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Trial record 16 of 33 for:    "multiple sclerosis" | "vitamin d"

A Multicentre Study of the Efficacy and Safety of Supplementary Treatment With Cholecalciferol in Patients With Relapsing Multiple Sclerosis Treated With Subcutaneous Interferon Beta-1a 44 µg 3 Times Weekly (CHOLINE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01198132
Recruitment Status : Completed
First Posted : September 9, 2010
Results First Posted : December 14, 2017
Last Update Posted : December 14, 2017
Sponsor:
Collaborator:
Merck Serono S.A.S, France
Information provided by (Responsible Party):
Merck KGaA, Darmstadt, Germany

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Supportive Care
Condition Multiple Sclerosis
Interventions Dietary Supplement: Cholecalciferol (Vitamin D3)
Dietary Supplement: Placebo
Drug: Rebif
Enrollment 129
Recruitment Details  
Pre-assignment Details A total of 129 subjects were randomized. Out of which 126 subjects treated in the study and 90 subjects completed the study.
Arm/Group Title Cholecalciferol Placebo
Hide Arm/Group Description Subjects received Cholecalciferol 100,000 IU one dose fortnightly (equivalent to a daily dose of approximately 7142 IU) for 96 weeks treatment period along with subcutaneous Rebif 44 mcg 3 times a week. Subjects received matching placebo to Cholecalciferol once every two weeks orally along with subcutaneous injection of Rebif 44 mcg 3 times weekly.
Period Title: Overall Study
Started 63 66
Completed 45 45
Not Completed 18 21
Reason Not Completed
Withdrawal by Subject             4             5
Physician Decision             5             4
Other Unspecified             3             6
Lack of Efficacy             2             3
Sign/symptoms of underlying disease             2             1
Abnormal/clinically significant biologic             1             1
Adverse Event             0             1
Protocol Violation             1             0
Arm/Group Title Cholecalciferol Placebo Total
Hide Arm/Group Description Subjects received Cholecalciferol 100,000 IU one dose fortnightly (equivalent to a daily dose of approximately 7142 IU) for 96 weeks treatment period along with subcutaneous Rebif 44 mcg 3 times a week. Subjects received matching placebo to Cholecalciferol once every two weeks orally along with subcutaneous injection of Rebif 44 mcg 3 times weekly. Total of all reporting groups
Overall Number of Baseline Participants 63 66 129
Hide Baseline Analysis Population Description
Intent-to-Treat (ITT) set included all randomized subjects.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 63 participants 66 participants 129 participants
38.5  (9.29) 36.9  (8.34) 37.7  (8.81)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 63 participants 66 participants 129 participants
Female
50
  79.4%
39
  59.1%
89
  69.0%
Male
13
  20.6%
27
  40.9%
40
  31.0%
1.Primary Outcome
Title Annualized Relapse Rate
Hide Description The annualized relapse rate was calculated for each treatment group as follows: the number of relapses observed during the study period divided by the time spent in the study (in years).
Time Frame 2 years post treatment (IMP) administration
Hide Outcome Measure Data
Hide Analysis Population Description
ITT set included all randomized subjects.
Arm/Group Title Cholecalciferol Placebo
Hide Arm/Group Description:
Subjects received Cholecalciferol 100,000 IU one dose fortnightly (equivalent to a daily dose of approximately 7142 IU) for 96 weeks treatment period along with subcutaneous Rebif 44 mcg 3 times a week.
Subjects received matching placebo to Cholecalciferol once every two weeks orally along with subcutaneous injection of Rebif 44 mcg 3 times weekly.
Overall Number of Participants Analyzed 63 66
Mean (95% Confidence Interval)
Unit of Measure: Relapse per year
0.45
(0.20 to 0.69)
0.34
(0.22 to 0.46)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cholecalciferol, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3797
Comments [Not Specified]
Method Poisson log-linear model
Comments [Not Specified]
Method of Estimation Estimation Parameter Rate ratio
Estimated Value 0.80
Confidence Interval (2-Sided) 95%
0.48 to 1.32
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Time to First Documented Relapse
Hide Description Time to First Documented Relapse was calculated using Kaplan-Meier survival methods.
