ORACLE MS: Oral Cladribine in Early Multiple Sclerosis (MS)

Sponsor

EMD Serono Research & Development Institute, Inc. (Industry)

Overall Status

Completed

CT.gov ID

NCT00725985

Collaborator

(none)

617

Enrollment

158

Locations

Arms

Actual Duration (Months)

3.9

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

A randomized, double-blind, clinical trial to assess the safety and efficacy of two doses of oral cladribine versus placebo in participants who had a first clinical demyelinating event (clinically isolated syndrome). Participants in either the cladribine or placebo group may also enter treatment periods with open-label interferon-beta or open-label cladribine depending upon the disease status. The primary objective of this study is to evaluate the effect of two dosage regimens of oral cladribine versus placebo on the time to conversion to multiple sclerosis (MS) (from randomization) according to the Poser criteria in participants with first clinical demyelinating event at high risk of converting to MS.

Condition or Disease	Intervention/Treatment	Phase
Multiple Sclerosis	Drug: Cladribine Drug: Placebo Drug: Rebif® new formulation (RNF)	Phase 3

Detailed Description

This will be a randomized, double blind, three-arm, placebo-controlled, multi-center trial to evaluate the safety and efficacy of oral cladribine versus placebo in the treatment of participants who have sustained a first clinical demyelinating event within 75 days prior to the Screening. Participants must have a minimum of 2 clinically silent lesions on the Screening magnetic resonance imaging (MRI).

The study will include a pre-study evaluation period (Screening period: between 10 and 28 days prior to the start of treatment with blinded study medication (oral cladribine or placebo).

Depending upon the clinical course of their MS, participants will then proceed from the ITP to either the Maintenance Treatment Period (with open-label interferon-beta treatment) or LTFU period (with either open-label low-dose cladribine or no additional treatment (if no progression to MS has been noted after the initial treatment period). The single primary endpoint for the overall study, which will be determined during the ITP, is time to conversion to MS (from randomization), according to the Poser criteria.

For every participants, eligibility for study enrollment and entry into each of the study periods, and diagnosis of conversion to either McDonald MS or CDMS must be confirmed and approved by a Sponsor appointed study Adjudication Committee.

Study Design

Study Type:

Interventional

Actual Enrollment :

617 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

A Phase III, Randomized, Double-blind, Placebo-controlled, Multi-center Clinical Trial of Oral Cladribine in Subjects With a First Clinical Event at High Risk of Converting to MS

Actual Study Start Date :

Dec 31, 2008

Actual Primary Completion Date :

Jul 31, 2011

Actual Study Completion Date :

Apr 30, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cladribine 5.25 mg/kg (ITP) Cladribine tablets administered as cumulative dose of 0.875 mg/kg over a course of 5 consecutive days at Weeks 1, 5, 9, 13, 48, and 52 resulting in total cladribine dose of 5.25 milligrams per kilograms (mg/kg) during the ITP of 96 weeks or until clinically definite multiple sclerosis (CDMS) conversion, whichever occurred first.	Drug: Cladribine Cladribine tablets were administered until CDMS conversion, whichever occur first. Drug: Rebif® new formulation (RNF) Participants who converted to CDMS during ITP entered in open-label maintenance period (OLMP) and received RNF subcutaneously at a dose of 44 microgram (mcg) three times a week. Participants who converted to CDMS during long-term follow-up (LTFU) period, received RNF subcutaneously at a dose of 44 mcg three times a week.
Experimental: Cladribine 3.5 mg/kg (ITP) Cladribine tablets administered as cumulative dose of 0.875 mg/kg over a course of 5 consecutive days at Weeks 1, 5, 48, 52 and placebo matched to cladribine tablets was administered at Week 9 and 13 resulting in total cladribine dose of 3.5 mg/kg during the ITP of 96 weeks or until CDMS conversion, whichever occurred first.	Drug: Cladribine Cladribine tablets were administered until CDMS conversion, whichever occur first. Drug: Rebif® new formulation (RNF) Participants who converted to CDMS during ITP entered in open-label maintenance period (OLMP) and received RNF subcutaneously at a dose of 44 microgram (mcg) three times a week. Participants who converted to CDMS during long-term follow-up (LTFU) period, received RNF subcutaneously at a dose of 44 mcg three times a week.
Placebo Comparator: Placebo (ITP) Placebo matched to cladribine tablets administered over a course of 5 consecutive days at Weeks 1, 5, 9, 13, 48 and 52 during the ITP of 96 weeks or until CDMS conversion, whichever occurred first.	Drug: Placebo Placebo matched to cladribine tablets were administered. Drug: Rebif® new formulation (RNF) Participants who converted to CDMS during ITP entered in open-label maintenance period (OLMP) and received RNF subcutaneously at a dose of 44 microgram (mcg) three times a week. Participants who converted to CDMS during long-term follow-up (LTFU) period, received RNF subcutaneously at a dose of 44 mcg three times a week.
Experimental: Cladribine 5.25 mg/kg, Rebif (OLMP) Participants who received cladribine 5.25 mg/kg and converted to CDMS during ITP entered in open-label maintenance period (OLMP) and received Rebif® new formulation (RNF) subcutaneously at a dose of 44 microgram (mcg) three times a week for up to 96 weeks. Due to trial termination, the OLMP duration was reduced for some participants.	Drug: Cladribine Cladribine tablets were administered until CDMS conversion, whichever occur first. Drug: Rebif® new formulation (RNF) Participants who converted to CDMS during ITP entered in open-label maintenance period (OLMP) and received RNF subcutaneously at a dose of 44 microgram (mcg) three times a week. Participants who converted to CDMS during long-term follow-up (LTFU) period, received RNF subcutaneously at a dose of 44 mcg three times a week.
Experimental: Cladribine 3.5 mg/kg, Rebif (OLMP) Participants who received cladribine 3.5 mg/kg and converted to CDMS during ITP entered in OLMP and received RNF subcutaneously at a dose of 44 mcg three times a week for up to 96 weeks. Due to trial termination, the OLMP duration was reduced for some participants.	Drug: Cladribine Cladribine tablets were administered until CDMS conversion, whichever occur first. Drug: Rebif® new formulation (RNF) Participants who converted to CDMS during ITP entered in open-label maintenance period (OLMP) and received RNF subcutaneously at a dose of 44 microgram (mcg) three times a week. Participants who converted to CDMS during long-term follow-up (LTFU) period, received RNF subcutaneously at a dose of 44 mcg three times a week.
Experimental: Placebo, Rebif (OLMP) Participants who received placebo and converted to CDMS during ITP entered in OLMP and received RNF subcutaneously at a dose of 44 mcg three times a week for up to 96 weeks. Due to trial termination, the OLMP duration was reduced for some participants.	Drug: Placebo Placebo matched to cladribine tablets were administered.
Experimental: Cladribine 5.25 mg/kg, Rebif, Cladribine 3.5 mg/kg (LTFU) Participants who received cladribine 5.25 mg/kg and did not convert to CDMS during ITP, entered in long-term follow-up (LTFU) period. Participants who converted to McDonald multiple sclerosis (MS) during ITP or during LTFU period received open-label cladribine tablets (3.5 mg/kg) during LTFU period. Participants who converted to CDMS during LTFU received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.	Drug: Cladribine Cladribine tablets were administered until CDMS conversion, whichever occur first. Drug: Rebif® new formulation (RNF) Participants who converted to CDMS during ITP entered in open-label maintenance period (OLMP) and received RNF subcutaneously at a dose of 44 microgram (mcg) three times a week. Participants who converted to CDMS during long-term follow-up (LTFU) period, received RNF subcutaneously at a dose of 44 mcg three times a week.
Experimental: Cladribine 3.5 mg/kg, Rebif, Cladribine 3.5 mg/kg (LTFU) Participants who received cladribine 3.5 mg/kg and did not convert to CDMS during ITP, entered in long-term follow-up (LTFU) period. Participants who converted to McDonald multiple sclerosis (MS) during ITP or during LTFU period received open-label cladribine tablets (3.5 mg/kg) during LTFU period. Participants who converted to CDMS during LTFU received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.	Drug: Cladribine Cladribine tablets were administered until CDMS conversion, whichever occur first. Drug: Rebif® new formulation (RNF) Participants who converted to CDMS during ITP entered in open-label maintenance period (OLMP) and received RNF subcutaneously at a dose of 44 microgram (mcg) three times a week. Participants who converted to CDMS during long-term follow-up (LTFU) period, received RNF subcutaneously at a dose of 44 mcg three times a week.
Experimental: Placebo, Rebif, Cladribine 3.5 mg/kg (LTFU) Participants who received placebo and did not convert to CDMS during ITP, entered in long-term follow-up (LTFU) period. Participants who converted to McDonald multiple sclerosis (MS) during ITP or during LTFU period received open-label cladribine tablets (3.5 mg/kg) during LTFU period. Participants who converted to CDMS during LTFU received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.	Drug: Placebo Placebo matched to cladribine tablets were administered.
Experimental: Cladribine 5.25 mg/kg, Rebif (LTFU) Participants who received cladribine 5.25 mg/kg and did not convert to CDMS during ITP, entered in LTFU period. Participants who did not convert to McDonald MS during ITP did not receive any treatment during LTFU period. Participants who converted to CDMS during LTFU period received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.	Drug: Cladribine Cladribine tablets were administered until CDMS conversion, whichever occur first. Drug: Rebif® new formulation (RNF) Participants who converted to CDMS during ITP entered in open-label maintenance period (OLMP) and received RNF subcutaneously at a dose of 44 microgram (mcg) three times a week. Participants who converted to CDMS during long-term follow-up (LTFU) period, received RNF subcutaneously at a dose of 44 mcg three times a week.
Experimental: Cladribine 3.5 mg/kg, Rebif (LTFU) Participants who received cladribine 3.5 mg/kg and did not convert to CDMS during ITP, entered in LTFU period. Participants who did not convert to McDonald MS during ITP did not receive any treatment during LTFU period. Participants who converted to CDMS during LTFU period received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.	Drug: Cladribine Cladribine tablets were administered until CDMS conversion, whichever occur first. Drug: Rebif® new formulation (RNF) Participants who converted to CDMS during ITP entered in open-label maintenance period (OLMP) and received RNF subcutaneously at a dose of 44 microgram (mcg) three times a week. Participants who converted to CDMS during long-term follow-up (LTFU) period, received RNF subcutaneously at a dose of 44 mcg three times a week.
Experimental: Placebo, Rebif (LTFU) Participants who received placebo and did not convert to CDMS during ITP, entered in LTFU period. Participants who did not convert to McDonald MS during ITP did not receive any treatment during LTFU period. Participants who convert to CDMS during LTFU period received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.	Drug: Placebo Placebo matched to cladribine tablets were administered.

Outcome Measures

Primary Outcome Measures

ITP: Time to Clinically Definite Multiple Sclerosis (CDMS) Conversion Represented by Kaplan-Meier Estimates of the Cumulative Percentage of Participants With CDMS [ITP: Baseline up to Week 96]
CDMS according to the Poser criteria is defined as the occurrence of a second attack or a sustained increase in the expanded disability status scale (EDSS) Score. EDSS assesses disability in 8 functional systems. An overall score ranging from 0 (normal) to 10 (death due to Multiple Sclerosis [MS]) was calculated. Sustained EDSS progression was defined as an increase in the EDSS score of greater than or equal to (>=) 1 point if baseline EDSS was between >= 1.0 and less than or equal to (=<) 4.5; or >= 1.5 points if baseline EDSS was 0, or >= 0.5 if baseline EDSS >= 5.0 over a period of at least 3 months. Kaplan-Meier estimates were provided for of the cumulative (cum.) percentage (%) of participants with CDMS over time. The probability of patients remaining event-free over time (from randomization) in each of the three treatment groups was displayed in the form of survival curves estimated using the non-parametric Kaplan-Meier method.

Secondary Outcome Measures

ITP: Time to Develop Multiple Sclerosis (MS) Conversion According to the Revised McDonald Criteria (2005) Represented by Kaplan-Meier Estimates of the Cumulative Percentage of Participants With McDonald MS [ITP: Baseline up to Week 96]
The McDonald criteria use dissemination in time and space established by magnetic resonance imaging (MRI) findings to provide a clinical diagnosis for MS. Dissemination in time is established by a new time constant 2 (T2) or gadolinium enhanced (Gd+) lesion found on a repeat MRI. Dissemination in space is established by the presence of any 3 of the following: 1 Gd+ lesion or 9 T2 bright lesions if there is no enhancement; greater than or equal to 1 infratentorial lesion; greater than or equal to 1 juxtacortical lesion; greater than or equal to 3 periventricular lesions. Kaplan-Meier estimates were provided for the cum. percentage (%) of participants with McDonald MS over time.
ITP: Number of Combined Unique Active (CUA) Lesions, New or Enlarging Time Constant 2 (T2) Lesions, and New or Persisting Time Constant 1 (T1) Gadolinium Enhanced (Gd+) Lesions Per Participant Per Scan [ITP: Baseline up to Week 96]
Number of CUA lesions, new or enlarging T2 lesions, and new or persisting T1 Gd+ lesions were measured by using magnetic resonance imaging (MRI) scans.
OLMP: Time to 3 Month Confirmed Expanded Disability Status Scale (EDSS) Progression From Randomization Represented by Kaplan-Meier Estimates of Probability of Disability Progression [OLMP: Day 1, 90, 180, 270, 360, 450, 540, 630, 720 and 810]
EDSS progression is based on a standardized neurological exam and focuses on symptoms that commonly occur in Multiple Sclerosis (MS). Overall scores ranges from 0.0 (normal) to 10.0 (death due to MS). A sustained progression on EDSS score was defined as an EDSS progression confirmed into two consecutive assessment. Probability of disability progression at different time points was estimated using Kaplan-Meier method on the time to disability progression defined as the time from randomization to first EDSS increase.
LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Time to Conversion to Multiple Sclerosis (MS) According to the 2005 McDonald Criteria [Time from Randomization up to 1217 days]
The McDonald criteria use dissemination in time and space established by magnetic resonance imaging (MRI) findings to provide a clinical diagnosis for MS. Dissemination in time is established by a new time constant 2 (T2) or gadolinium enhanced (Gd+) lesion found on a repeat MRI.
LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Time to Conversion to Clinically Definite Multiple Sclerosis (CDMS) According to Poser Criteria [Time from Randomization up to 1217 days]
CDMS according to the Poser criteria is defined as the occurrence of a second attack or a sustained increase in the expanded disability status scale (EDSS) Score. EDSS assesses disability in 8 functional systems. An overall score ranging from 0 (normal) to 10 (death due to MS) was calculated. Sustained EDSS progression was defined as an increase in the EDSS score of greater than or equal to (>=) 1 point if baseline EDSS was between >= 1.0 and less than or equal to (=<) 4.5; or >= 1.5 points if baseline EDSS was 0, or >= 0.5 if baseline EDSS >= 5.0 over a period of at least 3 months.
LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Time to Conversion to Clinically Definite Multiple Sclerosis (CDMS) According to Poser Criteria [Time from Randomization up to 1217 days]
CDMS according to the Poser criteria is defined as the occurrence of a second attack or a sustained increase in the expanded disability status scale (EDSS) Score. EDSS assesses disability in 8 functional systems. An overall score ranging from 0 (normal) to 10 (death due to MS) was calculated. Sustained EDSS progression was defined as an increase in the EDSS score of greater than or equal to (>=) 1 point if baseline EDSS was between >= 1.0 and less than or equal to (=<) 4.5; or >= 1.5 points if baseline EDSS was 0, or >= 0.5 if baseline EDSS >= 5.0 over a period of at least 3 months.
ITP: Percentage of Participants Converting to Clinically Definite Multiple Sclerosis (CDMS) as Per Poser Criteria [ITP: Baseline up to week 96]
Clinically definite multiple sclerosis (CDMS) according to the Poser criteria is defined as the occurrence of a second attack or a sustained increase in the expanded disability status scale (EDSS) Score. EDSS assesses disability in 8 functional systems. An overall score ranging from 0 (normal) to 10 (death due to MS) was calculated. Sustained EDSS progression was defined as an increase in the EDSS score of greater than or equal to (>=) 1 point if baseline EDSS was between >= 1.0 and less than or equal to (=<) 4.5; or >= 1.5 points if baseline EDSS was 0, or >= 0.5 if baseline EDSS >= 5.0 over a period of at least 3 months. The percentage of participants who converted to CDMS are reported here.
ITP: Percentage of Participants Converting to McDonald Multiple Sclerosis (MS) (2005) [ITP: Baseline up to week 96]
Percentage of participants converting to mcDonald multiple sclerosis (2005) were reported.
ITP: Number of New or Persisting Gd-enhanced Lesions [ITP: Week 13, 24, 36, 48, 60, 72, 84 and 96]
Number of new or persisting Gd-enhanced lesions were measured by using magnetic resonance imaging (MRI) scans.
OLMP: Number of New or Persisting Gd-enhanced Lesions [OLMP: Baseline, Week 24, 48, 72 and 96]
Number of new or persisting Gd-Enhanced lesions were measured by using magnetic resonance imaging (MRI) scans.
LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Number of New or Persisting Gd-enhanced Lesions [LTFU: Baseline, Week 13, 24 and 36]
Number of new or persisting Gd-Enhanced lesions were measured by using magnetic resonance imaging (MRI) scans.
LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Number of New or Persisting Gd-enhanced Lesions [LTFU: Baseline, Week 13, 24, 36 and 48]
Number of new or persisting Gd-Enhanced lesions were measured by using magnetic resonance imaging (MRI) scans.
ITP: Number of New or Enlarging T2 Lesions [ITP: Week 13, 24, 36, 48, 60, 72, 84 and 96]
Number of new or enlarging T2 lesions were measured by using magnetic resonance imaging (MRI) scans.
OLMP: Number of New or Enlarging T2 Lesions [OLMP: Baseline, Week 24, 48, 72 and 96]
Number of new or enlarging T2 lesions were measured by using magnetic resonance imaging (MRI) scans.
LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Number of New or Enlarging T2 Lesions [LTFU: Baseline, Week 13, 24 and 36]
Number of new or enlarging T2 Lesions were measured by using magnetic resonance imaging (MRI) scans.
LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Number of New or Enlarging T2 Lesions [LTFU: Baseline, Week 13, 24, 36 and 48]
Number of new or enlarging T2 lesions were measured by using magnetic resonance imaging (MRI) scans.
ITP: Number of Combined Unique Active (CUA) Magnetic Resonance Imaging (MRI) Lesions [ITP: Week 13, 24, 36, 48, 60, 72, 84 and 96]
Number of CUA lesions were measured by using magnetic resonance imaging (MRI) scans.
OLMP: Number of Combined Unique Active (CUA) Magnetic Resonance Imaging (MRI) Lesions [OLMP: Baseline, Week 24, 48, 72 and 96]
Number of combined unique active (CUA) lesions were measured by using magnetic resonance imaging (MRI) scans.
LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Number of Combined Unique Active (CUA) Magnetic Resonance Imaging (MRI) Lesions [LTFU: Baseline, Week 13, 24 and 36]
Number of CUA MRI lesions were measured by using magnetic resonance imaging (MRI) scans.
LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Number of Combined Unique Active (CUA) Magnetic Resonance Imaging (MRI) Lesions [LTFU: Baseline, Week 13, 24, 36 and 48]
Number of CUA lesions were measured by using magnetic resonance imaging (MRI) scans.
ITP: Change From Baseline in Volume of T1 Gd-Enhanced Lesions [ITP: Baseline, Week 96]
Change in volume of T1 Gd-Enhanced lesions was measured by using magnetic resonance imaging (MRI) scans.
OLMP: Mean Volume of T1 Gd-Enhanced Lesions and Changes From Baseline in Volume of T1 Gd-Enhanced Lesions [OLMP: Baseline, Week 24, 48, 72 and 96]
Volume of T1 Gd-Enhanced lesions was measured by using magnetic resonance imaging (MRI) scans.
LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Mean Volume of T1 Gd-Enhanced Lesions and Changes From Baseline in Volume of T1 Gd-Enhanced Lesions [LTFU: Baseline, Week 13, 24 and 36]
Volume of T1 Gd-Enhanced lesions was measured by using magnetic resonance imaging (MRI) scans.
LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Mean Volume of T1 Gd-Enhanced Lesions and Changes From Baseline in Volume of T1 Gd-Enhanced Lesions [LTFU: Baseline, Week 13, 24, 36 and 48]
Volume of T1 Gd-Enhanced lesions was measured by using magnetic resonance imaging (MRI) scans.
ITP: Changes From Baseline in Volume of T2 Lesions [ITP: Baseline, Week 48 and 96]
Change in volume of T2 lesions from baseline was measured by using magnetic resonance imaging (MRI) scans.
OLMP: Mean Volume of T2 Lesions and Changes From Baseline in Volume of T2 Lesions [OLMP: Baseline, Week 48 and 96]
Volume of T2 lesions was measured by using magnetic resonance imaging (MRI) scans.
LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Mean Volume of T2 Lesions [LTFU: Baseline (Day 1)]
Volume of T2 lesions was measured by using magnetic resonance imaging (MRI) scans.
LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Mean Volume of T2 Lesions and Changes From Baseline in Volume of T2 Lesions [Baseline, Week 48]
Volume of T2 lesions was measured by using magnetic resonance imaging (MRI) scans.
ITP: Number of T1 Hypointense Lesions [ITP: Baseline, Week 48 and 96]
Number of T1 Hypointense lesions were measured by using magnetic resonance imaging (MRI) scans.
OLMP: Number of T1 Hypointense Lesions [OLMP: Baseline, Week 48 and 96]
Number of T1 Hypointense lesions were measured by using magnetic resonance imaging (MRI) scans.
LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Number of T1 Hypointense Lesions [LTFU: Baseline (Day 1)]
Number of T1 Hypointense lesions were measured by using magnetic resonance imaging (MRI) scans.
LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Number of T1 Hypointense Lesions [LTFU: Baseline, Week 48]
Number of T1 Hypointense lesions were measured by using magnetic resonance imaging (MRI) scans.
ITP: Percentage of Participants With no New or Persisting T1 Gd-Enhanced Lesions [ITP: Baseline up to Week 96]
T1 Gd-enhanced lesions were measured by using magnetic resonance imaging (MRI) scans. Percentage of participants with no new or persisting T1 Gd-enhanced lesions were reported.
OLMP: Percentage of Participants With no New or Persisting T1 Gd-Enhanced Lesions [OLMP: Baseline up to Week 96]
T1 Gd-enhanced lesions were measured by using magnetic resonance imaging (MRI) scans. Percentage of participants with no new or persisting T1 Gd-enhanced lesions were reported.
LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Percentage of Participants With no New or Persisting T1 Gd-Enhanced Lesions [LTFU: Baseline up to Week 48]
T1 Gd-enhanced lesions were measured by using magnetic resonance imaging (MRI) scans. Percentage of participants with no new or persisting T1 Gd-enhanced lesions were reported.
LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Percentage of Participants With no New or Persisting T1 Gd-Enhanced Lesions [Baseline up to Week 48]
T1 Gd-enhanced lesions were measured by using magnetic resonance imaging (MRI) scans. Percentage of participants with no new or persisting T1 Gd-enhanced lesions were reported.
ITP: Percentage of Participants With no New or Enlarging T2 Lesions [ITP: Baseline up to Week 96]
T2 lesions were measured by using magnetic resonance imaging (MRI) scans. Percentage of participants with no new or enlarging T2 lesions were reported.
OLMP: Percentage of Participants With no New or Enlarging T2 Lesions [OLMP: Baseline up to 96]
T2 Gd-enhanced lesions were measured by using magnetic resonance imaging (MRI) scans. Percentage of participants with no new or enlarging T2 Lesions were reported.
LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Percentage of Participants With no New or Enlarging T2 Lesions [Baseline up to Week 48]
Enlarging T2 Lesions were measured by using magnetic resonance imaging (MRI) scans. Percentage of participants with no New or Enlarging T2 Lesions were reported.
LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Percentage of Participants With no New or Enlarging T2 Lesions [LTFU: Baseline up to Week 48]
Enlarging T2 lesions were measured by using magnetic resonance imaging (MRI) scans. Percentage of participants with no New or Enlarging T2 lesions were reported.
ITP: Percent Change From Baseline in Brain Volume [ITP: Baseline, Week 48 and 96]
Brain volume was measured by using magnetic resonance imaging (MRI) scans. Percent change from baseline in brain volume at Week 48 and 96 was reported.
OLMP: Percent Change From Baseline in Brain Volume [OLMP: Baseline, Week 48 and 96]
Brain volume was measured by using magnetic resonance imaging (MRI) scans. Percent change from baseline in brain volume at Week 48 and 96 was reported.
OLMP: Number of Relapses [Baseline up to Week 96]
Relapse was defined as new, worsening or recurrent neurological symptoms attributed to multiple sclerosis that last for at least 24 hours without fever or infection, or adverse reaction to prescribed medication, preceded by a stable or improving neurological status of at least 30 days.
LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Number of Relapses [Baseline up to Week 48]
Relapse was defined as new, worsening or recurrent neurological symptoms attributed to multiple sclerosis that last for at least 24 hours without fever or infection, or adverse reaction to prescribed medication, preceded by a stable or improving neurological status of at least 30 days.
LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Number of Relapses [Baseline up to Week 48]
Relapse was defined as new, worsening or recurrent neurological symptoms attributed to multiple sclerosis that last for at least 24 hours without fever or infection, or adverse reaction to prescribed medication, preceded by a stable or improving neurological status of at least 30 days.
OLMP: Annualized Relapse Rate [Baseline up to Week 96]
The annualized relapse rate for each treatment group was the mean of the annualized relapse rates for all the participants in the group, calculated as the total number of confirmed relapses divided by the total number of days on study multiplied by 365.25. Where, Relapse was defined as new, worsening or recurrent neurological symptoms attributed to multiple sclerosis that last for at least 24 hours without fever or infection, or adverse reaction to prescribed medication, preceded by a stable or improving neurological status of at least 30 days.
OLMP: Percentage of Relapse-Free Participants [Baseline up to Week 96]
Relapse was defined as new, worsening or recurrent neurological symptoms attributed to multiple sclerosis that last for at least 24 hours without fever or infection, or adverse reaction to prescribed medication, preceded by a stable or improving neurological status of at least 30 days. Percentage of relapse-free participants were reported.
ITP: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs [ITP: Baseline up to Week 96]
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. TEAEs include both Serious TEAEs and non-serious TEAEs. Number of Participants with TEAEs and serious TEAEs were reported.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 55 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Male or female between 18 and 55 years old, inclusive
Weighed between 40 to 120 kilogram (kg), inclusive
Participant has experienced a single, first clinical event suggestive of MS within 75 days prior to the Screening visit, (clock starts 24 hours after onset). The event must be a new neurological abnormality present for at least 24 hours, either mono- or polysymptomatic
Participant has at least two clinically silent lesions on the T2-weighted MRI scan, at screening, with a size of at least 3 millimeter (mm), at least one of which is ovoid or periventricular or infratentorial on screening MRI
Participant has EDSS 0 - 5.0 at Screening
Participant has no medical history or evidence of latent tuberculosis infection (LTBI) or active tubercular disease, as evidenced by the Mantoux tuberculosis (TB) skin test or a comparable sensitive test according to local regulations/guidelines (if the Mantoux test is not available), and/or a chest X-ray
Participant has normal hematological parameters at Screening, as defined by the central laboratory that performed all the assessments
If female, she must:
be neither pregnant nor breast-feeding, nor attempting to conceive and
use a highly effective method of contraception throughout the entire duration of the study and for 90 days following completion of the last dose of study medication. A highly effective method of contraception is defined as those which result in a low failure rate (that is less than 1 percent per year) when used consistently and correctly such as implants, injectables, combined oral contraceptives, some intrauterine devices, sexual abstinence or vasectomized partner, or
be post-menopausal or surgically sterilized (Note: for Danish sites only, participants should use a hormonal contraceptive or intrauterine device for the duration of the trial)
Male participants must be willing to use contraception to avoid impregnating partners throughout the study, and for 90 days following the last dose of study medication
Be willing and able to comply with study procedures for the duration of the study
Participant has to provide written informed consent voluntarily, including, for United states of America (USA), participant authorization under Health Insurance Portability and Accountability Act (HIPAA), prior to any study-related procedure that is not part of normal medical care
Participant has refused any treatment already available for clinically isolated syndrome (CIS) such as interferons or glatiramer acetate, at the time of entry into the Initial Treatment Period of this study

