Trial Outcomes & Findings for A Phase 2 Study of Cladribine Add-on to Interferon-beta (IFN-beta) Therapy in Multiple Sclerosis (MS) Subjects With Active Disease (ONWARD) (NCT NCT00436826)
NCT ID: NCT00436826
Last Updated: 2020-10-12
Results Overview
Percentage of participants with Grade 3 or 4 CTCAE v 4.0 toxicity on the following hematology and liver function parameters were reported: lymphocytes, cluster of differentiation 4 (CD4) cell, neutrophils, white blood cells, hemoglobin, Alanine transaminase (ALT), Aspartate transaminase (AST), Platelets and Bilirubin. According to CTCAE v 4.0: Grade 1=mild, Grade 2=moderate, Grade 3=severe, Grade 4=life threatening or disabling and Grade 5=Death.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
172 participants
Primary outcome timeframe
Baseline up to Week 96
Results posted on
2020-10-12
Participant Flow
Initially 42 participants randomized under original protocol but enrollment terminated because of hematological toxicities. Protocol amendment 1 and 2 were implemented and enrolled 172 participants. Protocol amendment 5 was generated, resulting in discontinuation of Cladribine and reduction of Extension period and Safety Follow up to 48 weeks.
Participant milestones
| Measure |
Cladribine 3.5 mg/kg, IFN-beta (DB Period)
Participants received cladribine tablets orally as cumulative dose of 0.875 mg/kg over a course of 4-5 consecutive days at Week 1, 5, 48, and 52 resulting in total cladribine dose of 3.5 milligram per kilogram (mg/kg) along with interferon (IFN)-beta therapy (Rebif® new formulation \[RNF\] 44 mcg three times a week, subcutaneously; Avonex® 30 microgram (mcg) every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) during the Double blind period (DBP) of 96 weeks.
|
Placebo, IFN-beta (DB Period)
Participants received matching placebo tablets orally over a course of 4-5 consecutive days at Week 1, 5, 48, and 52 along with IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) during the DB period of 96 weeks.
|
Cladribine 3.5 mg/kg, IFN-beta, Cladribine 3.5 mg/kg (OL Ext)
Participants who received cladribine 3.5 mg/kg initially and completed DB period entered in the open label (OL) extension (Ext.) period. In OL Ext. period, participant who met the eligibility criteria received OL oral cladribine 3.5 mg/kg over maximum of 48 weeks along with IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) up to 48 weeks.
|
Placebo, IFN-beta, Cladribine 3.5 mg/kg (OL Ext)
Participants who received placebo initially and completed DB period entered in the OL Ext. period. In OL Ext. period, participant who met the eligibility criteria received OL oral cladribine 3.5 mg/kg over maximum of 48 weeks along with IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) up to 48 weeks.
|
Cladribine 3.5 mg/kg, IFN-beta (Safety Follow up)
Participants who received cladribine 3.5 mg/kg initially and completed DB period entered in the OL ext. safety follow up period. In this period, participants who did not meet eligibility criteria received only IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) up to 48 weeks.
|
Placebo, IFN-beta (Safety Follow up)
Participants who received placebo initially and completed DB period entered in the OL ext. safety follow up period. In this period, participants who did not meet eligibility criteria received only IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) up to 48 weeks.
|
|---|---|---|---|---|---|---|
|
Double Blind Period (DBP)
STARTED
|
124
|
48
|
0
|
0
|
0
|
0
|
|
Double Blind Period (DBP)
COMPLETED
|
111
|
37
|
0
|
0
|
0
|
0
|
|
Double Blind Period (DBP)
NOT COMPLETED
|
13
|
11
|
0
|
0
|
0
|
0
|
|
Ext. Period (With Cladribine Treatment)
STARTED
|
0
|
0
|
47
|
28
|
0
|
0
|
|
Ext. Period (With Cladribine Treatment)
COMPLETED
|
0
|
0
|
1
|
2
|
0
|
0
|
|
Ext. Period (With Cladribine Treatment)
NOT COMPLETED
|
0
|
0
|
46
|
26
|
0
|
0
|
|
Ext. Period (No Cladribine Treatment)
STARTED
|
0
|
0
|
0
|
0
|
52
|
7
|
|
Ext. Period (No Cladribine Treatment)
COMPLETED
|
0
|
0
|
0
|
0
|
1
|
0
|
|
Ext. Period (No Cladribine Treatment)
NOT COMPLETED
|
0
|
0
|
0
|
0
|
51
|
7
|
Reasons for withdrawal
| Measure |
Cladribine 3.5 mg/kg, IFN-beta (DB Period)
Participants received cladribine tablets orally as cumulative dose of 0.875 mg/kg over a course of 4-5 consecutive days at Week 1, 5, 48, and 52 resulting in total cladribine dose of 3.5 milligram per kilogram (mg/kg) along with interferon (IFN)-beta therapy (Rebif® new formulation \[RNF\] 44 mcg three times a week, subcutaneously; Avonex® 30 microgram (mcg) every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) during the Double blind period (DBP) of 96 weeks.
|
Placebo, IFN-beta (DB Period)
Participants received matching placebo tablets orally over a course of 4-5 consecutive days at Week 1, 5, 48, and 52 along with IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) during the DB period of 96 weeks.
|
Cladribine 3.5 mg/kg, IFN-beta, Cladribine 3.5 mg/kg (OL Ext)
Participants who received cladribine 3.5 mg/kg initially and completed DB period entered in the open label (OL) extension (Ext.) period. In OL Ext. period, participant who met the eligibility criteria received OL oral cladribine 3.5 mg/kg over maximum of 48 weeks along with IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) up to 48 weeks.
|
Placebo, IFN-beta, Cladribine 3.5 mg/kg (OL Ext)
Participants who received placebo initially and completed DB period entered in the OL Ext. period. In OL Ext. period, participant who met the eligibility criteria received OL oral cladribine 3.5 mg/kg over maximum of 48 weeks along with IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) up to 48 weeks.
|
Cladribine 3.5 mg/kg, IFN-beta (Safety Follow up)
Participants who received cladribine 3.5 mg/kg initially and completed DB period entered in the OL ext. safety follow up period. In this period, participants who did not meet eligibility criteria received only IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) up to 48 weeks.
|
Placebo, IFN-beta (Safety Follow up)
Participants who received placebo initially and completed DB period entered in the OL ext. safety follow up period. In this period, participants who did not meet eligibility criteria received only IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) up to 48 weeks.
|
|---|---|---|---|---|---|---|
|
Double Blind Period (DBP)
Adverse Event
|
2
|
0
|
0
|
0
|
0
|
0
|
|
Double Blind Period (DBP)
Protocol Violation
|
1
|
0
|
0
|
0
|
0
|
0
|
|
Double Blind Period (DBP)
Other
|
10
|
11
|
0
|
0
|
0
|
0
|
|
Ext. Period (With Cladribine Treatment)
Lost to Follow-up
|
0
|
0
|
0
|
1
|
0
|
0
|
|
Ext. Period (With Cladribine Treatment)
Other un-specified
|
0
|
0
|
46
|
25
|
0
|
0
|
|
Ext. Period (No Cladribine Treatment)
Sponsor's decision to terminate study
|
0
|
0
|
0
|
0
|
51
|
7
|
Baseline Characteristics
A Phase 2 Study of Cladribine Add-on to Interferon-beta (IFN-beta) Therapy in Multiple Sclerosis (MS) Subjects With Active Disease (ONWARD)
Baseline characteristics by cohort
| Measure |
Cladribine 3.5 mg/kg, IFN-beta
n=124 Participants
Participants received cladribine tablets orally as cumulative dose of 0.875 milligram per kilogram (mg/kg) over a course of 4-5 consecutive days at Week 1, 5, 48, and 52 resulting in total cladribine dose of 3.5 mg/kg along with IFN-beta therapy (Rebif® new formulation \[RNF\] 44 microgram \[mcg\] three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) during the double blind (DB) period of 96 weeks. After completing DB period, participants entered in OL extension period. In OL extension period, participant who met eligibility criteria received OL oral cladribine 3.5 mg/kg and participants who did not meet the eligibility criteria received IFN-beta only and were followed for safety only.
|
Placebo, IFN-beta
n=48 Participants
Participants received matching placebo tablets orally over a course of 4-5 consecutive days at Week 1, 5, 48, and 52 along with IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) during the double blind (DB) period of 96 weeks. After completing DB period, participants entered in OL extension period. In OL extension period, participant who met eligibility criteria received OL oral cladribine 3.5 mg/kg and participants participants who did not meet the eligibility criteria received IFN-beta only and were followed for safety only.
|
Total
n=172 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
38.5 years
STANDARD_DEVIATION 10.2 • n=5 Participants
|
40.1 years
STANDARD_DEVIATION 10.3 • n=7 Participants
|
38.9 years
STANDARD_DEVIATION 10.2 • n=5 Participants
|
|
Sex: Female, Male
Female
|
84 Participants
n=5 Participants
|
36 Participants
n=7 Participants
|
120 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
40 Participants
n=5 Participants
|
12 Participants
n=7 Participants
|
52 Participants
n=5 Participants
|
|
Time (years) from first attack to study Day 1
|
9.98 years
STANDARD_DEVIATION 7.24 • n=5 Participants
|
10.83 years
STANDARD_DEVIATION 7.98 • n=7 Participants
|
10.22 years
STANDARD_DEVIATION 7.44 • n=5 Participants
|
|
Expanded disability status scale (EDSS) score
|
2.9 unit on scale
STANDARD_DEVIATION 1.2 • n=5 Participants
|
3.0 unit on scale
STANDARD_DEVIATION 1.2 • n=7 Participants
|
2.9 unit on scale
STANDARD_DEVIATION 1.2 • n=5 Participants
|
|
Number of Gadolinium-enhanced lesions
|
1.1 lesions
STANDARD_DEVIATION 4.0 • n=5 Participants
|
0.6 lesions
STANDARD_DEVIATION 1.2 • n=7 Participants
|
0.9 lesions
STANDARD_DEVIATION 3.4 • n=5 Participants
|
|
Number of Time constant 1 (T1) hypointense lesions
|
9.0 lesions
STANDARD_DEVIATION 9.2 • n=5 Participants
|
9.3 lesions
STANDARD_DEVIATION 9.9 • n=7 Participants
|
9.1 lesions
STANDARD_DEVIATION 9.3 • n=5 Participants
|
|
T1 Gd+ volume
|
150.3 cubic millimetre (mm^3)
STANDARD_DEVIATION 592.2 • n=5 Participants
|
99.4 cubic millimetre (mm^3)
STANDARD_DEVIATION 210.0 • n=7 Participants
|
136.1 cubic millimetre (mm^3)
STANDARD_DEVIATION 514.5 • n=5 Participants
|
|
T2 lesions volume
|
10791.2 mm^3
STANDARD_DEVIATION 11298.0 • n=5 Participants
|
13669.1 mm^3
STANDARD_DEVIATION 16605.2 • n=7 Participants
|
11596.3 mm^3
STANDARD_DEVIATION 13013.5 • n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline up to Week 96Population: Safety population: all randomized participants who received at least 1 dose of study drug in DBP and had follow-up safety data.
Percentage of participants with Grade 3 or 4 CTCAE v 4.0 toxicity on the following hematology and liver function parameters were reported: lymphocytes, cluster of differentiation 4 (CD4) cell, neutrophils, white blood cells, hemoglobin, Alanine transaminase (ALT), Aspartate transaminase (AST), Platelets and Bilirubin. According to CTCAE v 4.0: Grade 1=mild, Grade 2=moderate, Grade 3=severe, Grade 4=life threatening or disabling and Grade 5=Death.
Outcome measures
| Measure |
Cladribine 3.5 mg/kg, IFN-beta (DB Period)
n=124 Participants
Participants received cladribine tablets orally as cumulative dose of 0.875 mg/kg over a course of 4-5 consecutive days at Week 1, 5, 48, and 52 resulting in total cladribine dose of 3.5 milligram per kilogram (mg/kg) along with interferon (IFN)-beta therapy (Rebif® new formulation \[RNF\] 44 mcg three times a week, subcutaneously; Avonex® 30 microgram (mcg) every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) during the Double blind period (DBP) of 96 weeks.
|
Placebo, IFN-beta (DB Period)
n=48 Participants
Participants received matching placebo tablets orally over a course of 4-5 consecutive days at Week 1, 5, 48, and 52 along with IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) during the DB period of 96 weeks.
|
Cladribine 3.5 mg/kg, IFN-beta, Cladribine 3.5 mg/kg (OL Ext)
Participants who received cladribine 3.5 mg/kg initially and completed DB period entered in the open label (OL) extension (Ext.) period. In OL Ext. period, participant who met the eligibility criteria received OL oral cladribine 3.5 mg/kg over maximum of 48 weeks along with IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) up to 48 weeks.
|
Placebo, IFN-beta, Cladribine 3.5 mg/kg (OL Ext)
Participants who received placebo initially and completed DB period entered in the OL Ext. period. In OL Ext. period, participant who met the eligibility criteria received OL oral cladribine 3.5 mg/kg over maximum of 48 weeks along with IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) up to 48 weeks.
|
|---|---|---|---|---|
|
Double Blind Period: Percentage of Participants With Grade 3 or 4 (Common Terminology Criteria for Adverse Events [CTCAE] v 4.0) Hematological or Liver Toxicity
Grade 3 or 4 Lymphocyte toxicity
|
63.71 Percentage of participants
|
2.08 Percentage of participants
|
—
|
—
|
|
Double Blind Period: Percentage of Participants With Grade 3 or 4 (Common Terminology Criteria for Adverse Events [CTCAE] v 4.0) Hematological or Liver Toxicity
Grade 3 or 4 Hemoglobin toxicity
|
2.42 Percentage of participants
|
0.00 Percentage of participants
|
—
|
—
|
|
Double Blind Period: Percentage of Participants With Grade 3 or 4 (Common Terminology Criteria for Adverse Events [CTCAE] v 4.0) Hematological or Liver Toxicity
Grade 3 or 4 White Blood Cell toxicity
|
10.48 Percentage of participants
|
0.00 Percentage of participants
|
—
|
—
|
|
Double Blind Period: Percentage of Participants With Grade 3 or 4 (Common Terminology Criteria for Adverse Events [CTCAE] v 4.0) Hematological or Liver Toxicity
Grade 3 or 4 Neutrophil toxicity
|
12.10 Percentage of participants
|
2.08 Percentage of participants
|
—
|
—
|
|
Double Blind Period: Percentage of Participants With Grade 3 or 4 (Common Terminology Criteria for Adverse Events [CTCAE] v 4.0) Hematological or Liver Toxicity
Grade 3 or 4 CD4+ toxicity
|
50.81 Percentage of participants
|
2.08 Percentage of participants
|
—
|
—
|
|
Double Blind Period: Percentage of Participants With Grade 3 or 4 (Common Terminology Criteria for Adverse Events [CTCAE] v 4.0) Hematological or Liver Toxicity
Grade 3 or 4 AST toxicity
|
0.81 Percentage of participants
|
0.00 Percentage of participants
|
—
|
—
|
|
Double Blind Period: Percentage of Participants With Grade 3 or 4 (Common Terminology Criteria for Adverse Events [CTCAE] v 4.0) Hematological or Liver Toxicity
Grade 3 or 4 ALT toxicity
|
0.81 Percentage of participants
|
2.08 Percentage of participants
|
—
|
—
|
|
Double Blind Period: Percentage of Participants With Grade 3 or 4 (Common Terminology Criteria for Adverse Events [CTCAE] v 4.0) Hematological or Liver Toxicity
Grade 3 or 4 Platelet toxicity
|
0.00 Percentage of participants
|
0.00 Percentage of participants
|
—
|
—
|
|
Double Blind Period: Percentage of Participants With Grade 3 or 4 (Common Terminology Criteria for Adverse Events [CTCAE] v 4.0) Hematological or Liver Toxicity
Grade 3 or 4 Bilirubin toxicity
|
0.00 Percentage of participants
|
0.00 Percentage of participants
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline up to Week 96Population: Safety population included all randomized participants who received at least one dose of study medication in the DBP and had follow-up safety data.