Time Frame 2 years post treatment (IMP) administration
Hide Outcome Measure Data
Hide Analysis Population Description
ITT set included all randomized subjects. Here "Number of participant analyzed" signifies those subjects who were evaluable for this outcome measure.
Arm/Group Title Cholecalciferol Rebif +Placebo
Hide Arm/Group Description:
Subjects received Cholecalciferol 100,000 IU one dose fortnightly (equivalent to a daily dose of approximately 7142 IU) for 96 weeks treatment period along with subcutaneous Rebif 44 mcg 3 times a week.
Subjects received matching placebo to Cholecalciferol once every two weeks orally along with subcutaneous injection of Rebif 44 mcg 3 times weekly.
Overall Number of Participants Analyzed 61 65
Median (95% Confidence Interval)
Unit of Measure: weeks
NA [1] 
(NA to NA)
NA [1] 
(60.1 to NA)
[1]
Median and Confidence interval could not be calculated due to a limited number of events .
3.Secondary Outcome
Title Mean Number of Relapses Per Subject
Hide Description Relapse was defined as new, worsening or recurrent neurological symptoms attributed to multiple sclerosis that last for at least 24 hours without fever or infection, or adverse reaction to prescribed medication, preceded by a stable or improving neurological status of at least 30 days. Mean and standard deviation were reported.
Time Frame 2 years post treatment (IMP) administration
Hide Outcome Measure Data
Hide Analysis Population Description
ITT set included all randomized subjects.
Arm/Group Title Cholecalciferol Placebo
Hide Arm/Group Description:
Subjects received Cholecalciferol 100,000 IU one dose fortnightly (equivalent to a daily dose of approximately 7142 IU) for 96 weeks treatment period along with subcutaneous Rebif 44 mcg 3 times a week.
Subjects received matching placebo to Cholecalciferol once every two weeks orally along with subcutaneous injection of Rebif 44 mcg 3 times weekly.
Overall Number of Participants Analyzed 63 66
Mean (Standard Deviation)
Unit of Measure: relapses
0.5  (0.78) 0.5  (0.75)
4.Secondary Outcome
Title Number of Relapse-Free (Documented) Subjects
Hide Description The relapse-free patients after 2 years of treatment was calculated using Cochran-Mantel-Haenszel test using the site as control variable.
Time Frame 2 years post treatment (IMP) administration
Hide Outcome Measure Data
Hide Analysis Population Description
ITT set included all randomized subjects. Here "Number of participants analyzed" signifies those subjects who were evaluable for this outcome measure.
Arm/Group Title Cholecalciferol Placebo
Hide Arm/Group Description:
Subjects received Cholecalciferol 100,000 IU one dose fortnightly (equivalent to a daily dose of approximately 7142 IU) for 96 weeks treatment period along with subcutaneous Rebif 44 mcg 3 times a week.
Subjects received matching placebo to Cholecalciferol once every two weeks orally along with subcutaneous injection of Rebif 44 mcg 3 times weekly.
Overall Number of Participants Analyzed 45 46
Measure Type: Number
Unit of Measure: subjects
35 27
5.Secondary Outcome
Title Cumulative Probability of Progression of Disability (Kaplan-Meier Curves)
Hide Description Disability progression was assessed using Expanded disability status scale (EDSS). EDSS assesses disability in 8 functional systems. An overall score ranging from 0 (normal) to 10 (death due to MS) was calculated. A one-point increase on the EDSS scale was considered as a progression in disability. The time to disability progression was summarized using Kaplan-Meier survival methods. The cumulative probability of confirmed disease progression at each visit was obtained by applying a Kaplan-Meier method to the time to confirmed disease progression.
Time Frame Baseline up to week 96
Hide Outcome Measure Data
Hide Analysis Population Description
ITT set included all randomized subjects. Here "Number of participant analyzed" signifies those subjects who were evaluable for this outcome measure.
Arm/Group Title Cholecalciferol Placebo
Hide Arm/Group Description:
Subjects received Cholecalciferol 100,000 IU one dose fortnightly (equivalent to a daily dose of approximately 7142 IU) for 96 weeks treatment period along with subcutaneous Rebif 44 mcg 3 times a week.
Subjects received matching placebo to Cholecalciferol once every two weeks orally along with subcutaneous injection of Rebif 44 mcg 3 times weekly.
