CLARITY Extension Study
Sponsor
EMD Serono Research & Development Institute, Inc. (Industry)
Overall Status
Completed
CT.gov ID
NCT00641537
Collaborator
(none)
867
117
8
46
7.4
0.2
Study Details
Study Description
Brief Summary
The purpose of this extension trial was to further evaluate the safety and tolerability of oral cladribine in subjects who have previously completed treatment within Trial 25643 (CLARITY). This trial also explored clinical benefit of prolonged 192-week versus 96-week treatment.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
867 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Phase IIIb, Double-Blind, Placebo-Controlled, Multicenter, Parallel Group, Extension Trial to Evaluate the Safety and Tolerability of Oral Cladribine in Subjects With Relapsing-Remitting Multiple Sclerosis Who Have Completed Trial 25643 (CLARITY)
Actual Study Start Date
:
Feb 29, 2008
Actual Primary Completion Date
:
Dec 31, 2011
Actual Study Completion Date
:
Dec 31, 2011
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Placebo Comparator: Cladribine Low/Placebo (LLPP)
|
Drug: Placebo
Participants who received Cladribine 3.5 mg/kg in the previous study 25643 (NCT00213135) and completed will be re-randomized in this extension study and receive placebo matched to cladribine tablet 0.875 mg/kg orally administered over a course of 4 or 5 consecutive days of 28-day period at Week 1, 5, 48, and 52 during the treatment period of 96 weeks.
|
| Placebo Comparator: Cladribine High Dose/Placebo (HLPP)
|
Drug: Placebo
Participants who received Cladribine 5.25 mg/kg in the previous study 25643 (NCT00213135) and completed will be re-randomized in this extension study and receive placebo matched to cladribine tablet 0.875 mg/kg orally administered over a course of 4 or 5 consecutive days of 28-day period at Week 1, 5, 48, and 52 during the treatment period of 96 weeks.
|
| Experimental: Cladribine Low/Low Dose (LLLL)
|
Drug: Cladribine
Participants who received Cladribine 3.5 mg/kg in the previous study 25643 (NCT00213135) and completed will be re-randomized in this extension study and receive cladribine tablet orally as cumulative dose of 0.875 mg/kg over a course of 4 or 5 consecutive days of 28-day period at Week 1, 5, 48, and 52 resulting in total cladribine dose of 3.5 mg/kg during the treatment period of 96 weeks.
|
| Experimental: Cladribine High/Low Dose (HLLL)
|
Drug: Cladribine
Participants who received Cladribine 5.25 mg/kg in the previous study 25643 (NCT00213135) and completed will be re-randomized in this extension study and receive cladribine tablet orally as cumulative dose of 0.875 mg/kg over a course of 4 or 5 consecutive days of 28-day period at Week 1, 5, 48, and 52 resulting in total cladribine dose of 3.5 mg/kg during the treatment period of 96 weeks.
|
| Experimental: Placebo/Cladribine Low Dose (PPLL)
|
Drug: Cladribine
Participants who received placebo in the previous study 25643 (NCT00213135) and completed will be re-randomized in this extension study and receive cladribine tablet orally as cumulative dose of 0.875 mg/kg over a course of 4 or 5 consecutive days of 28-day period at Week 1, 5, 48, and 52 resulting in total cladribine dose of 3.5 mg/kg during the treatment period of 96 weeks.
|
| No Intervention: Placebo/No Treatment
|
|
| No Intervention: Cladribine 3.5 mg/kg/No Treatment Participants who received cladribine 3.5 mg/kg in previous study 25643 (NCT00213135) and completed were enrolled in this extension study and received no cladribine treatment and were followed up for safety assessment for 96 weeks (during the treatment period) and followed up for 24 weeks (during supplemental follow-up period). |
|
| No Intervention: Cladribine 5.25 mg/kg/No Treatment Participants who received cladribine 5.25 mg/kg in previous study 25643 (NCT00213135) and completed were enrolled in this extension study and received no cladribine treatment and were followed up for safety assessment for 96 weeks (during the treatment period) and followed up for 24 weeks (during supplemental follow-up period). |
Outcome Measures
Primary Outcome Measures
- Safety Population: Percentage of Participants With at Least 1 Common Terminology Criteria for Adverse Events Version 3.0 (CTCAE) Grade 4 Hematologic and Hepatic Toxicity [Baseline up to Week 120]
Hematologic and hepatic toxicity was assessed using Common Terminology Criteria for Adverse Events v 3.0 (CTCAE). Hematologic and hepatic function included absolute lymphocyte count (ALC), hemoglobin level, white blood cell (WBC) count, absolute neutrophil count (ANC), platelets, alanine transaminase (ALT), aspartate transaminase (AST) and bilirubin. According to CTCAE v3.0: Grade 1=mild, Grade 2=moderate, Grade 3=severe, Grade 4=life threatening or disabling and Grade 5=Death.
- Safety Population: Mean Change From Baseline in Absolute Lymphocyte Count, Platelet, Neutrophils and Leukocytes at Week 120 [Baseline, Week 120]
Mean change from baseline in absolute lymphocyte count, platelet, neutrophils and leukocytes at week 120 were reported.
- Safety Population: Mean Change From Baseline in Hemoglobin at Week 120 [Baseline, Week 120]
Mean change from baseline in hemoglobin at Week 120 was reported.
- Safety Population: Mean Change From Baseline in Aspartate Aminotransferase and Alanine Aminotransferase at Week 120 [Baseline, Week 120]
Mean change from baseline in aspartate aminotransferase and alanine aminotransferase at week 120 were reported.
- Safety Population: Mean Change From Baseline in Bilirubin at Week 120 [Baseline, Week 120]
Mean Change From Baseline in Bilirubin at week 120 was reported.
- Safety Population: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs [Baseline up to Week 120]
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered. Serious AE (SAE): Any AE that resulted in death; was life threatening; resulted in persistent/significant disability/incapacity; resulted in/prolonged an existing in-patient hospitalization; was a congenital anomaly/birth defect; or was a medically important condition. The term TEAE is defined as AEs starting or worsening after the first intake of the study drug. Number of participants with TEAEs included participants with both non-serious TEAEs and serious TEAEs.
- SAFUP Analysis Set: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs [Baseline up to Week 120]
An AE was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered. SAE: Any AE that resulted in death; was life threatening; resulted in persistent/significant disability/incapacity; resulted in/prolonged an existing in-patient hospitalization; was a congenital anomaly/birth defect; or was a medically important condition. The term TEAE is defined as AEs starting or worsening after the first intake of the study drug. Number of participants with TEAEs included participants with both non-serious TEAEs and serious TEAEs.
- Safety Population: Number of Participants Who Developed Infections (Herpes Viral Infection, Viral Infectious Disorder and Opportunistic Infection), Infection-related Adverse Events and Malignancies [Baseline up to Week 120]
Number of participants who developed Herpes viral infection, Viral infectious disorder and Opportunistic infection are reported. Number of participants with infection related adverse events are the number of participants who had at least one adverse event coded to medical dictionary for regulatory activities (MedDRA) preferred terms under infection and infestation system organ class. Malignancy is defined as having at least one adverse event coded to MedDRA preferred terms under the pre-specified grouping Malignant and unspecified tumors.
- SAFUP Analysis Set: Number of Participants Who Developed Infections (Herpes Viral Infection, Viral Infectious Disorder and Opportunistic Infection), Infection-related Adverse Events and Malignancies [Baseline up to Week 120]
Number of participants who developed Herpes viral infection, Viral infectious disorder and Opportunistic infection were reported. Number of participants with infection related adverse events are the number of participants who had at least one adverse event coded to medical dictionary for regulatory activities (MedDRA) preferred terms under infection and infestation system organ class. Malignancy is defined as having at least one adverse event coded to MedDRA preferred terms under the pre-specified grouping Malignant and unspecified tumors.
- Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity [Baseline up to Week 120]
Hematologic and hepatic toxicity was assessed using Common Terminology Criteria for Adverse Events version 3.0 (CTCAE). Hematologic and hepatic function included absolute lymphocyte count (ALC), hemoglobin level, white blood cell (WBC) count, absolute neutrophil count (ANC), platelets, alanine transaminase (ALT), aspartate transaminase (AST) and bilirubin. Time to first CTCAE Grade 3 or 4 hematological or liver toxicity was analyzed by treatment group using Kaplan-Meier plots of probability of surviving toxicity-free and point estimates of percentiles. According to CTCAE version 3.0: Grade 1=mild, Grade 2=moderate, Grade 3=severe, Grade 4=life threatening or disabling and Grade 5=Death. 10th, 20th, 25th, 50th and 75th percentiles were estimated from Kaplan-Meier survival curve.
- Safety Population: Median Time to Recovery From Grade 3 or 4 Hematological and Hepatic Toxicity [Baseline up to Week 120]
Hematologic and hepatic toxicity was assessed using Common Terminology Criteria for Adverse Events (CTCAE). Hematologic and hepatic function included absolute lymphocyte count (ALC), hemoglobin level, white blood cell (WBC) count, absolute neutrophil count (ANC), platelets, alanine transaminase (ALT), aspartate transaminase (AST) and bilirubin. According to CTCAE version 3.0: Grade 1=mild, Grade 2=moderate, Grade 3=severe, Grade 4=life threatening or disabling and Grade 5=Death. Time to recovery from grade 3 or 4 hematological or liver toxicity were reported: lymphocytes, platelets, neutrophils, white blood cells, hemoglobin, Alanine transaminase (ALT), Aspartate transaminase (AST), Platelets and Bilirubin. Recovery from a Grade 3 or 4 toxicity is defined as a return to a Grade 0 or 1.
- Safety Population: Mean Time to Recovery From Grade 3 or 4 Hematological and Liver Toxicity [Baseline up to Week 120]
Hematologic and hepatic toxicity was assessed using Common Terminology Criteria for Adverse Events (CTCAE). Hematologic and hepatic function included absolute lymphocyte count (ALC), hemoglobin level, white blood cell (WBC) count, absolute neutrophil count (ANC), platelets, alanine transaminase (ALT), aspartate transaminase (AST) and bilirubin. According to CTCAE v3.0: Grade 1=mild, Grade 2=moderate, Grade 3=severe, Grade 4=life threatening or disabling and Grade 5=Death. Time to recovery from grade 3 or 4 hematological or liver toxicity were reported: lymphocytes, platelets, neutrophils, white blood cells, hemoglobin, Alanine transaminase (ALT), Aspartate transaminase (AST) and Platelets. Recovery from a Grade 3 or 4 toxicity is defined as a return to a Grade 0 or 1.
- Safety Population: Median Time to Nadir of Absolute Lymphocyte Count [Baseline up to Week 120]
Median time to nadir of absolute lymphocyte count was reported.
- Safety Population: Mean Time to Nadir of Absolute Lymphocyte Count [Baseline up to Week 120]
Mean time to nadir of absolute lymphocyte count was reported.
- Safety Population: Mean Time to Recovery From Nadir of Absolute Lymphocyte Count to Normal Value [Baseline up to Week 120]
Mean time to recovery from nadir of absolute lymphocyte count to normal was reported. Recovery from Nadir is defined as a return to baseline value. Normal absolute lymphocyte count is 1.02 x 10^3 cells/microliter.
- Safety Population: Mean Change in Corrected QT (QTc) Interval From Baseline [Baseline, Week 5, 48, 52 and 96]
The QT interval is a measure of the time between the start of the Q wave and the end of the T wave. Corrected QT (QTc) is the QT interval corrected for heart rate and RR, which is the interval between two R waves. Mean change in corrected QT (QTc) interval from baseline was reported.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
to 65 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Randomized in Trial 25643 and satisfied one of the following:
-
Completed randomized treatment course and scheduled visits for the full 96 weeks; or
-
Did not complete the randomized treatment course in Trial 25643 but elected to receive rescue treatment with Rebif®, another beta-interferon, or glatiramer acetate and completed scheduled clinic visits for the full 96 weeks; or
-
Did not complete the randomized treatment course in Trial 25643, declined rescue with Rebif®, another beta-interferon, or glatiramer acetate and still completed scheduled clinic visits for the full 96 weeks; or
-
Did not complete the randomized treatment course in Trial 25643, were not eligible for rescue option with Rebif®, and still completed scheduled clinic visits for the full 96 weeks
-
Male or female, between 18 and 65 years of age (inclusive, at time of informed consent for Trial 25643)
-
No medical history or evidence of latent tuberculosis infection (LTBI) or tuberculosis (TB), as evidenced by TB skin test or chest X-ray
-
All of the following laboratory hematologic parameters evaluated as normal (as define below, inclusively) within 28 days of first dosing of blinded study medication at study Day 1:
-
Hemoglobin = 11.6 to 16.2 gram per deciliter (g/dL)
-
Leukocytes (total white blood cell) = 4.1 to 12.3*10^3 per microliter
-
Absolute lymphocyte count (ALC) = 1.02 to 3.36*10^3 per microliter
-
Absolute neutrophil count (ANC) = 2.03 to 8.36*10^3 per microliter
-
Platelet count = 140 to 450*10^3 per microliter
-
Other protocol-defined inclusion/exclusion criteria may apply
Exclusion Criteria:
-
Participants who were not enrolled in Trial 25643
-
Participant has moderate to severe renal impairment
-
Use of mitoxantrone, total lymphoid irradiation, myelosuppressive therapy, campath-1h, cyclophosphamide, azathioprine, methotrexate or natalizumab at any time during and since Trial 25643
-
Use of cytokine or anti-cytokine therapy, intravenous immunoglobulin (IVIG) or plasmapheresis at any time during and since Trial 25643
-
Treatment with oral or systemic corticosteroids or adrenocorticotropic hormone within 28 days before Study Day 1
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Research Site | Boulder | Colorado | United States | |
| 2 | Research Site | Atlanta | Georgia | United States | |
| 3 | Research Site | Chicago | Illinois | United States | |
| 4 | Research Site | Northbrook | Illinois | United States | |
| 5 | Research Site | Baltimore | Maryland | United States | |
| 6 | Research Site | Ann Arbor | Michigan | United States | |
| 7 | Research Site | Henderson | Nevada | United States | |
| 8 | Research Site | Newark | New Jersey | United States | |
| 9 | Research Site | Charlotte | North Carolina | United States | |
| 10 | Research Site | Durham | North Carolina | United States | |
| 11 | Research Site | Columbus | Ohio | United States | |
| 12 | Research Site | Oklahoma City | Oklahoma | United States | |
| 13 | Research Site | Tulsa | Oklahoma | United States | |
| 14 | Research Site | Medford | Oregon | United States | |
| 15 | Research Site | Seattle | Washington | United States | |
| 16 | Research Site | Tacoma | Washington | United States | |
| 17 | Research Site | Charleston | West Virginia | United States | |
| 18 | Research Site | Camperdown | Australia | ||
| 19 | Research Site | Melbourne | Australia | ||
| 20 | Research Site | Victoria | Australia | ||
| 21 | Research Site | Linz | Austria | ||
| 22 | Research Site | Diepenbeek | Belgium | ||
| 23 | Research Site | Esneux | Belgium | ||
| 24 | Research Site | Recife | Brazil | ||
| 25 | Research Site | Pleven | Bulgaria | ||
| 26 | Research Site | Plovdiv | Bulgaria | ||
| 27 | Research Site | Ruse | Bulgaria | ||
| 28 | Research Site | Shuman | Bulgaria | ||
| 29 | Research Site | Sofia | Bulgaria | ||
| 30 | Research Site | Varna | Bulgaria | ||
| 31 | Research Site | Zagora | Bulgaria | ||
| 32 | Research Site | Burnaby | Canada | ||
| 33 | Research Site | Greenfield Park | Canada | ||
| 34 | Research Site | Ottawa | Canada | ||
| 35 | Research Site | Quebec | Canada | ||
| 36 | Research Site | Karlovac | Croatia | ||
| 37 | Research Site | Sisak | Croatia | ||
| 38 | Research Site | Split | Croatia | ||
| 39 | Research Site | Hradec Králové | Czechia | ||
| 40 | Research Site | Olomouc | Czechia | ||
| 41 | Research Site | Praha | Czechia | ||
| 42 | Research Site | Copenhagen | Denmark | ||
| 43 | Research Site | Tallinn | Estonia | ||
| 44 | Research Site | Tartu | Estonia | ||
| 45 | Research Site | Oulu | Finland | ||
| 46 | Research Site | Turku | Finland | ||
| 47 | Research Site | Clermont-Ferrand | France | ||
| 48 | Research Site | Lille | France | ||
| 49 | Research Site | Nancy | France | ||
| 50 | Research Site | Nimes | France | ||
| 51 | Research Site | Paris | France | ||
| 52 | Research Site | Rennes | France | ||
| 53 | Research Site | Saint Herblain | France | ||
| 54 | Research Site | Bochum | Germany | ||
| 55 | Research Site | Frankfurt | Germany | ||
| 56 | Research Site | Giessen | Germany | ||
| 57 | Research Site | Hannover | Germany | ||
| 58 | Research Site | Regensburg | Germany | ||
| 59 | Research Site | Rostock | Germany | ||
| 60 | Research Site | Athens | Greece | ||
| 61 | Research Site | Bari | Italy | ||
| 62 | Research Site | Cagliari | Italy | ||
| 63 | Research Site | Catania | Italy | ||
| 64 | Research Site | Firenze | Italy | ||
| 65 | Research Site | Genova | Italy | ||
| 66 | Research Site | Milano | Italy | ||
| 67 | Research Site | Napoli | Italy | ||
| 68 | Research Site | Padova | Italy | ||
| 69 | Research Site | Roma | Italy | ||
| 70 | Research Site | Riga | Latvia | ||
| 71 | Research Site | Beirut | Lebanon | ||
| 72 | Research Site | Beyrouth | Lebanon | ||
| 73 | Research Site | Kaunas | Lithuania | ||
| 74 | Research Site | Casablanca | Morocco | ||
| 75 | Research Site | Fes | Morocco | ||
| 76 | Research Site | Rabat | Morocco | ||
| 77 | Research Site | Sittard- Geleen | Netherlands | ||
| 78 | Research Site | Gdansk | Poland | ||
| 79 | Research Site | Krakow | Poland | ||
| 80 | Research Site | Lodz | Poland | ||
| 81 | Research Site | Poznan | Poland | ||
| 82 | Research Site | Warszawy | Poland | ||
| 83 | Research Site | Lisboa | Portugal | ||
| 84 | Research Site | Ekaterinburg | Russian Federation | ||
| 85 | Research Site | Kaluga | Russian Federation | ||
| 86 | Research Site | Kazan | Russian Federation | ||
| 87 | Research Site | Kemerovo | Russian Federation | ||
| 88 | Research Site | Kursk | Russian Federation | ||
| 89 | Research Site | Moscow | Russian Federation | ||
| 90 | Research Site | Nizhny Novgorod | Russian Federation | ||
| 91 | Research Site | Novosibirsk | Russian Federation | ||
| 92 | Research Site | Rostov-on-Don | Russian Federation | ||
| 93 | Research Site | Samara | Russian Federation | ||
| 94 | Reseach Site | Saratov | Russian Federation | ||
| 95 | Research Site | St-Petersburg | Russian Federation | ||
| 96 | Research Site | Tomsk | Russian Federation | ||
| 97 | Research Site | Vladimir | Russian Federation | ||
| 98 | Research Site | Yaroslavl | Russian Federation | ||
| 99 | Research Site | Riyadh | Saudi Arabia | ||
| 100 | Research Site | Belgrade | Serbia | ||
| 101 | Research Site | Lausanne | Switzerland | ||
| 102 | Research Site | St. Gallen | Switzerland | ||
| 103 | Research Site | Monastir | Tunisia | ||
| 104 | Research Site | Sfax | Tunisia | ||
| 105 | Research Site | Tunis | Tunisia | ||
| 106 | Research Site | Bursa | Turkey | ||
| 107 | Research Site | Izmir | Turkey | ||
| 108 | Research Site | Kharkov | Ukraine | ||
| 109 | Research Site | Kiev | Ukraine | ||
| 110 | Research Site | Lviv | Ukraine | ||
| 111 | Research Site | Vinnitsa | Ukraine | ||
| 112 | Research Site | Hull | United Kingdom | ||
| 113 | Research Site | London | United Kingdom | ||
| 114 | Research Site | Nottingham | United Kingdom | ||
| 115 | Research Site | Oxford | United Kingdom | ||
| 116 | Research Site | Sheffield | United Kingdom | ||
| 117 | Research Site | Stoke-on-Trent | United Kingdom |
Sponsors and Collaborators
- EMD Serono Research & Development Institute, Inc.