An Adverse event (AE) was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease associated with the use of study drug, whether or not considered related to the study drug or worsening of pre-existing medical condition, whether or not related to study drug. A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. An AE was considered as 'treatment emergent' if it occurred after the first drug administration of each period or if it was present prior to drug administration but exacerbated after the drug administration.TEAEs were entered in infections and infestations SOC as per medical dictionary for regulatory activities (MedDRA) version 11.0
Outcome measures
| Measure |
Cladribine 3.5 mg/kg, IFN-beta (DB Period)
n=124 Participants
Participants received cladribine tablets orally as cumulative dose of 0.875 mg/kg over a course of 4-5 consecutive days at Week 1, 5, 48, and 52 resulting in total cladribine dose of 3.5 milligram per kilogram (mg/kg) along with interferon (IFN)-beta therapy (Rebif® new formulation \[RNF\] 44 mcg three times a week, subcutaneously; Avonex® 30 microgram (mcg) every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) during the Double blind period (DBP) of 96 weeks.
|
Placebo, IFN-beta (DB Period)
n=48 Participants
Participants received matching placebo tablets orally over a course of 4-5 consecutive days at Week 1, 5, 48, and 52 along with IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) during the DB period of 96 weeks.
|
Cladribine 3.5 mg/kg, IFN-beta, Cladribine 3.5 mg/kg (OL Ext)
Participants who received cladribine 3.5 mg/kg initially and completed DB period entered in the open label (OL) extension (Ext.) period. In OL Ext. period, participant who met the eligibility criteria received OL oral cladribine 3.5 mg/kg over maximum of 48 weeks along with IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) up to 48 weeks.
|
Placebo, IFN-beta, Cladribine 3.5 mg/kg (OL Ext)
Participants who received placebo initially and completed DB period entered in the OL Ext. period. In OL Ext. period, participant who met the eligibility criteria received OL oral cladribine 3.5 mg/kg over maximum of 48 weeks along with IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) up to 48 weeks.
|
|---|---|---|---|---|
|
Double Blind Period: Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) in Infections and Infestations System Organ Class (SOC)
|
61.3 Percentage of participants
|
54.2 Percentage of participants
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline up to Week 96Population: Safety population included all randomized participants who received at least one dose of study medication in the DBP and had follow-up safety data.
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. An AE was considered as 'treatment emergent' if it occurred after the first drug administration of each period or if it was present prior to drug administration but exacerbated after the drug administration. TEAEs included both Serious TEAEs and non-serious TEAEs.
Outcome measures
| Measure |
Cladribine 3.5 mg/kg, IFN-beta (DB Period)
n=124 Participants
Participants received cladribine tablets orally as cumulative dose of 0.875 mg/kg over a course of 4-5 consecutive days at Week 1, 5, 48, and 52 resulting in total cladribine dose of 3.5 milligram per kilogram (mg/kg) along with interferon (IFN)-beta therapy (Rebif® new formulation \[RNF\] 44 mcg three times a week, subcutaneously; Avonex® 30 microgram (mcg) every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) during the Double blind period (DBP) of 96 weeks.
|
Placebo, IFN-beta (DB Period)
n=48 Participants
Participants received matching placebo tablets orally over a course of 4-5 consecutive days at Week 1, 5, 48, and 52 along with IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) during the DB period of 96 weeks.
|
Cladribine 3.5 mg/kg, IFN-beta, Cladribine 3.5 mg/kg (OL Ext)
Participants who received cladribine 3.5 mg/kg initially and completed DB period entered in the open label (OL) extension (Ext.) period. In OL Ext. period, participant who met the eligibility criteria received OL oral cladribine 3.5 mg/kg over maximum of 48 weeks along with IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) up to 48 weeks.
|
Placebo, IFN-beta, Cladribine 3.5 mg/kg (OL Ext)
Participants who received placebo initially and completed DB period entered in the OL Ext. period. In OL Ext. period, participant who met the eligibility criteria received OL oral cladribine 3.5 mg/kg over maximum of 48 weeks along with IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) up to 48 weeks.
|
|---|---|---|---|---|
|
Double Blind Period: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs
Participants with Serious TEAEs
|
12 Participants
|
5 Participants
|
—
|
—
|
|
Double Blind Period: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs
Participants with TEAEs
|
119 Participants
|
36 Participants
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline up to Week 96Population: Safety population included all randomized participants who received at least one dose of study medication in the DBP and had follow-up safety data. Here "Number of Participants analyzed"= participants evaluable for this outcome measure and "number analyzed"= participants who were evaluable for specified category.
Time to first Grade 3 or 4 hematological toxicity or liver toxicity (lymphocytes, cluster of differentiation 4 (CD4) cell, neutrophils, white blood cells, hemoglobin, Alanine transaminase (ALT), Aspartate transaminase (AST), Platelets and Bilirubin) were estimated using the Kaplan-Meier method. According to CTCAE v 4.0: Grade 1=mild, Grade 2=moderate, Grade 3=severe, Grade 4=life threatening or disabling and Grade 5=Death. 10th and 20th percentiles estimated from Kaplan-Meier survival curve. Due to the small number of events, estimates from Kaplan-Meier survival curves could only be derived for lower percentiles. The median (50th percentile) could not be estimated if less than 50% of the participants had an event during the time of the study. Accordingly, lower percentiles are presented according to the number of events observed.
Outcome measures
| Measure |
Cladribine 3.5 mg/kg, IFN-beta (DB Period)
n=79 Participants
Participants received cladribine tablets orally as cumulative dose of 0.875 mg/kg over a course of 4-5 consecutive days at Week 1, 5, 48, and 52 resulting in total cladribine dose of 3.5 milligram per kilogram (mg/kg) along with interferon (IFN)-beta therapy (Rebif® new formulation \[RNF\] 44 mcg three times a week, subcutaneously; Avonex® 30 microgram (mcg) every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) during the Double blind period (DBP) of 96 weeks.
|
Placebo, IFN-beta (DB Period)
n=2 Participants
Participants received matching placebo tablets orally over a course of 4-5 consecutive days at Week 1, 5, 48, and 52 along with IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) during the DB period of 96 weeks.
|
Cladribine 3.5 mg/kg, IFN-beta, Cladribine 3.5 mg/kg (OL Ext)
Participants who received cladribine 3.5 mg/kg initially and completed DB period entered in the open label (OL) extension (Ext.) period. In OL Ext. period, participant who met the eligibility criteria received OL oral cladribine 3.5 mg/kg over maximum of 48 weeks along with IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) up to 48 weeks.
|
Placebo, IFN-beta, Cladribine 3.5 mg/kg (OL Ext)
Participants who received placebo initially and completed DB period entered in the OL Ext. period. In OL Ext. period, participant who met the eligibility criteria received OL oral cladribine 3.5 mg/kg over maximum of 48 weeks along with IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) up to 48 weeks.
|
|---|---|---|---|---|
|
Double Blind Period: Time to First Grade 3 or 4 Hematological Toxicity or Liver Toxicity
10th percentile: Lymphocytes toxicity
|
1.61 Months
|
NA Months
Due to small number of events, estimates from Kaplan-Meier survival curves could not be derived.
|
—
|
—
|
|
Double Blind Period: Time to First Grade 3 or 4 Hematological Toxicity or Liver Toxicity
20th percentile: White Blood Cell toxicity
|
NA Months
Due to small number of events, estimates from Kaplan-Meier survival curves could not be derived.
|
—
|
—
|
—
|
|
Double Blind Period: Time to First Grade 3 or 4 Hematological Toxicity or Liver Toxicity
10th percentile: Neutrophil toxicity
|
12.55 Months
|
NA Months
Due to small number of events, estimates from Kaplan-Meier survival curves could not be derived.
|
—
|
—
|
|
Double Blind Period: Time to First Grade 3 or 4 Hematological Toxicity or Liver Toxicity
20th percentile: Lymphocytes toxicity
|
2.00 Months
|
NA Months
Due to small number of events, estimates from Kaplan-Meier survival curves could not be derived.
|
—
|
—
|
|
Double Blind Period: Time to First Grade 3 or 4 Hematological Toxicity or Liver Toxicity
10th percentile:Hemoglobin toxicity
|
NA Months
Due to small number of events, estimates from Kaplan-Meier survival curves could not be derived.
|
—
|
—
|
—
|
|
Double Blind Period: Time to First Grade 3 or 4 Hematological Toxicity or Liver Toxicity
20th percentile:Hemoglobin toxicity
|
NA Months
Due to small number of events, estimates from Kaplan-Meier survival curves could not be derived.
|
—
|
—
|
—
|
|
Double Blind Period: Time to First Grade 3 or 4 Hematological Toxicity or Liver Toxicity
10th percentile: White Blood Cell toxicity
|
17.74 Months
|
—
|
—
|
—
|
|
Double Blind Period: Time to First Grade 3 or 4 Hematological Toxicity or Liver Toxicity
20th percentile: Neutrophil toxicity
|
NA Months
Due to small number of events, estimates from Kaplan-Meier survival curves could not be derived.
|
NA Months
Due to small number of events, estimates from Kaplan-Meier survival curves could not be derived.
|
—
|
—
|
|
Double Blind Period: Time to First Grade 3 or 4 Hematological Toxicity or Liver Toxicity
10th percentile: CD4+ count toxicity
|
1.87 Months
|
NA Months
Due to small number of events, estimates from Kaplan-Meier survival curves could not be derived.
|
—
|
—
|
|
Double Blind Period: Time to First Grade 3 or 4 Hematological Toxicity or Liver Toxicity
20th percentile: CD4+ count toxicity
|
2.99 Months
|
NA Months
Due to small number of events, estimates from Kaplan-Meier survival curves could not be derived.
|
—
|
—
|
|
Double Blind Period: Time to First Grade 3 or 4 Hematological Toxicity or Liver Toxicity
10th percentile: AST toxicity
|
NA Months
Due to small number of events, estimates from Kaplan-Meier survival curves could not be derived.
|
—
|
—
|
—
|
|
Double Blind Period: Time to First Grade 3 or 4 Hematological Toxicity or Liver Toxicity
20th percentile: AST toxicity
|
NA Months
Due to small number of events, estimates from Kaplan-Meier survival curves could not be derived.
|
—
|
—
|
—
|
|
Double Blind Period: Time to First Grade 3 or 4 Hematological Toxicity or Liver Toxicity
10th percentile: ALT toxicity
|
NA Months
Due to small number of events, estimates from Kaplan-Meier survival curves could not be derived.
|
NA Months
Due to small number of events, estimates from Kaplan-Meier survival curves could not be derived.
|
—
|
—
|
|
Double Blind Period: Time to First Grade 3 or 4 Hematological Toxicity or Liver Toxicity
20th percentile: ALT toxicity
|
NA Months
Due to small number of events, estimates from Kaplan-Meier survival curves could not be derived.
|
NA Months
Due to small number of events, estimates from Kaplan-Meier survival curves could not be derived.
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline up to Week 96Population: Safety population: all randomized participants who received at least 1 dose of study drug in DBP and had follow-up safety data. Here "Number of Participants analyzed"= participants evaluable for this outcome measure and "number analyzed"= participants who had a Grade 3 or 4 abnormality and evaluable at specified category.
Time to recovery from grade 3 or 4 hematological were reported: lymphocytes, platelets, neutrophils, white blood cells and hemoglobin. According to CTCAE v 4.0: Grade 1=mild, Grade 2=moderate, Grade 3=severe, Grade 4=life threatening or disabling and Grade 5=Death. Recovery" as "Recovery from a Grade 3 or 4 toxicity is defined as a return to a Grade 0 or 1.
Outcome measures
| Measure |
Cladribine 3.5 mg/kg, IFN-beta (DB Period)
n=76 Participants
Participants received cladribine tablets orally as cumulative dose of 0.875 mg/kg over a course of 4-5 consecutive days at Week 1, 5, 48, and 52 resulting in total cladribine dose of 3.5 milligram per kilogram (mg/kg) along with interferon (IFN)-beta therapy (Rebif® new formulation \[RNF\] 44 mcg three times a week, subcutaneously; Avonex® 30 microgram (mcg) every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) during the Double blind period (DBP) of 96 weeks.
|
Placebo, IFN-beta (DB Period)
n=2 Participants
Participants received matching placebo tablets orally over a course of 4-5 consecutive days at Week 1, 5, 48, and 52 along with IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) during the DB period of 96 weeks.
|
Cladribine 3.5 mg/kg, IFN-beta, Cladribine 3.5 mg/kg (OL Ext)
Participants who received cladribine 3.5 mg/kg initially and completed DB period entered in the open label (OL) extension (Ext.) period. In OL Ext. period, participant who met the eligibility criteria received OL oral cladribine 3.5 mg/kg over maximum of 48 weeks along with IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) up to 48 weeks.
|
Placebo, IFN-beta, Cladribine 3.5 mg/kg (OL Ext)
Participants who received placebo initially and completed DB period entered in the OL Ext. period. In OL Ext. period, participant who met the eligibility criteria received OL oral cladribine 3.5 mg/kg over maximum of 48 weeks along with IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) up to 48 weeks.
|
|---|---|---|---|---|
|
Double Blind Period: Time to Recovery From Grade 3 or 4 Hematological Toxicity
Hemoglobin
|
19.50 Days
Standard Deviation 10.61
|
—
|
—
|
—
|
|
Double Blind Period: Time to Recovery From Grade 3 or 4 Hematological Toxicity
White Blood Cell
|
31.27 Days
Standard Deviation 27.69
|
—
|
—
|
—
|
|
Double Blind Period: Time to Recovery From Grade 3 or 4 Hematological Toxicity
Neutrophil
|
41.17 Days
Standard Deviation 37.90
|
56.75 Days
Standard Deviation 30.76
|
—
|
—
|
|
Double Blind Period: Time to Recovery From Grade 3 or 4 Hematological Toxicity
Lymphocyte
|
142.53 Days
Standard Deviation 109.86
|
28.00 Days
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline, Week 96Population: Safety population: all randomized participants who received at least 1 dose of study drug in DBP and had follow-up safety data. Here "Number of Participants analyzed"= participants evaluable for this outcome measure and "number analyzed"= participants who were evaluable for specified category.
Mean changes in lymphocytes, WBC, neutrophils and platelets from baseline to week 96 were reported.
Outcome measures
| Measure |
Cladribine 3.5 mg/kg, IFN-beta (DB Period)
n=102 Participants
Participants received cladribine tablets orally as cumulative dose of 0.875 mg/kg over a course of 4-5 consecutive days at Week 1, 5, 48, and 52 resulting in total cladribine dose of 3.5 milligram per kilogram (mg/kg) along with interferon (IFN)-beta therapy (Rebif® new formulation \[RNF\] 44 mcg three times a week, subcutaneously; Avonex® 30 microgram (mcg) every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) during the Double blind period (DBP) of 96 weeks.
|
Placebo, IFN-beta (DB Period)
n=33 Participants
Participants received matching placebo tablets orally over a course of 4-5 consecutive days at Week 1, 5, 48, and 52 along with IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) during the DB period of 96 weeks.
|
Cladribine 3.5 mg/kg, IFN-beta, Cladribine 3.5 mg/kg (OL Ext)
Participants who received cladribine 3.5 mg/kg initially and completed DB period entered in the open label (OL) extension (Ext.) period. In OL Ext. period, participant who met the eligibility criteria received OL oral cladribine 3.5 mg/kg over maximum of 48 weeks along with IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) up to 48 weeks.
|
Placebo, IFN-beta, Cladribine 3.5 mg/kg (OL Ext)
Participants who received placebo initially and completed DB period entered in the OL Ext. period. In OL Ext. period, participant who met the eligibility criteria received OL oral cladribine 3.5 mg/kg over maximum of 48 weeks along with IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) up to 48 weeks.
|
|---|---|---|---|---|
|
Double Blind Period: Mean Changes in Lymphocytes, White Blood Cells (WBC), Neutrophils and Platelets Values From Baseline to Week 96
Platelet
|
-29.8 10^9 cells per liter
Standard Deviation 37.9
|
-12.4 10^9 cells per liter
Standard Deviation 56.9
|
—
|
—
|
|
Double Blind Period: Mean Changes in Lymphocytes, White Blood Cells (WBC), Neutrophils and Platelets Values From Baseline to Week 96
Lymphocytes
|
-0.8 10^9 cells per liter
Standard Deviation 0.5
|
0.0 10^9 cells per liter
Standard Deviation 0.7
|
—
|
—
|
|
Double Blind Period: Mean Changes in Lymphocytes, White Blood Cells (WBC), Neutrophils and Platelets Values From Baseline to Week 96
WBC
|
-1.5 10^9 cells per liter
Standard Deviation 1.8
|
-0.4 10^9 cells per liter
Standard Deviation 1.6
|
—
|
—
|
|
Double Blind Period: Mean Changes in Lymphocytes, White Blood Cells (WBC), Neutrophils and Platelets Values From Baseline to Week 96
Neutrophils
|
-0.7 10^9 cells per liter
Standard Deviation 1.6
|
-0.4 10^9 cells per liter
Standard Deviation 1.2
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline up to Week 96Population: Safety population included all randomized participants who received at least one dose of study medication in the DB period and had follow-up safety data.