Overall Number of Participants Analyzed 60 65
Measure Type: Number
Unit of Measure: percentage of subjects
12.7 9.1
6.Secondary Outcome
Title Number of New or Extended Lesions by T1- and T2-Weighted Magnetic Resonance Imaging (MRI)
Hide Description [Not Specified]
Time Frame 2 years post treatment (IMP) administration
Hide Outcome Measure Data
Hide Analysis Population Description
ITT set included all randomized subjects. Here "Number of participant analyzed" signifies those subjects who were evaluable for this outcome measure.
Arm/Group Title Cholecalciferol Placebo
Hide Arm/Group Description:
Subjects received Cholecalciferol 100,000 IU one dose fortnightly (equivalent to a daily dose of approximately 7142 IU) for 96 weeks treatment period along with subcutaneous Rebif 44 mcg 3 times a week.
Subjects received matching placebo to Cholecalciferol once every two weeks orally along with subcutaneous injection of Rebif 44 mcg 3 times weekly.
Overall Number of Participants Analyzed 44 41
Mean (Standard Deviation)
Unit of Measure: lesions
T1-weighted MRI 0.4  (0.76) 1.9  (3.76)
T2-weighted MRI 0.5  (0.79) 2.0  (4.71)
7.Secondary Outcome
Title Changes From Baseline in Measured Lesion Load (T2)
Hide Description Baseline defined as last value recorded prior to first intake of study drug.
Time Frame Baseline, Week 96
Hide Outcome Measure Data
Hide Analysis Population Description
ITT set included all randomized subjects. Here “n” signifies those subjects who were evaluable for this outcome measure at the specified time points.
Arm/Group Title Cholecalciferol Placebo
Hide Arm/Group Description:
Subjects received Cholecalciferol 100,000 IU one dose fortnightly (equivalent to a daily dose of approximately 7142 IU) for 96 weeks treatment period along with subcutaneous Rebif 44 mcg 3 times a week.
Subjects received matching placebo to Cholecalciferol once every two weeks orally along with subcutaneous injection of Rebif 44 mcg 3 times weekly.
Overall Number of Participants Analyzed 63 66
Mean (Standard Deviation)
Unit of Measure: cubic millimeter (mm^3)
Baseline (n=49, 43) 5305.4  (10858.86) 3520.1  (4954.44)
Change at Week 96 (n=44, 38) -315.0  (2523.97) 596.3  (2034.80)
8.Secondary Outcome
Title Change From Baseline in Measurement and Evaluation of Cognitive Ability by Paced Auditory Serial Addition Task (PASAT) Total Score At Week 96
Hide Description The Adapted Paced Auditory Serial Addition Task (PASAT) is a measure of cognitive function that specifically assesses auditory information processing speed and flexibility, as well as calculation ability. The total score for PASAT is the total number of correct answers (out of 60, for a total possible score ranging from 0-60 with higher score indicates higher auditory processing speed) for each trial. Change from baseline in PASAT total score at Week 96 was summarized.
Time Frame Baseline, Week 96
Hide Outcome Measure Data
Hide Analysis Population Description
ITT set included all randomized subjects.
Arm/Group Title Cholecalciferol Placebo
Hide Arm/Group Description:
Subjects received Cholecalciferol 100,000 IU one dose fortnightly (equivalent to a daily dose of approximately 7142 IU) for 96 weeks treatment period along with subcutaneous Rebif 44 mcg 3 times a week.
Subjects received matching placebo to Cholecalciferol once every two weeks orally along with sub-cutaneous injection of Rebif 44 mcg 3 times weekly.
Overall Number of Participants Analyzed 63 66
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline 39.9  (14.80) 43.3  (12.49)
Change at Week 96 6.4  (8.49) 6.0  (8.02)
9.Secondary Outcome
Title Change From Baseline in Euro Quality of Life Scale (EuroQol) 5-Dimension-3 Level (EQ-5D-3L)
Hide Description The EQ-5D health questionnaire is a generic self-reported health-related quality of life instrument that includes a 100 mm Visual Analog Scale (VAS) to measure the general health state, as well as 5 items corresponding to one dimension each: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. In this study, the VAS scale is not collected and the version 3L of the scale was used: Each dimension had 3 possible levels: 1 = no problem, 2 = some problems and 3 = extreme problems. EQ-5D-3L weighted health state index exists that combines the score of the 5 dimensions and ranges from 0 to 1 (full health). The variables for the 5 dimensions of the EQ-5D descriptive system was named 'mobility','selfcare', 'activity', 'pain', and 'anxiety'. The 5 variables contained the values for the different dimensions in the EQ-5D health profile (i.e. 1, 2, or 3).
