 2
The Pharmacokinetic (PK) parameters are assessed for ulocuplumab following study drug administration. EOT = end of treatment AUC(0-T) calculated by log- and linear-trapezoidal summation Measure type and method of dispersion are Geometric mean and %CV, respectively
Time frame: Cycle 1 Day 1
Population: All treated participants who have evaluable PK profiles
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| ULO 600mg + LDAC - Ph1 | Area Under the Ulocuplumab Concentration-time Curve From Time Zero to the Last Quantifiable Concentration [AUC(0-T)] - Phases 1 and 2 | 9455.529 µg.h/mL | Geometric Coefficient of Variation 10 |
| ULO 800mg + LDAC - Ph1 | Area Under the Ulocuplumab Concentration-time Curve From Time Zero to the Last Quantifiable Concentration [AUC(0-T)] - Phases 1 and 2 | 21158.725 µg.h/mL | Geometric Coefficient of Variation 9 |
| LDAC - Ph2 | Area Under the Ulocuplumab Concentration-time Curve From Time Zero to the Last Quantifiable Concentration [AUC(0-T)] - Phases 1 and 2 | 8152.698 µg.h/mL | Geometric Coefficient of Variation 50 |
| ULO 1000mg + LDAC - Ph2 | Area Under the Ulocuplumab Concentration-time Curve From Time Zero to the Last Quantifiable Concentration [AUC(0-T)] - Phases 1 and 2 | 13744.382 µg.h/mL | Geometric Coefficient of Variation 37 |
| LDAC - Ph2 | Area Under the Ulocuplumab Concentration-time Curve From Time Zero to the Last Quantifiable Concentration [AUC(0-T)] - Phases 1 and 2 | 16502.463 µg.h/mL | — |
Secondary
Area Under the Ulocuplumab Concentration-time Curve in One Dosing Interval [AUC(TAU)] - Phases 1 and 2
The Pharmacokinetic (PK) parameters are assessed for ulocuplumab following study drug administration. EOT = end of treatment Measure type and method of dispersion are Geometric mean and %CV, respectively
Time frame: Cycle 1 Day 1
Population: All treated participants who have evaluable PK profiles
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| ULO 600mg + LDAC - Ph1 | Area Under the Ulocuplumab Concentration-time Curve in One Dosing Interval [AUC(TAU)] - Phases 1 and 2 | 9455.529 µg.h/mL | Geometric Coefficient of Variation 10 |
| ULO 800mg + LDAC - Ph1 | Area Under the Ulocuplumab Concentration-time Curve in One Dosing Interval [AUC(TAU)] - Phases 1 and 2 | 21158.725 µg.h/mL | Geometric Coefficient of Variation 9 |
| LDAC - Ph2 | Area Under the Ulocuplumab Concentration-time Curve in One Dosing Interval [AUC(TAU)] - Phases 1 and 2 | 10082.624 µg.h/mL | Geometric Coefficient of Variation 38 |
| ULO 1000mg + LDAC - Ph2 | Area Under the Ulocuplumab Concentration-time Curve in One Dosing Interval [AUC(TAU)] - Phases 1 and 2 | 13826.833 µg.h/mL | Geometric Coefficient of Variation 36 |
| LDAC - Ph2 | Area Under the Ulocuplumab Concentration-time Curve in One Dosing Interval [AUC(TAU)] - Phases 1 and 2 | 14257.807 µg.h/mL | — |
Secondary
Best Overall Response (BOR) - Phase 1
Investigator assessed best overall response prior to the initiation of any alternative therapy for Phase 1 participants.
Time frame: From first dose until a minimum follow-up of up to 2 months
Population: All randomized participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ULO 600mg + LDAC - Ph1 | Best Overall Response (BOR) - Phase 1 | 1 Participants |
| ULO 800mg + LDAC - Ph1 | Best Overall Response (BOR) - Phase 1 | 3 Participants |
Secondary
Change From Baseline of Electrocardiogram (ECG) Endpoints: Heart Rate - Phases 1 and 2
Change from baseline of ECG endpoints Heart rate measured in beats per minute (bpm)
Time frame: From first dose until a minimum follow-up of up to 2 months
Population: All treated participants
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ULO 600mg + LDAC - Ph1 | Change From Baseline of Electrocardiogram (ECG) Endpoints: Heart Rate - Phases 1 and 2 | Cycle 4, Day 1 | -1.0 change from baseline bpm | — |
| ULO 600mg + LDAC - Ph1 | Change From Baseline of Electrocardiogram (ECG) Endpoints: Heart Rate - Phases 1 and 2 | Cycle 13, Day 1 | -9.0 change from baseline bpm | — |
| ULO 600mg + LDAC - Ph1 | Change From Baseline of Electrocardiogram (ECG) Endpoints: Heart Rate - Phases 1 and 2 | Cycle 6, Day 1 | -6.0 change from baseline bpm | — |
| ULO 600mg + LDAC - Ph1 | Change From Baseline of Electrocardiogram (ECG) Endpoints: Heart Rate - Phases 1 and 2 | Cycle 5, Day 1 | -6.0 change from baseline bpm | — |
| ULO 600mg + LDAC - Ph1 | Change From Baseline of Electrocardiogram (ECG) Endpoints: Heart Rate - Phases 1 and 2 | Cycle 11, Day 1 | -12.0 change from baseline bpm | — |
| ULO 600mg + LDAC - Ph1 | Change From Baseline of Electrocardiogram (ECG) Endpoints: Heart Rate - Phases 1 and 2 | Cycle 3, Day 1 | -2.3 change from baseline bpm | Standard Deviation 18.8 |
| ULO 600mg + LDAC - Ph1 | Change From Baseline of Electrocardiogram (ECG) Endpoints: Heart Rate - Phases 1 and 2 | Cycle 15, Day 1 | -10.0 change from baseline bpm | — |
| ULO 600mg + LDAC - Ph1 | Change From Baseline of Electrocardiogram (ECG) Endpoints: Heart Rate - Phases 1 and 2 | Cycle 10, Day 1 | -3.0 change from baseline bpm | — |
| ULO 600mg + LDAC - Ph1 | Change From Baseline of Electrocardiogram (ECG) Endpoints: Heart Rate - Phases 1 and 2 | Cycle 2 Day 1 | 26.0 change from baseline bpm | Standard Deviation 63.6 |
| ULO 600mg + LDAC - Ph1 | Change From Baseline of Electrocardiogram (ECG) Endpoints: Heart Rate - Phases 1 and 2 | Cycle 8, Day 1 | -1.0 change from baseline bpm | — |
| ULO 800mg + LDAC - Ph1 | Change From Baseline of Electrocardiogram (ECG) Endpoints: Heart Rate - Phases 1 and 2 | Cycle 9, Day 1 | -17.0 change from baseline bpm | Standard Deviation 11.3 |
| ULO 800mg + LDAC - Ph1 | Change From Baseline of Electrocardiogram (ECG) Endpoints: Heart Rate - Phases 1 and 2 | Cycle 2 Day 1 | 4.0 change from baseline bpm | Standard Deviation 18.4 |
| ULO 800mg + LDAC - Ph1 | Change From Baseline of Electrocardiogram (ECG) Endpoints: Heart Rate - Phases 1 and 2 | Cycle 3, Day 1 | 0.0 change from baseline bpm | Standard Deviation 15.6 |
| ULO 800mg + LDAC - Ph1 | Change From Baseline of Electrocardiogram (ECG) Endpoints: Heart Rate - Phases 1 and 2 | Cycle 4, Day 1 | -16.0 change from baseline bpm | Standard Deviation 5.7 |
| ULO 800mg + LDAC - Ph1 | Change From Baseline of Electrocardiogram (ECG) Endpoints: Heart Rate - Phases 1 and 2 | Cycle 5, Day 1 | 1.5 change from baseline bpm | Standard Deviation 7.8 |
| ULO 800mg + LDAC - Ph1 | Change From Baseline of Electrocardiogram (ECG) Endpoints: Heart Rate - Phases 1 and 2 | Cycle 6, Day 1 | -6.0 change from baseline bpm | Standard Deviation 16.5 |
| ULO 800mg + LDAC - Ph1 | Change From Baseline of Electrocardiogram (ECG) Endpoints: Heart Rate - Phases 1 and 2 | Cycle 7, Day 1 | -11.7 change from baseline bpm | Standard Deviation 18.6 |
| ULO 800mg + LDAC - Ph1 | Change From Baseline of Electrocardiogram (ECG) Endpoints: Heart Rate - Phases 1 and 2 | Cycle 10, Day 1 | -16.0 change from baseline bpm | — |
| LDAC - Ph2 | Change From Baseline of Electrocardiogram (ECG) Endpoints: Heart Rate - Phases 1 and 2 | Cycle 4, Day 1 | -0.1 change from baseline bpm | Standard Deviation 9.9 |
| LDAC - Ph2 | Change From Baseline of Electrocardiogram (ECG) Endpoints: Heart Rate - Phases 1 and 2 | Cycle 3, Day 1 | 5.8 change from baseline bpm | Standard Deviation 14.2 |
| LDAC - Ph2 | Change From Baseline of Electrocardiogram (ECG) Endpoints: Heart Rate - Phases 1 and 2 | Cycle 2 Day 1 | 1.8 change from baseline bpm | Standard Deviation 11.3 |
| LDAC - Ph2 | Change From Baseline of Electrocardiogram (ECG) Endpoints: Heart Rate - Phases 1 and 2 | Cycle 9, Day 1 | 7.0 change from baseline bpm | Standard Deviation 7.1 |
| LDAC - Ph2 | Change From Baseline of Electrocardiogram (ECG) Endpoints: Heart Rate - Phases 1 and 2 | Cycle 6, Day 1 | 6.8 change from baseline bpm | Standard Deviation 5.3 |
| LDAC - Ph2 | Change From Baseline of Electrocardiogram (ECG) Endpoints: Heart Rate - Phases 1 and 2 | Cycle 14, Day 1 | 14.0 change from baseline bpm | — |
| LDAC - Ph2 | Change From Baseline of Electrocardiogram (ECG) Endpoints: Heart Rate - Phases 1 and 2 | Cycle 13, Day 1 | 8.0 change from baseline bpm | — |
| LDAC - Ph2 | Change From Baseline of Electrocardiogram (ECG) Endpoints: Heart Rate - Phases 1 and 2 | Cycle 7, Day 1 | -3.5 change from baseline bpm | Standard Deviation 5.9 |
| LDAC - Ph2 | Change From Baseline of Electrocardiogram (ECG) Endpoints: Heart Rate - Phases 1 and 2 | Cycle 5, Day 1 | 4.3 change from baseline bpm | Standard Deviation 12.3 |
| LDAC - Ph2 | Change From Baseline of Electrocardiogram (ECG) Endpoints: Heart Rate - Phases 1 and 2 | Cycle 12, Day 1 | 5.0 change from baseline bpm | — |
| LDAC - Ph2 | Change From Baseline of Electrocardiogram (ECG) Endpoints: Heart Rate - Phases 1 and 2 | Cycle 10, Day 1 | 9.3 change from baseline bpm | Standard Deviation 5.1 |
| LDAC - Ph2 | Change From Baseline of Electrocardiogram (ECG) Endpoints: Heart Rate - Phases 1 and 2 | Cycle 8, Day 1 | 0.7 change from baseline bpm | Standard Deviation 2.1 |
| ULO 1000mg + LDAC - Ph2 | Change From Baseline of Electrocardiogram (ECG) Endpoints: Heart Rate - Phases 1 and 2 | Cycle 5, Day 1 | 10.5 change from baseline bpm | Standard Deviation 2.1 |
| ULO 1000mg + LDAC - Ph2 | Change From Baseline of Electrocardiogram (ECG) Endpoints: Heart Rate - Phases 1 and 2 | Cycle 7, Day 1 | 12.0 change from baseline bpm | — |
| ULO 1000mg + LDAC - Ph2 | Change From Baseline of Electrocardiogram (ECG) Endpoints: Heart Rate - Phases 1 and 2 | Cycle 8, Day 1 | 11.0 change from baseline bpm | — |