Exclusion Criteria:

Participant has a diagnosis of MS (per McDonald criteria, 2005)
Participant has any other disease that could better explain the participant's signs and symptoms
Participant has complete transverse myelitis or bilateral optic neuritis
Participant using or has used any other approved MS disease modifying drug (DMD)
Participant has used any investigational drug or undergone an experimental procedure within 12 weeks prior to Study day 1
Participant received oral or systemic corticosteroids or adrenocorticotropic hormone (ACTH) within 30 days prior to screening MRI. The MRI had to be performed 30 days after the oral or systemic corticosteroids or ACTH treatment. In case this interfered with MRI timing the screening period could be extended accordingly.
Participant has abnormal total bilirubin, or aspartate aminotransferase (AST) or alanine aminotransferase (ALT) or alkaline phosphatase greater than 2.5 times the upper limit of normal
Participant suffered from current autoimmune disease other than MS
Participant suffered from psychiatric illness (including history of, or concurrent, severe depressive disorders and/or suicidal ideation) that in the opinion of the investigator creates undue risk to the participant or could affect compliance with the study protocol
Participant suffered from major medical illness such as cardiac (for example angina, congestive heart failure or arrhythmia), endocrinologic, hepatic, immunologic, metabolic, renal, pulmonary, gastrointestinal, dermatologic, or other major disease that would preclude the administration of oral cladribine
Participant has a history of seizures not adequately controlled by medications
Participant has a known allergy to cladribine, interferon-beta, the excipient(s) of the study medications, or to gadolinium- diethylenetriamine penta-acetic acid (DTPA)
Participant has any renal condition that would preclude the administration of gadolinium (for example acute or chronic severe renal insufficiency (glomerular filtration rate [GFR] less than 30 milliliter per minute per 1.73 square meter [mL/min/1.73 m^2])
Participant has a history of chronic or clinically significant hematological abnormalities
Participant has a history of active or chronic infectious disease or any disease that compromises immune function (for example human immunodeficiency virus positive [HIV+], human T-lymphotrophic virus [HTLV-1], Lyme disease, latent tuberculosis infection [LTBI] or TB, insulin-dependent diabetes).
Participant has previously been screened in this study (signed an informed consent) and then withdrawn
Participant has received any immunomodulatory or immunosuppressive therapy) at any time prior to Study Day 1, including, but not limited to, the following products: any interferon, glatiramer acetate (Copolymer I), cyclophosphamide, cyclosporine, methotrexate, linomide, azathioprine, mitoxantrone, teriflunomide, laquinimod, cladribine, total lymphoid irradiation, anti-lymphocyte monoclonal antibody treatment (for example natalizumab, alemtuzumab/Campath, anti-cluster of differentiation 4 [CD4]), intravenous immunoglobulin G (IVIG), cytokines or anti-cytokine therapy
Participant has received experimental MS treatment
Participant has a history of alcohol or drug abuse
Participant has intolerance or any contraindication to both paracetamol (acetaminophen) and ibuprofen
Participant has inability to administer subcutaneous injections either by self or by caregiver
Participant has prior or current malignancy (with the exception of in situ basal or squamous cell skin cancer surgically removed without recurrence for at least five years)
Participant has a positive stool hemoccult test at Screening

Contacts and Locations

Locations

	Site	City	State	Country
1	Hope Research Institute Medical Plaza LLC Desert Hills	Phoenix	Arizona	United States
2	Multiple Sclerosis Center Drive, Neurology Suite 701	Newport Beach	California	United States
3	University of Colorado at Denver Health Sciences	Denver	Colorado	United States
4	Fort Collins Neurology	Fort Collins	Colorado	United States
5	MS Center of Brevard MIMA Centry Research Associates	Melbourne	Florida	United States
6	University of South Florida	Tampa	Florida	United States
7	MS Center of Atlanta	Atlanta	Georgia	United States
8	Bruce Hughes West Building	Des Moines	Iowa	United States
9	Michigan Neurology Associates	Clinton Township	Michigan	United States
10	Henry Ford Hospital	Detroit	Michigan	United States
11	University of Minnesota	Minneapolis	Minnesota	United States
12	Dennis Dietrich	Great Falls	Montana	United States
13	University of Medicine and Dentistry of New Jersey School of Neurology	Stratford	New Jersey	United States
14	Upstate Clinical Research LLC 3	Albany	New York	United States
15	Neurological Specialists of Long Island	Great Neck	New York	United States
16	Multiple Sclerosis Center of Northeastern NY	New York	New York	United States
17	Comprehensive MS Care Clinic at South Shore Multiple Sclerosis	Patchogue	New York	United States
18	Carolinas Medical Center	Charlotte	North Carolina	United States
19	Meritcare Neuroscience Center Neurology	Fargo	North Dakota	United States
20	University of Cincinnati	Cincinnati	Ohio	United States
21	MS Center of Oklahoma	Oklahoma City	Oklahoma	United States
22	Neurology and Sleep Medicine	Bethlehem	Pennsylvania	United States
23	Swedish Medical Center Cherry Hill	Seattle	Washington	United States
24	Neurology & Neurological Association of Tacoma	Tacoma	Washington	United States
25	Instituto Medico Rodriguez Alfici	Godoy Cruz		Argentina
26	Fundacion Rosarina de Neurorehabilitacion	Rosario		Argentina
27	Krankenhaus der Barmherzigen Brüder	Linz		Austria
28	Algemeen Ziekenhuis St Jan	Brugge		Belgium
29	Cliniques Universitaires St-Luc	Brussels		Belgium
30	Hopital Erasme	Bruxelles		Belgium
31	CHU de Liege - Domaine Universitaire du Sart Tilman,	Liège		Belgium
32	Clinical Center University of Sarajevo	Sarajevo		Bosnia and Herzegovina
33	Military Medical Academy- Sofia (MMA)	Pleven		Bulgaria
34	MBAL Rousse AD 1st	Rousse		Bulgaria
35	Central Clinic Hospital	Sofia		Bulgaria
36	Military Medical Academy	Sofia		Bulgaria
37	National Heart Hospital	Sofia		Bulgaria
38	Second MHAT	Sofia		Bulgaria
39	Tokuda Hospital	Sofia		Bulgaria
40	University Hospital St Naum	Sofia		Bulgaria
41	Medical Centre Centromed 2000	Veliko Tarnovo		Bulgaria
42	Ottawa General Hospital	Ottawa		Canada
43	General Hospital Varazdin	Varazdin		Croatia
44	University Hospital Zagreb	Zagreb		Croatia
45	Faculty Hospital Brno	Brno		Czechia
46	Neurological dept of Faculty	Hradec Kralove		Czechia
47	Fakultní nemocnice s poliklinikou Ostrava	Ostrava		Czechia
48	Faculty Hospital Motol	Prague		Czechia
49	Klinika Vseobecne	Prague		Czechia
50	Nemocnice Teplice	Teplice		Czechia
51	East Tallinn Central Hospital	Tallinn		Estonia
52	West Tallinn Central Hospital	Tallinn		Estonia
53	HUS Hyvinkaa Central Hospital	Hyvinkaa		Finland
54	OYKS Neurologian Klinikka	Oulu		Finland
55	Neurologian Klinikka Seinajoen Keskussairaala	Seinajoki		Finland
56	Tampere University Hospital	Tampere		Finland
57	Turun Yliopistollinen Keskussairaala Rakennus 3 1	Turku		Finland
58	CHU de Lille	Lille Cedex		France
59	CHU de Nantes	Nantes		France
60	American Memorial Hospital	Reims Cedex		France
61	David Tatishvili Medical Center	Tbilisi		Georgia
62	Medical Center Health	Tbilisi		Georgia
63	S. Khechinashvili Tbilisi State Medical University	Tbilisi		Georgia
64	Universitaetsklinikum und Medizinische Fakultaet Heidelberg	Heidelberg		Germany
65	Philipps-Universitaet Marburg	Marburg		Germany
66	M S Ramaiah Medical College Hospital	Bangalore	Karnataka	India
67	St.John's Medical College and Hospital	Bangalore	Karnataka	India
68	Amrita Institute of Medical Sciences and Research	Kochi	Kerala	India
69	Kovai Medical Centre and Hospital	Coimbatore		India
70	Sanjay Gandhi Post Graduate Institute of Medical Sciences	Lucknow		India
71	Mallikatta Neuro and Research Centre	Mangalore		India
72	Ospedale Regionale Torrette	Ancona		Italy
73	Università de Bari	Bari		Italy
74	Ospedale Binaghi Centro Sclerosi Multipla	Cagliari		Italy
75	Azienda Ospedaliera Garibaldi	Catania		Italy
76	Dipartimento di Neuroscienze	Catania		Italy
77	Università G. D'Annunzio	Chieti		Italy
78	Ospedale San Antonio Abate	Gallarate		Italy
79	Universita degli Studi di Genova	Genova		Italy
80	Ospedale e casa di riposo P. Richiedei	Gussago		Italy
81	Ospedale San Raffaele	Milano		Italy
82	Dipartimento di Scienze Neurologiche	Napoli		Italy
83	Azienda Sanitaria Ospedaliera San Luigi Gonzaga	Orbassano		Italy
84	Villa Sofia Hospital Azienda Ospedaliera Villa Sofia P.zza Salerno e Resuttana 1	Palermo		Italy
85	Istituto Neurologico C. Mondino	Pavia		Italy
86	Azienda Ospedaliera S. Camillo Forlanini	Roma		Italy
87	Azienda Ospedaliera Universitaria Policlinico Tor Vergata	Roma		Italy
88	Università di Roma La Sapienza	Roma		Italy
89	National Cancer Center, Department of Neurology,	Gyeonggi-do		Korea, Republic of
90	Department of Neurology, 50 Ilwon-dong, Gangnam-gu	Seoul		Korea, Republic of
91	Department of Neurology, Asan Medical Center, 388-1 Pungnap 2-dong, Songpa-gu	Seoul		Korea, Republic of
92	Seoul National University Hospital, Department of Neurology	Seoul		Korea, Republic of
93	Yonsei University Medical Center, Department of Neurology, Yonsei University Medical Center	Seoul		Korea, Republic of
94	American University of Beirut	Beirut		Lebanon
95	Clinic of Neurology "Klinicki Centar"	Skopje		North Macedonia
96	Helse Bergen HF Kvinneklinikken Haukeland Universitetssykehus Jonas	Bergen		Norway
97	Regionsykehuset I Trondheim, Nevrologisk avd.	Trondheim		Norway
98	10 Wojskowy Szpital Kliniczny	Bydgoszcz		Poland
99	Wojewodzki Szpital Specjalistyczny im. M. Kopernika	Gdansk		Poland
100	Niepubliczny Zespol Opieki Zdrowotnej	Krakow		Poland
101	Medical Academy of Lodz	Lodz		Poland
102	Panstwowy Szpital Kliniczny	Lublin		Poland
103	Wojewodzki Szpital Specjalistyczny Oddział Neurologii z Pododdziałem Udarowym	Olsztyn		Poland
104	Medical Academy	Poznan		Poland
105	Medical Academy II	Warsaw		Poland
106	Medical Academy	Warsaw		Poland
107	Hospital Fernando da Fonseca	Amadora		Portugal
108	Hospitais da Universidade de Coimbra	Coimbra		Portugal
109	Hospital de Santa Maria	Lisboa		Portugal
110	Centro Hospitalar de Coimbra	S. Martinho Do Bispo		Portugal
111	"Dr. Carol Davilla" Military Clinical Hospital	Bucharest		Romania
112	Centrul Medical SANA	Bucharest		Romania
113	Spitalul Clinic Judetean Mures	Targu-Mures		Romania
114	County Hospital Timisoara	Timisoara		Romania
115	Municipal Healthcare Institution "City Clinical Hospital #3"	Chelyabinsk		Russian Federation
116	State Healthcare Institution "Sverdlovsk Regional Clinical Hospital #1"	Ekaterinburg		Russian Federation
117	State Healthcare Institution "Kaluga Regional Hospital"	Kaluga		Russian Federation
118	State Medical Institution "Republican Rehabilitation Clinic of Tatarstan Ministry of Health"	Kazan		Russian Federation
119	State Healthcare Institution "Kemerovo Regional Clinical Hospital"	Kemerovo		Russian Federation
120	State Medical Institution " Jursk Regional Clinical Hospital"	Kursk		Russian Federation
121	Moscow State Healthcare Institution City Clinical Hospital #11	Moscow		Russian Federation
122	Non-State Healthcare Institution "Central Clinical Hospital #2 named after N.A. Semasko of Russian Railways"	Moscow		Russian Federation
123	State Educational Institute of Higher Professional Education "I.M. Sechenov Moscow Medical Academy of Roszdrav" Russia based on A. Ya. Kozhevnikov Nervous Disease Clinic	Moscow		Russian Federation
124	Municipal Treatment Prophylactic Institution "City Hospital #33"	Nizhny Novgorod		Russian Federation
125	Federal State Institution " Siberian Reginal Medical Center of Roszdarv"	Novosibirsk		Russian Federation
126	State institution Science Research Institute Clinical and Experimental Lymphology of Russian Academy of Medical Sciences	Novosibirsk		Russian Federation
127	State Educational Institute of Higher Professional Education "Rostov State Medical University of Roszdrav"	Rostov-on-Don		Russian Federation
128	State Healthcare Institution "Rostov Region Clinical Hospital"	Rostov-on-Don		Russian Federation
129	State Educational Institution of Higher Professional Education "Military Medical Academy named after S. M. Korov of Dept of Defense of Russian Federation based on Clinic of Neurology of State Institution	Saint-Petersburg		Russian Federation
130	State Educational Institution of Higher Professional Education "Samara State Medical University of Roszdrav" on State Healthcare Institution "Samara Regional Clinical Hospital named after M. I. Kalinin"	Samara		Russian Federation
131	State Educational Institution of Higher Professional Education "Saratov State Medical University of Roszdrav" based on Clincial Hosptial #3 of Saratov State Medical University	Saratov		Russian Federation
132	Regional State Healthcare Institution "State Smolensk Region Clinical Hospital"	Smolensk		Russian Federation
133	Institute of Human Brain of Russian Academy of Science Dept. of Multiple Sclerosis	St Petersburg		Russian Federation
134	International Clinic and Hospital, Neurology	St Petersburg		Russian Federation
135	St. Petersburg State Healthcare Institution "Multifield City Hospital #2"	St. Petersburg		Russian Federation
136	State Educational Institution of Higher Professional Education "Siberian State Medical University of Roszdrav"	Tomsk		Russian Federation
137	Closed joint-stock society Medical sanitary unit "Nephtaynik" based the hospital	Tyumen		Russian Federation
138	Vladimir Regional State Healthcare Institution "Regional Clinical Hospital"	Vladimir		Russian Federation
139	Municipal Healthcare Institution "Yaroslavi Clinical Hospital #8"	Yaroslavl		Russian Federation
140	Clinical Centre of Serbia	Belgrade		Serbia
141	Hospital for Prevention and Treatment of Cerebro-Vascular Diseases	Belgrade		Serbia
142	Clinical Centre Niš	Niš		Serbia
143	National Neuroscience Institute (TTSH Campus)	Singapore		Singapore
144	Hospital Reina Sofia Cordoba	Cordoba		Spain
145	Hospital Universitario Nuestra Senora de la Candelaria	Sta. Cruz de Tenerife		Spain
146	Sahlgrenskasjukhuset	Goteborg		Sweden
147	Karolinska University Hospital	Stockholm		Sweden
148	Umea University Hospital	Umea		Sweden
149	Taipei Veterans	Taipei		Taiwan
150	Chang Gung Medical Foundation- Linkou Branch No5	Taoyuan		Taiwan
151	Srinagarind Hospital	Khon Kaen		Thailand
152	Dokuz Eylul University	Izmir		Turkey
153	Ondokuz Mayis Universitesi	Samsun		Turkey
154	State Established "Institute of Neurology, Psychiatry and Narcology of the AMS of Ukraine", Depart of Neurinfections and Multiple Sclorosis	Kharkiv		Ukraine
155	Institue for Clinical Radiology of the State Establishment "Research Centre for Radiation Medicine of the AMS of Ukraino" Depart of Radiation Psychoneurology	Kiev		Ukraine
156	Vinnylsia Regional Psychoneurological Hosptial Named After O. I Yushchenko, Neurological Depart, Vinnytsia National Medical University Named After M. I. Pirogov, Chair of Neurology	Vinnitsa		Ukraine
157	Rashid Hospital	Dubai		United Arab Emirates
158	Kings College London	London		United Kingdom

Sponsors and Collaborators

EMD Serono Research & Development Institute, Inc.

Investigators

Study Director: Bettina Stubinski, MD, Merck Serono S.A., Geneva

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

Publications

None provided.

Responsible Party:

EMD Serono Research & Development Institute, Inc.

ClinicalTrials.gov Identifier:

NCT00725985

Other Study ID Numbers:

28821

First Posted:

Jul 31, 2008

Last Update Posted:

Mar 22, 2021

Last Verified:

Feb 1, 2021

Keywords provided by EMD Serono Research & Development Institute, Inc.