Investigators
- Study Director: Medical Responsible, Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.Responsible Party:
EMD Serono Research & Development Institute, Inc.
ClinicalTrials.gov Identifier:
NCT00641537
Other Study ID Numbers:
- 27820
- 2007-000381-20
First Posted:
Mar 24, 2008
Last Update Posted:
Dec 7, 2020
Last Verified:
Oct 1, 2020
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail | A total of 1326 subjects were randomized into CLARITY from study 25643 (NCT00213135), of whom 867 consented to participate in this phase 3b extension Study 27820. 806 subjects were randomized or assigned to treatment and a further 61 subjects were followed for safety only (Supplemental follow-up period [no study treatment] [SAFUP]). |
| Arm/Group Title | Cladribine Low/Placebo (LLPP) | Cladribine High Dose/Placebo (HLPP) | Cladribine Low/Low Dose (LLLL) | Cladribine High/Low Dose (HLLL) | Placebo/Cladribine Low Dose (PPLL) | Placebo/No Treatment | Cladribine 3.5 mg/kg/No Treatment | Cladribine 5.25 mg/kg/No Treatment |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants who received cladribine 3.5 mg/kg in previous study 25643 (NCT00213135) and completed the study who were randomized or assigned to placebo (matched to cladribine tablet) during the treatment period of 96 weeks. Participants were followed up for 24 weeks in Supplemental follow-up period (SUPF). | Participants who received cladribine 5.25 mg/kg in previous study 25643 (NCT00213135) and completed the study who were randomized or assigned to placebo (matched to cladribine tablet) during the treatment period of 96 weeks. Participants were followed up for 24 weeks in SUPF. | Participants who received cladribine 3.5 mg/kg in previous study 25643 (NCT00213135) and completed the study who were randomized or assigned to cladribine 3.5 mg/kg orally provided as 0.875 mg/kg treatment weeks at Week 1, Week 5, Week 48 and Week 52 resulting in total dose of 3.5 mg/kg during the treatment period of 96 weeks. Participants were followed up for 24 weeks in SUPF. | Participants who received cladribine 5.25 mg/kg in previous study 25643 (NCT00213135) and completed the study who were randomized or assigned to cladribine 3.5 mg/kg orally provided as 0.875 mg/kg treatment weeks at Week 1, Week 5, Week 48 and Week 52 resulting in total dose of 3.5 mg/kg during the treatment period of 96 weeks. Participants were followed up for 24 weeks in SUPF. | Participants who received placebo in previous study 25643 (NCT00213135) and completed the study who were randomized or assigned to cladribine 3.5 mg/kg orally provided as 0.875 mg/kg treatment weeks at Week 1, Week 5, Week 48 and Week 52 resulting in total dose of 3.5 mg/kg during the treatment period of 96 weeks. Participants were followed up for 24 weeks in SUPF. | Participants who received placebo matched to cladribine in previous study 25643 (NCT00213135) and were enrolled in this extension study and received no cladribine treatment and were followed up for safety assessment for 96 weeks (during the treatment period) and followed up for 24 weeks (during supplemental follow-up period). | Participants who received cladribine 3.5 mg/kg in previous study 25643 (NCT00213135) and completed were enrolled in this extension study and received no cladribine treatment and were followed up for safety assessment for 96 weeks (during the treatment period) and followed up for 24 weeks (during supplemental follow-up period). | Participants who received cladribine 5.25 mg/kg in previous study 25643 (NCT00213135) and completed were enrolled in this extension study and received no cladribine treatment and were followed up for safety assessment for 96 weeks (during the treatment period) and followed up for 24 weeks (during supplemental follow-up period). |
| Period Title: 96-week Period | ||||||||
| STARTED | 98 | 92 | 186 | 186 | 244 | 22 | 17 | 22 |
| COMPLETED | 89 | 82 | 166 | 174 | 227 | 15 | 12 | 16 |
| NOT COMPLETED | 9 | 10 | 20 | 12 | 17 | 7 | 5 | 6 |
| Period Title: 96-week Period | ||||||||
| STARTED | 75 | 69 | 143 | 151 | 198 | 15 | 9 | 11 |
| COMPLETED | 75 | 66 | 140 | 147 | 193 | 14 | 8 | 10 |
| NOT COMPLETED | 0 | 3 | 3 | 4 | 5 | 1 | 1 | 1 |
Baseline Characteristics
| Arm/Group Title | Cladribine Low/Placebo (LLPP) | Cladribine High Dose/Placebo (HLPP) | Cladribine Low/Low Dose (LLLL) | Cladribine High/Low Dose (HLLL) | Placebo/Cladribine Low Dose (PPLL) | Total |
|---|---|---|---|---|---|---|
| Arm/Group Description | Participants who received cladribine 3.5 mg/kg in previous study 25643 (NCT00213135) and completed the study who were randomized or assigned to placebo (matched to cladribine tablet) during the treatment period of 96 weeks. Participants were followed up for 24 weeks in Supplemental follow-up period (SUPF). | Participants who received cladribine 5.25 mg/kg in previous study 25643 (NCT00213135) and completed the study who were randomized or assigned to placebo (matched to cladribine tablet) during the treatment period of 96 weeks. Participants were followed up for 24 weeks in SUPF. | Participants who received cladribine 3.5 mg/kg in previous study 25643 (NCT00213135) and completed the study who were randomized or assigned to cladribine 3.5 mg/kg orally provided as 0.875 mg/kg treatment weeks at Week 1, Week 5, Week 48 and Week 52 resulting in total dose of 3.5 mg/kg during the treatment period of 96 weeks. Participants were followed up for 24 weeks in SUPF. | Participants who received cladribine 5.25 mg/kg in previous study 25643 (NCT00213135) and completed the study who were randomized or assigned to cladribine 3.5 mg/kg orally provided as 0.875 mg/kg treatment weeks at Week 1, Week 5, Week 48 and Week 52 resulting in total dose of 3.5 mg/kg during the treatment period of 96 weeks. Participants were followed up for 24 weeks in SUPF. | Participants who received placebo in previous study 25643 (NCT00213135) and completed the study who were randomized or assigned to cladribine 3.5 mg/kg orally provided as 0.875 mg/kg treatment weeks at Week 1, Week 5, Week 48 and Week 52 resulting in total dose of 3.5 mg/kg during the treatment period of 96 weeks. Participants were followed up for 24 weeks in SUPF. | Total of all reporting groups |
| Overall Participants | 98 | 92 | 186 | 186 | 244 | 806 |
| Age (years) [Mean (Standard Deviation) ] | ||||||
| Mean (Standard Deviation) [years] |
40.7
(10.7)
|
40.8
(9.6)
|
40.6
(10.5)
|
41.4
(10.1)
|
41.6
(9.6)
|
41.1
(10.1)
|
| Sex: Female, Male (Count of Participants) | ||||||
| Female |
67
68.4%
|
59
64.1%
|
124
66.7%
|
125
67.2%
|
156
63.9%
|
531
65.9%
|
| Male |
31
31.6%
|
33
35.9%
|
62
33.3%
|
61
32.8%
|
88
36.1%
|
275
34.1%
|
Outcome Measures
| Title | Safety Population: Percentage of Participants With at Least 1 Common Terminology Criteria for Adverse Events Version 3.0 (CTCAE) Grade 4 Hematologic and Hepatic Toxicity |
|---|---|
| Description | Hematologic and hepatic toxicity was assessed using Common Terminology Criteria for Adverse Events v 3.0 (CTCAE). Hematologic and hepatic function included absolute lymphocyte count (ALC), hemoglobin level, white blood cell (WBC) count, absolute neutrophil count (ANC), platelets, alanine transaminase (ALT), aspartate transaminase (AST) and bilirubin. According to CTCAE v3.0: Grade 1=mild, Grade 2=moderate, Grade 3=severe, Grade 4=life threatening or disabling and Grade 5=Death. |
| Time Frame | Baseline up to Week 120 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety population included all the randomized participants who had received at least 1 dose of study medication and had follow-up safety data. |
| Arm/Group Title | Cladribine Low/Placebo (LLPP) | Cladribine High Dose/Placebo (HLPP) | Cladribine Low/Low Dose (LLLL) | Cladribine High/Low Dose (HLLL) | Placebo/Cladribine Low Dose (PPLL) |
|---|---|---|---|---|---|
| Arm/Group Description | Participants who received cladribine 3.5 mg/kg in previous study 25643 (NCT00213135) and completed the study who were randomized or assigned to placebo (matched to cladribine tablet) during the treatment period of 96 weeks. Participants were followed up for 24 weeks in Supplemental follow-up period (SUPF). | Participants who received cladribine 5.25 mg/kg in previous study 25643 (NCT00213135) and completed the study who were randomized or assigned to placebo (matched to cladribine tablet) during the treatment period of 96 weeks. Participants were followed up for 24 weeks in SUPF. | Participants who received cladribine 3.5 mg/kg in previous study 25643 (NCT00213135) and completed the study who were randomized or assigned to cladribine 3.5 mg/kg orally provided as 0.875 mg/kg treatment weeks at Week 1, Week 5, Week 48 and Week 52 resulting in total dose of 3.5 mg/kg during the treatment period of 96 weeks. Participants were followed up for 24 weeks in SUPF. | Participants who received cladribine 5.25 mg/kg in previous study 25643 (NCT00213135) and completed the study who were randomized or assigned to cladribine 3.5 mg/kg orally provided as 0.875 mg/kg treatment weeks at Week 1, Week 5, Week 48 and Week 52 resulting in total dose of 3.5 mg/kg during the treatment period of 96 weeks. Participants were followed up for 24 weeks in SUPF. | Participants who received placebo in previous study 25643 (NCT00213135) and completed the study who were randomized or assigned to cladribine 3.5 mg/kg orally provided as 0.875 mg/kg treatment weeks at Week 1, Week 5, Week 48 and Week 52 resulting in total dose of 3.5 mg/kg during the treatment period of 96 weeks. Participants were followed up for 24 weeks in SUPF. |
| Measure Participants | 98 | 92 | 186 | 186 | 244 |
| Lymphocyte toxicity |
0.0
0%
|
0.0
0%
|
2.7
1.5%
|
3.2
1.7%
|
0.4
0.2%
|
| Hemoglobin Toxicity |
0.0
0%
|
0.0
0%
|
0.0
0%
|
0.0
0%
|
0.0
0%
|
| White Blood Cell Toxicity |
0.0
0%
|
0.0
0%
|
0.5
0.3%
|
0.0
0%
|
0.0
0%
|
| Absolute Neutrophil Count Toxicity |
0.0
0%
|
2.2
2.4%
|
0.5
0.3%
|
0.0
0%
|
0.4
0.2%
|
| Platelets Toxicity |
0.0
0%
|
0.0
0%
|
0.5
0.3%
|
0.0
0%
|
0.0
0%
|
| Alanine Transaminase Toxicity |
0.0
0%
|
0.0
0%
|
0.0
0%
|
0.0
0%
|
0.0
0%
|
| AsparateTransaminase Toxicity |
0.0
0%
|
0.0
0%
|
0.0
0%
|
0.0
0%
|
0.0
0%
|
| Bilirubin Toxicity |
0.0
0%
|
0.0
0%
|
0.0
0%
|
0.0
0%
|
0.0
0%
|
| Title | Safety Population: Mean Change From Baseline in Absolute Lymphocyte Count, Platelet, Neutrophils and Leukocytes at Week 120 |
|---|---|
| Description | Mean change from baseline in absolute lymphocyte count, platelet, neutrophils and leukocytes at week 120 were reported. |
| Time Frame | Baseline, Week 120 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety population included all the randomized participants who had received at least 1 dose of study medication and had follow-up safety data. Here 'Number of participants analyzed' signifies number of participants who were evaluable for this outcome measure and "Number analyzed" are those who were evaluable at specified category. |
| Arm/Group Title | Cladribine Low/Placebo (LLPP) | Cladribine High Dose/Placebo (HLPP) | Cladribine Low/Low Dose (LLLL) | Cladribine High/Low Dose (HLLL) | Placebo/Cladribine Low Dose (PPLL) |
|---|---|---|---|---|---|
| Arm/Group Description | Participants who received cladribine 3.5 mg/kg in previous study 25643 (NCT00213135) and completed the study who were randomized or assigned to placebo (matched to cladribine tablet) during the treatment period of 96 weeks. Participants were followed up for 24 weeks in Supplemental follow-up period (SUPF). | Participants who received cladribine 5.25 mg/kg in previous study 25643 (NCT00213135) and completed the study who were randomized or assigned to placebo (matched to cladribine tablet) during the treatment period of 96 weeks. Participants were followed up for 24 weeks in SUPF. | Participants who received cladribine 3.5 mg/kg in previous study 25643 (NCT00213135) and completed the study who were randomized or assigned to cladribine 3.5 mg/kg orally provided as 0.875 mg/kg treatment weeks at Week 1, Week 5, Week 48 and Week 52 resulting in total dose of 3.5 mg/kg during the treatment period of 96 weeks. Participants were followed up for 24 weeks in SUPF. | Participants who received cladribine 5.25 mg/kg in previous study 25643 (NCT00213135) and completed the study who were randomized or assigned to cladribine 3.5 mg/kg orally provided as 0.875 mg/kg treatment weeks at Week 1, Week 5, Week 48 and Week 52 resulting in total dose of 3.5 mg/kg during the treatment period of 96 weeks. Participants were followed up for 24 weeks in SUPF. | Participants who received placebo in previous study 25643 (NCT00213135) and completed the study who were randomized or assigned to cladribine 3.5 mg/kg orally provided as 0.875 mg/kg treatment weeks at Week 1, Week 5, Week 48 and Week 52 resulting in total dose of 3.5 mg/kg during the treatment period of 96 weeks. Participants were followed up for 24 weeks in SUPF. |
| Measure Participants | 73 | 62 | 137 | 144 | 187 |
| Lymphocyte Count |
0.3
(0.4)
|
0.3
(0.4)
|
0.0
(0.4)
|
0.0
(0.5)
|
-0.6
(0.6)
|
| Platelet |
-7.7
(26.2)
|
-11.9
(35.3)
|
-20.6
(37.9)
|
-9.7
(51.2)
|
-34.0
(37.2)
|
| Leukocytes |
0.8
(1.5)
|
0.5
(1.2)
|
-0.2
(1.5)
|
-0.1
(1.4)
|
-0.9
(1.7)
|
| Neutrophils |
0.4
(1.3)
|
0.1
(1.2)
|
-0.2
(1.4)
|
-0.2
(1.3)
|
-0.3
(1.7)
|
| Title | Safety Population: Mean Change From Baseline in Hemoglobin at Week 120 |
|---|---|
| Description | Mean change from baseline in hemoglobin at Week 120 was reported. |
| Time Frame | Baseline, Week 120 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety population included all the randomized participants who had received at least 1 dose of study medication and had follow-up safety data. Here 'Number of participants analyzed' signifies number of participants who were evaluable for this outcome measure. |
| Arm/Group Title | Cladribine Low/Placebo (LLPP) | Cladribine High Dose/Placebo (HLPP) | Cladribine Low/Low Dose (LLLL) | Cladribine High/Low Dose (HLLL) | Placebo/Cladribine Low Dose (PPLL) |
|---|---|---|---|---|---|