| ULO 1000mg + LDAC - Ph2 | Change From Baseline of Electrocardiogram (ECG) Endpoints: Heart Rate - Phases 1 and 2 | Cycle 3, Day 1 | 12.7 change from baseline bpm | Standard Deviation 14.3 |
| ULO 1000mg + LDAC - Ph2 | Change From Baseline of Electrocardiogram (ECG) Endpoints: Heart Rate - Phases 1 and 2 | Cycle 9, Day 1 | 3.0 change from baseline bpm | — |
| ULO 1000mg + LDAC - Ph2 | Change From Baseline of Electrocardiogram (ECG) Endpoints: Heart Rate - Phases 1 and 2 | Cycle 11, Day 1 | 10.0 change from baseline bpm | — |
| ULO 1000mg + LDAC - Ph2 | Change From Baseline of Electrocardiogram (ECG) Endpoints: Heart Rate - Phases 1 and 2 | Cycle 12, Day 1 | 19.0 change from baseline bpm | — |
| ULO 1000mg + LDAC - Ph2 | Change From Baseline of Electrocardiogram (ECG) Endpoints: Heart Rate - Phases 1 and 2 | Cycle 2 Day 1 | -0.9 change from baseline bpm | Standard Deviation 20 |
| ULO 1000mg + LDAC - Ph2 | Change From Baseline of Electrocardiogram (ECG) Endpoints: Heart Rate - Phases 1 and 2 | Cycle 4, Day 1 | 11.0 change from baseline bpm | Standard Deviation 40.6 |
| LDAC - Ph2 | Change From Baseline of Electrocardiogram (ECG) Endpoints: Heart Rate - Phases 1 and 2 | Cycle 10, Day 1 | 2.0 change from baseline bpm | Standard Deviation 1.4 |
| LDAC - Ph2 | Change From Baseline of Electrocardiogram (ECG) Endpoints: Heart Rate - Phases 1 and 2 | Cycle 2 Day 1 | -3.0 change from baseline bpm | Standard Deviation 7.6 |
| LDAC - Ph2 | Change From Baseline of Electrocardiogram (ECG) Endpoints: Heart Rate - Phases 1 and 2 | Cycle 4, Day 1 | 1.3 change from baseline bpm | Standard Deviation 16.7 |
| LDAC - Ph2 | Change From Baseline of Electrocardiogram (ECG) Endpoints: Heart Rate - Phases 1 and 2 | Cycle 11, Day 1 | -0.3 change from baseline bpm | Standard Deviation 6.7 |
| LDAC - Ph2 | Change From Baseline of Electrocardiogram (ECG) Endpoints: Heart Rate - Phases 1 and 2 | Cycle 7, Day 1 | 6.5 change from baseline bpm | Standard Deviation 13.5 |
| LDAC - Ph2 | Change From Baseline of Electrocardiogram (ECG) Endpoints: Heart Rate - Phases 1 and 2 | Cycle 5, Day 1 | 8.8 change from baseline bpm | Standard Deviation 27.5 |
| LDAC - Ph2 | Change From Baseline of Electrocardiogram (ECG) Endpoints: Heart Rate - Phases 1 and 2 | Cycle 12, Day 1 | 7.0 change from baseline bpm | Standard Deviation 2.8 |
| LDAC - Ph2 | Change From Baseline of Electrocardiogram (ECG) Endpoints: Heart Rate - Phases 1 and 2 | Cycle 6, Day 1 | 7.4 change from baseline bpm | Standard Deviation 14.9 |
| LDAC - Ph2 | Change From Baseline of Electrocardiogram (ECG) Endpoints: Heart Rate - Phases 1 and 2 | Cycle 15, Day 1 | 8.0 change from baseline bpm | — |
| LDAC - Ph2 | Change From Baseline of Electrocardiogram (ECG) Endpoints: Heart Rate - Phases 1 and 2 | Cycle 13, Day 1 | 4.0 change from baseline bpm | Standard Deviation 2.8 |
| LDAC - Ph2 | Change From Baseline of Electrocardiogram (ECG) Endpoints: Heart Rate - Phases 1 and 2 | Cycle 9, Day 1 | 0.6 change from baseline bpm | Standard Deviation 8.9 |
| LDAC - Ph2 | Change From Baseline of Electrocardiogram (ECG) Endpoints: Heart Rate - Phases 1 and 2 | Cycle 8, Day 1 | 0.8 change from baseline bpm | Standard Deviation 11.4 |
| LDAC - Ph2 | Change From Baseline of Electrocardiogram (ECG) Endpoints: Heart Rate - Phases 1 and 2 | Cycle 16, Day 1 | 18.0 change from baseline bpm | — |
| LDAC - Ph2 | Change From Baseline of Electrocardiogram (ECG) Endpoints: Heart Rate - Phases 1 and 2 | Cycle 3, Day 1 | 1.7 change from baseline bpm | Standard Deviation 10.2 |
Secondary
Change From Baseline of Electrocardiogram (ECG) Endpoints: PR Interval - Phases 1 and 2
Change from baseline of ECG endpoints PR interval measured in milliseconds (msec)
Time frame: From first dose until a minimum follow-up of up to 2 months
Population: All treated participants
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ULO 600mg + LDAC - Ph1 | Change From Baseline of Electrocardiogram (ECG) Endpoints: PR Interval - Phases 1 and 2 | Cycle 4, Day 1 | 14.0 change from baseline msec | — |
| ULO 600mg + LDAC - Ph1 | Change From Baseline of Electrocardiogram (ECG) Endpoints: PR Interval - Phases 1 and 2 | Cycle 13, Day 1 | -2.0 change from baseline msec | — |
| ULO 600mg + LDAC - Ph1 | Change From Baseline of Electrocardiogram (ECG) Endpoints: PR Interval - Phases 1 and 2 | Cycle 6, Day 1 | -44.0 change from baseline msec | — |
| ULO 600mg + LDAC - Ph1 | Change From Baseline of Electrocardiogram (ECG) Endpoints: PR Interval - Phases 1 and 2 | Cycle 5, Day 1 | -2.0 change from baseline msec | — |
| ULO 600mg + LDAC - Ph1 | Change From Baseline of Electrocardiogram (ECG) Endpoints: PR Interval - Phases 1 and 2 | Cycle 11, Day 1 | 4.0 change from baseline msec | — |
| ULO 600mg + LDAC - Ph1 | Change From Baseline of Electrocardiogram (ECG) Endpoints: PR Interval - Phases 1 and 2 | Cycle 3, Day 1 | 8.0 change from baseline msec | Standard Deviation 6 |
| ULO 600mg + LDAC - Ph1 | Change From Baseline of Electrocardiogram (ECG) Endpoints: PR Interval - Phases 1 and 2 | Cycle 15, Day 1 | 0.0 change from baseline msec | — |
| ULO 600mg + LDAC - Ph1 | Change From Baseline of Electrocardiogram (ECG) Endpoints: PR Interval - Phases 1 and 2 | Cycle 10, Day 1 | -4.0 change from baseline msec | — |
| ULO 600mg + LDAC - Ph1 | Change From Baseline of Electrocardiogram (ECG) Endpoints: PR Interval - Phases 1 and 2 | Cycle 2 Day 1 | 4.0 change from baseline msec | — |
| ULO 600mg + LDAC - Ph1 | Change From Baseline of Electrocardiogram (ECG) Endpoints: PR Interval - Phases 1 and 2 | Cycle 8, Day 1 | 4.0 change from baseline msec | — |
| ULO 800mg + LDAC - Ph1 | Change From Baseline of Electrocardiogram (ECG) Endpoints: PR Interval - Phases 1 and 2 | Cycle 9, Day 1 | -10.0 change from baseline msec | Standard Deviation 0 |
| ULO 800mg + LDAC - Ph1 | Change From Baseline of Electrocardiogram (ECG) Endpoints: PR Interval - Phases 1 and 2 | Cycle 2 Day 1 | -14.0 change from baseline msec | Standard Deviation 19.8 |
| ULO 800mg + LDAC - Ph1 | Change From Baseline of Electrocardiogram (ECG) Endpoints: PR Interval - Phases 1 and 2 | Cycle 3, Day 1 | -12.0 change from baseline msec | Standard Deviation 0 |
| ULO 800mg + LDAC - Ph1 | Change From Baseline of Electrocardiogram (ECG) Endpoints: PR Interval - Phases 1 and 2 | Cycle 4, Day 1 | -13.0 change from baseline msec | Standard Deviation 1.4 |
| ULO 800mg + LDAC - Ph1 | Change From Baseline of Electrocardiogram (ECG) Endpoints: PR Interval - Phases 1 and 2 | Cycle 5, Day 1 | -16.0 change from baseline msec | Standard Deviation 2.8 |
| ULO 800mg + LDAC - Ph1 | Change From Baseline of Electrocardiogram (ECG) Endpoints: PR Interval - Phases 1 and 2 | Cycle 6, Day 1 | -19.3 change from baseline msec | Standard Deviation 9.2 |
| ULO 800mg + LDAC - Ph1 | Change From Baseline of Electrocardiogram (ECG) Endpoints: PR Interval - Phases 1 and 2 | Cycle 7, Day 1 | -17.3 change from baseline msec | Standard Deviation 9.5 |
| ULO 800mg + LDAC - Ph1 | Change From Baseline of Electrocardiogram (ECG) Endpoints: PR Interval - Phases 1 and 2 | Cycle 10, Day 1 | -2.0 change from baseline msec | — |
| LDAC - Ph2 | Change From Baseline of Electrocardiogram (ECG) Endpoints: PR Interval - Phases 1 and 2 | Cycle 4, Day 1 | -16.3 change from baseline msec | Standard Deviation 28.4 |
| LDAC - Ph2 | Change From Baseline of Electrocardiogram (ECG) Endpoints: PR Interval - Phases 1 and 2 | Cycle 3, Day 1 | -5.3 change from baseline msec | Standard Deviation 26.2 |
| LDAC - Ph2 | Change From Baseline of Electrocardiogram (ECG) Endpoints: PR Interval - Phases 1 and 2 | Cycle 2 Day 1 | 1.1 change from baseline msec | Standard Deviation 23.9 |
| LDAC - Ph2 | Change From Baseline of Electrocardiogram (ECG) Endpoints: PR Interval - Phases 1 and 2 | Cycle 9, Day 1 | -17.0 change from baseline msec | Standard Deviation 46.7 |
| LDAC - Ph2 | Change From Baseline of Electrocardiogram (ECG) Endpoints: PR Interval - Phases 1 and 2 | Cycle 6, Day 1 | -12.8 change from baseline msec | Standard Deviation 21.8 |
| LDAC - Ph2 | Change From Baseline of Electrocardiogram (ECG) Endpoints: PR Interval - Phases 1 and 2 | Cycle 14, Day 1 | -54.0 change from baseline msec | — |
| LDAC - Ph2 | Change From Baseline of Electrocardiogram (ECG) Endpoints: PR Interval - Phases 1 and 2 | Cycle 13, Day 1 | -44.0 change from baseline msec | — |
| LDAC - Ph2 | Change From Baseline of Electrocardiogram (ECG) Endpoints: PR Interval - Phases 1 and 2 | Cycle 7, Day 1 | -6.8 change from baseline msec | Standard Deviation 12 |
| LDAC - Ph2 | Change From Baseline of Electrocardiogram (ECG) Endpoints: PR Interval - Phases 1 and 2 | Cycle 5, Day 1 | -7.6 change from baseline msec | Standard Deviation 24.5 |
| LDAC - Ph2 | Change From Baseline of Electrocardiogram (ECG) Endpoints: PR Interval - Phases 1 and 2 | Cycle 12, Day 1 | -60.0 change from baseline msec | — |
| LDAC - Ph2 | Change From Baseline of Electrocardiogram (ECG) Endpoints: PR Interval - Phases 1 and 2 | Cycle 10, Day 1 | -11.3 change from baseline msec | Standard Deviation 30.1 |
| LDAC - Ph2 | Change From Baseline of Electrocardiogram (ECG) Endpoints: PR Interval - Phases 1 and 2 | Cycle 8, Day 1 | -5.3 change from baseline msec | Standard Deviation 27.2 |
| ULO 1000mg + LDAC - Ph2 | Change From Baseline of Electrocardiogram (ECG) Endpoints: PR Interval - Phases 1 and 2 | Cycle 5, Day 1 | -11.0 change from baseline msec | Standard Deviation 7.1 |
| ULO 1000mg + LDAC - Ph2 | Change From Baseline of Electrocardiogram (ECG) Endpoints: PR Interval - Phases 1 and 2 | Cycle 7, Day 1 | -2.0 change from baseline msec | — |
