Relapsing-Remitting Multiple Sclerosis
Conditions
Brief summary
The purpose of this extension trial was to further evaluate the safety and tolerability of oral cladribine in subjects who have previously completed treatment within Trial 25643 (CLARITY). This trial also explored clinical benefit of prolonged 192-week versus 96-week treatment.
Interventions
DRUGCladribine
Participants who received Cladribine 3.5 mg/kg in the previous study 25643 (NCT00213135) and completed will be re-randomized in this extension study and receive cladribine tablet orally as cumulative dose of 0.875 mg/kg over a course of 4 or 5 consecutive days of 28-day period at Week 1, 5, 48, and 52 resulting in total cladribine dose of 3.5 mg/kg during the treatment period of 96 weeks.
DRUGPlacebo
Participants who received Cladribine 3.5 mg/kg in the previous study 25643 (NCT00213135) and completed will be re-randomized in this extension study and receive placebo matched to cladribine tablet 0.875 mg/kg orally administered over a course of 4 or 5 consecutive days of 28-day period at Week 1, 5, 48, and 52 during the treatment period of 96 weeks.
Sponsors
EMD Serono Research & Development Institute, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Randomized in Trial 25643 and satisfied one of the following: * Completed randomized treatment course and scheduled visits for the full 96 weeks; or * Did not complete the randomized treatment course in Trial 25643 but elected to receive rescue treatment with Rebif®, another beta-interferon, or glatiramer acetate and completed scheduled clinic visits for the full 96 weeks; or * Did not complete the randomized treatment course in Trial 25643, declined rescue with Rebif®, another beta-interferon, or glatiramer acetate and still completed scheduled clinic visits for the full 96 weeks; or * Did not complete the randomized treatment course in Trial 25643, were not eligible for rescue option with Rebif®, and still completed scheduled clinic visits for the full 96 weeks * Male or female, between 18 and 65 years of age (inclusive, at time of informed consent for Trial 25643) * No medical history or evidence of latent tuberculosis infection (LTBI) or tuberculosis (TB), as evidenced by TB skin test or chest X-ray * All of the following laboratory hematologic parameters evaluated as normal (as define below, inclusively) within 28 days of first dosing of blinded study medication at study Day 1: * Hemoglobin = 11.6 to 16.2 gram per deciliter (g/dL) * Leukocytes (total white blood cell) = 4.1 to 12.3\*10\^3 per microliter * Absolute lymphocyte count (ALC) = 1.02 to 3.36\*10\^3 per microliter * Absolute neutrophil count (ANC) = 2.03 to 8.36\*10\^3 per microliter * Platelet count = 140 to 450\*10\^3 per microliter * Other protocol-defined inclusion/
Exclusion criteria
may apply
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety Population: Percentage of Participants With at Least 1 Common Terminology Criteria for Adverse Events Version 3.0 (CTCAE) Grade 4 Hematologic and Hepatic Toxicity | Baseline up to Week 120 | Hematologic and hepatic toxicity was assessed using Common Terminology Criteria for Adverse Events v 3.0 (CTCAE). Hematologic and hepatic function included absolute lymphocyte count (ALC), hemoglobin level, white blood cell (WBC) count, absolute neutrophil count (ANC), platelets, alanine transaminase (ALT), aspartate transaminase (AST) and bilirubin. According to CTCAE v3.0: Grade 1=mild, Grade 2=moderate, Grade 3=severe, Grade 4=life threatening or disabling and Grade 5=Death. |
| Safety Population: Mean Change From Baseline in Absolute Lymphocyte Count, Platelet, Neutrophils and Leukocytes at Week 120 | Baseline, Week 120 | Mean change from baseline in absolute lymphocyte count, platelet, neutrophils and leukocytes at week 120 were reported. |
| Safety Population: Mean Change From Baseline in Hemoglobin at Week 120 | Baseline, Week 120 | Mean change from baseline in hemoglobin at Week 120 was reported. |
| Safety Population: Mean Change From Baseline in Aspartate Aminotransferase and Alanine Aminotransferase at Week 120 | Baseline, Week 120 | Mean change from baseline in aspartate aminotransferase and alanine aminotransferase at week 120 were reported. |
| Safety Population: Mean Change From Baseline in Bilirubin at Week 120 | Baseline, Week 120 | Mean Change From Baseline in Bilirubin at week 120 was reported. |
| Safety Population: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs | Baseline up to Week 120 | An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered. Serious AE (SAE): Any AE that resulted in death; was life threatening; resulted in persistent/significant disability/incapacity; resulted in/prolonged an existing in-patient hospitalization; was a congenital anomaly/birth defect; or was a medically important condition. The term TEAE is defined as AEs starting or worsening after the first intake of the study drug. Number of participants with TEAEs included participants with both non-serious TEAEs and serious TEAEs. |
| SAFUP Analysis Set: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs | Baseline up to Week 120 | An AE was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered. SAE: Any AE that resulted in death; was life threatening; resulted in persistent/significant disability/incapacity; resulted in/prolonged an existing in-patient hospitalization; was a congenital anomaly/birth defect; or was a medically important condition. The term TEAE is defined as AEs starting or worsening after the first intake of the study drug. Number of participants with TEAEs included participants with both non-serious TEAEs and serious TEAEs. |
| Safety Population: Number of Participants Who Developed Infections (Herpes Viral Infection, Viral Infectious Disorder and Opportunistic Infection), Infection-related Adverse Events and Malignancies | Baseline up to Week 120 | Number of participants who developed Herpes viral infection, Viral infectious disorder and Opportunistic infection are reported. Number of participants with infection related adverse events are the number of participants who had at least one adverse event coded to medical dictionary for regulatory activities (MedDRA) preferred terms under infection and infestation system organ class. Malignancy is defined as having at least one adverse event coded to MedDRA preferred terms under the pre-specified grouping Malignant and unspecified tumors. |
| SAFUP Analysis Set: Number of Participants Who Developed Infections (Herpes Viral Infection, Viral Infectious Disorder and Opportunistic Infection), Infection-related Adverse Events and Malignancies | Baseline up to Week 120 | Number of participants who developed Herpes viral infection, Viral infectious disorder and Opportunistic infection were reported. Number of participants with infection related adverse events are the number of participants who had at least one adverse event coded to medical dictionary for regulatory activities (MedDRA) preferred terms under infection and infestation system organ class. Malignancy is defined as having at least one adverse event coded to MedDRA preferred terms under the pre-specified grouping Malignant and unspecified tumors. |
| Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity | Baseline up to Week 120 | Hematologic and hepatic toxicity was assessed using Common Terminology Criteria for Adverse Events version 3.0 (CTCAE). Hematologic and hepatic function included absolute lymphocyte count (ALC), hemoglobin level, white blood cell (WBC) count, absolute neutrophil count (ANC), platelets, alanine transaminase (ALT), aspartate transaminase (AST) and bilirubin. Time to first CTCAE Grade 3 or 4 hematological or liver toxicity was analyzed by treatment group using Kaplan-Meier plots of probability of surviving toxicity-free and point estimates of percentiles. According to CTCAE version 3.0: Grade 1=mild, Grade 2=moderate, Grade 3=severe, Grade 4=life threatening or disabling and Grade 5=Death. 10th, 20th, 25th, 50th and 75th percentiles were estimated from Kaplan-Meier survival curve. |
| Safety Population: Median Time to Recovery From Grade 3 or 4 Hematological and Hepatic Toxicity | Baseline up to Week 120 | Hematologic and hepatic toxicity was assessed using Common Terminology Criteria for Adverse Events (CTCAE). Hematologic and hepatic function included absolute lymphocyte count (ALC), hemoglobin level, white blood cell (WBC) count, absolute neutrophil count (ANC), platelets, alanine transaminase (ALT), aspartate transaminase (AST) and bilirubin. According to CTCAE version 3.0: Grade 1=mild, Grade 2=moderate, Grade 3=severe, Grade 4=life threatening or disabling and Grade 5=Death. Time to recovery from grade 3 or 4 hematological or liver toxicity were reported: lymphocytes, platelets, neutrophils, white blood cells, hemoglobin, Alanine transaminase (ALT), Aspartate transaminase (AST), Platelets and Bilirubin. Recovery from a Grade 3 or 4 toxicity is defined as a return to a Grade 0 or 1. |
| Safety Population: Mean Time to Recovery From Grade 3 or 4 Hematological and Liver Toxicity | Baseline up to Week 120 | Hematologic and hepatic toxicity was assessed using Common Terminology Criteria for Adverse Events (CTCAE). Hematologic and hepatic function included absolute lymphocyte count (ALC), hemoglobin level, white blood cell (WBC) count, absolute neutrophil count (ANC), platelets, alanine transaminase (ALT), aspartate transaminase (AST) and bilirubin. According to CTCAE v3.0: Grade 1=mild, Grade 2=moderate, Grade 3=severe, Grade 4=life threatening or disabling and Grade 5=Death. Time to recovery from grade 3 or 4 hematological or liver toxicity were reported: lymphocytes, platelets, neutrophils, white blood cells, hemoglobin, Alanine transaminase (ALT), Aspartate transaminase (AST) and Platelets. Recovery from a Grade 3 or 4 toxicity is defined as a return to a Grade 0 or 1. |
| Safety Population: Median Time to Nadir of Absolute Lymphocyte Count | Baseline up to Week 120 | Median time to nadir of absolute lymphocyte count was reported. |
| Safety Population: Mean Time to Nadir of Absolute Lymphocyte Count | Baseline up to Week 120 | Mean time to nadir of absolute lymphocyte count was reported. |
| Safety Population: Mean Time to Recovery From Nadir of Absolute Lymphocyte Count to Normal Value | Baseline up to Week 120 | Mean time to recovery from nadir of absolute lymphocyte count to normal was reported. Recovery from Nadir is defined as a return to baseline value. Normal absolute lymphocyte count is 1.02 x 10\^3 cells/microliter. |
| Safety Population: Mean Change in Corrected QT (QTc) Interval From Baseline | Baseline, Week 5, 48, 52 and 96 | The QT interval is a measure of the time between the start of the Q wave and the end of the T wave. Corrected QT (QTc) is the QT interval corrected for heart rate and RR, which is the interval between two R waves. Mean change in corrected QT (QTc) interval from baseline was reported. |
Countries
Australia, Austria, Belgium, Brazil, Bulgaria, Canada, Croatia, Czechia, Denmark, Estonia, Finland, France, Germany, Greece, Italy, Latvia, Lebanon, Lithuania, Morocco, Netherlands, Poland, Portugal, Russia, Saudi Arabia, Serbia, Switzerland, Tunisia, Turkey (Türkiye), Ukraine, United Kingdom, United States
Participant flow
Pre-assignment details
A total of 1326 subjects were randomized into CLARITY from study 25643 (NCT00213135), of whom 867 consented to participate in this phase 3b extension Study 27820. 806 subjects were randomized or assigned to treatment and a further 61 subjects were followed for safety only (Supplemental follow-up period \[no study treatment\] \[SAFUP\]).