Time Frame 2 years post treatment (IMP) administration
Hide Outcome Measure Data
Hide Analysis Population Description
ITT set included all randomized subjects.
Arm/Group Title Cholecalciferol Placebo
Hide Arm/Group Description:
Subjects received Cholecalciferol 100,000 IU one dose fortnightly (equivalent to a daily dose of approximately 7142 IU) for 96 weeks treatment period along with subcutaneous Rebif 44 mcg 3 times a week.
Subjects received matching placebo to Cholecalciferol once every two weeks orally along with subcutaneous injection of Rebif 44 mcg 3 times weekly.
Overall Number of Participants Analyzed 63 66
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline (n=60, 63) 0.7834  (0.24090) 0.7937  (0.21447)
Change at Week 96 (n=43, 45) -0.0051  (0.13742) 0.0043  (0.19654)
10.Secondary Outcome
Title Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs and Abnormal Clinical Laboratory
Hide Description A serious TEAE was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect and TEAE was defined as newly occurring or worsening after first dose. Clinical laboratory abnormalities are expected to be reported as adverse events if they met any criterion for seriousness, led to treatment discontinuation, required a medical intervention or were considered clinically significant by the investigator.
Time Frame Baseline up to end of treatment (week 96)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety set included all subjects who receive at least one administration of trial medication.
Arm/Group Title Cholecalciferol Placebo
Hide Arm/Group Description:
Subjects received Cholecalciferol 100,000 IU one dose fortnightly (equivalent to a daily dose of approximately 7142 IU) for 96 weeks treatment period along with subcutaneous Rebif 44 mcg 3 times a week.
Subjects received matching placebo to Cholecalciferol once every two weeks orally along with subcutaneous injection of Rebif 44 mcg 3 times weekly.
Overall Number of Participants Analyzed 61 65
Measure Type: Number
Unit of Measure: subjects
TEAEs 43 35
Serious TEAEs 11 10
Time Frame Baseline till the end of the study (week 96)
Adverse Event Reporting Description Adverse events were collected for Safety population. Safety set included all subjects who receive at least one administration of trial medication.
 
Arm/Group Title Cholecalciferol Placebo
Hide Arm/Group Description Subjects received Cholecalciferol 100,000 IU one dose fortnightly (equivalent to a daily dose of approximately 7142 IU) for 96 weeks treatment period along with subcutaneous Rebif 44 mcg 3 times a week. Subjects received matching placebo to Cholecalciferol once every two weeks orally along with subcutaneous injection of Rebif 44 mcg 3 times weekly.