| ULO 1000mg + LDAC - Ph2 | Change From Baseline of Electrocardiogram (ECG) Endpoints: PR Interval - Phases 1 and 2 | Cycle 8, Day 1 | -6.0 change from baseline msec | — |
| ULO 1000mg + LDAC - Ph2 | Change From Baseline of Electrocardiogram (ECG) Endpoints: PR Interval - Phases 1 and 2 | Cycle 3, Day 1 | -2.8 change from baseline msec | Standard Deviation 8.4 |
| ULO 1000mg + LDAC - Ph2 | Change From Baseline of Electrocardiogram (ECG) Endpoints: PR Interval - Phases 1 and 2 | Cycle 9, Day 1 | 6.0 change from baseline msec | — |
| ULO 1000mg + LDAC - Ph2 | Change From Baseline of Electrocardiogram (ECG) Endpoints: PR Interval - Phases 1 and 2 | Cycle 11, Day 1 | 4.0 change from baseline msec | — |
| ULO 1000mg + LDAC - Ph2 | Change From Baseline of Electrocardiogram (ECG) Endpoints: PR Interval - Phases 1 and 2 | Cycle 12, Day 1 | -4.0 change from baseline msec | — |
| ULO 1000mg + LDAC - Ph2 | Change From Baseline of Electrocardiogram (ECG) Endpoints: PR Interval - Phases 1 and 2 | Cycle 2 Day 1 | -5.1 change from baseline msec | Standard Deviation 9.9 |
| ULO 1000mg + LDAC - Ph2 | Change From Baseline of Electrocardiogram (ECG) Endpoints: PR Interval - Phases 1 and 2 | Cycle 4, Day 1 | -10.0 change from baseline msec | — |
| LDAC - Ph2 | Change From Baseline of Electrocardiogram (ECG) Endpoints: PR Interval - Phases 1 and 2 | Cycle 10, Day 1 | 1.0 change from baseline msec | Standard Deviation 1.4 |
| LDAC - Ph2 | Change From Baseline of Electrocardiogram (ECG) Endpoints: PR Interval - Phases 1 and 2 | Cycle 2 Day 1 | 1.2 change from baseline msec | Standard Deviation 5.3 |
| LDAC - Ph2 | Change From Baseline of Electrocardiogram (ECG) Endpoints: PR Interval - Phases 1 and 2 | Cycle 4, Day 1 | -11.9 change from baseline msec | Standard Deviation 15.7 |
| LDAC - Ph2 | Change From Baseline of Electrocardiogram (ECG) Endpoints: PR Interval - Phases 1 and 2 | Cycle 11, Day 1 | -1.7 change from baseline msec | Standard Deviation 12.7 |
| LDAC - Ph2 | Change From Baseline of Electrocardiogram (ECG) Endpoints: PR Interval - Phases 1 and 2 | Cycle 7, Day 1 | -8.3 change from baseline msec | Standard Deviation 20.9 |
| LDAC - Ph2 | Change From Baseline of Electrocardiogram (ECG) Endpoints: PR Interval - Phases 1 and 2 | Cycle 5, Day 1 | -24.6 change from baseline msec | Standard Deviation 7.2 |
| LDAC - Ph2 | Change From Baseline of Electrocardiogram (ECG) Endpoints: PR Interval - Phases 1 and 2 | Cycle 12, Day 1 | -5.0 change from baseline msec | Standard Deviation 1.4 |
| LDAC - Ph2 | Change From Baseline of Electrocardiogram (ECG) Endpoints: PR Interval - Phases 1 and 2 | Cycle 6, Day 1 | -3.4 change from baseline msec | Standard Deviation 19.5 |
| LDAC - Ph2 | Change From Baseline of Electrocardiogram (ECG) Endpoints: PR Interval - Phases 1 and 2 | Cycle 15, Day 1 | -10.0 change from baseline msec | — |
| LDAC - Ph2 | Change From Baseline of Electrocardiogram (ECG) Endpoints: PR Interval - Phases 1 and 2 | Cycle 13, Day 1 | 3.0 change from baseline msec | Standard Deviation 1.4 |
| LDAC - Ph2 | Change From Baseline of Electrocardiogram (ECG) Endpoints: PR Interval - Phases 1 and 2 | Cycle 9, Day 1 | 0.6 change from baseline msec | Standard Deviation 8.5 |
| LDAC - Ph2 | Change From Baseline of Electrocardiogram (ECG) Endpoints: PR Interval - Phases 1 and 2 | Cycle 8, Day 1 | -9.4 change from baseline msec | Standard Deviation 16.2 |
| LDAC - Ph2 | Change From Baseline of Electrocardiogram (ECG) Endpoints: PR Interval - Phases 1 and 2 | Cycle 16, Day 1 | -2.0 change from baseline msec | — |
| LDAC - Ph2 | Change From Baseline of Electrocardiogram (ECG) Endpoints: PR Interval - Phases 1 and 2 | Cycle 3, Day 1 | -1.9 change from baseline msec | Standard Deviation 7.5 |
Secondary
Change From Baseline of Electrocardiogram (ECG) Endpoints: QRS Interval - Phases 1 and 2
Change from baseline of ECG endpoints QRS interval measured in milliseconds (msec)
Time frame: From first dose until a minimum follow-up of up to 2 months
Population: All treated participants
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ULO 600mg + LDAC - Ph1 | Change From Baseline of Electrocardiogram (ECG) Endpoints: QRS Interval - Phases 1 and 2 | Cycle 4, Day 1 | 0.0 change from baseline msec | — |
| ULO 600mg + LDAC - Ph1 | Change From Baseline of Electrocardiogram (ECG) Endpoints: QRS Interval - Phases 1 and 2 | Cycle 13, Day 1 | 2.0 change from baseline msec | — |
| ULO 600mg + LDAC - Ph1 | Change From Baseline of Electrocardiogram (ECG) Endpoints: QRS Interval - Phases 1 and 2 | Cycle 6, Day 1 | 6.0 change from baseline msec | — |
| ULO 600mg + LDAC - Ph1 | Change From Baseline of Electrocardiogram (ECG) Endpoints: QRS Interval - Phases 1 and 2 | Cycle 5, Day 1 | 8.0 change from baseline msec | — |
| ULO 600mg + LDAC - Ph1 | Change From Baseline of Electrocardiogram (ECG) Endpoints: QRS Interval - Phases 1 and 2 | Cycle 11, Day 1 | 6.0 change from baseline msec | — |
| ULO 600mg + LDAC - Ph1 | Change From Baseline of Electrocardiogram (ECG) Endpoints: QRS Interval - Phases 1 and 2 | Cycle 3, Day 1 | 3.3 change from baseline msec | Standard Deviation 7.6 |
| ULO 600mg + LDAC - Ph1 | Change From Baseline of Electrocardiogram (ECG) Endpoints: QRS Interval - Phases 1 and 2 | Cycle 15, Day 1 | 6.0 change from baseline msec | — |
| ULO 600mg + LDAC - Ph1 | Change From Baseline of Electrocardiogram (ECG) Endpoints: QRS Interval - Phases 1 and 2 | Cycle 10, Day 1 | 2.0 change from baseline msec | — |
| ULO 600mg + LDAC - Ph1 | Change From Baseline of Electrocardiogram (ECG) Endpoints: QRS Interval - Phases 1 and 2 | Cycle 2 Day 1 | 0.0 change from baseline msec | Standard Deviation 5.7 |
| ULO 600mg + LDAC - Ph1 | Change From Baseline of Electrocardiogram (ECG) Endpoints: QRS Interval - Phases 1 and 2 | Cycle 8, Day 1 | 2.0 change from baseline msec | — |
| ULO 800mg + LDAC - Ph1 | Change From Baseline of Electrocardiogram (ECG) Endpoints: QRS Interval - Phases 1 and 2 | Cycle 9, Day 1 | -1.0 change from baseline msec | Standard Deviation 1.4 |
| ULO 800mg + LDAC - Ph1 | Change From Baseline of Electrocardiogram (ECG) Endpoints: QRS Interval - Phases 1 and 2 | Cycle 2 Day 1 | -2.0 change from baseline msec | Standard Deviation 5.7 |
| ULO 800mg + LDAC - Ph1 | Change From Baseline of Electrocardiogram (ECG) Endpoints: QRS Interval - Phases 1 and 2 | Cycle 3, Day 1 | -2.0 change from baseline msec | Standard Deviation 5.7 |
| ULO 800mg + LDAC - Ph1 | Change From Baseline of Electrocardiogram (ECG) Endpoints: QRS Interval - Phases 1 and 2 | Cycle 4, Day 1 | 1.0 change from baseline msec | Standard Deviation 1.4 |
| ULO 800mg + LDAC - Ph1 | Change From Baseline of Electrocardiogram (ECG) Endpoints: QRS Interval - Phases 1 and 2 | Cycle 5, Day 1 | -4.0 change from baseline msec | Standard Deviation 2.8 |
| ULO 800mg + LDAC - Ph1 | Change From Baseline of Electrocardiogram (ECG) Endpoints: QRS Interval - Phases 1 and 2 | Cycle 6, Day 1 | -2.7 change from baseline msec | Standard Deviation 4.2 |
| ULO 800mg + LDAC - Ph1 | Change From Baseline of Electrocardiogram (ECG) Endpoints: QRS Interval - Phases 1 and 2 | Cycle 7, Day 1 | -2.7 change from baseline msec | Standard Deviation 4.2 |
| ULO 800mg + LDAC - Ph1 | Change From Baseline of Electrocardiogram (ECG) Endpoints: QRS Interval - Phases 1 and 2 | Cycle 10, Day 1 | -4.0 change from baseline msec | — |
| LDAC - Ph2 | Change From Baseline of Electrocardiogram (ECG) Endpoints: QRS Interval - Phases 1 and 2 | Cycle 4, Day 1 | 2.7 change from baseline msec | Standard Deviation 8.8 |
| LDAC - Ph2 | Change From Baseline of Electrocardiogram (ECG) Endpoints: QRS Interval - Phases 1 and 2 | Cycle 3, Day 1 | -1.3 change from baseline msec | Standard Deviation 7.6 |
| LDAC - Ph2 | Change From Baseline of Electrocardiogram (ECG) Endpoints: QRS Interval - Phases 1 and 2 | Cycle 2 Day 1 | 5.1 change from baseline msec | Standard Deviation 11.3 |
| LDAC - Ph2 | Change From Baseline of Electrocardiogram (ECG) Endpoints: QRS Interval - Phases 1 and 2 | Cycle 9, Day 1 | -2.0 change from baseline msec | Standard Deviation 8.5 |
| LDAC - Ph2 | Change From Baseline of Electrocardiogram (ECG) Endpoints: QRS Interval - Phases 1 and 2 | Cycle 6, Day 1 | -1.8 change from baseline msec | Standard Deviation 6.2 |
| LDAC - Ph2 | Change From Baseline of Electrocardiogram (ECG) Endpoints: QRS Interval - Phases 1 and 2 | Cycle 14, Day 1 | -10.0 change from baseline msec | — |
| LDAC - Ph2 | Change From Baseline of Electrocardiogram (ECG) Endpoints: QRS Interval - Phases 1 and 2 | Cycle 13, Day 1 | -12.0 change from baseline msec | — |
| LDAC - Ph2 | Change From Baseline of Electrocardiogram (ECG) Endpoints: QRS Interval - Phases 1 and 2 | Cycle 7, Day 1 | -3.3 change from baseline msec | Standard Deviation 7 |
| LDAC - Ph2 | Change From Baseline of Electrocardiogram (ECG) Endpoints: QRS Interval - Phases 1 and 2 | Cycle 5, Day 1 | 1.8 change from baseline msec | Standard Deviation 9.5 |
| LDAC - Ph2 | Change From Baseline of Electrocardiogram (ECG) Endpoints: QRS Interval - Phases 1 and 2 | Cycle 12, Day 1 | -6.0 change from baseline msec | — |
| LDAC - Ph2 | Change From Baseline of Electrocardiogram (ECG) Endpoints: QRS Interval - Phases 1 and 2 | Cycle 10, Day 1 | -2.3 change from baseline msec | Standard Deviation 8.6 |
| LDAC - Ph2 | Change From Baseline of Electrocardiogram (ECG) Endpoints: QRS Interval - Phases 1 and 2 | Cycle 8, Day 1 | 0.7 change from baseline msec | Standard Deviation 2.3 |
| ULO 1000mg + LDAC - Ph2 | Change From Baseline of Electrocardiogram (ECG) Endpoints: QRS Interval - Phases 1 and 2 | Cycle 5, Day 1 | 2.0 change from baseline msec | Standard Deviation 5.7 |
| ULO 1000mg + LDAC - Ph2 | Change From Baseline of Electrocardiogram (ECG) Endpoints: QRS Interval - Phases 1 and 2 | Cycle 7, Day 1 | -10.0 change from baseline msec | — |
| ULO 1000mg + LDAC - Ph2 | Change From Baseline of Electrocardiogram (ECG) Endpoints: QRS Interval - Phases 1 and 2 | Cycle 8, Day 1 | -8.0 change from baseline msec | — |
| ULO 1000mg + LDAC - Ph2 | Change From Baseline of Electrocardiogram (ECG) Endpoints: QRS Interval - Phases 1 and 2 | Cycle 3, Day 1 | 2.0 change from baseline msec | Standard Deviation 3.4 |
| ULO 1000mg + LDAC - Ph2 | Change From Baseline of Electrocardiogram (ECG) Endpoints: QRS Interval - Phases 1 and 2 | Cycle 9, Day 1 | -6.0 change from baseline msec | — |
| ULO 1000mg + LDAC - Ph2 | Change From Baseline of Electrocardiogram (ECG) Endpoints: QRS Interval - Phases 1 and 2 | Cycle 11, Day 1 | -4.0 change from baseline msec | — |
| ULO 1000mg + LDAC - Ph2 | Change From Baseline of Electrocardiogram (ECG) Endpoints: QRS Interval - Phases 1 and 2 | Cycle 12, Day 1 | -8.0 change from baseline msec | — |
| ULO 1000mg + LDAC - Ph2 | Change From Baseline of Electrocardiogram (ECG) Endpoints: QRS Interval - Phases 1 and 2 | Cycle 2 Day 1 | 0.5 change from baseline msec | Standard Deviation 9.6 |
| ULO 1000mg + LDAC - Ph2 | Change From Baseline of Electrocardiogram (ECG) Endpoints: QRS Interval - Phases 1 and 2 | Cycle 4, Day 1 | -3.3 change from baseline msec | Standard Deviation 6.1 |
| LDAC - Ph2 | Change From Baseline of Electrocardiogram (ECG) Endpoints: QRS Interval - Phases 1 and 2 | Cycle 10, Day 1 | 9.5 change from baseline msec | Standard Deviation 4.9 |
| LDAC - Ph2 | Change From Baseline of Electrocardiogram (ECG) Endpoints: QRS Interval - Phases 1 and 2 | Cycle 2 Day 1 | 4.8 change from baseline msec | Standard Deviation 12.5 |
| LDAC - Ph2 | Change From Baseline of Electrocardiogram (ECG) Endpoints: QRS Interval - Phases 1 and 2 | Cycle 4, Day 1 | 6.4 change from baseline msec | Standard Deviation 16.1 |
| LDAC - Ph2 | Change From Baseline of Electrocardiogram (ECG) Endpoints: QRS Interval - Phases 1 and 2 | Cycle 11, Day 1 | 9.0 change from baseline msec | Standard Deviation 7.5 |
| LDAC - Ph2 | Change From Baseline of Electrocardiogram (ECG) Endpoints: QRS Interval - Phases 1 and 2 | Cycle 7, Day 1 | -1.5 change from baseline msec | Standard Deviation 4.9 |
| LDAC - Ph2 | Change From Baseline of Electrocardiogram (ECG) Endpoints: QRS Interval - Phases 1 and 2 | Cycle 5, Day 1 | -1.4 change from baseline msec | Standard Deviation 2.4 |
| LDAC - Ph2 | Change From Baseline of Electrocardiogram (ECG) Endpoints: QRS Interval - Phases 1 and 2 | Cycle 12, Day 1 | 10.0 change from baseline msec | Standard Deviation 5.7 |
| LDAC - Ph2 | Change From Baseline of Electrocardiogram (ECG) Endpoints: QRS Interval - Phases 1 and 2 | Cycle 6, Day 1 | 5.4 change from baseline msec | Standard Deviation 14.7 |
| LDAC - Ph2 | Change From Baseline of Electrocardiogram (ECG) Endpoints: QRS Interval - Phases 1 and 2 | Cycle 15, Day 1 | 8.0 change from baseline msec | — |
| LDAC - Ph2 | Change From Baseline of Electrocardiogram (ECG) Endpoints: QRS Interval - Phases 1 and 2 | Cycle 13, Day 1 | 3.5 change from baseline msec | Standard Deviation 10.6 |
| LDAC - Ph2 | Change From Baseline of Electrocardiogram (ECG) Endpoints: QRS Interval - Phases 1 and 2 | Cycle 9, Day 1 | 0.0 change from baseline msec | Standard Deviation 3.2 |
| LDAC - Ph2 | Change From Baseline of Electrocardiogram (ECG) Endpoints: QRS Interval - Phases 1 and 2 | Cycle 8, Day 1 | 2.6 change from baseline msec | Standard Deviation 6.9 |
| LDAC - Ph2 | Change From Baseline of Electrocardiogram (ECG) Endpoints: QRS Interval - Phases 1 and 2 | Cycle 16, Day 1 | 7.0 change from baseline msec | — |
| LDAC - Ph2 | Change From Baseline of Electrocardiogram (ECG) Endpoints: QRS Interval - Phases 1 and 2 | Cycle 3, Day 1 | 1.4 change from baseline msec | Standard Deviation 8.2 |
Secondary
Change From Baseline of Electrocardiogram (ECG) Endpoints: QT Interval - Phases 1 and 2
Change from baseline of ECG endpoints QT interval measured in milliseconds (msec)
Time frame: From first dose until a minimum follow-up of up to 2 months
Population: All treated participants
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ULO 600mg + LDAC - Ph1 | Change From Baseline of Electrocardiogram (ECG) Endpoints: QT Interval - Phases 1 and 2 | Cycle 4, Day 1 | -60.0 change from baseline msec | — |
| ULO 600mg + LDAC - Ph1 | Change From Baseline of Electrocardiogram (ECG) Endpoints: QT Interval - Phases 1 and 2 | Cycle 2 Day 1 | -41.0 change from baseline msec | Standard Deviation 94.8 |
| ULO 600mg + LDAC - Ph1 | Change From Baseline of Electrocardiogram (ECG) Endpoints: QT Interval - Phases 1 and 2 | Cycle 5, Day 1 | 12.0 change from baseline msec | — |
| ULO 600mg + LDAC - Ph1 | Change From Baseline of Electrocardiogram (ECG) Endpoints: QT Interval - Phases 1 and 2 | Cycle 15, Day 1 | 36.0 change from baseline msec | — |
| ULO 600mg + LDAC - Ph1 | Change From Baseline of Electrocardiogram (ECG) Endpoints: QT Interval - Phases 1 and 2 | Cycle 13, Day 1 | 20.0 change from baseline msec | — |
| ULO 600mg + LDAC - Ph1 | Change From Baseline of Electrocardiogram (ECG) Endpoints: QT Interval - Phases 1 and 2 | Cycle 11, Day 1 | 16.0 change from baseline msec | — |
| ULO 600mg + LDAC - Ph1 | Change From Baseline of Electrocardiogram (ECG) Endpoints: QT Interval - Phases 1 and 2 | Cycle 3, Day 1 | 10.0 change from baseline msec | Standard Deviation 36.7 |
| ULO 600mg + LDAC - Ph1 | Change From Baseline of Electrocardiogram (ECG) Endpoints: QT Interval - Phases 1 and 2 | Cycle 10, Day 1 | 6.0 change from baseline msec | — |
| ULO 600mg + LDAC - Ph1 | Change From Baseline of Electrocardiogram (ECG) Endpoints: QT Interval - Phases 1 and 2 | Cycle 8, Day 1 | 2.0 change from baseline msec | — |
| ULO 600mg + LDAC - Ph1 | Change From Baseline of Electrocardiogram (ECG) Endpoints: QT Interval - Phases 1 and 2 | Cycle 6, Day 1 | 2.0 change from baseline msec | — |
| ULO 800mg + LDAC - Ph1 | Change From Baseline of Electrocardiogram (ECG) Endpoints: QT Interval - Phases 1 and 2 | Cycle 9, Day 1 | 37.0 change from baseline msec | Standard Deviation 9.9 |
| ULO 800mg + LDAC - Ph1 | Change From Baseline of Electrocardiogram (ECG) Endpoints: QT Interval - Phases 1 and 2 | Cycle 2 Day 1 | -5.0 change from baseline msec | Standard Deviation 7.1 |
| ULO 800mg + LDAC - Ph1 | Change From Baseline of Electrocardiogram (ECG) Endpoints: QT Interval - Phases 1 and 2 | Cycle 4, Day 1 | 35.0 change from baseline msec | Standard Deviation 32.5 |
| ULO 800mg + LDAC - Ph1 | Change From Baseline of Electrocardiogram (ECG) Endpoints: QT Interval - Phases 1 and 2 | Cycle 5, Day 1 | 13.0 change from baseline msec | Standard Deviation 15.6 |
| ULO 800mg + LDAC - Ph1 | Change From Baseline of Electrocardiogram (ECG) Endpoints: QT Interval - Phases 1 and 2 | Cycle 6, Day 1 | 6.0 change from baseline msec | Standard Deviation 26.9 |
| ULO 800mg + LDAC - Ph1 | Change From Baseline of Electrocardiogram (ECG) Endpoints: QT Interval - Phases 1 and 2 | Cycle 7, Day 1 | 29.3 change from baseline msec | Standard Deviation 20 |
| ULO 800mg + LDAC - Ph1 | Change From Baseline of Electrocardiogram (ECG) Endpoints: QT Interval - Phases 1 and 2 | Cycle 3, Day 1 | 7.0 change from baseline msec | Standard Deviation 29.7 |
| ULO 800mg + LDAC - Ph1 | Change From Baseline of Electrocardiogram (ECG) Endpoints: QT Interval - Phases 1 and 2 | Cycle 10, Day 1 | 14.0 change from baseline msec | — |
| LDAC - Ph2 | Change From Baseline of Electrocardiogram (ECG) Endpoints: QT Interval - Phases 1 and 2 | Cycle 14, Day 1 | -44.0 change from baseline msec | — |
| LDAC - Ph2 | Change From Baseline of Electrocardiogram (ECG) Endpoints: QT Interval - Phases 1 and 2 | Cycle 10, Day 1 | -18.3 change from baseline msec | Standard Deviation 18.6 |
| LDAC - Ph2 | Change From Baseline of Electrocardiogram (ECG) Endpoints: QT Interval - Phases 1 and 2 | Cycle 3, Day 1 | -15.4 change from baseline msec | Standard Deviation 30.6 |
| LDAC - Ph2 | Change From Baseline of Electrocardiogram (ECG) Endpoints: QT Interval - Phases 1 and 2 | Cycle 9, Day 1 | -23.0 change from baseline msec | Standard Deviation 21.2 |
| LDAC - Ph2 | Change From Baseline of Electrocardiogram (ECG) Endpoints: QT Interval - Phases 1 and 2 | Cycle 6, Day 1 | -11.8 change from baseline msec | Standard Deviation 19.1 |
| LDAC - Ph2 | Change From Baseline of Electrocardiogram (ECG) Endpoints: QT Interval - Phases 1 and 2 | Cycle 13, Day 1 | -40.0 change from baseline msec | — |
| LDAC - Ph2 | Change From Baseline of Electrocardiogram (ECG) Endpoints: QT Interval - Phases 1 and 2 | Cycle 2 Day 1 | 4.5 change from baseline msec | Standard Deviation 25.5 |
| LDAC - Ph2 | Change From Baseline of Electrocardiogram (ECG) Endpoints: QT Interval - Phases 1 and 2 | Cycle 7, Day 1 | 11.8 change from baseline msec | Standard Deviation 13.6 |
| LDAC - Ph2 | Change From Baseline of Electrocardiogram (ECG) Endpoints: QT Interval - Phases 1 and 2 | Cycle 5, Day 1 | 2.2 change from baseline msec | Standard Deviation 32.1 |
| LDAC - Ph2 | Change From Baseline of Electrocardiogram (ECG) Endpoints: QT Interval - Phases 1 and 2 | Cycle 12, Day 1 | -4.0 change from baseline msec | — |
| LDAC - Ph2 | Change From Baseline of Electrocardiogram (ECG) Endpoints: QT Interval - Phases 1 and 2 | Cycle 4, Day 1 | 10.1 change from baseline msec | Standard Deviation 22.8 |
| LDAC - Ph2 | Change From Baseline of Electrocardiogram (ECG) Endpoints: QT Interval - Phases 1 and 2 | Cycle 8, Day 1 | 2.0 change from baseline msec | Standard Deviation 2 |
| ULO 1000mg + LDAC - Ph2 | Change From Baseline of Electrocardiogram (ECG) Endpoints: QT Interval - Phases 1 and 2 | Cycle 5, Day 1 | -5.0 change from baseline msec | Standard Deviation 26.9 |
| ULO 1000mg + LDAC - Ph2 | Change From Baseline of Electrocardiogram (ECG) Endpoints: QT Interval - Phases 1 and 2 | Cycle 7, Day 1 | -8.0 change from baseline msec | — |
| ULO 1000mg + LDAC - Ph2 | Change From Baseline of Electrocardiogram (ECG) Endpoints: QT Interval - Phases 1 and 2 | Cycle 3, Day 1 | -10.7 change from baseline msec | Standard Deviation 41.3 |
| ULO 1000mg + LDAC - Ph2 | Change From Baseline of Electrocardiogram (ECG) Endpoints: QT Interval - Phases 1 and 2 | Cycle 8, Day 1 | -24.0 change from baseline msec | — |
| ULO 1000mg + LDAC - Ph2 | Change From Baseline of Electrocardiogram (ECG) Endpoints: QT Interval - Phases 1 and 2 | Cycle 9, Day 1 | -14.0 change from baseline msec | — |
| ULO 1000mg + LDAC - Ph2 | Change From Baseline of Electrocardiogram (ECG) Endpoints: QT Interval - Phases 1 and 2 | Cycle 11, Day 1 | -22.0 change from baseline msec | — |
| ULO 1000mg + LDAC - Ph2 | Change From Baseline of Electrocardiogram (ECG) Endpoints: QT Interval - Phases 1 and 2 | Cycle 12, Day 1 | -36.0 change from baseline msec | — |
| ULO 1000mg + LDAC - Ph2 | Change From Baseline of Electrocardiogram (ECG) Endpoints: QT Interval - Phases 1 and 2 | Cycle 2 Day 1 | 10.4 change from baseline msec | Standard Deviation 50.1 |
| ULO 1000mg + LDAC - Ph2 | Change From Baseline of Electrocardiogram (ECG) Endpoints: QT Interval - Phases 1 and 2 | Cycle 4, Day 1 | -12.7 change from baseline msec | Standard Deviation 104.3 |
| LDAC - Ph2 | Change From Baseline of Electrocardiogram (ECG) Endpoints: QT Interval - Phases 1 and 2 | Cycle 10, Day 1 | -6.0 change from baseline msec | Standard Deviation 11.3 |
| LDAC - Ph2 | Change From Baseline of Electrocardiogram (ECG) Endpoints: QT Interval - Phases 1 and 2 | Cycle 2 Day 1 | 14.2 change from baseline msec | Standard Deviation 33.7 |
| LDAC - Ph2 | Change From Baseline of Electrocardiogram (ECG) Endpoints: QT Interval - Phases 1 and 2 | Cycle 4, Day 1 | -1.4 change from baseline msec | Standard Deviation 47.9 |
| LDAC - Ph2 | Change From Baseline of Electrocardiogram (ECG) Endpoints: QT Interval - Phases 1 and 2 | Cycle 11, Day 1 | 7.0 change from baseline msec | Standard Deviation 2.6 |
| LDAC - Ph2 | Change From Baseline of Electrocardiogram (ECG) Endpoints: QT Interval - Phases 1 and 2 | Cycle 7, Day 1 | -8.8 change from baseline msec | Standard Deviation 28.3 |
| LDAC - Ph2 | Change From Baseline of Electrocardiogram (ECG) Endpoints: QT Interval - Phases 1 and 2 | Cycle 3, Day 1 | 13.7 change from baseline msec | Standard Deviation 41.7 |
| LDAC - Ph2 | Change From Baseline of Electrocardiogram (ECG) Endpoints: QT Interval - Phases 1 and 2 | Cycle 12, Day 1 | -6.5 change from baseline msec | Standard Deviation 27.6 |
| LDAC - Ph2 | Change From Baseline of Electrocardiogram (ECG) Endpoints: QT Interval - Phases 1 and 2 | Cycle 13, Day 1 | -15.0 change from baseline msec | Standard Deviation 18.4 |
| LDAC - Ph2 | Change From Baseline of Electrocardiogram (ECG) Endpoints: QT Interval - Phases 1 and 2 | Cycle 6, Day 1 | -3.6 change from baseline msec | Standard Deviation 39.3 |
| LDAC - Ph2 | Change From Baseline of Electrocardiogram (ECG) Endpoints: QT Interval - Phases 1 and 2 | Cycle 5, Day 1 | -27.6 change from baseline msec | Standard Deviation 75.5 |
| LDAC - Ph2 | Change From Baseline of Electrocardiogram (ECG) Endpoints: QT Interval - Phases 1 and 2 | Cycle 9, Day 1 | -24.4 change from baseline msec | Standard Deviation 23 |
| LDAC - Ph2 | Change From Baseline of Electrocardiogram (ECG) Endpoints: QT Interval - Phases 1 and 2 | Cycle 15, Day 1 | -19.0 change from baseline msec | — |
| LDAC - Ph2 | Change From Baseline of Electrocardiogram (ECG) Endpoints: QT Interval - Phases 1 and 2 | Cycle 16, Day 1 | -105.0 change from baseline msec | — |
| LDAC - Ph2 | Change From Baseline of Electrocardiogram (ECG) Endpoints: QT Interval - Phases 1 and 2 | Cycle 8, Day 1 | 0.8 change from baseline msec | Standard Deviation 35.5 |
Secondary
Duration of Response in Participants With CR/CRi Treated With LDAC Only - Phase 2
This phase 2 secondary endpoint was based on the duration of complete remission prior to the initiation of any alternative therapy (including any subsequent ulocuplumab 800 mg for participants in the LDAC alone arm). The phase 2 analysis was conducted after all participants had an opportunity for 6 months of follow-up.
Time frame: From first dose until a minimum follow-up of up to 2 months
Population: All randomized participants with CR/CRi
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| ULO 600mg + LDAC - Ph1 | Duration of Response in Participants With CR/CRi Treated With LDAC Only - Phase 2 | 5.7 Months |
Secondary
Duration of Response in Participants With CR/CRi Treated With Ulocuplumab at Two Different Dose Levels 800 mg and 1000 mg in Combination With LDAC - Phase 2
This phase 2 secondary endpoint was based on the duration of complete remission prior to the initiation of any alternative therapy (including any subsequent ulocuplumab 800 mg for participants in the LDAC alone arm). The phase 2 analysis was conducted after all participants had an opportunity for 6 months of follow-up.
Time frame: From first dose until a minimum follow-up of up to 2 months
Population: All randomized participants with CR/CRi
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| ULO 600mg + LDAC - Ph1 | Duration of Response in Participants With CR/CRi Treated With Ulocuplumab at Two Different Dose Levels 800 mg and 1000 mg in Combination With LDAC - Phase 2 | 2.4 Months |
| ULO 800mg + LDAC - Ph1 | Duration of Response in Participants With CR/CRi Treated With Ulocuplumab at Two Different Dose Levels 800 mg and 1000 mg in Combination With LDAC - Phase 2 | 4.3 Months |
Secondary
Elimination Half-life (T-HALF) - Phases 1 and 2
The Pharmacokinetic (PK) parameters are assessed for ulocuplumab following study drug administration. EOT = end of treatment T-HALF determined as 0.693/λz
Time frame: Days 1, 8, 15 for cycles 1 and 2; Days 1, 8 for cycles 3-5; Day 1 every 4th cycle thereafter; EOT; 30 days post last dose (follow-up)
Population: Based on the PK sample collections, PK parameters depended on terminal phase time points including AUC(INF), T-HALF; or at steady-state, including CLT, Vss are not reportable
Secondary
Maximum Observed Serum Concentration (Cmax) - Phases 1 and 2
The Pharmacokinetic (PK) parameters are assessed for ulocuplumab following study drug administration EOT = end of treatment Measure type and method of dispersion are Geometric mean and %CV, respectively
Time frame: Cycle 1 Day 1
Population: All treated participants who have evaluable PK profiles
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| ULO 600mg + LDAC - Ph1 | Maximum Observed Serum Concentration (Cmax) - Phases 1 and 2 | 219.354 µg/mL | Geometric Coefficient of Variation 19 |
| ULO 800mg + LDAC - Ph1 | Maximum Observed Serum Concentration (Cmax) - Phases 1 and 2 | 265.294 µg/mL | Geometric Coefficient of Variation 8 |
| LDAC - Ph2 | Maximum Observed Serum Concentration (Cmax) - Phases 1 and 2 | 183.456 µg/mL | Geometric Coefficient of Variation 25 |
| ULO 1000mg + LDAC - Ph2 | Maximum Observed Serum Concentration (Cmax) - Phases 1 and 2 | 256.906 µg/mL | Geometric Coefficient of Variation 22 |
| LDAC - Ph2 | Maximum Observed Serum Concentration (Cmax) - Phases 1 and 2 | 212.564 µg/mL | — |
Secondary
Number of Deaths- Phase 2
The number of participants who died. Safety data are evaluated for deaths, defined and evaluated using the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03 (NCI CTCAE v4.03).
Time frame: From first dose until a minimum follow-up of up to 2 months
Population: All treated participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ULO 600mg + LDAC - Ph1 | Number of Deaths- Phase 2 | 19 Participants |
| ULO 800mg + LDAC - Ph1 | Number of Deaths- Phase 2 | 10 Participants |
| LDAC - Ph2 | Number of Deaths- Phase 2 | 16 Participants |
Secondary
Number of Participants With AEs Leading to Discontinuation - Phase 2
The number of participants with an on-study adverse event (AE) leading to discontinuation. Safety data are evaluated for AEs leading to discontinuation, defined and evaluated using the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03 (NCI CTCAE v4.03).
Time frame: From first dose until a minimum follow-up of up to 2 months
Population: All treated participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ULO 600mg + LDAC - Ph1 | Number of Participants With AEs Leading to Discontinuation - Phase 2 | 7 Participants |
| ULO 800mg + LDAC - Ph1 | Number of Participants With AEs Leading to Discontinuation - Phase 2 | 3 Participants |
| LDAC - Ph2 | Number of Participants With AEs Leading to Discontinuation - Phase 2 | 4 Participants |
Secondary
Number of Participants With AEs - Phase 2
The number of participants with an on-study adverse event (AE). Safety data are evaluated for AEs, defined and evaluated using the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03 (NCI CTCAE v4.03).