Criteria for potential clinical concern in ECG parameters: Maximum corrected QT interval (QTc) in range of 450 to less than 480 millisecond (msec).
Outcome measures
| Measure |
Cladribine 3.5 mg/kg, IFN-beta (DB Period)
n=124 Participants
Participants received cladribine tablets orally as cumulative dose of 0.875 mg/kg over a course of 4-5 consecutive days at Week 1, 5, 48, and 52 resulting in total cladribine dose of 3.5 milligram per kilogram (mg/kg) along with interferon (IFN)-beta therapy (Rebif® new formulation \[RNF\] 44 mcg three times a week, subcutaneously; Avonex® 30 microgram (mcg) every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) during the Double blind period (DBP) of 96 weeks.
|
Placebo, IFN-beta (DB Period)
n=48 Participants
Participants received matching placebo tablets orally over a course of 4-5 consecutive days at Week 1, 5, 48, and 52 along with IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) during the DB period of 96 weeks.
|
Cladribine 3.5 mg/kg, IFN-beta, Cladribine 3.5 mg/kg (OL Ext)
Participants who received cladribine 3.5 mg/kg initially and completed DB period entered in the open label (OL) extension (Ext.) period. In OL Ext. period, participant who met the eligibility criteria received OL oral cladribine 3.5 mg/kg over maximum of 48 weeks along with IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) up to 48 weeks.
|
Placebo, IFN-beta, Cladribine 3.5 mg/kg (OL Ext)
Participants who received placebo initially and completed DB period entered in the OL Ext. period. In OL Ext. period, participant who met the eligibility criteria received OL oral cladribine 3.5 mg/kg over maximum of 48 weeks along with IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) up to 48 weeks.
|
|---|---|---|---|---|
|
Double Blind Period: Maximum Corrected QT Interval (QTc)
|
0.4381 Milliseconds
Standard Deviation 0.0194
|
0.4361 Milliseconds
Standard Deviation 0.0176
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline, Week 96Population: Safety population included all randomized participants who received at least one dose of study medication in the DB period and had follow-up safety data. Here "Number of participants analyzed" signifies those participants who were evaluable for this outcome measure.
Mean change from baseline in vital signs- systolic and diastolic blood pressure was reported.
Outcome measures
| Measure |
Cladribine 3.5 mg/kg, IFN-beta (DB Period)
n=113 Participants
Participants received cladribine tablets orally as cumulative dose of 0.875 mg/kg over a course of 4-5 consecutive days at Week 1, 5, 48, and 52 resulting in total cladribine dose of 3.5 milligram per kilogram (mg/kg) along with interferon (IFN)-beta therapy (Rebif® new formulation \[RNF\] 44 mcg three times a week, subcutaneously; Avonex® 30 microgram (mcg) every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) during the Double blind period (DBP) of 96 weeks.
|
Placebo, IFN-beta (DB Period)
n=38 Participants
Participants received matching placebo tablets orally over a course of 4-5 consecutive days at Week 1, 5, 48, and 52 along with IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) during the DB period of 96 weeks.
|
Cladribine 3.5 mg/kg, IFN-beta, Cladribine 3.5 mg/kg (OL Ext)
Participants who received cladribine 3.5 mg/kg initially and completed DB period entered in the open label (OL) extension (Ext.) period. In OL Ext. period, participant who met the eligibility criteria received OL oral cladribine 3.5 mg/kg over maximum of 48 weeks along with IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) up to 48 weeks.
|
Placebo, IFN-beta, Cladribine 3.5 mg/kg (OL Ext)
Participants who received placebo initially and completed DB period entered in the OL Ext. period. In OL Ext. period, participant who met the eligibility criteria received OL oral cladribine 3.5 mg/kg over maximum of 48 weeks along with IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) up to 48 weeks.
|
|---|---|---|---|---|
|
Double Blind Period: Mean Change From Baseline in Vital Signs- Systolic and Diastolic Blood Pressure
Systolic Blood Pressure
|
-0.6 Millimeter of mercury (mm*hg)
Standard Deviation 13.2
|
0.0 Millimeter of mercury (mm*hg)
Standard Deviation 13.1
|
—
|
—
|
|
Double Blind Period: Mean Change From Baseline in Vital Signs- Systolic and Diastolic Blood Pressure
Diastolic Blood Pressure
|
-0.6 Millimeter of mercury (mm*hg)
Standard Deviation 10.1
|
-2.2 Millimeter of mercury (mm*hg)
Standard Deviation 8.9
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline, Week 96Population: Safety population: all randomized participants who received at least 1 dose of study drug in DBP and had follow-up safety data. Here "Number of Participants analyzed"= participants evaluable for this outcome measure.
Mean change from baseline in vital signs- Pulse Rate was reported.
Outcome measures
| Measure |
Cladribine 3.5 mg/kg, IFN-beta (DB Period)
n=112 Participants
Participants received cladribine tablets orally as cumulative dose of 0.875 mg/kg over a course of 4-5 consecutive days at Week 1, 5, 48, and 52 resulting in total cladribine dose of 3.5 milligram per kilogram (mg/kg) along with interferon (IFN)-beta therapy (Rebif® new formulation \[RNF\] 44 mcg three times a week, subcutaneously; Avonex® 30 microgram (mcg) every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) during the Double blind period (DBP) of 96 weeks.
|
Placebo, IFN-beta (DB Period)
n=38 Participants
Participants received matching placebo tablets orally over a course of 4-5 consecutive days at Week 1, 5, 48, and 52 along with IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) during the DB period of 96 weeks.
|
Cladribine 3.5 mg/kg, IFN-beta, Cladribine 3.5 mg/kg (OL Ext)
Participants who received cladribine 3.5 mg/kg initially and completed DB period entered in the open label (OL) extension (Ext.) period. In OL Ext. period, participant who met the eligibility criteria received OL oral cladribine 3.5 mg/kg over maximum of 48 weeks along with IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) up to 48 weeks.
|
Placebo, IFN-beta, Cladribine 3.5 mg/kg (OL Ext)
Participants who received placebo initially and completed DB period entered in the OL Ext. period. In OL Ext. period, participant who met the eligibility criteria received OL oral cladribine 3.5 mg/kg over maximum of 48 weeks along with IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) up to 48 weeks.
|
|---|---|---|---|---|
|
Double Blind Period: Mean Change From Baseline in Vital Signs- Pulse Rate
|
1.0 beats per minutes
Standard Deviation 11.6
|
0.4 beats per minutes
Standard Deviation 9.2
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline, Week 96Population: Safety population included all randomized participants who received at least one dose of study medication in the DB period and had follow-up safety data. Here "Number of participants analyzed" signifies those participants who were evaluable for this outcome measure.
Mean change from baseline in vital signs- weight was reported.
Outcome measures
| Measure |
Cladribine 3.5 mg/kg, IFN-beta (DB Period)
n=111 Participants
Participants received cladribine tablets orally as cumulative dose of 0.875 mg/kg over a course of 4-5 consecutive days at Week 1, 5, 48, and 52 resulting in total cladribine dose of 3.5 milligram per kilogram (mg/kg) along with interferon (IFN)-beta therapy (Rebif® new formulation \[RNF\] 44 mcg three times a week, subcutaneously; Avonex® 30 microgram (mcg) every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) during the Double blind period (DBP) of 96 weeks.
|
Placebo, IFN-beta (DB Period)
n=38 Participants
Participants received matching placebo tablets orally over a course of 4-5 consecutive days at Week 1, 5, 48, and 52 along with IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) during the DB period of 96 weeks.
|
Cladribine 3.5 mg/kg, IFN-beta, Cladribine 3.5 mg/kg (OL Ext)
Participants who received cladribine 3.5 mg/kg initially and completed DB period entered in the open label (OL) extension (Ext.) period. In OL Ext. period, participant who met the eligibility criteria received OL oral cladribine 3.5 mg/kg over maximum of 48 weeks along with IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) up to 48 weeks.
|
Placebo, IFN-beta, Cladribine 3.5 mg/kg (OL Ext)
Participants who received placebo initially and completed DB period entered in the OL Ext. period. In OL Ext. period, participant who met the eligibility criteria received OL oral cladribine 3.5 mg/kg over maximum of 48 weeks along with IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) up to 48 weeks.
|
|---|---|---|---|---|
|
Double Blind Period: Mean Change From Baseline in Vital Signs- Weight
|
-0.6 Kilogram
Standard Deviation 8.0
|
-0.4 Kilogram
Standard Deviation 5.0
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline, Week 96Population: Safety population included all randomized participants who received at least one dose of study medication in the DB period and had follow-up safety data. Here "Number of participants analyzed" signifies those participants who were evaluable for this outcome measure.
Mean change from baseline in vital signs- temperature was reported.
Outcome measures
| Measure |
Cladribine 3.5 mg/kg, IFN-beta (DB Period)
n=112 Participants
Participants received cladribine tablets orally as cumulative dose of 0.875 mg/kg over a course of 4-5 consecutive days at Week 1, 5, 48, and 52 resulting in total cladribine dose of 3.5 milligram per kilogram (mg/kg) along with interferon (IFN)-beta therapy (Rebif® new formulation \[RNF\] 44 mcg three times a week, subcutaneously; Avonex® 30 microgram (mcg) every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) during the Double blind period (DBP) of 96 weeks.
|
Placebo, IFN-beta (DB Period)
n=38 Participants
Participants received matching placebo tablets orally over a course of 4-5 consecutive days at Week 1, 5, 48, and 52 along with IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) during the DB period of 96 weeks.
|
Cladribine 3.5 mg/kg, IFN-beta, Cladribine 3.5 mg/kg (OL Ext)
Participants who received cladribine 3.5 mg/kg initially and completed DB period entered in the open label (OL) extension (Ext.) period. In OL Ext. period, participant who met the eligibility criteria received OL oral cladribine 3.5 mg/kg over maximum of 48 weeks along with IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) up to 48 weeks.
|
Placebo, IFN-beta, Cladribine 3.5 mg/kg (OL Ext)
Participants who received placebo initially and completed DB period entered in the OL Ext. period. In OL Ext. period, participant who met the eligibility criteria received OL oral cladribine 3.5 mg/kg over maximum of 48 weeks along with IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) up to 48 weeks.
|
|---|---|---|---|---|
|
Double Blind Period: Mean Change From Baseline in Vital Signs- Temperature
|
-0.1 Degree celsius
Standard Deviation 0.3
|
-0.1 Degree celsius
Standard Deviation 0.4
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline, Week 96Population: Safety population included all randomized participants who received at least one dose of study medication in the DB period and had follow-up safety data. Here "Number of participants analyzed" signifies those participants who were evaluable for this outcome measure.
Mean change from baseline in ECG parameters- Heart Rate was reported.
Outcome measures
| Measure |
Cladribine 3.5 mg/kg, IFN-beta (DB Period)
n=37 Participants
Participants received cladribine tablets orally as cumulative dose of 0.875 mg/kg over a course of 4-5 consecutive days at Week 1, 5, 48, and 52 resulting in total cladribine dose of 3.5 milligram per kilogram (mg/kg) along with interferon (IFN)-beta therapy (Rebif® new formulation \[RNF\] 44 mcg three times a week, subcutaneously; Avonex® 30 microgram (mcg) every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) during the Double blind period (DBP) of 96 weeks.
|
Placebo, IFN-beta (DB Period)
n=22 Participants
Participants received matching placebo tablets orally over a course of 4-5 consecutive days at Week 1, 5, 48, and 52 along with IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) during the DB period of 96 weeks.
|
Cladribine 3.5 mg/kg, IFN-beta, Cladribine 3.5 mg/kg (OL Ext)
Participants who received cladribine 3.5 mg/kg initially and completed DB period entered in the open label (OL) extension (Ext.) period. In OL Ext. period, participant who met the eligibility criteria received OL oral cladribine 3.5 mg/kg over maximum of 48 weeks along with IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) up to 48 weeks.
|
Placebo, IFN-beta, Cladribine 3.5 mg/kg (OL Ext)
Participants who received placebo initially and completed DB period entered in the OL Ext. period. In OL Ext. period, participant who met the eligibility criteria received OL oral cladribine 3.5 mg/kg over maximum of 48 weeks along with IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) up to 48 weeks.
|
|---|---|---|---|---|
|
Double Blind Period: Mean Change From Baseline in Electrocardiogram (ECG) Parameters- Heart Rate
|
-3.114 beats per minutes
Standard Deviation 8.990
|
1.981 beats per minutes
Standard Deviation 7.857
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline, Week 96Population: Safety population included all randomized participants who received at least one dose of study medication in the DB period and had follow-up safety data. Here "Number of participants analyzed" signifies those participants who were evaluable for this outcome measure.
Mean change from baseline in ECG parameters- PR, RR, QRS and OT interval was reported.
Outcome measures
| Measure |
Cladribine 3.5 mg/kg, IFN-beta (DB Period)
n=37 Participants
Participants received cladribine tablets orally as cumulative dose of 0.875 mg/kg over a course of 4-5 consecutive days at Week 1, 5, 48, and 52 resulting in total cladribine dose of 3.5 milligram per kilogram (mg/kg) along with interferon (IFN)-beta therapy (Rebif® new formulation \[RNF\] 44 mcg three times a week, subcutaneously; Avonex® 30 microgram (mcg) every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) during the Double blind period (DBP) of 96 weeks.
|
Placebo, IFN-beta (DB Period)
n=22 Participants
Participants received matching placebo tablets orally over a course of 4-5 consecutive days at Week 1, 5, 48, and 52 along with IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) during the DB period of 96 weeks.
|
Cladribine 3.5 mg/kg, IFN-beta, Cladribine 3.5 mg/kg (OL Ext)
Participants who received cladribine 3.5 mg/kg initially and completed DB period entered in the open label (OL) extension (Ext.) period. In OL Ext. period, participant who met the eligibility criteria received OL oral cladribine 3.5 mg/kg over maximum of 48 weeks along with IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) up to 48 weeks.
|
Placebo, IFN-beta, Cladribine 3.5 mg/kg (OL Ext)
Participants who received placebo initially and completed DB period entered in the OL Ext. period. In OL Ext. period, participant who met the eligibility criteria received OL oral cladribine 3.5 mg/kg over maximum of 48 weeks along with IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) up to 48 weeks.
|
|---|---|---|---|---|
|
Double Blind Period: Mean Change From Baseline in Electrocardiogram (ECG) Parameters- PR, RR, QRS and OT Interval
PR Interval
|
0.0001 milliseconds
Standard Deviation 0.0094
|
0.0033 milliseconds
Standard Deviation 0.0108
|
—
|
—
|
|
Double Blind Period: Mean Change From Baseline in Electrocardiogram (ECG) Parameters- PR, RR, QRS and OT Interval
RR Interval
|
0.0361 milliseconds
Standard Deviation 0.1068
|
-0.0272 milliseconds
Standard Deviation 0.1175
|
—
|
—
|
|
Double Blind Period: Mean Change From Baseline in Electrocardiogram (ECG) Parameters- PR, RR, QRS and OT Interval
QRS Interval
|
0.0028 milliseconds
Standard Deviation 0.0060
|
0.0043 milliseconds
Standard Deviation 0.0054
|
—
|
—
|
|
Double Blind Period: Mean Change From Baseline in Electrocardiogram (ECG) Parameters- PR, RR, QRS and OT Interval
QT Interval
|
0.0135 milliseconds
Standard Deviation 0.0214
|
0.0037 milliseconds
Standard Deviation 0.0189
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline, Week 96Population: Safety population included all randomized participants who received at least one dose of study medication in the DB period and had follow-up safety data. Here "Number of participants analyzed" signifies those participants who were evaluable for this outcome measure.
Mean changes in hemoglobin level from baseline to week 96 was reported.
Outcome measures
| Measure |
Cladribine 3.5 mg/kg, IFN-beta (DB Period)
n=102 Participants
Participants received cladribine tablets orally as cumulative dose of 0.875 mg/kg over a course of 4-5 consecutive days at Week 1, 5, 48, and 52 resulting in total cladribine dose of 3.5 milligram per kilogram (mg/kg) along with interferon (IFN)-beta therapy (Rebif® new formulation \[RNF\] 44 mcg three times a week, subcutaneously; Avonex® 30 microgram (mcg) every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) during the Double blind period (DBP) of 96 weeks.
|
Placebo, IFN-beta (DB Period)
n=33 Participants
Participants received matching placebo tablets orally over a course of 4-5 consecutive days at Week 1, 5, 48, and 52 along with IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) during the DB period of 96 weeks.
|
Cladribine 3.5 mg/kg, IFN-beta, Cladribine 3.5 mg/kg (OL Ext)
Participants who received cladribine 3.5 mg/kg initially and completed DB period entered in the open label (OL) extension (Ext.) period. In OL Ext. period, participant who met the eligibility criteria received OL oral cladribine 3.5 mg/kg over maximum of 48 weeks along with IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) up to 48 weeks.
|
Placebo, IFN-beta, Cladribine 3.5 mg/kg (OL Ext)
Participants who received placebo initially and completed DB period entered in the OL Ext. period. In OL Ext. period, participant who met the eligibility criteria received OL oral cladribine 3.5 mg/kg over maximum of 48 weeks along with IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) up to 48 weeks.
|
|---|---|---|---|---|
|
Double Blind Period: Mean Changes From Baseline in Hemoglobin Level to Week 96
|
-2.9 gram per liter (g/L)
Standard Deviation 8.1
|
-2.5 gram per liter (g/L)
Standard Deviation 10.6
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline, Week 96Population: Safety population included all randomized participants who received at least one dose of study medication in the DB period and had follow-up safety data. Here "Number of participants analyzed" signifies those participants who were evaluable for this outcome measure.
Mean changes CD4+ Count, CD8+ Count, and CD19+ from baseline to Week 96 were reported.
Outcome measures
| Measure |
Cladribine 3.5 mg/kg, IFN-beta (DB Period)
n=99 Participants
Participants received cladribine tablets orally as cumulative dose of 0.875 mg/kg over a course of 4-5 consecutive days at Week 1, 5, 48, and 52 resulting in total cladribine dose of 3.5 milligram per kilogram (mg/kg) along with interferon (IFN)-beta therapy (Rebif® new formulation \[RNF\] 44 mcg three times a week, subcutaneously; Avonex® 30 microgram (mcg) every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) during the Double blind period (DBP) of 96 weeks.
|
Placebo, IFN-beta (DB Period)
n=31 Participants
Participants received matching placebo tablets orally over a course of 4-5 consecutive days at Week 1, 5, 48, and 52 along with IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) during the DB period of 96 weeks.
|
Cladribine 3.5 mg/kg, IFN-beta, Cladribine 3.5 mg/kg (OL Ext)
Participants who received cladribine 3.5 mg/kg initially and completed DB period entered in the open label (OL) extension (Ext.) period. In OL Ext. period, participant who met the eligibility criteria received OL oral cladribine 3.5 mg/kg over maximum of 48 weeks along with IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) up to 48 weeks.
|
Placebo, IFN-beta, Cladribine 3.5 mg/kg (OL Ext)
Participants who received placebo initially and completed DB period entered in the OL Ext. period. In OL Ext. period, participant who met the eligibility criteria received OL oral cladribine 3.5 mg/kg over maximum of 48 weeks along with IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) up to 48 weeks.
|
|---|---|---|---|---|
|
Double Blind Period: Mean Changes From Baseline in CD4+ Count, CD8+ Count, and CD19+ to Week 96
CD4+
|
-604.1 Cells per microliter
Standard Deviation 301.3
|
7.1 Cells per microliter
Standard Deviation 344.7
|
—
|
—
|
|
Double Blind Period: Mean Changes From Baseline in CD4+ Count, CD8+ Count, and CD19+ to Week 96
CD8+
|
-137.8 Cells per microliter
Standard Deviation 178.1
|
23.9 Cells per microliter
Standard Deviation 188.3
|
—
|
—
|
|
Double Blind Period: Mean Changes From Baseline in CD4+ Count, CD8+ Count, and CD19+ to Week 96
CD19+
|
22.0 Cells per microliter
Standard Deviation 141.2
|
30.7 Cells per microliter
Standard Deviation 121.5
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline, Week 96Population: Safety population included all randomized participants who received at least one dose of study medication in the DB period and had follow-up safety data. Here "Number of participants analyzed" signifies those participants who were evaluable for this outcome measure.
Mean changes in ALT and AST from baseline to week 96 were reported.
Outcome measures
| Measure |
Cladribine 3.5 mg/kg, IFN-beta (DB Period)
n=102 Participants
Participants received cladribine tablets orally as cumulative dose of 0.875 mg/kg over a course of 4-5 consecutive days at Week 1, 5, 48, and 52 resulting in total cladribine dose of 3.5 milligram per kilogram (mg/kg) along with interferon (IFN)-beta therapy (Rebif® new formulation \[RNF\] 44 mcg three times a week, subcutaneously; Avonex® 30 microgram (mcg) every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) during the Double blind period (DBP) of 96 weeks.
|
Placebo, IFN-beta (DB Period)
n=32 Participants
Participants received matching placebo tablets orally over a course of 4-5 consecutive days at Week 1, 5, 48, and 52 along with IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) during the DB period of 96 weeks.
|
Cladribine 3.5 mg/kg, IFN-beta, Cladribine 3.5 mg/kg (OL Ext)
Participants who received cladribine 3.5 mg/kg initially and completed DB period entered in the open label (OL) extension (Ext.) period. In OL Ext. period, participant who met the eligibility criteria received OL oral cladribine 3.5 mg/kg over maximum of 48 weeks along with IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) up to 48 weeks.
|
Placebo, IFN-beta, Cladribine 3.5 mg/kg (OL Ext)
Participants who received placebo initially and completed DB period entered in the OL Ext. period. In OL Ext. period, participant who met the eligibility criteria received OL oral cladribine 3.5 mg/kg over maximum of 48 weeks along with IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) up to 48 weeks.
|
|---|---|---|---|---|
|
Double Blind Period: Mean Changes From Baseline in Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) to Week 96
ALT
|
-3.0 Units per liter
Standard Deviation 11.5
|
1.3 Units per liter
Standard Deviation 11.5
|
—
|
—
|
|
Double Blind Period: Mean Changes From Baseline in Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) to Week 96
AST
|
-1.7 Units per liter
Standard Deviation 6.9
|
1.1 Units per liter
Standard Deviation 6.2
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline up to Week 96Population: Safety population included all randomized participants who received at least one dose of study medication in the DB period and had follow-up safety data. Here "Number of participants analyzed" signifies those participants who were evaluable for this outcome measure.
Criteria for potential clinical concern in ECG parameters: Maximum corrected QT interval (QTc) in range of 450 to less than 480 millisecond (msec).
Outcome measures
| Measure |
Cladribine 3.5 mg/kg, IFN-beta (DB Period)
n=47 Participants
Participants received cladribine tablets orally as cumulative dose of 0.875 mg/kg over a course of 4-5 consecutive days at Week 1, 5, 48, and 52 resulting in total cladribine dose of 3.5 milligram per kilogram (mg/kg) along with interferon (IFN)-beta therapy (Rebif® new formulation \[RNF\] 44 mcg three times a week, subcutaneously; Avonex® 30 microgram (mcg) every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) during the Double blind period (DBP) of 96 weeks.
|
Placebo, IFN-beta (DB Period)
n=27 Participants
Participants received matching placebo tablets orally over a course of 4-5 consecutive days at Week 1, 5, 48, and 52 along with IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) during the DB period of 96 weeks.
|
Cladribine 3.5 mg/kg, IFN-beta, Cladribine 3.5 mg/kg (OL Ext)
Participants who received cladribine 3.5 mg/kg initially and completed DB period entered in the open label (OL) extension (Ext.) period. In OL Ext. period, participant who met the eligibility criteria received OL oral cladribine 3.5 mg/kg over maximum of 48 weeks along with IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) up to 48 weeks.
|
Placebo, IFN-beta, Cladribine 3.5 mg/kg (OL Ext)
Participants who received placebo initially and completed DB period entered in the OL Ext. period. In OL Ext. period, participant who met the eligibility criteria received OL oral cladribine 3.5 mg/kg over maximum of 48 weeks along with IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) up to 48 weeks.
|
|---|---|---|---|---|
|
Open Label Extension Period: Maximum Corrected QT Interval (Qtc)
|
0.4370 Milliseconds
Standard Deviation 0.0219
|
0.4317 Milliseconds
Standard Deviation 0.0181
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline, Week 72Population: Safety population was used. Here "Number of participants analyzed" signifies those participants who were evaluable for this outcome measure. Only those participants with data available at the specified time point were reported.
Mean change from baseline in vital signs- systolic and diastolic blood pressure was reported.
Outcome measures
| Measure |
Cladribine 3.5 mg/kg, IFN-beta (DB Period)
n=3 Participants
Participants received cladribine tablets orally as cumulative dose of 0.875 mg/kg over a course of 4-5 consecutive days at Week 1, 5, 48, and 52 resulting in total cladribine dose of 3.5 milligram per kilogram (mg/kg) along with interferon (IFN)-beta therapy (Rebif® new formulation \[RNF\] 44 mcg three times a week, subcutaneously; Avonex® 30 microgram (mcg) every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) during the Double blind period (DBP) of 96 weeks.
|
Placebo, IFN-beta (DB Period)
Participants received matching placebo tablets orally over a course of 4-5 consecutive days at Week 1, 5, 48, and 52 along with IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) during the DB period of 96 weeks.
|
Cladribine 3.5 mg/kg, IFN-beta, Cladribine 3.5 mg/kg (OL Ext)
Participants who received cladribine 3.5 mg/kg initially and completed DB period entered in the open label (OL) extension (Ext.) period. In OL Ext. period, participant who met the eligibility criteria received OL oral cladribine 3.5 mg/kg over maximum of 48 weeks along with IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) up to 48 weeks.
|
Placebo, IFN-beta, Cladribine 3.5 mg/kg (OL Ext)
Participants who received placebo initially and completed DB period entered in the OL Ext. period. In OL Ext. period, participant who met the eligibility criteria received OL oral cladribine 3.5 mg/kg over maximum of 48 weeks along with IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) up to 48 weeks.
|
|---|---|---|---|---|
|
Open Label Extension Period: Mean Change From Baseline in Vital Signs- Systolic and Diastolic Blood Pressure
Systolic Blood Pressure
|
0.3 Millimeter of mercury (mm*hg)
Standard Deviation 10.2
|
—
|
—
|
—
|
|
Open Label Extension Period: Mean Change From Baseline in Vital Signs- Systolic and Diastolic Blood Pressure
Diastolic Blood Pressure
|
-1.7 Millimeter of mercury (mm*hg)
Standard Deviation 5.0
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline, Week 72Population: Safety population: all randomized participants who received at least 1 dose of study drug in DBP and had follow-up safety data. Here "Number of Participants analyzed"= participants evaluable for this outcome measure. Only those participants with data available at the specified time point were reported.
Mean change from baseline in vital signs- Pulse Rate was reported.
Outcome measures
| Measure |
Cladribine 3.5 mg/kg, IFN-beta (DB Period)
n=3 Participants
Participants received cladribine tablets orally as cumulative dose of 0.875 mg/kg over a course of 4-5 consecutive days at Week 1, 5, 48, and 52 resulting in total cladribine dose of 3.5 milligram per kilogram (mg/kg) along with interferon (IFN)-beta therapy (Rebif® new formulation \[RNF\] 44 mcg three times a week, subcutaneously; Avonex® 30 microgram (mcg) every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) during the Double blind period (DBP) of 96 weeks.
|
Placebo, IFN-beta (DB Period)
Participants received matching placebo tablets orally over a course of 4-5 consecutive days at Week 1, 5, 48, and 52 along with IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) during the DB period of 96 weeks.
|
Cladribine 3.5 mg/kg, IFN-beta, Cladribine 3.5 mg/kg (OL Ext)
Participants who received cladribine 3.5 mg/kg initially and completed DB period entered in the open label (OL) extension (Ext.) period. In OL Ext. period, participant who met the eligibility criteria received OL oral cladribine 3.5 mg/kg over maximum of 48 weeks along with IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) up to 48 weeks.
|
Placebo, IFN-beta, Cladribine 3.5 mg/kg (OL Ext)
Participants who received placebo initially and completed DB period entered in the OL Ext. period. In OL Ext. period, participant who met the eligibility criteria received OL oral cladribine 3.5 mg/kg over maximum of 48 weeks along with IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) up to 48 weeks.
|
|---|---|---|---|---|
|
Open Label Extension Period: Mean Change From Baseline in Vital Signs- Pulse Rate
|
4.7 beats per minutes
Standard Deviation 11.5
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline, Week 72Population: Safety population was used. Here "Number of participants analyzed" signifies those participants who were evaluable for this outcome measure. Only those participants with data available at the specified time point were reported.
Mean change from baseline in vital signs- weight was reported.
Outcome measures
| Measure |
Cladribine 3.5 mg/kg, IFN-beta (DB Period)
n=3 Participants
Participants received cladribine tablets orally as cumulative dose of 0.875 mg/kg over a course of 4-5 consecutive days at Week 1, 5, 48, and 52 resulting in total cladribine dose of 3.5 milligram per kilogram (mg/kg) along with interferon (IFN)-beta therapy (Rebif® new formulation \[RNF\] 44 mcg three times a week, subcutaneously; Avonex® 30 microgram (mcg) every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) during the Double blind period (DBP) of 96 weeks.
|
Placebo, IFN-beta (DB Period)
Participants received matching placebo tablets orally over a course of 4-5 consecutive days at Week 1, 5, 48, and 52 along with IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) during the DB period of 96 weeks.
|
Cladribine 3.5 mg/kg, IFN-beta, Cladribine 3.5 mg/kg (OL Ext)
Participants who received cladribine 3.5 mg/kg initially and completed DB period entered in the open label (OL) extension (Ext.) period. In OL Ext. period, participant who met the eligibility criteria received OL oral cladribine 3.5 mg/kg over maximum of 48 weeks along with IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) up to 48 weeks.
|
Placebo, IFN-beta, Cladribine 3.5 mg/kg (OL Ext)
Participants who received placebo initially and completed DB period entered in the OL Ext. period. In OL Ext. period, participant who met the eligibility criteria received OL oral cladribine 3.5 mg/kg over maximum of 48 weeks along with IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) up to 48 weeks.
|
|---|---|---|---|---|
|
Open Label Extension Period: Mean Change From Baseline in Vital Signs- Weight
|
-9.4 Kilogram
Standard Deviation 6.9
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline, Week 72Population: Safety population was used. Here "Number of participants analyzed" signifies those participants who were evaluable for this outcome measure. Only those participants with data available at the specified time point were reported.