All-Cause Mortality
Cholecalciferol Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Cholecalciferol Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   11/61 (18.03%)   10/65 (15.38%) 
Blood and lymphatic system disorders     
Pancytopenia * 1  0/61 (0.00%)  1/65 (1.54%) 
Cardiac disorders     
Stress cardiomyopathy * 1  1/61 (1.64%)  0/65 (0.00%) 
Endocrine disorders     
Adrenal mass * 1  0/61 (0.00%)  1/65 (1.54%) 
Gastrointestinal disorders     
Abdominal pain * 1  1/61 (1.64%)  0/65 (0.00%) 
Gastritis * 1  1/61 (1.64%)  0/65 (0.00%) 
Infections and infestations     
Appendicitis * 1  1/61 (1.64%)  0/65 (0.00%) 
Abdominal abscess * 1  0/61 (0.00%)  1/65 (1.54%) 
Injury, poisoning and procedural complications     
Foot fracture * 1  1/61 (1.64%)  0/65 (0.00%) 
Radius fracture * 1  0/61 (0.00%)  1/65 (1.54%) 
Metabolism and nutrition disorders     
Type 2 diabetes mellitus * 1  1/61 (1.64%)  1/65 (1.54%) 
Hypercalcaemia * 1  0/61 (0.00%)  1/65 (1.54%) 
Musculoskeletal and connective tissue disorders     
Psoriatic arthropathy * 1  0/61 (0.00%)  1/65 (1.54%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Breast cancer * 1  1/61 (1.64%)  0/65 (0.00%) 
Lung neoplasm malignant * 1  0/61 (0.00%)  1/65 (1.54%) 
Meningioma * 1  0/61 (0.00%)  1/65 (1.54%) 
Nervous system disorders     
Epilepsy * 1  1/61 (1.64%)  0/65 (0.00%) 
Pregnancy, puerperium and perinatal conditions     
Pregnancy on contraceptive * 1  1/61 (1.64%)  0/65 (0.00%) 
Pregnancy on oral contraceptive * 1  1/61 (1.64%)  0/65 (0.00%) 
Pregnancy after post coital contraception * 1  0/61 (0.00%)  1/65 (1.54%) 
Foetal death * 1  1/61 (1.64%)  0/65 (0.00%) 
Renal and urinary disorders     
Nephrolithiasis * 1  0/61 (0.00%)  1/65 (1.54%) 
Respiratory, thoracic and mediastinal disorders     
Pulmonary hypertension * 1  1/61 (1.64%)  0/65 (0.00%) 
Sleep apnoea syndrome * 1  1/61 (1.64%)  0/65 (0.00%) 
Surgical and medical procedures     
Abortion induced complete * 1  1/61 (1.64%)  0/65 (0.00%) 
Plastic surgery to the face * 1  1/61 (1.64%)  0/65 (0.00%) 
Vascular disorders     
Peripheral arterial occlusive disease * 1  0/61 (0.00%)  1/65 (1.54%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 18.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Cholecalciferol Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   40/61 (65.57%)   31/65 (47.69%) 
Blood and lymphatic system disorders     
Thrombocytopenia * 1  1/61 (1.64%)  0/65 (0.00%) 
Lymphopenia * 1  0/61 (0.00%)  1/65 (1.54%) 
Cardiac disorders     
Palpitations * 1  0/61 (0.00%)  1/65 (1.54%) 
Endocrine disorders     
Diabetes insipidus * 1  1/61 (1.64%)  0/65 (0.00%) 
Eye disorders     
Eye pain * 1  0/61 (0.00%)  1/65 (1.54%) 
Gastrointestinal disorders     
Haemorrhoids * 1  2/61 (3.28%)  0/65 (0.00%) 
Abdominal pain * 1  1/61 (1.64%)  1/65 (1.54%) 
Aphthous stomatitis * 1  1/61 (1.64%)  0/65 (0.00%) 
Gastritis * 1  1/61 (1.64%)  0/65 (0.00%) 
Gingival pain * 1  1/61 (1.64%)  0/65 (0.00%) 
Nausea * 1  1/61 (1.64%)  0/65 (0.00%) 
Vomiting * 1  1/61 (1.64%)  0/65 (0.00%) 
Constipation * 1  0/61 (0.00%)  2/65 (3.08%) 
Dental discomfort * 1  0/61 (0.00%)  1/65 (1.54%) 
Diarrhoea * 1  0/61 (0.00%)  1/65 (1.54%) 