| Arm/Group Description | Participants who received cladribine 3.5 mg/kg in previous study 25643 (NCT00213135) and completed the study who were randomized or assigned to placebo (matched to cladribine tablet) during the treatment period of 96 weeks. Participants were followed up for 24 weeks in Supplemental follow-up period (SUPF). | Participants who received cladribine 5.25 mg/kg in previous study 25643 (NCT00213135) and completed the study who were randomized or assigned to placebo (matched to cladribine tablet) during the treatment period of 96 weeks. Participants were followed up for 24 weeks in SUPF. | Participants who received cladribine 3.5 mg/kg in previous study 25643 (NCT00213135) and completed the study who were randomized or assigned to cladribine 3.5 mg/kg orally provided as 0.875 mg/kg treatment weeks at Week 1, Week 5, Week 48 and Week 52 resulting in total dose of 3.5 mg/kg during the treatment period of 96 weeks. Participants were followed up for 24 weeks in SUPF. | Participants who received cladribine 5.25 mg/kg in previous study 25643 (NCT00213135) and completed the study who were randomized or assigned to cladribine 3.5 mg/kg orally provided as 0.875 mg/kg treatment weeks at Week 1, Week 5, Week 48 and Week 52 resulting in total dose of 3.5 mg/kg during the treatment period of 96 weeks. Participants were followed up for 24 weeks in SUPF. | Participants who received placebo in previous study 25643 (NCT00213135) and completed the study who were randomized or assigned to cladribine 3.5 mg/kg orally provided as 0.875 mg/kg treatment weeks at Week 1, Week 5, Week 48 and Week 52 resulting in total dose of 3.5 mg/kg during the treatment period of 96 weeks. Participants were followed up for 24 weeks in SUPF. |
| Measure Participants | 73 | 62 | 137 | 144 | 187 |
| Mean (Standard Deviation) [grams per deciliter (g/dL)] |
0.2
(0.9)
|
0.2
(0.7)
|
-0.1
(0.9)
|
0.1
(0.9)
|
-0.1
(0.9)
|
| Title | Safety Population: Mean Change From Baseline in Aspartate Aminotransferase and Alanine Aminotransferase at Week 120 |
|---|---|
| Description | Mean change from baseline in aspartate aminotransferase and alanine aminotransferase at week 120 were reported. |
| Time Frame | Baseline, Week 120 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety population included all the randomized participants who had received at least 1 dose of study medication and had follow-up safety data. Here 'Number of participants analyzed' signifies number of participants who were evaluable for this outcome measure and "Number analyzed" are those who were evaluable at specified category. |
| Arm/Group Title | Cladribine Low/Placebo (LLPP) | Cladribine High Dose/Placebo (HLPP) | Cladribine Low/Low Dose (LLLL) | Cladribine High/Low Dose (HLLL) | Placebo/Cladribine Low Dose (PPLL) |
|---|---|---|---|---|---|
| Arm/Group Description | Participants who received cladribine 3.5 mg/kg in previous study 25643 (NCT00213135) and completed the study who were randomized or assigned to placebo (matched to cladribine tablet) during the treatment period of 96 weeks. Participants were followed up for 24 weeks in Supplemental follow-up period (SUPF). | Participants who received cladribine 5.25 mg/kg in previous study 25643 (NCT00213135) and completed the study who were randomized or assigned to placebo (matched to cladribine tablet) during the treatment period of 96 weeks. Participants were followed up for 24 weeks in SUPF. | Participants who received cladribine 3.5 mg/kg in previous study 25643 (NCT00213135) and completed the study who were randomized or assigned to cladribine 3.5 mg/kg orally provided as 0.875 mg/kg treatment weeks at Week 1, Week 5, Week 48 and Week 52 resulting in total dose of 3.5 mg/kg during the treatment period of 96 weeks. Participants were followed up for 24 weeks in SUPF. | Participants who received cladribine 5.25 mg/kg in previous study 25643 (NCT00213135) and completed the study who were randomized or assigned to cladribine 3.5 mg/kg orally provided as 0.875 mg/kg treatment weeks at Week 1, Week 5, Week 48 and Week 52 resulting in total dose of 3.5 mg/kg during the treatment period of 96 weeks. Participants were followed up for 24 weeks in SUPF. | Participants who received placebo in previous study 25643 (NCT00213135) and completed the study who were randomized or assigned to cladribine 3.5 mg/kg orally provided as 0.875 mg/kg treatment weeks at Week 1, Week 5, Week 48 and Week 52 resulting in total dose of 3.5 mg/kg during the treatment period of 96 weeks. Participants were followed up for 24 weeks in SUPF. |
| Measure Participants | 72 | 62 | 137 | 142 | 185 |
| Aspartate Aminotransferase |
0.7
(10.6)
|
-1.1
(6.4)
|
2.2
(7.3)
|
0.7
(11.3)
|
0.5
(5.1)
|
| Alanine Aminotransferase |
2.2
(26.0)
|
-1.0
(11.7)
|
4.3
(14.3)
|
0.7
(17.5)
|
1.4
(12.2)
|
| Title | Safety Population: Mean Change From Baseline in Bilirubin at Week 120 |
|---|---|
| Description | Mean Change From Baseline in Bilirubin at week 120 was reported. |
| Time Frame | Baseline, Week 120 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety population included all the randomized participants who had received at least 1 dose of study medication and had follow-up safety data. Here 'Number of participants analyzed' signifies number of participants who were evaluable for this outcome measure. |
| Arm/Group Title | Cladribine Low/Placebo (LLPP) | Cladribine High Dose/Placebo (HLPP) | Cladribine Low/Low Dose (LLLL) | Cladribine High/Low Dose (HLLL) | Placebo/Cladribine Low Dose (PPLL) |
|---|---|---|---|---|---|
| Arm/Group Description | Participants who received cladribine 3.5 mg/kg in previous study 25643 (NCT00213135) and completed the study who were randomized or assigned to placebo (matched to cladribine tablet) during the treatment period of 96 weeks. Participants were followed up for 24 weeks in Supplemental follow-up period (SUPF). | Participants who received cladribine 5.25 mg/kg in previous study 25643 (NCT00213135) and completed the study who were randomized or assigned to placebo (matched to cladribine tablet) during the treatment period of 96 weeks. Participants were followed up for 24 weeks in SUPF. | Participants who received cladribine 3.5 mg/kg in previous study 25643 (NCT00213135) and completed the study who were randomized or assigned to cladribine 3.5 mg/kg orally provided as 0.875 mg/kg treatment weeks at Week 1, Week 5, Week 48 and Week 52 resulting in total dose of 3.5 mg/kg during the treatment period of 96 weeks. Participants were followed up for 24 weeks in SUPF. | Participants who received cladribine 5.25 mg/kg in previous study 25643 (NCT00213135) and completed the study who were randomized or assigned to cladribine 3.5 mg/kg orally provided as 0.875 mg/kg treatment weeks at Week 1, Week 5, Week 48 and Week 52 resulting in total dose of 3.5 mg/kg during the treatment period of 96 weeks. Participants were followed up for 24 weeks in SUPF. | Participants who received placebo in previous study 25643 (NCT00213135) and completed the study who were randomized or assigned to cladribine 3.5 mg/kg orally provided as 0.875 mg/kg treatment weeks at Week 1, Week 5, Week 48 and Week 52 resulting in total dose of 3.5 mg/kg during the treatment period of 96 weeks. Participants were followed up for 24 weeks in SUPF. |
| Measure Participants | 73 | 62 | 137 | 144 | 186 |
| Mean (Standard Deviation) [micromoles per liter (mcmol/L)] |
0.1
(3.7)
|
0.0
(3.5)
|
-0.8
(3.7)
|
-0.8
(3.3)
|
-0.4
(3.7)
|
| Title | Safety Population: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs |
|---|---|
| Description | An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered. Serious AE (SAE): Any AE that resulted in death; was life threatening; resulted in persistent/significant disability/incapacity; resulted in/prolonged an existing in-patient hospitalization; was a congenital anomaly/birth defect; or was a medically important condition. The term TEAE is defined as AEs starting or worsening after the first intake of the study drug. Number of participants with TEAEs included participants with both non-serious TEAEs and serious TEAEs. |
| Time Frame | Baseline up to Week 120 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety population included all the randomized participants who had received at least 1 dose of study medication and had follow-up safety data. |
| Arm/Group Title | Cladribine Low/Placebo (LLPP) | Cladribine High Dose/Placebo (HLPP) | Cladribine Low/Low Dose (LLLL) | Cladribine High/Low Dose (HLLL) | Placebo/Cladribine Low Dose (PPLL) |
|---|---|---|---|---|---|
| Arm/Group Description | Participants who received cladribine 3.5 mg/kg in previous study 25643 (NCT00213135) and completed the study who were randomized or assigned to placebo (matched to cladribine tablet) during the treatment period of 96 weeks. Participants were followed up for 24 weeks in Supplemental follow-up period (SUPF). | Participants who received cladribine 5.25 mg/kg in previous study 25643 (NCT00213135) and completed the study who were randomized or assigned to placebo (matched to cladribine tablet) during the treatment period of 96 weeks. Participants were followed up for 24 weeks in SUPF. | Participants who received cladribine 3.5 mg/kg in previous study 25643 (NCT00213135) and completed the study who were randomized or assigned to cladribine 3.5 mg/kg orally provided as 0.875 mg/kg treatment weeks at Week 1, Week 5, Week 48 and Week 52 resulting in total dose of 3.5 mg/kg during the treatment period of 96 weeks. Participants were followed up for 24 weeks in SUPF. | Participants who received cladribine 5.25 mg/kg in previous study 25643 (NCT00213135) and completed the study who were randomized or assigned to cladribine 3.5 mg/kg orally provided as 0.875 mg/kg treatment weeks at Week 1, Week 5, Week 48 and Week 52 resulting in total dose of 3.5 mg/kg during the treatment period of 96 weeks. Participants were followed up for 24 weeks in SUPF. | Participants who received placebo in previous study 25643 (NCT00213135) and completed the study who were randomized or assigned to cladribine 3.5 mg/kg orally provided as 0.875 mg/kg treatment weeks at Week 1, Week 5, Week 48 and Week 52 resulting in total dose of 3.5 mg/kg during the treatment period of 96 weeks. Participants were followed up for 24 weeks in SUPF. |
| Measure Participants | 98 | 92 | 186 | 186 | 244 |
| TEAEs |
74
75.5%
|
71
77.2%
|
149
80.1%
|
149
80.1%
|
194
79.5%
|
| Serious TEAEs |
16
16.3%
|
8
8.7%
|
25
13.4%
|
23
12.4%
|
22
9%
|
| Title | SAFUP Analysis Set: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs |
|---|---|
| Description | An AE was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered. SAE: Any AE that resulted in death; was life threatening; resulted in persistent/significant disability/incapacity; resulted in/prolonged an existing in-patient hospitalization; was a congenital anomaly/birth defect; or was a medically important condition. The term TEAE is defined as AEs starting or worsening after the first intake of the study drug. Number of participants with TEAEs included participants with both non-serious TEAEs and serious TEAEs. |
| Time Frame | Baseline up to Week 120 |
Outcome Measure Data
| Analysis Population Description |
|---|
| SAFUP Analysis Set included all participants who were enrolled and had at least one safety assessment, but were not randomized or assigned to treatment because they were not eligible to receive study medication. |
| Arm/Group Title | Placebo/No Treatment | Cladribine 3.5 mg/kg/No Treatment | Cladribine 5.25 mg/kg/No Treatment |
|---|---|---|---|
| Arm/Group Description | Participants who received placebo matched to cladribine in previous study 25643 (NCT00213135) and were enrolled in this extension study and received no cladribine treatment and were followed up for safety assessment for 96 weeks (during the treatment period) and followed up for 24 weeks (during supplemental follow-up period). | Participants who received cladribine 3.5 mg/kg in previous study 25643 (NCT00213135) and completed were enrolled in this extension study and received no cladribine treatment and were followed up for safety assessment for 96 weeks (during the treatment period) and followed up for 24 weeks (during supplemental follow-up period). | Participants who received cladribine 5.25 mg/kg in previous study 25643 (NCT00213135) and completed were enrolled in this extension study and received no cladribine treatment and were followed up for safety assessment for 96 weeks (during the treatment period) and followed up for 24 weeks (during supplemental follow-up period). |
| Measure Participants | 22 | 17 | 22 |
| TEAEs |
16
16.3%
|
13
14.1%
|
18
9.7%
|
| Serious TEAEs |
2
2%
|
1
1.1%
|
3
1.6%
|
| Title | Safety Population: Number of Participants Who Developed Infections (Herpes Viral Infection, Viral Infectious Disorder and Opportunistic Infection), Infection-related Adverse Events and Malignancies |
|---|---|
| Description | Number of participants who developed Herpes viral infection, Viral infectious disorder and Opportunistic infection are reported. Number of participants with infection related adverse events are the number of participants who had at least one adverse event coded to medical dictionary for regulatory activities (MedDRA) preferred terms under infection and infestation system organ class. Malignancy is defined as having at least one adverse event coded to MedDRA preferred terms under the pre-specified grouping Malignant and unspecified tumors. |
| Time Frame | Baseline up to Week 120 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety population included all the randomized participants who had received at least 1 dose of study medication and had follow-up safety data. |
| Arm/Group Title | Cladribine Low/Placebo (LLPP) | Cladribine High Dose/Placebo (HLPP) | Cladribine Low/Low Dose (LLLL) | Cladribine High/Low Dose (HLLL) | Placebo/Cladribine Low Dose (PPLL) |
|---|---|---|---|---|---|