Mean change from baseline in vital signs- temperature was reported.
Outcome measures
| Measure |
Cladribine 3.5 mg/kg, IFN-beta (DB Period)
n=3 Participants
Participants received cladribine tablets orally as cumulative dose of 0.875 mg/kg over a course of 4-5 consecutive days at Week 1, 5, 48, and 52 resulting in total cladribine dose of 3.5 milligram per kilogram (mg/kg) along with interferon (IFN)-beta therapy (Rebif® new formulation \[RNF\] 44 mcg three times a week, subcutaneously; Avonex® 30 microgram (mcg) every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) during the Double blind period (DBP) of 96 weeks.
|
Placebo, IFN-beta (DB Period)
Participants received matching placebo tablets orally over a course of 4-5 consecutive days at Week 1, 5, 48, and 52 along with IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) during the DB period of 96 weeks.
|
Cladribine 3.5 mg/kg, IFN-beta, Cladribine 3.5 mg/kg (OL Ext)
Participants who received cladribine 3.5 mg/kg initially and completed DB period entered in the open label (OL) extension (Ext.) period. In OL Ext. period, participant who met the eligibility criteria received OL oral cladribine 3.5 mg/kg over maximum of 48 weeks along with IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) up to 48 weeks.
|
Placebo, IFN-beta, Cladribine 3.5 mg/kg (OL Ext)
Participants who received placebo initially and completed DB period entered in the OL Ext. period. In OL Ext. period, participant who met the eligibility criteria received OL oral cladribine 3.5 mg/kg over maximum of 48 weeks along with IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) up to 48 weeks.
|
|---|---|---|---|---|
|
Open Label Extension Period: Mean Change From Baseline in Vital Signs- Temperature
|
-0.3 Degree celsius
Standard Deviation 0.3
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline, Week 72Population: Safety population was used. Here "Number of participants analyzed" signifies those participants who were evaluable for this outcome measure. Only those participants with data available at the specified time point were reported.
Mean change from baseline in ECG parameters- Heart Rate was reported.
Outcome measures
| Measure |
Cladribine 3.5 mg/kg, IFN-beta (DB Period)
n=6 Participants
Participants received cladribine tablets orally as cumulative dose of 0.875 mg/kg over a course of 4-5 consecutive days at Week 1, 5, 48, and 52 resulting in total cladribine dose of 3.5 milligram per kilogram (mg/kg) along with interferon (IFN)-beta therapy (Rebif® new formulation \[RNF\] 44 mcg three times a week, subcutaneously; Avonex® 30 microgram (mcg) every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) during the Double blind period (DBP) of 96 weeks.
|
Placebo, IFN-beta (DB Period)
Participants received matching placebo tablets orally over a course of 4-5 consecutive days at Week 1, 5, 48, and 52 along with IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) during the DB period of 96 weeks.
|
Cladribine 3.5 mg/kg, IFN-beta, Cladribine 3.5 mg/kg (OL Ext)
Participants who received cladribine 3.5 mg/kg initially and completed DB period entered in the open label (OL) extension (Ext.) period. In OL Ext. period, participant who met the eligibility criteria received OL oral cladribine 3.5 mg/kg over maximum of 48 weeks along with IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) up to 48 weeks.
|
Placebo, IFN-beta, Cladribine 3.5 mg/kg (OL Ext)
Participants who received placebo initially and completed DB period entered in the OL Ext. period. In OL Ext. period, participant who met the eligibility criteria received OL oral cladribine 3.5 mg/kg over maximum of 48 weeks along with IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) up to 48 weeks.
|
|---|---|---|---|---|
|
Open Label Extension Period: Mean Change From Baseline in Electrocardiogram (ECG) Parameters- Heart Rate
|
-4.889 beats per minutes
Standard Deviation 6.160
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline, Week 72Population: Safety population was used. Here "Number of participants analyzed" signifies those participants who were evaluable for this outcome measure. Only those participants with data available at the specified time point were reported.
Mean change from baseline in ECG parameters- PR, RR, QRS and OT interval was reported.
Outcome measures
| Measure |
Cladribine 3.5 mg/kg, IFN-beta (DB Period)
n=6 Participants
Participants received cladribine tablets orally as cumulative dose of 0.875 mg/kg over a course of 4-5 consecutive days at Week 1, 5, 48, and 52 resulting in total cladribine dose of 3.5 milligram per kilogram (mg/kg) along with interferon (IFN)-beta therapy (Rebif® new formulation \[RNF\] 44 mcg three times a week, subcutaneously; Avonex® 30 microgram (mcg) every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) during the Double blind period (DBP) of 96 weeks.
|
Placebo, IFN-beta (DB Period)
Participants received matching placebo tablets orally over a course of 4-5 consecutive days at Week 1, 5, 48, and 52 along with IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) during the DB period of 96 weeks.
|
Cladribine 3.5 mg/kg, IFN-beta, Cladribine 3.5 mg/kg (OL Ext)
Participants who received cladribine 3.5 mg/kg initially and completed DB period entered in the open label (OL) extension (Ext.) period. In OL Ext. period, participant who met the eligibility criteria received OL oral cladribine 3.5 mg/kg over maximum of 48 weeks along with IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) up to 48 weeks.
|
Placebo, IFN-beta, Cladribine 3.5 mg/kg (OL Ext)
Participants who received placebo initially and completed DB period entered in the OL Ext. period. In OL Ext. period, participant who met the eligibility criteria received OL oral cladribine 3.5 mg/kg over maximum of 48 weeks along with IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) up to 48 weeks.
|
|---|---|---|---|---|
|
Open Label Extension Period: Mean Change From Baseline in Electrocardiogram (ECG) Parameters- PR, RR, QRS and OT Interval
PR Interval
|
-0.0044 milliseconds
Standard Deviation 0.0108
|
—
|
—
|
—
|
|
Open Label Extension Period: Mean Change From Baseline in Electrocardiogram (ECG) Parameters- PR, RR, QRS and OT Interval
RR Interval
|
0.0643 milliseconds
Standard Deviation 0.0721
|
—
|
—
|
—
|
|
Open Label Extension Period: Mean Change From Baseline in Electrocardiogram (ECG) Parameters- PR, RR, QRS and OT Interval
QRS Interval
|
-0.0026 milliseconds
Standard Deviation 0.0090
|
—
|
—
|
—
|
|
Open Label Extension Period: Mean Change From Baseline in Electrocardiogram (ECG) Parameters- PR, RR, QRS and OT Interval
QT Interval
|
0.0109 milliseconds
Standard Deviation 0.0206
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline (OLEP) up to Week 96Population: Safety population: all randomized participants who received at least 1 dose of study drug in DBP and had follow-up safety data. Here "Number of Participants analyzed"= participants evaluable for this outcome measure and "number analyzed"= participants who were evaluable for specified category.
Percentage of participants with Grade 3 or 4 CTCAE v 4.0 toxicity on the following hematology and liver function parameters were reported: lymphocytes, cluster of differentiation 4 (CD4) cell, neutrophils, white blood cells, hemoglobin, Alanine transaminase (ALT), Aspartate transaminase (AST), Platelets and Bilirubin. According to CTCAE v 4.0: Grade 1=mild, Grade 2=moderate, Grade 3=severe, Grade 4=life threatening or disabling and Grade 5=Death.
Outcome measures
| Measure |
Cladribine 3.5 mg/kg, IFN-beta (DB Period)
n=47 Participants
Participants received cladribine tablets orally as cumulative dose of 0.875 mg/kg over a course of 4-5 consecutive days at Week 1, 5, 48, and 52 resulting in total cladribine dose of 3.5 milligram per kilogram (mg/kg) along with interferon (IFN)-beta therapy (Rebif® new formulation \[RNF\] 44 mcg three times a week, subcutaneously; Avonex® 30 microgram (mcg) every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) during the Double blind period (DBP) of 96 weeks.
|
Placebo, IFN-beta (DB Period)
n=28 Participants
Participants received matching placebo tablets orally over a course of 4-5 consecutive days at Week 1, 5, 48, and 52 along with IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) during the DB period of 96 weeks.
|
Cladribine 3.5 mg/kg, IFN-beta, Cladribine 3.5 mg/kg (OL Ext)
n=51 Participants
Participants who received cladribine 3.5 mg/kg initially and completed DB period entered in the open label (OL) extension (Ext.) period. In OL Ext. period, participant who met the eligibility criteria received OL oral cladribine 3.5 mg/kg over maximum of 48 weeks along with IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) up to 48 weeks.
|
Placebo, IFN-beta, Cladribine 3.5 mg/kg (OL Ext)
n=7 Participants
Participants who received placebo initially and completed DB period entered in the OL Ext. period. In OL Ext. period, participant who met the eligibility criteria received OL oral cladribine 3.5 mg/kg over maximum of 48 weeks along with IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) up to 48 weeks.
|
|---|---|---|---|---|
|
OLE and Safety Follow-up Period: Percentage of Participants With Grade 3 or 4 (Common Terminology Criteria for Adverse Events [CTCAE] v 4.0) Hematological or Liver Toxicity
Grade 3 or 4 Neutrophil toxicity
|
6.4 Percentage of participants
|
14.3 Percentage of participants
|
0.00 Percentage of participants
|
0.00 Percentage of participants
|
|
OLE and Safety Follow-up Period: Percentage of Participants With Grade 3 or 4 (Common Terminology Criteria for Adverse Events [CTCAE] v 4.0) Hematological or Liver Toxicity
Grade 3 or 4 CD4+ toxicity
|
66.0 Percentage of participants
|
21.4 Percentage of participants
|
14.0 Percentage of participants
|
0.00 Percentage of participants
|
|
OLE and Safety Follow-up Period: Percentage of Participants With Grade 3 or 4 (Common Terminology Criteria for Adverse Events [CTCAE] v 4.0) Hematological or Liver Toxicity
Grade 3 or 4 White Blood Cell toxicity
|
4.3 Percentage of participants
|
3.6 Percentage of participants
|
0.00 Percentage of participants
|
0.00 Percentage of participants
|
|
OLE and Safety Follow-up Period: Percentage of Participants With Grade 3 or 4 (Common Terminology Criteria for Adverse Events [CTCAE] v 4.0) Hematological or Liver Toxicity
Grade 3 or 4 Platelet toxicity
|
0.00 Percentage of participants
|
0.00 Percentage of participants
|
0.00 Percentage of participants
|
0.00 Percentage of participants
|
|
OLE and Safety Follow-up Period: Percentage of Participants With Grade 3 or 4 (Common Terminology Criteria for Adverse Events [CTCAE] v 4.0) Hematological or Liver Toxicity
Grade 3 or 4 Lymphocyte toxicity
|
48.9 Percentage of participants
|
28.6 Percentage of participants
|
3.9 Percentage of participants
|
0.00 Percentage of participants
|
|
OLE and Safety Follow-up Period: Percentage of Participants With Grade 3 or 4 (Common Terminology Criteria for Adverse Events [CTCAE] v 4.0) Hematological or Liver Toxicity
Grade 3 or 4 Hemoglobin toxicity
|
0.00 Percentage of participants
|
0.00 Percentage of participants
|
2.0 Percentage of participants
|
0.00 Percentage of participants
|
|
OLE and Safety Follow-up Period: Percentage of Participants With Grade 3 or 4 (Common Terminology Criteria for Adverse Events [CTCAE] v 4.0) Hematological or Liver Toxicity
Grade 3 or 4 Bilirubin toxicity
|
0.00 Percentage of participants
|
0.00 Percentage of participants
|
0.00 Percentage of participants
|
0.00 Percentage of participants
|
|
OLE and Safety Follow-up Period: Percentage of Participants With Grade 3 or 4 (Common Terminology Criteria for Adverse Events [CTCAE] v 4.0) Hematological or Liver Toxicity
Grade 3 or 4 AST toxicity
|
0.00 Percentage of participants
|
0.00 Percentage of participants
|
0.00 Percentage of participants
|
0.00 Percentage of participants
|
|
OLE and Safety Follow-up Period: Percentage of Participants With Grade 3 or 4 (Common Terminology Criteria for Adverse Events [CTCAE] v 4.0) Hematological or Liver Toxicity
Grade 3 or 4 ALT toxicity
|
0.00 Percentage of participants
|
3.6 Percentage of participants
|
0.00 Percentage of participants
|
0.00 Percentage of participants
|
PRIMARY outcome
Timeframe: Baseline (OLEP) up to Week 96Population: Safety population included all randomized participants who received at least one dose of study medication in the DBP and had follow-up safety data.
An Adverse event (AE) was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease associated with the use of study drug, whether or not considered related to the study drug or worsening of pre-existing medical condition, whether or not related to study drug. A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. An AE was considered as 'treatment emergent' if it occurred after the first drug administration of each period or if it was present prior to drug administration but exacerbated after the drug administration.TEAEs were entered in infections and infestations SOC as per medical dictionary for regulatory activities (MedDRA) version 11.0
Outcome measures
| Measure |
Cladribine 3.5 mg/kg, IFN-beta (DB Period)
n=47 Participants
Participants received cladribine tablets orally as cumulative dose of 0.875 mg/kg over a course of 4-5 consecutive days at Week 1, 5, 48, and 52 resulting in total cladribine dose of 3.5 milligram per kilogram (mg/kg) along with interferon (IFN)-beta therapy (Rebif® new formulation \[RNF\] 44 mcg three times a week, subcutaneously; Avonex® 30 microgram (mcg) every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) during the Double blind period (DBP) of 96 weeks.
|
Placebo, IFN-beta (DB Period)
n=28 Participants
Participants received matching placebo tablets orally over a course of 4-5 consecutive days at Week 1, 5, 48, and 52 along with IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) during the DB period of 96 weeks.
|
Cladribine 3.5 mg/kg, IFN-beta, Cladribine 3.5 mg/kg (OL Ext)
n=52 Participants
Participants who received cladribine 3.5 mg/kg initially and completed DB period entered in the open label (OL) extension (Ext.) period. In OL Ext. period, participant who met the eligibility criteria received OL oral cladribine 3.5 mg/kg over maximum of 48 weeks along with IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) up to 48 weeks.
|
Placebo, IFN-beta, Cladribine 3.5 mg/kg (OL Ext)
n=7 Participants
Participants who received placebo initially and completed DB period entered in the OL Ext. period. In OL Ext. period, participant who met the eligibility criteria received OL oral cladribine 3.5 mg/kg over maximum of 48 weeks along with IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) up to 48 weeks.
|
|---|---|---|---|---|
|
OLE and Safety Follow-up Period: Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) in Infections and Infestations System Organ Class (SOC)
|
38.3 Percentage of participants
|
21.4 Percentage of participants
|
11.5 Percentage of participants
|
0 Percentage of participants
|
PRIMARY outcome
Timeframe: Baseline (OLEP) up to Week 96Population: Safety population included all randomized participants who received at least one dose of study medication in the DBP and had follow-up safety data.
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. An AE was considered as 'treatment emergent' if it occurred after the first drug administration of each period or if it was present prior to drug administration but exacerbated after the drug administration. TEAEs included both Serious TEAEs and non-serious TEAEs.