Participants by arm
| Arm | Count |
|---|---|
| Cladribine Low/Placebo (LLPP) Participants who received cladribine 3.5 mg/kg in previous study 25643 (NCT00213135) and completed the study who were randomized or assigned to placebo (matched to cladribine tablet) during the treatment period of 96 weeks. Participants were followed up for 24 weeks in Supplemental follow-up period (SUPF). | 98 |
| Cladribine High Dose/Placebo (HLPP) Participants who received cladribine 5.25 mg/kg in previous study 25643 (NCT00213135) and completed the study who were randomized or assigned to placebo (matched to cladribine tablet) during the treatment period of 96 weeks. Participants were followed up for 24 weeks in SUPF. | 92 |
| Cladribine Low/Low Dose (LLLL) Participants who received cladribine 3.5 mg/kg in previous study 25643 (NCT00213135) and completed the study who were randomized or assigned to cladribine 3.5 mg/kg orally provided as 0.875 mg/kg treatment weeks at Week 1, Week 5, Week 48 and Week 52 resulting in total dose of 3.5 mg/kg during the treatment period of 96 weeks. Participants were followed up for 24 weeks in SUPF. | 186 |
| Cladribine High/Low Dose (HLLL) Participants who received cladribine 5.25 mg/kg in previous study 25643 (NCT00213135) and completed the study who were randomized or assigned to cladribine 3.5 mg/kg orally provided as 0.875 mg/kg treatment weeks at Week 1, Week 5, Week 48 and Week 52 resulting in total dose of 3.5 mg/kg during the treatment period of 96 weeks. Participants were followed up for 24 weeks in SUPF. | 186 |
| Placebo/Cladribine Low Dose (PPLL) Participants who received placebo in previous study 25643 (NCT00213135) and completed the study who were randomized or assigned to cladribine 3.5 mg/kg orally provided as 0.875 mg/kg treatment weeks at Week 1, Week 5, Week 48 and Week 52 resulting in total dose of 3.5 mg/kg during the treatment period of 96 weeks. Participants were followed up for 24 weeks in SUPF. | 244 |
| Total | 806 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 |
|---|---|---|---|---|---|---|---|---|---|
| 24-Week Supplemental Follow-up Period | Lost to Follow-up | 0 | 1 | 1 | 3 | 2 | 1 | 0 | 0 |
| 24-Week Supplemental Follow-up Period | Other | 0 | 2 | 2 | 1 | 3 | 0 | 1 | 1 |
| 96-week Period | Adverse Event | 0 | 1 | 3 | 0 | 2 | 0 | 0 | 0 |
| 96-week Period | Death | 2 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| 96-week Period | Lost to Follow-up | 3 | 1 | 2 | 2 | 4 | 0 | 1 | 0 |
| 96-week Period | Other | 4 | 7 | 14 | 9 | 11 | 6 | 4 | 6 |
| 96-week Period | Protocol Violation | 0 | 1 | 0 | 1 | 0 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Cladribine Low/Placebo (LLPP) | Cladribine High Dose/Placebo (HLPP) | Cladribine Low/Low Dose (LLLL) | Cladribine High/Low Dose (HLLL) | Placebo/Cladribine Low Dose (PPLL) | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 40.7 years STANDARD_DEVIATION 10.7 | 40.8 years STANDARD_DEVIATION 9.6 | 40.6 years STANDARD_DEVIATION 10.5 | 41.4 years STANDARD_DEVIATION 10.1 | 41.6 years STANDARD_DEVIATION 9.6 | 41.1 years STANDARD_DEVIATION 10.1 |
| Sex: Female, Male Female | 67 Participants | 59 Participants | 124 Participants | 125 Participants | 156 Participants | 531 Participants |
| Sex: Female, Male Male | 31 Participants | 33 Participants | 62 Participants | 61 Participants | 88 Participants | 275 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 | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 2 / 98 | 0 / 92 | 1 / 186 | 0 / 186 | 0 / 244 | 0 / 22 | 0 / 17 | 0 / 22 |
| other Total, other adverse events | 73 / 98 | 69 / 92 | 143 / 186 | 146 / 186 | 192 / 244 | 16 / 22 | 13 / 17 | 18 / 22 |
| serious Total, serious adverse events | 16 / 98 | 8 / 92 | 25 / 186 | 23 / 186 | 22 / 244 | 2 / 22 | 1 / 17 | 3 / 22 |
Outcome results
Primary
Safety Population: Mean Change From Baseline in Absolute Lymphocyte Count, Platelet, Neutrophils and Leukocytes at Week 120
Mean change from baseline in absolute lymphocyte count, platelet, neutrophils and leukocytes at week 120 were reported.
Time frame: Baseline, Week 120
Population: Safety population included all the randomized participants who had received at least 1 dose of study medication and had follow-up safety data. Here 'Number of participants analyzed' signifies number of participants who were evaluable for this outcome measure and Number analyzed are those who were evaluable at specified category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cladribine Low/Placebo (LLPP) | Safety Population: Mean Change From Baseline in Absolute Lymphocyte Count, Platelet, Neutrophils and Leukocytes at Week 120 | Lymphocyte Count | 0.3 10^9 cells per liter | Standard Deviation 0.4 |
| Cladribine Low/Placebo (LLPP) | Safety Population: Mean Change From Baseline in Absolute Lymphocyte Count, Platelet, Neutrophils and Leukocytes at Week 120 | Platelet | -7.7 10^9 cells per liter | Standard Deviation 26.2 |
| Cladribine Low/Placebo (LLPP) | Safety Population: Mean Change From Baseline in Absolute Lymphocyte Count, Platelet, Neutrophils and Leukocytes at Week 120 | Leukocytes | 0.8 10^9 cells per liter | Standard Deviation 1.5 |
| Cladribine Low/Placebo (LLPP) | Safety Population: Mean Change From Baseline in Absolute Lymphocyte Count, Platelet, Neutrophils and Leukocytes at Week 120 | Neutrophils | 0.4 10^9 cells per liter | Standard Deviation 1.3 |
| Cladribine High Dose/Placebo (HLPP) | Safety Population: Mean Change From Baseline in Absolute Lymphocyte Count, Platelet, Neutrophils and Leukocytes at Week 120 | Lymphocyte Count | 0.3 10^9 cells per liter | Standard Deviation 0.4 |
| Cladribine High Dose/Placebo (HLPP) | Safety Population: Mean Change From Baseline in Absolute Lymphocyte Count, Platelet, Neutrophils and Leukocytes at Week 120 | Neutrophils | 0.1 10^9 cells per liter | Standard Deviation 1.2 |
| Cladribine High Dose/Placebo (HLPP) | Safety Population: Mean Change From Baseline in Absolute Lymphocyte Count, Platelet, Neutrophils and Leukocytes at Week 120 | Platelet | -11.9 10^9 cells per liter | Standard Deviation 35.3 |
| Cladribine High Dose/Placebo (HLPP) | Safety Population: Mean Change From Baseline in Absolute Lymphocyte Count, Platelet, Neutrophils and Leukocytes at Week 120 | Leukocytes | 0.5 10^9 cells per liter | Standard Deviation 1.2 |
| Cladribine Low/Low Dose (LLLL) | Safety Population: Mean Change From Baseline in Absolute Lymphocyte Count, Platelet, Neutrophils and Leukocytes at Week 120 | Neutrophils | -0.2 10^9 cells per liter | Standard Deviation 1.4 |
| Cladribine Low/Low Dose (LLLL) | Safety Population: Mean Change From Baseline in Absolute Lymphocyte Count, Platelet, Neutrophils and Leukocytes at Week 120 | Platelet | -20.6 10^9 cells per liter | Standard Deviation 37.9 |
| Cladribine Low/Low Dose (LLLL) | Safety Population: Mean Change From Baseline in Absolute Lymphocyte Count, Platelet, Neutrophils and Leukocytes at Week 120 | Leukocytes | -0.2 10^9 cells per liter | Standard Deviation 1.5 |
| Cladribine Low/Low Dose (LLLL) | Safety Population: Mean Change From Baseline in Absolute Lymphocyte Count, Platelet, Neutrophils and Leukocytes at Week 120 | Lymphocyte Count | 0.0 10^9 cells per liter | Standard Deviation 0.4 |
| Cladribine High/Low Dose (HLLL) | Safety Population: Mean Change From Baseline in Absolute Lymphocyte Count, Platelet, Neutrophils and Leukocytes at Week 120 | Lymphocyte Count | 0.0 10^9 cells per liter | Standard Deviation 0.5 |
| Cladribine High/Low Dose (HLLL) | Safety Population: Mean Change From Baseline in Absolute Lymphocyte Count, Platelet, Neutrophils and Leukocytes at Week 120 | Platelet | -9.7 10^9 cells per liter | Standard Deviation 51.2 |
| Cladribine High/Low Dose (HLLL) | Safety Population: Mean Change From Baseline in Absolute Lymphocyte Count, Platelet, Neutrophils and Leukocytes at Week 120 | Neutrophils | -0.2 10^9 cells per liter | Standard Deviation 1.3 |
| Cladribine High/Low Dose (HLLL) | Safety Population: Mean Change From Baseline in Absolute Lymphocyte Count, Platelet, Neutrophils and Leukocytes at Week 120 | Leukocytes | -0.1 10^9 cells per liter | Standard Deviation 1.4 |
| Placebo/Cladribine Low Dose (PPLL) | Safety Population: Mean Change From Baseline in Absolute Lymphocyte Count, Platelet, Neutrophils and Leukocytes at Week 120 | Neutrophils | -0.3 10^9 cells per liter | Standard Deviation 1.7 |
| Placebo/Cladribine Low Dose (PPLL) | Safety Population: Mean Change From Baseline in Absolute Lymphocyte Count, Platelet, Neutrophils and Leukocytes at Week 120 | Leukocytes | -0.9 10^9 cells per liter | Standard Deviation 1.7 |
| Placebo/Cladribine Low Dose (PPLL) | Safety Population: Mean Change From Baseline in Absolute Lymphocyte Count, Platelet, Neutrophils and Leukocytes at Week 120 | Platelet | -34.0 10^9 cells per liter | Standard Deviation 37.2 |
| Placebo/Cladribine Low Dose (PPLL) | Safety Population: Mean Change From Baseline in Absolute Lymphocyte Count, Platelet, Neutrophils and Leukocytes at Week 120 | Lymphocyte Count | -0.6 10^9 cells per liter | Standard Deviation 0.6 |
Primary
Safety Population: Mean Change From Baseline in Aspartate Aminotransferase and Alanine Aminotransferase at Week 120
Mean change from baseline in aspartate aminotransferase and alanine aminotransferase at week 120 were reported.
Time frame: Baseline, Week 120
Population: Safety population included all the randomized participants who had received at least 1 dose of study medication and had follow-up safety data. Here 'Number of participants analyzed' signifies number of participants who were evaluable for this outcome measure and Number analyzed are those who were evaluable at specified category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cladribine Low/Placebo (LLPP) | Safety Population: Mean Change From Baseline in Aspartate Aminotransferase and Alanine Aminotransferase at Week 120 | Alanine Aminotransferase | 2.2 Units per litre (U/L) | Standard Deviation 26 |
| Cladribine Low/Placebo (LLPP) | Safety Population: Mean Change From Baseline in Aspartate Aminotransferase and Alanine Aminotransferase at Week 120 | Aspartate Aminotransferase | 0.7 Units per litre (U/L) | Standard Deviation 10.6 |
| Cladribine High Dose/Placebo (HLPP) | Safety Population: Mean Change From Baseline in Aspartate Aminotransferase and Alanine Aminotransferase at Week 120 | Aspartate Aminotransferase | -1.1 Units per litre (U/L) | Standard Deviation 6.4 |
| Cladribine High Dose/Placebo (HLPP) | Safety Population: Mean Change From Baseline in Aspartate Aminotransferase and Alanine Aminotransferase at Week 120 | Alanine Aminotransferase | -1.0 Units per litre (U/L) | Standard Deviation 11.7 |
| Cladribine Low/Low Dose (LLLL) | Safety Population: Mean Change From Baseline in Aspartate Aminotransferase and Alanine Aminotransferase at Week 120 | Alanine Aminotransferase | 4.3 Units per litre (U/L) | Standard Deviation 14.3 |
| Cladribine Low/Low Dose (LLLL) | Safety Population: Mean Change From Baseline in Aspartate Aminotransferase and Alanine Aminotransferase at Week 120 | Aspartate Aminotransferase | 2.2 Units per litre (U/L) | Standard Deviation 7.3 |
| Cladribine High/Low Dose (HLLL) | Safety Population: Mean Change From Baseline in Aspartate Aminotransferase and Alanine Aminotransferase at Week 120 | Aspartate Aminotransferase | 0.7 Units per litre (U/L) | Standard Deviation 11.3 |
| Cladribine High/Low Dose (HLLL) | Safety Population: Mean Change From Baseline in Aspartate Aminotransferase and Alanine Aminotransferase at Week 120 | Alanine Aminotransferase | 0.7 Units per litre (U/L) | Standard Deviation 17.5 |
| Placebo/Cladribine Low Dose (PPLL) | Safety Population: Mean Change From Baseline in Aspartate Aminotransferase and Alanine Aminotransferase at Week 120 | Alanine Aminotransferase | 1.4 Units per litre (U/L) | Standard Deviation 12.2 |
| Placebo/Cladribine Low Dose (PPLL) | Safety Population: Mean Change From Baseline in Aspartate Aminotransferase and Alanine Aminotransferase at Week 120 | Aspartate Aminotransferase | 0.5 Units per litre (U/L) | Standard Deviation 5.1 |
Primary
Safety Population: Mean Change From Baseline in Bilirubin at Week 120
Mean Change From Baseline in Bilirubin at week 120 was reported.