Clinically Isolated Syndrome (CIS)

Early MS

Multiple Sclerosis

Additional relevant MeSH terms:

Multiple Sclerosis

Sclerosis

Cladribine

Study Results

Participant Flow

Recruitment Details	A total of 617 participants were randomized for initial treatment period (ITP) and 616 participants received study drug.
Pre-assignment Detail

Arm/Group Title	Cladribine 5.25 mg/kg (ITP)	Cladribine 3.5 mg/kg (ITP)	Placebo (ITP)	Cladribine 5.25 mg/kg, Rebif (OLMP)	Cladribine 3.5 mg/kg, Rebif (OLMP)	Placebo, Rebif (OLMP)	Cladribine 5.25 mg/kg, Rebif, Cladribine 3.5 mg/kg (LTFU)	Cladribine 3.5 mg/kg, Rebif, Cladribine 3.5 mg/kg (LTFU)	Placebo, Rebif, Cladribine 3.5 mg/kg (LTFU)	Cladribine 5.25 mg/kg, Rebif (LTFU)	Cladribine 3.5 mg/kg, Rebif (LTFU)	Placebo, Rebif (LTFU)
Arm/Group Description	Cladribine tablets administered as cumulative dose of 0.875 milligrams per kilograms (mg/kg) over a course of 5 consecutive days at Weeks 1, 5, 9, 13, 48, and 52 resulting in total cladribine dose of 5.25 mg/kg during the ITP of 96 weeks or until clinically definite multiple sclerosis (CDMS) conversion, whichever occurred first.	Cladribine tablets administered as cumulative dose of 0.875 mg/kg over a course of 5 consecutive days at Weeks 1, 5, 48, 52 and placebo matched to cladribine tablets was administered at Week 9 and 13 resulting in total cladribine dose of 3.5 mg/kg during the ITP of 96 weeks or until CDMS conversion, whichever occurred first.	Placebo matched to cladribine tablets administered over a course of 5 consecutive days at Weeks 1, 5, 9, 13, 48 and 52 during the ITP of 96 weeks or until CDMS conversion, whichever occurred first.	Participants who received cladribine 5.25 mg/kg and converted to CDMS during ITP entered in open-label maintenance period (OLMP) and received Rebif® new formulation (RNF) subcutaneously at a dose of 44 microgram (mcg) three times a week for up to 96 weeks. Due to trial termination, the OLMP duration was reduced for some participants.	Participants who received cladribine 3.5 mg/kg and converted to CDMS during ITP entered in OLMP and received RNF subcutaneously at a dose of 44 mcg three times a week for up to 96 weeks. Due to trial termination, the OLMP duration was reduced for some participants.	Participants who received placebo and converted to CDMS during ITP entered in OLMP and received RNF subcutaneously at a dose of 44 mcg three times a week for up to 96 weeks. Due to trial termination, the OLMP duration was reduced for some participants.	Participants who received cladribine 5.25 mg/kg and did not convert to CDMS during ITP, entered in long-term follow-up (LTFU) period. Participants who converted to McDonald multiple sclerosis (MS) during ITP or during LTFU period received open-label cladribine tablets (3.5 mg/kg) during LTFU period. Participants who converted to CDMS during LTFU received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.	Participants who received cladribine 3.5 mg/kg and did not convert to CDMS during ITP, entered in long-term follow-up (LTFU) period. Participants who converted to McDonald multiple sclerosis (MS) during ITP or during LTFU period received open-label cladribine tablets (3.5 mg/kg) during LTFU period. Participants who converted to CDMS during LTFU received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.	Participants who received placebo and did not convert to CDMS during ITP, entered in long-term follow-up (LTFU) period. Participants who converted to McDonald multiple sclerosis (MS) during ITP or during LTFU period received open-label cladribine tablets (3.5 mg/kg) during LTFU period. Participants who converted to CDMS during LTFU received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.	Participants who received cladribine 5.25 mg/kg and did not convert to CDMS during ITP, entered in LTFU period. Participants who did not convert to McDonald MS during ITP did not receive any treatment during LTFU period. Participants who converted to CDMS during LTFU period received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.	Participants who received cladribine 3.5 mg/kg and did not convert to CDMS during ITP, entered in LTFU period. Participants who did not convert to McDonald MS during ITP did not receive any treatment during LTFU period. Participants who converted to CDMS during LTFU period received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.	Participants who received placebo and did not convert to CDMS during ITP, entered in LTFU period. Participants who did not convert to McDonald MS during ITP did not receive any treatment during LTFU period. Participants who convert to CDMS during LTFU period received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.
Period Title: ITP- Treatment Disposition
STARTED	205	206	206	0	0	0	0	0	0	0	0	0
Treated	204	206	206	0	0	0	0	0	0	0	0	0
COMPLETED	104	131	104	0	0	0	0	0	0	0	0	0
NOT COMPLETED	101	75	102	0	0	0	0	0	0	0	0	0
Period Title: ITP- Treatment Disposition
STARTED	0	0	0	24	25	60	0	0	0	0	0	0
COMPLETED	0	0	0	6	2	7	0	0	0	0	0	0
NOT COMPLETED	0	0	0	18	23	53	0	0	0	0	0	0
Period Title: ITP- Treatment Disposition
STARTED	0	0	0	0	0	0	9	9	17	0	0	0
COMPLETED	0	0	0	0	0	0	0	0	0	0	0	0
NOT COMPLETED	0	0	0	0	0	0	9	9	17	0	0	0
Period Title: ITP- Treatment Disposition
STARTED	0	0	0	0	0	0	0	0	0	34	36	14
COMPLETED	0	0	0	0	0	0	0	0	0	0	0	0
NOT COMPLETED	0	0	0	0	0	0	0	0	0	34	36	14

Baseline Characteristics

Arm/Group Title	Cladribine 5.25 mg/kg	Cladribine 3.5 mg/kg	Placebo	Total
Arm/Group Description	Cladribine tablets administered as cumulative dose of 0.875 mg/kg over a course of 5 consecutive days at Weeks 1, 5, 9, 13, 48, and 52 resulting in total cladribine dose of 5.25 mg/kg during the ITP of 96 weeks or until CDMS conversion, whichever occurred first. Participants who converted to CDMS during ITP entered OLMP and received RNF subcutaneously at a dose of 44 mcg three times a week for up to 96 weeks. Participants who did not convert to CDMS during ITP, entered in LTFU period. Participants who converted to McDonald MS during ITP or during LTFU period received open-label cladribine tablets (3.5 mg/kg) during LTFU period. Participants who did not convert to McDonald MS during ITP did not receive any treatment during LTFU period. Participants who converted to CDMS during LTFU received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period.	Cladribine tablets administered as cumulative dose of 0.875 mg/kg over a course of 5 consecutive days at Weeks 1, 5, 48, 52 and placebo matched to cladribine tablets was administered at Week 9 and 13 resulting in total cladribine dose of 3.5 mg/kg during the ITP of 96 weeks or until CDMS conversion, whichever occurred first. Participants who converted to CDMS during ITP entered OLMP and received RNF subcutaneously at a dose of 44 mcg three times a week for up to 96 weeks. Participants who did not convert to CDMS during ITP, entered in LTFU period. Participants who converted to McDonald MS during ITP or during LTFU period received open-label cladribine tablets (3.5 mg/kg) during LTFU period. Participants who did not convert to McDonald MS during ITP did not receive any study treatment during LTFU period. Participants who converted to CDMS during LTFU received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period.	Placebo matched to cladribine tablets administered over a course of 5 consecutive days at Weeks 1, 5, 9, 13, 48 and 52 during the ITP of 96 weeks or until CDMS conversion, whichever occurred first. Participants who converted to CDMS during ITP entered OLMP and received RNF subcutaneously at a dose of 44 mcg three times a week for up to 96 weeks. Participants who did not convert to CDMS during ITP, entered in LTFU period. Participants who converted to McDonald MS during ITP or during LTFU period received open-label cladribine tablets (3.5 mg/kg) during LTFU period. Participants who did not convert to McDonald MS during ITP did not receive any study treatment during LTFU period. Participants who converted to CDMS during LTFU received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period.	Total of all reporting groups
Overall Participants	204	206	206	616
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	31.9 (8.8)	31.7 (9.2)	32.2 (8.2)	31.9 (8.7)
Age, Customized (Count of Participants)
Greater than or equal to 30 years	111 54.4%	110 53.4%	113 54.9%	334 54.2%
Less than 30 years	93 45.6%	96 46.6%	93 45.1%	282 45.8%
Sex: Female, Male (Count of Participants)
Female	132 64.7%	130 63.1%	138 67%	400 64.9%
Male	72 35.3%	76 36.9%	68 33%	216 35.1%
Expanded disability status scale (EDSS) score (units on scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on scale]	1.6 (0.9)	1.6 (0.9)	1.7 (0.9)	1.6 (0.9)
Number of Time Constant 1 (T1) Gadolinium Enhanced (GD+) lesions (lesions) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [lesions]	1.9 (5.8)	1.5 (4.5)	0.9 (2.5)	1.4 (4.5)
Number of T2 Lesions (lesions) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [lesions]	29.7 (29.6)	26.8 (28.3)	26.3 (27.4)	27.6 (28.4)
Time from First Demyelinating Event to Randomization (Days) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Days]	79.35 (17.61)	78.67 (15.97)	79.40 (17.94)	79.14 (17.17)
Monofocal/Multifocal Classification (By Adjudication Committee) (Count of Participants)
Monofocal	108 52.9%	112 54.4%	101 49%	321 52.1%
Multifocal	96 47.1%	94 45.6%	105 51%	295 47.9%
Number of participants Using Steroid Treatment (Count of Participants)
Count of Participants [Participants]	133 65.2%	131 63.6%	140 68%	404 65.6%
Number of Participants with Time Constant 1 (T1) Gd-enhanced Lesions (Count of Participants)
Count of Participants [Participants]	90 44.1%	74 35.9%	73 35.4%	237 38.5%

Outcome Measures

1. Primary Outcome

Title	ITP: Time to Clinically Definite Multiple Sclerosis (CDMS) Conversion Represented by Kaplan-Meier Estimates of the Cumulative Percentage of Participants With CDMS
Description	CDMS according to the Poser criteria is defined as the occurrence of a second attack or a sustained increase in the expanded disability status scale (EDSS) Score. EDSS assesses disability in 8 functional systems. An overall score ranging from 0 (normal) to 10 (death due to Multiple Sclerosis [MS]) was calculated. Sustained EDSS progression was defined as an increase in the EDSS score of greater than or equal to (>=) 1 point if baseline EDSS was between >= 1.0 and less than or equal to (=<) 4.5; or >= 1.5 points if baseline EDSS was 0, or >= 0.5 if baseline EDSS >= 5.0 over a period of at least 3 months. Kaplan-Meier estimates were provided for of the cumulative (cum.) percentage (%) of participants with CDMS over time. The probability of patients remaining event-free over time (from randomization) in each of the three treatment groups was displayed in the form of survival curves estimated using the non-parametric Kaplan-Meier method.
Time Frame	ITP: Baseline up to Week 96

Outcome Measure Data

Analysis Population Description
The intent-to-treat (ITT) population included all randomized participants who received at least 1 dose of ITP study medication (cladribine or placebo).

Arm/Group Title	Cladribine 5.25 mg/kg (ITP)	Cladribine 3.5 mg/kg (ITP)	Placebo (ITP)
Arm/Group Description	Cladribine tablets administered as cumulative dose of 0.875 milligrams per kilograms (mg/kg) over a course of 5 consecutive days at Weeks 1, 5, 9, 13, 48, and 52 resulting in total cladribine dose of 5.25 mg/kg during the ITP of 96 weeks or until clinically definite multiple sclerosis (CDMS) conversion, whichever occurred first.	Cladribine tablets administered as cumulative dose of 0.875 mg/kg over a course of 5 consecutive days at Weeks 1, 5, 48, 52 and placebo matched to cladribine tablets was administered at Week 9 and 13 resulting in total cladribine dose of 3.5 mg/kg during the ITP of 96 weeks or until CDMS conversion, whichever occurred first.	Placebo matched to cladribine tablets administered over a course of 5 consecutive days at Weeks 1, 5, 9, 13, 48 and 52 during the ITP of 96 weeks or until CDMS conversion, whichever occurred first.
Measure Participants	204	206	206
Number [Cum. % of participants with CDMS]	15.8 7.7%	14.0 6.8%	37.8 18.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cladribine 5.25 mg/kg (ITP), Placebo (ITP)
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	The treatment effect was also assessed by hazard ratios using the Cox's proportional hazards model.
	Method	two-sided Wald test
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.381
	Confidence Interval	(2-Sided) 95% 0.248 to 0.584
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Cladribine 3.5 mg/kg (ITP), Placebo (ITP)
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments	The treatment effect was also assessed by hazard ratios using the Cox's proportional hazards model.
	Method	two-sided Wald test
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.327
	Confidence Interval	(2-Sided) 95% 0.210 to 0.509
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	ITP: Time to Develop Multiple Sclerosis (MS) Conversion According to the Revised McDonald Criteria (2005) Represented by Kaplan-Meier Estimates of the Cumulative Percentage of Participants With McDonald MS
Description	The McDonald criteria use dissemination in time and space established by magnetic resonance imaging (MRI) findings to provide a clinical diagnosis for MS. Dissemination in time is established by a new time constant 2 (T2) or gadolinium enhanced (Gd+) lesion found on a repeat MRI. Dissemination in space is established by the presence of any 3 of the following: 1 Gd+ lesion or 9 T2 bright lesions if there is no enhancement; greater than or equal to 1 infratentorial lesion; greater than or equal to 1 juxtacortical lesion; greater than or equal to 3 periventricular lesions. Kaplan-Meier estimates were provided for the cum. percentage (%) of participants with McDonald MS over time.
Time Frame	ITP: Baseline up to Week 96

Outcome Measure Data

Analysis Population Description
The ITT population included all randomized participants who received at least 1 dose of ITP study medication (cladribine or placebo).

Arm/Group Title	Cladribine 5.25 mg/kg (ITP)	Cladribine 3.5 mg/kg (ITP)	Placebo (ITP)
Arm/Group Description	Cladribine tablets administered as cumulative dose of 0.875 milligrams per kilograms (mg/kg) over a course of 5 consecutive days at Weeks 1, 5, 9, 13, 48, and 52 resulting in total cladribine dose of 5.25 mg/kg during the ITP of 96 weeks or until clinically definite multiple sclerosis (CDMS) conversion, whichever occurred first.	Cladribine tablets administered as cumulative dose of 0.875 mg/kg over a course of 5 consecutive days at Weeks 1, 5, 48, 52 and placebo matched to cladribine tablets was administered at Week 9 and 13 resulting in total cladribine dose of 3.5 mg/kg during the ITP of 96 weeks or until CDMS conversion, whichever occurred first.	Placebo matched to cladribine tablets administered over a course of 5 consecutive days at Weeks 1, 5, 9, 13, 48 and 52 during the ITP of 96 weeks or until CDMS conversion, whichever occurred first.
Measure Participants	204	206	206
Number [Cum. % of participants with McDonald MS]	51.36 25.2%	56.05 27.2%	87.14 42.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cladribine 5.25 mg/kg (ITP), Placebo (ITP)
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments	The treatment effect was also assessed by hazard ratios using the Cox's proportional hazards model.
	Method	two-sided Wald test
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.425
	Confidence Interval	(2-Sided) 95% 0.331 to 0.547
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Cladribine 3.5 mg/kg (ITP), Placebo (ITP)
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments	The treatment effect was also assessed by hazard ratios using the Cox's proportional hazards model.
	Method	two-sided Wald test
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.497
	Confidence Interval	(2-Sided) 95% 0.390 to 0.633
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	ITP: Number of Combined Unique Active (CUA) Lesions, New or Enlarging Time Constant 2 (T2) Lesions, and New or Persisting Time Constant 1 (T1) Gadolinium Enhanced (Gd+) Lesions Per Participant Per Scan
Description	Number of CUA lesions, new or enlarging T2 lesions, and new or persisting T1 Gd+ lesions were measured by using magnetic resonance imaging (MRI) scans.
Time Frame	ITP: Baseline up to Week 96

Outcome Measure Data

Analysis Population Description
The ITT population included all randomized participants who received at least 1 dose of ITP study medication (cladribine or placebo). Here "Number of participants analyzed" signifies those participants who were evaluable for this outcome measure.

Arm/Group Title	Cladribine 5.25 mg/kg (ITP)	Cladribine 3.5 mg/kg (ITP)	Placebo (ITP)
Arm/Group Description	Cladribine tablets administered as cumulative dose of 0.875 milligrams per kilograms (mg/kg) over a course of 5 consecutive days at Weeks 1, 5, 9, 13, 48, and 52 resulting in total cladribine dose of 5.25 mg/kg during the ITP of 96 weeks or until clinically definite multiple sclerosis (CDMS) conversion, whichever occurred first.	Cladribine tablets administered as cumulative dose of 0.875 mg/kg over a course of 5 consecutive days at Weeks 1, 5, 48, 52 and placebo matched to cladribine tablets was administered at Week 9 and 13 resulting in total cladribine dose of 3.5 mg/kg during the ITP of 96 weeks or until CDMS conversion, whichever occurred first.	Placebo matched to cladribine tablets administered over a course of 5 consecutive days at Weeks 1, 5, 9, 13, 48 and 52 during the ITP of 96 weeks or until CDMS conversion, whichever occurred first.
Measure Participants	203	202	196
CUA lesions	1.20 (5.79)	0.65 (1.80)	2.13 (2.87)
New or persisting T1 Gd+ lesions	0.61 (5.33)	0.29 (0.97)	0.97 (1.62)
New or enlarging T2 lesions	0.62 (1.90)	0.40 (1.12)	1.17 (1.87)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cladribine 3.5 mg/kg (ITP), Placebo (ITP)
	Comments	CUA lesions
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	Median Difference (Final Values)
	Estimated Value	-0.667
	Confidence Interval	(2-Sided) 95% -0.971 to -0.500
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Cladribine 5.25 mg/kg (ITP), Placebo (ITP)
	Comments	CUA lesions
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	Median Difference (Final Values)
	Estimated Value	-0.625
	Confidence Interval	(2-Sided) 95% -0.857 to -0.429
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Cladribine 3.5 mg/kg (ITP), Placebo (ITP)
	Comments	T1 Gd-Enhancing Lesions
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	Median Difference (Final Values)
	Estimated Value	-0.286
	Confidence Interval	(2-Sided) 95% -0.333 to -0.167
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Cladribine 5.25 mg/kg (ITP), Placebo (ITP)
	Comments	T1 Gd-Enhancing Lesions
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	Median Difference (Final Values)
	Estimated Value	-0.286
	Confidence Interval	(2-Sided) 95% -0.375 to -0.167
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Cladribine 3.5 mg/kg (ITP), Placebo (ITP)
	Comments	T2 Lesions
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	Median Difference (Final Values)
	Estimated Value	-0.333
	Confidence Interval	(2-Sided) 95% -0.500 to -0.167
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Cladribine 5.25 mg/kg (ITP), Placebo (ITP)
	Comments	T2 Lesions
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	Median Difference (Final Values)
	Estimated Value	-0.286
	Confidence Interval	(2-Sided) 95% -0.429 to -0.143
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	OLMP: Time to 3 Month Confirmed Expanded Disability Status Scale (EDSS) Progression From Randomization Represented by Kaplan-Meier Estimates of Probability of Disability Progression
Description	EDSS progression is based on a standardized neurological exam and focuses on symptoms that commonly occur in Multiple Sclerosis (MS). Overall scores ranges from 0.0 (normal) to 10.0 (death due to MS). A sustained progression on EDSS score was defined as an EDSS progression confirmed into two consecutive assessment. Probability of disability progression at different time points was estimated using Kaplan-Meier method on the time to disability progression defined as the time from randomization to first EDSS increase.
Time Frame	OLMP: Day 1, 90, 180, 270, 360, 450, 540, 630, 720 and 810

Outcome Measure Data

Analysis Population Description
OLMP Analysis Set included all participants who received at least 1 dose of study medication, converted to CDMS in the ITP period, entered the OLMP and received at least 1 dose of OLMP study drug (Rebif). Here "Number analyzed" signifies those participants who were evaluable at specified time point for this outcome measure.

Arm/Group Title	Cladribine 5.25 mg/kg, Rebif (OLMP)	Cladribine 3.5 mg/kg, Rebif (OLMP)	Placebo, Rebif (OLMP)
Arm/Group Description	Participants who received cladribine 5.25 mg/kg and converted to CDMS during ITP entered in open-label maintenance period (OLMP) and received Rebif® new formulation (RNF) subcutaneously at a dose of 44 microgram (mcg) three times a week for up to 96 weeks. Due to trial termination, the OLMP duration was reduced for some participants.	Participants who received cladribine 3.5 mg/kg and converted to CDMS during ITP entered in OLMP and received RNF subcutaneously at a dose of 44 mcg three times a week for up to 96 weeks. Due to trial termination, the OLMP duration was reduced for some participants.	Participants who received placebo and converted to CDMS during ITP entered in OLMP and received RNF subcutaneously at a dose of 44 mcg three times a week for up to 96 weeks. Due to trial termination, the OLMP duration was reduced for some participants.
Measure Participants	24	25	60
Day 1	0.0000	0.0000	0.0000
Day 90	0.0000	0.0000	0.0000
Day 180	0.0417	0.0417	0.0527
Day 270	0.0417	0.0417	0.0527
Day 360	0.0417	0.0417	0.0527
Day 450	0.0417	0.0417	0.0764
Day 540	0.0417	0.0417	0.1094
Day 630	0.0417	0.0417	0.1094
Day 720	0.0417	0.0417	0.1094

5. Secondary Outcome

Title	LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Time to Conversion to Multiple Sclerosis (MS) According to the 2005 McDonald Criteria
Description	The McDonald criteria use dissemination in time and space established by magnetic resonance imaging (MRI) findings to provide a clinical diagnosis for MS. Dissemination in time is established by a new time constant 2 (T2) or gadolinium enhanced (Gd+) lesion found on a repeat MRI.
Time Frame	Time from Randomization up to 1217 days

Outcome Measure Data

Analysis Population Description
LTFU analysis set (No Treatment at LTFU Entry) consists of all participants who completed the 96-week ITP and entered the LTFU for safety follow-up and did not receive study treatment upon entry to the LTFU. Here "Number of Participants analyzed" signifies those participants who have been converted to CDMS.

Arm/Group Title	Cladribine 5.25 mg/kg, Rebif (LTFU)	Cladribine 3.5 mg/kg, Rebif (LTFU)	Placebo, Rebif (LTFU)
Arm/Group Description	Participants who received cladribine 5.25 mg/kg and did not convert to CDMS during ITP, entered in LTFU period. Participants who did not convert to McDonald MS during ITP did not receive any treatment during LTFU period. Participants who converted to CDMS during LTFU period received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.	Participants who received cladribine 3.5 mg/kg and did not convert to CDMS during ITP, entered in LTFU period. Participants who did not convert to McDonald MS during ITP did not receive any treatment during LTFU period. Participants who converted to CDMS during LTFU period received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.	Participants who received placebo and did not convert to CDMS during ITP, entered in LTFU period. Participants who did not convert to McDonald MS during ITP did not receive any treatment during LTFU period. Participants who convert to CDMS during LTFU period received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.
Measure Participants	1	0	0
Number [Days]	773

6. Secondary Outcome

Title	LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Time to Conversion to Clinically Definite Multiple Sclerosis (CDMS) According to Poser Criteria
Description	CDMS according to the Poser criteria is defined as the occurrence of a second attack or a sustained increase in the expanded disability status scale (EDSS) Score. EDSS assesses disability in 8 functional systems. An overall score ranging from 0 (normal) to 10 (death due to MS) was calculated. Sustained EDSS progression was defined as an increase in the EDSS score of greater than or equal to (>=) 1 point if baseline EDSS was between >= 1.0 and less than or equal to (=<) 4.5; or >= 1.5 points if baseline EDSS was 0, or >= 0.5 if baseline EDSS >= 5.0 over a period of at least 3 months.
Time Frame	Time from Randomization up to 1217 days

Outcome Measure Data

Analysis Population Description
LTFU analysis set (No Treatment at LTFU Entry) was used. Here "Number of Participants Analyzed" signifies those participants who have been converted to CDMS.

Arm/Group Title	Cladribine 5.25 mg/kg, Rebif (LTFU)	Cladribine 3.5 mg/kg, Rebif (LTFU)	Placebo, Rebif (LTFU)
Arm/Group Description	Participants who received cladribine 5.25 mg/kg and did not convert to CDMS during ITP, entered in LTFU period. Participants who did not convert to McDonald MS during ITP did not receive any treatment during LTFU period. Participants who converted to CDMS during LTFU period received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.	Participants who received cladribine 3.5 mg/kg and did not convert to CDMS during ITP, entered in LTFU period. Participants who did not convert to McDonald MS during ITP did not receive any treatment during LTFU period. Participants who converted to CDMS during LTFU period received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.	Participants who received placebo and did not convert to CDMS during ITP, entered in LTFU period. Participants who did not convert to McDonald MS during ITP did not receive any treatment during LTFU period. Participants who convert to CDMS during LTFU period received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.
Measure Participants	1	0	0
Number [Days]	773

7. Secondary Outcome

Title	LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Time to Conversion to Clinically Definite Multiple Sclerosis (CDMS) According to Poser Criteria
Description	CDMS according to the Poser criteria is defined as the occurrence of a second attack or a sustained increase in the expanded disability status scale (EDSS) Score. EDSS assesses disability in 8 functional systems. An overall score ranging from 0 (normal) to 10 (death due to MS) was calculated. Sustained EDSS progression was defined as an increase in the EDSS score of greater than or equal to (>=) 1 point if baseline EDSS was between >= 1.0 and less than or equal to (=<) 4.5; or >= 1.5 points if baseline EDSS was 0, or >= 0.5 if baseline EDSS >= 5.0 over a period of at least 3 months.
Time Frame	Time from Randomization up to 1217 days

Outcome Measure Data

Analysis Population Description
LTFU analysis set (Treated at LTFU Entry) analysis set consisted of all participants who converted to McDonald MS (2005) during the ITP, completed ITP 96-weeks and entered the LTFU. Here "Number of Participants analyzed" signifies those participants who have been converted to CDMS.

Arm/Group Title	Cladribine 5.25 mg/kg, Rebif (LTFU)	Cladribine 3.5 mg/kg, Rebif (LTFU)	Placebo, Rebif (LTFU)
Arm/Group Description	Participants who received cladribine 5.25 mg/kg and did not convert to CDMS during ITP, entered in LTFU period. Participants who did not convert to McDonald MS during ITP did not receive any treatment during LTFU period. Participants who converted to CDMS during LTFU period received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.	Participants who received cladribine 3.5 mg/kg and did not convert to CDMS during ITP, entered in LTFU period. Participants who did not convert to McDonald MS during ITP did not receive any treatment during LTFU period. Participants who converted to CDMS during LTFU period received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.	Participants who received placebo and did not convert to CDMS during ITP, entered in LTFU period. Participants who did not convert to McDonald MS during ITP did not receive any treatment during LTFU period. Participants who convert to CDMS during LTFU period received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.
Measure Participants	0	0	1
Number [Days]	767

8. Secondary Outcome

Title	ITP: Percentage of Participants Converting to Clinically Definite Multiple Sclerosis (CDMS) as Per Poser Criteria
Description	Clinically definite multiple sclerosis (CDMS) according to the Poser criteria is defined as the occurrence of a second attack or a sustained increase in the expanded disability status scale (EDSS) Score. EDSS assesses disability in 8 functional systems. An overall score ranging from 0 (normal) to 10 (death due to MS) was calculated. Sustained EDSS progression was defined as an increase in the EDSS score of greater than or equal to (>=) 1 point if baseline EDSS was between >= 1.0 and less than or equal to (=<) 4.5; or >= 1.5 points if baseline EDSS was 0, or >= 0.5 if baseline EDSS >= 5.0 over a period of at least 3 months. The percentage of participants who converted to CDMS are reported here.
Time Frame	ITP: Baseline up to week 96

Outcome Measure Data

Analysis Population Description
ITT analysis set included all randomized participants who received at least 1 dose of ITP study medication (cladribine or placebo).