| Arm/Group Description | Participants who received cladribine 3.5 mg/kg in previous study 25643 (NCT00213135) and completed the study who were randomized or assigned to placebo (matched to cladribine tablet) during the treatment period of 96 weeks. Participants were followed up for 24 weeks in Supplemental follow-up period (SUPF). | Participants who received cladribine 5.25 mg/kg in previous study 25643 (NCT00213135) and completed the study who were randomized or assigned to placebo (matched to cladribine tablet) during the treatment period of 96 weeks. Participants were followed up for 24 weeks in SUPF. | Participants who received cladribine 3.5 mg/kg in previous study 25643 (NCT00213135) and completed the study who were randomized or assigned to cladribine 3.5 mg/kg orally provided as 0.875 mg/kg treatment weeks at Week 1, Week 5, Week 48 and Week 52 resulting in total dose of 3.5 mg/kg during the treatment period of 96 weeks. Participants were followed up for 24 weeks in SUPF. | Participants who received cladribine 5.25 mg/kg in previous study 25643 (NCT00213135) and completed the study who were randomized or assigned to cladribine 3.5 mg/kg orally provided as 0.875 mg/kg treatment weeks at Week 1, Week 5, Week 48 and Week 52 resulting in total dose of 3.5 mg/kg during the treatment period of 96 weeks. Participants were followed up for 24 weeks in SUPF. | Participants who received placebo in previous study 25643 (NCT00213135) and completed the study who were randomized or assigned to cladribine 3.5 mg/kg orally provided as 0.875 mg/kg treatment weeks at Week 1, Week 5, Week 48 and Week 52 resulting in total dose of 3.5 mg/kg during the treatment period of 96 weeks. Participants were followed up for 24 weeks in SUPF. |
| Measure Participants | 98 | 92 | 186 | 186 | 244 |
| Herpes viral infection |
6
6.1%
|
4
4.3%
|
6
3.2%
|
13
7%
|
11
4.5%
|
| Opportunistic infection |
8
8.2%
|
4
4.3%
|
9
4.8%
|
17
9.1%
|
15
6.1%
|
| Viral infectious disorder |
20
20.4%
|
16
17.4%
|
28
15.1%
|
41
22%
|
39
16%
|
| Infections related adverse event |
49
50%
|
45
48.9%
|
92
49.5%
|
88
47.3%
|
112
45.9%
|
| Malignancies |
2
2%
|
1
1.1%
|
7
3.8%
|
2
1.1%
|
2
0.8%
|
| Title | SAFUP Analysis Set: Number of Participants Who Developed Infections (Herpes Viral Infection, Viral Infectious Disorder and Opportunistic Infection), Infection-related Adverse Events and Malignancies |
|---|---|
| Description | Number of participants who developed Herpes viral infection, Viral infectious disorder and Opportunistic infection were reported. Number of participants with infection related adverse events are the number of participants who had at least one adverse event coded to medical dictionary for regulatory activities (MedDRA) preferred terms under infection and infestation system organ class. Malignancy is defined as having at least one adverse event coded to MedDRA preferred terms under the pre-specified grouping Malignant and unspecified tumors. |
| Time Frame | Baseline up to Week 120 |
Outcome Measure Data
| Analysis Population Description |
|---|
| SAFUP Analysis Set included all participants who were enrolled and had at least one safety assessment, but were not randomized or assigned to treatment because they were not eligible to receive study medication. |
| Arm/Group Title | Placebo/No Treatment | Cladribine 3.5 mg/kg/No Treatment | Cladribine 5.25 mg/kg/No Treatment |
|---|---|---|---|
| Arm/Group Description | Participants who received placebo matched to cladribine in previous study 25643 (NCT00213135) and were enrolled in this extension study and received no cladribine treatment and were followed up for safety assessment for 96 weeks (during the treatment period) and followed up for 24 weeks (during supplemental follow-up period). | Participants who received cladribine 3.5 mg/kg in previous study 25643 (NCT00213135) and completed were enrolled in this extension study and received no cladribine treatment and were followed up for safety assessment for 96 weeks (during the treatment period) and followed up for 24 weeks (during supplemental follow-up period). | Participants who received cladribine 5.25 mg/kg in previous study 25643 (NCT00213135) and completed were enrolled in this extension study and received no cladribine treatment and were followed up for safety assessment for 96 weeks (during the treatment period) and followed up for 24 weeks (during supplemental follow-up period). |
| Measure Participants | 22 | 17 | 22 |
| Herpes viral infection |
0
0%
|
1
1.1%
|
1
0.5%
|
| Opportunistic infection |
0
0%
|
1
1.1%
|
2
1.1%
|
| Viral infectious disorder |
6
6.1%
|
5
5.4%
|
3
1.6%
|
| Infections related adverse event |
11
11.2%
|
6
6.5%
|
12
6.5%
|
| Malignancies |
2
2%
|
0
0%
|
1
0.5%
|
| Title | Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity |
|---|---|
| Description | Hematologic and hepatic toxicity was assessed using Common Terminology Criteria for Adverse Events version 3.0 (CTCAE). Hematologic and hepatic function included absolute lymphocyte count (ALC), hemoglobin level, white blood cell (WBC) count, absolute neutrophil count (ANC), platelets, alanine transaminase (ALT), aspartate transaminase (AST) and bilirubin. Time to first CTCAE Grade 3 or 4 hematological or liver toxicity was analyzed by treatment group using Kaplan-Meier plots of probability of surviving toxicity-free and point estimates of percentiles. According to CTCAE version 3.0: Grade 1=mild, Grade 2=moderate, Grade 3=severe, Grade 4=life threatening or disabling and Grade 5=Death. 10th, 20th, 25th, 50th and 75th percentiles were estimated from Kaplan-Meier survival curve. |
| Time Frame | Baseline up to Week 120 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety population included all the randomized participants who had received at least 1dose of study medication and had follow-up safety data. Here 'Number of participants analyzed' signifies number of participants who were evaluable for this outcome measure and "Number Analyzed"signifies those participants who were evaluable for specified category. |
| Arm/Group Title | Cladribine Low/Placebo (LLPP) | Cladribine High Dose/Placebo (HLPP) | Cladribine Low/Low Dose (LLLL) | Cladribine High/Low Dose (HLLL) | Placebo/Cladribine Low Dose (PPLL) |
|---|---|---|---|---|---|
| Arm/Group Description | Participants who received cladribine 3.5 mg/kg in previous study 25643 (NCT00213135) and completed the study who were randomized or assigned to placebo (matched to cladribine tablet) during the treatment period of 96 weeks. Participants were followed up for 24 weeks in Supplemental follow-up period (SUPF). | Participants who received cladribine 5.25 mg/kg in previous study 25643 (NCT00213135) and completed the study who were randomized or assigned to placebo (matched to cladribine tablet) during the treatment period of 96 weeks. Participants were followed up for 24 weeks in SUPF. | Participants who received cladribine 3.5 mg/kg in previous study 25643 (NCT00213135) and completed the study who were randomized or assigned to cladribine 3.5 mg/kg orally provided as 0.875 mg/kg treatment weeks at Week 1, Week 5, Week 48 and Week 52 resulting in total dose of 3.5 mg/kg during the treatment period of 96 weeks. Participants were followed up for 24 weeks in SUPF. | Participants who received cladribine 5.25 mg/kg in previous study 25643 (NCT00213135) and completed the study who were randomized or assigned to cladribine 3.5 mg/kg orally provided as 0.875 mg/kg treatment weeks at Week 1, Week 5, Week 48 and Week 52 resulting in total dose of 3.5 mg/kg during the treatment period of 96 weeks. Participants were followed up for 24 weeks in SUPF. | Participants who received placebo in previous study 25643 (NCT00213135) and completed the study who were randomized or assigned to cladribine 3.5 mg/kg orally provided as 0.875 mg/kg treatment weeks at Week 1, Week 5, Week 48 and Week 52 resulting in total dose of 3.5 mg/kg during the treatment period of 96 weeks. Participants were followed up for 24 weeks in SUPF. |
| Measure Participants | 5 | 6 | 76 | 99 | 61 |
| 10th percentile: Lymphocytes Count |
NA
|
NA
|
14
|
8
|
362
|
| 20th percentile: Lymphocytes Count |
NA
|
NA
|
58
|
15
|
412
|
| 25th percentile: Lymphocytes Count |
NA
|
NA
|
108
|
34
|
583
|
| 50th percentile: Lymphocytes Count |
NA
|
NA
|
NA
|
449
|
NA
|
| 75th percentile: Lymphocytes Count |
NA
|
NA
|
NA
|
NA
|
NA
|
| 10th percentile: Hemoglobin |
NA
|
NA
|
NA
|
NA
|
|
| 20th percentile: Hemoglobin |
NA
|
NA
|
NA
|
NA
|
|
| 25th percentile: Hemoglobin |
NA
|
NA
|
NA
|
NA
|
|
| 50th percentile: Hemoglobin |
NA
|
NA
|
NA
|
NA
|
|
| 75th percentile: Hemoglobin |
NA
|
NA
|
NA
|
NA
|
|
| 10th percentile: WBC |
NA
|
NA
|
NA
|
NA
|
|
| 20th percentile: WBC |
NA
|
NA
|
NA
|
NA
|
|
| 25th percentile: WBC |
NA
|
NA
|
NA
|
NA
|
|
| 50th percentile: WBC |
NA
|
NA
|
NA
|
NA
|
|
| 75th percentile: WBC |
NA
|
NA
|
NA
|
NA
|
|
| 10th percentile: ANC |
NA
|
NA
|
NA
|
NA
|
NA
|
| 20th percentile: ANC |
NA
|
NA
|
NA
|
NA
|
NA
|
| 25th percentile: ANC |
NA
|
NA
|
NA
|
NA
|
NA
|
| 50th percentile: ANC |
NA
|
NA
|
NA
|
NA
|
NA
|
| 75th percentile: ANC |
NA
|
NA
|
NA
|
NA
|
NA
|
| 10th percentile: Platelets |
NA
|
NA
|
|||
| 20th percentile: Platelets |
NA
|
NA
|
|||
| 25th percentile: Platelets |
NA
|
NA
|
|||
| 50th percentile: Platelets |
NA
|
NA
|
|||
| 75th percentile: Platelets |
NA
|
NA
|
|||
| 10th percentile: ALT |
NA
|
NA
|
NA
|
||
| 20th percentile: ALT |
NA
|
NA
|
NA
|
||
| 25th percentile: ALT |
NA
|
NA
|
NA
|
||
| 50th percentile: ALT |
NA
|
NA
|
NA
|
||
| 75th percentile: ALT |
NA
|
NA
|
NA
|
||
| 10th percentile: AST |
NA
|
NA
|
NA
|
NA
|
|
| 20th percentile: AST |
NA
|
NA
|
NA
|
NA
|
|
| 25th percentile: AST |
NA
|
NA
|
NA
|
NA
|
|
| 50th percentile: AST |
NA
|
NA
|
NA
|
NA
|
|
| 75th percentile: AST |
NA
|
NA
|
NA
|
NA
|
| Title | Safety Population: Median Time to Recovery From Grade 3 or 4 Hematological and Hepatic Toxicity |
|---|---|
| Description | Hematologic and hepatic toxicity was assessed using Common Terminology Criteria for Adverse Events (CTCAE). Hematologic and hepatic function included absolute lymphocyte count (ALC), hemoglobin level, white blood cell (WBC) count, absolute neutrophil count (ANC), platelets, alanine transaminase (ALT), aspartate transaminase (AST) and bilirubin. According to CTCAE version 3.0: Grade 1=mild, Grade 2=moderate, Grade 3=severe, Grade 4=life threatening or disabling and Grade 5=Death. Time to recovery from grade 3 or 4 hematological or liver toxicity were reported: lymphocytes, platelets, neutrophils, white blood cells, hemoglobin, Alanine transaminase (ALT), Aspartate transaminase (AST), Platelets and Bilirubin. Recovery from a Grade 3 or 4 toxicity is defined as a return to a Grade 0 or 1. |
| Time Frame | Baseline up to Week 120 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety population included all the randomized participants who had received at least 1dose of study medication and had follow-up safety data. Here 'Number of participants analyzed' signifies number of participants who were evaluable for this outcome measure and "Number Analyzed signifies those participants who were evaluable for specified category. |
| Arm/Group Title | Cladribine Low/Placebo (LLPP) | Cladribine High Dose/Placebo (HLPP) | Cladribine Low/Low Dose (LLLL) | Cladribine High/Low Dose (HLLL) | Placebo/Cladribine Low Dose (PPLL) |
|---|---|---|---|---|---|
| Arm/Group Description | Participants who received cladribine 3.5 mg/kg in previous study 25643 (NCT00213135) and completed the study who were randomized or assigned to placebo (matched to cladribine tablet) during the treatment period of 96 weeks. Participants were followed up for 24 weeks in Supplemental follow-up period (SUPF). | Participants who received cladribine 5.25 mg/kg in previous study 25643 (NCT00213135) and completed the study who were randomized or assigned to placebo (matched to cladribine tablet) during the treatment period of 96 weeks. Participants were followed up for 24 weeks in SUPF. | Participants who received cladribine 3.5 mg/kg in previous study 25643 (NCT00213135) and completed the study who were randomized or assigned to cladribine 3.5 mg/kg orally provided as 0.875 mg/kg treatment weeks at Week 1, Week 5, Week 48 and Week 52 resulting in total dose of 3.5 mg/kg during the treatment period of 96 weeks. Participants were followed up for 24 weeks in SUPF. | Participants who received cladribine 5.25 mg/kg in previous study 25643 (NCT00213135) and completed the study who were randomized or assigned to cladribine 3.5 mg/kg orally provided as 0.875 mg/kg treatment weeks at Week 1, Week 5, Week 48 and Week 52 resulting in total dose of 3.5 mg/kg during the treatment period of 96 weeks. Participants were followed up for 24 weeks in SUPF. | Participants who received placebo in previous study 25643 (NCT00213135) and completed the study who were randomized or assigned to cladribine 3.5 mg/kg orally provided as 0.875 mg/kg treatment weeks at Week 1, Week 5, Week 48 and Week 52 resulting in total dose of 3.5 mg/kg during the treatment period of 96 weeks. Participants were followed up for 24 weeks in SUPF. |
| Measure Participants | 5 | 4 | 69 | 89 | 50 |
| Lymphocyte |
22.0
|
31.5
|
212.0
|
168.0
|
111.3
|
| Hemoglobin |
99.0
|
64.0
|
57.0
|
173.5
|
|
| White Blood Cell Count |
29.0
|
30.0
|
42.5
|
79.0
|
|
| Absolute Neutrophil Count |
43.0
|
57.0
|
23.8
|
34.0
|
37.5
|
| Platelets |
197.0
|
||||
| Alanine Transaminase (ALT) |
72.5
|
73.0
|
15.0
|
||
| Aspartate Transaminase (AST) |
72.5
|
84.0
|
18.0
|
55.0
|
| Title | Safety Population: Mean Time to Recovery From Grade 3 or 4 Hematological and Liver Toxicity |
|---|---|
| Description | Hematologic and hepatic toxicity was assessed using Common Terminology Criteria for Adverse Events (CTCAE). Hematologic and hepatic function included absolute lymphocyte count (ALC), hemoglobin level, white blood cell (WBC) count, absolute neutrophil count (ANC), platelets, alanine transaminase (ALT), aspartate transaminase (AST) and bilirubin. According to CTCAE v3.0: Grade 1=mild, Grade 2=moderate, Grade 3=severe, Grade 4=life threatening or disabling and Grade 5=Death. Time to recovery from grade 3 or 4 hematological or liver toxicity were reported: lymphocytes, platelets, neutrophils, white blood cells, hemoglobin, Alanine transaminase (ALT), Aspartate transaminase (AST) and Platelets. Recovery from a Grade 3 or 4 toxicity is defined as a return to a Grade 0 or 1. |