Outcome measures
| Measure |
Cladribine 3.5 mg/kg, IFN-beta (DB Period)
n=47 Participants
Participants received cladribine tablets orally as cumulative dose of 0.875 mg/kg over a course of 4-5 consecutive days at Week 1, 5, 48, and 52 resulting in total cladribine dose of 3.5 milligram per kilogram (mg/kg) along with interferon (IFN)-beta therapy (Rebif® new formulation \[RNF\] 44 mcg three times a week, subcutaneously; Avonex® 30 microgram (mcg) every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) during the Double blind period (DBP) of 96 weeks.
|
Placebo, IFN-beta (DB Period)
n=28 Participants
Participants received matching placebo tablets orally over a course of 4-5 consecutive days at Week 1, 5, 48, and 52 along with IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) during the DB period of 96 weeks.
|
Cladribine 3.5 mg/kg, IFN-beta, Cladribine 3.5 mg/kg (OL Ext)
n=52 Participants
Participants who received cladribine 3.5 mg/kg initially and completed DB period entered in the open label (OL) extension (Ext.) period. In OL Ext. period, participant who met the eligibility criteria received OL oral cladribine 3.5 mg/kg over maximum of 48 weeks along with IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) up to 48 weeks.
|
Placebo, IFN-beta, Cladribine 3.5 mg/kg (OL Ext)
n=7 Participants
Participants who received placebo initially and completed DB period entered in the OL Ext. period. In OL Ext. period, participant who met the eligibility criteria received OL oral cladribine 3.5 mg/kg over maximum of 48 weeks along with IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) up to 48 weeks.
|
|---|---|---|---|---|
|
OLE and Safety Follow-up Period: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs
Participants with TEAEs
|
37 Participants
|
19 Participants
|
22 Participants
|
0 Participants
|
|
OLE and Safety Follow-up Period: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs
Participants with Serious TEAEs
|
0 Participants
|
1 Participants
|
1 Participants
|
0 Participants
|
PRIMARY outcome
Timeframe: Baseline up to Week 96Population: Safety population included all randomized participants who received at least one dose of study medication in the DBP and had follow-up safety data. Here "Number of Participants analyzed"= participants evaluable for this outcome measure and "number analyzed"= participants who were evaluable for specified category.
Time to first Grade 3 or 4 hematological toxicity or liver toxicity (lymphocytes, cluster of differentiation 4 (CD4+) cell, neutrophils, white blood cells, hemoglobin, Alanine transaminase (ALT), Aspartate transaminase (AST), Platelets and Bilirubin) were estimated using the Kaplan-Meier method. According to CTCAE v 4.0: Grade 1=mild, Grade 2=moderate, Grade 3=severe, Grade 4=life threatening or disabling and Grade 5=Death. 10th and 20th percentiles estimated from Kaplan-Meier survival curve. Due to the small number of events, estimates from Kaplan-Meier survival curves could only be derived for lower percentiles. The median (50th percentile) could not be estimated if less than 50% of the participants had an event during the time of the study. Accordingly, lower percentiles are presented according to the number of events observed.
Outcome measures
| Measure |
Cladribine 3.5 mg/kg, IFN-beta (DB Period)
n=31 Participants
Participants received cladribine tablets orally as cumulative dose of 0.875 mg/kg over a course of 4-5 consecutive days at Week 1, 5, 48, and 52 resulting in total cladribine dose of 3.5 milligram per kilogram (mg/kg) along with interferon (IFN)-beta therapy (Rebif® new formulation \[RNF\] 44 mcg three times a week, subcutaneously; Avonex® 30 microgram (mcg) every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) during the Double blind period (DBP) of 96 weeks.
|
Placebo, IFN-beta (DB Period)
n=8 Participants
Participants received matching placebo tablets orally over a course of 4-5 consecutive days at Week 1, 5, 48, and 52 along with IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) during the DB period of 96 weeks.
|
Cladribine 3.5 mg/kg, IFN-beta, Cladribine 3.5 mg/kg (OL Ext)
Participants who received cladribine 3.5 mg/kg initially and completed DB period entered in the open label (OL) extension (Ext.) period. In OL Ext. period, participant who met the eligibility criteria received OL oral cladribine 3.5 mg/kg over maximum of 48 weeks along with IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) up to 48 weeks.
|
Placebo, IFN-beta, Cladribine 3.5 mg/kg (OL Ext)
Participants who received placebo initially and completed DB period entered in the OL Ext. period. In OL Ext. period, participant who met the eligibility criteria received OL oral cladribine 3.5 mg/kg over maximum of 48 weeks along with IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) up to 48 weeks.
|
|---|---|---|---|---|
|
Open Label Extension Period: Time to First Grade 3 or 4 Hematological Toxicity or Liver Toxicity
10th percentile: Lymphocytes toxicity
|
0.30 Months
|
0.36 Months
|
—
|
—
|
|
Open Label Extension Period: Time to First Grade 3 or 4 Hematological Toxicity or Liver Toxicity
20th percentile: Lymphocytes toxicity
|
1.64 Months
|
2.23 Months
|
—
|
—
|
|
Open Label Extension Period: Time to First Grade 3 or 4 Hematological Toxicity or Liver Toxicity
10th percentile: White Blood Cell toxicity
|
NA Months
Due to small number of events, estimates from Kaplan-Meier survival curves could not be derived.
|
NA Months
Due to small number of events, estimates from Kaplan-Meier survival curves could not be derived.
|
—
|
—
|
|
Open Label Extension Period: Time to First Grade 3 or 4 Hematological Toxicity or Liver Toxicity
20th percentile: White Blood Cell toxicity
|
NA Months
Due to small number of events, estimates from Kaplan-Meier survival curves could not be derived.
|
NA Months
Due to small number of events, estimates from Kaplan-Meier survival curves could not be derived.
|
—
|
—
|
|
Open Label Extension Period: Time to First Grade 3 or 4 Hematological Toxicity or Liver Toxicity
10th percentile: Neutrophil toxicity
|
NA Months
Due to small number of events, estimates from Kaplan-Meier survival curves could not be derived.
|
0.92 Months
|
—
|
—
|
|
Open Label Extension Period: Time to First Grade 3 or 4 Hematological Toxicity or Liver Toxicity
20th percentile: Neutrophil toxicity
|
NA Months
Due to small number of events, estimates from Kaplan-Meier survival curves could not be derived.
|
NA Months
Due to small number of events, estimates from Kaplan-Meier survival curves could not be derived.
|
—
|
—
|
|
Open Label Extension Period: Time to First Grade 3 or 4 Hematological Toxicity or Liver Toxicity
10th percentile: CD4+ count toxicity
|
0.92 Months
|
2.96 Months
|
—
|
—
|
|
Open Label Extension Period: Time to First Grade 3 or 4 Hematological Toxicity or Liver Toxicity
20th percentile: CD4+ count toxicity
|
0.99 Months
|
7.00 Months
|
—
|
—
|
|
Open Label Extension Period: Time to First Grade 3 or 4 Hematological Toxicity or Liver Toxicity
10th percentile: ALT toxicity
|
—
|
NA Months
Due to small number of events, estimates from Kaplan-Meier survival curves could not be derived.
|
—
|
—
|
|
Open Label Extension Period: Time to First Grade 3 or 4 Hematological Toxicity or Liver Toxicity
20th percentile: ALT toxicity
|
—
|
NA Months
Due to small number of events, estimates from Kaplan-Meier survival curves could not be derived.
|
—
|
—
|
SECONDARY outcome
Timeframe: Week 96Population: ITT population included all randomized participants who had received at least one dose of study medication in the DB period. Here "Number of Participants analyzed"= participants evaluable for this outcome measure.
Number of CUA lesions, active T2 lesions, and T1 Gd+ lesions were measured by using magnetic resonance imaging (MRI) scans.
Outcome measures
| Measure |
Cladribine 3.5 mg/kg, IFN-beta (DB Period)
n=121 Participants
Participants received cladribine tablets orally as cumulative dose of 0.875 mg/kg over a course of 4-5 consecutive days at Week 1, 5, 48, and 52 resulting in total cladribine dose of 3.5 milligram per kilogram (mg/kg) along with interferon (IFN)-beta therapy (Rebif® new formulation \[RNF\] 44 mcg three times a week, subcutaneously; Avonex® 30 microgram (mcg) every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) during the Double blind period (DBP) of 96 weeks.
|
Placebo, IFN-beta (DB Period)
n=48 Participants
Participants received matching placebo tablets orally over a course of 4-5 consecutive days at Week 1, 5, 48, and 52 along with IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) during the DB period of 96 weeks.
|
Cladribine 3.5 mg/kg, IFN-beta, Cladribine 3.5 mg/kg (OL Ext)
Participants who received cladribine 3.5 mg/kg initially and completed DB period entered in the open label (OL) extension (Ext.) period. In OL Ext. period, participant who met the eligibility criteria received OL oral cladribine 3.5 mg/kg over maximum of 48 weeks along with IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) up to 48 weeks.
|
Placebo, IFN-beta, Cladribine 3.5 mg/kg (OL Ext)
Participants who received placebo initially and completed DB period entered in the OL Ext. period. In OL Ext. period, participant who met the eligibility criteria received OL oral cladribine 3.5 mg/kg over maximum of 48 weeks along with IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) up to 48 weeks.
|
|---|---|---|---|---|
|
Double Blind Period: Number of Combined Unique Active (CUA) Lesions, Active Time Constant 2 (T2) Lesions, and Time Constant 1 (T1) Gadolinium Enhanced (Gd+) Lesions Per Participant Per Scan
T2 lesions
|
0.53 Lesions
Standard Deviation 1.26
|
1.04 Lesions
Standard Deviation 1.81
|
—
|
—
|
|
Double Blind Period: Number of Combined Unique Active (CUA) Lesions, Active Time Constant 2 (T2) Lesions, and Time Constant 1 (T1) Gadolinium Enhanced (Gd+) Lesions Per Participant Per Scan
T1 Gd+ lesions
|
0.06 Lesions
Standard Deviation 0.37
|
0.34 Lesions
Standard Deviation 0.87
|
—
|
—
|
|
Double Blind Period: Number of Combined Unique Active (CUA) Lesions, Active Time Constant 2 (T2) Lesions, and Time Constant 1 (T1) Gadolinium Enhanced (Gd+) Lesions Per Participant Per Scan
CUA lesions
|
0.55 Lesions
Standard Deviation 1.27
|
1.12 Lesions
Standard Deviation 1.94
|
—
|
—
|
SECONDARY outcome
Timeframe: Week 96Population: ITT population included all randomized participants who had received at least one dose of study medication in the DB period. Here "Number of participants analyzed" signifies those participants who were evaluable for this outcome measure.
Mean number of T1 hypointense lesions per participant per scan at 96 weeks were reported. T1 hypointense lesions were measured by using magnetic resonance imaging (MRI) scans.
Outcome measures
| Measure |
Cladribine 3.5 mg/kg, IFN-beta (DB Period)
n=121 Participants
Participants received cladribine tablets orally as cumulative dose of 0.875 mg/kg over a course of 4-5 consecutive days at Week 1, 5, 48, and 52 resulting in total cladribine dose of 3.5 milligram per kilogram (mg/kg) along with interferon (IFN)-beta therapy (Rebif® new formulation \[RNF\] 44 mcg three times a week, subcutaneously; Avonex® 30 microgram (mcg) every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) during the Double blind period (DBP) of 96 weeks.
|
Placebo, IFN-beta (DB Period)
n=48 Participants
Participants received matching placebo tablets orally over a course of 4-5 consecutive days at Week 1, 5, 48, and 52 along with IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) during the DB period of 96 weeks.
|
Cladribine 3.5 mg/kg, IFN-beta, Cladribine 3.5 mg/kg (OL Ext)
Participants who received cladribine 3.5 mg/kg initially and completed DB period entered in the open label (OL) extension (Ext.) period. In OL Ext. period, participant who met the eligibility criteria received OL oral cladribine 3.5 mg/kg over maximum of 48 weeks along with IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) up to 48 weeks.
|
Placebo, IFN-beta, Cladribine 3.5 mg/kg (OL Ext)
Participants who received placebo initially and completed DB period entered in the OL Ext. period. In OL Ext. period, participant who met the eligibility criteria received OL oral cladribine 3.5 mg/kg over maximum of 48 weeks along with IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) up to 48 weeks.
|
|---|---|---|---|---|
|
Double Blind Period: Mean Number of T1 Hypointense Lesions Per Participant Per Scan at Week 96
|
0.28 Lesions
Standard Deviation 0.63
|
0.43 Lesions
Standard Deviation 1.00
|
—
|
—
|
SECONDARY outcome
Timeframe: Week 96Population: ITT population included all randomized participants who had received at least one dose of study medication in the DB period. Here "Number of participants analyzed" signifies those participants who were evaluable for this outcome measure.
Percentage of participants with no active T2 lesions at week 96 were reported. Active T2 lesions were measured by using magnetic resonance imaging (MRI) scans.
Outcome measures
| Measure |
Cladribine 3.5 mg/kg, IFN-beta (DB Period)
n=121 Participants
Participants received cladribine tablets orally as cumulative dose of 0.875 mg/kg over a course of 4-5 consecutive days at Week 1, 5, 48, and 52 resulting in total cladribine dose of 3.5 milligram per kilogram (mg/kg) along with interferon (IFN)-beta therapy (Rebif® new formulation \[RNF\] 44 mcg three times a week, subcutaneously; Avonex® 30 microgram (mcg) every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) during the Double blind period (DBP) of 96 weeks.
|
Placebo, IFN-beta (DB Period)
n=48 Participants
Participants received matching placebo tablets orally over a course of 4-5 consecutive days at Week 1, 5, 48, and 52 along with IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) during the DB period of 96 weeks.
|
Cladribine 3.5 mg/kg, IFN-beta, Cladribine 3.5 mg/kg (OL Ext)
Participants who received cladribine 3.5 mg/kg initially and completed DB period entered in the open label (OL) extension (Ext.) period. In OL Ext. period, participant who met the eligibility criteria received OL oral cladribine 3.5 mg/kg over maximum of 48 weeks along with IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) up to 48 weeks.
|
Placebo, IFN-beta, Cladribine 3.5 mg/kg (OL Ext)
Participants who received placebo initially and completed DB period entered in the OL Ext. period. In OL Ext. period, participant who met the eligibility criteria received OL oral cladribine 3.5 mg/kg over maximum of 48 weeks along with IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) up to 48 weeks.
|
|---|---|---|---|---|
|
Double Blind Period: Percentage of Participants With no Active T2 Lesions at Week 96
|
56.2 Percentage of Participants
|
29.2 Percentage of Participants
|
—
|
—
|
SECONDARY outcome
Timeframe: Week 96Population: ITT population included all randomized participants who had received at least one dose of study medication in the DB period. Here "Number of participants analyzed" signifies those participants who were evaluable for this outcome measure.
Percentage of participants with no active T1 Gd-enhanced lesions at week 96 were reported. Active T1 Gd-Enhanced lesions were measured by using magnetic resonance imaging (MRI) scans.
Outcome measures
| Measure |
Cladribine 3.5 mg/kg, IFN-beta (DB Period)
n=121 Participants
Participants received cladribine tablets orally as cumulative dose of 0.875 mg/kg over a course of 4-5 consecutive days at Week 1, 5, 48, and 52 resulting in total cladribine dose of 3.5 milligram per kilogram (mg/kg) along with interferon (IFN)-beta therapy (Rebif® new formulation \[RNF\] 44 mcg three times a week, subcutaneously; Avonex® 30 microgram (mcg) every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) during the Double blind period (DBP) of 96 weeks.
|
Placebo, IFN-beta (DB Period)
n=48 Participants
Participants received matching placebo tablets orally over a course of 4-5 consecutive days at Week 1, 5, 48, and 52 along with IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) during the DB period of 96 weeks.
|
Cladribine 3.5 mg/kg, IFN-beta, Cladribine 3.5 mg/kg (OL Ext)
Participants who received cladribine 3.5 mg/kg initially and completed DB period entered in the open label (OL) extension (Ext.) period. In OL Ext. period, participant who met the eligibility criteria received OL oral cladribine 3.5 mg/kg over maximum of 48 weeks along with IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) up to 48 weeks.
|
Placebo, IFN-beta, Cladribine 3.5 mg/kg (OL Ext)
Participants who received placebo initially and completed DB period entered in the OL Ext. period. In OL Ext. period, participant who met the eligibility criteria received OL oral cladribine 3.5 mg/kg over maximum of 48 weeks along with IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) up to 48 weeks.
|
|---|---|---|---|---|
|
Double Blind Period: Percentage of Participants With no Active T1 Gd-Enhanced Lesions at Week 96
|
86.0 Percentage of Participants
|
56.3 Percentage of Participants
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, Week 96Population: ITT population included all randomized participants who had received at least one dose of study medication in the DB period. Here "Number of participants analyzed" signifies those participants who were evaluated for this outcome measure.