General disorders     
Influenza like illness * 1  1/61 (1.64%)  5/65 (7.69%) 
Asthenia * 1  4/61 (6.56%)  2/65 (3.08%) 
Injection site erythema * 1  2/61 (3.28%)  0/65 (0.00%) 
Injection site pain * 1  1/61 (1.64%)  0/65 (0.00%) 
Injection site reaction * 1  1/61 (1.64%)  2/65 (3.08%) 
Malaise * 1  1/61 (1.64%)  0/65 (0.00%) 
Pain * 1  1/61 (1.64%)  0/65 (0.00%) 
Cyst * 1  0/61 (0.00%)  1/65 (1.54%) 
Infections and infestations     
Urinary tract infection * 1  4/61 (6.56%)  4/65 (6.15%) 
Nasopharyngitis * 1  3/61 (4.92%)  4/65 (6.15%) 
Bronchitis * 1  1/61 (1.64%)  4/65 (6.15%) 
Gastroenteritis * 1  1/61 (1.64%)  4/65 (6.15%) 
Influenza * 1  3/61 (4.92%)  1/65 (1.54%) 
Cystitis * 1  2/61 (3.28%)  0/65 (0.00%) 
Gingivitis * 1  2/61 (3.28%)  0/65 (0.00%) 
Hordeolum * 1  1/61 (1.64%)  0/65 (0.00%) 
Oral candidiasis * 1  1/61 (1.64%)  0/65 (0.00%) 
Oral herpes * 1  1/61 (1.64%)  0/65 (0.00%) 
Sinusitis * 1  1/61 (1.64%)  2/65 (3.08%) 
Paronychia * 1  1/61 (1.64%)  0/65 (0.00%) 
Tooth abscess * 1  1/61 (1.64%)  0/65 (0.00%) 
Tooth infection * 1  1/61 (1.64%)  0/65 (0.00%) 
Tracheobronchitis * 1  1/61 (1.64%)  0/65 (0.00%) 
Bronchitis viral * 1  0/61 (0.00%)  1/65 (1.54%) 
Pharyngitis * 1  0/61 (0.00%)  1/65 (1.54%) 
Injury, poisoning and procedural complications     
Fall * 1  3/61 (4.92%)  0/65 (0.00%) 
Head injury * 1  2/61 (3.28%)  0/65 (0.00%) 
Breast injury * 1  1/61 (1.64%)  0/65 (0.00%) 
Ligament sprain * 1  1/61 (1.64%)  1/65 (1.54%) 
Tooth fracture * 1  1/61 (1.64%)  0/65 (0.00%) 
Limb injury * 1  0/61 (0.00%)  1/65 (1.54%) 
Road traffic accident * 1  0/61 (0.00%)  2/65 (3.08%) 
Skin abrasion * 1  0/61 (0.00%)  1/65 (1.54%) 
Spinal column injury * 1  0/61 (0.00%)  1/65 (1.54%) 
Investigations     
Gamma-glutamyltransferase increased * 1  2/61 (3.28%)  0/65 (0.00%) 
Transaminases increased * 1  2/61 (3.28%)  0/65 (0.00%) 
Creatinine urine increased * 1  1/61 (1.64%)  0/65 (0.00%) 
Serum ferritin increased * 1  1/61 (1.64%)  0/65 (0.00%) 
Urine calcium/creatinine ratio increased * 1  1/61 (1.64%)  0/65 (0.00%) 
White blood cell count decreased * 1  1/61 (1.64%)  0/65 (0.00%) 
Blood creatinine increased * 1  0/61 (0.00%)  1/65 (1.54%) 
Creatinine renal clearance decreased * 1  0/61 (0.00%)  1/65 (1.54%) 
Hepatic enzyme increased * 1  0/61 (0.00%)  1/65 (1.54%) 
Normetanephrine urine increased * 1  0/61 (0.00%)  1/65 (1.54%) 
Weight increased * 1  0/61 (0.00%)  1/65 (1.54%) 
Metabolism and nutrition disorders     
Dyslipidaemia * 1  1/61 (1.64%)  0/65 (0.00%) 
Hyperglycaemia * 1  1/61 (1.64%)  0/65 (0.00%) 
Metabolic syndrome * 1  1/61 (1.64%)  0/65 (0.00%) 
Hypercholesterolaemia * 1  0/61 (0.00%)  1/65 (1.54%) 
Musculoskeletal and connective tissue disorders     
Back pain * 1  2/61 (3.28%)  0/65 (0.00%) 
Pain in extremity * 1  2/61 (3.28%)  2/65 (3.08%) 
Arthralgia * 1  1/61 (1.64%)  1/65 (1.54%) 
Muscle spasms * 1  1/61 (1.64%)  0/65 (0.00%) 
Musculoskeletal pain * 1  1/61 (1.64%)  0/65 (0.00%) 
Articular calcification * 1  0/61 (0.00%)  1/65 (1.54%) 
Intervertebral disc protrusion * 1  0/61 (0.00%)  1/65 (1.54%) 
Psoriatic arthropathy * 1  0/61 (0.00%)  1/65 (1.54%) 