| Time Frame | Baseline up to Week 120 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety population included all the randomized participants who had received at least 1 dose of study medication and had follow-up safety data. Here 'Number of participants analyzed' signifies number of participants who were evaluable for this outcome measure and "Number analyzed" are those who were evaluable at specified category. |
| Arm/Group Title | Cladribine Low/Placebo (LLPP) | Cladribine High Dose/Placebo (HLPP) | Cladribine Low/Low Dose (LLLL) | Cladribine High/Low Dose (HLLL) | Placebo/Cladribine Low Dose (PPLL) |
|---|---|---|---|---|---|
| Arm/Group Description | Participants who received cladribine 3.5 mg/kg in previous study 25643 (NCT00213135) and completed the study who were randomized or assigned to placebo (matched to cladribine tablet) during the treatment period of 96 weeks. Participants were followed up for 24 weeks in Supplemental follow-up period (SUPF). | Participants who received cladribine 5.25 mg/kg in previous study 25643 (NCT00213135) and completed the study who were randomized or assigned to placebo (matched to cladribine tablet) during the treatment period of 96 weeks. Participants were followed up for 24 weeks in SUPF. | Participants who received cladribine 3.5 mg/kg in previous study 25643 (NCT00213135) and completed the study who were randomized or assigned to cladribine 3.5 mg/kg orally provided as 0.875 mg/kg treatment weeks at Week 1, Week 5, Week 48 and Week 52 resulting in total dose of 3.5 mg/kg during the treatment period of 96 weeks. Participants were followed up for 24 weeks in SUPF. | Participants who received cladribine 5.25 mg/kg in previous study 25643 (NCT00213135) and completed the study who were randomized or assigned to cladribine 3.5 mg/kg orally provided as 0.875 mg/kg treatment weeks at Week 1, Week 5, Week 48 and Week 52 resulting in total dose of 3.5 mg/kg during the treatment period of 96 weeks. Participants were followed up for 24 weeks in SUPF. | Participants who received placebo in previous study 25643 (NCT00213135) and completed the study who were randomized or assigned to cladribine 3.5 mg/kg orally provided as 0.875 mg/kg treatment weeks at Week 1, Week 5, Week 48 and Week 52 resulting in total dose of 3.5 mg/kg during the treatment period of 96 weeks. Participants were followed up for 24 weeks in SUPF. |
| Measure Participants | 5 | 4 | 69 | 89 | 50 |
| Lymphocyte |
41.0
(33.5)
|
34.9
(11.7)
|
256.7
(239.7)
|
241.8
(216.1)
|
160.2
(160.4)
|
| Hemoglobin |
99.0
|
64.0
|
57.0
|
173.5
(214.3)
|
|
| White Blood Cell Count |
29.0
|
79.3
(91.9)
|
132.0
(213.9)
|
71.5
(39.7)
|
|
| Absolute Neutrophil Count |
49.0
(39.3)
|
57.0
(39.6)
|
35.3
(29.9)
|
46.8
(35.1)
|
61.0
(55.3)
|
| Platelets |
197.0
|
||||
| Alanine Transaminase |
72.5
(30.4)
|
73.0
(76.4)
|
23.7
(28.0)
|
||
| Aspartate Transaminase |
72.5
(30.4)
|
84.0
|
18.0
|
55.0
|
| Title | Safety Population: Median Time to Nadir of Absolute Lymphocyte Count |
|---|---|
| Description | Median time to nadir of absolute lymphocyte count was reported. |
| Time Frame | Baseline up to Week 120 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety population included all the randomized participants who had received at least 1 dose of study medication and had follow-up safety data. Here 'Number of participants analyzed' signifies number of participants who were evaluable for this outcome measure. |
| Arm/Group Title | Cladribine Low/Placebo (LLPP) | Cladribine High Dose/Placebo (HLPP) | Cladribine Low/Low Dose (LLLL) | Cladribine High/Low Dose (HLLL) | Placebo/Cladribine Low Dose (PPLL) |
|---|---|---|---|---|---|
| Arm/Group Description | Participants who received cladribine 3.5 mg/kg in previous study 25643 (NCT00213135) and completed the study who were randomized or assigned to placebo (matched to cladribine tablet) during the treatment period of 96 weeks. Participants were followed up for 24 weeks in Supplemental follow-up period (SUPF). | Participants who received cladribine 5.25 mg/kg in previous study 25643 (NCT00213135) and completed the study who were randomized or assigned to placebo (matched to cladribine tablet) during the treatment period of 96 weeks. Participants were followed up for 24 weeks in SUPF. | Participants who received cladribine 3.5 mg/kg in previous study 25643 (NCT00213135) and completed the study who were randomized or assigned to cladribine 3.5 mg/kg orally provided as 0.875 mg/kg treatment weeks at Week 1, Week 5, Week 48 and Week 52 resulting in total dose of 3.5 mg/kg during the treatment period of 96 weeks. Participants were followed up for 24 weeks in SUPF. | Participants who received cladribine 5.25 mg/kg in previous study 25643 (NCT00213135) and completed the study who were randomized or assigned to cladribine 3.5 mg/kg orally provided as 0.875 mg/kg treatment weeks at Week 1, Week 5, Week 48 and Week 52 resulting in total dose of 3.5 mg/kg during the treatment period of 96 weeks. Participants were followed up for 24 weeks in SUPF. | Participants who received placebo in previous study 25643 (NCT00213135) and completed the study who were randomized or assigned to cladribine 3.5 mg/kg orally provided as 0.875 mg/kg treatment weeks at Week 1, Week 5, Week 48 and Week 52 resulting in total dose of 3.5 mg/kg during the treatment period of 96 weeks. Participants were followed up for 24 weeks in SUPF. |
| Measure Participants | 54 | 57 | 177 | 175 | 227 |
| Median (97.5% Confidence Interval) [Days] |
162.0
|
93.0
|
365.0
|
162.0
|
380.0
|
| Title | Safety Population: Mean Time to Nadir of Absolute Lymphocyte Count |
|---|---|
| Description | Mean time to nadir of absolute lymphocyte count was reported. |
| Time Frame | Baseline up to Week 120 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety population included all the randomized participants who had received at least 1 dose of study medication and had follow-up safety data. Here 'Number of participants analyzed' signifies number of participants who were evaluable for this outcome measure. |
| Arm/Group Title | Cladribine Low/Placebo (LLPP) | Cladribine High Dose/Placebo (HLPP) | Cladribine Low/Low Dose (LLLL) | Cladribine High/Low Dose (HLLL) | Placebo/Cladribine Low Dose (PPLL) |
|---|---|---|---|---|---|
| Arm/Group Description | Participants who received cladribine 3.5 mg/kg in previous study 25643 (NCT00213135) and completed the study who were randomized or assigned to placebo (matched to cladribine tablet) during the treatment period of 96 weeks. Participants were followed up for 24 weeks in Supplemental follow-up period (SUPF). | Participants who received cladribine 5.25 mg/kg in previous study 25643 (NCT00213135) and completed the study who were randomized or assigned to placebo (matched to cladribine tablet) during the treatment period of 96 weeks. Participants were followed up for 24 weeks in SUPF. | Participants who received cladribine 3.5 mg/kg in previous study 25643 (NCT00213135) and completed the study who were randomized or assigned to cladribine 3.5 mg/kg orally provided as 0.875 mg/kg treatment weeks at Week 1, Week 5, Week 48 and Week 52 resulting in total dose of 3.5 mg/kg during the treatment period of 96 weeks. Participants were followed up for 24 weeks in SUPF. | Participants who received cladribine 5.25 mg/kg in previous study 25643 (NCT00213135) and completed the study who were randomized or assigned to cladribine 3.5 mg/kg orally provided as 0.875 mg/kg treatment weeks at Week 1, Week 5, Week 48 and Week 52 resulting in total dose of 3.5 mg/kg during the treatment period of 96 weeks. Participants were followed up for 24 weeks in SUPF. | Participants who received placebo in previous study 25643 (NCT00213135) and completed the study who were randomized or assigned to cladribine 3.5 mg/kg orally provided as 0.875 mg/kg treatment weeks at Week 1, Week 5, Week 48 and Week 52 resulting in total dose of 3.5 mg/kg during the treatment period of 96 weeks. Participants were followed up for 24 weeks in SUPF. |
| Measure Participants | 54 | 57 | 177 | 175 | 227 |
| Mean (Standard Deviation) [Days] |
292.0
(296.7)
|
193.6
(219.1)
|
276.7
(191.7)
|
241.1
(200.3)
|
362.9
(177.5)
|
| Title | Safety Population: Mean Time to Recovery From Nadir of Absolute Lymphocyte Count to Normal Value |
|---|---|
| Description | Mean time to recovery from nadir of absolute lymphocyte count to normal was reported. Recovery from Nadir is defined as a return to baseline value. Normal absolute lymphocyte count is 1.02 x 10^3 cells/microliter. |
| Time Frame | Baseline up to Week 120 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety population included all the randomized participants who had received at least 1 dose of study medication and had follow-up safety data. Here 'Number of participants analyzed' signifies number of participants who were evaluable for this outcome measure. |
| Arm/Group Title | Cladribine Low/Placebo (LLPP) | Cladribine High Dose/Placebo (HLPP) | Cladribine Low/Low Dose (LLLL) | Cladribine High/Low Dose (HLLL) | Placebo/Cladribine Low Dose (PPLL) |
|---|---|---|---|---|---|
| Arm/Group Description | Participants who received cladribine 3.5 mg/kg in previous study 25643 (NCT00213135) and completed the study who were randomized or assigned to placebo (matched to cladribine tablet) during the treatment period of 96 weeks. Participants were followed up for 24 weeks in Supplemental follow-up period (SUPF). | Participants who received cladribine 5.25 mg/kg in previous study 25643 (NCT00213135) and completed the study who were randomized or assigned to placebo (matched to cladribine tablet) during the treatment period of 96 weeks. Participants were followed up for 24 weeks in SUPF. | Participants who received cladribine 3.5 mg/kg in previous study 25643 (NCT00213135) and completed the study who were randomized or assigned to cladribine 3.5 mg/kg orally provided as 0.875 mg/kg treatment weeks at Week 1, Week 5, Week 48 and Week 52 resulting in total dose of 3.5 mg/kg during the treatment period of 96 weeks. Participants were followed up for 24 weeks in SUPF. | Participants who received cladribine 5.25 mg/kg in previous study 25643 (NCT00213135) and completed the study who were randomized or assigned to cladribine 3.5 mg/kg orally provided as 0.875 mg/kg treatment weeks at Week 1, Week 5, Week 48 and Week 52 resulting in total dose of 3.5 mg/kg during the treatment period of 96 weeks. Participants were followed up for 24 weeks in SUPF. | Participants who received placebo in previous study 25643 (NCT00213135) and completed the study who were randomized or assigned to cladribine 3.5 mg/kg orally provided as 0.875 mg/kg treatment weeks at Week 1, Week 5, Week 48 and Week 52 resulting in total dose of 3.5 mg/kg during the treatment period of 96 weeks. Participants were followed up for 24 weeks in SUPF. |
| Measure Participants | 47 | 52 | 130 | 128 | 185 |
| Mean (Standard Deviation) [Days] |
79.0
(72.4)
|
72.7
(61.3)
|
237.5
(214.7)
|
245.3
(222.3)
|
187.8
(180.9)
|
| Title | Safety Population: Mean Change in Corrected QT (QTc) Interval From Baseline |
|---|---|
| Description | The QT interval is a measure of the time between the start of the Q wave and the end of the T wave. Corrected QT (QTc) is the QT interval corrected for heart rate and RR, which is the interval between two R waves. Mean change in corrected QT (QTc) interval from baseline was reported. |
| Time Frame | Baseline, Week 5, 48, 52 and 96 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety population included all the randomized participants who had received at least 1 dose of study medication and had follow-up safety data. Here 'Number of participants analyzed' signifies number of participants who were evaluable for this outcome measure and and "Number analyzed" are those who were evaluable at specified category. |
| Arm/Group Title | Cladribine Low/Placebo (LLPP) | Cladribine High Dose/Placebo (HLPP) | Cladribine Low/Low Dose (LLLL) | Cladribine High/Low Dose (HLLL) | Placebo/Cladribine Low Dose (PPLL) |
|---|---|---|---|---|---|
| Arm/Group Description | Participants who received cladribine 3.5 mg/kg in previous study 25643 (NCT00213135) and completed the study who were randomized or assigned to placebo (matched to cladribine tablet) during the treatment period of 96 weeks. Participants were followed up for 24 weeks in Supplemental follow-up period (SUPF). | Participants who received cladribine 5.25 mg/kg in previous study 25643 (NCT00213135) and completed the study who were randomized or assigned to placebo (matched to cladribine tablet) during the treatment period of 96 weeks. Participants were followed up for 24 weeks in SUPF. | Participants who received cladribine 3.5 mg/kg in previous study 25643 (NCT00213135) and completed the study who were randomized or assigned to cladribine 3.5 mg/kg orally provided as 0.875 mg/kg treatment weeks at Week 1, Week 5, Week 48 and Week 52 resulting in total dose of 3.5 mg/kg during the treatment period of 96 weeks. Participants were followed up for 24 weeks in SUPF. | Participants who received cladribine 5.25 mg/kg in previous study 25643 (NCT00213135) and completed the study who were randomized or assigned to cladribine 3.5 mg/kg orally provided as 0.875 mg/kg treatment weeks at Week 1, Week 5, Week 48 and Week 52 resulting in total dose of 3.5 mg/kg during the treatment period of 96 weeks. Participants were followed up for 24 weeks in SUPF. | Participants who received placebo in previous study 25643 (NCT00213135) and completed the study who were randomized or assigned to cladribine 3.5 mg/kg orally provided as 0.875 mg/kg treatment weeks at Week 1, Week 5, Week 48 and Week 52 resulting in total dose of 3.5 mg/kg during the treatment period of 96 weeks. Participants were followed up for 24 weeks in SUPF. |
| Measure Participants | 25 | 18 | 31 | 35 | 41 |
| Week 5 |
7.0
(21.6)
|
7.4
(21.2)
|
4.5
(20.6)
|
4.3
(16.2)
|
0.7
(18.8)
|
| Week 48 |
16.9
(18.6)
|
7.4
(23.6)
|
9.3
(19.8)
|
11.3
(19.5)
|
7.2
(19.6)
|
| Week 52 |
14.9
(17.5)
|
22.3
(25.4)
|
8.4
(22.8)
|
5.2
(18.8)
|
-1.2
(16.6)
|
| Week 96 |
5.8
(25.5)
|
-4.5
(32.5)
|
-12.5
(22.2)
|
1.6
(22.7)
|
-6.2
(19.2)