Arm/Group Title	Cladribine 5.25 mg/kg (ITP)	Cladribine 3.5 mg/kg (ITP)	Placebo (ITP)
Arm/Group Description	Cladribine tablets administered as cumulative dose of 0.875 milligrams per kilograms (mg/kg) over a course of 5 consecutive days at Weeks 1, 5, 9, 13, 48, and 52 resulting in total cladribine dose of 5.25 mg/kg during the ITP of 96 weeks or until clinically definite multiple sclerosis (CDMS) conversion, whichever occurred first.	Cladribine tablets administered as cumulative dose of 0.875 mg/kg over a course of 5 consecutive days at Weeks 1, 5, 48, 52 and placebo matched to cladribine tablets was administered at Week 9 and 13 resulting in total cladribine dose of 3.5 mg/kg during the ITP of 96 weeks or until CDMS conversion, whichever occurred first.	Placebo matched to cladribine tablets administered over a course of 5 consecutive days at Weeks 1, 5, 9, 13, 48 and 52 during the ITP of 96 weeks or until CDMS conversion, whichever occurred first.
Measure Participants	204	206	206
Number [Percentage of participants]	28.8 14.1%	23.1 11.2%	56.3 27.3%

9. Secondary Outcome

Title	ITP: Percentage of Participants Converting to McDonald Multiple Sclerosis (MS) (2005)
Description	Percentage of participants converting to mcDonald multiple sclerosis (2005) were reported.
Time Frame	ITP: Baseline up to week 96

Outcome Measure Data

Analysis Population Description
Intent-to-Treat analysis set included all randomized participants who received at least 1 dose of ITP study medication (cladribine or placebo).

Arm/Group Title	Cladribine 5.25 mg/kg (ITP)	Cladribine 3.5 mg/kg (ITP)	Placebo (ITP)
Arm/Group Description	Cladribine tablets administered as cumulative dose of 0.875 milligrams per kilograms (mg/kg) over a course of 5 consecutive days at Weeks 1, 5, 9, 13, 48, and 52 resulting in total cladribine dose of 5.25 mg/kg during the ITP of 96 weeks or until clinically definite multiple sclerosis (CDMS) conversion, whichever occurred first.	Cladribine tablets administered as cumulative dose of 0.875 mg/kg over a course of 5 consecutive days at Weeks 1, 5, 48, 52 and placebo matched to cladribine tablets was administered at Week 9 and 13 resulting in total cladribine dose of 3.5 mg/kg during the ITP of 96 weeks or until CDMS conversion, whichever occurred first.	Placebo matched to cladribine tablets administered over a course of 5 consecutive days at Weeks 1, 5, 9, 13, 48 and 52 during the ITP of 96 weeks or until CDMS conversion, whichever occurred first.
Measure Participants	204	206	206
Number [Percentage of participants]	70.7 34.7%	71.6 34.8%	91.8 44.6%

10. Secondary Outcome

Title	ITP: Number of New or Persisting Gd-enhanced Lesions
Description	Number of new or persisting Gd-enhanced lesions were measured by using magnetic resonance imaging (MRI) scans.
Time Frame	ITP: Week 13, 24, 36, 48, 60, 72, 84 and 96

Outcome Measure Data

Analysis Population Description
The intent-to-treat (ITT) population included all randomized participants who received at least 1 dose of ITP study medication (cladribine or placebo). Here "Number analyzed" signifies those participants who were evaluable at specified time point for this outcome measure.

Arm/Group Title	Cladribine 5.25 mg/kg (ITP)	Cladribine 3.5 mg/kg (ITP)	Placebo (ITP)
Arm/Group Description	Cladribine tablets administered as cumulative dose of 0.875 milligrams per kilograms (mg/kg) over a course of 5 consecutive days at Weeks 1, 5, 9, 13, 48, and 52 resulting in total cladribine dose of 5.25 mg/kg during the ITP of 96 weeks or until clinically definite multiple sclerosis (CDMS) conversion, whichever occurred first.	Cladribine tablets administered as cumulative dose of 0.875 mg/kg over a course of 5 consecutive days at Weeks 1, 5, 48, 52 and placebo matched to cladribine tablets was administered at Week 9 and 13 resulting in total cladribine dose of 3.5 mg/kg during the ITP of 96 weeks or until CDMS conversion, whichever occurred first.	Placebo matched to cladribine tablets administered over a course of 5 consecutive days at Weeks 1, 5, 9, 13, 48 and 52 during the ITP of 96 weeks or until CDMS conversion, whichever occurred first.
Measure Participants	204	206	206
Week 13	0.86 (5.60)	0.37 (1.52)	1.00 (1.98)
Week 24	0.03 (0.20)	0.13 (0.51)	0.92 (1.69)
Week 36	0.08 (0.38)	0.14 (0.44)	0.74 (1.28)
Week 48	0.02 (0.13)	0.27 (0.92)	0.87 (1.81)
Week 60	0.10 (0.84)	0.22 (0.94)	0.74 (1.61)
Week 72	0.05 (0.53)	0.16 (0.81)	0.90 (1.88)
Week 84	0.02 (0.13)	0.32 (2.62)	0.60 (1.20)
Week 96	0.07 (0.43)	0.18 (0.84)	0.64 (1.25)

11. Secondary Outcome

Title	OLMP: Number of New or Persisting Gd-enhanced Lesions
Description	Number of new or persisting Gd-Enhanced lesions were measured by using magnetic resonance imaging (MRI) scans.
Time Frame	OLMP: Baseline, Week 24, 48, 72 and 96

Outcome Measure Data

Analysis Population Description
OLMP Analysis Set included all participants who received at least 1 dose of study drug, converted to CDMS in ITP period, entered OLMP and received at least 1 dose of OLMP study drug. Here "Number of participants analyzed" = participants who were evaluable for this outcome measure and "Number analyzed" = who were evaluable at specified time point.

Arm/Group Title	Cladribine 5.25 mg/kg, Rebif (OLMP)	Cladribine 3.5 mg/kg, Rebif (OLMP)	Placebo, Rebif (OLMP)
Arm/Group Description	Participants who received cladribine 5.25 mg/kg and converted to CDMS during ITP entered in open-label maintenance period (OLMP) and received Rebif® new formulation (RNF) subcutaneously at a dose of 44 microgram (mcg) three times a week for up to 96 weeks. Due to trial termination, the OLMP duration was reduced for some participants.	Participants who received cladribine 3.5 mg/kg and converted to CDMS during ITP entered in OLMP and received RNF subcutaneously at a dose of 44 mcg three times a week for up to 96 weeks. Due to trial termination, the OLMP duration was reduced for some participants.	Participants who received placebo and converted to CDMS during ITP entered in OLMP and received RNF subcutaneously at a dose of 44 mcg three times a week for up to 96 weeks. Due to trial termination, the OLMP duration was reduced for some participants.
Measure Participants	24	24	59
Baseline	1.38 (5.52)	0.88 (1.80)	1.27 (2.58)
Week 24	0.17 (0.48)	0.05 (0.21)	0.11 (0.56)
Week 48	0.07 (0.24)	0.00 (0.00)	0.20 (0.50)
Week 72	1.50 (3.28)	0.13 (0.35)	0.33 (1.18)
Week 96	1.58 (2.69)	0.00 (0.00)	0.07 (0.26)

12. Secondary Outcome

Title	LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Number of New or Persisting Gd-enhanced Lesions
Description	Number of new or persisting Gd-Enhanced lesions were measured by using magnetic resonance imaging (MRI) scans.
Time Frame	LTFU: Baseline, Week 13, 24 and 36

Outcome Measure Data

Analysis Population Description
LTFU analysis set (Treated at LTFU Entry) analysis set consisted of all participants who converted to McDonald MS (2005) during the ITP, completed ITP 96-weeks and entered the LTFU. Here "Number analyzed" signifies those participants who were evaluable at specified time point for this outcome measure.

Arm/Group Title	Cladribine 5.25 mg/kg, Rebif, Cladribine 3.5 mg/kg (LTFU)	Cladribine 3.5 mg/kg, Rebif, Cladribine 3.5 mg/kg (LTFU)	Placebo, Rebif, Cladribine 3.5 mg/kg (LTFU)
Arm/Group Description	Participants who received cladribine 5.25 mg/kg and did not convert to CDMS during ITP, entered in long-term follow-up (LTFU) period. Participants who converted to McDonald multiple sclerosis (MS) during ITP or during LTFU period received open-label cladribine tablets (3.5 mg/kg) during LTFU period. Participants who converted to CDMS during LTFU received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.	Participants who received cladribine 3.5 mg/kg and did not convert to CDMS during ITP, entered in long-term follow-up (LTFU) period. Participants who converted to McDonald multiple sclerosis (MS) during ITP or during LTFU period received open-label cladribine tablets (3.5 mg/kg) during LTFU period. Participants who converted to CDMS during LTFU received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.	Participants who received placebo and did not convert to CDMS during ITP, entered in long-term follow-up (LTFU) period. Participants who converted to McDonald multiple sclerosis (MS) during ITP or during LTFU period received open-label cladribine tablets (3.5 mg/kg) during LTFU period. Participants who converted to CDMS during LTFU received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.
Measure Participants	9	9	17
Baseline	0.00 (0.00)	0.00 (0.00)	0.71 (1.16)
Week 13	0.00 (0.00)	0.00 (0.00)	0.13 (0.34)
Week 24	0.00 (0.00)	0.00 (0.00)	0.18 (0.40)
Week 36	0.00 (0.00)	0.00 (0.00)	0.00 (0.00)

13. Secondary Outcome

Title	LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Number of New or Persisting Gd-enhanced Lesions
Description	Number of new or persisting Gd-Enhanced lesions were measured by using magnetic resonance imaging (MRI) scans.
Time Frame	LTFU: Baseline, Week 13, 24, 36 and 48

Outcome Measure Data

Analysis Population Description
LTFU analysis set (No Treatment at LTFU Entry) was used. Here "Number analyzed" signifies those participants who were evaluable at specified time point for this outcome measure.

Arm/Group Title	Cladribine 5.25 mg/kg, Rebif (LTFU)	Cladribine 3.5 mg/kg, Rebif (LTFU)	Placebo, Rebif (LTFU)
Arm/Group Description	Participants who received cladribine 5.25 mg/kg and did not convert to CDMS during ITP, entered in LTFU period. Participants who did not convert to McDonald MS during ITP did not receive any treatment during LTFU period. Participants who converted to CDMS during LTFU period received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.	Participants who received cladribine 3.5 mg/kg and did not convert to CDMS during ITP, entered in LTFU period. Participants who did not convert to McDonald MS during ITP did not receive any treatment during LTFU period. Participants who converted to CDMS during LTFU period received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.	Participants who received placebo and did not convert to CDMS during ITP, entered in LTFU period. Participants who did not convert to McDonald MS during ITP did not receive any treatment during LTFU period. Participants who convert to CDMS during LTFU period received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.
Measure Participants	34	36	14
Baseline	0.00 (0.00)	0.06 (0.23)	0.14 (0.36)
Week 13	0.00 (0.00)	0.07 (0.23)	0.09 (0.30)
Week 24	0.00 (0.00)	0.00 (0.00)	0.20 (0.45)
Week 36	0.00 (0.00)	0.00 (0.00)	0.17 (0.29)
Week 48	0.00

14. Secondary Outcome

Title	ITP: Number of New or Enlarging T2 Lesions
Description	Number of new or enlarging T2 lesions were measured by using magnetic resonance imaging (MRI) scans.
Time Frame	ITP: Week 13, 24, 36, 48, 60, 72, 84 and 96

Outcome Measure Data

Analysis Population Description
The intent-to-treat (ITT) population included all randomized participants who received at least 1 dose of ITP study medication (cladribine or placebo). Here "Number analyzed" signifies those participants who were evaluable at specified time point for this outcome measure.

Arm/Group Title	Cladribine 5.25 mg/kg (ITP)	Cladribine 3.5 mg/kg (ITP)	Placebo (ITP)
Arm/Group Description	Cladribine tablets administered as cumulative dose of 0.875 milligrams per kilograms (mg/kg) over a course of 5 consecutive days at Weeks 1, 5, 9, 13, 48, and 52 resulting in total cladribine dose of 5.25 mg/kg during the ITP of 96 weeks or until clinically definite multiple sclerosis (CDMS) conversion, whichever occurred first.	Cladribine tablets administered as cumulative dose of 0.875 mg/kg over a course of 5 consecutive days at Weeks 1, 5, 48, 52 and placebo matched to cladribine tablets was administered at Week 9 and 13 resulting in total cladribine dose of 3.5 mg/kg during the ITP of 96 weeks or until CDMS conversion, whichever occurred first.	Placebo matched to cladribine tablets administered over a course of 5 consecutive days at Weeks 1, 5, 9, 13, 48 and 52 during the ITP of 96 weeks or until CDMS conversion, whichever occurred first.
Measure Participants	204	206	206
Week 13	1.56 (3.52)	1.25 (3.33)	1.43 (2.56)
Week 24	0.24 (0.95)	0.20 (0.66)	1.01 (1.70)
Week 36	0.09 (0.40)	0.12 (0.42)	1.14 (1.87)
Week 48	0.07 (0.50)	0.32 (2.52)	1.04 (1.54)
Week 60	0.13 (0.63)	0.25 (1.09)	0.71 (1.57)
Week 72	0.03 (0.22)	0.10 (0.34)	0.83 (1.77)
Week 84	0.09 (0.46)	0.28 (2.03)	0.61 (1.31)
Week 96	0.04 (0.25)	0.10 (0.59)	0.38 (0.85)

15. Secondary Outcome

Title	OLMP: Number of New or Enlarging T2 Lesions
Description	Number of new or enlarging T2 lesions were measured by using magnetic resonance imaging (MRI) scans.
Time Frame	OLMP: Baseline, Week 24, 48, 72 and 96

Outcome Measure Data

Analysis Population Description
OLMP Analysis Set included all participants who received at least 1 dose of study drug, converted to CDMS in ITP period, entered OLMP and received at least 1 dose of OLMP study drug. Here "Number of participants analyzed" = participants who were evaluable for this outcome measure and "Number analyzed" = who were evaluable at specified time point.

Arm/Group Title	Cladribine 5.25 mg/kg, Rebif (OLMP)	Cladribine 3.5 mg/kg, Rebif (OLMP)	Placebo, Rebif (OLMP)
Arm/Group Description	Participants who received cladribine 5.25 mg/kg and converted to CDMS during ITP entered in open-label maintenance period (OLMP) and received Rebif® new formulation (RNF) subcutaneously at a dose of 44 microgram (mcg) three times a week for up to 96 weeks. Due to trial termination, the OLMP duration was reduced for some participants.	Participants who received cladribine 3.5 mg/kg and converted to CDMS during ITP entered in OLMP and received RNF subcutaneously at a dose of 44 mcg three times a week for up to 96 weeks. Due to trial termination, the OLMP duration was reduced for some participants.	Participants who received placebo and converted to CDMS during ITP entered in OLMP and received RNF subcutaneously at a dose of 44 mcg three times a week for up to 96 weeks. Due to trial termination, the OLMP duration was reduced for some participants.
Measure Participants	24	24	60
Baseline	0.29 (0.75)	1.54 (6.72)	2.13 (7.29)
Week 24	0.26 (0.69)	0.43 (1.35)	0.68 (1.10)
Week 48	0.32 (0.65)	0.38 (1.09)	0.41 (0.71)
Week 72	0.95 (1.85)	0.25 (0.46)	0.97 (1.69)
Week 96	2.00 (3.52)	0.67 (1.15)	0.47 (1.06)

16. Secondary Outcome

Title	LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Number of New or Enlarging T2 Lesions
Description	Number of new or enlarging T2 Lesions were measured by using magnetic resonance imaging (MRI) scans.
Time Frame	LTFU: Baseline, Week 13, 24 and 36

Outcome Measure Data

Analysis Population Description
LTFU analysis set (Treated at LTFU Entry) analysis set consisted of all participants who converted to McDonald MS (2005) during the ITP, completed ITP 96-weeks and entered the LTFU. Here "Number analyzed" signifies those participants who were evaluable at specified time point for this outcome measure.

Arm/Group Title	Cladribine 5.25 mg/kg, Rebif, Cladribine 3.5 mg/kg (LTFU)	Cladribine 3.5 mg/kg, Rebif, Cladribine 3.5 mg/kg (LTFU)	Placebo, Rebif, Cladribine 3.5 mg/kg (LTFU)
Arm/Group Description	Participants who received cladribine 5.25 mg/kg and did not convert to CDMS during ITP, entered in long-term follow-up (LTFU) period. Participants who converted to McDonald multiple sclerosis (MS) during ITP or during LTFU period received open-label cladribine tablets (3.5 mg/kg) during LTFU period. Participants who converted to CDMS during LTFU received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.	Participants who received cladribine 3.5 mg/kg and did not convert to CDMS during ITP, entered in long-term follow-up (LTFU) period. Participants who converted to McDonald multiple sclerosis (MS) during ITP or during LTFU period received open-label cladribine tablets (3.5 mg/kg) during LTFU period. Participants who converted to CDMS during LTFU received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.	Participants who received placebo and did not convert to CDMS during ITP, entered in long-term follow-up (LTFU) period. Participants who converted to McDonald multiple sclerosis (MS) during ITP or during LTFU period received open-label cladribine tablets (3.5 mg/kg) during LTFU period. Participants who converted to CDMS during LTFU received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.
Measure Participants	9	9	17
Baseline	0.00 (0.00)	0.00 (0.00)	0.71 (1.53)
Week 13	0.00 (0.00)	0.25 (0.46)	2.06 (4.25)
Week 24	0.00 (0.00)	0.00 (0.00)	0.00 (0.00)
Week 36	0.00 (0.00)	0.00 (0.00)	0.10 (0.32)

17. Secondary Outcome

Title	LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Number of New or Enlarging T2 Lesions
Description	Number of new or enlarging T2 lesions were measured by using magnetic resonance imaging (MRI) scans.
Time Frame	LTFU: Baseline, Week 13, 24, 36 and 48

Outcome Measure Data

Analysis Population Description
LTFU analysis set (No Treatment at LTFU Entry) was used. Here "Number analyzed" signifies those participants who were evaluable at specified time point for this outcome measure.

Arm/Group Title	Cladribine 5.25 mg/kg, Rebif (LTFU)	Cladribine 3.5 mg/kg, Rebif (LTFU)	Placebo, Rebif (LTFU)
Arm/Group Description	Participants who received cladribine 5.25 mg/kg and did not convert to CDMS during ITP, entered in LTFU period. Participants who did not convert to McDonald MS during ITP did not receive any treatment during LTFU period. Participants who converted to CDMS during LTFU period received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.	Participants who received cladribine 3.5 mg/kg and did not convert to CDMS during ITP, entered in LTFU period. Participants who did not convert to McDonald MS during ITP did not receive any treatment during LTFU period. Participants who converted to CDMS during LTFU period received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.	Participants who received placebo and did not convert to CDMS during ITP, entered in LTFU period. Participants who did not convert to McDonald MS during ITP did not receive any treatment during LTFU period. Participants who convert to CDMS during LTFU period received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.
Measure Participants	34	36	14
Baseline	0.00 (0.00)	0.03 (0.17)	0.07 (0.27)
Week 13	0.00 (0.00)	0.04 (0.21)	0.18 (0.40)
Week 24	0.00 (0.00)	0.13 (0.35)	0.00 (0.00)
Week 36	0.00 (0.00)	0.00 (0.00)	0.33 (0.58)
Week 48	0.00

18. Secondary Outcome

Title	ITP: Number of Combined Unique Active (CUA) Magnetic Resonance Imaging (MRI) Lesions
Description	Number of CUA lesions were measured by using magnetic resonance imaging (MRI) scans.
Time Frame	ITP: Week 13, 24, 36, 48, 60, 72, 84 and 96

Outcome Measure Data

Analysis Population Description
ITT population included all randomized participants who received at least 1 dose of ITP study medication. Here "Number of participants analyzed" signifies those who were evaluable for this outcome measure and "Number analyzed" signifies those participants who were evaluable at specified time point.

Arm/Group Title	Cladribine 5.25 mg/kg (ITP)	Cladribine 3.5 mg/kg (ITP)	Placebo (ITP)
Arm/Group Description	Cladribine tablets administered as cumulative dose of 0.875 milligrams per kilograms (mg/kg) over a course of 5 consecutive days at Weeks 1, 5, 9, 13, 48, and 52 resulting in total cladribine dose of 5.25 mg/kg during the ITP of 96 weeks or until clinically definite multiple sclerosis (CDMS) conversion, whichever occurred first.	Cladribine tablets administered as cumulative dose of 0.875 mg/kg over a course of 5 consecutive days at Weeks 1, 5, 48, 52 and placebo matched to cladribine tablets was administered at Week 9 and 13 resulting in total cladribine dose of 3.5 mg/kg during the ITP of 96 weeks or until CDMS conversion, whichever occurred first.	Placebo matched to cladribine tablets administered over a course of 5 consecutive days at Weeks 1, 5, 9, 13, 48 and 52 during the ITP of 96 weeks or until CDMS conversion, whichever occurred first.
Measure Participants	189	189	192
Week 13	2.37 (6.87)	1.56 (4.04)	2.41 (3.89)
Week 24	0.26 (1.03)	0.29 (0.89)	1.91 (2.93)
Week 36	0.16 (0.71)	0.25 (0.70)	1.84 (2.64)
Week 48	0.09 (0.59)	0.56 (3.05)	1.89 (2.78)
Week 60	0.23 (1.40)	0.42 (1.87)	1.44 (2.70)
Week 72	0.08 (0.72)	0.22 (1.03)	1.66 (3.05)
Week 84	0.11 (0.51)	0.55 (4.52)	1.14 (1.95)
Week 96	0.11 (0.60)	0.23 (1.39)	0.99 (1.89)

19. Secondary Outcome

Title	OLMP: Number of Combined Unique Active (CUA) Magnetic Resonance Imaging (MRI) Lesions
Description	Number of combined unique active (CUA) lesions were measured by using magnetic resonance imaging (MRI) scans.
Time Frame	OLMP: Baseline, Week 24, 48, 72 and 96

Outcome Measure Data

Analysis Population Description
OLMP Analysis Set included all participants who received at least 1 dose of study drug, converted to CDMS in ITP period, entered OLMP and received at least 1 dose of OLMP study drug. Here "Number of participants analyzed" = participants who were evaluable for this outcome measure and "Number analyzed" = who were evaluable at specified time point.