Time frame: From first dose until a minimum follow-up of up to 2 months
Population: All treated participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ULO 600mg + LDAC - Ph1 | Number of Participants With AEs - Phase 2 | 25 Participants |
| ULO 800mg + LDAC - Ph1 | Number of Participants With AEs - Phase 2 | 14 Participants |
| LDAC - Ph2 | Number of Participants With AEs - Phase 2 | 22 Participants |
Secondary
Number of Participants With Anti-drug Antibodies (ADA) Positive for Ulocuplumab - Phases 1 and 2
Serum samples from ulocuplumab treated participants were evaluated for the presence of anti-ulocuplumab antibodies
Time frame: From first dose until a minimum follow-up of up to 2 months
Population: All participants treated with ulocuplumab
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ULO 600mg + LDAC - Ph1 | Number of Participants With Anti-drug Antibodies (ADA) Positive for Ulocuplumab - Phases 1 and 2 | 0 Participants |
| ULO 800mg + LDAC - Ph1 | Number of Participants With Anti-drug Antibodies (ADA) Positive for Ulocuplumab - Phases 1 and 2 | 0 Participants |
| LDAC - Ph2 | Number of Participants With Anti-drug Antibodies (ADA) Positive for Ulocuplumab - Phases 1 and 2 | 6 Participants |
| ULO 1000mg + LDAC - Ph2 | Number of Participants With Anti-drug Antibodies (ADA) Positive for Ulocuplumab - Phases 1 and 2 | 0 Participants |
Secondary
Number of Participants With Laboratory Abnormalities - Phase 2
The number of participants with an on-study laboratory abnormality, assessed from Grade 1-4 Serum Chemistry, Electrolytes, and Hematology Laboratory Test results, with grade 4 being the worst. Safety data are evaluated for laboratory abnormalities, defined and evaluated using the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03 (NCI CTCAE v4.03).
Time frame: From first dose until a minimum follow-up of up to 2 months
Population: All treated participants
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| ULO 600mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 2 | CREATININE, grade 2 | 5 Participants |
| ULO 600mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 2 | ALANINE AMINOTRANSFERASE (ALT), grade 2 | 0 Participants |
| ULO 600mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 2 | ALANINE AMINOTRANSFERASE (ALT), grade 3 | 2 Participants |
| ULO 600mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 2 | ALKALINE PHOSPHATASE (ALP), grade 1 | 9 Participants |
| ULO 600mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 2 | ALKALINE PHOSPHATASE (ALP), grade 2 | 1 Participants |
| ULO 600mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 2 | ASPARTATE AMINOTRANSFERASE (AST), grade 1 | 7 Participants |
| ULO 600mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 2 | ASPARTATE AMINOTRANSFERASE (AST), grade 2 | 1 Participants |
| ULO 600mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 2 | ASPARTATE AMINOTRANSFERASE (AST), grade 3 | 0 Participants |
| ULO 600mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 2 | BILIRUBIN, TOTAL, grade 1 | 3 Participants |
| ULO 600mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 2 | BILIRUBIN, TOTAL, grade 2 | 4 Participants |
| ULO 600mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 2 | BILIRUBIN, TOTAL, grade 3 | 1 Participants |
| ULO 600mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 2 | CREATININE, grade 1 | 7 Participants |
| ULO 600mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 2 | ALANINE AMINOTRANSFERASE (ALT), grade 1 | 5 Participants |
| ULO 600mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 2 | CALCIUM, TOTAL, grade 1 | 7 Participants |
| ULO 600mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 2 | CALCIUM, TOTAL, grade 2 | 5 Participants |
| ULO 600mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 2 | CALCIUM, TOTAL, grade 3 | 0 Participants |
| ULO 600mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 2 | PHOSPHORUS, INORGANIC, grade 1 | 0 Participants |
| ULO 600mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 2 | PHOSPHORUS, INORGANIC, grade 2 | 3 Participants |
| ULO 600mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 2 | PHOSPHORUS, INORGANIC, grade 3 | 2 Participants |
| ULO 600mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 2 | PHOSPHORUS, INORGANIC, grade 4 | 0 Participants |
| ULO 600mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 2 | POTASSIUM, SERUM, grade 1 | 4 Participants |
| ULO 600mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 2 | POTASSIUM, SERUM, grade 2 | 0 Participants |
| ULO 600mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 2 | POTASSIUM, SERUM, grade 3 | 1 Participants |
| ULO 600mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 2 | POTASSIUM, SERUM, grade 4 | 1 Participants |
| ULO 600mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 2 | SODIUM, SERUM, grade 1 | 9 Participants |
| ULO 600mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 2 | SODIUM, SERUM, grade 2 | 0 Participants |
| ULO 600mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 2 | SODIUM, SERUM, grade 3 | 0 Participants |
| ULO 600mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 2 | HEMOGLOBIN, grade 2 | 2 Participants |
| ULO 600mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 2 | HEMOGLOBIN, grade 3 | 22 Participants |
| ULO 600mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 2 | PLATELET COUNT, grade 2 | 0 Participants |
| ULO 600mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 2 | PLATELET COUNT, grade 3 | 1 Participants |
| ULO 600mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 2 | PLATELET COUNT, grade 4 | 23 Participants |
| ULO 600mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 2 | ABSOLUTE NEUTROPHIL COUNT, grade 1 | 2 Participants |
| ULO 600mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 2 | ABSOLUTE NEUTROPHIL COUNT, grade 2 | 0 Participants |
| ULO 600mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 2 | ABSOLUTE NEUTROPHIL COUNT, grade 3 | 3 Participants |
| ULO 600mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 2 | ABSOLUTE NEUTROPHIL COUNT, grade 4 | 18 Participants |
| ULO 600mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 2 | LEUKOCYTES, grade 1 | 3 Participants |
| ULO 600mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 2 | LEUKOCYTES, grade 2 | 3 Participants |
| ULO 600mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 2 | LEUKOCYTES, grade 3 | 6 Participants |
| ULO 600mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 2 | LEUKOCYTES, grade 4 | 8 Participants |
| ULO 600mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 2 | LYMPHOCYTES (ABSOLUTE), grade 1 | 3 Participants |
| ULO 600mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 2 | LYMPHOCYTES (ABSOLUTE), grade 2 | 7 Participants |
| ULO 600mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 2 | LYMPHOCYTES (ABSOLUTE), grade 3 | 5 Participants |
| ULO 600mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 2 | LYMPHOCYTES (ABSOLUTE), grade 4 | 0 Participants |
| ULO 600mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 2 | NEUTROPHILS (ABSOLUTE), grade 1 | 1 Participants |
| ULO 600mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 2 | NEUTROPHILS (ABSOLUTE), grade 2 | 1 Participants |
| ULO 600mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 2 | NEUTROPHILS (ABSOLUTE), grade 3 | 3 Participants |
| ULO 600mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 2 | NEUTROPHILS (ABSOLUTE), grade 4 | 18 Participants |
| ULO 800mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 2 | LEUKOCYTES, grade 2 | 4 Participants |
| ULO 800mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 2 | PHOSPHORUS, INORGANIC, grade 1 | 0 Participants |
| ULO 800mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 2 | PHOSPHORUS, INORGANIC, grade 2 | 2 Participants |
| ULO 800mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 2 | PHOSPHORUS, INORGANIC, grade 3 | 0 Participants |
| ULO 800mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 2 | LEUKOCYTES, grade 3 | 4 Participants |
| ULO 800mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 2 | PHOSPHORUS, INORGANIC, grade 4 | 1 Participants |
| ULO 800mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 2 | POTASSIUM, SERUM, grade 1 | 3 Participants |
| ULO 800mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 2 | POTASSIUM, SERUM, grade 2 | 1 Participants |
| ULO 800mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 2 | LEUKOCYTES, grade 4 | 1 Participants |
| ULO 800mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 2 | POTASSIUM, SERUM, grade 3 | 2 Participants |
| ULO 800mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 2 | POTASSIUM, SERUM, grade 4 | 1 Participants |
| ULO 800mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 2 | NEUTROPHILS (ABSOLUTE), grade 2 | 2 Participants |
| ULO 800mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 2 | SODIUM, SERUM, grade 1 | 3 Participants |
| ULO 800mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 2 | LYMPHOCYTES (ABSOLUTE), grade 1 | 4 Participants |
| ULO 800mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 2 | SODIUM, SERUM, grade 2 | 1 Participants |
| ULO 800mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 2 | SODIUM, SERUM, grade 3 | 3 Participants |
| ULO 800mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 2 | HEMOGLOBIN, grade 2 | 4 Participants |
| ULO 800mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 2 | LYMPHOCYTES (ABSOLUTE), grade 2 | 1 Participants |
| ULO 800mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 2 | HEMOGLOBIN, grade 3 | 10 Participants |
| ULO 800mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 2 | PLATELET COUNT, grade 2 | 0 Participants |
| ULO 800mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 2 | NEUTROPHILS (ABSOLUTE), grade 4 | 10 Participants |
| ULO 800mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 2 | PLATELET COUNT, grade 3 | 1 Participants |
| ULO 800mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 2 | LYMPHOCYTES (ABSOLUTE), grade 3 | 0 Participants |
| ULO 800mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 2 | PLATELET COUNT, grade 4 | 13 Participants |
| ULO 800mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 2 | ALANINE AMINOTRANSFERASE (ALT), grade 1 | 5 Participants |
| ULO 800mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 2 | ABSOLUTE NEUTROPHIL COUNT, grade 1 | 1 Participants |
| ULO 800mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 2 | ALANINE AMINOTRANSFERASE (ALT), grade 2 | 1 Participants |
| ULO 800mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 2 | ALANINE AMINOTRANSFERASE (ALT), grade 3 | 2 Participants |