|
Adverse Events
| Time Frame | Baseline up to Week 120 | |||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | For LLPP, HLPP, LLLL, HLLL and PPLL arms: Safety population included all the randomized participants who had received at least 1dose of study medication and had follow-up safety data. For Placebo/No treatment, Cladribine 3.5 mg/kg/No Treatment and Cladribine 5.25 mg/kg/No Treatment: SAFUP Analysis Set included all participants who were enrolled and had at least one safety assessment, but were not randomized or assigned to treatment because they were not eligible to receive study medication. | |||||||||||||||
| Arm/Group Title | Cladribine Low/Placebo (LLPP) | Cladribine High Dose/Placebo (HLPP) | Cladribine Low/Low Dose (LLLL) | Cladribine High/Low Dose (HLLL) | Placebo/Cladribine Low Dose (PPLL) | Placebo/No Treatment | Cladribine 3.5 mg/kg/No Treatment | Cladribine 5.25 mg/kg/No Treatment | ||||||||
| Arm/Group Description | Participants who received cladribine 3.5 mg/kg in previous study 25643 (NCT00213135) and completed the study who were randomized or assigned to placebo (matched to cladribine tablet) during the treatment period of 96 weeks. Participants were followed up for 24 weeks in Supplemental follow-up period (SUPF). | Participants who received cladribine 5.25 mg/kg in previous study 25643 (NCT00213135) and completed the study who were randomized or assigned to placebo (matched to cladribine tablet) during the treatment period of 96 weeks. Participants were followed up for 24 weeks in SUPF. | Participants who received cladribine 3.5 mg/kg in previous study 25643 (NCT00213135) and completed the study who were randomized or assigned to cladribine 3.5 mg/kg orally provided as 0.875 mg/kg treatment weeks at Week 1, Week 5, Week 48 and Week 52 resulting in total dose of 3.5 mg/kg during the treatment period of 96 weeks. Participants were followed up for 24 weeks in SUPF. | Participants who received cladribine 5.25 mg/kg in previous study 25643 (NCT00213135) and completed the study who were randomized or assigned to cladribine 3.5 mg/kg orally provided as 0.875 mg/kg treatment weeks at Week 1, Week 5, Week 48 and Week 52 resulting in total dose of 3.5 mg/kg during the treatment period of 96 weeks. Participants were followed up for 24 weeks in SUPF. | Participants who received placebo in previous study 25643 (NCT00213135) and completed the study who were randomized or assigned to cladribine 3.5 mg/kg orally provided as 0.875 mg/kg treatment weeks at Week 1, Week 5, Week 48 and Week 52 resulting in total dose of 3.5 mg/kg during the treatment period of 96 weeks. Participants were followed up for 24 weeks in SUPF. | Participants who received placebo matched to cladribine in previous study 25643 (NCT00213135) and were enrolled in this extension study and received no cladribine treatment and were followed up for safety assessment for 96 weeks (during the treatment period) and followed up for 24 weeks (during supplemental follow-up period). | Participants who received cladribine 3.5 mg/kg in previous study 25643 (NCT00213135) and completed were enrolled in this extension study and received no cladribine treatment and were followed up for safety assessment for 96 weeks (during the treatment period) and followed up for 24 weeks (during supplemental follow-up period). | Participants who received cladribine 5.25 mg/kg in previous study 25643 (NCT00213135) and completed were enrolled in this extension study and received no cladribine treatment and were followed up for safety assessment for 96 weeks (during the treatment period) and followed up for 24 weeks (during supplemental follow-up period). | ||||||||
All Cause Mortality |
||||||||||||||||
| Cladribine Low/Placebo (LLPP) | Cladribine High Dose/Placebo (HLPP) | Cladribine Low/Low Dose (LLLL) | Cladribine High/Low Dose (HLLL) | Placebo/Cladribine Low Dose (PPLL) | Placebo/No Treatment | Cladribine 3.5 mg/kg/No Treatment | Cladribine 5.25 mg/kg/No Treatment | |||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 2/98 (2%) | 0/92 (0%) | 1/186 (0.5%) | 0/186 (0%) | 0/244 (0%) | 0/22 (0%) | 0/17 (0%) | 0/22 (0%) | ||||||||
Serious Adverse Events |
||||||||||||||||
| Cladribine Low/Placebo (LLPP) | Cladribine High Dose/Placebo (HLPP) | Cladribine Low/Low Dose (LLLL) | Cladribine High/Low Dose (HLLL) | Placebo/Cladribine Low Dose (PPLL) | Placebo/No Treatment | Cladribine 3.5 mg/kg/No Treatment | Cladribine 5.25 mg/kg/No Treatment | |||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 16/98 (16.3%) | 8/92 (8.7%) | 25/186 (13.4%) | 23/186 (12.4%) | 22/244 (9%) | 2/22 (9.1%) | 1/17 (5.9%) | 3/22 (13.6%) | ||||||||
| Blood and lymphatic system disorders | ||||||||||||||||
| Lymphopenia | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 1/186 (0.5%) | 1/244 (0.4%) | 0/22 (0%) | 0/17 (0%) | 0/22 (0%) | ||||||||
| Iron deficiency anaemia | 0/98 (0%) | 0/92 (0%) | 1/186 (0.5%) | 0/186 (0%) | 0/244 (0%) | 0/22 (0%) | 0/17 (0%) | 0/22 (0%) | ||||||||
| Thrombocytopenia | 1/98 (1%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 0/22 (0%) | 0/17 (0%) | 0/22 (0%) | ||||||||
| Lymphadenopathy | 1/98 (1%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 0/22 (0%) | 0/17 (0%) | 0/22 (0%) | ||||||||
| Cardiac disorders | ||||||||||||||||
| Adams-Stokes syndrome | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 1/186 (0.5%) | 0/244 (0%) | 0/22 (0%) | 0/17 (0%) | 0/22 (0%) | ||||||||
| Atrial fibrillation | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 1/244 (0.4%) | 0/22 (0%) | 0/17 (0%) | 0/22 (0%) | ||||||||
| Myocardial infarction | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 1/244 (0.4%) | 0/22 (0%) | 0/17 (0%) | 0/22 (0%) | ||||||||
| Tachycardia | 1/98 (1%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 0/22 (0%) | 0/17 (0%) | 0/22 (0%) | ||||||||
| Ear and labyrinth disorders | ||||||||||||||||
| Vertigo positional | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 1/186 (0.5%) | 0/244 (0%) | 0/22 (0%) | 0/17 (0%) | 0/22 (0%) | ||||||||
| Endocrine disorders | ||||||||||||||||
| Basedow's disease | 1/98 (1%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 0/22 (0%) | 0/17 (0%) | 0/22 (0%) | ||||||||
| Thyroiditis | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 1/186 (0.5%) | 0/244 (0%) | 0/22 (0%) | 0/17 (0%) | 0/22 (0%) | ||||||||
| Autoimmune thyroiditis | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 0/22 (0%) | 0/17 (0%) | 1/22 (4.5%) | ||||||||
| Eye disorders | ||||||||||||||||
| Iridocyclitis | 2/98 (2%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 0/22 (0%) | 0/17 (0%) | 0/22 (0%) | ||||||||
| Macular degeneration | 1/98 (1%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 0/22 (0%) | 0/17 (0%) | 0/22 (0%) | ||||||||
| Gastrointestinal disorders | ||||||||||||||||
| Abdominal pain | 0/98 (0%) | 0/92 (0%) | 1/186 (0.5%) | 0/186 (0%) | 1/244 (0.4%) | 0/22 (0%) | 0/17 (0%) | 0/22 (0%) | ||||||||
| Colonic polyp | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 1/186 (0.5%) | 0/244 (0%) | 0/22 (0%) | 0/17 (0%) | 0/22 (0%) | ||||||||
| Duodenal ulcer | 1/98 (1%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 0/22 (0%) | 0/17 (0%) | 0/22 (0%) | ||||||||
| Duodenal ulcer perforation | 0/98 (0%) | 1/92 (1.1%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 0/22 (0%) | 0/17 (0%) | 0/22 (0%) | ||||||||
| Gastric haemorrhage | 1/98 (1%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 0/22 (0%) | 0/17 (0%) | 0/22 (0%) | ||||||||
| Gastritis | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 1/244 (0.4%) | 0/22 (0%) | 0/17 (0%) | 0/22 (0%) | ||||||||
| Gastrooesophageal reflux disease | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 1/244 (0.4%) | 0/22 (0%) | 0/17 (0%) | 0/22 (0%) | ||||||||
| Ileus paralytic | 0/98 (0%) | 0/92 (0%) | 1/186 (0.5%) | 0/186 (0%) | 0/244 (0%) | 0/22 (0%) | 0/17 (0%) | 0/22 (0%) | ||||||||
| Irritable bowel syndrome | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 1/244 (0.4%) | 0/22 (0%) | 0/17 (0%) | 0/22 (0%) | ||||||||
| Peritonitis | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 1/186 (0.5%) | 0/244 (0%) | 0/22 (0%) | 0/17 (0%) | 0/22 (0%) | ||||||||
| Crohn's disease | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 0/22 (0%) | 0/17 (0%) | 1/22 (4.5%) | ||||||||
| General disorders | ||||||||||||||||
| Chest pain | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 1/186 (0.5%) | 0/244 (0%) | 0/22 (0%) | 0/17 (0%) | 0/22 (0%) | ||||||||
| Death | 1/98 (1%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 0/22 (0%) | 0/17 (0%) | 0/22 (0%) | ||||||||
| Drowning | 1/98 (1%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 0/22 (0%) | 0/17 (0%) | 0/22 (0%) | ||||||||
| Influenza like illness | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 1/244 (0.4%) | 0/22 (0%) | 0/17 (0%) | 0/22 (0%) | ||||||||
| Hepatobiliary disorders | ||||||||||||||||
| Cholelithiasis | 1/98 (1%) | 0/92 (0%) | 2/186 (1.1%) | 1/186 (0.5%) | 0/244 (0%) | 0/22 (0%) | 0/17 (0%) | 0/22 (0%) | ||||||||
| Cholecystitis | 1/98 (1%) | 0/92 (0%) | 0/186 (0%) | 1/186 (0.5%) | 0/244 (0%) | 0/22 (0%) | 0/17 (0%) | 0/22 (0%) | ||||||||
| Biliary colic | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 1/186 (0.5%) | 0/244 (0%) | 0/22 (0%) | 0/17 (0%) | 0/22 (0%) | ||||||||
| Biliary tract disorder | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 1/186 (0.5%) | 0/244 (0%) | 0/22 (0%) | 0/17 (0%) | 0/22 (0%) | ||||||||
| Immune system disorders | ||||||||||||||||
| Secondary immunodeficiency | 0/98 (0%) | 0/92 (0%) | 1/186 (0.5%) | 0/186 (0%) | 0/244 (0%) | 0/22 (0%) | 0/17 (0%) | 0/22 (0%) | ||||||||
| Infections and infestations | ||||||||||||||||
| Herpes zoster | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 2/186 (1.1%) | 1/244 (0.4%) | 0/22 (0%) | 0/17 (0%) | 0/22 (0%) | ||||||||
| Pneumonia | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 3/244 (1.2%) | 0/22 (0%) | 0/17 (0%) | 1/22 (4.5%) | ||||||||
| Urinary tract infection | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 2/244 (0.8%) | 0/22 (0%) | 0/17 (0%) | 0/22 (0%) | ||||||||
| Abscess oral | 0/98 (0%) | 0/92 (0%) | 1/186 (0.5%) | 0/186 (0%) | 0/244 (0%) | 0/22 (0%) | 0/17 (0%) | 0/22 (0%) | ||||||||
| Appendicitis | 1/98 (1%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 0/22 (0%) | 0/17 (0%) | 0/22 (0%) | ||||||||
| Bacterial sepsis | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 1/186 (0.5%) | 0/244 (0%) | 0/22 (0%) | 0/17 (0%) | 0/22 (0%) | ||||||||
| Breast abscess | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 1/244 (0.4%) | 0/22 (0%) | 0/17 (0%) | 0/22 (0%) | ||||||||
| Gastroenteritis | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 1/244 (0.4%) | 0/22 (0%) | 0/17 (0%) | 0/22 (0%) | ||||||||
| Infection | 1/98 (1%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 0/22 (0%) | 0/17 (0%) | 0/22 (0%) | ||||||||
| Influenza | 0/98 (0%) | 0/92 (0%) | 1/186 (0.5%) | 0/186 (0%) | 0/244 (0%) | 0/22 (0%) | 0/17 (0%) | 0/22 (0%) | ||||||||
| Pulmonary tuberculosis | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 1/186 (0.5%) | 0/244 (0%) | 0/22 (0%) | 0/17 (0%) | 0/22 (0%) | ||||||||
| Pyelonephritis | 0/98 (0%) | 1/92 (1.1%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 0/22 (0%) | 0/17 (0%) | 0/22 (0%) | ||||||||
| Pyelonephritis chronic | 0/98 (0%) | 1/92 (1.1%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 0/22 (0%) | 0/17 (0%) | 0/22 (0%) | ||||||||
| Urethral abscess | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 1/244 (0.4%) | 0/22 (0%) | 0/17 (0%) | 0/22 (0%) | ||||||||
| Injury, poisoning and procedural complications | ||||||||||||||||
| Femoral neck fracture | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 1/244 (0.4%) | 0/22 (0%) | 0/17 (0%) | 0/22 (0%) | ||||||||
| Humerus fracture | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 1/186 (0.5%) | 0/244 (0%) | 0/22 (0%) | 0/17 (0%) | 0/22 (0%) | ||||||||
| Intentional overdose | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 1/244 (0.4%) | 0/22 (0%) | 0/17 (0%) | 0/22 (0%) | ||||||||
| Limb injury | 0/98 (0%) | 0/92 (0%) | 1/186 (0.5%) | 0/186 (0%) | 0/244 (0%) | 0/22 (0%) | 0/17 (0%) | 0/22 (0%) | ||||||||
| Radius fracture | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 1/186 (0.5%) | 0/244 (0%) | 0/22 (0%) | 0/17 (0%) | 0/22 (0%) | ||||||||
| Road traffic accident | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 1/186 (0.5%) | 0/244 (0%) | 0/22 (0%) | 0/17 (0%) | 0/22 (0%) | ||||||||
| Subdural haematoma | 0/98 (0%) | 0/92 (0%) | 1/186 (0.5%) | 0/186 (0%) | 0/244 (0%) | 0/22 (0%) | 0/17 (0%) | 0/22 (0%) | ||||||||
| Investigations | ||||||||||||||||
| Blood culture positive | 1/98 (1%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 0/22 (0%) | 0/17 (0%) | 0/22 (0%) | ||||||||
| Pregnancy test positive | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 1/244 (0.4%) | 0/22 (0%) | 0/17 (0%) | 0/22 (0%) | ||||||||
| Tuberculin test positive | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 1/244 (0.4%) | 0/22 (0%) | 0/17 (0%) | 0/22 (0%) | ||||||||
| Weight decreased | 0/98 (0%) | 0/92 (0%) | 1/186 (0.5%) | 0/186 (0%) | 0/244 (0%) | 0/22 (0%) | 0/17 (0%) | 0/22 (0%) | ||||||||
| Metabolism and nutrition disorders | ||||||||||||||||
| Diabetic ketoacidosis | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 1/244 (0.4%) | 0/22 (0%) | 0/17 (0%) | 0/22 (0%) | ||||||||
| Type 2 diabetes mellitus | 0/98 (0%) | 0/92 (0%) | 1/186 (0.5%) | 0/186 (0%) | 0/244 (0%) | 0/22 (0%) | 0/17 (0%) | 0/22 (0%) | ||||||||
| Musculoskeletal and connective tissue disorders | ||||||||||||||||
| Intervertebral disc protrusion | 1/98 (1%) | 1/92 (1.1%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 0/22 (0%) | 0/17 (0%) | 0/22 (0%) | ||||||||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||||||||
| Uterine leiomyoma | 0/98 (0%) | 0/92 (0%) | 2/186 (1.1%) | 2/186 (1.1%) | 0/244 (0%) | 0/22 (0%) | 1/17 (5.9%) | 0/22 (0%) | ||||||||
| Lipoma | 0/98 (0%) | 2/92 (2.2%) | 0/186 (0%) | 0/186 (0%) | 1/244 (0.4%) | 0/22 (0%) | 0/17 (0%) | 0/22 (0%) | ||||||||
| Malignant melanoma | 1/98 (1%) | 0/92 (0%) | 0/186 (0%) | 1/186 (0.5%) | 0/244 (0%) | 0/22 (0%) | 0/17 (0%) | 0/22 (0%) | ||||||||