Arm/Group Title	Cladribine 5.25 mg/kg, Rebif (OLMP)	Cladribine 3.5 mg/kg, Rebif (OLMP)	Placebo, Rebif (OLMP)
Arm/Group Description	Participants who received cladribine 5.25 mg/kg and converted to CDMS during ITP entered in open-label maintenance period (OLMP) and received Rebif® new formulation (RNF) subcutaneously at a dose of 44 microgram (mcg) three times a week for up to 96 weeks. Due to trial termination, the OLMP duration was reduced for some participants.	Participants who received cladribine 3.5 mg/kg and converted to CDMS during ITP entered in OLMP and received RNF subcutaneously at a dose of 44 mcg three times a week for up to 96 weeks. Due to trial termination, the OLMP duration was reduced for some participants.	Participants who received placebo and converted to CDMS during ITP entered in OLMP and received RNF subcutaneously at a dose of 44 mcg three times a week for up to 96 weeks. Due to trial termination, the OLMP duration was reduced for some participants.
Measure Participants	24	24	60
Baseline	0.63 (1.17)	2.17 (7.72)	3.23 (8.07)
Week 24	0.42 (1.02)	0.48 (1.40)	0.79 (1.33)
Week 48	0.39 (0.81)	0.38 (1.09)	0.61 (1.02)
Week 72	2.45 (5.01)	0.38 (0.74)	1.30 (2.71)
Week 96	3.33 (6.03)	0.67 (1.15)	0.53 (1.25)

20. Secondary Outcome

Title	LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Number of Combined Unique Active (CUA) Magnetic Resonance Imaging (MRI) Lesions
Description	Number of CUA MRI lesions were measured by using magnetic resonance imaging (MRI) scans.
Time Frame	LTFU: Baseline, Week 13, 24 and 36

Outcome Measure Data

Analysis Population Description
LTFU analysis set (Treated at LTFU Entry) analysis set consisted of all participants who converted to McDonald MS (2005) during the ITP, completed ITP 96-weeks and entered the LTFU. Here "Number analyzed" signifies those participants who were evaluable at specified time point for this outcome measure.

Arm/Group Title	Cladribine 5.25 mg/kg, Rebif, Cladribine 3.5 mg/kg (LTFU)	Cladribine 3.5 mg/kg, Rebif, Cladribine 3.5 mg/kg (LTFU)	Placebo, Rebif, Cladribine 3.5 mg/kg (LTFU)
Arm/Group Description	Participants who received cladribine 5.25 mg/kg and did not convert to CDMS during ITP, entered in long-term follow-up (LTFU) period. Participants who converted to McDonald multiple sclerosis (MS) during ITP or during LTFU period received open-label cladribine tablets (3.5 mg/kg) during LTFU period. Participants who converted to CDMS during LTFU received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.	Participants who received cladribine 3.5 mg/kg and did not convert to CDMS during ITP, entered in long-term follow-up (LTFU) period. Participants who converted to McDonald multiple sclerosis (MS) during ITP or during LTFU period received open-label cladribine tablets (3.5 mg/kg) during LTFU period. Participants who converted to CDMS during LTFU received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.	Participants who received placebo and did not convert to CDMS during ITP, entered in long-term follow-up (LTFU) period. Participants who converted to McDonald multiple sclerosis (MS) during ITP or during LTFU period received open-label cladribine tablets (3.5 mg/kg) during LTFU period. Participants who converted to CDMS during LTFU received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.
Measure Participants	9	9	17
Baseline	0.00 (0.00)	0.00 (0.00)	1.24 (2.49)
Week 13	0.00 (0.00)	0.00 (0.00)	2.19 (4.46)
Week 24	0.00 (0.00)	0.25 (0.46)	0.18 (0.40)
Week 36	0.00 (0.00)	0.00 (0.00)	0.10 (0.32)

21. Secondary Outcome

Title	LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Number of Combined Unique Active (CUA) Magnetic Resonance Imaging (MRI) Lesions
Description	Number of CUA lesions were measured by using magnetic resonance imaging (MRI) scans.
Time Frame	LTFU: Baseline, Week 13, 24, 36 and 48

Outcome Measure Data

Analysis Population Description
LTFU analysis set (No Treatment at LTFU Entry) was used. Here "Number analyzed" signifies those participants who were evaluable at specified time point for this outcome measure.

Arm/Group Title	Cladribine 5.25 mg/kg, Rebif (LTFU)	Cladribine 3.5 mg/kg, Rebif (LTFU)	Placebo, Rebif (LTFU)
Arm/Group Description	Participants who received cladribine 5.25 mg/kg and did not convert to CDMS during ITP, entered in LTFU period. Participants who did not convert to McDonald MS during ITP did not receive any treatment during LTFU period. Participants who converted to CDMS during LTFU period received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.	Participants who received cladribine 3.5 mg/kg and did not convert to CDMS during ITP, entered in LTFU period. Participants who did not convert to McDonald MS during ITP did not receive any treatment during LTFU period. Participants who converted to CDMS during LTFU period received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.	Participants who received placebo and did not convert to CDMS during ITP, entered in LTFU period. Participants who did not convert to McDonald MS during ITP did not receive any treatment during LTFU period. Participants who convert to CDMS during LTFU period received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.
Measure Participants	34	36	14
Baseline	0.00 (0.00)	0.03 (0.17)	0.14 (0.36)
Week 13	0.00 (0.00)	0.04 (0.21)	0.18 (0.40)
Week 24	0.00 (0.00)	0.13 (0.35)	0.00 (0.00)
Week 36	0.00 (0.00)	0.00 (0.00)	0.33 (0.58)
Week 48	0.00

22. Secondary Outcome

Title	ITP: Change From Baseline in Volume of T1 Gd-Enhanced Lesions
Description	Change in volume of T1 Gd-Enhanced lesions was measured by using magnetic resonance imaging (MRI) scans.
Time Frame	ITP: Baseline, Week 96

Outcome Measure Data

Analysis Population Description
ITT population included all randomized participants who received at least 1 dose of ITP study medication (cladribine or placebo). Here "Number of participants analyzed" signifies those participants who were evaluable for this outcome measure and "Number analyzed" = participants evaluable at specified timepoint.

Arm/Group Title	Cladribine 5.25 mg/kg (ITP)	Cladribine 3.5 mg/kg (ITP)	Placebo (ITP)
Arm/Group Description	Cladribine tablets administered as cumulative dose of 0.875 milligrams per kilograms (mg/kg) over a course of 5 consecutive days at Weeks 1, 5, 9, 13, 48, and 52 resulting in total cladribine dose of 5.25 mg/kg during the ITP of 96 weeks or until clinically definite multiple sclerosis (CDMS) conversion, whichever occurred first.	Cladribine tablets administered as cumulative dose of 0.875 mg/kg over a course of 5 consecutive days at Weeks 1, 5, 48, 52 and placebo matched to cladribine tablets was administered at Week 9 and 13 resulting in total cladribine dose of 3.5 mg/kg during the ITP of 96 weeks or until CDMS conversion, whichever occurred first.	Placebo matched to cladribine tablets administered over a course of 5 consecutive days at Weeks 1, 5, 9, 13, 48 and 52 during the ITP of 96 weeks or until CDMS conversion, whichever occurred first.
Measure Participants	203	203	197
Mean (Standard Deviation) [cubic millimeters (mm^3)]	-73.97 (204.80)	-126.64 (399.39)	48.63 (239.03)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cladribine 3.5 mg/kg (ITP), Placebo (ITP)
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	Point Estimate
	Estimated Value	-1.700
	Confidence Interval	(2-Sided) 95% -37.200 to 0.000
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Cladribine 5.25 mg/kg (ITP), Placebo (ITP)
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	Point Estimate
	Estimated Value	-28.600
	Confidence Interval	(2-Sided) 95% -117.300 to 0.000
	Parameter Dispersion	Type: Value:
	Estimation Comments

23. Secondary Outcome

Title	OLMP: Mean Volume of T1 Gd-Enhanced Lesions and Changes From Baseline in Volume of T1 Gd-Enhanced Lesions
Description	Volume of T1 Gd-Enhanced lesions was measured by using magnetic resonance imaging (MRI) scans.
Time Frame	OLMP: Baseline, Week 24, 48, 72 and 96

Outcome Measure Data

Analysis Population Description
OLMP Analysis Set was used. Here "Number of participants analyzed" signifies those participants who were evaluable for this outcome measure and "Number analyzed" = participants evaluable at specified timepoint.

Arm/Group Title	Cladribine 5.25 mg/kg, Rebif (OLMP)	Cladribine 3.5 mg/kg, Rebif (OLMP)	Placebo, Rebif (OLMP)
Arm/Group Description	Participants who received cladribine 5.25 mg/kg and converted to CDMS during ITP entered in open-label maintenance period (OLMP) and received Rebif® new formulation (RNF) subcutaneously at a dose of 44 microgram (mcg) three times a week for up to 96 weeks. Due to trial termination, the OLMP duration was reduced for some participants.	Participants who received cladribine 3.5 mg/kg and converted to CDMS during ITP entered in OLMP and received RNF subcutaneously at a dose of 44 mcg three times a week for up to 96 weeks. Due to trial termination, the OLMP duration was reduced for some participants.	Participants who received placebo and converted to CDMS during ITP entered in OLMP and received RNF subcutaneously at a dose of 44 mcg three times a week for up to 96 weeks. Due to trial termination, the OLMP duration was reduced for some participants.
Measure Participants	24	24	60
Baseline	91.06 (368.98)	113.64 (248.74)	136.61 (344.31)
Week 24	7.71 (26.35)	3.48 (16.70)	9.14 (55.62)
Week 48	5.22 (19.75)	0.00 (0.00)	39.00 (188.80)
Week 72	219.52 (377.85)	56.86 (160.83)	25.85 (96.18)
Week 96	330.20 (442.02)	0.00 (0.00)	22.51 (87.17)
Change at Week 24	-87.30 (379.50)	-120.04 (250.42)	-134.67 (343.19)
Change at Week 48	-106.82 (415.70)	-146.62 (298.86)	-116.06 (429.90)
Change at Week 72	26.00 (600.82)	-155.91 (341.97)	-192.24 (439.11)
Change at Week 96	275.83 (360.07)	-391.93 (523.92)	-247.76 (593.34)

24. Secondary Outcome

Title	LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Mean Volume of T1 Gd-Enhanced Lesions and Changes From Baseline in Volume of T1 Gd-Enhanced Lesions
Description	Volume of T1 Gd-Enhanced lesions was measured by using magnetic resonance imaging (MRI) scans.
Time Frame	LTFU: Baseline, Week 13, 24 and 36

Outcome Measure Data

Analysis Population Description
LTFU analysis set (Treated at LTFU Entry) was used. Here "Number analyzed" = participants evaluable at specified timepoint for this outcome measure.

Arm/Group Title	Cladribine 5.25 mg/kg, Rebif, Cladribine 3.5 mg/kg (LTFU)	Cladribine 3.5 mg/kg, Rebif, Cladribine 3.5 mg/kg (LTFU)	Placebo, Rebif, Cladribine 3.5 mg/kg (LTFU)
Arm/Group Description	Participants who received cladribine 5.25 mg/kg and did not convert to CDMS during ITP, entered in long-term follow-up (LTFU) period. Participants who converted to McDonald multiple sclerosis (MS) during ITP or during LTFU period received open-label cladribine tablets (3.5 mg/kg) during LTFU period. Participants who converted to CDMS during LTFU received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.	Participants who received cladribine 3.5 mg/kg and did not convert to CDMS during ITP, entered in long-term follow-up (LTFU) period. Participants who converted to McDonald multiple sclerosis (MS) during ITP or during LTFU period received open-label cladribine tablets (3.5 mg/kg) during LTFU period. Participants who converted to CDMS during LTFU received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.	Participants who received placebo and did not convert to CDMS during ITP, entered in long-term follow-up (LTFU) period. Participants who converted to McDonald multiple sclerosis (MS) during ITP or during LTFU period received open-label cladribine tablets (3.5 mg/kg) during LTFU period. Participants who converted to CDMS during LTFU received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.
Measure Participants	9	9	17
Baseline	0.00 (0.00)	0.00 (0.00)	79.43 (143.64)
Week 13	0.00 (0.00)	0.00 (0.00)	20.56 (70.96)
Week 24	0.00 (0.00)	0.00 (0.00)	25.23 (66.24)
Week 36	0.00 (0.00)	0.00 (0.00)	0.00 (0.00)
Change at Week 13	0.00 (0.00)	0.00 (0.00)	-63.83 (147.43)
Change at Week 24	0.00 (0.00)	0.00 (0.00)	-32.25 (113.96)
Change at Week 36	0.00 (0.00)	0.00 (0.00)	-58.93 (85.19)

25. Secondary Outcome

Title	LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Mean Volume of T1 Gd-Enhanced Lesions and Changes From Baseline in Volume of T1 Gd-Enhanced Lesions
Description	Volume of T1 Gd-Enhanced lesions was measured by using magnetic resonance imaging (MRI) scans.
Time Frame	LTFU: Baseline, Week 13, 24, 36 and 48

Outcome Measure Data

Analysis Population Description
LTFU analysis set (No Treatment at LTFU Entry) was used. Here "Number analyzed" = participants evaluable at specified timepoint for this outcome measure.

Arm/Group Title	Cladribine 5.25 mg/kg, Rebif (LTFU)	Cladribine 3.5 mg/kg, Rebif (LTFU)	Placebo, Rebif (LTFU)
Arm/Group Description	Participants who received cladribine 5.25 mg/kg and did not convert to CDMS during ITP, entered in LTFU period. Participants who did not convert to McDonald MS during ITP did not receive any treatment during LTFU period. Participants who converted to CDMS during LTFU period received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.	Participants who received cladribine 3.5 mg/kg and did not convert to CDMS during ITP, entered in LTFU period. Participants who did not convert to McDonald MS during ITP did not receive any treatment during LTFU period. Participants who converted to CDMS during LTFU period received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.	Participants who received placebo and did not convert to CDMS during ITP, entered in LTFU period. Participants who did not convert to McDonald MS during ITP did not receive any treatment during LTFU period. Participants who convert to CDMS during LTFU period received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.
Measure Participants	34	36	14
Baseline	0.00 (0.00)	4.45 (21.25)	27.79 (76.02)
Week 13	0.00 (0.00)	7.34 (27.76)	17.43 (57.80)
Week 24	0.00 (0.00)	0.00 (0.00)	57.22 (127.95)
Week 36	0.00 (0.00)	0.00 (0.00)	57.22 (99.10)
Week 48	0.00
Change at Week 13	0.00 (0.00)	0.38 (1.32)	-17.95 (41.38)
Change at Week 24	0.00 (0.00)	-2.48 (9.60)	-20.60 (57.89)
Change at Week 36	0.00 (0.00)	-5.31 (14.06)	-31.48 (54.53)
Change at Week 48	0.00

26. Secondary Outcome

Title	ITP: Changes From Baseline in Volume of T2 Lesions
Description	Change in volume of T2 lesions from baseline was measured by using magnetic resonance imaging (MRI) scans.
Time Frame	ITP: Baseline, Week 48 and 96

Outcome Measure Data

Analysis Population Description
ITT population included all randomized participants who received at least 1 dose of ITP study medication (cladribine or placebo). Here "Number analyzed" = participants evaluable at specified timepoint for this outcome measure.

Arm/Group Title	Cladribine 5.25 mg/kg (ITP)	Cladribine 3.5 mg/kg (ITP)	Placebo (ITP)
Arm/Group Description	Cladribine tablets administered as cumulative dose of 0.875 milligrams per kilograms (mg/kg) over a course of 5 consecutive days at Weeks 1, 5, 9, 13, 48, and 52 resulting in total cladribine dose of 5.25 mg/kg during the ITP of 96 weeks or until clinically definite multiple sclerosis (CDMS) conversion, whichever occurred first.	Cladribine tablets administered as cumulative dose of 0.875 mg/kg over a course of 5 consecutive days at Weeks 1, 5, 48, 52 and placebo matched to cladribine tablets was administered at Week 9 and 13 resulting in total cladribine dose of 3.5 mg/kg during the ITP of 96 weeks or until CDMS conversion, whichever occurred first.	Placebo matched to cladribine tablets administered over a course of 5 consecutive days at Weeks 1, 5, 9, 13, 48 and 52 during the ITP of 96 weeks or until CDMS conversion, whichever occurred first.
Measure Participants	204	206	206
Baseline	3825.73 (5093.52)	3435.22 (5184.12)	3436.69 (4613.43)
Change at Week 48	-654.20 (2061.85)	-828.97 (3513.04)	-29.57 (2581.44)
Change at Week 96	-1237.44 (2718.76)	-1605.63 (2889.61)	-886.39 (2955.44)

27. Secondary Outcome

Title	OLMP: Mean Volume of T2 Lesions and Changes From Baseline in Volume of T2 Lesions
Description	Volume of T2 lesions was measured by using magnetic resonance imaging (MRI) scans.
Time Frame	OLMP: Baseline, Week 48 and 96

Outcome Measure Data

Analysis Population Description
OLMP Analysis Set was used. Here "Number analyzed" = participants evaluable at specified timepoint for this outcome measure.

Arm/Group Title	Cladribine 5.25 mg/kg, Rebif (OLMP)	Cladribine 3.5 mg/kg, Rebif (OLMP)	Placebo, Rebif (OLMP)
Arm/Group Description	Participants who received cladribine 5.25 mg/kg and converted to CDMS during ITP entered in open-label maintenance period (OLMP) and received Rebif® new formulation (RNF) subcutaneously at a dose of 44 microgram (mcg) three times a week for up to 96 weeks. Due to trial termination, the OLMP duration was reduced for some participants.	Participants who received cladribine 3.5 mg/kg and converted to CDMS during ITP entered in OLMP and received RNF subcutaneously at a dose of 44 mcg three times a week for up to 96 weeks. Due to trial termination, the OLMP duration was reduced for some participants.	Participants who received placebo and converted to CDMS during ITP entered in OLMP and received RNF subcutaneously at a dose of 44 mcg three times a week for up to 96 weeks. Due to trial termination, the OLMP duration was reduced for some participants.
Measure Participants	24	25	60
Baseline	398.88 (1102.27)	630.70 (1707.24)	1019.30 (2872.03)
Week 48	767.66 (1875.86)	458.13 (984.12)	508.97 (1159.97)
Week 96	2606.15 (5542.81)	0.00 (0.00)	647.17 (1345.62)
Change at Week 48	523.27 (2065.54)	-20.20 (2025.21)	-77.67 (1760.20)
Change at Week 96	2245.18 (5810.53)	0.00 (0.00)	255.39 (1352.80)

28. Secondary Outcome

Title	LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Mean Volume of T2 Lesions
Description	Volume of T2 lesions was measured by using magnetic resonance imaging (MRI) scans.
Time Frame	LTFU: Baseline (Day 1)

Outcome Measure Data

Analysis Population Description
LTFU analysis set (Treated at LTFU Entry) was used.

Arm/Group Title	Cladribine 5.25 mg/kg, Rebif, Cladribine 3.5 mg/kg (LTFU)	Cladribine 3.5 mg/kg, Rebif, Cladribine 3.5 mg/kg (LTFU)	Placebo, Rebif, Cladribine 3.5 mg/kg (LTFU)
Arm/Group Description	Participants who received cladribine 5.25 mg/kg and did not convert to CDMS during ITP, entered in long-term follow-up (LTFU) period. Participants who converted to McDonald multiple sclerosis (MS) during ITP or during LTFU period received open-label cladribine tablets (3.5 mg/kg) during LTFU period. Participants who converted to CDMS during LTFU received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.	Participants who received cladribine 3.5 mg/kg and did not convert to CDMS during ITP, entered in long-term follow-up (LTFU) period. Participants who converted to McDonald multiple sclerosis (MS) during ITP or during LTFU period received open-label cladribine tablets (3.5 mg/kg) during LTFU period. Participants who converted to CDMS during LTFU received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.	Participants who received placebo and did not convert to CDMS during ITP, entered in long-term follow-up (LTFU) period. Participants who converted to McDonald multiple sclerosis (MS) during ITP or during LTFU period received open-label cladribine tablets (3.5 mg/kg) during LTFU period. Participants who converted to CDMS during LTFU received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.
Measure Participants	9	9	17
Mean (Standard Deviation) [mm^3]	1217.53 (1991.21)	587.79 (1491.20)	702.30 (1254.66)

29. Secondary Outcome

Title	LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Mean Volume of T2 Lesions and Changes From Baseline in Volume of T2 Lesions
Description	Volume of T2 lesions was measured by using magnetic resonance imaging (MRI) scans.
Time Frame	Baseline, Week 48

Outcome Measure Data

Analysis Population Description
LTFU analysis set (No Treatment at LTFU Entry) was used. Here "Number analyzed" = participants evaluable at specified timepoint.

Arm/Group Title	Cladribine 5.25 mg/kg, Rebif (LTFU)	Cladribine 3.5 mg/kg, Rebif (LTFU)	Placebo, Rebif (LTFU)
Arm/Group Description	Participants who received cladribine 5.25 mg/kg and did not convert to CDMS during ITP, entered in LTFU period. Participants who did not convert to McDonald MS during ITP did not receive any treatment during LTFU period. Participants who converted to CDMS during LTFU period received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.	Participants who received cladribine 3.5 mg/kg and did not convert to CDMS during ITP, entered in LTFU period. Participants who did not convert to McDonald MS during ITP did not receive any treatment during LTFU period. Participants who converted to CDMS during LTFU period received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.	Participants who received placebo and did not convert to CDMS during ITP, entered in LTFU period. Participants who did not convert to McDonald MS during ITP did not receive any treatment during LTFU period. Participants who convert to CDMS during LTFU period received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.
Measure Participants	34	36	14
Baseline	1402.08 (1799.96)	962.26 (1026.99)	1407.75 (1890.94)
Week 48	0.00
Change at Week 48	-969.90

30. Secondary Outcome

Title	ITP: Number of T1 Hypointense Lesions
Description	Number of T1 Hypointense lesions were measured by using magnetic resonance imaging (MRI) scans.
Time Frame	ITP: Baseline, Week 48 and 96

Outcome Measure Data

Analysis Population Description
ITT population included all randomized participants who received at least 1 dose of ITP study medication (cladribine or placebo). Here "Number analyzed" = participants evaluable at specified timepoint for this outcome measure.

Arm/Group Title	Cladribine 5.25 mg/kg (ITP)	Cladribine 3.5 mg/kg (ITP)	Placebo (ITP)
Arm/Group Description	Cladribine tablets administered as cumulative dose of 0.875 milligrams per kilograms (mg/kg) over a course of 5 consecutive days at Weeks 1, 5, 9, 13, 48, and 52 resulting in total cladribine dose of 5.25 mg/kg during the ITP of 96 weeks or until clinically definite multiple sclerosis (CDMS) conversion, whichever occurred first.	Cladribine tablets administered as cumulative dose of 0.875 mg/kg over a course of 5 consecutive days at Weeks 1, 5, 48, 52 and placebo matched to cladribine tablets was administered at Week 9 and 13 resulting in total cladribine dose of 3.5 mg/kg during the ITP of 96 weeks or until CDMS conversion, whichever occurred first.	Placebo matched to cladribine tablets administered over a course of 5 consecutive days at Weeks 1, 5, 9, 13, 48 and 52 during the ITP of 96 weeks or until CDMS conversion, whichever occurred first.
Measure Participants	204	206	206
Baseline	8.0 (11.7)	7.3 (12.2)	7.0 (8.6)
Week 48	8.39 (12.60)	6.95 (12.86)	7.07 (8.75)
Week 96	5.35 (8.14)	3.82 (6.89)	5.06 (6.82)

31. Secondary Outcome

Title	OLMP: Number of T1 Hypointense Lesions
Description	Number of T1 Hypointense lesions were measured by using magnetic resonance imaging (MRI) scans.
Time Frame	OLMP: Baseline, Week 48 and 96

Outcome Measure Data

Analysis Population Description
OLMP Analysis Set included all participants who received at least 1 dose of study medication, converted to CDMS in the ITP period, entered the OLMP and received at least 1 dose of OLMP study drug (Rebif). Here "Number analyzed" = participants evaluable at specified timepoint for this outcome measure.

Arm/Group Title	Cladribine 5.25 mg/kg, Rebif (OLMP)	Cladribine 3.5 mg/kg, Rebif (OLMP)	Placebo, Rebif (OLMP)
Arm/Group Description	Participants who received cladribine 5.25 mg/kg and converted to CDMS during ITP entered in open-label maintenance period (OLMP) and received Rebif® new formulation (RNF) subcutaneously at a dose of 44 microgram (mcg) three times a week for up to 96 weeks. Due to trial termination, the OLMP duration was reduced for some participants.	Participants who received cladribine 3.5 mg/kg and converted to CDMS during ITP entered in OLMP and received RNF subcutaneously at a dose of 44 mcg three times a week for up to 96 weeks. Due to trial termination, the OLMP duration was reduced for some participants.	Participants who received placebo and converted to CDMS during ITP entered in OLMP and received RNF subcutaneously at a dose of 44 mcg three times a week for up to 96 weeks. Due to trial termination, the OLMP duration was reduced for some participants.
Measure Participants	24	25	60
Baseline	0.92 (2.22)	2.32 (9.52)	1.45 (3.53)
Week 48	3.79 (8.32)	1.00 (2.85)	0.74 (1.83)
Week 96	0.50 (0.84)	0.00 (0.00)	1.47 (2.80)

32. Secondary Outcome

Title	LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Number of T1 Hypointense Lesions
Description	Number of T1 Hypointense lesions were measured by using magnetic resonance imaging (MRI) scans.
Time Frame	LTFU: Baseline (Day 1)

Outcome Measure Data

Analysis Population Description
LTFU analysis set (Treated at LTFU Entry) analysis set consisted of all participants who converted to McDonald MS (2005) during the ITP, completed ITP 96-weeks and entered the LTFU.