| ULO 800mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 2 | NEUTROPHILS (ABSOLUTE), grade 3 | 0 Participants |
| ULO 800mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 2 | ALKALINE PHOSPHATASE (ALP), grade 1 | 3 Participants |
| ULO 800mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 2 | ABSOLUTE NEUTROPHIL COUNT, grade 2 | 1 Participants |
| ULO 800mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 2 | ALKALINE PHOSPHATASE (ALP), grade 2 | 5 Participants |
| ULO 800mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 2 | ASPARTATE AMINOTRANSFERASE (AST), grade 1 | 8 Participants |
| ULO 800mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 2 | LYMPHOCYTES (ABSOLUTE), grade 4 | 0 Participants |
| ULO 800mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 2 | ASPARTATE AMINOTRANSFERASE (AST), grade 2 | 0 Participants |
| ULO 800mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 2 | ABSOLUTE NEUTROPHIL COUNT, grade 3 | 0 Participants |
| ULO 800mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 2 | ASPARTATE AMINOTRANSFERASE (AST), grade 3 | 1 Participants |
| ULO 800mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 2 | BILIRUBIN, TOTAL, grade 1 | 2 Participants |
| ULO 800mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 2 | BILIRUBIN, TOTAL, grade 2 | 3 Participants |
| ULO 800mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 2 | ABSOLUTE NEUTROPHIL COUNT, grade 4 | 10 Participants |
| ULO 800mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 2 | BILIRUBIN, TOTAL, grade 3 | 0 Participants |
| ULO 800mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 2 | CREATININE, grade 1 | 5 Participants |
| ULO 800mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 2 | CREATININE, grade 2 | 2 Participants |
| ULO 800mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 2 | LEUKOCYTES, grade 1 | 0 Participants |
| ULO 800mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 2 | CALCIUM, TOTAL, grade 1 | 3 Participants |
| ULO 800mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 2 | CALCIUM, TOTAL, grade 2 | 5 Participants |
| ULO 800mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 2 | NEUTROPHILS (ABSOLUTE), grade 1 | 0 Participants |
| ULO 800mg + LDAC - Ph1 | Number of Participants With Laboratory Abnormalities - Phase 2 | CALCIUM, TOTAL, grade 3 | 1 Participants |
| LDAC - Ph2 | Number of Participants With Laboratory Abnormalities - Phase 2 | LYMPHOCYTES (ABSOLUTE), grade 3 | 7 Participants |
| LDAC - Ph2 | Number of Participants With Laboratory Abnormalities - Phase 2 | ABSOLUTE NEUTROPHIL COUNT, grade 3 | 1 Participants |
| LDAC - Ph2 | Number of Participants With Laboratory Abnormalities - Phase 2 | PHOSPHORUS, INORGANIC, grade 1 | 1 Participants |
| LDAC - Ph2 | Number of Participants With Laboratory Abnormalities - Phase 2 | LEUKOCYTES, grade 2 | 0 Participants |
| LDAC - Ph2 | Number of Participants With Laboratory Abnormalities - Phase 2 | ALANINE AMINOTRANSFERASE (ALT), grade 1 | 4 Participants |
| LDAC - Ph2 | Number of Participants With Laboratory Abnormalities - Phase 2 | PHOSPHORUS, INORGANIC, grade 2 | 1 Participants |
| LDAC - Ph2 | Number of Participants With Laboratory Abnormalities - Phase 2 | NEUTROPHILS (ABSOLUTE), grade 1 | 0 Participants |
| LDAC - Ph2 | Number of Participants With Laboratory Abnormalities - Phase 2 | LEUKOCYTES, grade 1 | 1 Participants |
| LDAC - Ph2 | Number of Participants With Laboratory Abnormalities - Phase 2 | PHOSPHORUS, INORGANIC, grade 3 | 2 Participants |
| LDAC - Ph2 | Number of Participants With Laboratory Abnormalities - Phase 2 | BILIRUBIN, TOTAL, grade 1 | 1 Participants |
| LDAC - Ph2 | Number of Participants With Laboratory Abnormalities - Phase 2 | ALANINE AMINOTRANSFERASE (ALT), grade 2 | 2 Participants |
| LDAC - Ph2 | Number of Participants With Laboratory Abnormalities - Phase 2 | PHOSPHORUS, INORGANIC, grade 4 | 0 Participants |
| LDAC - Ph2 | Number of Participants With Laboratory Abnormalities - Phase 2 | LEUKOCYTES, grade 3 | 5 Participants |
| LDAC - Ph2 | Number of Participants With Laboratory Abnormalities - Phase 2 | ABSOLUTE NEUTROPHIL COUNT, grade 1 | 0 Participants |
| LDAC - Ph2 | Number of Participants With Laboratory Abnormalities - Phase 2 | POTASSIUM, SERUM, grade 1 | 5 Participants |
| LDAC - Ph2 | Number of Participants With Laboratory Abnormalities - Phase 2 | NEUTROPHILS (ABSOLUTE), grade 4 | 16 Participants |
| LDAC - Ph2 | Number of Participants With Laboratory Abnormalities - Phase 2 | LYMPHOCYTES (ABSOLUTE), grade 4 | 1 Participants |
| LDAC - Ph2 | Number of Participants With Laboratory Abnormalities - Phase 2 | POTASSIUM, SERUM, grade 2 | 0 Participants |
| LDAC - Ph2 | Number of Participants With Laboratory Abnormalities - Phase 2 | ALANINE AMINOTRANSFERASE (ALT), grade 3 | 0 Participants |
| LDAC - Ph2 | Number of Participants With Laboratory Abnormalities - Phase 2 | CREATININE, grade 2 | 2 Participants |
| LDAC - Ph2 | Number of Participants With Laboratory Abnormalities - Phase 2 | POTASSIUM, SERUM, grade 3 | 4 Participants |
| LDAC - Ph2 | Number of Participants With Laboratory Abnormalities - Phase 2 | LEUKOCYTES, grade 4 | 10 Participants |
| LDAC - Ph2 | Number of Participants With Laboratory Abnormalities - Phase 2 | BILIRUBIN, TOTAL, grade 2 | 1 Participants |
| LDAC - Ph2 | Number of Participants With Laboratory Abnormalities - Phase 2 | POTASSIUM, SERUM, grade 4 | 0 Participants |
| LDAC - Ph2 | Number of Participants With Laboratory Abnormalities - Phase 2 | ALKALINE PHOSPHATASE (ALP), grade 1 | 8 Participants |
| LDAC - Ph2 | Number of Participants With Laboratory Abnormalities - Phase 2 | CALCIUM, TOTAL, grade 3 | 0 Participants |
| LDAC - Ph2 | Number of Participants With Laboratory Abnormalities - Phase 2 | SODIUM, SERUM, grade 1 | 7 Participants |
| LDAC - Ph2 | Number of Participants With Laboratory Abnormalities - Phase 2 | CALCIUM, TOTAL, grade 2 | 7 Participants |
| LDAC - Ph2 | Number of Participants With Laboratory Abnormalities - Phase 2 | ALKALINE PHOSPHATASE (ALP), grade 2 | 2 Participants |
| LDAC - Ph2 | Number of Participants With Laboratory Abnormalities - Phase 2 | SODIUM, SERUM, grade 2 | 0 Participants |
| LDAC - Ph2 | Number of Participants With Laboratory Abnormalities - Phase 2 | LYMPHOCYTES (ABSOLUTE), grade 1 | 1 Participants |
| LDAC - Ph2 | Number of Participants With Laboratory Abnormalities - Phase 2 | ABSOLUTE NEUTROPHIL COUNT, grade 2 | 1 Participants |
| LDAC - Ph2 | Number of Participants With Laboratory Abnormalities - Phase 2 | SODIUM, SERUM, grade 3 | 4 Participants |
| LDAC - Ph2 | Number of Participants With Laboratory Abnormalities - Phase 2 | NEUTROPHILS (ABSOLUTE), grade 2 | 1 Participants |
| LDAC - Ph2 | Number of Participants With Laboratory Abnormalities - Phase 2 | BILIRUBIN, TOTAL, grade 3 | 0 Participants |
| LDAC - Ph2 | Number of Participants With Laboratory Abnormalities - Phase 2 | HEMOGLOBIN, grade 2 | 4 Participants |
| LDAC - Ph2 | Number of Participants With Laboratory Abnormalities - Phase 2 | ASPARTATE AMINOTRANSFERASE (AST), grade 1 | 4 Participants |
| LDAC - Ph2 | Number of Participants With Laboratory Abnormalities - Phase 2 | ABSOLUTE NEUTROPHIL COUNT, grade 4 | 16 Participants |
| LDAC - Ph2 | Number of Participants With Laboratory Abnormalities - Phase 2 | HEMOGLOBIN, grade 3 | 17 Participants |
| LDAC - Ph2 | Number of Participants With Laboratory Abnormalities - Phase 2 | LYMPHOCYTES (ABSOLUTE), grade 2 | 7 Participants |
| LDAC - Ph2 | Number of Participants With Laboratory Abnormalities - Phase 2 | CALCIUM, TOTAL, grade 1 | 3 Participants |
| LDAC - Ph2 | Number of Participants With Laboratory Abnormalities - Phase 2 | PLATELET COUNT, grade 2 | 1 Participants |
| LDAC - Ph2 | Number of Participants With Laboratory Abnormalities - Phase 2 | ASPARTATE AMINOTRANSFERASE (AST), grade 2 | 2 Participants |
| LDAC - Ph2 | Number of Participants With Laboratory Abnormalities - Phase 2 | CREATININE, grade 1 | 6 Participants |
| LDAC - Ph2 | Number of Participants With Laboratory Abnormalities - Phase 2 | PLATELET COUNT, grade 3 | 3 Participants |
| LDAC - Ph2 | Number of Participants With Laboratory Abnormalities - Phase 2 | NEUTROPHILS (ABSOLUTE), grade 3 | 1 Participants |
| LDAC - Ph2 | Number of Participants With Laboratory Abnormalities - Phase 2 | ASPARTATE AMINOTRANSFERASE (AST), grade 3 | 0 Participants |
| LDAC - Ph2 | Number of Participants With Laboratory Abnormalities - Phase 2 | PLATELET COUNT, grade 4 | 17 Participants |
Secondary
Number of Participants With SAEs - Phase 2
The number of participants with an on-study serious adverse event (SAE). Safety data are evaluated for SAEs, defined and evaluated using the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03 (NCI CTCAE v4.03).
Time frame: From first dose until a minimum follow-up of up to 2 months
Population: All treated participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ULO 600mg + LDAC - Ph1 | Number of Participants With SAEs - Phase 2 | 21 Participants |
| ULO 800mg + LDAC - Ph1 | Number of Participants With SAEs - Phase 2 | 8 Participants |
| LDAC - Ph2 | Number of Participants With SAEs - Phase 2 | 15 Participants |
Secondary
Overall Rate of Remission in Participants Treated With Ulocuplumab at Two Different Dose Levels 800 mg and 1000 mg in Combination With LDAC - Phase 2
This phase 2 secondary endpoint was based on the rate of Overall Remission (OR=PR+CR +CRi) prior to the initiation of any alternative therapy (including any subsequent ulocuplumab 800 mg for participants in the LDAC alone arm). The phase 2 analysis was conducted after all participants had an opportunity for 6 months of follow-up. Overall remission rate: CR + CRi, + PR confidence interval based on the Clopper and Pearson method. CR = complete response CRi = complete response, incomplete blood count PR = partial remission
Time frame: From first dose until a minimum follow-up of up to 2 months
Population: All randomized participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ULO 600mg + LDAC - Ph1 | Overall Rate of Remission in Participants Treated With Ulocuplumab at Two Different Dose Levels 800 mg and 1000 mg in Combination With LDAC - Phase 2 | 19.2 Percentage of participants |
| ULO 800mg + LDAC - Ph1 | Overall Rate of Remission in Participants Treated With Ulocuplumab at Two Different Dose Levels 800 mg and 1000 mg in Combination With LDAC - Phase 2 | 7.1 Percentage of participants |
Secondary
Overall Survival (OS) - Phases 1 and 2
OS is defined as the time between the first date of treatment and the date of death due to any cause. A participant who has not died was be censored at the last known alive date.