Time frame: Baseline, Week 120
Population: Safety population included all the randomized participants who had received at least 1 dose of study medication and had follow-up safety data. Here 'Number of participants analyzed' signifies number of participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cladribine Low/Placebo (LLPP) | Safety Population: Mean Change From Baseline in Bilirubin at Week 120 | 0.1 micromoles per liter (mcmol/L) | Standard Deviation 3.7 |
| Cladribine High Dose/Placebo (HLPP) | Safety Population: Mean Change From Baseline in Bilirubin at Week 120 | 0.0 micromoles per liter (mcmol/L) | Standard Deviation 3.5 |
| Cladribine Low/Low Dose (LLLL) | Safety Population: Mean Change From Baseline in Bilirubin at Week 120 | -0.8 micromoles per liter (mcmol/L) | Standard Deviation 3.7 |
| Cladribine High/Low Dose (HLLL) | Safety Population: Mean Change From Baseline in Bilirubin at Week 120 | -0.8 micromoles per liter (mcmol/L) | Standard Deviation 3.3 |
| Placebo/Cladribine Low Dose (PPLL) | Safety Population: Mean Change From Baseline in Bilirubin at Week 120 | -0.4 micromoles per liter (mcmol/L) | Standard Deviation 3.7 |
Primary
Safety Population: Mean Change From Baseline in Hemoglobin at Week 120
Mean change from baseline in hemoglobin at Week 120 was reported.
Time frame: Baseline, Week 120
Population: Safety population included all the randomized participants who had received at least 1 dose of study medication and had follow-up safety data. Here 'Number of participants analyzed' signifies number of participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cladribine Low/Placebo (LLPP) | Safety Population: Mean Change From Baseline in Hemoglobin at Week 120 | 0.2 grams per deciliter (g/dL) | Standard Deviation 0.9 |
| Cladribine High Dose/Placebo (HLPP) | Safety Population: Mean Change From Baseline in Hemoglobin at Week 120 | 0.2 grams per deciliter (g/dL) | Standard Deviation 0.7 |
| Cladribine Low/Low Dose (LLLL) | Safety Population: Mean Change From Baseline in Hemoglobin at Week 120 | -0.1 grams per deciliter (g/dL) | Standard Deviation 0.9 |
| Cladribine High/Low Dose (HLLL) | Safety Population: Mean Change From Baseline in Hemoglobin at Week 120 | 0.1 grams per deciliter (g/dL) | Standard Deviation 0.9 |
| Placebo/Cladribine Low Dose (PPLL) | Safety Population: Mean Change From Baseline in Hemoglobin at Week 120 | -0.1 grams per deciliter (g/dL) | Standard Deviation 0.9 |
Primary
Safety Population: Mean Change in Corrected QT (QTc) Interval From Baseline
The QT interval is a measure of the time between the start of the Q wave and the end of the T wave. Corrected QT (QTc) is the QT interval corrected for heart rate and RR, which is the interval between two R waves. Mean change in corrected QT (QTc) interval from baseline was reported.
Time frame: Baseline, Week 5, 48, 52 and 96
Population: Safety population included all the randomized participants who had received at least 1 dose of study medication and had follow-up safety data. Here 'Number of participants analyzed' signifies number of participants who were evaluable for this outcome measure and and Number analyzed are those who were evaluable at specified category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cladribine Low/Placebo (LLPP) | Safety Population: Mean Change in Corrected QT (QTc) Interval From Baseline | Week 5 | 7.0 milliseconds | Standard Deviation 21.6 |
| Cladribine Low/Placebo (LLPP) | Safety Population: Mean Change in Corrected QT (QTc) Interval From Baseline | Week 48 | 16.9 milliseconds | Standard Deviation 18.6 |
| Cladribine Low/Placebo (LLPP) | Safety Population: Mean Change in Corrected QT (QTc) Interval From Baseline | Week 52 | 14.9 milliseconds | Standard Deviation 17.5 |
| Cladribine Low/Placebo (LLPP) | Safety Population: Mean Change in Corrected QT (QTc) Interval From Baseline | Week 96 | 5.8 milliseconds | Standard Deviation 25.5 |
| Cladribine High Dose/Placebo (HLPP) | Safety Population: Mean Change in Corrected QT (QTc) Interval From Baseline | Week 5 | 7.4 milliseconds | Standard Deviation 21.2 |
| Cladribine High Dose/Placebo (HLPP) | Safety Population: Mean Change in Corrected QT (QTc) Interval From Baseline | Week 96 | -4.5 milliseconds | Standard Deviation 32.5 |
| Cladribine High Dose/Placebo (HLPP) | Safety Population: Mean Change in Corrected QT (QTc) Interval From Baseline | Week 48 | 7.4 milliseconds | Standard Deviation 23.6 |
| Cladribine High Dose/Placebo (HLPP) | Safety Population: Mean Change in Corrected QT (QTc) Interval From Baseline | Week 52 | 22.3 milliseconds | Standard Deviation 25.4 |
| Cladribine Low/Low Dose (LLLL) | Safety Population: Mean Change in Corrected QT (QTc) Interval From Baseline | Week 96 | -12.5 milliseconds | Standard Deviation 22.2 |
| Cladribine Low/Low Dose (LLLL) | Safety Population: Mean Change in Corrected QT (QTc) Interval From Baseline | Week 48 | 9.3 milliseconds | Standard Deviation 19.8 |
| Cladribine Low/Low Dose (LLLL) | Safety Population: Mean Change in Corrected QT (QTc) Interval From Baseline | Week 52 | 8.4 milliseconds | Standard Deviation 22.8 |
| Cladribine Low/Low Dose (LLLL) | Safety Population: Mean Change in Corrected QT (QTc) Interval From Baseline | Week 5 | 4.5 milliseconds | Standard Deviation 20.6 |
| Cladribine High/Low Dose (HLLL) | Safety Population: Mean Change in Corrected QT (QTc) Interval From Baseline | Week 5 | 4.3 milliseconds | Standard Deviation 16.2 |
| Cladribine High/Low Dose (HLLL) | Safety Population: Mean Change in Corrected QT (QTc) Interval From Baseline | Week 48 | 11.3 milliseconds | Standard Deviation 19.5 |
| Cladribine High/Low Dose (HLLL) | Safety Population: Mean Change in Corrected QT (QTc) Interval From Baseline | Week 96 | 1.6 milliseconds | Standard Deviation 22.7 |
| Cladribine High/Low Dose (HLLL) | Safety Population: Mean Change in Corrected QT (QTc) Interval From Baseline | Week 52 | 5.2 milliseconds | Standard Deviation 18.8 |
| Placebo/Cladribine Low Dose (PPLL) | Safety Population: Mean Change in Corrected QT (QTc) Interval From Baseline | Week 96 | -6.2 milliseconds | Standard Deviation 19.2 |
| Placebo/Cladribine Low Dose (PPLL) | Safety Population: Mean Change in Corrected QT (QTc) Interval From Baseline | Week 52 | -1.2 milliseconds | Standard Deviation 16.6 |
| Placebo/Cladribine Low Dose (PPLL) | Safety Population: Mean Change in Corrected QT (QTc) Interval From Baseline | Week 48 | 7.2 milliseconds | Standard Deviation 19.6 |
| Placebo/Cladribine Low Dose (PPLL) | Safety Population: Mean Change in Corrected QT (QTc) Interval From Baseline | Week 5 | 0.7 milliseconds | Standard Deviation 18.8 |
Primary
Safety Population: Mean Time to Nadir of Absolute Lymphocyte Count
Mean time to nadir of absolute lymphocyte count was reported.
Time frame: Baseline up to Week 120
Population: Safety population included all the randomized participants who had received at least 1 dose of study medication and had follow-up safety data. Here 'Number of participants analyzed' signifies number of participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cladribine Low/Placebo (LLPP) | Safety Population: Mean Time to Nadir of Absolute Lymphocyte Count | 292.0 Days | Standard Deviation 296.7 |
| Cladribine High Dose/Placebo (HLPP) | Safety Population: Mean Time to Nadir of Absolute Lymphocyte Count | 193.6 Days | Standard Deviation 219.1 |
| Cladribine Low/Low Dose (LLLL) | Safety Population: Mean Time to Nadir of Absolute Lymphocyte Count | 276.7 Days | Standard Deviation 191.7 |
| Cladribine High/Low Dose (HLLL) | Safety Population: Mean Time to Nadir of Absolute Lymphocyte Count | 241.1 Days | Standard Deviation 200.3 |
| Placebo/Cladribine Low Dose (PPLL) | Safety Population: Mean Time to Nadir of Absolute Lymphocyte Count | 362.9 Days | Standard Deviation 177.5 |
Primary
Safety Population: Mean Time to Recovery From Grade 3 or 4 Hematological and Liver Toxicity
Hematologic and hepatic toxicity was assessed using Common Terminology Criteria for Adverse Events (CTCAE). Hematologic and hepatic function included absolute lymphocyte count (ALC), hemoglobin level, white blood cell (WBC) count, absolute neutrophil count (ANC), platelets, alanine transaminase (ALT), aspartate transaminase (AST) and bilirubin. According to CTCAE v3.0: Grade 1=mild, Grade 2=moderate, Grade 3=severe, Grade 4=life threatening or disabling and Grade 5=Death. Time to recovery from grade 3 or 4 hematological or liver toxicity were reported: lymphocytes, platelets, neutrophils, white blood cells, hemoglobin, Alanine transaminase (ALT), Aspartate transaminase (AST) and Platelets. Recovery from a Grade 3 or 4 toxicity is defined as a return to a Grade 0 or 1.