| Adrenal adenoma | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 1/186 (0.5%) | 0/244 (0%) | 0/22 (0%) | 0/17 (0%) | 0/22 (0%) | ||||||||
| Basal cell carcinoma | 1/98 (1%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 1/22 (4.5%) | 0/17 (0%) | 1/22 (4.5%) | ||||||||
| Bile duct cancer | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 1/244 (0.4%) | 0/22 (0%) | 0/17 (0%) | 0/22 (0%) | ||||||||
| Breast cancer | 0/98 (0%) | 0/92 (0%) | 1/186 (0.5%) | 0/186 (0%) | 0/244 (0%) | 0/22 (0%) | 0/17 (0%) | 0/22 (0%) | ||||||||
| Breast fibroma | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 1/186 (0.5%) | 0/244 (0%) | 0/22 (0%) | 0/17 (0%) | 0/22 (0%) | ||||||||
| Colorectal cancer metastatic | 0/98 (0%) | 0/92 (0%) | 1/186 (0.5%) | 0/186 (0%) | 0/244 (0%) | 0/22 (0%) | 0/17 (0%) | 0/22 (0%) | ||||||||
| Fibrous histiocytoma | 1/98 (1%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 0/22 (0%) | 0/17 (0%) | 0/22 (0%) | ||||||||
| Haemangioma of liver | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 1/186 (0.5%) | 0/244 (0%) | 0/22 (0%) | 0/17 (0%) | 0/22 (0%) | ||||||||
| Juvenile melanoma benign | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 1/244 (0.4%) | 0/22 (0%) | 0/17 (0%) | 0/22 (0%) | ||||||||
| Lung neoplasm | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 1/244 (0.4%) | 0/22 (0%) | 0/17 (0%) | 0/22 (0%) | ||||||||
| Melanocytic naevus | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 1/186 (0.5%) | 0/244 (0%) | 0/22 (0%) | 0/17 (0%) | 0/22 (0%) | ||||||||
| Metastases to lung | 0/98 (0%) | 0/92 (0%) | 1/186 (0.5%) | 0/186 (0%) | 0/244 (0%) | 0/22 (0%) | 0/17 (0%) | 0/22 (0%) | ||||||||
| Metastases to lymph nodes | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 1/244 (0.4%) | 0/22 (0%) | 0/17 (0%) | 0/22 (0%) | ||||||||
| Neurilemmoma benign | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 1/244 (0.4%) | 0/22 (0%) | 0/17 (0%) | 0/22 (0%) | ||||||||
| Prostatic adenoma | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 1/186 (0.5%) | 0/244 (0%) | 0/22 (0%) | 0/17 (0%) | 0/22 (0%) | ||||||||
| Rectal cancer | 0/98 (0%) | 0/92 (0%) | 1/186 (0.5%) | 0/186 (0%) | 0/244 (0%) | 0/22 (0%) | 0/17 (0%) | 0/22 (0%) | ||||||||
| Renal cell carcinoma | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 1/186 (0.5%) | 0/244 (0%) | 0/22 (0%) | 0/17 (0%) | 0/22 (0%) | ||||||||
| Seborrhoeic keratosis | 0/98 (0%) | 0/92 (0%) | 1/186 (0.5%) | 0/186 (0%) | 0/244 (0%) | 0/22 (0%) | 0/17 (0%) | 0/22 (0%) | ||||||||
| Skin papilloma | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 1/186 (0.5%) | 0/244 (0%) | 0/22 (0%) | 0/17 (0%) | 0/22 (0%) | ||||||||
| Squamous cell carcinoma | 0/98 (0%) | 0/92 (0%) | 1/186 (0.5%) | 0/186 (0%) | 0/244 (0%) | 0/22 (0%) | 0/17 (0%) | 0/22 (0%) | ||||||||
| Thyroid adenoma | 0/98 (0%) | 0/92 (0%) | 1/186 (0.5%) | 0/186 (0%) | 0/244 (0%) | 0/22 (0%) | 0/17 (0%) | 0/22 (0%) | ||||||||
| Thyroid cancer | 0/98 (0%) | 1/92 (1.1%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 0/22 (0%) | 0/17 (0%) | 0/22 (0%) | ||||||||
| Ovarian cancer | 0/98 (0%) | 0/92 (0%) | 1/186 (0.5%) | 0/186 (0%) | 0/244 (0%) | 0/22 (0%) | 0/17 (0%) | 0/22 (0%) | ||||||||
| Cervix Carcinoma Stage 0 | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 1/22 (4.5%) | 0/17 (0%) | 1/22 (4.5%) | ||||||||
| Nervous system disorders | ||||||||||||||||
| Brain injury | 0/98 (0%) | 0/92 (0%) | 1/186 (0.5%) | 0/186 (0%) | 0/244 (0%) | 0/22 (0%) | 0/17 (0%) | 0/22 (0%) | ||||||||
| Cauda equina syndrome | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 1/186 (0.5%) | 0/244 (0%) | 0/22 (0%) | 0/17 (0%) | 0/22 (0%) | ||||||||
| Radicular syndrome | 1/98 (1%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 0/22 (0%) | 0/17 (0%) | 0/22 (0%) | ||||||||
| Sciatica | 1/98 (1%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 0/22 (0%) | 0/17 (0%) | 0/22 (0%) | ||||||||
| Status epilepticus | 0/98 (0%) | 0/92 (0%) | 1/186 (0.5%) | 0/186 (0%) | 0/244 (0%) | 0/22 (0%) | 0/17 (0%) | 0/22 (0%) | ||||||||
| Pregnancy, puerperium and perinatal conditions | ||||||||||||||||
| Abortion missed | 0/98 (0%) | 0/92 (0%) | 1/186 (0.5%) | 0/186 (0%) | 0/244 (0%) | 0/22 (0%) | 0/17 (0%) | 0/22 (0%) | ||||||||
| Abortion threatened | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 0/22 (0%) | 1/17 (5.9%) | 0/22 (0%) | ||||||||
| Psychiatric disorders | ||||||||||||||||
| Mental disorder | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 1/244 (0.4%) | 0/22 (0%) | 0/17 (0%) | 0/22 (0%) | ||||||||
| Suicidal ideation | 1/98 (1%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 0/22 (0%) | 0/17 (0%) | 0/22 (0%) | ||||||||
| Suicide attempt | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 1/244 (0.4%) | 0/22 (0%) | 0/17 (0%) | 0/22 (0%) | ||||||||
| Renal and urinary disorders | ||||||||||||||||
| Cystitis noninfective | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 1/186 (0.5%) | 0/244 (0%) | 0/22 (0%) | 0/17 (0%) | 0/22 (0%) | ||||||||
| Renal failure acute | 0/98 (0%) | 0/92 (0%) | 1/186 (0.5%) | 0/186 (0%) | 0/244 (0%) | 0/22 (0%) | 0/17 (0%) | 0/22 (0%) | ||||||||
| Renal failure chronic | 0/98 (0%) | 0/92 (0%) | 1/186 (0.5%) | 0/186 (0%) | 0/244 (0%) | 0/22 (0%) | 0/17 (0%) | 0/22 (0%) | ||||||||
| Nephrolithiasis | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 0/22 (0%) | 0/17 (0%) | 1/22 (4.5%) | ||||||||
| Reproductive system and breast disorders | ||||||||||||||||
| Menorrhagia | 0/98 (0%) | 0/92 (0%) | 1/186 (0.5%) | 0/186 (0%) | 1/244 (0.4%) | 0/22 (0%) | 0/17 (0%) | 0/22 (0%) | ||||||||
| Ovarian cyst | 0/98 (0%) | 0/92 (0%) | 1/186 (0.5%) | 0/186 (0%) | 1/244 (0.4%) | 0/22 (0%) | 0/17 (0%) | 0/22 (0%) | ||||||||
| Ovarian cyst ruptured | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 1/186 (0.5%) | 0/244 (0%) | 0/22 (0%) | 0/17 (0%) | 0/22 (0%) | ||||||||
| Respiratory, thoracic and mediastinal disorders | ||||||||||||||||
| Asthma | 1/98 (1%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 0/22 (0%) | 0/17 (0%) | 1/22 (4.5%) | ||||||||
| Bronchitis chronic | 0/98 (0%) | 0/92 (0%) | 1/186 (0.5%) | 0/186 (0%) | 0/244 (0%) | 0/22 (0%) | 0/17 (0%) | 0/22 (0%) | ||||||||
| Pneumothorax | 0/98 (0%) | 0/92 (0%) | 1/186 (0.5%) | 0/186 (0%) | 0/244 (0%) | 0/22 (0%) | 0/17 (0%) | 0/22 (0%) | ||||||||
| Respiratory failure | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 1/244 (0.4%) | 0/22 (0%) | 0/17 (0%) | 0/22 (0%) | ||||||||
| Skin and subcutaneous tissue disorders | ||||||||||||||||
| Pain of skin | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 1/244 (0.4%) | 0/22 (0%) | 0/17 (0%) | 0/22 (0%) | ||||||||
| Acarodermatitis | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 0/22 (0%) | 0/17 (0%) | 1/22 (4.5%) | ||||||||
| Surgical and medical procedures | ||||||||||||||||
| Abortion induced | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 1/186 (0.5%) | 0/244 (0%) | 0/22 (0%) | 0/17 (0%) | 0/22 (0%) | ||||||||
| Vascular disorders | ||||||||||||||||
| Varicose vein | 0/98 (0%) | 1/92 (1.1%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 0/22 (0%) | 0/17 (0%) | 0/22 (0%) | ||||||||
| Venous Stasis | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 1/186 (0.5%) | 0/244 (0%) | 0/22 (0%) | 0/17 (0%) | 0/22 (0%) | ||||||||
Other (Not Including Serious) Adverse Events |
||||||||||||||||
| Cladribine Low/Placebo (LLPP) | Cladribine High Dose/Placebo (HLPP) | Cladribine Low/Low Dose (LLLL) | Cladribine High/Low Dose (HLLL) | Placebo/Cladribine Low Dose (PPLL) | Placebo/No Treatment | Cladribine 3.5 mg/kg/No Treatment | Cladribine 5.25 mg/kg/No Treatment | |||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 73/98 (74.5%) | 69/92 (75%) | 143/186 (76.9%) | 146/186 (78.5%) | 192/244 (78.7%) | 16/22 (72.7%) | 13/17 (76.5%) | 18/22 (81.8%) | ||||||||
| Blood and lymphatic system disorders | ||||||||||||||||
| Lymphopenia | 9/98 (9.2%) | 7/92 (7.6%) | 68/186 (36.6%) | 75/186 (40.3%) | 69/244 (28.3%) | 2/22 (9.1%) | 2/17 (11.8%) | 5/22 (22.7%) | ||||||||
| Leukopenia | 1/98 (1%) | 2/92 (2.2%) | 19/186 (10.2%) | 20/186 (10.8%) | 12/244 (4.9%) | 2/22 (9.1%) | 0/17 (0%) | 3/22 (13.6%) | ||||||||
| Neutropenia | 2/98 (2%) | 2/92 (2.2%) | 7/186 (3.8%) | 10/186 (5.4%) | 7/244 (2.9%) | 1/22 (4.5%) | 1/5 (20%) | 5/22 (22.7%) | ||||||||
| Thrombocytopenia | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 2/22 (9.1%) | 0/17 (0%) | 1/22 (4.5%) | ||||||||
| Anaemia of pregnancy | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 0/22 (0%) | 1/17 (5.9%) | 0/22 (0%) | ||||||||
| Iron deficiency anaemia | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 0/22 (0%) | 1/17 (5.9%) | 0/22 (0%) | ||||||||
| Anaemia | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 1/22 (4.5%) | 0/17 (0%) | 0/22 (0%) | ||||||||
| Anisocytosis | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 0/22 (0%) | 0/17 (0%) | 1/22 (4.5%) | ||||||||
| Eosinophil Count Decreased | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 0/22 (0%) | 0/17 (0%) | 1/22 (4.5%) | ||||||||
| Eosinophil Count Increased | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 0/22 (0%) | 0/17 (0%) | 1/22 (4.5%) | ||||||||
| Eosinophilia | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 1/22 (4.5%) | 0/17 (0%) | 1/22 (4.5%) | ||||||||
| Leukocytosis | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 1/22 (4.5%) | 0/17 (0%) | 0/22 (0%) | ||||||||
| Lymphocytosis | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 0/22 (0%) | 0/17 (0%) | 1/22 (4.5%) | ||||||||
| Macrocytosis | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 0/22 (0%) | 0/17 (0%) | 1/22 (4.5%) | ||||||||
| Poikilocytosis | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 0/22 (0%) | 0/17 (0%) | 1/22 (4.5%) | ||||||||
| Red Blood Cell Abnormality | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 0/22 (0%) | 0/17 (0%) | 1/22 (4.5%) | ||||||||
| Congenital, familial and genetic disorders | ||||||||||||||||
| Hyperbilirubinaemia | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 1/22 (4.5%) | 0/17 (0%) | 0/22 (0%) | ||||||||
| Ear and labyrinth disorders | ||||||||||||||||
| Vertigo | 5/98 (5.1%) | 1/92 (1.1%) | 6/186 (3.2%) | 5/186 (2.7%) | 5/244 (2%) | 0/22 (0%) | 0/17 (0%) | 0/22 (0%) | ||||||||
| Ear pain | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 0/22 (0%) | 0/17 (0%) | 2/22 (9.1%) | ||||||||
| Eye disorders | ||||||||||||||||
| Eye irritation | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 0/22 (0%) | 1/17 (5.9%) | 0/22 (0%) | ||||||||
| Eye pruritus | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 0/22 (0%) | 1/17 (5.9%) | 0/22 (0%) | ||||||||
| Retinal Tear | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 0/22 (0%) | 0/17 (0%) | 1/22 (4.5%) | ||||||||
| Gastrointestinal disorders | ||||||||||||||||
| Diarrhoea | 7/98 (7.1%) | 6/92 (6.5%) | 6/186 (3.2%) | 9/186 (4.8%) | 14/244 (5.7%) | 1/22 (4.5%) | 0/17 (0%) | 1/22 (4.5%) | ||||||||
| Nausea | 8/98 (8.2%) | 4/92 (4.3%) | 11/186 (5.9%) | 7/186 (3.8%) | 10/244 (4.1%) | 0/22 (0%) | 0/17 (0%) | 2/22 (9.1%) | ||||||||
| Toothache | 4/98 (4.1%) | 6/92 (6.5%) | 5/186 (2.7%) | 3/186 (1.6%) | 4/244 (1.6%) | 0/22 (0%) | 0/17 (0%) | 3/22 (13.6%) | ||||||||
| Vomiting | 1/98 (1%) | 5/92 (5.4%) | 5/186 (2.7%) | 0/186 (0%) | 4/244 (1.6%) | 0/22 (0%) | 0/17 (0%) | 1/22 (4.5%) | ||||||||
| Tooth disorder | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 1/22 (4.5%) | 1/17 (5.9%) | 0/22 (0%) | ||||||||
| Faecal incontinence | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 0/22 (0%) | 1/17 (5.9%) | 0/22 (0%) | ||||||||
| Gastrooesophageal reflux disease | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 0/22 (0%) | 1/17 (5.9%) | 0/22 (0%) | ||||||||
| Abdominal Pain Lower | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 1/22 (4.5%) | 0/17 (0%) | 1/22 (4.5%) | ||||||||
| Aphthous Stomatitis | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 0/22 (0%) | 0/17 (0%) | 1/22 (4.5%) | ||||||||
| Gastroenteritis | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 0/22 (0%) | 0/17 (0%) | 1/22 (4.5%) | ||||||||
| Gingivitis | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 0/22 (0%) | 0/17 (0%) | 1/22 (4.5%) | ||||||||
| Mouth Ulceration | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 0/22 (0%) | 0/17 (0%) | 1/22 (4.5%) | ||||||||
| Oesophagitis | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 0/22 (0%) | 0/17 (0%) | 1/22 (4.5%) | ||||||||
| Oral Candidiasis | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 0/22 (0%) | 0/17 (0%) | 1/22 (4.5%) | ||||||||
| General disorders | ||||||||||||||||
| Fatigue | 5/98 (5.1%) | 5/92 (5.4%) | 8/186 (4.3%) | 10/186 (5.4%) | 12/244 (4.9%) | 1/22 (4.5%) | 2/17 (11.8%) | 1/22 (4.5%) | ||||||||
| Influenza like illness | 5/98 (5.1%) | 2/92 (2.2%) | 14/186 (7.5%) | 9/186 (4.8%) | 10/244 (4.1%) | 1/22 (4.5%) | 2/17 (11.8%) | 2/22 (9.1%) | ||||||||
| Asthenia | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 2/22 (9.1%) | 0/17 (0%) | 2/22 (9.1%) | ||||||||
| Hyperthermia | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 0/22 (0%) | 2/17 (11.8%) | 0/22 (0%) | ||||||||
| Chest Pain | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 1/22 (4.5%) | 0/17 (0%) | 1/22 (4.5%) | ||||||||
| Hemicephalalgia | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 0/22 (0%) | 0/17 (0%) | 1/22 (4.5%) | ||||||||
| Pyrexia | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 1/22 (4.5%) | 0/17 (0%) | 0/22 (0%) | ||||||||
| Immune system disorders | ||||||||||||||||
| Hypersensitivity | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 0/22 (0%) | 1/17 (5.9%) | 0/22 (0%) | ||||||||
| Lower Respiratory Tract Infection | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 0/22 (0%) | 0/17 (0%) | 1/22 (4.5%) | ||||||||
| Infections and infestations | ||||||||||||||||
| Nasopharyngitis | 19/98 (19.4%) | 15/92 (16.3%) | 22/186 (11.8%) | 28/186 (15.1%) | 45/244 (18.4%) | 1/22 (4.5%) | 0/17 (0%) | 6/22 (27.3%) | ||||||||
| Influenza | 11/98 (11.2%) | 10/92 (10.9%) | 15/186 (8.1%) | 23/186 (12.4%) | 17/244 (7%) | 4/22 (18.2%) | 2/17 (11.8%) | 2/22 (9.1%) | ||||||||