Time frame: From first dose until a minimum follow-up of up to 2 months
Population: All treated participants for phase 2. Phase 1 OS data not collected.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| LDAC - Ph2 | Overall Survival (OS) - Phases 1 and 2 | 3.3 Months |
| ULO 1000mg + LDAC - Ph2 | Overall Survival (OS) - Phases 1 and 2 | 3.0 Months |
| LDAC - Ph2 | Overall Survival (OS) - Phases 1 and 2 | 6.9 Months |
Secondary
Rate of Complete Remission (CR/CRi) and Overall Rate of Remission in Participants Treated With LDAC Only - Phase 2
This phase 2 secondary endpoint was based on the rate of Complete Remission (CR/CRi) and rate of Overall Remission (OR=PR+CR +CRi) prior to the initiation of any alternative therapy (including any subsequent ulocuplumab 800 mg for participants in the LDAC alone arm). The phase 2 analysis was conducted after all participants had an opportunity for 6 months of follow-up. Overall remission rate: CR + CRi, + PR confidence interval based on the Clopper and Pearson method. CR = complete response CRi = complete response, incomplete blood count PR = partial remission
Time frame: From first dose until a minimum follow-up of up to 2 months
Population: All randomized participants
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| ULO 600mg + LDAC - Ph1 | Rate of Complete Remission (CR/CRi) and Overall Rate of Remission in Participants Treated With LDAC Only - Phase 2 | CR/CRi | 25.0 Percentage of participants |
| ULO 600mg + LDAC - Ph1 | Rate of Complete Remission (CR/CRi) and Overall Rate of Remission in Participants Treated With LDAC Only - Phase 2 | Overall remission rate | 25.0 Percentage of participants |
Secondary
Time of Maximum Observed Ulocuplumab Serum Concentration (Tmax) - Phases 1 and 2
The Pharmacokinetic (PK) parameters are assessed for ulocuplumab following study drug administration. EOT = end of treatment
Time frame: Cycle 1 Day 1
Population: All treated participants who have evaluable PK profiles
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| ULO 600mg + LDAC - Ph1 | Time of Maximum Observed Ulocuplumab Serum Concentration (Tmax) - Phases 1 and 2 | 1.850 hour (H) |
| ULO 800mg + LDAC - Ph1 | Time of Maximum Observed Ulocuplumab Serum Concentration (Tmax) - Phases 1 and 2 | 1.933 hour (H) |
| LDAC - Ph2 | Time of Maximum Observed Ulocuplumab Serum Concentration (Tmax) - Phases 1 and 2 | 1.500 hour (H) |
| ULO 1000mg + LDAC - Ph2 | Time of Maximum Observed Ulocuplumab Serum Concentration (Tmax) - Phases 1 and 2 | 2.117 hour (H) |
| LDAC - Ph2 | Time of Maximum Observed Ulocuplumab Serum Concentration (Tmax) - Phases 1 and 2 | 2.03 hour (H) |
Secondary
Total Body Clearance of Ulocuplumab (CLT) - Phases 1 and 2
The Pharmacokinetic (PK) parameters are assessed for ulocuplumab following study drug administration. EOT = end of treatment CLT calculated by dividing the total dose of ulocuplumab by its corresponding AUC(INF) value Measure type and method of dispersion are Geometric mean and %CV, respectively
Time frame: Days 1, 8, 15 for cycles 1 and 2; Days 1, 8 for cycles 3-5; Day 1 every 4th cycle thereafter; EOT; 30 days post last dose (follow-up)
Population: Based on the PK sample collections, PK parameters depended on terminal phase time points including AUC(INF), T-HALF; or at steady-state, including CLT, Vss are not reportable
Secondary
Trough Observed Serum Concentration (Ctrough) - Phases 1 and 2
The Pharmacokinetic (PK) parameters are assessed for ulocuplumab following study drug administration. EOT = end of treatment Measure type and method of dispersion are Geometric mean and %CV, respectively
Time frame: Days 1, 8, 15 for cycle 1; Days 8, 15 for cycle 2; Days 1, 8 for cycles 3-5; Day 1 every 4th cycle thereafter; EOT; 30 days post last dose (follow-up)
Population: All treated participants who have evaluable PK profiles
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| ULO 600mg + LDAC - Ph1 | Trough Observed Serum Concentration (Ctrough) - Phases 1 and 2 | Cycle 1 Day 8 | 5.308 µg/mL | Geometric Coefficient of Variation 89 |
| ULO 600mg + LDAC - Ph1 | Trough Observed Serum Concentration (Ctrough) - Phases 1 and 2 | Cycle 1 Day 1 | 0.100 µg/mL | Geometric Coefficient of Variation 0 |
| ULO 600mg + LDAC - Ph1 | Trough Observed Serum Concentration (Ctrough) - Phases 1 and 2 | Cycle 5 Day 8 | 102.751 µg/mL | — |
| ULO 600mg + LDAC - Ph1 | Trough Observed Serum Concentration (Ctrough) - Phases 1 and 2 | Cycle 4 Day 8 | 112.048 µg/mL | — |
| ULO 600mg + LDAC - Ph1 | Trough Observed Serum Concentration (Ctrough) - Phases 1 and 2 | Cycle 2 Day 8 | 41.630 µg/mL | — |
| ULO 600mg + LDAC - Ph1 | Trough Observed Serum Concentration (Ctrough) - Phases 1 and 2 | Cycle 3 Day 8 | 85.993 µg/mL | — |
| ULO 600mg + LDAC - Ph1 | Trough Observed Serum Concentration (Ctrough) - Phases 1 and 2 | Cycle 1 Day 15 | 21.748 µg/mL | Geometric Coefficient of Variation 91 |
| ULO 600mg + LDAC - Ph1 | Trough Observed Serum Concentration (Ctrough) - Phases 1 and 2 | Cycle 2 Day 15 | 72.104 µg/mL | — |
| ULO 800mg + LDAC - Ph1 | Trough Observed Serum Concentration (Ctrough) - Phases 1 and 2 | Cycle 4 Day 8 | 133.650 µg/mL | Geometric Coefficient of Variation 41 |
| ULO 800mg + LDAC - Ph1 | Trough Observed Serum Concentration (Ctrough) - Phases 1 and 2 | Cycle 2 Day 8 | 96.333 µg/mL | Geometric Coefficient of Variation 36 |
| ULO 800mg + LDAC - Ph1 | Trough Observed Serum Concentration (Ctrough) - Phases 1 and 2 | Cycle 5 Day 8 | 124.996 µg/mL | Geometric Coefficient of Variation 48 |
| ULO 800mg + LDAC - Ph1 | Trough Observed Serum Concentration (Ctrough) - Phases 1 and 2 | Cycle 4 Day 1 | 80.409 µg/mL | Geometric Coefficient of Variation 64 |
| ULO 800mg + LDAC - Ph1 | Trough Observed Serum Concentration (Ctrough) - Phases 1 and 2 | Cycle 2 Day 15 | 126.029 µg/mL | Geometric Coefficient of Variation 49 |
| ULO 800mg + LDAC - Ph1 | Trough Observed Serum Concentration (Ctrough) - Phases 1 and 2 | Cycle 3 Day 8 | 129.580 µg/mL | Geometric Coefficient of Variation 42 |
| ULO 800mg + LDAC - Ph1 | Trough Observed Serum Concentration (Ctrough) - Phases 1 and 2 | Cycle 3 Day 1 | 78.218 µg/mL | — |
| ULO 800mg + LDAC - Ph1 | Trough Observed Serum Concentration (Ctrough) - Phases 1 and 2 | Cycle 1 Day 8 | 75.890 µg/mL | Geometric Coefficient of Variation 30 |
| ULO 800mg + LDAC - Ph1 | Trough Observed Serum Concentration (Ctrough) - Phases 1 and 2 | Cycle 1 Day 1 | 0.100 µg/mL | Geometric Coefficient of Variation 0 |
| ULO 800mg + LDAC - Ph1 | Trough Observed Serum Concentration (Ctrough) - Phases 1 and 2 | Cycle 5 Day 1 | 32.621 µg/mL | — |
| ULO 800mg + LDAC - Ph1 | Trough Observed Serum Concentration (Ctrough) - Phases 1 and 2 | Cycle 1 Day 15 | 125.797 µg/mL | Geometric Coefficient of Variation 18 |
| LDAC - Ph2 | Trough Observed Serum Concentration (Ctrough) - Phases 1 and 2 | EOT | 0.100 µg/mL | — |
| LDAC - Ph2 | Trough Observed Serum Concentration (Ctrough) - Phases 1 and 2 | Cycle 1 Day 1 | 0.100 µg/mL | Geometric Coefficient of Variation 0 |
| LDAC - Ph2 | Trough Observed Serum Concentration (Ctrough) - Phases 1 and 2 | Cycle 1 Day 8 | 10.321 µg/mL | Geometric Coefficient of Variation 85 |
| LDAC - Ph2 | Trough Observed Serum Concentration (Ctrough) - Phases 1 and 2 | Cycle 1 Day 15 | 37.263 µg/mL | Geometric Coefficient of Variation 66 |
| LDAC - Ph2 | Trough Observed Serum Concentration (Ctrough) - Phases 1 and 2 | Cycle 2 Day 8 | 30.916 µg/mL | Geometric Coefficient of Variation 83 |
| LDAC - Ph2 | Trough Observed Serum Concentration (Ctrough) - Phases 1 and 2 | Cycle 2 Day 15 | 48.421 µg/mL | Geometric Coefficient of Variation 73 |
| LDAC - Ph2 | Trough Observed Serum Concentration (Ctrough) - Phases 1 and 2 | Cycle 3 Day 1 | 13.905 µg/mL | Geometric Coefficient of Variation 101 |
| LDAC - Ph2 | Trough Observed Serum Concentration (Ctrough) - Phases 1 and 2 | Cycle 3 Day 8 | 37.602 µg/mL | Geometric Coefficient of Variation 94 |
| LDAC - Ph2 | Trough Observed Serum Concentration (Ctrough) - Phases 1 and 2 | Cycle 4 Day 1 | 4.012 µg/mL | Geometric Coefficient of Variation 145 |
| LDAC - Ph2 | Trough Observed Serum Concentration (Ctrough) - Phases 1 and 2 | Cycle 4 Day 8 | 116.657 µg/mL | Geometric Coefficient of Variation 83 |
| LDAC - Ph2 | Trough Observed Serum Concentration (Ctrough) - Phases 1 and 2 | Cycle 5 Day 1 | 4.558 µg/mL | Geometric Coefficient of Variation 166 |
| LDAC - Ph2 | Trough Observed Serum Concentration (Ctrough) - Phases 1 and 2 | Cycle 5 Day 8 | 34.783 µg/mL | Geometric Coefficient of Variation 137 |
| LDAC - Ph2 | Trough Observed Serum Concentration (Ctrough) - Phases 1 and 2 | Cycle 9 Day 1 | 35.144 µg/mL | Geometric Coefficient of Variation 110 |
| ULO 1000mg + LDAC - Ph2 | Trough Observed Serum Concentration (Ctrough) - Phases 1 and 2 | Cycle 9 Day 1 | 187.930 µg/mL | — |
| ULO 1000mg + LDAC - Ph2 | Trough Observed Serum Concentration (Ctrough) - Phases 1 and 2 | Cycle 3 Day 8 | 82.033 µg/mL | Geometric Coefficient of Variation 21 |
| ULO 1000mg + LDAC - Ph2 | Trough Observed Serum Concentration (Ctrough) - Phases 1 and 2 | Cycle 2 Day 8 | 103.322 µg/mL | Geometric Coefficient of Variation 67 |
| ULO 1000mg + LDAC - Ph2 | Trough Observed Serum Concentration (Ctrough) - Phases 1 and 2 | Cycle 4 Day 1 | 212.793 µg/mL | — |
| ULO 1000mg + LDAC - Ph2 | Trough Observed Serum Concentration (Ctrough) - Phases 1 and 2 | Cycle 1 Day 15 | 61.250 µg/mL | Geometric Coefficient of Variation 64 |
| ULO 1000mg + LDAC - Ph2 | Trough Observed Serum Concentration (Ctrough) - Phases 1 and 2 | Cycle 5 Day 8 | 202.552 µg/mL | — |
| ULO 1000mg + LDAC - Ph2 | Trough Observed Serum Concentration (Ctrough) - Phases 1 and 2 | Cycle 4 Day 8 | 77.095 µg/mL | Geometric Coefficient of Variation 119 |
| ULO 1000mg + LDAC - Ph2 | Trough Observed Serum Concentration (Ctrough) - Phases 1 and 2 | Cycle 1 Day 1 | 0.100 µg/mL | Geometric Coefficient of Variation 0 |
| ULO 1000mg + LDAC - Ph2 | Trough Observed Serum Concentration (Ctrough) - Phases 1 and 2 | Cycle 5 Day 1 | 224.703 µg/mL | — |
| ULO 1000mg + LDAC - Ph2 | Trough Observed Serum Concentration (Ctrough) - Phases 1 and 2 | Cycle 1 Day 8 | 17.766 µg/mL | Geometric Coefficient of Variation 79 |
| ULO 1000mg + LDAC - Ph2 | Trough Observed Serum Concentration (Ctrough) - Phases 1 and 2 | Cycle 3 Day 1 | 153.871 µg/mL | Geometric Coefficient of Variation 70 |
| ULO 1000mg + LDAC - Ph2 | Trough Observed Serum Concentration (Ctrough) - Phases 1 and 2 | Cycle 2 Day 15 | 143.724 µg/mL | Geometric Coefficient of Variation 58 |
| LDAC - Ph2 | Trough Observed Serum Concentration (Ctrough) - Phases 1 and 2 | Cycle 1 Day 15 | 175.315 µg/mL | — |
| LDAC - Ph2 | Trough Observed Serum Concentration (Ctrough) - Phases 1 and 2 | Cycle 1 Day 1 | 0.100 µg/mL | — |
| LDAC - Ph2 | Trough Observed Serum Concentration (Ctrough) - Phases 1 and 2 | Cycle 1 Day 8 | 39.609 µg/mL | — |
Secondary
Volume of Distribution at Steady State (Vss) - Phases 1 and 2
The Pharmacokinetic (PK) parameters are assessed for ulocuplumab following study drug administration. EOT = end of treatment Measure type and method of dispersion are Geometric mean and %CV, respectively
Time frame: Days 1, 8, 15 for cycles 1 and 2; Days 1, 8 for cycles 3-5; Day 1 every 4th cycle thereafter; EOT; 30 days post last dose (follow-up)
Population: Based on the PK sample collections, PK parameters depended on terminal phase time points including AUC(INF), T-HALF; or at steady-state, including CLT, Vss are not reportable