Time frame: Baseline up to Week 120
Population: Safety population included all the randomized participants who had received at least 1 dose of study medication and had follow-up safety data. Here 'Number of participants analyzed' signifies number of participants who were evaluable for this outcome measure and Number analyzed are those who were evaluable at specified category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cladribine Low/Placebo (LLPP) | Safety Population: Mean Time to Recovery From Grade 3 or 4 Hematological and Liver Toxicity | Absolute Neutrophil Count | 49.0 Days | Standard Deviation 39.3 |
| Cladribine Low/Placebo (LLPP) | Safety Population: Mean Time to Recovery From Grade 3 or 4 Hematological and Liver Toxicity | Lymphocyte | 41.0 Days | Standard Deviation 33.5 |
| Cladribine Low/Placebo (LLPP) | Safety Population: Mean Time to Recovery From Grade 3 or 4 Hematological and Liver Toxicity | Aspartate Transaminase | 72.5 Days | Standard Deviation 30.4 |
| Cladribine Low/Placebo (LLPP) | Safety Population: Mean Time to Recovery From Grade 3 or 4 Hematological and Liver Toxicity | Alanine Transaminase | 72.5 Days | Standard Deviation 30.4 |
| Cladribine High Dose/Placebo (HLPP) | Safety Population: Mean Time to Recovery From Grade 3 or 4 Hematological and Liver Toxicity | Hemoglobin | 99.0 Days | — |
| Cladribine High Dose/Placebo (HLPP) | Safety Population: Mean Time to Recovery From Grade 3 or 4 Hematological and Liver Toxicity | White Blood Cell Count | 29.0 Days | — |
| Cladribine High Dose/Placebo (HLPP) | Safety Population: Mean Time to Recovery From Grade 3 or 4 Hematological and Liver Toxicity | Lymphocyte | 34.9 Days | Standard Deviation 11.7 |
| Cladribine High Dose/Placebo (HLPP) | Safety Population: Mean Time to Recovery From Grade 3 or 4 Hematological and Liver Toxicity | Absolute Neutrophil Count | 57.0 Days | Standard Deviation 39.6 |
| Cladribine Low/Low Dose (LLLL) | Safety Population: Mean Time to Recovery From Grade 3 or 4 Hematological and Liver Toxicity | Hemoglobin | 64.0 Days | — |
| Cladribine Low/Low Dose (LLLL) | Safety Population: Mean Time to Recovery From Grade 3 or 4 Hematological and Liver Toxicity | Lymphocyte | 256.7 Days | Standard Deviation 239.7 |
| Cladribine Low/Low Dose (LLLL) | Safety Population: Mean Time to Recovery From Grade 3 or 4 Hematological and Liver Toxicity | White Blood Cell Count | 79.3 Days | Standard Deviation 91.9 |
| Cladribine Low/Low Dose (LLLL) | Safety Population: Mean Time to Recovery From Grade 3 or 4 Hematological and Liver Toxicity | Absolute Neutrophil Count | 35.3 Days | Standard Deviation 29.9 |
| Cladribine Low/Low Dose (LLLL) | Safety Population: Mean Time to Recovery From Grade 3 or 4 Hematological and Liver Toxicity | Aspartate Transaminase | 84.0 Days | — |
| Cladribine High/Low Dose (HLLL) | Safety Population: Mean Time to Recovery From Grade 3 or 4 Hematological and Liver Toxicity | Alanine Transaminase | 73.0 Days | Standard Deviation 76.4 |
| Cladribine High/Low Dose (HLLL) | Safety Population: Mean Time to Recovery From Grade 3 or 4 Hematological and Liver Toxicity | Absolute Neutrophil Count | 46.8 Days | Standard Deviation 35.1 |
| Cladribine High/Low Dose (HLLL) | Safety Population: Mean Time to Recovery From Grade 3 or 4 Hematological and Liver Toxicity | Lymphocyte | 241.8 Days | Standard Deviation 216.1 |
| Cladribine High/Low Dose (HLLL) | Safety Population: Mean Time to Recovery From Grade 3 or 4 Hematological and Liver Toxicity | Hemoglobin | 57.0 Days | — |
| Cladribine High/Low Dose (HLLL) | Safety Population: Mean Time to Recovery From Grade 3 or 4 Hematological and Liver Toxicity | White Blood Cell Count | 132.0 Days | Standard Deviation 213.9 |
| Cladribine High/Low Dose (HLLL) | Safety Population: Mean Time to Recovery From Grade 3 or 4 Hematological and Liver Toxicity | Platelets | 197.0 Days | — |
| Cladribine High/Low Dose (HLLL) | Safety Population: Mean Time to Recovery From Grade 3 or 4 Hematological and Liver Toxicity | Aspartate Transaminase | 18.0 Days | — |
| Placebo/Cladribine Low Dose (PPLL) | Safety Population: Mean Time to Recovery From Grade 3 or 4 Hematological and Liver Toxicity | White Blood Cell Count | 71.5 Days | Standard Deviation 39.7 |
| Placebo/Cladribine Low Dose (PPLL) | Safety Population: Mean Time to Recovery From Grade 3 or 4 Hematological and Liver Toxicity | Absolute Neutrophil Count | 61.0 Days | Standard Deviation 55.3 |
| Placebo/Cladribine Low Dose (PPLL) | Safety Population: Mean Time to Recovery From Grade 3 or 4 Hematological and Liver Toxicity | Lymphocyte | 160.2 Days | Standard Deviation 160.4 |
| Placebo/Cladribine Low Dose (PPLL) | Safety Population: Mean Time to Recovery From Grade 3 or 4 Hematological and Liver Toxicity | Alanine Transaminase | 23.7 Days | Standard Deviation 28 |
| Placebo/Cladribine Low Dose (PPLL) | Safety Population: Mean Time to Recovery From Grade 3 or 4 Hematological and Liver Toxicity | Aspartate Transaminase | 55.0 Days | — |
| Placebo/Cladribine Low Dose (PPLL) | Safety Population: Mean Time to Recovery From Grade 3 or 4 Hematological and Liver Toxicity | Hemoglobin | 173.5 Days | Standard Deviation 214.3 |
Primary
Safety Population: Mean Time to Recovery From Nadir of Absolute Lymphocyte Count to Normal Value
Mean time to recovery from nadir of absolute lymphocyte count to normal was reported. Recovery from Nadir is defined as a return to baseline value. Normal absolute lymphocyte count is 1.02 x 10\^3 cells/microliter.
Time frame: Baseline up to Week 120
Population: Safety population included all the randomized participants who had received at least 1 dose of study medication and had follow-up safety data. Here 'Number of participants analyzed' signifies number of participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cladribine Low/Placebo (LLPP) | Safety Population: Mean Time to Recovery From Nadir of Absolute Lymphocyte Count to Normal Value | 79.0 Days | Standard Deviation 72.4 |
| Cladribine High Dose/Placebo (HLPP) | Safety Population: Mean Time to Recovery From Nadir of Absolute Lymphocyte Count to Normal Value | 72.7 Days | Standard Deviation 61.3 |
| Cladribine Low/Low Dose (LLLL) | Safety Population: Mean Time to Recovery From Nadir of Absolute Lymphocyte Count to Normal Value | 237.5 Days | Standard Deviation 214.7 |
| Cladribine High/Low Dose (HLLL) | Safety Population: Mean Time to Recovery From Nadir of Absolute Lymphocyte Count to Normal Value | 245.3 Days | Standard Deviation 222.3 |
| Placebo/Cladribine Low Dose (PPLL) | Safety Population: Mean Time to Recovery From Nadir of Absolute Lymphocyte Count to Normal Value | 187.8 Days | Standard Deviation 180.9 |
Primary
Safety Population: Median Time to Nadir of Absolute Lymphocyte Count
Median time to nadir of absolute lymphocyte count was reported.
Time frame: Baseline up to Week 120
Population: Safety population included all the randomized participants who had received at least 1 dose of study medication and had follow-up safety data. Here 'Number of participants analyzed' signifies number of participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cladribine Low/Placebo (LLPP) | Safety Population: Median Time to Nadir of Absolute Lymphocyte Count | 162.0 Days |
| Cladribine High Dose/Placebo (HLPP) | Safety Population: Median Time to Nadir of Absolute Lymphocyte Count | 93.0 Days |
| Cladribine Low/Low Dose (LLLL) | Safety Population: Median Time to Nadir of Absolute Lymphocyte Count | 365.0 Days |
| Cladribine High/Low Dose (HLLL) | Safety Population: Median Time to Nadir of Absolute Lymphocyte Count | 162.0 Days |
| Placebo/Cladribine Low Dose (PPLL) | Safety Population: Median Time to Nadir of Absolute Lymphocyte Count | 380.0 Days |
Primary
Safety Population: Median Time to Recovery From Grade 3 or 4 Hematological and Hepatic Toxicity
Hematologic and hepatic toxicity was assessed using Common Terminology Criteria for Adverse Events (CTCAE). Hematologic and hepatic function included absolute lymphocyte count (ALC), hemoglobin level, white blood cell (WBC) count, absolute neutrophil count (ANC), platelets, alanine transaminase (ALT), aspartate transaminase (AST) and bilirubin. According to CTCAE version 3.0: Grade 1=mild, Grade 2=moderate, Grade 3=severe, Grade 4=life threatening or disabling and Grade 5=Death. Time to recovery from grade 3 or 4 hematological or liver toxicity were reported: lymphocytes, platelets, neutrophils, white blood cells, hemoglobin, Alanine transaminase (ALT), Aspartate transaminase (AST), Platelets and Bilirubin. Recovery from a Grade 3 or 4 toxicity is defined as a return to a Grade 0 or 1.