| Upper respiratory tract infection | 8/98 (8.2%) | 9/92 (9.8%) | 17/186 (9.1%) | 20/186 (10.8%) | 19/244 (7.8%) | 1/22 (4.5%) | 1/17 (5.9%) | 2/22 (9.1%) | ||||||||
| Urinary tract infection | 6/98 (6.1%) | 4/92 (4.3%) | 17/186 (9.1%) | 16/186 (8.6%) | 16/244 (6.6%) | 0/22 (0%) | 0/17 (0%) | 0/22 (0%) | ||||||||
| Bronchitis | 6/98 (6.1%) | 7/92 (7.6%) | 1/186 (0.5%) | 12/186 (6.5%) | 17/244 (7%) | 0/22 (0%) | 0/17 (0%) | 1/22 (4.5%) | ||||||||
| Respiratory tract infection viral | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 2/22 (9.1%) | 1/17 (5.9%) | 0/22 (0%) | ||||||||
| Pneumonia | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 0/22 (0%) | 0/17 (0%) | 2/22 (9.1%) | ||||||||
| Sinusitis | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 0/22 (0%) | 1/17 (5.9%) | 1/22 (4.5%) | ||||||||
| Viral infection | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 1/22 (4.5%) | 1/17 (5.9%) | 0/22 (0%) | ||||||||
| Viral upper respiratory tract infection | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 1/22 (4.5%) | 1/17 (5.9%) | 0/22 (0%) | ||||||||
| Erythema infectiosum | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 0/22 (0%) | 1/17 (5.9%) | 0/22 (0%) | ||||||||
| Herpes zoster | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 0/22 (0%) | 1/17 (5.9%) | 0/22 (0%) | ||||||||
| Infected insect bite | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 0/22 (0%) | 1/17 (5.9%) | 0/22 (0%) | ||||||||
| Injection site abscess | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 0/22 (0%) | 1/17 (5.9%) | 0/22 (0%) | ||||||||
| Skin bacterial infection | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 0/22 (0%) | 1/17 (5.9%) | 0/22 (0%) | ||||||||
| Abscess Limb | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 0/22 (0%) | 0/17 (0%) | 1/22 (4.5%) | ||||||||
| Acute Tonsillitis | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 1/22 (4.5%) | 0/17 (0%) | 0/22 (0%) | ||||||||
| Bundle Branch Block Left | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 1/22 (4.5%) | 0/17 (0%) | 0/22 (0%) | ||||||||
| Hordeolum | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 0/22 (0%) | 0/17 (0%) | 1/22 (4.5%) | ||||||||
| Oral Herpes | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 0/22 (0%) | 0/17 (0%) | 1/22 (4.5%) | ||||||||
| Paronychia | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 0/22 (0%) | 0/17 (0%) | 1/22 (4.5%) | ||||||||
| Respiratory Tract Infection | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 1/22 (4.5%) | 0/17 (0%) | 0/22 (0%) | ||||||||
| Tooth Abscess | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 0/22 (0%) | 0/17 (0%) | 1/22 (4.5%) | ||||||||
| Tooth Infection | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 1/22 (4.5%) | 0/17 (0%) | 0/22 (0%) | ||||||||
| Urinary Tract Infection Bacterial | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 1/22 (4.5%) | 0/17 (0%) | 0/22 (0%) | ||||||||
| Injury, poisoning and procedural complications | ||||||||||||||||
| Contusion | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 0/22 (0%) | 1/17 (5.9%) | 1/22 (4.5%) | ||||||||
| Joint sprain | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 1/22 (4.5%) | 1/17 (5.9%) | 0/22 (0%) | ||||||||
| Fall | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 0/22 (0%) | 0/17 (0%) | 1/22 (4.5%) | ||||||||
| Foot Fracture | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 0/22 (0%) | 0/17 (0%) | 1/22 (4.5%) | ||||||||
| Injection Site Erythema | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 0/22 (0%) | 0/17 (0%) | 1/22 (4.5%) | ||||||||
| Injection Site Extravasation | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 1/22 (4.5%) | 0/17 (0%) | 0/22 (0%) | ||||||||
| Injection Site Inflammation | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 1/22 (4.5%) | 0/17 (0%) | 0/22 (0%) | ||||||||
| Injection Site Pain | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 1/22 (4.5%) | 0/17 (0%) | 0/22 (0%) | ||||||||
| Tendonitis | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 1/22 (4.5%) | 0/17 (0%) | 0/22 (0%) | ||||||||
| Investigations | ||||||||||||||||
| White blood cell count decreased | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 0/22 (0%) | 1/17 (5.9%) | 2/22 (9.1%) | ||||||||
| Alanine aminotransferase increased | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 2/22 (9.1%) | 0/17 (0%) | 0/22 (0%) | ||||||||
| Blood creatine phosphokinase increased | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 0/22 (0%) | 0/17 (0%) | 2/22 (9.1%) | ||||||||
| Red blood cell burr cells present | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 0/22 (0%) | 0/17 (0%) | 2/22 (9.1%) | ||||||||
| Liver function test abnormal | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 0/22 (0%) | 1/17 (5.9%) | 0/22 (0%) | ||||||||
| Weight decreased | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 0/22 (0%) | 1/17 (5.9%) | 0/22 (0%) | ||||||||
| Aspartate Aminotransferase Increased | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 1/22 (4.5%) | 0/17 (0%) | 0/22 (0%) | ||||||||
| Blood Potassium Decreased | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 0/22 (0%) | 0/17 (0%) | 1/22 (4.5%) | ||||||||
| Blood Thyroid Stimulating Hormone Increased | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 0/22 (0%) | 0/17 (0%) | 1/22 (4.5%) | ||||||||
| Blood Urea Increased | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 1/22 (4.5%) | 0/17 (0%) | 0/22 (0%) | ||||||||
| Blood Urine Present | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 0/22 (0%) | 0/17 (0%) | 1/22 (4.5%) | ||||||||
| Haemoglobin Decreased | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 1/22 (4.5%) | 0/17 (0%) | 0/22 (0%) | ||||||||
| Local Swelling | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 0/22 (0%) | 0/17 (0%) | 1/22 (4.5%) | ||||||||
| Monocyte Count Decreased | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 1/22 (4.5%) | 0/17 (0%) | 1/22 (4.5%) | ||||||||
| Red Blood Cell Morphology Abnormal | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 0/22 (0%) | 0/17 (0%) | 1/22 (4.5%) | ||||||||
| Smear Cervix Abnormal | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 1/22 (4.5%) | 0/17 (0%) | 0/22 (0%) | ||||||||
| Thyroid Function Test Abnormal | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 0/22 (0%) | 0/17 (0%) | 1/22 (4.5%) | ||||||||
| Weight Increased | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 1/22 (4.5%) | 0/17 (0%) | 0/22 (0%) | ||||||||
| White Blood Cell Count Increased | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 0/22 (0%) | 0/17 (0%) | 1/22 (4.5%) | ||||||||
| Metabolism and nutrition disorders | ||||||||||||||||
| Haemorrhoids | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 1/22 (4.5%) | 0/17 (0%) | 0/22 (0%) | ||||||||
| Musculoskeletal and connective tissue disorders | ||||||||||||||||
| Back pain | 9/98 (9.2%) | 9/92 (9.8%) | 16/186 (8.6%) | 18/186 (9.7%) | 28/244 (11.5%) | 1/22 (4.5%) | 4/17 (23.5%) | 2/22 (9.1%) | ||||||||
| Pain in extremity | 8/98 (8.2%) | 6/92 (6.5%) | 10/186 (5.4%) | 10/186 (5.4%) | 11/244 (4.5%) | 2/22 (9.1%) | 1/17 (5.9%) | 1/22 (4.5%) | ||||||||
| Arthralgia | 5/98 (5.1%) | 4/92 (4.3%) | 5/186 (2.7%) | 8/186 (4.3%) | 13/244 (5.3%) | 0/22 (0%) | 1/17 (5.9%) | 3/22 (13.6%) | ||||||||
| Musculoskeletal pain | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 2/22 (9.1%) | 0/17 (0%) | 1/22 (4.5%) | ||||||||
| Joint swelling | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 0/22 (0%) | 1/17 (5.9%) | 0/22 (0%) | ||||||||
| Sensation of heaviness | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 0/22 (0%) | 1/17 (5.9%) | 0/22 (0%) | ||||||||
| Arthritis | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 0/22 (0%) | 0/17 (0%) | 1/22 (4.5%) | ||||||||
| Cervical Dysplasia | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 1/22 (4.5%) | 0/17 (0%) | 0/22 (0%) | ||||||||
| Muscle Spasms | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 0/22 (0%) | 0/17 (0%) | 1/22 (4.5%) | ||||||||
| Musculoskeletal Disorder | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 0/22 (0%) | 0/17 (0%) | 1/22 (4.5%) | ||||||||
| Neck Pain | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 0/22 (0%) | 0/17 (0%) | 1/22 (4.5%) | ||||||||
| Osteoarthritis | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 0/22 (0%) | 0/17 (0%) | 1/22 (4.5%) | ||||||||
| Patellofemoral Pain Syndrome | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 0/22 (0%) | 0/17 (0%) | 1/22 (4.5%) | ||||||||
| Tenosynovitis | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 0/22 (0%) | 0/17 (0%) | 1/22 (4.5%) | ||||||||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||||||||
| Bone Cyst | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 1/22 (4.5%) | 0/17 (0%) | 0/22 (0%) | ||||||||
| Pancreatic Cyst | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 1/22 (4.5%) | 0/17 (0%) | 0/22 (0%) | ||||||||
| Nervous system disorders | ||||||||||||||||
| Headache | 20/98 (20.4%) | 16/92 (17.4%) | 21/186 (11.3%) | 25/186 (13.4%) | 38/244 (15.6%) | 3/22 (13.6%) | 1/17 (5.9%) | 4/22 (18.2%) | ||||||||
| Dizziness | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 1/22 (4.5%) | 1/17 (5.9%) | 2/22 (9.1%) | ||||||||
| Carpal tunnel syndrome | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 0/22 (0%) | 1/17 (5.9%) | 0/22 (0%) | ||||||||
| Restless legs syndrome | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 0/22 (0%) | 1/17 (5.9%) | 0/22 (0%) | ||||||||
| Syncope | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 0/22 (0%) | 1/17 (5.9%) | 0/22 (0%) | ||||||||
| Facial Pain | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 0/22 (0%) | 0/17 (0%) | 1/22 (4.5%) | ||||||||
| Neuralgia | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 0/22 (0%) | 0/17 (0%) | 1/22 (4.5%) | ||||||||
| Oedema Peripheral | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 1/22 (4.5%) | 0/17 (0%) | 0/22 (0%) | ||||||||
| Paraesthesia | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 0/22 (0%) | 0/17 (0%) | 1/22 (4.5%) | ||||||||
| Tension Headache | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 0/22 (0%) | 0/17 (0%) | 1/22 (4.5%) | ||||||||
| Tremor | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 1/22 (4.5%) | 0/17 (0%) | 0/22 (0%) | ||||||||
| Vertigo Positional | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 0/22 (0%) | 0/17 (0%) | 1/22 (4.5%) | ||||||||
| Pregnancy, puerperium and perinatal conditions | ||||||||||||||||
| Pregnancy | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 0/22 (0%) | 1/17 (5.9%) | 0/22 (0%) | ||||||||
| Psychiatric disorders | ||||||||||||||||
| Depression | 6/98 (6.1%) | 1/92 (1.1%) | 6/186 (3.2%) | 5/186 (2.7%) | 9/244 (3.7%) | 1/22 (4.5%) | 1/17 (5.9%) | 1/22 (4.5%) | ||||||||
| Anxiety | 5/98 (5.1%) | 2/92 (2.2%) | 4/186 (2.2%) | 5/186 (2.7%) | 7/244 (2.9%) | 0/22 (0%) | 1/17 (5.9%) | 2/22 (9.1%) | ||||||||
| Depressed mood | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 0/22 (0%) | 1/17 (5.9%) | 0/22 (0%) | ||||||||
| Excoriation | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 0/22 (0%) | 0/17 (0%) | 1/22 (4.5%) | ||||||||
| Renal and urinary disorders | ||||||||||||||||
| Dysuria | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 1/22 (4.5%) | 0/17 (0%) | 0/22 (0%) | ||||||||
| Protein Urine Present | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 0/22 (0%) | 0/17 (0%) | 1/22 (4.5%) | ||||||||
| Proteinuria | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 0/22 (0%) | 0/17 (0%) | 1/22 (4.5%) | ||||||||
| Reproductive system and breast disorders | ||||||||||||||||
| Breast Discharge | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 0/22 (0%) | 0/17 (0%) | 1/22 (4.5%) | ||||||||
| Respiratory, thoracic and mediastinal disorders | ||||||||||||||||
| Pharyngolaryngeal pain | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 0/22 (0%) | 1/17 (5.9%) | 2/22 (9.1%) | ||||||||
| Cough | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 0/22 (0%) | 1/17 (5.9%) | 1/22 (4.5%) | ||||||||
| Atelectasis | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 1/22 (4.5%) | 0/17 (0%) | 0/22 (0%) | ||||||||
| Breath Sounds Abnormal | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 0/22 (0%) | 0/17 (0%) | 1/22 (4.5%) | ||||||||
| Chronic Obstructive Pulmonary Disease | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 1/22 (4.5%) | 0/17 (0%) | 0/22 (0%) | ||||||||
| Pleural Effusion | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 1/22 (4.5%) | 0/17 (0%) | 0/22 (0%) | ||||||||
| Productive Cough | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 0/22 (0%) | 0/17 (0%) | 1/22 (4.5%) | ||||||||
| Rhinorrhoea | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 0/22 (0%) | 0/17 (0%) | 1/22 (4.5%) | ||||||||
| Tonsillitis | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 1/22 (4.5%) | 0/17 (0%) | 0/22 (0%) | ||||||||
| Skin and subcutaneous tissue disorders | ||||||||||||||||
| Eczema | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 1/22 (4.5%) | 0/17 (0%) | 1/22 (4.5%) | ||||||||
| Furuncle | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 1/22 (4.5%) | 0/17 (0%) | 0/22 (0%) | ||||||||
| Ingrowing Nail | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 0/22 (0%) | 0/17 (0%) | 1/22 (4.5%) | ||||||||
| Rash | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 0/22 (0%) | 0/17 (0%) | 1/22 (4.5%) | ||||||||
| Vascular disorders | ||||||||||||||||
| Hypertension | 4/98 (4.1%) | 5/92 (5.4%) | 5/186 (2.7%) | 2/186 (1.1%) | 7/244 (2.9%) | 1/22 (4.5%) | 1/17 (5.9%) | 0/22 (0%) | ||||||||
| Hot Flush | 0/98 (0%) | 0/92 (0%) | 0/186 (0%) | 0/186 (0%) | 0/244 (0%) | 1/22 (4.5%) | 0/17 (0%) | 1/22 (4.5%) | ||||||||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Results Point of Contact
| Name/Title | Communication Center |
|---|---|
| Organization | Merck KGaA, Darmstadt, Germany |
| Phone | +49-6151-72-5200 |
| service@emdgroup.com |
Responsible Party:
EMD Serono Research & Development Institute, Inc.
ClinicalTrials.gov Identifier:
NCT00641537
Other Study ID Numbers:
- 27820
- 2007-000381-20
First Posted:
Mar 24, 2008
Last Update Posted:
Dec 7, 2020
Last Verified:
Oct 1, 2020