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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00641537




Registration number
NCT00641537
Ethics application status
Date submitted
13/03/2008
Date registered
24/03/2008
Date last updated
7/02/2014

Titles & IDs
Public title
CLARITY Extension Study
Scientific 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)
Secondary ID [1] 0 0
27820
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Relapsing-Remitting Multiple Sclerosis 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Cladribine
Treatment: Drugs - Placebo
Treatment: Drugs - Cladribine
Treatment: Drugs - Cladribine
Treatment: Drugs - Placebo

Placebo Comparator: Cladribine Low/Placebo (LLPP) -

Placebo Comparator: Cladribine High Dose/Placebo (HLPP) -

Experimental: Cladribine Low/Low Dose (LLLL) -

Experimental: Cladribine High/Low Dose (HLLL) -

Experimental: Placebo/Cladribine Low Dose (PPLL) -


Treatment: Drugs: 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.

Treatment: Drugs: 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.

Treatment: Drugs: 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.

Treatment: Drugs: 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.

Treatment: Drugs: 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.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Participants With at Least 1 Common Terminology Criteria for Adverse Events (CTCAE) Grade 3 or 4 Lymphocyte Toxicity - Lymphocyte toxicity was assessed using Common Terminology Criteria for Adverse Events (CTCAE). CTCAE grade for absolute lymphocyte counts included: Grade 1 = less than lower limit of normal; Grade 2 = less than 800 per cubic millimeter (/mm^3); Grade 3 = less than 500/mm^3; Grade 4 = less than 200/mm^3.
Timepoint [1] 0 0
Baseline up to Week 120
Primary outcome [2] 0 0
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) - 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.
Timepoint [2] 0 0
Baseline up to week 120
Primary outcome [3] 0 0
Median Time to Recovery From Grade 3 or 4 Lymphocyte Toxicity - Lymphocyte toxicity was assessed using Common Terminology Criteria for Adverse Events (CTCAE). CTCAE grade for absolute lymphocyte counts included: Grade 1 = less than lower limit of normal; Grade 2 = less than 800 per cubic millimeter (/mm^3); Grade 3 = less than 500/mm^3; Grade 4 = less than 200/mm^3. Recovery from a Grade 3 or 4 toxicity is defined as a return to a Grade 0 or 1 during the CLARITY Extension Study.
Timepoint [3] 0 0
Baseline up to Week 120
Primary outcome [4] 0 0
Number of Participants Who Developed Herpes Zoster Infections and Malignancies - Herpes zoster infection is defined as having at least one adverse event coded to medical dictionary for regulatory activities (MedDRA) preferred terms herpes zoster, herpes zoster iridocyclitis, herpes zoster ophthalmic, herpes zoster multi-dermatomal, herpes zoster infection neurological, herpes zoster oticus. Malignancy is defined as having at least one adverse event coded to MedDRA preferred terms under the pre_specified grouping Malignant and unspecified tumors.
Timepoint [4] 0 0
Baseline up to Week 120
Secondary outcome [1] 0 0
Annualized Qualifying Relapse Rate - A qualifying relapse was defined as an increase of 2 points in at least one functional system of the expanded disability status scale (EDSS) or an increase of 1 point in at least two functional systems (excluding changes in bowel or bladder function or cognition) in the absence of fever, lasting for at least 24 hours and to have been preceded by at least 30 days of clinical stability or improvement. Expanded disability status scale (EDSS) assesses disability in 8 functional systems. An overall score ranging from 0 (normal) to 10 (death due to multiple sclerosis [MS]) was calculated. The annualized relapse rate for each treatment group was calculated as the total number of confirmed relapses divided by the total number of days on study multiplied by 365.25.
Timepoint [1] 0 0
Week 96
Secondary outcome [2] 0 0
Mean Number of Combined Unique (CU) Lesions - Mean Number of CU lesions were measured by using magnetic resonance imaging (MRI) scans.
Timepoint [2] 0 0
Week 96
Secondary outcome [3] 0 0
Time to Disability Progression (Confirmed After 3 Months) - Time to disability progression was defined as the time to a sustained increase in EDSS score of at least 1 point if baseline EDSS score between 0.5 and 4.5 inclusively, or at least 1.5 points if the baseline EDSS score was 0, or at least 0.5 point if the baseline EDSS score was at least 5, over a period of at least three months. Expanded disability status scale (EDSS) assesses disability in 8 functional systems. An overall score ranging from 0 (normal) to 10 (death due to MS) was calculated. As few participants have reached EDSS progression, fourth Percentile of time to sustained increase in EDSS score was reported using Kaplan-Meier survival curve.
Timepoint [3] 0 0
Baseline up to Week 96