Time frame: Baseline up to Week 120
Population: Safety population included all the randomized participants who had received at least 1dose of study medication and had follow-up safety data. Here 'Number of participants analyzed' signifies number of participants who were evaluable for this outcome measure and Number Analyzed signifies those participants who were evaluable for specified category.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cladribine Low/Placebo (LLPP) | Safety Population: Median Time to Recovery From Grade 3 or 4 Hematological and Hepatic Toxicity | Lymphocyte | 22.0 Days |
| Cladribine Low/Placebo (LLPP) | Safety Population: Median Time to Recovery From Grade 3 or 4 Hematological and Hepatic Toxicity | Absolute Neutrophil Count | 43.0 Days |
| Cladribine Low/Placebo (LLPP) | Safety Population: Median Time to Recovery From Grade 3 or 4 Hematological and Hepatic Toxicity | Alanine Transaminase (ALT) | 72.5 Days |
| Cladribine Low/Placebo (LLPP) | Safety Population: Median Time to Recovery From Grade 3 or 4 Hematological and Hepatic Toxicity | Aspartate Transaminase (AST) | 72.5 Days |
| Cladribine High Dose/Placebo (HLPP) | Safety Population: Median Time to Recovery From Grade 3 or 4 Hematological and Hepatic Toxicity | White Blood Cell Count | 29.0 Days |
| Cladribine High Dose/Placebo (HLPP) | Safety Population: Median Time to Recovery From Grade 3 or 4 Hematological and Hepatic Toxicity | Hemoglobin | 99.0 Days |
| Cladribine High Dose/Placebo (HLPP) | Safety Population: Median Time to Recovery From Grade 3 or 4 Hematological and Hepatic Toxicity | Absolute Neutrophil Count | 57.0 Days |
| Cladribine High Dose/Placebo (HLPP) | Safety Population: Median Time to Recovery From Grade 3 or 4 Hematological and Hepatic Toxicity | Lymphocyte | 31.5 Days |
| Cladribine Low/Low Dose (LLLL) | Safety Population: Median Time to Recovery From Grade 3 or 4 Hematological and Hepatic Toxicity | Hemoglobin | 64.0 Days |
| Cladribine Low/Low Dose (LLLL) | Safety Population: Median Time to Recovery From Grade 3 or 4 Hematological and Hepatic Toxicity | Lymphocyte | 212.0 Days |
| Cladribine Low/Low Dose (LLLL) | Safety Population: Median Time to Recovery From Grade 3 or 4 Hematological and Hepatic Toxicity | Absolute Neutrophil Count | 23.8 Days |
| Cladribine Low/Low Dose (LLLL) | Safety Population: Median Time to Recovery From Grade 3 or 4 Hematological and Hepatic Toxicity | Aspartate Transaminase (AST) | 84.0 Days |
| Cladribine Low/Low Dose (LLLL) | Safety Population: Median Time to Recovery From Grade 3 or 4 Hematological and Hepatic Toxicity | White Blood Cell Count | 30.0 Days |
| Cladribine High/Low Dose (HLLL) | Safety Population: Median Time to Recovery From Grade 3 or 4 Hematological and Hepatic Toxicity | Lymphocyte | 168.0 Days |
| Cladribine High/Low Dose (HLLL) | Safety Population: Median Time to Recovery From Grade 3 or 4 Hematological and Hepatic Toxicity | Hemoglobin | 57.0 Days |
| Cladribine High/Low Dose (HLLL) | Safety Population: Median Time to Recovery From Grade 3 or 4 Hematological and Hepatic Toxicity | White Blood Cell Count | 42.5 Days |
| Cladribine High/Low Dose (HLLL) | Safety Population: Median Time to Recovery From Grade 3 or 4 Hematological and Hepatic Toxicity | Absolute Neutrophil Count | 34.0 Days |
| Cladribine High/Low Dose (HLLL) | Safety Population: Median Time to Recovery From Grade 3 or 4 Hematological and Hepatic Toxicity | Platelets | 197.0 Days |
| Cladribine High/Low Dose (HLLL) | Safety Population: Median Time to Recovery From Grade 3 or 4 Hematological and Hepatic Toxicity | Aspartate Transaminase (AST) | 18.0 Days |
| Cladribine High/Low Dose (HLLL) | Safety Population: Median Time to Recovery From Grade 3 or 4 Hematological and Hepatic Toxicity | Alanine Transaminase (ALT) | 73.0 Days |
| Placebo/Cladribine Low Dose (PPLL) | Safety Population: Median Time to Recovery From Grade 3 or 4 Hematological and Hepatic Toxicity | Lymphocyte | 111.3 Days |
| Placebo/Cladribine Low Dose (PPLL) | Safety Population: Median Time to Recovery From Grade 3 or 4 Hematological and Hepatic Toxicity | Alanine Transaminase (ALT) | 15.0 Days |
| Placebo/Cladribine Low Dose (PPLL) | Safety Population: Median Time to Recovery From Grade 3 or 4 Hematological and Hepatic Toxicity | Aspartate Transaminase (AST) | 55.0 Days |
| Placebo/Cladribine Low Dose (PPLL) | Safety Population: Median Time to Recovery From Grade 3 or 4 Hematological and Hepatic Toxicity | Absolute Neutrophil Count | 37.5 Days |
| Placebo/Cladribine Low Dose (PPLL) | Safety Population: Median Time to Recovery From Grade 3 or 4 Hematological and Hepatic Toxicity | White Blood Cell Count | 79.0 Days |
| Placebo/Cladribine Low Dose (PPLL) | Safety Population: Median Time to Recovery From Grade 3 or 4 Hematological and Hepatic Toxicity | Hemoglobin | 173.5 Days |
Primary
Safety Population: Number of Participants Who Developed Infections (Herpes Viral Infection, Viral Infectious Disorder and Opportunistic Infection), Infection-related Adverse Events and Malignancies
Number of participants who developed Herpes viral infection, Viral infectious disorder and Opportunistic infection are reported. Number of participants with infection related adverse events are the number of participants who had at least one adverse event coded to medical dictionary for regulatory activities (MedDRA) preferred terms under infection and infestation system organ class. Malignancy is defined as having at least one adverse event coded to MedDRA preferred terms under the pre-specified grouping Malignant and unspecified tumors.
Time frame: Baseline up to Week 120
Population: Safety population included all the randomized participants who had received at least 1 dose of study medication and had follow-up safety data.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cladribine Low/Placebo (LLPP) | Safety Population: Number of Participants Who Developed Infections (Herpes Viral Infection, Viral Infectious Disorder and Opportunistic Infection), Infection-related Adverse Events and Malignancies | Herpes viral infection | 6 Participants |
| Cladribine Low/Placebo (LLPP) | Safety Population: Number of Participants Who Developed Infections (Herpes Viral Infection, Viral Infectious Disorder and Opportunistic Infection), Infection-related Adverse Events and Malignancies | Viral infectious disorder | 20 Participants |
| Cladribine Low/Placebo (LLPP) | Safety Population: Number of Participants Who Developed Infections (Herpes Viral Infection, Viral Infectious Disorder and Opportunistic Infection), Infection-related Adverse Events and Malignancies | Malignancies | 2 Participants |
| Cladribine Low/Placebo (LLPP) | Safety Population: Number of Participants Who Developed Infections (Herpes Viral Infection, Viral Infectious Disorder and Opportunistic Infection), Infection-related Adverse Events and Malignancies | Opportunistic infection | 8 Participants |
| Cladribine Low/Placebo (LLPP) | Safety Population: Number of Participants Who Developed Infections (Herpes Viral Infection, Viral Infectious Disorder and Opportunistic Infection), Infection-related Adverse Events and Malignancies | Infections related adverse event | 49 Participants |
| Cladribine High Dose/Placebo (HLPP) | Safety Population: Number of Participants Who Developed Infections (Herpes Viral Infection, Viral Infectious Disorder and Opportunistic Infection), Infection-related Adverse Events and Malignancies | Opportunistic infection | 4 Participants |
| Cladribine High Dose/Placebo (HLPP) | Safety Population: Number of Participants Who Developed Infections (Herpes Viral Infection, Viral Infectious Disorder and Opportunistic Infection), Infection-related Adverse Events and Malignancies | Viral infectious disorder | 16 Participants |
| Cladribine High Dose/Placebo (HLPP) | Safety Population: Number of Participants Who Developed Infections (Herpes Viral Infection, Viral Infectious Disorder and Opportunistic Infection), Infection-related Adverse Events and Malignancies | Infections related adverse event | 45 Participants |
| Cladribine High Dose/Placebo (HLPP) | Safety Population: Number of Participants Who Developed Infections (Herpes Viral Infection, Viral Infectious Disorder and Opportunistic Infection), Infection-related Adverse Events and Malignancies | Herpes viral infection | 4 Participants |
| Cladribine High Dose/Placebo (HLPP) | Safety Population: Number of Participants Who Developed Infections (Herpes Viral Infection, Viral Infectious Disorder and Opportunistic Infection), Infection-related Adverse Events and Malignancies | Malignancies | 1 Participants |
| Cladribine Low/Low Dose (LLLL) | Safety Population: Number of Participants Who Developed Infections (Herpes Viral Infection, Viral Infectious Disorder and Opportunistic Infection), Infection-related Adverse Events and Malignancies | Infections related adverse event | 92 Participants |
| Cladribine Low/Low Dose (LLLL) | Safety Population: Number of Participants Who Developed Infections (Herpes Viral Infection, Viral Infectious Disorder and Opportunistic Infection), Infection-related Adverse Events and Malignancies | Herpes viral infection | 6 Participants |
| Cladribine Low/Low Dose (LLLL) | Safety Population: Number of Participants Who Developed Infections (Herpes Viral Infection, Viral Infectious Disorder and Opportunistic Infection), Infection-related Adverse Events and Malignancies | Opportunistic infection | 9 Participants |
| Cladribine Low/Low Dose (LLLL) | Safety Population: Number of Participants Who Developed Infections (Herpes Viral Infection, Viral Infectious Disorder and Opportunistic Infection), Infection-related Adverse Events and Malignancies | Viral infectious disorder | 28 Participants |
| Cladribine Low/Low Dose (LLLL) | Safety Population: Number of Participants Who Developed Infections (Herpes Viral Infection, Viral Infectious Disorder and Opportunistic Infection), Infection-related Adverse Events and Malignancies | Malignancies | 7 Participants |
| Cladribine High/Low Dose (HLLL) | Safety Population: Number of Participants Who Developed Infections (Herpes Viral Infection, Viral Infectious Disorder and Opportunistic Infection), Infection-related Adverse Events and Malignancies | Malignancies | 2 Participants |
| Cladribine High/Low Dose (HLLL) | Safety Population: Number of Participants Who Developed Infections (Herpes Viral Infection, Viral Infectious Disorder and Opportunistic Infection), Infection-related Adverse Events and Malignancies | Opportunistic infection | 17 Participants |
| Cladribine High/Low Dose (HLLL) | Safety Population: Number of Participants Who Developed Infections (Herpes Viral Infection, Viral Infectious Disorder and Opportunistic Infection), Infection-related Adverse Events and Malignancies | Herpes viral infection | 13 Participants |
| Cladribine High/Low Dose (HLLL) | Safety Population: Number of Participants Who Developed Infections (Herpes Viral Infection, Viral Infectious Disorder and Opportunistic Infection), Infection-related Adverse Events and Malignancies | Infections related adverse event | 88 Participants |
| Cladribine High/Low Dose (HLLL) | Safety Population: Number of Participants Who Developed Infections (Herpes Viral Infection, Viral Infectious Disorder and Opportunistic Infection), Infection-related Adverse Events and Malignancies | Viral infectious disorder | 41 Participants |
| Placebo/Cladribine Low Dose (PPLL) | Safety Population: Number of Participants Who Developed Infections (Herpes Viral Infection, Viral Infectious Disorder and Opportunistic Infection), Infection-related Adverse Events and Malignancies | Malignancies | 2 Participants |
| Placebo/Cladribine Low Dose (PPLL) | Safety Population: Number of Participants Who Developed Infections (Herpes Viral Infection, Viral Infectious Disorder and Opportunistic Infection), Infection-related Adverse Events and Malignancies | Viral infectious disorder | 39 Participants |
| Placebo/Cladribine Low Dose (PPLL) | Safety Population: Number of Participants Who Developed Infections (Herpes Viral Infection, Viral Infectious Disorder and Opportunistic Infection), Infection-related Adverse Events and Malignancies | Opportunistic infection | 15 Participants |
| Placebo/Cladribine Low Dose (PPLL) | Safety Population: Number of Participants Who Developed Infections (Herpes Viral Infection, Viral Infectious Disorder and Opportunistic Infection), Infection-related Adverse Events and Malignancies | Herpes viral infection | 11 Participants |
| Placebo/Cladribine Low Dose (PPLL) | Safety Population: Number of Participants Who Developed Infections (Herpes Viral Infection, Viral Infectious Disorder and Opportunistic Infection), Infection-related Adverse Events and Malignancies | Infections related adverse event | 112 Participants |
Primary
Safety Population: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered. Serious AE (SAE): Any AE that resulted in death; was life threatening; resulted in persistent/significant disability/incapacity; resulted in/prolonged an existing in-patient hospitalization; was a congenital anomaly/birth defect; or was a medically important condition. The term TEAE is defined as AEs starting or worsening after the first intake of the study drug. Number of participants with TEAEs included participants with both non-serious TEAEs and serious TEAEs.
Time frame: Baseline up to Week 120
Population: Safety population included all the randomized participants who had received at least 1 dose of study medication and had follow-up safety data.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cladribine Low/Placebo (LLPP) | Safety Population: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs | TEAEs | 74 Participants |
| Cladribine Low/Placebo (LLPP) | Safety Population: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs | Serious TEAEs | 16 Participants |
| Cladribine High Dose/Placebo (HLPP) | Safety Population: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs | Serious TEAEs | 8 Participants |
| Cladribine High Dose/Placebo (HLPP) | Safety Population: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs | TEAEs | 71 Participants |
| Cladribine Low/Low Dose (LLLL) | Safety Population: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs | Serious TEAEs | 25 Participants |
| Cladribine Low/Low Dose (LLLL) | Safety Population: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs | TEAEs | 149 Participants |
| Cladribine High/Low Dose (HLLL) | Safety Population: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs | TEAEs | 149 Participants |
| Cladribine High/Low Dose (HLLL) | Safety Population: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs | Serious TEAEs | 23 Participants |
| Placebo/Cladribine Low Dose (PPLL) | Safety Population: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs | Serious TEAEs | 22 Participants |
| Placebo/Cladribine Low Dose (PPLL) | Safety Population: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs | TEAEs | 194 Participants |
Primary
Safety Population: Percentage of Participants With at Least 1 Common Terminology Criteria for Adverse Events Version 3.0 (CTCAE) Grade 4 Hematologic and Hepatic Toxicity
Hematologic and hepatic toxicity was assessed using Common Terminology Criteria for Adverse Events v 3.0 (CTCAE). Hematologic and hepatic function included absolute lymphocyte count (ALC), hemoglobin level, white blood cell (WBC) count, absolute neutrophil count (ANC), platelets, alanine transaminase (ALT), aspartate transaminase (AST) and bilirubin. According to CTCAE v3.0: Grade 1=mild, Grade 2=moderate, Grade 3=severe, Grade 4=life threatening or disabling and Grade 5=Death.