Temporomandibular joint syndrome * 1  0/61 (0.00%)  1/65 (1.54%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Skin papilloma * 1  0/61 (0.00%)  1/65 (1.54%) 
Nervous system disorders     
Headache * 1  4/61 (6.56%)  1/65 (1.54%) 
Migraine * 1  3/61 (4.92%)  1/65 (1.54%) 
Dizziness * 1  1/61 (1.64%)  0/65 (0.00%) 
Optic neuritis * 1  1/61 (1.64%)  0/65 (0.00%) 
Presyncope * 1  1/61 (1.64%)  1/65 (1.54%) 
Radiculitis * 1  1/61 (1.64%)  0/65 (0.00%) 
Sciatica * 1  0/61 (0.00%)  1/65 (1.54%) 
Pregnancy, puerperium and perinatal conditions     
Pregnancy * 1  1/61 (1.64%)  0/65 (0.00%) 
Psychiatric disorders     
Depression * 1  5/61 (8.20%)  3/65 (4.62%) 
Anxiety * 1  2/61 (3.28%)  0/65 (0.00%) 
Depressive symptom * 1  0/61 (0.00%)  1/65 (1.54%) 
Stress * 1  0/61 (0.00%)  1/65 (1.54%) 
Renal and urinary disorders     
Nephrolithiasis * 1  0/61 (0.00%)  1/65 (1.54%) 
Reproductive system and breast disorders     
Erectile dysfunction * 1  1/61 (1.64%)  0/65 (0.00%) 
Menorrhagia * 1  1/61 (1.64%)  0/65 (0.00%) 
Dysmenorrhoea * 1  0/61 (0.00%)  1/65 (1.54%) 
Respiratory, thoracic and mediastinal disorders     
Oropharyngeal pain * 1  1/61 (1.64%)  4/65 (6.15%) 
Cough * 1  2/61 (3.28%)  0/65 (0.00%) 
Dyspnoea * 1  1/61 (1.64%)  1/65 (1.54%) 
Pulmonary hypertension * 1  1/61 (1.64%)  0/65 (0.00%) 
Sleep apnoea syndrome * 1  1/61 (1.64%)  0/65 (0.00%) 
Snoring * 1  1/61 (1.64%)  0/65 (0.00%) 
Asthma * 1  0/61 (0.00%)  1/65 (1.54%) 
Rhinitis allergic * 1  0/61 (0.00%)  2/65 (3.08%) 
Skin and subcutaneous tissue disorders     
Skin necrosis * 1  2/61 (3.28%)  0/65 (0.00%) 
Rash maculo-papular * 1  1/61 (1.64%)  0/65 (0.00%) 
Skin reaction * 1  1/61 (1.64%)  0/65 (0.00%) 
Dermatitis allergic * 1  0/61 (0.00%)  1/65 (1.54%) 
Dry skin * 1  0/61 (0.00%)  1/65 (1.54%) 
Erythema nodosum * 1  0/61 (0.00%)  1/65 (1.54%) 
Hyperhidrosis * 1  0/61 (0.00%)  1/65 (1.54%) 
Social circumstances     
Menopause * 1  3/61 (4.92%)  0/65 (0.00%) 
Vascular disorders     
Hypertension * 1  1/61 (1.64%)  1/65 (1.54%) 
Arterial disorder * 1  0/61 (0.00%)  1/65 (1.54%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 18.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The first publication will be publication of results of the analysis of primary endpoint(s) that will include data from all trial centers. Any publications and presentations of results, either in whole or in part, by investigators or their representatives will require pre-submission review by the sponsor/CRO. Sponsor will not suppress or veto publications, but maintains right to delay publication in order to protect intellectual property rights.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Title: Merck KGaA Communication Center
Organization: Merck KGaA
Phone: +49-6151-72-5200
EMail: service@merckgroup.com
Layout table for additonal information
Responsible Party: Merck KGaA, Darmstadt, Germany
ClinicalTrials.gov Identifier: NCT01198132     History of Changes
Other Study ID Numbers: 701068-524
2009-013695-46 ( EudraCT Number )
First Submitted: September 8, 2010
First Posted: September 9, 2010
Results First Submitted: December 6, 2016
Results First Posted: December 14, 2017
Last Update Posted: December 14, 2017