Arm/Group Title	Cladribine 5.25 mg/kg, Rebif, Cladribine 3.5 mg/kg (LTFU)	Cladribine 3.5 mg/kg, Rebif, Cladribine 3.5 mg/kg (LTFU)	Placebo, Rebif, Cladribine 3.5 mg/kg (LTFU)
Arm/Group Description	Participants who received cladribine 5.25 mg/kg and did not convert to CDMS during ITP, entered in long-term follow-up (LTFU) period. Participants who converted to McDonald multiple sclerosis (MS) during ITP or during LTFU period received open-label cladribine tablets (3.5 mg/kg) during LTFU period. Participants who converted to CDMS during LTFU received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.	Participants who received cladribine 3.5 mg/kg and did not convert to CDMS during ITP, entered in long-term follow-up (LTFU) period. Participants who converted to McDonald multiple sclerosis (MS) during ITP or during LTFU period received open-label cladribine tablets (3.5 mg/kg) during LTFU period. Participants who converted to CDMS during LTFU received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.	Participants who received placebo and did not convert to CDMS during ITP, entered in long-term follow-up (LTFU) period. Participants who converted to McDonald multiple sclerosis (MS) during ITP or during LTFU period received open-label cladribine tablets (3.5 mg/kg) during LTFU period. Participants who converted to CDMS during LTFU received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.
Measure Participants	9	9	17
Mean (Standard Deviation) [Lesions]	4.44 (7.25)	1.22 (3.31)	2.24 (5.01)

33. Secondary Outcome

Title	LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Number of T1 Hypointense Lesions
Description	Number of T1 Hypointense lesions were measured by using magnetic resonance imaging (MRI) scans.
Time Frame	LTFU: Baseline, Week 48

Outcome Measure Data

Analysis Population Description
LTFU analysis set (No Treatment at LTFU Entry) was used. Here "Number analyzed" signifies those participants who were evaluable at specified time point for this outcome measure.

Arm/Group Title	Cladribine 5.25 mg/kg, Rebif (LTFU)	Cladribine 3.5 mg/kg, Rebif (LTFU)	Placebo, Rebif (LTFU)
Arm/Group Description	Participants who received cladribine 5.25 mg/kg and did not convert to CDMS during ITP, entered in LTFU period. Participants who did not convert to McDonald MS during ITP did not receive any treatment during LTFU period. Participants who converted to CDMS during LTFU period received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.	Participants who received cladribine 3.5 mg/kg and did not convert to CDMS during ITP, entered in LTFU period. Participants who did not convert to McDonald MS during ITP did not receive any treatment during LTFU period. Participants who converted to CDMS during LTFU period received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.	Participants who received placebo and did not convert to CDMS during ITP, entered in LTFU period. Participants who did not convert to McDonald MS during ITP did not receive any treatment during LTFU period. Participants who convert to CDMS during LTFU period received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.
Measure Participants	34	36	14
Baseline	5.74 (8.21)	3.53 (5.78)	2.93 (4.46)
Week 48	4.50

34. Secondary Outcome

Title	ITP: Percentage of Participants With no New or Persisting T1 Gd-Enhanced Lesions
Description	T1 Gd-enhanced lesions were measured by using magnetic resonance imaging (MRI) scans. Percentage of participants with no new or persisting T1 Gd-enhanced lesions were reported.
Time Frame	ITP: Baseline up to Week 96

Outcome Measure Data

Analysis Population Description
The ITT population included all randomized participants who received at least 1 dose of ITP study medication (cladribine or placebo).

Arm/Group Title	Cladribine 5.25 mg/kg (ITP)	Cladribine 3.5 mg/kg (ITP)	Placebo (ITP)
Arm/Group Description	Cladribine tablets administered as cumulative dose of 0.875 milligrams per kilograms (mg/kg) over a course of 5 consecutive days at Weeks 1, 5, 9, 13, 48, and 52 resulting in total cladribine dose of 5.25 mg/kg during the ITP of 96 weeks or until clinically definite multiple sclerosis (CDMS) conversion, whichever occurred first.	Cladribine tablets administered as cumulative dose of 0.875 mg/kg over a course of 5 consecutive days at Weeks 1, 5, 48, 52 and placebo matched to cladribine tablets was administered at Week 9 and 13 resulting in total cladribine dose of 3.5 mg/kg during the ITP of 96 weeks or until CDMS conversion, whichever occurred first.	Placebo matched to cladribine tablets administered over a course of 5 consecutive days at Weeks 1, 5, 9, 13, 48 and 52 during the ITP of 96 weeks or until CDMS conversion, whichever occurred first.
Measure Participants	204	206	206
Number [Percentage of Participants]	67.0 32.8%	57.1 27.7%	21.6 10.5%

35. Secondary Outcome

Title	OLMP: Percentage of Participants With no New or Persisting T1 Gd-Enhanced Lesions
Description	T1 Gd-enhanced lesions were measured by using magnetic resonance imaging (MRI) scans. Percentage of participants with no new or persisting T1 Gd-enhanced lesions were reported.
Time Frame	OLMP: Baseline up to Week 96

Outcome Measure Data

Analysis Population Description
OLMP Analysis Set included all participants who received at least 1 dose of study medication, converted to CDMS in the ITP period, entered the OLMP and received at least 1 dose of OLMP study drug (Rebif).

Arm/Group Title	Cladribine 5.25 mg/kg, Rebif (OLMP)	Cladribine 3.5 mg/kg, Rebif (OLMP)	Placebo, Rebif (OLMP)
Arm/Group Description	Participants who received cladribine 5.25 mg/kg and converted to CDMS during ITP entered in open-label maintenance period (OLMP) and received Rebif® new formulation (RNF) subcutaneously at a dose of 44 microgram (mcg) three times a week for up to 96 weeks. Due to trial termination, the OLMP duration was reduced for some participants.	Participants who received cladribine 3.5 mg/kg and converted to CDMS during ITP entered in OLMP and received RNF subcutaneously at a dose of 44 mcg three times a week for up to 96 weeks. Due to trial termination, the OLMP duration was reduced for some participants.	Participants who received placebo and converted to CDMS during ITP entered in OLMP and received RNF subcutaneously at a dose of 44 mcg three times a week for up to 96 weeks. Due to trial termination, the OLMP duration was reduced for some participants.
Measure Participants	24	25	60
Number [Percentage of participants]	25.0 12.3%	50.0 24.3%	35.3 17.1%

36. Secondary Outcome

Title	LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Percentage of Participants With no New or Persisting T1 Gd-Enhanced Lesions
Description	T1 Gd-enhanced lesions were measured by using magnetic resonance imaging (MRI) scans. Percentage of participants with no new or persisting T1 Gd-enhanced lesions were reported.
Time Frame	LTFU: Baseline up to Week 48

Outcome Measure Data

Analysis Population Description
LTFU analysis set (Treated at LTFU Entry) was used.

Arm/Group Title	Cladribine 5.25 mg/kg, Rebif, Cladribine 3.5 mg/kg (LTFU)	Cladribine 3.5 mg/kg, Rebif, Cladribine 3.5 mg/kg (LTFU)	Placebo, Rebif, Cladribine 3.5 mg/kg (LTFU)
Arm/Group Description	Participants who received cladribine 5.25 mg/kg and did not convert to CDMS during ITP, entered in long-term follow-up (LTFU) period. Participants who converted to McDonald multiple sclerosis (MS) during ITP or during LTFU period received open-label cladribine tablets (3.5 mg/kg) during LTFU period. Participants who converted to CDMS during LTFU received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.	Participants who received cladribine 3.5 mg/kg and did not convert to CDMS during ITP, entered in long-term follow-up (LTFU) period. Participants who converted to McDonald multiple sclerosis (MS) during ITP or during LTFU period received open-label cladribine tablets (3.5 mg/kg) during LTFU period. Participants who converted to CDMS during LTFU received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.	Participants who received placebo and did not convert to CDMS during ITP, entered in long-term follow-up (LTFU) period. Participants who converted to McDonald multiple sclerosis (MS) during ITP or during LTFU period received open-label cladribine tablets (3.5 mg/kg) during LTFU period. Participants who converted to CDMS during LTFU received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.
Measure Participants	9	9	17
Number [Percentage of Participants]	0 0%	0 0%	0 0%

37. Secondary Outcome

Title	LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Percentage of Participants With no New or Persisting T1 Gd-Enhanced Lesions
Description	T1 Gd-enhanced lesions were measured by using magnetic resonance imaging (MRI) scans. Percentage of participants with no new or persisting T1 Gd-enhanced lesions were reported.
Time Frame	Baseline up to Week 48

Outcome Measure Data

Analysis Population Description
LTFU analysis set (No Treatment at LTFU Entry) was used.

Arm/Group Title	Cladribine 5.25 mg/kg, Rebif (LTFU)	Cladribine 3.5 mg/kg, Rebif (LTFU)	Placebo, Rebif (LTFU)
Arm/Group Description	Participants who received cladribine 5.25 mg/kg and did not convert to CDMS during ITP, entered in LTFU period. Participants who did not convert to McDonald MS during ITP did not receive any treatment during LTFU period. Participants who converted to CDMS during LTFU period received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.	Participants who received cladribine 3.5 mg/kg and did not convert to CDMS during ITP, entered in LTFU period. Participants who did not convert to McDonald MS during ITP did not receive any treatment during LTFU period. Participants who converted to CDMS during LTFU period received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.	Participants who received placebo and did not convert to CDMS during ITP, entered in LTFU period. Participants who did not convert to McDonald MS during ITP did not receive any treatment during LTFU period. Participants who convert to CDMS during LTFU period received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.
Measure Participants	34	36	14
Number [Percentage of participants]	0 0%	0 0%	0 0%

38. Secondary Outcome

Title	ITP: Percentage of Participants With no New or Enlarging T2 Lesions
Description	T2 lesions were measured by using magnetic resonance imaging (MRI) scans. Percentage of participants with no new or enlarging T2 lesions were reported.
Time Frame	ITP: Baseline up to Week 96

Outcome Measure Data

Analysis Population Description
The ITT population included all randomized participants who received at least 1 dose of ITP study medication (cladribine or placebo).

Arm/Group Title	Cladribine 5.25 mg/kg (ITP)	Cladribine 3.5 mg/kg (ITP)	Placebo (ITP)
Arm/Group Description	Cladribine tablets administered as cumulative dose of 0.875 milligrams per kilograms (mg/kg) over a course of 5 consecutive days at Weeks 1, 5, 9, 13, 48, and 52 resulting in total cladribine dose of 5.25 mg/kg during the ITP of 96 weeks or until clinically definite multiple sclerosis (CDMS) conversion, whichever occurred first.	Cladribine tablets administered as cumulative dose of 0.875 mg/kg over a course of 5 consecutive days at Weeks 1, 5, 48, 52 and placebo matched to cladribine tablets was administered at Week 9 and 13 resulting in total cladribine dose of 3.5 mg/kg during the ITP of 96 weeks or until CDMS conversion, whichever occurred first.	Placebo matched to cladribine tablets administered over a course of 5 consecutive days at Weeks 1, 5, 9, 13, 48 and 52 during the ITP of 96 weeks or until CDMS conversion, whichever occurred first.
Measure Participants	204	206	206
Number [Percentage of Participants]	32.9 16.1%	35.1 17%	19.0 9.2%

39. Secondary Outcome

Title	OLMP: Percentage of Participants With no New or Enlarging T2 Lesions
Description	T2 Gd-enhanced lesions were measured by using magnetic resonance imaging (MRI) scans. Percentage of participants with no new or enlarging T2 Lesions were reported.
Time Frame	OLMP: Baseline up to 96

Outcome Measure Data

Analysis Population Description
OLMP Analysis Set included all participants who received at least 1 dose of study medication, converted to CDMS in the ITP period, entered the OLMP and received at least 1 dose of OLMP study drug (Rebif).

Arm/Group Title	Cladribine 5.25 mg/kg, Rebif (OLMP)	Cladribine 3.5 mg/kg, Rebif (OLMP)	Placebo, Rebif (OLMP)
Arm/Group Description	Participants who received cladribine 5.25 mg/kg and converted to CDMS during ITP entered in open-label maintenance period (OLMP) and received Rebif® new formulation (RNF) subcutaneously at a dose of 44 microgram (mcg) three times a week for up to 96 weeks. Due to trial termination, the OLMP duration was reduced for some participants.	Participants who received cladribine 3.5 mg/kg and converted to CDMS during ITP entered in OLMP and received RNF subcutaneously at a dose of 44 mcg three times a week for up to 96 weeks. Due to trial termination, the OLMP duration was reduced for some participants.	Participants who received placebo and converted to CDMS during ITP entered in OLMP and received RNF subcutaneously at a dose of 44 mcg three times a week for up to 96 weeks. Due to trial termination, the OLMP duration was reduced for some participants.
Measure Participants	24	25	60
Number [Percentage of participants]	18.2 8.9%	16.7 8.1%	13.5 6.6%

40. Secondary Outcome

Title	LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Percentage of Participants With no New or Enlarging T2 Lesions
Description	Enlarging T2 Lesions were measured by using magnetic resonance imaging (MRI) scans. Percentage of participants with no New or Enlarging T2 Lesions were reported.
Time Frame	Baseline up to Week 48

Outcome Measure Data

Analysis Population Description
LTFU analysis set (Treated at LTFU Entry) was used.

Arm/Group Title	Cladribine 5.25 mg/kg, Rebif, Cladribine 3.5 mg/kg (LTFU)	Cladribine 3.5 mg/kg, Rebif, Cladribine 3.5 mg/kg (LTFU)	Placebo, Rebif, Cladribine 3.5 mg/kg (LTFU)
Arm/Group Description	Participants who received cladribine 5.25 mg/kg and did not convert to CDMS during ITP, entered in long-term follow-up (LTFU) period. Participants who converted to McDonald multiple sclerosis (MS) during ITP or during LTFU period received open-label cladribine tablets (3.5 mg/kg) during LTFU period. Participants who converted to CDMS during LTFU received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.	Participants who received cladribine 3.5 mg/kg and did not convert to CDMS during ITP, entered in long-term follow-up (LTFU) period. Participants who converted to McDonald multiple sclerosis (MS) during ITP or during LTFU period received open-label cladribine tablets (3.5 mg/kg) during LTFU period. Participants who converted to CDMS during LTFU received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.	Participants who received placebo and did not convert to CDMS during ITP, entered in long-term follow-up (LTFU) period. Participants who converted to McDonald multiple sclerosis (MS) during ITP or during LTFU period received open-label cladribine tablets (3.5 mg/kg) during LTFU period. Participants who converted to CDMS during LTFU received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.
Measure Participants	9	9	17
Number [Percentage of Participants]	0 0%	0 0%	0 0%

41. Secondary Outcome

Title	LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Percentage of Participants With no New or Enlarging T2 Lesions
Description	Enlarging T2 lesions were measured by using magnetic resonance imaging (MRI) scans. Percentage of participants with no New or Enlarging T2 lesions were reported.
Time Frame	LTFU: Baseline up to Week 48

Outcome Measure Data

Analysis Population Description
LTFU analysis set (No Treatment at LTFU Entry) was used.

Arm/Group Title	Cladribine 5.25 mg/kg, Rebif (LTFU)	Cladribine 3.5 mg/kg, Rebif (LTFU)	Placebo, Rebif (LTFU)
Arm/Group Description	Participants who received cladribine 5.25 mg/kg and did not convert to CDMS during ITP, entered in LTFU period. Participants who did not convert to McDonald MS during ITP did not receive any treatment during LTFU period. Participants who converted to CDMS during LTFU period received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.	Participants who received cladribine 3.5 mg/kg and did not convert to CDMS during ITP, entered in LTFU period. Participants who did not convert to McDonald MS during ITP did not receive any treatment during LTFU period. Participants who converted to CDMS during LTFU period received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.	Participants who received placebo and did not convert to CDMS during ITP, entered in LTFU period. Participants who did not convert to McDonald MS during ITP did not receive any treatment during LTFU period. Participants who convert to CDMS during LTFU period received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.
Measure Participants	34	36	14
Number [Percentage of participants]	0 0%	0 0%	0 0%

42. Secondary Outcome

Title	ITP: Percent Change From Baseline in Brain Volume
Description	Brain volume was measured by using magnetic resonance imaging (MRI) scans. Percent change from baseline in brain volume at Week 48 and 96 was reported.
Time Frame	ITP: Baseline, Week 48 and 96

Outcome Measure Data

Analysis Population Description
The ITT population included all randomized participants who received at least 1 dose of ITP study medication (cladribine or placebo). Here "Number of participants analyzed" signifies those participants who were evaluable for this outcome measure and "Number analyzed" = participants evaluable at specified timepoint.

Arm/Group Title	Cladribine 5.25 mg/kg (ITP)	Cladribine 3.5 mg/kg (ITP)	Placebo (ITP)
Arm/Group Description	Cladribine tablets administered as cumulative dose of 0.875 milligrams per kilograms (mg/kg) over a course of 5 consecutive days at Weeks 1, 5, 9, 13, 48, and 52 resulting in total cladribine dose of 5.25 mg/kg during the ITP of 96 weeks or until clinically definite multiple sclerosis (CDMS) conversion, whichever occurred first.	Cladribine tablets administered as cumulative dose of 0.875 mg/kg over a course of 5 consecutive days at Weeks 1, 5, 48, 52 and placebo matched to cladribine tablets was administered at Week 9 and 13 resulting in total cladribine dose of 3.5 mg/kg during the ITP of 96 weeks or until CDMS conversion, whichever occurred first.	Placebo matched to cladribine tablets administered over a course of 5 consecutive days at Weeks 1, 5, 9, 13, 48 and 52 during the ITP of 96 weeks or until CDMS conversion, whichever occurred first.
Measure Participants	155	163	135
Week 48	-0.47 (0.63)	-0.48 (0.69)	-0.33 (0.76)
Week 96	-0.59 (0.80)	-0.72 (0.73)	-0.75 (0.65)

43. Secondary Outcome

Title	OLMP: Percent Change From Baseline in Brain Volume
Description	Brain volume was measured by using magnetic resonance imaging (MRI) scans. Percent change from baseline in brain volume at Week 48 and 96 was reported.
Time Frame	OLMP: Baseline, Week 48 and 96

Outcome Measure Data

Analysis Population Description
OLMP Analysis Set was used. Here "Number of participants analyzed" signifies those participants who were evaluable for this outcome measure and "Number analyzed" = participants evaluable at specified timepoint.

Arm/Group Title	Cladribine 5.25 mg/kg, Rebif (OLMP)	Cladribine 3.5 mg/kg, Rebif (OLMP)	Placebo, Rebif (OLMP)
Arm/Group Description	Participants who received cladribine 5.25 mg/kg and converted to CDMS during ITP entered in open-label maintenance period (OLMP) and received Rebif® new formulation (RNF) subcutaneously at a dose of 44 microgram (mcg) three times a week for up to 96 weeks. Due to trial termination, the OLMP duration was reduced for some participants.	Participants who received cladribine 3.5 mg/kg and converted to CDMS during ITP entered in OLMP and received RNF subcutaneously at a dose of 44 mcg three times a week for up to 96 weeks. Due to trial termination, the OLMP duration was reduced for some participants.	Participants who received placebo and converted to CDMS during ITP entered in OLMP and received RNF subcutaneously at a dose of 44 mcg three times a week for up to 96 weeks. Due to trial termination, the OLMP duration was reduced for some participants.
Measure Participants	5	4	11
Week 48	-0.41 (0.98)	-1.60 (1.40)	-0.56 (1.11)
Week 96	0.06 (1.36)	-1.31 (0.76)

44. Secondary Outcome

Title	OLMP: Number of Relapses
Description	Relapse was defined as new, worsening or recurrent neurological symptoms attributed to multiple sclerosis that last for at least 24 hours without fever or infection, or adverse reaction to prescribed medication, preceded by a stable or improving neurological status of at least 30 days.
Time Frame	Baseline up to Week 96

Outcome Measure Data

Analysis Population Description
OLMP Analysis Set included all participants who received at least 1 dose of study medication, converted to CDMS in the ITP period, entered the OLMP and received at least 1 dose of OLMP study drug (Rebif).

Arm/Group Title	Cladribine 5.25 mg/kg (ITP)	Cladribine 3.5 mg/kg (ITP)	Placebo (ITP)
Arm/Group Description	Cladribine tablets administered as cumulative dose of 0.875 milligrams per kilograms (mg/kg) over a course of 5 consecutive days at Weeks 1, 5, 9, 13, 48, and 52 resulting in total cladribine dose of 5.25 mg/kg during the ITP of 96 weeks or until clinically definite multiple sclerosis (CDMS) conversion, whichever occurred first.	Cladribine tablets administered as cumulative dose of 0.875 mg/kg over a course of 5 consecutive days at Weeks 1, 5, 48, 52 and placebo matched to cladribine tablets was administered at Week 9 and 13 resulting in total cladribine dose of 3.5 mg/kg during the ITP of 96 weeks or until CDMS conversion, whichever occurred first.	Placebo matched to cladribine tablets administered over a course of 5 consecutive days at Weeks 1, 5, 9, 13, 48 and 52 during the ITP of 96 weeks or until CDMS conversion, whichever occurred first.
Measure Participants	24	25	60
Mean (Standard Deviation) [Relapses]	0.33 (0.64)	0.16 (0.37)	0.55 (1.00)

45. Secondary Outcome

Title	LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Number of Relapses
Description	Relapse was defined as new, worsening or recurrent neurological symptoms attributed to multiple sclerosis that last for at least 24 hours without fever or infection, or adverse reaction to prescribed medication, preceded by a stable or improving neurological status of at least 30 days.
Time Frame	Baseline up to Week 48

Outcome Measure Data

Analysis Population Description
LTFU analysis set (Treated at LTFU Entry) was used.

Arm/Group Title	Cladribine 5.25 mg/kg, Rebif, Cladribine 3.5 mg/kg (LTFU)	Cladribine 3.5 mg/kg, Rebif, Cladribine 3.5 mg/kg (LTFU)	Placebo, Rebif, Cladribine 3.5 mg/kg (LTFU)
Arm/Group Description	Participants who received cladribine 5.25 mg/kg and did not convert to CDMS during ITP, entered in long-term follow-up (LTFU) period. Participants who converted to McDonald multiple sclerosis (MS) during ITP or during LTFU period received open-label cladribine tablets (3.5 mg/kg) during LTFU period. Participants who converted to CDMS during LTFU received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.	Participants who received cladribine 3.5 mg/kg and did not convert to CDMS during ITP, entered in long-term follow-up (LTFU) period. Participants who converted to McDonald multiple sclerosis (MS) during ITP or during LTFU period received open-label cladribine tablets (3.5 mg/kg) during LTFU period. Participants who converted to CDMS during LTFU received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.	Participants who received placebo and did not convert to CDMS during ITP, entered in long-term follow-up (LTFU) period. Participants who converted to McDonald multiple sclerosis (MS) during ITP or during LTFU period received open-label cladribine tablets (3.5 mg/kg) during LTFU period. Participants who converted to CDMS during LTFU received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.
Measure Participants	9	9	17
Mean (Standard Deviation) [Relapses]	0.00 (0.00)	0.00 (0.00)	0.06 (0.24)

46. Secondary Outcome

Title	LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Number of Relapses
Description	Relapse was defined as new, worsening or recurrent neurological symptoms attributed to multiple sclerosis that last for at least 24 hours without fever or infection, or adverse reaction to prescribed medication, preceded by a stable or improving neurological status of at least 30 days.
Time Frame	Baseline up to Week 48

Outcome Measure Data

Analysis Population Description
LTFU analysis set (No Treatment at LTFU Entry) was used.