Time frame: Baseline up to Week 120
Population: Safety population included all the randomized participants who had received at least 1 dose of study medication and had follow-up safety data.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cladribine Low/Placebo (LLPP) | Safety Population: Percentage of Participants With at Least 1 Common Terminology Criteria for Adverse Events Version 3.0 (CTCAE) Grade 4 Hematologic and Hepatic Toxicity | AsparateTransaminase Toxicity | 0.0 percentage of participants |
| Cladribine Low/Placebo (LLPP) | Safety Population: Percentage of Participants With at Least 1 Common Terminology Criteria for Adverse Events Version 3.0 (CTCAE) Grade 4 Hematologic and Hepatic Toxicity | Bilirubin Toxicity | 0.0 percentage of participants |
| Cladribine Low/Placebo (LLPP) | Safety Population: Percentage of Participants With at Least 1 Common Terminology Criteria for Adverse Events Version 3.0 (CTCAE) Grade 4 Hematologic and Hepatic Toxicity | Hemoglobin Toxicity | 0.0 percentage of participants |
| Cladribine Low/Placebo (LLPP) | Safety Population: Percentage of Participants With at Least 1 Common Terminology Criteria for Adverse Events Version 3.0 (CTCAE) Grade 4 Hematologic and Hepatic Toxicity | White Blood Cell Toxicity | 0.0 percentage of participants |
| Cladribine Low/Placebo (LLPP) | Safety Population: Percentage of Participants With at Least 1 Common Terminology Criteria for Adverse Events Version 3.0 (CTCAE) Grade 4 Hematologic and Hepatic Toxicity | Absolute Neutrophil Count Toxicity | 0.0 percentage of participants |
| Cladribine Low/Placebo (LLPP) | Safety Population: Percentage of Participants With at Least 1 Common Terminology Criteria for Adverse Events Version 3.0 (CTCAE) Grade 4 Hematologic and Hepatic Toxicity | Platelets Toxicity | 0.0 percentage of participants |
| Cladribine Low/Placebo (LLPP) | Safety Population: Percentage of Participants With at Least 1 Common Terminology Criteria for Adverse Events Version 3.0 (CTCAE) Grade 4 Hematologic and Hepatic Toxicity | Lymphocyte toxicity | 0.0 percentage of participants |
| Cladribine Low/Placebo (LLPP) | Safety Population: Percentage of Participants With at Least 1 Common Terminology Criteria for Adverse Events Version 3.0 (CTCAE) Grade 4 Hematologic and Hepatic Toxicity | Alanine Transaminase Toxicity | 0.0 percentage of participants |
| Cladribine High Dose/Placebo (HLPP) | Safety Population: Percentage of Participants With at Least 1 Common Terminology Criteria for Adverse Events Version 3.0 (CTCAE) Grade 4 Hematologic and Hepatic Toxicity | White Blood Cell Toxicity | 0.0 percentage of participants |
| Cladribine High Dose/Placebo (HLPP) | Safety Population: Percentage of Participants With at Least 1 Common Terminology Criteria for Adverse Events Version 3.0 (CTCAE) Grade 4 Hematologic and Hepatic Toxicity | AsparateTransaminase Toxicity | 0.0 percentage of participants |
| Cladribine High Dose/Placebo (HLPP) | Safety Population: Percentage of Participants With at Least 1 Common Terminology Criteria for Adverse Events Version 3.0 (CTCAE) Grade 4 Hematologic and Hepatic Toxicity | Hemoglobin Toxicity | 0.0 percentage of participants |
| Cladribine High Dose/Placebo (HLPP) | Safety Population: Percentage of Participants With at Least 1 Common Terminology Criteria for Adverse Events Version 3.0 (CTCAE) Grade 4 Hematologic and Hepatic Toxicity | Alanine Transaminase Toxicity | 0.0 percentage of participants |
| Cladribine High Dose/Placebo (HLPP) | Safety Population: Percentage of Participants With at Least 1 Common Terminology Criteria for Adverse Events Version 3.0 (CTCAE) Grade 4 Hematologic and Hepatic Toxicity | Absolute Neutrophil Count Toxicity | 2.2 percentage of participants |
| Cladribine High Dose/Placebo (HLPP) | Safety Population: Percentage of Participants With at Least 1 Common Terminology Criteria for Adverse Events Version 3.0 (CTCAE) Grade 4 Hematologic and Hepatic Toxicity | Bilirubin Toxicity | 0.0 percentage of participants |
| Cladribine High Dose/Placebo (HLPP) | Safety Population: Percentage of Participants With at Least 1 Common Terminology Criteria for Adverse Events Version 3.0 (CTCAE) Grade 4 Hematologic and Hepatic Toxicity | Platelets Toxicity | 0.0 percentage of participants |
| Cladribine High Dose/Placebo (HLPP) | Safety Population: Percentage of Participants With at Least 1 Common Terminology Criteria for Adverse Events Version 3.0 (CTCAE) Grade 4 Hematologic and Hepatic Toxicity | Lymphocyte toxicity | 0.0 percentage of participants |
| Cladribine Low/Low Dose (LLLL) | Safety Population: Percentage of Participants With at Least 1 Common Terminology Criteria for Adverse Events Version 3.0 (CTCAE) Grade 4 Hematologic and Hepatic Toxicity | Bilirubin Toxicity | 0.0 percentage of participants |
| Cladribine Low/Low Dose (LLLL) | Safety Population: Percentage of Participants With at Least 1 Common Terminology Criteria for Adverse Events Version 3.0 (CTCAE) Grade 4 Hematologic and Hepatic Toxicity | AsparateTransaminase Toxicity | 0.0 percentage of participants |
| Cladribine Low/Low Dose (LLLL) | Safety Population: Percentage of Participants With at Least 1 Common Terminology Criteria for Adverse Events Version 3.0 (CTCAE) Grade 4 Hematologic and Hepatic Toxicity | Absolute Neutrophil Count Toxicity | 0.5 percentage of participants |
| Cladribine Low/Low Dose (LLLL) | Safety Population: Percentage of Participants With at Least 1 Common Terminology Criteria for Adverse Events Version 3.0 (CTCAE) Grade 4 Hematologic and Hepatic Toxicity | Hemoglobin Toxicity | 0.0 percentage of participants |
| Cladribine Low/Low Dose (LLLL) | Safety Population: Percentage of Participants With at Least 1 Common Terminology Criteria for Adverse Events Version 3.0 (CTCAE) Grade 4 Hematologic and Hepatic Toxicity | Lymphocyte toxicity | 2.7 percentage of participants |
| Cladribine Low/Low Dose (LLLL) | Safety Population: Percentage of Participants With at Least 1 Common Terminology Criteria for Adverse Events Version 3.0 (CTCAE) Grade 4 Hematologic and Hepatic Toxicity | Platelets Toxicity | 0.5 percentage of participants |
| Cladribine Low/Low Dose (LLLL) | Safety Population: Percentage of Participants With at Least 1 Common Terminology Criteria for Adverse Events Version 3.0 (CTCAE) Grade 4 Hematologic and Hepatic Toxicity | White Blood Cell Toxicity | 0.5 percentage of participants |
| Cladribine Low/Low Dose (LLLL) | Safety Population: Percentage of Participants With at Least 1 Common Terminology Criteria for Adverse Events Version 3.0 (CTCAE) Grade 4 Hematologic and Hepatic Toxicity | Alanine Transaminase Toxicity | 0.0 percentage of participants |
| Cladribine High/Low Dose (HLLL) | Safety Population: Percentage of Participants With at Least 1 Common Terminology Criteria for Adverse Events Version 3.0 (CTCAE) Grade 4 Hematologic and Hepatic Toxicity | White Blood Cell Toxicity | 0.0 percentage of participants |
| Cladribine High/Low Dose (HLLL) | Safety Population: Percentage of Participants With at Least 1 Common Terminology Criteria for Adverse Events Version 3.0 (CTCAE) Grade 4 Hematologic and Hepatic Toxicity | Absolute Neutrophil Count Toxicity | 0.0 percentage of participants |
| Cladribine High/Low Dose (HLLL) | Safety Population: Percentage of Participants With at Least 1 Common Terminology Criteria for Adverse Events Version 3.0 (CTCAE) Grade 4 Hematologic and Hepatic Toxicity | Alanine Transaminase Toxicity | 0.0 percentage of participants |
| Cladribine High/Low Dose (HLLL) | Safety Population: Percentage of Participants With at Least 1 Common Terminology Criteria for Adverse Events Version 3.0 (CTCAE) Grade 4 Hematologic and Hepatic Toxicity | Bilirubin Toxicity | 0.0 percentage of participants |
| Cladribine High/Low Dose (HLLL) | Safety Population: Percentage of Participants With at Least 1 Common Terminology Criteria for Adverse Events Version 3.0 (CTCAE) Grade 4 Hematologic and Hepatic Toxicity | Platelets Toxicity | 0.0 percentage of participants |
| Cladribine High/Low Dose (HLLL) | Safety Population: Percentage of Participants With at Least 1 Common Terminology Criteria for Adverse Events Version 3.0 (CTCAE) Grade 4 Hematologic and Hepatic Toxicity | AsparateTransaminase Toxicity | 0.0 percentage of participants |
| Cladribine High/Low Dose (HLLL) | Safety Population: Percentage of Participants With at Least 1 Common Terminology Criteria for Adverse Events Version 3.0 (CTCAE) Grade 4 Hematologic and Hepatic Toxicity | Hemoglobin Toxicity | 0.0 percentage of participants |
| Cladribine High/Low Dose (HLLL) | Safety Population: Percentage of Participants With at Least 1 Common Terminology Criteria for Adverse Events Version 3.0 (CTCAE) Grade 4 Hematologic and Hepatic Toxicity | Lymphocyte toxicity | 3.2 percentage of participants |
| Placebo/Cladribine Low Dose (PPLL) | Safety Population: Percentage of Participants With at Least 1 Common Terminology Criteria for Adverse Events Version 3.0 (CTCAE) Grade 4 Hematologic and Hepatic Toxicity | Bilirubin Toxicity | 0.0 percentage of participants |
| Placebo/Cladribine Low Dose (PPLL) | Safety Population: Percentage of Participants With at Least 1 Common Terminology Criteria for Adverse Events Version 3.0 (CTCAE) Grade 4 Hematologic and Hepatic Toxicity | White Blood Cell Toxicity | 0.0 percentage of participants |
| Placebo/Cladribine Low Dose (PPLL) | Safety Population: Percentage of Participants With at Least 1 Common Terminology Criteria for Adverse Events Version 3.0 (CTCAE) Grade 4 Hematologic and Hepatic Toxicity | Lymphocyte toxicity | 0.4 percentage of participants |
| Placebo/Cladribine Low Dose (PPLL) | Safety Population: Percentage of Participants With at Least 1 Common Terminology Criteria for Adverse Events Version 3.0 (CTCAE) Grade 4 Hematologic and Hepatic Toxicity | Hemoglobin Toxicity | 0.0 percentage of participants |
| Placebo/Cladribine Low Dose (PPLL) | Safety Population: Percentage of Participants With at Least 1 Common Terminology Criteria for Adverse Events Version 3.0 (CTCAE) Grade 4 Hematologic and Hepatic Toxicity | Absolute Neutrophil Count Toxicity | 0.4 percentage of participants |
| Placebo/Cladribine Low Dose (PPLL) | Safety Population: Percentage of Participants With at Least 1 Common Terminology Criteria for Adverse Events Version 3.0 (CTCAE) Grade 4 Hematologic and Hepatic Toxicity | Platelets Toxicity | 0.0 percentage of participants |
| Placebo/Cladribine Low Dose (PPLL) | Safety Population: Percentage of Participants With at Least 1 Common Terminology Criteria for Adverse Events Version 3.0 (CTCAE) Grade 4 Hematologic and Hepatic Toxicity | Alanine Transaminase Toxicity | 0.0 percentage of participants |
| Placebo/Cladribine Low Dose (PPLL) | Safety Population: Percentage of Participants With at Least 1 Common Terminology Criteria for Adverse Events Version 3.0 (CTCAE) Grade 4 Hematologic and Hepatic Toxicity | AsparateTransaminase Toxicity | 0.0 percentage of participants |
Primary
Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity
Hematologic and hepatic toxicity was assessed using Common Terminology Criteria for Adverse Events version 3.0 (CTCAE). Hematologic and hepatic function included absolute lymphocyte count (ALC), hemoglobin level, white blood cell (WBC) count, absolute neutrophil count (ANC), platelets, alanine transaminase (ALT), aspartate transaminase (AST) and bilirubin. Time to first CTCAE Grade 3 or 4 hematological or liver toxicity was analyzed by treatment group using Kaplan-Meier plots of probability of surviving toxicity-free and point estimates of percentiles. According to CTCAE version 3.0: Grade 1=mild, Grade 2=moderate, Grade 3=severe, Grade 4=life threatening or disabling and Grade 5=Death. 10th, 20th, 25th, 50th and 75th percentiles were estimated from Kaplan-Meier survival curve.