Mean change in T2 lesion volume From baseline to Week 96 were reported. T2 lesions were measured by using magnetic resonance imaging (MRI) scans.
Outcome measures
| Measure |
Cladribine 3.5 mg/kg, IFN-beta (DB Period)
n=105 Participants
Participants received cladribine tablets orally as cumulative dose of 0.875 mg/kg over a course of 4-5 consecutive days at Week 1, 5, 48, and 52 resulting in total cladribine dose of 3.5 milligram per kilogram (mg/kg) along with interferon (IFN)-beta therapy (Rebif® new formulation \[RNF\] 44 mcg three times a week, subcutaneously; Avonex® 30 microgram (mcg) every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) during the Double blind period (DBP) of 96 weeks.
|
Placebo, IFN-beta (DB Period)
n=37 Participants
Participants received matching placebo tablets orally over a course of 4-5 consecutive days at Week 1, 5, 48, and 52 along with IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) during the DB period of 96 weeks.
|
Cladribine 3.5 mg/kg, IFN-beta, Cladribine 3.5 mg/kg (OL Ext)
Participants who received cladribine 3.5 mg/kg initially and completed DB period entered in the open label (OL) extension (Ext.) period. In OL Ext. period, participant who met the eligibility criteria received OL oral cladribine 3.5 mg/kg over maximum of 48 weeks along with IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) up to 48 weeks.
|
Placebo, IFN-beta, Cladribine 3.5 mg/kg (OL Ext)
Participants who received placebo initially and completed DB period entered in the OL Ext. period. In OL Ext. period, participant who met the eligibility criteria received OL oral cladribine 3.5 mg/kg over maximum of 48 weeks along with IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) up to 48 weeks.
|
|---|---|---|---|---|
|
Double Blind Period: Mean Change in T2 Lesion Volume From Baseline to Week 96
|
-2007.2 cubic millimeters (mm^3)
Standard Deviation 3718.3
|
-1224.6 cubic millimeters (mm^3)
Standard Deviation 7056.3
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, Week 96Population: ITT population included all randomized participants who had received at least one dose of study medication in the DB period. Here "Number of participants analyzed" signifies those participants who were evaluated for this outcome measure.
Brain volume was measured using magnetic resonance imaging (MRI) scans of the brain. Percent change in normalized brain volume from baseline to week 96 was reported.
Outcome measures
| Measure |
Cladribine 3.5 mg/kg, IFN-beta (DB Period)
n=15 Participants
Participants received cladribine tablets orally as cumulative dose of 0.875 mg/kg over a course of 4-5 consecutive days at Week 1, 5, 48, and 52 resulting in total cladribine dose of 3.5 milligram per kilogram (mg/kg) along with interferon (IFN)-beta therapy (Rebif® new formulation \[RNF\] 44 mcg three times a week, subcutaneously; Avonex® 30 microgram (mcg) every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) during the Double blind period (DBP) of 96 weeks.
|
Placebo, IFN-beta (DB Period)
n=6 Participants
Participants received matching placebo tablets orally over a course of 4-5 consecutive days at Week 1, 5, 48, and 52 along with IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) during the DB period of 96 weeks.
|
Cladribine 3.5 mg/kg, IFN-beta, Cladribine 3.5 mg/kg (OL Ext)
Participants who received cladribine 3.5 mg/kg initially and completed DB period entered in the open label (OL) extension (Ext.) period. In OL Ext. period, participant who met the eligibility criteria received OL oral cladribine 3.5 mg/kg over maximum of 48 weeks along with IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) up to 48 weeks.
|
Placebo, IFN-beta, Cladribine 3.5 mg/kg (OL Ext)
Participants who received placebo initially and completed DB period entered in the OL Ext. period. In OL Ext. period, participant who met the eligibility criteria received OL oral cladribine 3.5 mg/kg over maximum of 48 weeks along with IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) up to 48 weeks.
|
|---|---|---|---|---|
|
Double Blind Period: Percent Change in Normalized Brain Volume From Baseline to Week 96
|
-1.01 Percent Change
Standard Deviation 1.03
|
-1.42 Percent Change
Standard Deviation 0.73
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, Week 96Population: ITT population included all randomized participants who had received at least one dose of study medication in the DB period. Here "Number of participants analyzed" signifies those participants who were evaluated for this outcome measure.
Mean change in T1 hypointense lesion volume from baseline to week 96 was reported. T1 Hypointense lesions were measured by using magnetic resonance imaging (MRI) scans.
Outcome measures
| Measure |
Cladribine 3.5 mg/kg, IFN-beta (DB Period)
n=105 Participants
Participants received cladribine tablets orally as cumulative dose of 0.875 mg/kg over a course of 4-5 consecutive days at Week 1, 5, 48, and 52 resulting in total cladribine dose of 3.5 milligram per kilogram (mg/kg) along with interferon (IFN)-beta therapy (Rebif® new formulation \[RNF\] 44 mcg three times a week, subcutaneously; Avonex® 30 microgram (mcg) every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) during the Double blind period (DBP) of 96 weeks.
|
Placebo, IFN-beta (DB Period)
n=37 Participants
Participants received matching placebo tablets orally over a course of 4-5 consecutive days at Week 1, 5, 48, and 52 along with IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) during the DB period of 96 weeks.
|
Cladribine 3.5 mg/kg, IFN-beta, Cladribine 3.5 mg/kg (OL Ext)
Participants who received cladribine 3.5 mg/kg initially and completed DB period entered in the open label (OL) extension (Ext.) period. In OL Ext. period, participant who met the eligibility criteria received OL oral cladribine 3.5 mg/kg over maximum of 48 weeks along with IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) up to 48 weeks.
|
Placebo, IFN-beta, Cladribine 3.5 mg/kg (OL Ext)
Participants who received placebo initially and completed DB period entered in the OL Ext. period. In OL Ext. period, participant who met the eligibility criteria received OL oral cladribine 3.5 mg/kg over maximum of 48 weeks along with IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) up to 48 weeks.
|
|---|---|---|---|---|
|
Double Blind Period: Mean Change in T1 Hypointense Lesion Volume From Baseline to Week 96
|
-481.8 millimeter cubic
Standard Deviation 1097.2
|
-263.0 millimeter cubic
Standard Deviation 1678.3
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline up to Week 96Population: ITT population included all randomized participants who had received at least one dose of study medication in the DB period.
A qualifying relapse was defined as a 2-grade increase in at least one, or a 1-grade increase in at least two, Kurtzke Functional Systems excluding bowel/bladder or cognition changes, in the absence of fever lasting more than or equal to 24 hours, and preceded by more than or equal to 30 days of clinical stability or improvement. 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.
Outcome measures
| Measure |
Cladribine 3.5 mg/kg, IFN-beta (DB Period)
n=124 Participants
Participants received cladribine tablets orally as cumulative dose of 0.875 mg/kg over a course of 4-5 consecutive days at Week 1, 5, 48, and 52 resulting in total cladribine dose of 3.5 milligram per kilogram (mg/kg) along with interferon (IFN)-beta therapy (Rebif® new formulation \[RNF\] 44 mcg three times a week, subcutaneously; Avonex® 30 microgram (mcg) every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) during the Double blind period (DBP) of 96 weeks.
|
Placebo, IFN-beta (DB Period)
n=48 Participants
Participants received matching placebo tablets orally over a course of 4-5 consecutive days at Week 1, 5, 48, and 52 along with IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) during the DB period of 96 weeks.
|
Cladribine 3.5 mg/kg, IFN-beta, Cladribine 3.5 mg/kg (OL Ext)
Participants who received cladribine 3.5 mg/kg initially and completed DB period entered in the open label (OL) extension (Ext.) period. In OL Ext. period, participant who met the eligibility criteria received OL oral cladribine 3.5 mg/kg over maximum of 48 weeks along with IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) up to 48 weeks.
|
Placebo, IFN-beta, Cladribine 3.5 mg/kg (OL Ext)
Participants who received placebo initially and completed DB period entered in the OL Ext. period. In OL Ext. period, participant who met the eligibility criteria received OL oral cladribine 3.5 mg/kg over maximum of 48 weeks along with IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) up to 48 weeks.
|
|---|---|---|---|---|
|
Double Blind Period: Annualized Qualifying Relapse Rate
|
0.12 relapses per year
Interval 0.08 to 0.17
|
0.32 relapses per year
Interval 0.2 to 0.45
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline up to Week 96Population: ITT population included all randomized participants who had received at least one dose of study medication in the DB period.
A qualifying relapse was defined as a 2-grade increase in 1 or more Kurtzke Functional Systems (KFS) or a 1-grade increase in 2 or more KFS, excluding changes in bowel/bladder or cognition, in the absence of fever, lasting for \>= 24 hours, and preceded by at least 30 days of clinical stability or improvement. Percentage of participants qualifying relapse-free were reported.
Outcome measures
| Measure |
Cladribine 3.5 mg/kg, IFN-beta (DB Period)
n=124 Participants
Participants received cladribine tablets orally as cumulative dose of 0.875 mg/kg over a course of 4-5 consecutive days at Week 1, 5, 48, and 52 resulting in total cladribine dose of 3.5 milligram per kilogram (mg/kg) along with interferon (IFN)-beta therapy (Rebif® new formulation \[RNF\] 44 mcg three times a week, subcutaneously; Avonex® 30 microgram (mcg) every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) during the Double blind period (DBP) of 96 weeks.
|
Placebo, IFN-beta (DB Period)
n=48 Participants
Participants received matching placebo tablets orally over a course of 4-5 consecutive days at Week 1, 5, 48, and 52 along with IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) during the DB period of 96 weeks.
|
Cladribine 3.5 mg/kg, IFN-beta, Cladribine 3.5 mg/kg (OL Ext)
Participants who received cladribine 3.5 mg/kg initially and completed DB period entered in the open label (OL) extension (Ext.) period. In OL Ext. period, participant who met the eligibility criteria received OL oral cladribine 3.5 mg/kg over maximum of 48 weeks along with IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) up to 48 weeks.
|
Placebo, IFN-beta, Cladribine 3.5 mg/kg (OL Ext)
Participants who received placebo initially and completed DB period entered in the OL Ext. period. In OL Ext. period, participant who met the eligibility criteria received OL oral cladribine 3.5 mg/kg over maximum of 48 weeks along with IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) up to 48 weeks.
|
|---|---|---|---|---|
|
Double Blind Period: Percentage of Participants Qualifying Relapse-free
|
75.0 Percentage of Participants
|
52.1 Percentage of Participants
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline up to Week 96Population: ITT population included all randomized participants who had received at least one dose of study medication in the DB period. Here "Number of Participants analyzed"= participants evaluable for this outcome measure and "number analyzed"= participants who were evaluable for specified category.
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. Time to sustained disability progression was analyzed using a Cox proportional hazards model. 10th and 20th percentiles estimated from Kaplan-Meier survival curve. Due to the small number of events, estimates from Kaplan-Meier survival curves could only be derived for lower percentiles. The median (50th percentile) could not be estimated if less than 50% of the participants had an event during the time of the study. Accordingly, lower percentiles are presented according to the number of events observed.
Outcome measures
| Measure |
Cladribine 3.5 mg/kg, IFN-beta (DB Period)
n=19 Participants
Participants received cladribine tablets orally as cumulative dose of 0.875 mg/kg over a course of 4-5 consecutive days at Week 1, 5, 48, and 52 resulting in total cladribine dose of 3.5 milligram per kilogram (mg/kg) along with interferon (IFN)-beta therapy (Rebif® new formulation \[RNF\] 44 mcg three times a week, subcutaneously; Avonex® 30 microgram (mcg) every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) during the Double blind period (DBP) of 96 weeks.
|
Placebo, IFN-beta (DB Period)
n=6 Participants
Participants received matching placebo tablets orally over a course of 4-5 consecutive days at Week 1, 5, 48, and 52 along with IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) during the DB period of 96 weeks.
|
Cladribine 3.5 mg/kg, IFN-beta, Cladribine 3.5 mg/kg (OL Ext)
n=10 Participants
Participants who received cladribine 3.5 mg/kg initially and completed DB period entered in the open label (OL) extension (Ext.) period. In OL Ext. period, participant who met the eligibility criteria received OL oral cladribine 3.5 mg/kg over maximum of 48 weeks along with IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) up to 48 weeks.
|
Placebo, IFN-beta, Cladribine 3.5 mg/kg (OL Ext)
n=5 Participants
Participants who received placebo initially and completed DB period entered in the OL Ext. period. In OL Ext. period, participant who met the eligibility criteria received OL oral cladribine 3.5 mg/kg over maximum of 48 weeks along with IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) up to 48 weeks.
|
|---|---|---|---|---|
|
Double Blind Period and OLE Period: Time to 3-Month Sustained Expanded Disability Status Scale (EDSS) Progression
20th percentile
|
NA Days
Due to small number of events, estimates from Kaplan-Meier survival curves could not be derived.
|
0 Days
|
246 Days
|
0 Days
|
|
Double Blind Period and OLE Period: Time to 3-Month Sustained Expanded Disability Status Scale (EDSS) Progression
10th percentile
|
244 Days
|
484 Days
|
87 Days
|
85 Days
|
SECONDARY outcome
Timeframe: Baseline up to Week 96Population: ITT population included all randomized participants who had received at least one dose of study medication in the DB period. Here "Number of Participants analyzed"= participants evaluable for this outcome measure and "number analyzed"= participants who were evaluable for specified category.
A qualifying relapse was defined as a 2-grade increase in at least one, or a 1-grade increase in at least two, Kurtzke Functional Systems excluding bowel/bladder or cognition changes, in the absence of fever lasting more than or equal to 24 hours, and preceded by more than or equal to 30 days of clinical stability or improvement. Time to first qualifying relapse were analyzed using a Cox proportional hazards model. 10th and 20th percentiles estimated from Kaplan-Meier survival curve. Due to the small number of events, estimates from Kaplan-Meier survival curves could only be derived for lower percentiles. The median (50th percentile) could not be estimated if less than 50% of the participants had an event during the time of the study. Accordingly, lower percentiles are presented according to the number of events observed.
Outcome measures
| Measure |
Cladribine 3.5 mg/kg, IFN-beta (DB Period)
n=23 Participants
Participants received cladribine tablets orally as cumulative dose of 0.875 mg/kg over a course of 4-5 consecutive days at Week 1, 5, 48, and 52 resulting in total cladribine dose of 3.5 milligram per kilogram (mg/kg) along with interferon (IFN)-beta therapy (Rebif® new formulation \[RNF\] 44 mcg three times a week, subcutaneously; Avonex® 30 microgram (mcg) every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) during the Double blind period (DBP) of 96 weeks.
|
Placebo, IFN-beta (DB Period)
n=16 Participants
Participants received matching placebo tablets orally over a course of 4-5 consecutive days at Week 1, 5, 48, and 52 along with IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) during the DB period of 96 weeks.
|
Cladribine 3.5 mg/kg, IFN-beta, Cladribine 3.5 mg/kg (OL Ext)
n=4 Participants
Participants who received cladribine 3.5 mg/kg initially and completed DB period entered in the open label (OL) extension (Ext.) period. In OL Ext. period, participant who met the eligibility criteria received OL oral cladribine 3.5 mg/kg over maximum of 48 weeks along with IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) up to 48 weeks.
|
Placebo, IFN-beta, Cladribine 3.5 mg/kg (OL Ext)
n=4 Participants
Participants who received placebo initially and completed DB period entered in the OL Ext. period. In OL Ext. period, participant who met the eligibility criteria received OL oral cladribine 3.5 mg/kg over maximum of 48 weeks along with IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) up to 48 weeks.
|
|---|---|---|---|---|
|
Double Blind Period and OLE Period: Time to First Qualifying Relapse
10th percentile
|
239 Days
|
252 Days
|
255 Days
|
155 Days
|
|
Double Blind Period and OLE Period: Time to First Qualifying Relapse
20th percentile
|
NA Days
Due to small number of events, estimates from Kaplan-Meier survival curves could not be derived.
|
481 Days
|
0 Days
|
0 Days
|
SECONDARY outcome
Timeframe: Baseline, Week 96Population: ITT population included all randomized participants who had received at least one dose of study medication in the DB period. Here "Number of participants analyzed" signifies those participants who were evaluated for this outcome measure.
Mean change in new T1 Gd+ lesions from baseline to week 96 was reported.
Outcome measures
| Measure |
Cladribine 3.5 mg/kg, IFN-beta (DB Period)
n=105 Participants
Participants received cladribine tablets orally as cumulative dose of 0.875 mg/kg over a course of 4-5 consecutive days at Week 1, 5, 48, and 52 resulting in total cladribine dose of 3.5 milligram per kilogram (mg/kg) along with interferon (IFN)-beta therapy (Rebif® new formulation \[RNF\] 44 mcg three times a week, subcutaneously; Avonex® 30 microgram (mcg) every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) during the Double blind period (DBP) of 96 weeks.
|
Placebo, IFN-beta (DB Period)
n=37 Participants
Participants received matching placebo tablets orally over a course of 4-5 consecutive days at Week 1, 5, 48, and 52 along with IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) during the DB period of 96 weeks.
|
Cladribine 3.5 mg/kg, IFN-beta, Cladribine 3.5 mg/kg (OL Ext)
Participants who received cladribine 3.5 mg/kg initially and completed DB period entered in the open label (OL) extension (Ext.) period. In OL Ext. period, participant who met the eligibility criteria received OL oral cladribine 3.5 mg/kg over maximum of 48 weeks along with IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) up to 48 weeks.
|
Placebo, IFN-beta, Cladribine 3.5 mg/kg (OL Ext)
Participants who received placebo initially and completed DB period entered in the OL Ext. period. In OL Ext. period, participant who met the eligibility criteria received OL oral cladribine 3.5 mg/kg over maximum of 48 weeks along with IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) up to 48 weeks.
|
|---|---|---|---|---|
|
Double Blind Period: Mean Change in New T1 Gd+ Lesions From Baseline to Week 96
|
-1.0 Lesions
Standard Deviation 4.4
|
-0.3 Lesions
Standard Deviation 1.1
|
—
|
—
|
Adverse Events
Cladribine 3.5 mg/kg, IFN-beta (DB Period)
Serious events: 12 serious events
Other events: 111 other events
Deaths: 0 deaths
Placebo, IFN-beta (DB Period)
Serious events: 5 serious events
Other events: 33 other events
Deaths: 0 deaths
Cladribine 3.5 mg/kg, IFN-beta, Cladribine 3.5 mg/kg (OL Ext)
Serious events: 0 serious events
Other events: 24 other events
Deaths: 0 deaths
Placebo, IFN-beta, Cladribine 3.5 mg/kg (OL Ext)
Serious events: 1 serious events
Other events: 12 other events
Deaths: 0 deaths
Cladribine 3.5 mg/kg, IFN-beta (Safety Follow up)
Serious events: 1 serious events
Other events: 0 other events
Deaths: 0 deaths
Placebo, IFN-beta (Safety Follow up)
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Cladribine 3.5 mg/kg, IFN-beta (DB Period)
n=124 participants at risk
Participants received cladribine tablets orally as cumulative dose of 0.875 mg/kg over a course of 4-5 consecutive days at Week 1, 5, 48, and 52 resulting in total cladribine dose of 3.5 milligram per kilogram (mg/kg) along with interferon (IFN)-beta therapy (Rebif® new formulation \[RNF\] 44 mcg three times a week, subcutaneously; Avonex® 30 microgram (mcg) every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) during the Double blind period (DBP) of 96 weeks.
|
Placebo, IFN-beta (DB Period)
n=48 participants at risk
Participants received matching placebo tablets orally over a course of 4-5 consecutive days at Week 1, 5, 48, and 52 along with IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) during the DB period of 96 weeks.
|
Cladribine 3.5 mg/kg, IFN-beta, Cladribine 3.5 mg/kg (OL Ext)
n=47 participants at risk
Participants who received cladribine 3.5 mg/kg initially and completed DB period entered in the open label (OL) extension (Ext.) period. In OL Ext. period, participant who met the eligibility criteria received OL oral cladribine 3.5 mg/kg over maximum of 48 weeks along with IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) up to 48 weeks.
|
Placebo, IFN-beta, Cladribine 3.5 mg/kg (OL Ext)
n=28 participants at risk
Participants who received placebo initially and completed DB period entered in the OL Ext. period. In OL Ext. period, participant who met the eligibility criteria received OL oral cladribine 3.5 mg/kg over maximum of 48 weeks along with IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) up to 48 weeks.
|
Cladribine 3.5 mg/kg, IFN-beta (Safety Follow up)
n=52 participants at risk
Participants who received cladribine 3.5 mg/kg initially and completed DB period entered in the OL ext. safety follow up period. In this period, participants who did not meet eligibility criteria received only IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) up to 48 weeks.
|
Placebo, IFN-beta (Safety Follow up)
n=7 participants at risk
Participants who received placebo initially and completed DB period entered in the OL ext. safety follow up period. In this period, participants who did not meet eligibility criteria received only IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) up to 48 weeks.
|
|---|---|---|---|---|---|---|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Benign breast neoplasm
|
0.81%
1/124 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/48 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/47 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/28 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/52 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/7 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lipoma
|
0.81%
1/124 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/48 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/47 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/28 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/52 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/7 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Melanocytic naevus
|
0.81%
1/124 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/48 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/47 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/28 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/52 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/7 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Seborrhoeic keratosis
|
0.81%
1/124 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/48 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/47 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/28 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/52 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/7 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Skin papilloma
|
0.81%
1/124 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/48 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/47 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/28 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/52 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/7 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
|
Infections and infestations
Genital herpes
|
0.81%
1/124 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/48 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/47 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/28 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/52 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/7 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
|
Infections and infestations
Human ehrlichiosis
|
0.81%
1/124 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/48 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/47 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/28 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/52 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/7 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
|
Infections and infestations
Pyelonephritis acute
|
0.81%
1/124 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/48 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/47 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/28 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/52 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/7 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
|
Infections and infestations
Urinary tract infection
|
0.81%
1/124 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/48 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/47 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/28 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/52 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/7 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
|
Hepatobiliary disorders
Cholecystitis
|
1.6%
2/124 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/48 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/47 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/28 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/52 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/7 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
|
Hepatobiliary disorders
Hepatic cyst
|
0.00%
0/124 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
2.1%
1/48 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/47 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/28 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/52 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/7 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
|
Gastrointestinal disorders
Anal fissure
|
0.81%
1/124 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/48 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/47 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/28 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/52 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/7 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
|
Gastrointestinal disorders
Pancreatitis acute
|
0.81%
1/124 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/48 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/47 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/28 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
1.9%
1/52 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/7 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
|
Renal and urinary disorders
Atonic urinary bladder
|
0.81%
1/124 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/48 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/47 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/28 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/52 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/7 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
|
Renal and urinary disorders
Hydronephrosis
|
0.81%
1/124 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/48 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/47 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/28 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/52 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/7 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
|
Renal and urinary disorders
Nephrolithiasis
|
0.81%
1/124 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/48 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/47 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/28 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/52 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/7 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
|
General disorders
Non-cardiac chest pain
|
0.00%
0/124 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
2.1%
1/48 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/47 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/28 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/52 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/7 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
|
Nervous system disorders
Grand mal convulsion
|
0.81%
1/124 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/48 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/47 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/28 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/52 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/7 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
|
Nervous system disorders
Status epilepticus
|
0.81%
1/124 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/48 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/47 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/28 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/52 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/7 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
|
Pregnancy, puerperium and perinatal conditions
Abortion spontaneous
|
0.00%
0/124 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
2.1%
1/48 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/47 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/28 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/52 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/7 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
|
Reproductive system and breast disorders
Menometrorrhagia
|
0.81%
1/124 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/48 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/47 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/28 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/52 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/7 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
|
Skin and subcutaneous tissue disorders
Skin lesion
|
0.00%
0/124 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
2.1%
1/48 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/47 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/28 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/52 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/7 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
|
Surgical and medical procedures
Abortion induced
|
0.00%
0/124 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
2.1%
1/48 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/47 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/28 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/52 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/7 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
|
Injury, poisoning and procedural complications
Traumatic haematoma
|
0.00%
0/124 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/48 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/47 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
3.6%
1/28 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/52 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/7 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
|
Injury, poisoning and procedural complications
Ulna fracture
|
0.00%
0/124 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/48 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/47 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
3.6%
1/28 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/52 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/7 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.00%
0/124 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/48 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/47 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
3.6%
1/28 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/52 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/7 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
Other adverse events
| Measure |
Cladribine 3.5 mg/kg, IFN-beta (DB Period)
n=124 participants at risk
Participants received cladribine tablets orally as cumulative dose of 0.875 mg/kg over a course of 4-5 consecutive days at Week 1, 5, 48, and 52 resulting in total cladribine dose of 3.5 milligram per kilogram (mg/kg) along with interferon (IFN)-beta therapy (Rebif® new formulation \[RNF\] 44 mcg three times a week, subcutaneously; Avonex® 30 microgram (mcg) every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) during the Double blind period (DBP) of 96 weeks.
|
Placebo, IFN-beta (DB Period)
n=48 participants at risk
Participants received matching placebo tablets orally over a course of 4-5 consecutive days at Week 1, 5, 48, and 52 along with IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) during the DB period of 96 weeks.
|
Cladribine 3.5 mg/kg, IFN-beta, Cladribine 3.5 mg/kg (OL Ext)
n=47 participants at risk
Participants who received cladribine 3.5 mg/kg initially and completed DB period entered in the open label (OL) extension (Ext.) period. In OL Ext. period, participant who met the eligibility criteria received OL oral cladribine 3.5 mg/kg over maximum of 48 weeks along with IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) up to 48 weeks.
|
Placebo, IFN-beta, Cladribine 3.5 mg/kg (OL Ext)
n=28 participants at risk
Participants who received placebo initially and completed DB period entered in the OL Ext. period. In OL Ext. period, participant who met the eligibility criteria received OL oral cladribine 3.5 mg/kg over maximum of 48 weeks along with IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) up to 48 weeks.
|
Cladribine 3.5 mg/kg, IFN-beta (Safety Follow up)
n=52 participants at risk
Participants who received cladribine 3.5 mg/kg initially and completed DB period entered in the OL ext. safety follow up period. In this period, participants who did not meet eligibility criteria received only IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) up to 48 weeks.
|
Placebo, IFN-beta (Safety Follow up)
n=7 participants at risk
Participants who received placebo initially and completed DB period entered in the OL ext. safety follow up period. In this period, participants who did not meet eligibility criteria received only IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) up to 48 weeks.
|
|---|---|---|---|---|---|---|
|
Blood and lymphatic system disorders
Lymphopenia
|
40.3%
50/124 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/48 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
23.4%
11/47 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
7.1%
2/28 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/52 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/7 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
|
Blood and lymphatic system disorders
Neutropenia
|
10.5%
13/124 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
6.2%
3/48 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
6.4%
3/47 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
10.7%
3/28 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/52 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/7 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
|
Blood and lymphatic system disorders
Leukopenia
|
11.3%
14/124 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/48 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/47 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/28 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/52 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/7 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
|
Gastrointestinal disorders
Nausea
|
14.5%
18/124 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
12.5%
6/48 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/47 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/28 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/52 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/7 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
|
Psychiatric disorders
Depression
|
5.6%
7/124 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
4.2%
2/48 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/47 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/28 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/52 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/7 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
|
Gastrointestinal disorders
Diarrhoea
|
7.3%
9/124 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
2.1%
1/48 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/47 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/28 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/52 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/7 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
|
Gastrointestinal disorders
Vomiting
|
3.2%
4/124 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
6.2%
3/48 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/47 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/28 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/52 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/7 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
|
Gastrointestinal disorders
Dyspepsia
|
1.6%
2/124 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
6.2%
3/48 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/47 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/28 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/52 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/7 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
|
General disorders
Influenza like illness
|
10.5%
13/124 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
8.3%
4/48 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/47 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/28 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/52 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/7 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
|
General disorders
Pyrexia
|
10.5%
13/124 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
8.3%
4/48 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/47 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/28 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/52 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/7 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
|
General disorders
Fatigue
|
5.6%
7/124 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
6.2%
3/48 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/47 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/28 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/52 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/7 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
|
General disorders
Pain
|
1.6%
2/124 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
8.3%
4/48 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/47 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/28 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/52 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/7 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
|
Infections and infestations
Nasopharyngitis
|
22.6%
28/124 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
16.7%
8/48 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
6.4%
3/47 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/28 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/52 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/7 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
|
Infections and infestations
Upper respiratory tract infection
|
11.3%
14/124 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
16.7%
8/48 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
6.4%
3/47 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
3.6%
1/28 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/52 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/7 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
|
Infections and infestations
Sinusitis
|
12.1%
15/124 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
12.5%
6/48 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/47 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/28 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/52 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/7 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
|
Infections and infestations
Urinary tract infection
|
11.3%
14/124 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
10.4%
5/48 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
2.1%
1/47 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
14.3%
4/28 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/52 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/7 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
|
Infections and infestations
Influenza
|
5.6%
7/124 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
8.3%
4/48 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/47 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/28 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/52 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/7 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
|
Infections and infestations
Bronchitis
|
5.6%
7/124 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
4.2%
2/48 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/47 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/28 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/52 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/7 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
|
Infections and infestations
Herpes zoster
|
5.6%
7/124 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/48 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/47 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/28 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/52 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/7 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
|
Investigations
Lymphocyte count decreased
|
10.5%
13/124 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/48 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
8.5%
4/47 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
3.6%
1/28 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/52 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/7 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
|
Investigations
Alanine aminotransferase increased
|
1.6%
2/124 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
6.2%
3/48 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/47 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/28 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/52 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/7 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
8.1%
10/124 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
8.3%
4/48 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/47 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/28 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/52 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/7 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
9.7%
12/124 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/48 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/47 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/28 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/52 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/7 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
6.5%
8/124 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
4.2%
2/48 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/47 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/28 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/52 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/7 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
|
Nervous system disorders
Headache
|
25.0%
31/124 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
20.8%
10/48 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
12.8%
6/47 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
3.6%
1/28 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/52 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/7 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
|
Nervous system disorders
Dizziness
|
4.8%
6/124 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
6.2%
3/48 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/47 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/28 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/52 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/7 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
|
Pregnancy, puerperium and perinatal conditions
Pregnancy
|
0.81%
1/124 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
6.2%
3/48 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/47 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/28 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/52 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/7 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
|
Psychiatric disorders
Insomnia
|
4.0%
5/124 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
6.2%
3/48 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/47 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/28 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/52 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/7 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
6.5%
8/124 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
8.3%
4/48 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/47 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/28 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/52 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/7 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
|
Respiratory, thoracic and mediastinal disorders
Pharyngolaryngeal pain
|
5.6%
7/124 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
6.2%
3/48 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/47 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/28 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/52 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/7 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
|
Respiratory, thoracic and mediastinal disorders
Sinus congestion
|
0.81%
1/124 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
6.2%
3/48 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/47 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/28 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/52 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/7 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
|
Skin and subcutaneous tissue disorders
Rash
|
4.8%
6/124 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
6.2%
3/48 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/47 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/28 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/52 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/7 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
|
Injury, poisoning and procedural complications
Fall
|
0.00%
0/124 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/48 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
2.1%
1/47 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
7.1%
2/28 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/52 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/7 • DB Period: Baseline up to Week 96; OL Extension Period and Safety follow-up period: Baseline up to Week 96
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
|
Additional Information
Communication Center
Merck KGaA, Darmstadt, Germany
Phone: +49-6151-72-5200
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: OTHER