Arm/Group Title	Cladribine 5.25 mg/kg, Rebif (LTFU)	Cladribine 3.5 mg/kg, Rebif (LTFU)	Placebo, Rebif (LTFU)
Arm/Group Description	Participants who received cladribine 5.25 mg/kg and did not convert to CDMS during ITP, entered in LTFU period. Participants who did not convert to McDonald MS during ITP did not receive any treatment during LTFU period. Participants who converted to CDMS during LTFU period received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.	Participants who received cladribine 3.5 mg/kg and did not convert to CDMS during ITP, entered in LTFU period. Participants who did not convert to McDonald MS during ITP did not receive any treatment during LTFU period. Participants who converted to CDMS during LTFU period received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.	Participants who received placebo and did not convert to CDMS during ITP, entered in LTFU period. Participants who did not convert to McDonald MS during ITP did not receive any treatment during LTFU period. Participants who convert to CDMS during LTFU period received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.
Measure Participants	34	36	14
Mean (Standard Deviation) [Relapses]	0.03 (0.17)	0.03 (0.17)	0.00 (0.00)

47. Secondary Outcome

Title	OLMP: Annualized Relapse Rate
Description	The annualized relapse rate for each treatment group was the mean of the annualized relapse rates for all the participants in the group, calculated as the total number of confirmed relapses divided by the total number of days on study multiplied by 365.25. Where, Relapse was defined as new, worsening or recurrent neurological symptoms attributed to multiple sclerosis that last for at least 24 hours without fever or infection, or adverse reaction to prescribed medication, preceded by a stable or improving neurological status of at least 30 days.
Time Frame	Baseline up to Week 96

Outcome Measure Data

Analysis Population Description
OLMP Analysis Set included all participants who received at least 1 dose of study medication, converted to CDMS in the ITP period, entered the OLMP and received at least 1 dose of OLMP study drug (Rebif).

Arm/Group Title	Cladribine 5.25 mg/kg (ITP)	Cladribine 3.5 mg/kg (ITP)	Placebo (ITP)
Arm/Group Description	Cladribine tablets administered as cumulative dose of 0.875 milligrams per kilograms (mg/kg) over a course of 5 consecutive days at Weeks 1, 5, 9, 13, 48, and 52 resulting in total cladribine dose of 5.25 mg/kg during the ITP of 96 weeks or until clinically definite multiple sclerosis (CDMS) conversion, whichever occurred first.	Cladribine tablets administered as cumulative dose of 0.875 mg/kg over a course of 5 consecutive days at Weeks 1, 5, 48, 52 and placebo matched to cladribine tablets was administered at Week 9 and 13 resulting in total cladribine dose of 3.5 mg/kg during the ITP of 96 weeks or until CDMS conversion, whichever occurred first.	Placebo matched to cladribine tablets administered over a course of 5 consecutive days at Weeks 1, 5, 9, 13, 48 and 52 during the ITP of 96 weeks or until CDMS conversion, whichever occurred first.
Measure Participants	24	25	60
Number (95% Confidence Interval) [relapses per year]	0.24	0.14	0.42

48. Secondary Outcome

Title	OLMP: Percentage of Relapse-Free Participants
Description	Relapse was defined as new, worsening or recurrent neurological symptoms attributed to multiple sclerosis that last for at least 24 hours without fever or infection, or adverse reaction to prescribed medication, preceded by a stable or improving neurological status of at least 30 days. Percentage of relapse-free participants were reported.
Time Frame	Baseline up to Week 96

Outcome Measure Data

Analysis Population Description
OLMP Analysis Set included all participants who received at least 1 dose of study medication, converted to CDMS in the ITP period, entered the OLMP and received at least 1 dose of OLMP study drug (Rebif). Here "Number of participants analyzed" signifies those participants who were evaluable for this outcome measure.

Arm/Group Title	Cladribine 5.25 mg/kg (ITP)	Cladribine 3.5 mg/kg (ITP)	Placebo (ITP)
Arm/Group Description	Cladribine tablets administered as cumulative dose of 0.875 milligrams per kilograms (mg/kg) over a course of 5 consecutive days at Weeks 1, 5, 9, 13, 48, and 52 resulting in total cladribine dose of 5.25 mg/kg during the ITP of 96 weeks or until clinically definite multiple sclerosis (CDMS) conversion, whichever occurred first.	Cladribine tablets administered as cumulative dose of 0.875 mg/kg over a course of 5 consecutive days at Weeks 1, 5, 48, 52 and placebo matched to cladribine tablets was administered at Week 9 and 13 resulting in total cladribine dose of 3.5 mg/kg during the ITP of 96 weeks or until CDMS conversion, whichever occurred first.	Placebo matched to cladribine tablets administered over a course of 5 consecutive days at Weeks 1, 5, 9, 13, 48 and 52 during the ITP of 96 weeks or until CDMS conversion, whichever occurred first.
Measure Participants	10	5	26
Number [Percentage of participants]	40.0 19.6%	20.0 9.7%	30.8 15%

49. Secondary Outcome

Title	ITP: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs
Description	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. TEAEs include both Serious TEAEs and non-serious TEAEs. Number of Participants with TEAEs and serious TEAEs were reported.
Time Frame	ITP: Baseline up to Week 96

Outcome Measure Data

Analysis Population Description
Safety analysis set included all randomized participants who received at least 1 dose of ITP study medication (cladribine or placebo) and had at least one safety assessment during the ITP.

Arm/Group Title	Cladribine 5.25 mg/kg (ITP)	Cladribine 3.5 mg/kg (ITP)	Placebo (ITP)
Arm/Group Description	Cladribine tablets administered as cumulative dose of 0.875 milligrams per kilograms (mg/kg) over a course of 5 consecutive days at Weeks 1, 5, 9, 13, 48, and 52 resulting in total cladribine dose of 5.25 mg/kg during the ITP of 96 weeks or until clinically definite multiple sclerosis (CDMS) conversion, whichever occurred first.	Cladribine tablets administered as cumulative dose of 0.875 mg/kg over a course of 5 consecutive days at Weeks 1, 5, 48, 52 and placebo matched to cladribine tablets was administered at Week 9 and 13 resulting in total cladribine dose of 3.5 mg/kg during the ITP of 96 weeks or until CDMS conversion, whichever occurred first.	Placebo matched to cladribine tablets administered over a course of 5 consecutive days at Weeks 1, 5, 9, 13, 48 and 52 during the ITP of 96 weeks or until CDMS conversion, whichever occurred first.
Measure Participants	204	206	206
TEAEs	165 80.9%	168 81.6%	162 78.6%
Serious TEAEs	12 5.9%	23 11.2%	22 10.7%

Adverse Events

	Cladribine 5.25 mg/kg (ITP)		Cladribine 3.5 mg/kg (ITP)		Placebo (ITP)		Cladribine 5.25 mg/kg, Rebif (OLMP)		Cladribine 3.5 mg/kg, Rebif (OLMP)		Placebo, Rebif (OLMP)		Cladribine 5.25 mg/kg, Rebif, Cladribine 3.5 mg/kg (LTFU)		Cladribine 3.5 mg/kg, Rebif, Cladribine 3.5 mg/kg (LTFU)		Placebo, Rebif, Cladribine 3.5 mg/kg (LTFU)		Cladribine 5.25 mg/kg, Rebif (LTFU)		Cladribine 3.5 mg/kg, Rebif (LTFU)		Placebo, Rebif (LTFU)
Time Frame	ITP: Baseline up to 96 weeks; OLMP: Baseline up to 96 weeks; LTFU: Baseline up to 48 weeks
Adverse Event Reporting Description	ITP Safety analysis set(SAF). OLMP SAF: participants who received atleast 1dose of ITP study drug, converted to CDMS in ITP, entered OLMP and received atleast 1dose of OLMP study drug. LTFU (Treated)SAF: Participants who converted to McDonald MS(2005)during ITP, completed ITP 96-weeks and entered LTFU and treated with cladribine when entering LTFU. LTFU(Not-Treated) SAF:Participants who completed ITP 96-weeks and entered LTFU for safety follow-up and didn't receive study drug upon entry to LTFU.

Arm/Group Title	Cladribine 5.25 mg/kg (ITP)		Cladribine 3.5 mg/kg (ITP)		Placebo (ITP)		Cladribine 5.25 mg/kg, Rebif (OLMP)		Cladribine 3.5 mg/kg, Rebif (OLMP)		Placebo, Rebif (OLMP)		Cladribine 5.25 mg/kg, Rebif, Cladribine 3.5 mg/kg (LTFU)		Cladribine 3.5 mg/kg, Rebif, Cladribine 3.5 mg/kg (LTFU)		Placebo, Rebif, Cladribine 3.5 mg/kg (LTFU)		Cladribine 5.25 mg/kg, Rebif (LTFU)		Cladribine 3.5 mg/kg, Rebif (LTFU)		Placebo, Rebif (LTFU)
Arm/Group Description	Cladribine tablets administered as cumulative dose of 0.875 milligrams per kilograms (mg/kg) over a course of 5 consecutive days at Weeks 1, 5, 9, 13, 48, and 52 resulting in total cladribine dose of 5.25 mg/kg during the ITP of 96 weeks or until clinically definite multiple sclerosis (CDMS) conversion, whichever occurred first.		Cladribine tablets administered as cumulative dose of 0.875 mg/kg over a course of 5 consecutive days at Weeks 1, 5, 48, 52 and placebo matched to cladribine tablets was administered at Week 9 and 13 resulting in total cladribine dose of 3.5 mg/kg during the ITP of 96 weeks or until CDMS conversion, whichever occurred first.		Placebo matched to cladribine tablets administered over a course of 5 consecutive days at Weeks 1, 5, 9, 13, 48 and 52 during the ITP of 96 weeks or until CDMS conversion, whichever occurred first.		Participants who received cladribine 5.25 mg/kg and converted to CDMS during ITP entered in open-label maintenance period (OLMP) and received Rebif® new formulation (RNF) subcutaneously at a dose of 44 microgram (mcg) three times a week for up to 96 weeks. Due to trial termination, the OLMP duration was reduced for some participants.		Participants who received cladribine 3.5 mg/kg and converted to CDMS during ITP entered in OLMP and received RNF subcutaneously at a dose of 44 mcg three times a week for up to 96 weeks. Due to trial termination, the OLMP duration was reduced for some participants.		Participants who received placebo and converted to CDMS during ITP entered in OLMP and received RNF subcutaneously at a dose of 44 mcg three times a week for up to 96 weeks. Due to trial termination, the OLMP duration was reduced for some participants.		Participants who received cladribine 5.25 mg/kg and did not convert to CDMS during ITP, entered in long-term follow-up (LTFU) period. Participants who converted to McDonald multiple sclerosis (MS) during ITP or during LTFU period received open-label cladribine tablets (3.5 mg/kg) during LTFU period . Participants who did not convert to McDonald MS during ITP did not receive any treatment during LTFU period. Participants who converted to CDMS during LTFU received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.		Participants who received cladribine 3.5 mg/kg and did not convert to CDMS during ITP, entered in long-term follow-up (LTFU) period. Participants who converted to McDonald multiple sclerosis (MS) during ITP or during LTFU period received open-label cladribine tablets (3.5 mg/kg) during LTFU period . Participants who did not convert to McDonald MS during ITP did not receive any treatment during LTFU period. Participants who converted to CDMS during LTFU received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.		Participants who received placebo and did not convert to CDMS during ITP, entered in long-term follow-up (LTFU) period. Participants who converted to McDonald multiple sclerosis (MS) during ITP or during LTFU period received open-label cladribine tablets (3.5 mg/kg) during LTFU period . Participants who did not convert to McDonald MS during ITP did not receive any treatment during LTFU period. Participants who converted to CDMS during LTFU received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.		Participants who received cladribine 5.25 mg/kg and did not convert to CDMS during ITP, entered in LTFU period. Participants who did not convert to McDonald MS during ITP did not receive any treatment during LTFU period. Participants who converted to CDMS during LTFU period received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.		Participants who received cladribine 3.5 mg/kg and did not convert to CDMS during ITP, entered in LTFU period. Participants who did not convert to McDonald MS during ITP did not receive any treatment during LTFU period. Participants who converted to CDMS during LTFU period received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.		Participants who received placebo and did not convert to CDMS during ITP, entered in LTFU period. Participants who did not convert to McDonald MS during ITP did not receive any treatment during LTFU period. Participants who convert to CDMS during LTFU period received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.
All Cause Mortality
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/204 (0%)		0/206 (0%)		0/206 (0%)		0/24 (0%)		1/25 (4%)		0/60 (0%)		0/9 (0%)		0/9 (0%)		0/16 (0%)		0/34 (0%)		0/36 (0%)		0/14 (0%)
Serious Adverse Events
	Cladribine 5.25 mg/kg (ITP)		Cladribine 3.5 mg/kg (ITP)		Placebo (ITP)		Cladribine 5.25 mg/kg, Rebif (OLMP)		Cladribine 3.5 mg/kg, Rebif (OLMP)		Placebo, Rebif (OLMP)		Cladribine 5.25 mg/kg, Rebif, Cladribine 3.5 mg/kg (LTFU)		Cladribine 3.5 mg/kg, Rebif, Cladribine 3.5 mg/kg (LTFU)		Placebo, Rebif, Cladribine 3.5 mg/kg (LTFU)		Cladribine 5.25 mg/kg, Rebif (LTFU)		Cladribine 3.5 mg/kg, Rebif (LTFU)		Placebo, Rebif (LTFU)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	12/204 (5.9%)		23/206 (11.2%)		22/206 (10.7%)		1/24 (4.2%)		4/25 (16%)		5/60 (8.3%)		0/9 (0%)		0/9 (0%)		1/16 (6.3%)		0/34 (0%)		1/36 (2.8%)		0/14 (0%)
Blood and lymphatic system disorders
Lymphopenia	1/204 (0.5%)		0/206 (0%)		0/206 (0%)		0/24 (0%)		0/25 (0%)		0/60 (0%)		0/9 (0%)		0/9 (0%)		0/16 (0%)		0/34 (0%)		0/36 (0%)		0/14 (0%)
Cardiac disorders
Cardio-respiratory arrest	0/204 (0%)		0/206 (0%)		0/206 (0%)		0/24 (0%)		1/25 (4%)		0/60 (0%)		0/9 (0%)		0/9 (0%)		0/16 (0%)		0/34 (0%)		0/36 (0%)		0/14 (0%)
Atrial fibrillation	1/204 (0.5%)		0/206 (0%)		0/206 (0%)		0/24 (0%)		0/25 (0%)		0/60 (0%)		0/9 (0%)		0/9 (0%)		0/16 (0%)		0/34 (0%)		0/36 (0%)		0/14 (0%)
Myocarditis	1/204 (0.5%)		0/206 (0%)		0/206 (0%)		0/24 (0%)		0/25 (0%)		0/60 (0%)		0/9 (0%)		0/9 (0%)		0/16 (0%)		0/34 (0%)		0/36 (0%)		0/14 (0%)
Endocrine disorders
Hyperprolactinaemia	0/204 (0%)		0/206 (0%)		0/206 (0%)		0/24 (0%)		1/25 (4%)		0/60 (0%)		0/9 (0%)		0/9 (0%)		0/16 (0%)		0/34 (0%)		0/36 (0%)		0/14 (0%)
Autoimmune thyroiditis	1/204 (0.5%)		0/206 (0%)		0/206 (0%)		0/24 (0%)		0/25 (0%)		0/60 (0%)		0/9 (0%)		0/9 (0%)		0/16 (0%)		0/34 (0%)		0/36 (0%)		0/14 (0%)
Hyperthyroidism	0/204 (0%)		0/206 (0%)		1/206 (0.5%)		0/24 (0%)		0/25 (0%)		0/60 (0%)		0/9 (0%)		0/9 (0%)		0/16 (0%)		0/34 (0%)		0/36 (0%)		0/14 (0%)
Eye disorders
Retinal vein thrombosis	0/204 (0%)		0/206 (0%)		1/206 (0.5%)		0/24 (0%)		0/25 (0%)		0/60 (0%)		0/9 (0%)		0/9 (0%)		0/16 (0%)		0/34 (0%)		0/36 (0%)		0/14 (0%)
Gastrointestinal disorders
Gastric ulcer perforation	0/204 (0%)		0/206 (0%)		0/206 (0%)		0/24 (0%)		1/25 (4%)		0/60 (0%)		0/9 (0%)		0/9 (0%)		0/16 (0%)		0/34 (0%)		0/36 (0%)		0/14 (0%)
Mechanical ileus	0/204 (0%)		0/206 (0%)		1/206 (0.5%)		0/24 (0%)		0/25 (0%)		0/60 (0%)		0/9 (0%)		0/9 (0%)		0/16 (0%)		0/34 (0%)		0/36 (0%)		0/14 (0%)
General disorders
Injection site necrosis	0/204 (0%)		0/206 (0%)		0/206 (0%)		0/24 (0%)		0/25 (0%)		1/60 (1.7%)		0/9 (0%)		0/9 (0%)		0/16 (0%)		0/34 (0%)		0/36 (0%)		0/14 (0%)
Infections and infestations
Erysipelas	0/204 (0%)		0/206 (0%)		0/206 (0%)		0/24 (0%)		0/25 (0%)		1/60 (1.7%)		0/9 (0%)		0/9 (0%)		0/16 (0%)		0/34 (0%)		0/36 (0%)		0/14 (0%)
Anogenital warts	0/204 (0%)		0/206 (0%)		1/206 (0.5%)		0/24 (0%)		0/25 (0%)		0/60 (0%)		0/9 (0%)		0/9 (0%)		0/16 (0%)		0/34 (0%)		0/36 (0%)		0/14 (0%)
Herpes zoster	1/204 (0.5%)		0/206 (0%)		0/206 (0%)		0/24 (0%)		0/25 (0%)		0/60 (0%)		0/9 (0%)		0/9 (0%)		0/16 (0%)		0/34 (0%)		0/36 (0%)		0/14 (0%)
Pilonidal cyst	0/204 (0%)		1/206 (0.5%)		0/206 (0%)		0/24 (0%)		0/25 (0%)		0/60 (0%)		0/9 (0%)		0/9 (0%)		0/16 (0%)		0/34 (0%)		0/36 (0%)		0/14 (0%)
Injury, poisoning and procedural complications
Road traffic accident	0/204 (0%)		0/206 (0%)		2/206 (1%)		0/24 (0%)		0/25 (0%)		0/60 (0%)		0/9 (0%)		0/9 (0%)		0/16 (0%)		0/34 (0%)		0/36 (0%)		0/14 (0%)
Accidental overdose	1/204 (0.5%)		0/206 (0%)		0/206 (0%)		0/24 (0%)		0/25 (0%)		0/60 (0%)		0/9 (0%)		0/9 (0%)		0/16 (0%)		0/34 (0%)		0/36 (0%)		0/14 (0%)
Back injury	0/204 (0%)		0/206 (0%)		1/206 (0.5%)		0/24 (0%)		0/25 (0%)		0/60 (0%)		0/9 (0%)		0/9 (0%)		0/16 (0%)		0/34 (0%)		0/36 (0%)		0/14 (0%)
Clavicle fracture	0/204 (0%)		0/206 (0%)		1/206 (0.5%)		0/24 (0%)		0/25 (0%)		0/60 (0%)		0/9 (0%)		0/9 (0%)		0/16 (0%)		0/34 (0%)		0/36 (0%)		0/14 (0%)
Fall	0/204 (0%)		1/206 (0.5%)		0/206 (0%)		0/24 (0%)		0/25 (0%)		0/60 (0%)		0/9 (0%)		0/9 (0%)		0/16 (0%)		0/34 (0%)		0/36 (0%)		0/14 (0%)
Gun shot wound	0/204 (0%)		1/206 (0.5%)		0/206 (0%)		0/24 (0%)		0/25 (0%)		0/60 (0%)		0/9 (0%)		0/9 (0%)		0/16 (0%)		0/34 (0%)		0/36 (0%)		0/14 (0%)
Injury	0/204 (0%)		0/206 (0%)		1/206 (0.5%)		0/24 (0%)		0/25 (0%)		0/60 (0%)		0/9 (0%)		0/9 (0%)		0/16 (0%)		0/34 (0%)		0/36 (0%)		0/14 (0%)
Joint sprain	0/204 (0%)		0/206 (0%)		1/206 (0.5%)		0/24 (0%)		0/25 (0%)		0/60 (0%)		0/9 (0%)		0/9 (0%)		0/16 (0%)		0/34 (0%)		0/36 (0%)		0/14 (0%)
Ligament rupture	0/204 (0%)		0/206 (0%)		1/206 (0.5%)		0/24 (0%)		0/25 (0%)		0/60 (0%)		0/9 (0%)		0/9 (0%)		0/16 (0%)		0/34 (0%)		0/36 (0%)		0/14 (0%)
Skin injury	0/204 (0%)		0/206 (0%)		1/206 (0.5%)		0/24 (0%)		0/25 (0%)		0/60 (0%)		0/9 (0%)		0/9 (0%)		0/16 (0%)		0/34 (0%)		0/36 (0%)		0/14 (0%)
Thoracic vertebral fracture	0/204 (0%)		1/206 (0.5%)		0/206 (0%)		0/24 (0%)		0/25 (0%)		0/60 (0%)		0/9 (0%)		0/9 (0%)		0/16 (0%)		0/34 (0%)		0/36 (0%)		0/14 (0%)
Investigations
Blood creatine phosphokinase increased	3/204 (1.5%)		7/206 (3.4%)		4/206 (1.9%)		1/24 (4.2%)		0/25 (0%)		0/60 (0%)		0/9 (0%)		0/9 (0%)		1/16 (6.3%)		0/34 (0%)		0/36 (0%)		0/14 (0%)
Blood uric acid increased	0/204 (0%)		0/206 (0%)		1/206 (0.5%)		0/24 (0%)		0/25 (0%)		1/60 (1.7%)		0/9 (0%)		0/9 (0%)		0/16 (0%)		0/34 (0%)		0/36 (0%)		0/14 (0%)
Alanine aminotransferase increased	0/204 (0%)		1/206 (0.5%)		1/206 (0.5%)		0/24 (0%)		0/25 (0%)		0/60 (0%)		0/9 (0%)		0/9 (0%)		0/16 (0%)		0/34 (0%)		0/36 (0%)		0/14 (0%)
Blood amylase increased	0/204 (0%)		2/206 (1%)		0/206 (0%)		0/24 (0%)		0/25 (0%)		0/60 (0%)		0/9 (0%)		0/9 (0%)		0/16 (0%)		0/34 (0%)		0/36 (0%)		0/14 (0%)
Lipase increased	0/204 (0%)		2/206 (1%)		0/206 (0%)		0/24 (0%)		0/25 (0%)		0/60 (0%)		0/9 (0%)		0/9 (0%)		0/16 (0%)		0/34 (0%)		0/36 (0%)		0/14 (0%)
Aspartate aminotransferase increased	0/204 (0%)		0/206 (0%)		1/206 (0.5%)		0/24 (0%)		0/25 (0%)		0/60 (0%)		0/9 (0%)		0/9 (0%)		0/16 (0%)		0/34 (0%)		0/36 (0%)		0/14 (0%)
Blood potassium increased	0/204 (0%)		0/206 (0%)		1/206 (0.5%)		0/24 (0%)		0/25 (0%)		0/60 (0%)		0/9 (0%)		0/9 (0%)		0/16 (0%)		0/34 (0%)		0/36 (0%)		0/14 (0%)
Platelet count decreased	0/204 (0%)		1/206 (0.5%)		0/206 (0%)		0/24 (0%)		0/25 (0%)		0/60 (0%)		0/9 (0%)		0/9 (0%)		0/16 (0%)		0/34 (0%)		0/36 (0%)		0/14 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	0/204 (0%)		1/206 (0.5%)		0/206 (0%)		0/24 (0%)		0/25 (0%)		0/60 (0%)		0/9 (0%)		0/9 (0%)		0/16 (0%)		0/34 (0%)		0/36 (0%)		0/14 (0%)
Arthropathy	0/204 (0%)		1/206 (0.5%)		0/206 (0%)		0/24 (0%)		0/25 (0%)		0/60 (0%)		0/9 (0%)		0/9 (0%)		0/16 (0%)		0/34 (0%)		0/36 (0%)		0/14 (0%)
Neck pain	0/204 (0%)		0/206 (0%)		1/206 (0.5%)		0/24 (0%)		0/25 (0%)		0/60 (0%)		0/9 (0%)		0/9 (0%)		0/16 (0%)		0/34 (0%)		0/36 (0%)		0/14 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Pituitary tumour benign	0/204 (0%)		0/206 (0%)		0/206 (0%)		0/24 (0%)		1/25 (4%)		0/60 (0%)		0/9 (0%)		0/9 (0%)		0/16 (0%)		0/34 (0%)		0/36 (0%)		0/14 (0%)
Thyroid neoplasm	0/204 (0%)		0/206 (0%)		3/206 (1.5%)		0/24 (0%)		0/25 (0%)		0/60 (0%)		0/9 (0%)		0/9 (0%)		0/16 (0%)		0/34 (0%)		0/36 (0%)		0/14 (0%)
Uterine leiomyoma	1/204 (0.5%)		0/206 (0%)		2/206 (1%)		0/24 (0%)		0/25 (0%)		0/60 (0%)		0/9 (0%)		0/9 (0%)		0/16 (0%)		0/34 (0%)		0/36 (0%)		0/14 (0%)
Papillary thyroid cancer	0/204 (0%)		1/206 (0.5%)		0/206 (0%)		0/24 (0%)		0/25 (0%)		0/60 (0%)		0/9 (0%)		0/9 (0%)		0/16 (0%)		0/34 (0%)		0/36 (0%)		0/14 (0%)
Skin papilloma	0/204 (0%)		1/206 (0.5%)		0/206 (0%)		0/24 (0%)		0/25 (0%)		0/60 (0%)		0/9 (0%)		0/9 (0%)		0/16 (0%)		0/34 (0%)		0/36 (0%)		0/14 (0%)
Squamous cell carcinoma of skin	0/204 (0%)		1/206 (0.5%)		0/206 (0%)		0/24 (0%)		0/25 (0%)		0/60 (0%)		0/9 (0%)		0/9 (0%)		0/16 (0%)		0/34 (0%)		0/36 (0%)		0/14 (0%)
Tonsillar neoplasm benign	0/204 (0%)		0/206 (0%)		1/206 (0.5%)		0/24 (0%)		0/25 (0%)		0/60 (0%)		0/9 (0%)		0/9 (0%)		0/16 (0%)		0/34 (0%)		0/36 (0%)		0/14 (0%)
Melanocytic naevus	0/204 (0%)		0/206 (0%)		0/206 (0%)		0/24 (0%)		0/25 (0%)		0/60 (0%)		0/9 (0%)		0/9 (0%)		0/16 (0%)		0/34 (0%)		1/36 (2.8%)		0/14 (0%)
Nervous system disorders
Cerebral haemorrhage	1/204 (0.5%)		0/206 (0%)		0/206 (0%)		0/24 (0%)		0/25 (0%)		0/60 (0%)		0/9 (0%)		0/9 (0%)		0/16 (0%)		0/34 (0%)		0/36 (0%)		0/14 (0%)
Pregnancy, puerperium and perinatal conditions
Abortion spontaneous	0/204 (0%)		0/206 (0%)		1/206 (0.5%)		0/24 (0%)		0/25 (0%)		0/60 (0%)		0/9 (0%)		0/9 (0%)		0/16 (0%)		0/34 (0%)		0/36 (0%)		0/14 (0%)
Pregnancy	2/204 (1%)		0/206 (0%)		1/206 (0.5%)		0/24 (0%)		0/25 (0%)		1/60 (1.7%)		0/9 (0%)		0/9 (0%)		0/16 (0%)		0/34 (0%)		0/36 (0%)		0/14 (0%)
Psychiatric disorders
Delirium	0/204 (0%)		0/206 (0%)		1/206 (0.5%)		0/24 (0%)		0/25 (0%)		0/60 (0%)		0/9 (0%)		0/9 (0%)		0/16 (0%)		0/34 (0%)		0/36 (0%)		0/14 (0%)
Renal and urinary disorders
Calculus ureteric	0/204 (0%)		0/206 (0%)		0/206 (0%)		0/24 (0%)		0/25 (0%)		1/60 (1.7%)		0/9 (0%)		0/9 (0%)		0/16 (0%)		0/34 (0%)		0/36 (0%)		0/14 (0%)
Calculus urinary	0/204 (0%)		1/206 (0.5%)		0/206 (0%)		0/24 (0%)		0/25 (0%)		0/60 (0%)		0/9 (0%)		0/9 (0%)		0/16 (0%)		0/34 (0%)		0/36 (0%)		0/14 (0%)
Renal colic	0/204 (0%)		1/206 (0.5%)		0/206 (0%)		0/24 (0%)		0/25 (0%)		0/60 (0%)		0/9 (0%)		0/9 (0%)		0/16 (0%)		0/34 (0%)		0/36 (0%)		0/14 (0%)
Reproductive system and breast disorders
Ovarian cyst	1/204 (0.5%)		1/206 (0.5%)		1/206 (0.5%)		0/24 (0%)		0/25 (0%)		0/60 (0%)		0/9 (0%)		0/9 (0%)		0/16 (0%)		0/34 (0%)		0/36 (0%)		0/14 (0%)
Bartholin's cyst	0/204 (0%)		1/206 (0.5%)		0/206 (0%)		0/24 (0%)		0/25 (0%)		0/60 (0%)		0/9 (0%)		0/9 (0%)		0/16 (0%)		0/34 (0%)		0/36 (0%)		0/14 (0%)
Fibrocystic breast disease	0/204 (0%)		1/206 (0.5%)		0/206 (0%)		0/24 (0%)		0/25 (0%)		0/60 (0%)		0/9 (0%)		0/9 (0%)		0/16 (0%)		0/34 (0%)		0/36 (0%)		0/14 (0%)
Respiratory, thoracic and mediastinal disorders
Nasal cyst	0/204 (0%)		0/206 (0%)		0/206 (0%)		0/24 (0%)		1/25 (4%)		0/60 (0%)		0/9 (0%)		0/9 (0%)		0/16 (0%)		0/34 (0%)		0/36 (0%)		0/14 (0%)
Pulmonary oedema	1/204 (0.5%)		0/206 (0%)		0/206 (0%)		0/24 (0%)		0/25 (0%)		0/60 (0%)		0/9 (0%)		0/9 (0%)		0/16 (0%)		0/34 (0%)		0/36 (0%)		0/14 (0%)
Tracheal mass	0/204 (0%)		0/206 (0%)		1/206 (0.5%)		0/24 (0%)		0/25 (0%)		0/60 (0%)		0/9 (0%)		0/9 (0%)		0/16 (0%)		0/34 (0%)		0/36 (0%)		0/14 (0%)
Skin and subcutaneous tissue disorders
Psoriasis	0/204 (0%)		0/206 (0%)		0/206 (0%)		0/24 (0%)		0/25 (0%)		1/60 (1.7%)		0/9 (0%)		0/9 (0%)		0/16 (0%)		0/34 (0%)		0/36 (0%)		0/14 (0%)
Vascular disorders
Hypertension	1/204 (0.5%)		0/206 (0%)		0/206 (0%)		0/24 (0%)		0/25 (0%)		0/60 (0%)		0/9 (0%)		0/9 (0%)		0/16 (0%)		0/34 (0%)		0/36 (0%)		0/14 (0%)
Other (Not Including Serious) Adverse Events
	Cladribine 5.25 mg/kg (ITP)		Cladribine 3.5 mg/kg (ITP)		Placebo (ITP)		Cladribine 5.25 mg/kg, Rebif (OLMP)		Cladribine 3.5 mg/kg, Rebif (OLMP)		Placebo, Rebif (OLMP)		Cladribine 5.25 mg/kg, Rebif, Cladribine 3.5 mg/kg (LTFU)		Cladribine 3.5 mg/kg, Rebif, Cladribine 3.5 mg/kg (LTFU)		Placebo, Rebif, Cladribine 3.5 mg/kg (LTFU)		Cladribine 5.25 mg/kg, Rebif (LTFU)		Cladribine 3.5 mg/kg, Rebif (LTFU)		Placebo, Rebif (LTFU)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	133/204 (65.2%)		132/206 (64.1%)		116/206 (56.3%)		18/24 (75%)		19/25 (76%)		41/60 (68.3%)		3/9 (33.3%)		4/9 (44.4%)		7/16 (43.8%)		2/34 (5.9%)		0/36 (0%)		2/14 (14.3%)
Blood and lymphatic system disorders
Lymphopenia	47/204 (23%)		25/206 (12.1%)		0/206 (0%)		2/24 (8.3%)		1/25 (4%)		2/60 (3.3%)		0/9 (0%)		1/9 (11.1%)		0/16 (0%)		0/34 (0%)		0/36 (0%)		0/14 (0%)
Leukopenia	0/204 (0%)		0/206 (0%)		0/206 (0%)		0/24 (0%)		2/25 (8%)		2/60 (3.3%)		0/9 (0%)		0/9 (0%)		0/16 (0%)		0/34 (0%)		0/36 (0%)		0/14 (0%)
Neutropenia	0/204 (0%)		0/206 (0%)		0/206 (0%)		0/24 (0%)		2/25 (8%)		1/60 (1.7%)		0/9 (0%)		0/9 (0%)		0/16 (0%)		0/34 (0%)		0/36 (0%)		0/14 (0%)
Ear and labyrinth disorders
Vertigo	0/204 (0%)		0/206 (0%)		0/206 (0%)		1/24 (4.2%)		0/25 (0%)		3/60 (5%)		0/9 (0%)		0/9 (0%)		0/16 (0%)		0/34 (0%)		0/36 (0%)		0/14 (0%)
Eye disorders
Eye pain	0/204 (0%)		0/206 (0%)		0/206 (0%)		0/24 (0%)		0/25 (0%)		3/60 (5%)		0/9 (0%)		0/9 (0%)		0/16 (0%)		0/34 (0%)		0/36 (0%)		0/14 (0%)
Gastrointestinal disorders
Nausea	23/204 (11.3%)		24/206 (11.7%)		19/206 (9.2%)		1/24 (4.2%)		1/25 (4%)		3/60 (5%)		0/9 (0%)		0/9 (0%)		0/16 (0%)		0/34 (0%)		0/36 (0%)		0/14 (0%)
Diarrhoea	11/204 (5.4%)		16/206 (7.8%)		13/206 (6.3%)		0/24 (0%)		0/25 (0%)		0/60 (0%)		0/9 (0%)		0/9 (0%)		0/16 (0%)		0/34 (0%)		0/36 (0%)		0/14 (0%)
Abdominal pain upper	10/204 (4.9%)		15/206 (7.3%)		4/206 (1.9%)		2/24 (8.3%)		0/25 (0%)		0/60 (0%)		0/9 (0%)		0/9 (0%)		0/16 (0%)		0/34 (0%)		0/36 (0%)		0/14 (0%)
Abdominal pain	7/204 (3.4%)		9/206 (4.4%)		12/206 (5.8%)		0/24 (0%)		0/25 (0%)		0/60 (0%)		0/9 (0%)		0/9 (0%)		0/16 (0%)		0/34 (0%)		0/36 (0%)		0/14 (0%)
Toothache	6/204 (2.9%)		14/206 (6.8%)		8/206 (3.9%)		0/24 (0%)		0/25 (0%)		0/60 (0%)		0/9 (0%)		1/9 (11.1%)		0/16 (0%)		0/34 (0%)		0/36 (0%)		0/14 (0%)
Dental caries	0/204 (0%)		0/206 (0%)		0/206 (0%)		2/24 (8.3%)		0/25 (0%)		1/60 (1.7%)		0/9 (0%)		0/9 (0%)		0/16 (0%)		0/34 (0%)		0/36 (0%)		1/14 (7.1%)
Food poisoning	0/204 (0%)		0/206 (0%)		0/206 (0%)		0/24 (0%)		0/25 (0%)		0/60 (0%)		0/9 (0%)		1/9 (11.1%)		1/16 (6.3%)		0/34 (0%)		0/36 (0%)		0/14 (0%)
Gastrointestinal toxicity	0/204 (0%)		0/206 (0%)		0/206 (0%)		0/24 (0%)		0/25 (0%)		0/60 (0%)		0/9 (0%)		0/9 (0%)		1/16 (6.3%)		0/34 (0%)		0/36 (0%)		0/14 (0%)
Radicular cyst	0/204 (0%)		0/206 (0%)		0/206 (0%)		0/24 (0%)		0/25 (0%)		0/60 (0%)		0/9 (0%)		0/9 (0%)		1/16 (6.3%)		0/34 (0%)		0/36 (0%)		0/14 (0%)
General disorders
Fatigue	15/204 (7.4%)		15/206 (7.3%)		19/206 (9.2%)		3/24 (12.5%)		0/25 (0%)		1/60 (1.7%)		0/9 (0%)		0/9 (0%)		0/16 (0%)		0/34 (0%)		0/36 (0%)		0/14 (0%)
Influenza like illness	0/204 (0%)		0/206 (0%)		0/206 (0%)		7/24 (29.2%)		9/25 (36%)		21/60 (35%)		0/9 (0%)		0/9 (0%)		0/16 (0%)		0/34 (0%)		0/36 (0%)		0/14 (0%)
Pyrexia	0/204 (0%)		0/206 (0%)		0/206 (0%)		1/24 (4.2%)		5/25 (20%)		5/60 (8.3%)		0/9 (0%)		0/9 (0%)		0/16 (0%)		0/34 (0%)		0/36 (0%)		0/14 (0%)
Injection site reaction	0/204 (0%)		0/206 (0%)		0/206 (0%)		2/24 (8.3%)		0/25 (0%)		4/60 (6.7%)		0/9 (0%)		0/9 (0%)		0/16 (0%)		0/34 (0%)		0/36 (0%)		0/14 (0%)
Injection site pain	0/204 (0%)		0/206 (0%)		0/206 (0%)		2/24 (8.3%)		0/25 (0%)		3/60 (5%)		0/9 (0%)		0/9 (0%)		0/16 (0%)		0/34 (0%)		0/36 (0%)		0/14 (0%)
Injection site erythema	0/204 (0%)		0/206 (0%)		0/206 (0%)		0/24 (0%)		2/25 (8%)		2/60 (3.3%)		0/9 (0%)		0/9 (0%)		0/16 (0%)		0/34 (0%)		0/36 (0%)		0/14 (0%)
Immune system disorders
Drug hypersensitivity	0/204 (0%)		0/206 (0%)		0/206 (0%)		0/24 (0%)		0/25 (0%)		0/60 (0%)		0/9 (0%)		0/9 (0%)		1/16 (6.3%)		0/34 (0%)		0/36 (0%)		0/14 (0%)
Hypersensitivity	0/204 (0%)		0/206 (0%)		0/206 (0%)		0/24 (0%)		0/25 (0%)		0/60 (0%)		0/9 (0%)		0/9 (0%)		1/16 (6.3%)		0/34 (0%)		0/36 (0%)		0/14 (0%)
Infections and infestations
Nasopharyngitis	36/204 (17.6%)		35/206 (17%)		38/206 (18.4%)		2/24 (8.3%)		1/25 (4%)		5/60 (8.3%)		0/9 (0%)		1/9 (11.1%)		0/16 (0%)		0/34 (0%)		0/36 (0%)		0/14 (0%)
Upper respiratory tract infection	23/204 (11.3%)		21/206 (10.2%)		17/206 (8.3%)		0/24 (0%)		0/25 (0%)		0/60 (0%)		1/9 (11.1%)		0/9 (0%)		2/16 (12.5%)		0/34 (0%)		0/36 (0%)		0/14 (0%)
Influenza	14/204 (6.9%)		21/206 (10.2%)		13/206 (6.3%)		2/24 (8.3%)		0/25 (0%)		6/60 (10%)		0/9 (0%)		0/9 (0%)		0/16 (0%)		0/34 (0%)		0/36 (0%)		0/14 (0%)
Pharyngitis	12/204 (5.9%)		10/206 (4.9%)		12/206 (5.8%)		2/24 (8.3%)		9/25 (36%)		3/60 (5%)		0/9 (0%)		0/9 (0%)		0/16 (0%)		0/34 (0%)		0/36 (0%)		0/14 (0%)
Vaginal candidiasis	0/204 (0%)		0/206 (0%)		0/206 (0%)		0/24 (0%)		0/25 (0%)		0/60 (0%)		0/9 (0%)		1/9 (11.1%)		1/16 (6.3%)		0/34 (0%)		0/36 (0%)		0/14 (0%)
Acute tonsillitis	0/204 (0%)		0/206 (0%)		0/206 (0%)		0/24 (0%)		0/25 (0%)		0/60 (0%)		0/9 (0%)		1/9 (11.1%)		0/16 (0%)		0/34 (0%)		0/36 (0%)		0/14 (0%)
Bronchitis	0/204 (0%)		0/206 (0%)		0/206 (0%)		0/24 (0%)		0/25 (0%)		0/60 (0%)		0/9 (0%)		1/9 (11.1%)		0/16 (0%)		0/34 (0%)		0/36 (0%)		0/14 (0%)
Hordeolum	0/204 (0%)		0/206 (0%)		0/206 (0%)		0/24 (0%)		0/25 (0%)		0/60 (0%)		0/9 (0%)		0/9 (0%)		1/16 (6.3%)		0/34 (0%)		0/36 (0%)		0/14 (0%)
Respiratory tract infection viral	0/204 (0%)		0/206 (0%)		0/206 (0%)		0/24 (0%)		0/25 (0%)		0/60 (0%)		0/9 (0%)		0/9 (0%)		1/16 (6.3%)		0/34 (0%)		0/36 (0%)		0/14 (0%)
Wound	0/204 (0%)		0/206 (0%)		0/206 (0%)		0/24 (0%)		0/25 (0%)		0/60 (0%)		0/9 (0%)		0/9 (0%)		1/16 (6.3%)		0/34 (0%)		0/36 (0%)		0/14 (0%)
Investigations
Alanine aminotransferase increased	0/204 (0%)		1/206 (0.5%)		1/206 (0.5%)		0/24 (0%)		0/25 (0%)		3/60 (5%)		0/9 (0%)		0/9 (0%)		1/16 (6.3%)		0/34 (0%)		0/36 (0%)		0/14 (0%)
Aspartate aminotransferase increased	0/204 (0%)		0/206 (0%)		1/206 (0.5%)		1/24 (4.2%)		0/25 (0%)		4/60 (6.7%)		0/9 (0%)		0/9 (0%)		0/16 (0%)		0/34 (0%)		0/36 (0%)		0/14 (0%)
Musculoskeletal and connective tissue disorders
Back pain	14/204 (6.9%)		17/206 (8.3%)		13/206 (6.3%)		2/24 (8.3%)		0/25 (0%)		3/60 (5%)		0/9 (0%)		0/9 (0%)		0/16 (0%)		0/34 (0%)		0/36 (0%)		0/14 (0%)
Arthralgia	10/204 (4.9%)		13/206 (6.3%)		13/206 (6.3%)		0/24 (0%)		2/25 (8%)		2/60 (3.3%)		0/9 (0%)		0/9 (0%)		0/16 (0%)		0/34 (0%)		0/36 (0%)		0/14 (0%)
Pain in extremity	10/204 (4.9%)		11/206 (5.3%)		9/206 (4.4%)		0/24 (0%)		0/25 (0%)		0/60 (0%)		0/9 (0%)		0/9 (0%)		0/16 (0%)		0/34 (0%)		0/36 (0%)		0/14 (0%)
Myalgia	0/204 (0%)		0/206 (0%)		0/206 (0%)		3/24 (12.5%)		0/25 (0%)		7/60 (11.7%)		0/9 (0%)		0/9 (0%)		0/16 (0%)		0/34 (0%)		0/36 (0%)		0/14 (0%)
Musculoskeletal pain	0/204 (0%)		0/206 (0%)		0/206 (0%)		0/24 (0%)		2/25 (8%)		3/60 (5%)		0/9 (0%)		0/9 (0%)		0/16 (0%)		0/34 (0%)		0/36 (0%)		0/14 (0%)
Nervous system disorders
Headache	58/204 (28.4%)		64/206 (31.1%)		57/206 (27.7%)		5/24 (20.8%)		8/25 (32%)		10/60 (16.7%)		1/9 (11.1%)		0/9 (0%)		3/16 (18.8%)		2/34 (5.9%)		0/36 (0%)		0/14 (0%)
Dizziness	12/204 (5.9%)		16/206 (7.8%)		19/206 (9.2%)		0/24 (0%)		0/25 (0%)		0/60 (0%)		0/9 (0%)		0/9 (0%)		0/16 (0%)		0/34 (0%)		0/36 (0%)		0/14 (0%)
Paraesthesia	9/204 (4.4%)		11/206 (5.3%)		10/206 (4.9%)		0/24 (0%)		0/25 (0%)		0/60 (0%)		0/9 (0%)		0/9 (0%)		1/16 (6.3%)		0/34 (0%)		0/36 (0%)		0/14 (0%)
Hypoaesthesia	0/204 (0%)		0/206 (0%)		0/206 (0%)		0/24 (0%)		0/25 (0%)		0/60 (0%)		0/9 (0%)		0/9 (0%)		1/16 (6.3%)		0/34 (0%)		0/36 (0%)		0/14 (0%)
Nystagmus	0/204 (0%)		0/206 (0%)		0/206 (0%)		0/24 (0%)		0/25 (0%)		0/60 (0%)		0/9 (0%)		0/9 (0%)		1/16 (6.3%)		0/34 (0%)		0/36 (0%)		0/14 (0%)
Psychiatric disorders
Insomnia	5/204 (2.5%)		9/206 (4.4%)		12/206 (5.8%)		1/24 (4.2%)		1/25 (4%)		4/60 (6.7%)		0/9 (0%)		0/9 (0%)		0/16 (0%)		0/34 (0%)		0/36 (0%)		0/14 (0%)
Neurosis	0/204 (0%)		0/206 (0%)		0/206 (0%)		0/24 (0%)		0/25 (0%)		0/60 (0%)		0/9 (0%)		1/9 (11.1%)		0/16 (0%)		0/34 (0%)		0/36 (0%)		0/14 (0%)
Reproductive system and breast disorders
Bartholin's cyst	0/204 (0%)		0/206 (0%)		0/206 (0%)		0/24 (0%)		0/25 (0%)		0/60 (0%)		1/9 (11.1%)		0/9 (0%)		0/16 (0%)		0/34 (0%)		0/36 (0%)		0/14 (0%)
Dysmenorrhoea	0/204 (0%)		0/206 (0%)		0/206 (0%)		0/24 (0%)		0/25 (0%)		0/60 (0%)		0/9 (0%)		0/9 (0%)		0/16 (0%)		0/34 (0%)		0/36 (0%)		1/14 (7.1%)
Respiratory, thoracic and mediastinal disorders
Pharyngolaryngeal pain	16/204 (7.8%)		10/206 (4.9%)		10/206 (4.9%)		0/24 (0%)		0/25 (0%)		0/60 (0%)		0/9 (0%)		0/9 (0%)		0/16 (0%)		0/34 (0%)		0/36 (0%)		0/14 (0%)
Cough	10/204 (4.9%)		8/206 (3.9%)		11/206 (5.3%)		2/24 (8.3%)		1/25 (4%)		1/60 (1.7%)		0/9 (0%)		0/9 (0%)		0/16 (0%)		0/34 (0%)		0/36 (0%)		0/14 (0%)
Skin and subcutaneous tissue disorders
Hyperhidrosis	0/204 (0%)		0/206 (0%)		0/206 (0%)		0/24 (0%)		0/25 (0%)		0/60 (0%)		0/9 (0%)		0/9 (0%)		1/16 (6.3%)		0/34 (0%)		0/36 (0%)		0/14 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Results Point of Contact

Name/Title	Communication Center
Organization	Merck KGaA, Darmstadt, Germany
Phone	+49-6151-72-5200
Email	service@emdgroup.com

Responsible Party:

EMD Serono Research & Development Institute, Inc.

ClinicalTrials.gov Identifier:

NCT00725985

Other Study ID Numbers:

28821

First Posted:

Jul 31, 2008

Last Update Posted:

Mar 22, 2021

Last Verified:

Feb 1, 2021