Time frame: Baseline up to Week 120
Population: Safety population included all the randomized participants who had received at least 1dose of study medication and had follow-up safety data. Here 'Number of participants analyzed' signifies number of participants who were evaluable for this outcome measure and Number Analyzedsignifies those participants who were evaluable for specified category.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cladribine Low/Placebo (LLPP) | Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity | 10th percentile: ANC | NA Days |
| Cladribine Low/Placebo (LLPP) | Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity | 10th percentile: ALT | NA Days |
| Cladribine Low/Placebo (LLPP) | Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity | 20th percentile: Lymphocytes Count | NA Days |
| Cladribine Low/Placebo (LLPP) | Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity | 75th percentile: Lymphocytes Count | NA Days |
| Cladribine Low/Placebo (LLPP) | Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity | 25th percentile: ALT | NA Days |
| Cladribine Low/Placebo (LLPP) | Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity | 50th percentile: AST | NA Days |
| Cladribine Low/Placebo (LLPP) | Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity | 75th percentile: ANC | NA Days |
| Cladribine Low/Placebo (LLPP) | Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity | 10th percentile: AST | NA Days |
| Cladribine Low/Placebo (LLPP) | Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity | 10th percentile: Lymphocytes Count | NA Days |
| Cladribine Low/Placebo (LLPP) | Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity | 75th percentile: ALT | NA Days |
| Cladribine Low/Placebo (LLPP) | Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity | 50th percentile: ANC | NA Days |
| Cladribine Low/Placebo (LLPP) | Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity | 25th percentile: Lymphocytes Count | NA Days |
| Cladribine Low/Placebo (LLPP) | Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity | 20th percentile: AST | NA Days |
| Cladribine Low/Placebo (LLPP) | Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity | 50th percentile: ALT | NA Days |
| Cladribine Low/Placebo (LLPP) | Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity | 25th percentile: ANC | NA Days |
| Cladribine Low/Placebo (LLPP) | Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity | 20th percentile: ALT | NA Days |
| Cladribine Low/Placebo (LLPP) | Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity | 75th percentile: AST | NA Days |
| Cladribine Low/Placebo (LLPP) | Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity | 50th percentile: Lymphocytes Count | NA Days |
| Cladribine Low/Placebo (LLPP) | Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity | 20th percentile: ANC | NA Days |
| Cladribine Low/Placebo (LLPP) | Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity | 25th percentile: AST | NA Days |
| Cladribine High Dose/Placebo (HLPP) | Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity | 50th percentile: Hemoglobin | NA Days |
| Cladribine High Dose/Placebo (HLPP) | Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity | 10th percentile: ANC | NA Days |
| Cladribine High Dose/Placebo (HLPP) | Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity | 75th percentile: Hemoglobin | NA Days |
| Cladribine High Dose/Placebo (HLPP) | Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity | 75th percentile: WBC | NA Days |
| Cladribine High Dose/Placebo (HLPP) | Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity | 50th percentile: WBC | NA Days |
| Cladribine High Dose/Placebo (HLPP) | Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity | 10th percentile: WBC | NA Days |
| Cladribine High Dose/Placebo (HLPP) | Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity | 25th percentile: WBC | NA Days |
| Cladribine High Dose/Placebo (HLPP) | Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity | 20th percentile: WBC | NA Days |
| Cladribine High Dose/Placebo (HLPP) | Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity | 20th percentile: Lymphocytes Count | NA Days |
| Cladribine High Dose/Placebo (HLPP) | Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity | 25th percentile: Lymphocytes Count | NA Days |
| Cladribine High Dose/Placebo (HLPP) | Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity | 50th percentile: Lymphocytes Count | NA Days |
| Cladribine High Dose/Placebo (HLPP) | Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity | 75th percentile: ANC | NA Days |
| Cladribine High Dose/Placebo (HLPP) | Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity | 75th percentile: Lymphocytes Count | NA Days |
| Cladribine High Dose/Placebo (HLPP) | Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity | 10th percentile: Hemoglobin | NA Days |
| Cladribine High Dose/Placebo (HLPP) | Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity | 50th percentile: ANC | NA Days |
| Cladribine High Dose/Placebo (HLPP) | Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity | 20th percentile: Hemoglobin | NA Days |
| Cladribine High Dose/Placebo (HLPP) | Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity | 10th percentile: Lymphocytes Count | NA Days |
| Cladribine High Dose/Placebo (HLPP) | Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity | 25th percentile: ANC | NA Days |
| Cladribine High Dose/Placebo (HLPP) | Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity | 25th percentile: Hemoglobin | NA Days |
| Cladribine High Dose/Placebo (HLPP) | Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity | 20th percentile: ANC | NA Days |
| Cladribine Low/Low Dose (LLLL) | Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity | 20th percentile: Hemoglobin | NA Days |
| Cladribine Low/Low Dose (LLLL) | Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity | 50th percentile: Lymphocytes Count | NA Days |
| Cladribine Low/Low Dose (LLLL) | Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity | 10th percentile: Lymphocytes Count | 14 Days |
| Cladribine Low/Low Dose (LLLL) | Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity | 20th percentile: Lymphocytes Count | 58 Days |
| Cladribine Low/Low Dose (LLLL) | Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity | 75th percentile: Lymphocytes Count | NA Days |
| Cladribine Low/Low Dose (LLLL) | Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity | 10th percentile: Hemoglobin | NA Days |
| Cladribine Low/Low Dose (LLLL) | Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity | 25th percentile: Lymphocytes Count | 108 Days |
| Cladribine Low/Low Dose (LLLL) | Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity | 25th percentile: Hemoglobin | NA Days |
| Cladribine Low/Low Dose (LLLL) | Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity | 50th percentile: Hemoglobin | NA Days |
| Cladribine Low/Low Dose (LLLL) | Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity | 75th percentile: Hemoglobin | NA Days |
| Cladribine Low/Low Dose (LLLL) | Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity | 10th percentile: WBC | NA Days |
| Cladribine Low/Low Dose (LLLL) | Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity | 20th percentile: WBC | NA Days |
| Cladribine Low/Low Dose (LLLL) | Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity | 25th percentile: WBC | NA Days |
| Cladribine Low/Low Dose (LLLL) | Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity | 50th percentile: WBC | NA Days |
| Cladribine Low/Low Dose (LLLL) | Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity | 75th percentile: WBC | NA Days |
| Cladribine Low/Low Dose (LLLL) | Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity | 10th percentile: ANC | NA Days |
| Cladribine Low/Low Dose (LLLL) | Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity | 20th percentile: ANC | NA Days |
| Cladribine Low/Low Dose (LLLL) | Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity | 25th percentile: ANC | NA Days |
| Cladribine Low/Low Dose (LLLL) | Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity | 50th percentile: ANC | NA Days |
| Cladribine Low/Low Dose (LLLL) | Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity | 75th percentile: ANC | NA Days |
| Cladribine Low/Low Dose (LLLL) | Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity | 10th percentile: Platelets | NA Days |
| Cladribine Low/Low Dose (LLLL) | Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity | 20th percentile: Platelets | NA Days |
| Cladribine Low/Low Dose (LLLL) | Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity | 25th percentile: Platelets | NA Days |
| Cladribine Low/Low Dose (LLLL) | Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity | 50th percentile: Platelets | NA Days |
| Cladribine Low/Low Dose (LLLL) | Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity | 75th percentile: Platelets | NA Days |
| Cladribine Low/Low Dose (LLLL) | Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity | 10th percentile: AST | NA Days |
| Cladribine Low/Low Dose (LLLL) | Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity | 20th percentile: AST | NA Days |
| Cladribine Low/Low Dose (LLLL) | Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity | 25th percentile: AST | NA Days |
| Cladribine Low/Low Dose (LLLL) | Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity | 50th percentile: AST | NA Days |
| Cladribine Low/Low Dose (LLLL) | Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity | 75th percentile: AST | NA Days |
| Cladribine High/Low Dose (HLLL) | Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity | 75th percentile: Lymphocytes Count | NA Days |
| Cladribine High/Low Dose (HLLL) | Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity | 25th percentile: ANC | NA Days |
| Cladribine High/Low Dose (HLLL) | Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity | 10th percentile: Hemoglobin | NA Days |
| Cladribine High/Low Dose (HLLL) | Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity | 10th percentile: Lymphocytes Count | 8 Days |
| Cladribine High/Low Dose (HLLL) | Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity | 50th percentile: ANC | NA Days |
| Cladribine High/Low Dose (HLLL) | Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity | 75th percentile: ANC | NA Days |
| Cladribine High/Low Dose (HLLL) | Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity | 25th percentile: AST | NA Days |
| Cladribine High/Low Dose (HLLL) | Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity | 10th percentile: Platelets | NA Days |
| Cladribine High/Low Dose (HLLL) | Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity | 20th percentile: Platelets | NA Days |
| Cladribine High/Low Dose (HLLL) | Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity | 75th percentile: ALT | NA Days |
| Cladribine High/Low Dose (HLLL) | Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity | 25th percentile: Platelets | NA Days |
| Cladribine High/Low Dose (HLLL) | Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity | 75th percentile: AST | NA Days |
| Cladribine High/Low Dose (HLLL) | Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity | 50th percentile: Platelets | NA Days |
| Cladribine High/Low Dose (HLLL) | Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity | 50th percentile: AST | NA Days |
| Cladribine High/Low Dose (HLLL) | Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity | 75th percentile: Platelets | NA Days |
| Cladribine High/Low Dose (HLLL) | Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity | 50th percentile: Lymphocytes Count | 449 Days |
| Cladribine High/Low Dose (HLLL) | Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity | 10th percentile: ALT | NA Days |
| Cladribine High/Low Dose (HLLL) | Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity | 20th percentile: ALT | NA Days |
| Cladribine High/Low Dose (HLLL) | Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity | 25th percentile: ALT | NA Days |
| Cladribine High/Low Dose (HLLL) | Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity | 25th percentile: Lymphocytes Count | 34 Days |
| Cladribine High/Low Dose (HLLL) | Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity | 50th percentile: ALT | NA Days |
| Cladribine High/Low Dose (HLLL) | Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity | 20th percentile: Lymphocytes Count | 15 Days |
| Cladribine High/Low Dose (HLLL) | Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity | 20th percentile: WBC | NA Days |
| Cladribine High/Low Dose (HLLL) | Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity | 10th percentile: WBC | NA Days |
| Cladribine High/Low Dose (HLLL) | Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity | 10th percentile: AST | NA Days |
| Cladribine High/Low Dose (HLLL) | Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity | 25th percentile: WBC | NA Days |
| Cladribine High/Low Dose (HLLL) | Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity | 50th percentile: WBC | NA Days |
| Cladribine High/Low Dose (HLLL) | Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity | 75th percentile: Hemoglobin | NA Days |
| Cladribine High/Low Dose (HLLL) | Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity | 75th percentile: WBC | NA Days |
| Cladribine High/Low Dose (HLLL) | Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity | 50th percentile: Hemoglobin | NA Days |
| Cladribine High/Low Dose (HLLL) | Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity | 10th percentile: ANC | NA Days |
| Cladribine High/Low Dose (HLLL) | Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity | 25th percentile: Hemoglobin | NA Days |
| Cladribine High/Low Dose (HLLL) | Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity | 20th percentile: AST | NA Days |
| Cladribine High/Low Dose (HLLL) | Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity | 20th percentile: ANC | NA Days |
| Cladribine High/Low Dose (HLLL) | Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity | 20th percentile: Hemoglobin | NA Days |
| Placebo/Cladribine Low Dose (PPLL) | Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity | 10th percentile: ANC | NA Days |
| Placebo/Cladribine Low Dose (PPLL) | Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity | 25th percentile: Hemoglobin | NA Days |
| Placebo/Cladribine Low Dose (PPLL) | Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity | 50th percentile: Hemoglobin | NA Days |
| Placebo/Cladribine Low Dose (PPLL) | Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity | 20th percentile: WBC | NA Days |
| Placebo/Cladribine Low Dose (PPLL) | Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity | 50th percentile: WBC | NA Days |
| Placebo/Cladribine Low Dose (PPLL) | Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity | 20th percentile: ANC | NA Days |
| Placebo/Cladribine Low Dose (PPLL) | Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity | 20th percentile: Hemoglobin | NA Days |
| Placebo/Cladribine Low Dose (PPLL) | Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity | 10th percentile: ALT | NA Days |
| Placebo/Cladribine Low Dose (PPLL) | Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity | 20th percentile: AST | NA Days |
| Placebo/Cladribine Low Dose (PPLL) | Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity | 25th percentile: Lymphocytes Count | 583 Days |
| Placebo/Cladribine Low Dose (PPLL) | Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity | 25th percentile: ANC | NA Days |
| Placebo/Cladribine Low Dose (PPLL) | Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity | 10th percentile: Hemoglobin | NA Days |
| Placebo/Cladribine Low Dose (PPLL) | Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity | 75th percentile: WBC | NA Days |
| Placebo/Cladribine Low Dose (PPLL) | Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity | 20th percentile: ALT | NA Days |
| Placebo/Cladribine Low Dose (PPLL) | Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity | 10th percentile: Lymphocytes Count | 362 Days |
| Placebo/Cladribine Low Dose (PPLL) | Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity | 50th percentile: ANC | NA Days |
| Placebo/Cladribine Low Dose (PPLL) | Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity | 75th percentile: Lymphocytes Count | NA Days |
| Placebo/Cladribine Low Dose (PPLL) | Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity | 50th percentile: Lymphocytes Count | NA Days |
| Placebo/Cladribine Low Dose (PPLL) | Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity | 75th percentile: AST | NA Days |
| Placebo/Cladribine Low Dose (PPLL) | Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity | 25th percentile: ALT | NA Days |
| Placebo/Cladribine Low Dose (PPLL) | Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity | 75th percentile: ANC | NA Days |
| Placebo/Cladribine Low Dose (PPLL) | Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity | 25th percentile: WBC | NA Days |
| Placebo/Cladribine Low Dose (PPLL) | Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity | 75th percentile: Hemoglobin | NA Days |
| Placebo/Cladribine Low Dose (PPLL) | Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity | 25th percentile: AST | NA Days |
| Placebo/Cladribine Low Dose (PPLL) | Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity | 50th percentile: ALT | NA Days |
| Placebo/Cladribine Low Dose (PPLL) | Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity | 20th percentile: Lymphocytes Count | 412 Days |
| Placebo/Cladribine Low Dose (PPLL) | Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity | 75th percentile: ALT | NA Days |
| Placebo/Cladribine Low Dose (PPLL) | Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity | 10th percentile: AST | NA Days |
| Placebo/Cladribine Low Dose (PPLL) | Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity | 10th percentile: WBC | NA Days |
| Placebo/Cladribine Low Dose (PPLL) | Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity | 50th percentile: AST | NA Days |
Primary
SAFUP Analysis Set: Number of Participants Who Developed Infections (Herpes Viral Infection, Viral Infectious Disorder and Opportunistic Infection), Infection-related Adverse Events and Malignancies
Number of participants who developed Herpes viral infection, Viral infectious disorder and Opportunistic infection were reported. Number of participants with infection related adverse events are the number of participants who had at least one adverse event coded to medical dictionary for regulatory activities (MedDRA) preferred terms under infection and infestation system organ class. Malignancy is defined as having at least one adverse event coded to MedDRA preferred terms under the pre-specified grouping Malignant and unspecified tumors.
Time frame: Baseline up to Week 120
Population: SAFUP Analysis Set included all participants who were enrolled and had at least one safety assessment, but were not randomized or assigned to treatment because they were not eligible to receive study medication.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cladribine Low/Placebo (LLPP) | SAFUP Analysis Set: Number of Participants Who Developed Infections (Herpes Viral Infection, Viral Infectious Disorder and Opportunistic Infection), Infection-related Adverse Events and Malignancies | Infections related adverse event | 11 Participants |
| Cladribine Low/Placebo (LLPP) | SAFUP Analysis Set: Number of Participants Who Developed Infections (Herpes Viral Infection, Viral Infectious Disorder and Opportunistic Infection), Infection-related Adverse Events and Malignancies | Viral infectious disorder | 6 Participants |
| Cladribine Low/Placebo (LLPP) | SAFUP Analysis Set: Number of Participants Who Developed Infections (Herpes Viral Infection, Viral Infectious Disorder and Opportunistic Infection), Infection-related Adverse Events and Malignancies | Herpes viral infection | 0 Participants |
| Cladribine Low/Placebo (LLPP) | SAFUP Analysis Set: Number of Participants Who Developed Infections (Herpes Viral Infection, Viral Infectious Disorder and Opportunistic Infection), Infection-related Adverse Events and Malignancies | Malignancies | 2 Participants |
| Cladribine Low/Placebo (LLPP) | SAFUP Analysis Set: Number of Participants Who Developed Infections (Herpes Viral Infection, Viral Infectious Disorder and Opportunistic Infection), Infection-related Adverse Events and Malignancies | Opportunistic infection | 0 Participants |
| Cladribine High Dose/Placebo (HLPP) | SAFUP Analysis Set: Number of Participants Who Developed Infections (Herpes Viral Infection, Viral Infectious Disorder and Opportunistic Infection), Infection-related Adverse Events and Malignancies | Opportunistic infection | 1 Participants |
| Cladribine High Dose/Placebo (HLPP) | SAFUP Analysis Set: Number of Participants Who Developed Infections (Herpes Viral Infection, Viral Infectious Disorder and Opportunistic Infection), Infection-related Adverse Events and Malignancies | Herpes viral infection | 1 Participants |
| Cladribine High Dose/Placebo (HLPP) | SAFUP Analysis Set: Number of Participants Who Developed Infections (Herpes Viral Infection, Viral Infectious Disorder and Opportunistic Infection), Infection-related Adverse Events and Malignancies | Viral infectious disorder | 5 Participants |
| Cladribine High Dose/Placebo (HLPP) | SAFUP Analysis Set: Number of Participants Who Developed Infections (Herpes Viral Infection, Viral Infectious Disorder and Opportunistic Infection), Infection-related Adverse Events and Malignancies | Infections related adverse event | 6 Participants |
| Cladribine High Dose/Placebo (HLPP) | SAFUP Analysis Set: Number of Participants Who Developed Infections (Herpes Viral Infection, Viral Infectious Disorder and Opportunistic Infection), Infection-related Adverse Events and Malignancies | Malignancies | 0 Participants |
| Cladribine Low/Low Dose (LLLL) | SAFUP Analysis Set: Number of Participants Who Developed Infections (Herpes Viral Infection, Viral Infectious Disorder and Opportunistic Infection), Infection-related Adverse Events and Malignancies | Malignancies | 1 Participants |
| Cladribine Low/Low Dose (LLLL) | SAFUP Analysis Set: Number of Participants Who Developed Infections (Herpes Viral Infection, Viral Infectious Disorder and Opportunistic Infection), Infection-related Adverse Events and Malignancies | Infections related adverse event | 12 Participants |
| Cladribine Low/Low Dose (LLLL) | SAFUP Analysis Set: Number of Participants Who Developed Infections (Herpes Viral Infection, Viral Infectious Disorder and Opportunistic Infection), Infection-related Adverse Events and Malignancies | Herpes viral infection | 1 Participants |
| Cladribine Low/Low Dose (LLLL) | SAFUP Analysis Set: Number of Participants Who Developed Infections (Herpes Viral Infection, Viral Infectious Disorder and Opportunistic Infection), Infection-related Adverse Events and Malignancies | Viral infectious disorder | 3 Participants |
| Cladribine Low/Low Dose (LLLL) | SAFUP Analysis Set: Number of Participants Who Developed Infections (Herpes Viral Infection, Viral Infectious Disorder and Opportunistic Infection), Infection-related Adverse Events and Malignancies | Opportunistic infection | 2 Participants |
Primary
SAFUP Analysis Set: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs
An AE was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered. SAE: Any AE that resulted in death; was life threatening; resulted in persistent/significant disability/incapacity; resulted in/prolonged an existing in-patient hospitalization; was a congenital anomaly/birth defect; or was a medically important condition. The term TEAE is defined as AEs starting or worsening after the first intake of the study drug. Number of participants with TEAEs included participants with both non-serious TEAEs and serious TEAEs.
Time frame: Baseline up to Week 120
Population: SAFUP Analysis Set included all participants who were enrolled and had at least one safety assessment, but were not randomized or assigned to treatment because they were not eligible to receive study medication.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cladribine Low/Placebo (LLPP) | SAFUP Analysis Set: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs | TEAEs | 16 Participants |
| Cladribine Low/Placebo (LLPP) | SAFUP Analysis Set: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs | Serious TEAEs | 2 Participants |
| Cladribine High Dose/Placebo (HLPP) | SAFUP Analysis Set: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs | TEAEs | 13 Participants |
| Cladribine High Dose/Placebo (HLPP) | SAFUP Analysis Set: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs | Serious TEAEs | 1 Participants |
| Cladribine Low/Low Dose (LLLL) | SAFUP Analysis Set: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs | TEAEs | 18 Participants |
| Cladribine Low/Low Dose (LLLL) | SAFUP Analysis Set: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs | Serious TEAEs | 3 Participants |