Eligibility
Key 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
Minimum age
18 Years
Maximum age
65 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Subjects who were not enrolled in Trial 25643

- Subject 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Research Site - Camperdown
Recruitment hospital [2] 0 0
Research Site - Melbourne
Recruitment hospital [3] 0 0
Research Site - Victoria
Recruitment postcode(s) [1] 0 0
- Camperdown
Recruitment postcode(s) [2] 0 0
- Melbourne
Recruitment postcode(s) [3] 0 0
- Victoria
Recruitment outside Australia
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United States of America
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Colorado
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Georgia
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Illinois
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Maryland
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Michigan
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Nevada
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North Carolina
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Ohio
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Oklahoma
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Oregon
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Washington
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West Virginia
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Austria
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Linz
Country [15] 0 0
Belgium
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Diepenbeek
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Belgium
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Esneux
Country [17] 0 0
Brazil
State/province [17] 0 0
Recife
Country [18] 0 0
Bulgaria
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Pleven
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Bulgaria
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Plovdiv
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Bulgaria
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Ruse
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Bulgaria
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Shuman
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Bulgaria
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Sofia
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Bulgaria
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Varna
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Bulgaria
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Zagora
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Canada
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Burnaby
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Canada
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Greenfield Park
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Canada
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Ottawa
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Canada
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Quebec
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Croatia
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Karlovac
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Sisak
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Split
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Czech Republic
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Hradec Králové
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Olomouc
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Praha
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Copenhagen
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Tallinn
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Tartu
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Oulu
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Turku
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Clermont-Ferrand
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Germany
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Bochum
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Frankfurt
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Germany
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Giessen
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Germany
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Hannover
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Germany
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Regensburg
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Germany
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Rostock
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Greece
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Athens
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Bari
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Cagliari
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Italy
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Catania
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Firenze
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Milano
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Napoli
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Beyrouth
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Lithuania
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Kaunas
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Morocco
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Casablanca
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Morocco
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Fes
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Morocco
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Rabat
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Netherlands
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Sittard- Geleen
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Krakow
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Poznan
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Portugal
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Lisboa
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Russian Federation
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Ekaterinburg
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Kaluga
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Kazan
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Kemerovo
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Kursk
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Moscow
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Russian Federation
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Nizhny Novgorod
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Russian Federation
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Novosibirsk
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Russian Federation
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Rostov-on-Don
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Russian Federation
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Samara
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Russian Federation
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Saratov
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Russian Federation
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St-Petersburg
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Russian Federation
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Tomsk
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Russian Federation
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Vladimir
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Russian Federation
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Yaroslavl
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Saudi Arabia
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Riyadh
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Serbia
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Belgrade
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Switzerland
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Lausanne
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Switzerland
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St. Gallen
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Tunisia
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Monastir
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Tunisia
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Sfax
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Tunisia
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Tunis
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Turkey
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Bursa
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Turkey
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Izmir
Country [101] 0 0
Ukraine
State/province [101] 0 0
Kharkov
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Ukraine
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Kiev
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Ukraine
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Lviv
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Ukraine
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Vinnitsa
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United Kingdom
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Hull
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United Kingdom
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London
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United Kingdom
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Nottingham
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United Kingdom
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Oxford
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United Kingdom
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Sheffield
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United Kingdom
State/province [110] 0 0
Stoke-on-Trent

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
EMD Serono
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this extension trial is 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.
Trial website
https://clinicaltrials.gov/show/NCT00641537
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications