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Supplementation of VigantOL® Oil Versus Placebo as Add-on in Patients With Relapsing Remitting Multiple Sclerosis Receiving Rebif® Treatment (SOLAR)

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ClinicalTrials.gov Identifier: NCT01285401
Recruitment Status : Completed
First Posted : January 28, 2011
Results First Posted : July 11, 2016
Last Update Posted : November 28, 2016
Sponsor:
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: Treatment
Condition Relapsing-Remitting Multiple Sclerosis
Interventions Drug: VigantOL oil plus interferon beta-1a (Rebif)
Drug: Placebo plus interferon beta-1a (Rebif)
Biological: Interferon beta-1a (Rebif®) alone
Enrollment 260
Recruitment Details  
Pre-assignment Details Total 260 subject were enrolled, out of which 232 subjects were randomized and started the study. 229 subjects were treated since 3 subjects of the 232 randomized subjects were excluded from analysis as they did not received any medication.
Arm/Group Title VigantOL Oil Interferon Beta-1a (Rebif) Placebo Interferon Beta-1a (Rebif)
Hide Arm/Group Description Subjects with 25-hydroxyvitamin D [25(OH)D3] serum levels below 150 nano mol per liter (nmol/L) received Vigantol oil 6,670 international unit per day (IU/d) [167 microgram per day (mcg/d)] orally for 4 weeks followed by 14,007 IU/d (350 mcg/d) for 44 weeks along with of Rebif 44 mcg administered subcutaneous three times a week (tiw). Subjects with 25(OH)D3 serum levels below 150 nmol/L, received matching placebo for 48 weeks on top of Rebif 44 mcg administered subcutaneous tiw.
Period Title: Overall Study
Started 115 117
Treated 113 116
Completed 98 88
Not Completed 17 29
Reason Not Completed
Prematurely withdrawn from the study             17             29
Arm/Group Title VigantOL Oil Interferon Beta-1a (Rebif) Placebo Interferon Beta-1a (Rebif) Total
Hide Arm/Group Description Subjects with 25(OH)D3 serum levels below 150 nmol/L received Vigantol oil 6,670 IU/d [167 mcg/d] orally for 4 weeks followed by 14,007 IU/d (350 mcg/d) for 44 weeks along with of Rebif 44 mcg administered subcutaneous tiw. Subjects with 25(OH)D3 serum levels below 150 nmol/L, received matching placebo for 48 weeks on top of Rebif 44 mcg administered subcutaneous tiw. Total of all reporting groups
Overall Number of Baseline Participants 115 117 232
Hide Baseline Analysis Population Description
Baseline analysis set included all randomized subjects.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 115 participants 117 participants 232 participants
34.2  (8.1) 33.6  (9.3) 33.9  (8.8)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 115 participants 117 participants 232 participants
Female
78
  67.8%
79
  67.5%
157
  67.7%
Male
37
  32.2%
38
  32.5%
75
  32.3%
1.Primary Outcome
Title Percentage of Subjects With Disease Activity Free Status up to Week 48
Hide Description Disease activity free status was defined as absence of any of the clinical and imaging parameters related to the assessment of disease activity; no relapses, no expanded disability status scale (EDSS) progression and no new gadolinium (Gd)-enhancing or relaxation time 2 (T2) magnetic resonance imaging (MRI) lesions.
Time Frame Up to Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
ITT set included all randomized subjects who received at least 1 dose of the IMP.
Arm/Group Title VigantOL Oil Interferon Beta-1a (Rebif) Placebo Interferon Beta-1a (Rebif)
Hide Arm/Group Description:
Subjects with 25(OH)D3 serum levels below 150 nmol/L received Vigantol oil 6,670 IU/d [167 mcg/d] orally for 4 weeks followed by 14,007 IU/d (350 mcg/d) for 44 weeks along with of Rebif 44 mcg administered subcutaneous tiw.
Subjects with 25(OH)D3 serum levels below 150 nmol/L, received matching placebo for 48 weeks on top of Rebif 44 mcg administered subcutaneous tiw.
Overall Number of Participants Analyzed 113 116
Measure Type: Number
Unit of Measure: percentage of subjects
37.2 35.3
2.Secondary Outcome
Title Percentage of Relapse-free Subjects at Week 48
Hide Description A relapse was defined as the development of new or the exacerbation of existing neurological symptoms or signs, in the absence of fever, lasting for 24 hours and with a previous period for more than 30 days with a stable or an improving condition.
Time Frame Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
ITT analysis set consisted of all randomized subjects who received at least 1 dose of the IMP.
Arm/Group Title VigantOL Oil Interferon Beta-1a (Rebif) Placebo Interferon Beta-1a (Rebif)
Hide Arm/Group Description:
Subjects with 25(OH)D3 serum levels below 150 nmol/L received Vigantol oil 6,670 IU/d [167 mcg/d] orally for 4 weeks followed by 14,007 IU/d (350 mcg/d) for 44 weeks along with of Rebif 44 mcg administered subcutaneous tiw.
Subjects with 25(OH)D3 serum levels below 150 nmol/L, received matching placebo for 48 weeks on top of Rebif 44 mcg administered subcutaneous tiw.
Overall Number of Participants Analyzed 113 116
Measure Type: Number
Unit of Measure: percentage of subjects
78.8 75.0
3.Secondary Outcome
Title Percentage of Subjects Free From Any Expanded Disability Status Scale (EDSS) Progression at Week 48
Hide Description EDSS assesses disability in 8 functional systems. An overall score ranging from 0 (normal) to 10 (death due to MS) was calculated. A confirmed EDSS progression was defined EDSS greater than or equal to 1.0 point confirmed during a visit performed 6 months later. An EDSS progression was defined as an increase of the EDSS score of at least 1.0 point compared to baseline (SD1) for subjects with a baseline EDSS ≤ 4.0. For subjects with an EDSS score of 0 at baseline (SD1), EDSS progression was defined as an increase of at least 1.5 points. A confirmed EDSS progression was defined as an EDSS progression confirmed after 24 weeks.
Time Frame Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
ITT analysis set consisted of all randomized subjects who received at least 1 dose of the IMP.
Arm/Group Title VigantOL Oil Interferon Beta-1a (Rebif) Placebo Interferon Beta-1a (Rebif)
Hide Arm/Group Description:
Subjects with 25(OH)D3 serum levels below 150 nmol/L received Vigantol oil 6,670 IU/d [167 mcg/d] orally for 4 weeks followed by 14,007 IU/d (350 mcg/d) for 44 weeks along with of Rebif 44 mcg administered subcutaneous tiw.
Subjects with 25(OH)D3 serum levels below 150 nmol/L, received matching placebo for 48 weeks on top of Rebif 44 mcg administered subcutaneous tiw.
Overall Number of Participants Analyzed 113 116
Measure Type: Number
Unit of Measure: percentage of subjects
71.7 75.0
4.Secondary Outcome
Title Number od Subjects With Confirmed EDSS Progression
Hide Description EDSS assesses disability in 8 functional systems. An overall score ranging from 0 (normal) to 10 (death due to MS) was calculated. A confirmed EDSS progression was defined EDSS greater than or equal to 1.0 point confirmed during a visit performed 6 months later. An EDSS progression was defined as an increase of the EDSS score of at least 1.0 point compared to baseline (SD1) for subjects with a baseline EDSS ≤ 4.0. For subjects with an EDSS score of 0 at baseline (SD1), EDSS progression was defined as an increase of at least 1.5 points. A confirmed EDSS progression was defined as an EDSS progression confirmed after 24 weeks.
Time Frame Baseline upto 48 Weeks
Hide Outcome Measure Data
Hide Analysis Population Description
ITT analysis set consisted of all randomized subjects who received at least 1 dose of the IMP.
Arm/Group Title VigantOL Oil Interferon Beta-1a (Rebif) Placebo Interferon Beta-1a (Rebif)
Hide Arm/Group Description:
Subjects with 25(OH)D3 serum levels below 150 nmol/L received Vigantol oil 6,670 IU/d [167 mcg/d] orally for 4 weeks followed by 14,007 IU/d (350 mcg/d) for 44 weeks along with of Rebif 44 mcg administered subcutaneous tiw.
Subjects with 25(OH)D3 serum levels below 150 nmol/L, received matching placebo for 48 weeks on top of Rebif 44 mcg administered subcutaneous tiw.
Overall Number of Participants Analyzed 113 116
Measure Type: Number
Unit of Measure: subjects
8 4
5.Secondary Outcome
Title Cumulative Number of Relaxation Time 1 (T1) Gadolinium Enhancing Lesions at Week 48
Hide Description [Not Specified]
Time Frame 48 Weeks
Hide Outcome Measure Data
Hide Analysis Population Description
ITT analysis set consisted of all randomized subjects who received at least 1 dose of the IMP. Here "N" signifies number of subject analyzed for respective outcome measure.
Arm/Group Title VigantOL Oil Interferon Beta-1a (Rebif) Placebo Interferon Beta-1a (Rebif)
Hide Arm/Group Description:
Subjects with 25(OH)D3 serum levels below 150 nmol/L received Vigantol oil 6,670 IU/d [167 mcg/d] orally for 4 weeks followed by 14,007 IU/d (350 mcg/d) for 44 weeks along with of Rebif 44 mcg administered subcutaneous tiw.
Subjects with 25(OH)D3 serum levels below 150 nmol/L, received matching placebo for 48 weeks on top of Rebif 44 mcg administered subcutaneous tiw.
Overall Number of Participants Analyzed 102 92
Mean (Standard Deviation)
Unit of Measure: lesions per subject per scan
0.36  (1.73) 0.25  (0.67)
6.Secondary Outcome
Title Mean Number of Combined Unique Active (CUA) Lesions Per Subject Per Scan at Week 48
Hide Description CUA lesions was defined as new T1 (Gd enhancing) lesions, new Relaxation time 2 (T2) lesions, or enlarging T2 lesions.
Time Frame 48 Weeks
Hide Outcome Measure Data
Hide Analysis Population Description
ITT analysis set consisted of all randomized subjects who received at least 1 dose of the IMP.
Arm/Group Title VigantOL Oil Interferon Beta-1a (Rebif) Placebo Interferon Beta-1a (Rebif)
Hide Arm/Group Description:
Subjects with 25(OH)D3 serum levels below 150 nmol/L received Vigantol oil 6,670 IU/d [167 mcg/d] orally for 4 weeks followed by 14,007 IU/d (350 mcg/d) for 44 weeks along with of Rebif 44 mcg administered subcutaneous tiw.
Subjects with 25(OH)D3 serum levels below 150 nmol/L, received matching placebo for 48 weeks on top of Rebif 44 mcg administered subcutaneous tiw.
Overall Number of Participants Analyzed 113 116
Mean (Standard Deviation)
Unit of Measure: lesions per subject per scan
1.09  (3.84) 1.49  (4.31)
7.Secondary Outcome
Title Cumulative Number of New Combined Unique Active (CUA) Lesions at Week 48
Hide Description CUA lesions was defined as new T1 (Gd enhancing) lesions, new T2 lesions, or enlarging T2 lesions.
Time Frame 48 Weeks
Hide Outcome Measure Data
Hide Analysis Population Description
ITT analysis set consisted of all randomized subjects who received at least 1 dose of the IMP.
Arm/Group Title VigantOL Oil Interferon Beta-1a (Rebif) Placebo Interferon Beta-1a (Rebif)
Hide Arm/Group Description:
Subjects with 25(OH)D3 serum levels below 150 nmol/L received Vigantol oil 6,670 IU/d [167 mcg/d] orally for 4 weeks followed by 14,007 IU/d (350 mcg/d) for 44 weeks along with of Rebif 44 mcg administered subcutaneous tiw.
Subjects with 25(OH)D3 serum levels below 150 nmol/L, received matching placebo for 48 weeks on top of Rebif 44 mcg administered subcutaneous tiw.
Overall Number of Participants Analyzed 113 116
Mean (Standard Deviation)
Unit of Measure: lesions per subject per scan
1.09  (3.84) 1.49  (4.31)
8.Secondary Outcome
Title Mean Change From Baseline in the Total Volume of T2 Lesions at Week 48 (T2 Burden of Disease)
Hide Description [Not Specified]
Time Frame Baseline, 48 Weeks
Hide Outcome Measure Data
Hide Analysis Population Description
ITT analysis set consisted of all randomized subjects who received at least 1 dose of the IMP. Here "N" signifies number of subjects analyzed for respective outcome measure.
Arm/Group Title VigantOL Oil Interferon Beta-1a (Rebif) Placebo Interferon Beta-1a (Rebif)
Hide Arm/Group Description:
Subjects with 25(OH)D3 serum levels below 150 nmol/L received Vigantol oil 6,670 IU/d [167 mcg/d] orally for 4 weeks followed by 14,007 IU/d (350 mcg/d) for 44 weeks along with of Rebif 44 mcg administered subcutaneous tiw.
Subjects with 25(OH)D3 serum levels below 150 nmol/L, received matching placebo for 48 weeks on top of Rebif 44 mcg administered subcutaneous tiw.
Overall Number of Participants Analyzed 103 92
Mean (Standard Deviation)
Unit of Measure: millimeter^3 (mm^3)
130.38  (830.82) 95.75  (401.87)
9.Secondary Outcome
Title Percentage of Subjects Free From T1 Gadolinium Enhancing Lesions at Week 48
Hide Description [Not Specified]
Time Frame 48 Weeks
Hide Outcome Measure Data
Hide Analysis Population Description
ITT analysis set consisted of all randomized subjects who received at least 1 dose of the IMP.
Arm/Group Title VigantOL Oil Interferon Beta-1a (Rebif) Placebo Interferon Beta-1a (Rebif)
Hide Arm/Group Description:
Subjects with 25(OH)D3 serum levels below 150 nmol/L received Vigantol oil 6,670 IU/d [167 mcg/d] orally for 4 weeks followed by 14,007 IU/d (350 mcg/d) for 44 weeks along with of Rebif 44 mcg administered subcutaneous tiw.
Subjects with 25(OH)D3 serum levels below 150 nmol/L, received matching placebo for 48 weeks on top of Rebif 44 mcg administered subcutaneous tiw.
Overall Number of Participants Analyzed 113 116
Measure Type: Number
Unit of Measure: percentage of subjects
83.2 70.7
10.Secondary Outcome
Title Percentage of Subjects Free From New T1 Hypointense Lesions (Black Holes) at Week 48
Hide Description [Not Specified]
Time Frame 48 Weeks
Hide Outcome Measure Data
Hide Analysis Population Description
ITT analysis set consisted of all randomized subjects who received at least 1 dose of the IMP.
Arm/Group Title VigantOL Oil Interferon Beta-1a (Rebif) Placebo Interferon Beta-1a (Rebif)
Hide Arm/Group Description:
Subjects with 25(OH)D3 serum levels below 150 nmol/L received Vigantol oil 6,670 IU/d [167 mcg/d] orally for 4 weeks followed by 14,007 IU/d (350 mcg/d) for 44 weeks along with of Rebif 44 mcg administered subcutaneous tiw.
Subjects with 25(OH)D3 serum levels below 150 nmol/L, received matching placebo for 48 weeks on top of Rebif 44 mcg administered subcutaneous tiw.
Overall Number of Participants Analyzed 113 116
Measure Type: Number
Unit of Measure: percentage of subjects
78.8 63.8
11.Secondary Outcome
Title Percentage of New T1 Hypointense Lesions (Black Holes) at Week 48 Within the Subgroup of New or Enlarging Non-enhancing T2 Lesions
Hide Description [Not Specified]
Time Frame 48 Weeks
Hide Outcome Measure Data
Hide Analysis Population Description
ITT analysis set consisted of all randomized subjects who received at least 1 dose of the IMP. Here “N” signifies number of subjects analyzed for respective outcome measure (here in the subgroup of subjects having new or enlarging T2 lesions).
Arm/Group Title VigantOL Oil Interferon Beta-1a (Rebif) Placebo Interferon Beta-1a (Rebif)
Hide Arm/Group Description:
Subjects with 25(OH)D3 serum levels below 150 nmol/L received Vigantol oil 6,670 IU/d [167 mcg/d] orally for 4 weeks followed by 14,007 IU/d (350 mcg/d) for 44 weeks along with of Rebif 44 mcg administered subcutaneous tiw.
Subjects with 25(OH)D3 serum levels below 150 nmol/L, received matching placebo for 48 weeks on top of Rebif 44 mcg administered subcutaneous tiw.
Overall Number of Participants Analyzed 25 36
Mean (Standard Deviation)
Unit of Measure: percentage of new T1 hypointense lesions
20.11  (34.72) 27.70  (39.33)
12.Secondary Outcome
Title Number of Subjects With Relapse
Hide Description Relapse was defined as neurological abnormality, either newly appearing or re-appearing, with abnormality specified by both as neurological abnormality separated by at least 30 days from onset of a preceding MS attack and Neurological abnormality lasting for at least 24 hours, absence of fever or known infection greater than 37.5 degree centigrade /99.5 degree fahrenheit , objective neurological impairment, correlating with the subject’s reported symptoms, defined as either increase in at least one of the functional systems of the EDSS or increase of the total EDSS score and occurrence of paraesthesia, fatigue, mental symptoms, and/or vegetative symptoms without any additional symptom will not be classified as an MS attack.
Time Frame Baseline upto 48 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
ITT analysis set consisted of all randomized subjects who received at least 1 dose of the IMP.
Arm/Group Title VigantOL Oil Interferon Beta-1a (Rebif) Placebo Interferon Beta-1a (Rebif)
Hide Arm/Group Description:
Subjects with 25(OH)D3 serum levels below 150 nmol/L received Vigantol oil 6,670 IU/d [167 mcg/d] orally for 4 weeks followed by 14,007 IU/d (350 mcg/d) for 44 weeks along with of Rebif 44 mcg administered subcutaneous tiw.
Subjects with 25(OH)D3 serum levels below 150 nmol/L, received matching placebo for 48 weeks on top of Rebif 44 mcg administered subcutaneous tiw.
Overall Number of Participants Analyzed 113 116
Measure Type: Number
Unit of Measure: subjects
24 29
13.Secondary Outcome
Title Annualized Relapse Rate at Week 48
Hide Description Relapse was defined as neurological abnormality, either newly appearing or re-appearing, with abnormality specified by both as neurological abnormality separated by at least 30 days from onset of a preceding MS attack and Neurological abnormality lasting for at least 24 hours, absence of fever or known infection greater than 37.5 degree centigrade /99.5 degree fahrenheit , objective neurological impairment, correlating with the subject’s reported symptoms, defined as either increase in at least one of the functional systems of the EDSS or increase of the total EDSS score and occurrence of paraesthesia, fatigue, mental symptoms, and/or vegetative symptoms without any additional symptom will not be classified as an MS attack.
Time Frame 48 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
ITT analysis set consisted of all randomized subjects who received at least 1 dose of the IMP.
Arm/Group Title VigantOL Oil Interferon Beta-1a (Rebif) Placebo Interferon Beta-1a (Rebif)
Hide Arm/Group Description:
Subjects with 25(OH)D3 serum levels below 150 nmol/L received Vigantol oil 6,670 IU/d [167 mcg/d] orally for 4 weeks followed by 14,007 IU/d (350 mcg/d) for 44 weeks along with of Rebif 44 mcg administered subcutaneous tiw.
Subjects with 25(OH)D3 serum levels below 150 nmol/L, received matching placebo for 48 weeks on top of Rebif 44 mcg administered subcutaneous tiw.
Overall Number of Participants Analyzed 113 116
Mean (Standard Deviation)
Unit of Measure: relapse per year
0.28  (0.59) 0.41  (0.83)
14.Secondary Outcome
Title Total Number of Reported Relapses at All Time Points up to 48 Weeks
Hide Description Relapse was defined as neurological abnormality, either newly appearing or re-appearing, with abnormality specified by both as neurological abnormality separated by at least 30 days from onset of a preceding MS attack and Neurological abnormality lasting for at least 24 hours, absence of fever or known infection greater than 37.5 degree centigrade /99.5 degree fahrenheit , objective neurological impairment, correlating with the subject’s reported symptoms, defined as either increase in at least one of the functional systems of the EDSS or increase of the total EDSS score and occurrence of paraesthesia, fatigue, mental symptoms, and/or vegetative symptoms without any additional symptom will not be classified as an MS attack.
Time Frame 48 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
ITT analysis set consisted of all randomized subjects who received at least 1 dose of the IMP.
Arm/Group Title VigantOL Oil Interferon Beta-1a (Rebif) Placebo Interferon Beta-1a (Rebif)
Hide Arm/Group Description:
Subjects with 25(OH)D3 serum levels below 150 nmol/L received Vigantol oil 6,670 IU/d [167 mcg/d] orally for 4 weeks followed by 14,007 IU/d (350 mcg/d) for 44 weeks along with of Rebif 44 mcg administered subcutaneous tiw.
Subjects with 25(OH)D3 serum levels below 150 nmol/L, received matching placebo for 48 weeks on top of Rebif 44 mcg administered subcutaneous tiw.
Overall Number of Participants Analyzed 113 116
Mean (Standard Deviation)
Unit of Measure: number of relapse per subject
0.25  (0.53) 0.34  (0.63)
15.Secondary Outcome
Title Percentage of Subjects Treated With Glucocorticoids Due to Relapses
Hide Description Relapse was defined as neurological abnormality, either newly appearing or re-appearing, with abnormality specified by both as neurological abnormality separated by at least 30 days from onset of a preceding MS attack and Neurological abnormality lasting for at least 24 hours, absence of fever or known infection greater than 37.5 degree centigrade /99.5 degree fahrenheit , objective neurological impairment, correlating with the subject’s reported symptoms, defined as either increase in at least one of the functional systems of the EDSS or increase of the total EDSS score and occurrence of paraesthesia, fatigue, mental symptoms, and/or vegetative symptoms without any additional symptom will not be classified as an MS attack.
Time Frame Baseline upto 48 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
ITT analysis set consisted of all randomized subjects who received at least 1 dose of the IMP.
Arm/Group Title VigantOL Oil Interferon Beta-1a (Rebif) Placebo Interferon Beta-1a (Rebif)
Hide Arm/Group Description:
Subjects with 25(OH)D3 serum levels below 150 nmol/L received Vigantol oil 6,670 IU/d [167 mcg/d] orally for 4 weeks followed by 14,007 IU/d (350 mcg/d) for 44 weeks along with of Rebif 44 mcg administered subcutaneous tiw.
Subjects with 25(OH)D3 serum levels below 150 nmol/L, received matching placebo for 48 weeks on top of Rebif 44 mcg administered subcutaneous tiw.
Overall Number of Participants Analyzed 113 116
Measure Type: Number
Unit of Measure: percentage of subjects
15.9 20.7
16.Secondary Outcome
Title Mean Change From Baseline in the Total Volume of T1 Hypo Intense Lesions at Week 48
Hide Description [Not Specified]
Time Frame Baseline, 48 Weeks
Hide Outcome Measure Data
Hide Analysis Population Description
ITT analysis set consisted of all randomized subjects who received at least 1 dose of the IMP.
Arm/Group Title VigantOL Oil Interferon Beta-1a (Rebif) Placebo Interferon Beta-1a (Rebif)
Hide Arm/Group Description:
Subjects with 25(OH)D3 serum levels below 150 nmol/L received Vigantol oil 6,670 IU/d [167 mcg/d] orally for 4 weeks followed by 14,007 IU/d (350 mcg/d) for 44 weeks along with of Rebif 44 mcg administered subcutaneous tiw.
Subjects with 25(OH)D3 serum levels below 150 nmol/L, received matching placebo for 48 weeks on top of Rebif 44 mcg administered subcutaneous tiw.
Overall Number of Participants Analyzed 113 116
Mean (Standard Deviation)
Unit of Measure: millimeter^3 (mm^3)
20.88  (140.56) 18.47  (68.08)
17.Post-Hoc Outcome
Title Percentage of Subjects With Disease Activity Free Status (Alternate Definition) at Week 48
Hide Description Disease activity free (DAF) status was defined as absence of any of the clinical and imaging parameters related to the assessment of disease activity; no relapses, no confirmed expanded disability status scale (EDSS) progression and no new gadolinium (Gd)-enhancing or relaxation time 2 (T2) magnetic resonance imaging (MRI) lesions. Confirmed EDSS progression was defined as an EDSS progression confirmed after 24 weeks.
Time Frame Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
ITT set included all randomized subjects who received at least 1 dose of the IMP.
Arm/Group Title VigantOL Oil Interferon Beta-1a (Rebif) Placebo Interferon Beta-1a (Rebif)
Hide Arm/Group Description:
Subjects with 25(OH)D3 serum levels below 150 nmol/L received Vigantol oil 6,670 IU/d [167 mcg/d] orally for 4 weeks followed by 14,007 IU/d (350 mcg/d) for 44 weeks along with of Rebif 44 mcg administered subcutaneous tiw.
Subjects with 25(OH)D3 serum levels below 150 nmol/L, received matching placebo for 48 weeks on top of Rebif 44 mcg administered subcutaneous tiw.
Overall Number of Participants Analyzed 113 116
Measure Type: Number
Unit of Measure: percentage of subjects
47.8 37.9
Time Frame Baseline up to end of trial (EOT: 50 months)
Adverse Event Reporting Description Safety Analysis Set: All randomized subjects who received at least 1 dose of the IMP
 
Arm/Group Title VigantOL Oil Interferon Beta-1a (Rebif) Placebo Interferon Beta-1a (Rebif)
Hide Arm/Group Description Subjects with 25(OH)D3 serum levels below 150 nmol/L received Vigantol oil 6,670 IU/d [167 mcg/d] orally for 4 weeks followed by 14,007 IU/d (350 mcg/d) for 44 weeks along with of Rebif 44 mcg administered subcutaneous tiw. Subjects with 25(OH)D3 serum levels below 150 nmol/L, received matching placebo for 48 weeks on top of Rebif 44 mcg administered subcutaneous tiw.
All-Cause Mortality
VigantOL Oil Interferon Beta-1a (Rebif) Placebo Interferon Beta-1a (Rebif)
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
VigantOL Oil Interferon Beta-1a (Rebif) Placebo Interferon Beta-1a (Rebif)
Affected / at Risk (%) Affected / at Risk (%)
Total   18/113 (15.93%)   8/116 (6.90%) 
Cardiac disorders     
Cardiac failure * 1  1/113 (0.88%)  0/116 (0.00%) 
Gastrointestinal disorders     
Abdominal pain * 1  1/113 (0.88%)  0/116 (0.00%) 
Haemorrhoids * 1  0/113 (0.00%)  1/116 (0.86%) 
Infections and infestations     
Abscess limb * 1  1/113 (0.88%)  0/116 (0.00%) 
Appendicitis * 1  1/113 (0.88%)  0/116 (0.00%) 
Cellulitis * 1  1/113 (0.88%)  0/116 (0.00%) 
Eye infection * 1  0/113 (0.00%)  1/116 (0.86%) 
Pneumonia * 1  1/113 (0.88%)  0/116 (0.00%) 
Pyelonephritis * 1  1/113 (0.88%)  0/116 (0.00%) 
Injury, poisoning and procedural complications     
Overdose * 1  8/113 (7.08%)  6/116 (5.17%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Breast cancer * 1  1/113 (0.88%)  0/116 (0.00%) 
Ovarian cancer * 1  1/113 (0.88%)  0/116 (0.00%) 
Nervous system disorders     
Headache * 1  0/113 (0.00%)  1/116 (0.86%) 
Syncope * 1  1/113 (0.88%)  0/116 (0.00%) 
Psychiatric disorders     
Depression * 1  1/113 (0.88%)  0/116 (0.00%) 
Reproductive system and breast disorders     
Menorrhagia * 1  1/113 (0.88%)  0/116 (0.00%) 
Uterine polyp * 1  1/113 (0.88%)  0/116 (0.00%) 
Vascular disorders     
Hypertension * 1  1/113 (0.88%)  0/116 (0.00%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 13.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
VigantOL Oil Interferon Beta-1a (Rebif) Placebo Interferon Beta-1a (Rebif)
Affected / at Risk (%) Affected / at Risk (%)
Total   99/113 (87.61%)   93/116 (80.17%) 
Blood and lymphatic system disorders     
Anaemia * 1  3/113 (2.65%)  0/116 (0.00%) 
Haematotoxicity * 1  0/113 (0.00%)  1/116 (0.86%) 
Leukopenia * 1  2/113 (1.77%)  0/116 (0.00%) 
Lymph node pain * 1  1/113 (0.88%)  0/116 (0.00%) 
Lymphadenopathy * 1  1/113 (0.88%)  1/116 (0.86%) 
Lymphopenia * 1  2/113 (1.77%)  0/116 (0.00%) 
Neutropenia * 1  1/113 (0.88%)  0/116 (0.00%) 
Thrombocytopenia * 1  1/113 (0.88%)  0/116 (0.00%) 
Cardiac disorders     
Angina pectoris * 1  2/113 (1.77%)  1/116 (0.86%) 
Atrioventricular block first degree * 1  1/113 (0.88%)  0/116 (0.00%) 
Palpitations * 1  1/113 (0.88%)  0/116 (0.00%) 
Tachycardia * 1  2/113 (1.77%)  1/116 (0.86%) 
Ventricular extrasystoles * 1  0/113 (0.00%)  1/116 (0.86%) 
Ear and labyrinth disorders     
Ear pain * 1  0/113 (0.00%)  1/116 (0.86%) 
Tinnitus * 1  1/113 (0.88%)  1/116 (0.86%) 
Vertigo * 1  1/113 (0.88%)  2/116 (1.72%) 
Endocrine disorders     
Hyperparathyroidism secondary * 1  0/113 (0.00%)  1/116 (0.86%) 
Hyperthyroidism * 1  1/113 (0.88%)  1/116 (0.86%) 
Hypothyroidism * 1  2/113 (1.77%)  3/116 (2.59%) 
Thyroid disorder * 1  1/113 (0.88%)  0/116 (0.00%) 
Eye disorders     
Conjunctivitis * 1  1/113 (0.88%)  2/116 (1.72%) 
Diplopia * 1  1/113 (0.88%)  1/116 (0.86%) 
Dry eye * 1  2/113 (1.77%)  0/116 (0.00%) 
Eye irritation * 1  1/113 (0.88%)  0/116 (0.00%) 
Eye pain * 1  3/113 (2.65%)  3/116 (2.59%) 
Glaucoma * 1  0/113 (0.00%)  1/116 (0.86%) 
Oscillopsia * 1  1/113 (0.88%)  0/116 (0.00%) 
Ulcerative keratitis * 1  1/113 (0.88%)  0/116 (0.00%) 
Vision blurred * 1  3/113 (2.65%)  3/116 (2.59%) 
Visual impairment * 1  1/113 (0.88%)  3/116 (2.59%) 
Gastrointestinal disorders     
Abdominal distension * 1  0/113 (0.00%)  1/116 (0.86%) 
Abdominal pain * 1  2/113 (1.77%)  4/116 (3.45%) 
Abdominal pain lower * 1  0/113 (0.00%)  1/116 (0.86%) 
Abdominal pain upper * 1  9/113 (7.96%)  3/116 (2.59%) 
Abdominal tenderness * 1  1/113 (0.88%)  0/116 (0.00%) 
Constipation * 1  6/113 (5.31%)  2/116 (1.72%) 
Diarrhoea * 1  10/113 (8.85%)  7/116 (6.03%) 
Dyspepsia * 1  2/113 (1.77%)  1/116 (0.86%) 
Dysphagia * 1  0/113 (0.00%)  1/116 (0.86%) 
Flatulence * 1  1/113 (0.88%)  0/116 (0.00%) 
Food poisoning * 1  1/113 (0.88%)  0/116 (0.00%) 
Gastritis * 1  0/113 (0.00%)  1/116 (0.86%) 
Gastrointestinal disorder * 1  0/113 (0.00%)  1/116 (0.86%) 
Gastrointestinal sounds abnormal * 1  1/113 (0.88%)  0/116 (0.00%) 
Gastrooesophageal reflux disease * 1  1/113 (0.88%)  0/116 (0.00%) 
Gingivitis * 1  1/113 (0.88%)  0/116 (0.00%) 
Haemorrhoidal haemorrhage * 1  1/113 (0.88%)  0/116 (0.00%) 
Haemorrhoids * 1  0/113 (0.00%)  1/116 (0.86%) 
Irritable bowel syndrome * 1  0/113 (0.00%)  1/116 (0.86%) 
Lip swelling * 1  0/113 (0.00%)  1/116 (0.86%) 
Nausea * 1  3/113 (2.65%)  4/116 (3.45%) 
Oral discomfort * 1  1/113 (0.88%)  0/116 (0.00%) 
Paraesthesia oral * 1  1/113 (0.88%)  1/116 (0.86%) 
Rectal haemorrhage * 1  0/113 (0.00%)  1/116 (0.86%) 
Tooth impacted * 1  0/113 (0.00%)  1/116 (0.86%) 
Toothache * 1  3/113 (2.65%)  2/116 (1.72%) 
Vomiting * 1  3/113 (2.65%)  4/116 (3.45%) 
Vomiting in pregnancy * 1  1/113 (0.88%)  0/116 (0.00%) 
General disorders     
Asthenia * 1  2/113 (1.77%)  1/116 (0.86%) 
Chest discomfort * 1  1/113 (0.88%)  0/116 (0.00%) 
Chest pain * 1  0/113 (0.00%)  4/116 (3.45%) 
Chills * 1  0/113 (0.00%)  1/116 (0.86%) 
Fatigue * 1  8/113 (7.08%)  13/116 (11.21%) 
Feeling cold * 1  2/113 (1.77%)  0/116 (0.00%) 
Gait disturbance * 1  3/113 (2.65%)  2/116 (1.72%) 
Inflammation * 1  1/113 (0.88%)  0/116 (0.00%) 
Influenza like illness * 1  12/113 (10.62%)  13/116 (11.21%) 
Injection site erythema * 1  4/113 (3.54%)  0/116 (0.00%) 
Injection site induration * 1  0/113 (0.00%)  1/116 (0.86%) 
Injection site inflammation * 1  1/113 (0.88%)  0/116 (0.00%) 
Injection site irritation * 1  1/113 (0.88%)  1/116 (0.86%) 
Injection site pain * 1  2/113 (1.77%)  2/116 (1.72%) 
Injection site pruritus * 1  0/113 (0.00%)  1/116 (0.86%) 
Injection site reaction * 1  5/113 (4.42%)  3/116 (2.59%) 
Injection site swelling * 1  1/113 (0.88%)  0/116 (0.00%) 
Injection site urticaria * 1  0/113 (0.00%)  3/116 (2.59%) 
Irritability * 1  0/113 (0.00%)  1/116 (0.86%) 
Malaise * 1  1/113 (0.88%)  1/116 (0.86%) 
Oedema peripheral * 1  2/113 (1.77%)  1/116 (0.86%) 
Pain * 1  1/113 (0.88%)  1/116 (0.86%) 
Pyrexia * 1  7/113 (6.19%)  12/116 (10.34%) 
Sensation of foreign body * 1  1/113 (0.88%)  1/116 (0.86%) 
Hepatobiliary disorders     
Hepatic steatosis * 1  1/113 (0.88%)  1/116 (0.86%) 
Immune system disorders     
Multiple allergies * 1  0/113 (0.00%)  1/116 (0.86%) 
Infections and infestations     
Acute tonsillitis * 1  1/113 (0.88%)  0/116 (0.00%) 
Bacterial infection * 1  1/113 (0.88%)  0/116 (0.00%) 
Bronchitis * 1  4/113 (3.54%)  2/116 (1.72%) 
Cystitis * 1  3/113 (2.65%)  7/116 (6.03%) 
Ear infection * 1  2/113 (1.77%)  1/116 (0.86%) 
Eye infection * 1  1/113 (0.88%)  1/116 (0.86%) 
Eyelid infection * 1  0/113 (0.00%)  1/116 (0.86%) 
Folliculitis * 1  0/113 (0.00%)  1/116 (0.86%) 
Fungal infection * 1  0/113 (0.00%)  1/116 (0.86%) 
Furuncle * 1  1/113 (0.88%)  1/116 (0.86%) 
Gastric infection * 1  0/113 (0.00%)  1/116 (0.86%) 
Gastroenteritis * 1  2/113 (1.77%)  5/116 (4.31%) 
Gastroenteritis viral * 1  2/113 (1.77%)  0/116 (0.00%) 
Gastrointestinal infection * 1  0/113 (0.00%)  1/116 (0.86%) 
Groin abscess * 1  0/113 (0.00%)  1/116 (0.86%) 
Herpes simplex * 1  1/113 (0.88%)  0/116 (0.00%) 
Herpes virus infection * 1  1/113 (0.88%)  0/116 (0.00%) 
Herpes zoster * 1  0/113 (0.00%)  1/116 (0.86%) 
Impetigo * 1  1/113 (0.88%)  0/116 (0.00%) 
Infected cyst * 1  0/113 (0.00%)  1/116 (0.86%) 
Infection * 1  1/113 (0.88%)  1/116 (0.86%) 
Influenza * 1  13/113 (11.50%)  19/116 (16.38%) 
Injection site abscess * 1  2/113 (1.77%)  0/116 (0.00%) 
Laryngitis * 1  3/113 (2.65%)  2/116 (1.72%) 
Localised infection * 1  0/113 (0.00%)  1/116 (0.86%) 
Nasopharyngitis * 1  18/113 (15.93%)  17/116 (14.66%) 
Oral herpes * 1  2/113 (1.77%)  0/116 (0.00%) 
Otitis media * 1  2/113 (1.77%)  1/116 (0.86%) 
Pharyngitis * 1  1/113 (0.88%)  2/116 (1.72%) 
Pneumonia * 1  0/113 (0.00%)  1/116 (0.86%) 
Pneumonia mycoplasmal * 1  1/113 (0.88%)  0/116 (0.00%) 
Pseudofolliculitis barbae * 1  1/113 (0.88%)  0/116 (0.00%) 
Respiratory tract infection * 1  4/113 (3.54%)  2/116 (1.72%) 
Rhinitis * 1  5/113 (4.42%)  1/116 (0.86%) 
Sinusitis * 1  5/113 (4.42%)  4/116 (3.45%) 
Skin infection * 1  1/113 (0.88%)  0/116 (0.00%) 
Tinea pedis * 1  1/113 (0.88%)  1/116 (0.86%) 
Tonsillitis * 1  1/113 (0.88%)  0/116 (0.00%) 
Tooth abscess * 1  0/113 (0.00%)  1/116 (0.86%) 
Tooth infection * 1  2/113 (1.77%)  1/116 (0.86%) 
Upper respiratory tract infection * 1  3/113 (2.65%)  4/116 (3.45%) 
Urinary tract infection * 1  12/113 (10.62%)  6/116 (5.17%) 
Vaginal infection * 1  1/113 (0.88%)  0/116 (0.00%) 
Viral upper respiratory tract infection * 1  1/113 (0.88%)  0/116 (0.00%) 
Vulvovaginal candidiasis * 1  2/113 (1.77%)  0/116 (0.00%) 
Vulvovaginal mycotic infection * 1  1/113 (0.88%)  0/116 (0.00%) 
Blood iron decreased * 1  1/113 (0.88%)  0/116 (0.00%) 
Injury, poisoning and procedural complications     
Ankle fracture * 1  1/113 (0.88%)  0/116 (0.00%) 
Arthropod bite * 1  1/113 (0.88%)  0/116 (0.00%) 
Arthropod sting * 1  1/113 (0.88%)  0/116 (0.00%) 
Concussion * 1  1/113 (0.88%)  0/116 (0.00%) 
Contusion * 1  1/113 (0.88%)  1/116 (0.86%) 
Epicondylitis * 1  1/113 (0.88%)  0/116 (0.00%) 
Fall * 1  1/113 (0.88%)  0/116 (0.00%) 
Joint injury * 1  3/113 (2.65%)  0/116 (0.00%) 
Joint sprain * 1  1/113 (0.88%)  1/116 (0.86%) 
Limb injury * 1  1/113 (0.88%)  0/116 (0.00%) 
Procedural headache * 1  1/113 (0.88%)  0/116 (0.00%) 
Tendon injury * 1  0/113 (0.00%)  1/116 (0.86%) 
Tooth injury * 1  0/113 (0.00%)  1/116 (0.86%) 
Traumatic brain injury * 1  0/113 (0.00%)  1/116 (0.86%) 
Whiplash injury * 1  0/113 (0.00%)  2/116 (1.72%) 
Wrist fracture * 1  0/113 (0.00%)  1/116 (0.86%) 
Investigations     
Alanine aminotransferase increased * 1  1/113 (0.88%)  0/116 (0.00%) 
Anti-thyroid antibody positive * 1  1/113 (0.88%)  0/116 (0.00%) 
Antibody test positive * 1  0/113 (0.00%)  2/116 (1.72%) 
Blood creatine phosphokinase increased * 1  3/113 (2.65%)  1/116 (0.86%) 
Blood creatinine decreased * 1  0/113 (0.00%)  1/116 (0.86%) 
Blood folate decreased * 1  2/113 (1.77%)  1/116 (0.86%) 
Blood glucose increased * 1  2/113 (1.77%)  0/116 (0.00%) 
Blood parathyroid hormone increased * 1  1/113 (0.88%)  0/116 (0.00%) 
Blood thyroid stimulating hormone abnormal * 1  0/113 (0.00%)  1/116 (0.86%) 
Blood thyroid stimulating hormone increased * 1  1/113 (0.88%)  0/116 (0.00%) 
Creatine urine abnormal * 1  0/113 (0.00%)  1/116 (0.86%) 
Creatinine urine increased * 1  0/113 (0.00%)  1/116 (0.86%) 
Drug specific antibody present * 1  0/113 (0.00%)  1/116 (0.86%) 
Electrocardiogram abnormal * 1  0/113 (0.00%)  1/116 (0.86%) 
Hepatic enzyme increased * 1  2/113 (1.77%)  0/116 (0.00%) 
Liver function test abnormal * 1  1/113 (0.88%)  0/116 (0.00%) 
Lymphocyte count decreased * 1  0/113 (0.00%)  2/116 (1.72%) 
Platelet count decreased * 1  0/113 (0.00%)  1/116 (0.86%) 
Thyroid function test abnormal * 1  0/113 (0.00%)  1/116 (0.86%) 
Urine calcium * 1  0/113 (0.00%)  1/116 (0.86%) 
Urine calcium/creatinine ratio increased * 1  1/113 (0.88%)  0/116 (0.00%) 
Vitamin B12 decreased * 1  2/113 (1.77%)  1/116 (0.86%) 
Weight decreased * 1  0/113 (0.00%)  1/116 (0.86%) 
Weight increased * 1  0/113 (0.00%)  1/116 (0.86%) 
White blood cell count increased * 1  1/113 (0.88%)  0/116 (0.00%) 
Metabolism and nutrition disorders     
Hypercholesterolaemia * 1  0/113 (0.00%)  1/116 (0.86%) 
Hypertriglyceridaemia * 1  1/113 (0.88%)  0/116 (0.00%) 
Iron deficiency * 1  1/113 (0.88%)  0/116 (0.00%) 
Vitamin B12 deficiency * 1  2/113 (1.77%)  0/116 (0.00%) 
Vitamin D deficiency * 1  0/113 (0.00%)  1/116 (0.86%) 
Musculoskeletal and connective tissue disorders     
Arthralgia * 1  4/113 (3.54%)  5/116 (4.31%) 
Back pain * 1  10/113 (8.85%)  7/116 (6.03%) 
Bursitis * 1  0/113 (0.00%)  1/116 (0.86%) 
Flank pain * 1  1/113 (0.88%)  0/116 (0.00%) 
Growing pains * 1  1/113 (0.88%)  0/116 (0.00%) 
Intervertebral disc protrusion * 1  1/113 (0.88%)  1/116 (0.86%) 
Joint swelling * 1  2/113 (1.77%)  0/116 (0.00%) 
Limb discomfort * 1  0/113 (0.00%)  1/116 (0.86%) 
Muscle spasms * 1  7/113 (6.19%)  1/116 (0.86%) 
Muscle tightness * 1  1/113 (0.88%)  0/116 (0.00%) 
Muscular weakness * 1  3/113 (2.65%)  1/116 (0.86%) 
Musculoskeletal discomfort * 1  1/113 (0.88%)  0/116 (0.00%) 
Musculoskeletal pain * 1  2/113 (1.77%)  2/116 (1.72%) 
Musculoskeletal stiffness * 1  2/113 (1.77%)  0/116 (0.00%) 
Myalgia * 1  2/113 (1.77%)  1/116 (0.86%) 
Myokymia * 1  0/113 (0.00%)  1/116 (0.86%) 
Neck pain * 1  5/113 (4.42%)  3/116 (2.59%) 
Osteopenia * 1  0/113 (0.00%)  5/116 (4.31%) 
Pain in extremity * 1  13/113 (11.50%)  6/116 (5.17%) 
Pain in jaw * 1  0/113 (0.00%)  1/116 (0.86%) 
Rheumatic fever * 1  1/113 (0.88%)  0/116 (0.00%) 
Tendonitis * 1  1/113 (0.88%)  2/116 (1.72%) 
Tenosynovitis * 1  1/113 (0.88%)  0/116 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Lipofibroma * 1  1/113 (0.88%)  0/116 (0.00%) 
Morton's neuroma * 1  1/113 (0.88%)  0/116 (0.00%) 
Mycosis fungoides * 1  1/113 (0.88%)  0/116 (0.00%) 
Thyroid neoplasm * 1  0/113 (0.00%)  1/116 (0.86%) 
Uterine leiomyoma * 1  0/113 (0.00%)  1/116 (0.86%) 
Nervous system disorders     
Balance disorder * 1  1/113 (0.88%)  0/116 (0.00%) 
Burning sensation * 1  1/113 (0.88%)  1/116 (0.86%) 
Carotid artery stenosis * 1  1/113 (0.88%)  0/116 (0.00%) 
Carpal tunnel syndrome * 1  1/113 (0.88%)  1/116 (0.86%) 
Cervicobrachial syndrome * 1  0/113 (0.00%)  1/116 (0.86%) 
Coordination abnormal * 1  0/113 (0.00%)  2/116 (1.72%) 
Dizziness * 1  5/113 (4.42%)  4/116 (3.45%) 
Dystonia * 1  1/113 (0.88%)  0/116 (0.00%) 
Facial neuralgia * 1  0/113 (0.00%)  1/116 (0.86%) 
Headache * 1  20/113 (17.70%)  21/116 (18.10%) 
Hypoaesthesia * 1  2/113 (1.77%)  2/116 (1.72%) 
Memory impairment * 1  2/113 (1.77%)  0/116 (0.00%) 
Meralgia paraesthetica * 1  1/113 (0.88%)  0/116 (0.00%) 
Migraine * 1  6/113 (5.31%)  5/116 (4.31%) 
Migraine with aura * 1  1/113 (0.88%)  0/116 (0.00%) 
Motor dysfunction * 1  1/113 (0.88%)  0/116 (0.00%) 
Multiple sclerosis relapse * 1  0/113 (0.00%)  2/116 (1.72%) 
Neuralgia * 1  1/113 (0.88%)  0/116 (0.00%) 
Paraesthesia * 1  5/113 (4.42%)  4/116 (3.45%) 
Presyncope * 1  0/113 (0.00%)  1/116 (0.86%) 
Restless legs syndrome * 1  0/113 (0.00%)  3/116 (2.59%) 
Sciatica * 1  1/113 (0.88%)  1/116 (0.86%) 
Sensory disturbance * 1  4/113 (3.54%)  3/116 (2.59%) 
Syncope * 1  2/113 (1.77%)  0/116 (0.00%) 
Tremor * 1  2/113 (1.77%)  2/116 (1.72%) 
Pregnancy, puerperium and perinatal conditions     
Pregnancy * 1  2/113 (1.77%)  0/116 (0.00%) 
Psychiatric disorders     
Affective disorder * 1  0/113 (0.00%)  2/116 (1.72%) 
Alcohol abuse * 1  0/113 (0.00%)  1/116 (0.86%) 
Anxiety * 1  2/113 (1.77%)  5/116 (4.31%) 
Anxiety disorder * 1  1/113 (0.88%)  0/116 (0.00%) 
Attention deficit/hyperactivity disorder * 1  0/113 (0.00%)  1/116 (0.86%) 
Delusional perception * 1  1/113 (0.88%)  0/116 (0.00%) 
Depression * 1  4/113 (3.54%)  2/116 (1.72%) 
Fear of needles * 1  0/113 (0.00%)  1/116 (0.86%) 
Insomnia * 1  4/113 (3.54%)  4/116 (3.45%) 
Loss of libido * 1  0/113 (0.00%)  1/116 (0.86%) 
Mood swings * 1  2/113 (1.77%)  0/116 (0.00%) 
Panic attack * 1  0/113 (0.00%)  3/116 (2.59%) 
Restlessness * 1  0/113 (0.00%)  1/116 (0.86%) 
Sleep disorder * 1  1/113 (0.88%)  4/116 (3.45%) 
Stress * 1  2/113 (1.77%)  0/116 (0.00%) 
Renal and urinary disorders     
Bladder dysfunction * 1  1/113 (0.88%)  1/116 (0.86%) 
Dysuria * 1  2/113 (1.77%)  4/116 (3.45%) 
Incontinence * 1  0/113 (0.00%)  1/116 (0.86%) 
Micturition urgency * 1  0/113 (0.00%)  1/116 (0.86%) 
Nephrolithiasis * 1  1/113 (0.88%)  0/116 (0.00%) 
Pollakiuria * 1  2/113 (1.77%)  0/116 (0.00%) 
Urinary incontinence * 1  2/113 (1.77%)  0/116 (0.00%) 
Urinary retention * 1  1/113 (0.88%)  0/116 (0.00%) 
Urinary tract pain * 1  1/113 (0.88%)  0/116 (0.00%) 
Reproductive system and breast disorders     
Cervical dysplasia * 1  0/113 (0.00%)  1/116 (0.86%) 
Dysmenorrhoea * 1  1/113 (0.88%)  1/116 (0.86%) 
Erectile dysfunction * 1  2/113 (1.77%)  1/116 (0.86%) 
Menopausal symptoms * 1  1/113 (0.88%)  0/116 (0.00%) 
Menstruation irregular * 1  1/113 (0.88%)  0/116 (0.00%) 
Metrorrhagia * 1  0/113 (0.00%)  1/116 (0.86%) 
Ovarian cyst * 1  1/113 (0.88%)  1/116 (0.86%) 
Premenstrual syndrome * 1  0/113 (0.00%)  1/116 (0.86%) 
Sexual dysfunction * 1  1/113 (0.88%)  0/116 (0.00%) 
Uterine enlargement * 1  0/113 (0.00%)  1/116 (0.86%) 
Vaginal discharge * 1  1/113 (0.88%)  0/116 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Asthma * 1  0/113 (0.00%)  1/116 (0.86%) 
Cough * 1  7/113 (6.19%)  6/116 (5.17%) 
Dysphonia * 1  2/113 (1.77%)  1/116 (0.86%) 
Dyspnoea * 1  1/113 (0.88%)  0/116 (0.00%) 
Epistaxis * 1  1/113 (0.88%)  1/116 (0.86%) 
Oropharyngeal pain * 1  7/113 (6.19%)  5/116 (4.31%) 
Paranasal sinus mucosal hypertrophy * 1  1/113 (0.88%)  0/116 (0.00%) 
Pulmonary hilum mass * 1  1/113 (0.88%)  0/116 (0.00%) 
Rhinitis allergic * 1  1/113 (0.88%)  1/116 (0.86%) 
Skin and subcutaneous tissue disorders     
Acne * 1  1/113 (0.88%)  1/116 (0.86%) 
Alopecia * 1  2/113 (1.77%)  1/116 (0.86%) 
Blister * 1  1/113 (0.88%)  0/116 (0.00%) 
Dermatitis * 1  1/113 (0.88%)  0/116 (0.00%) 
Dermatitis psoriasiform * 1  0/113 (0.00%)  1/116 (0.86%) 
Eczema * 1  1/113 (0.88%)  1/116 (0.86%) 
Erythema * 1  1/113 (0.88%)  1/116 (0.86%) 
Erythema nodosum * 1  0/113 (0.00%)  1/116 (0.86%) 
Hyperhidrosis * 1  0/113 (0.00%)  1/116 (0.86%) 
Pain of skin * 1  1/113 (0.88%)  0/116 (0.00%) 
Pigmentation disorder * 1  1/113 (0.88%)  0/116 (0.00%) 
Pityriasis rosea * 1  0/113 (0.00%)  1/116 (0.86%) 
Pruritus * 1  1/113 (0.88%)  0/116 (0.00%) 
Pruritus generalised * 1  0/113 (0.00%)  1/116 (0.86%) 
Rash pruritic * 1  0/113 (0.00%)  1/116 (0.86%) 
Seborrhoeic dermatitis * 1  0/113 (0.00%)  1/116 (0.86%) 
Skin lesion * 1  0/113 (0.00%)  1/116 (0.86%) 
Skin reaction * 1  0/113 (0.00%)  1/116 (0.86%) 
Skin ulcer * 1  1/113 (0.88%)  0/116 (0.00%) 
Urticaria * 1  2/113 (1.77%)  4/116 (3.45%) 
Rash * 1  0/113 (0.00%)  1/116 (0.86%) 
Surgical and medical procedures     
Endodontic procedure * 1  0/113 (0.00%)  1/116 (0.86%) 
Hospitalisation * 1  1/113 (0.88%)  0/116 (0.00%) 
Mammoplasty * 1  1/113 (0.88%)  0/116 (0.00%) 
Parotidectomy * 1  1/113 (0.88%)  0/116 (0.00%) 
Shoulder operation * 1  0/113 (0.00%)  1/116 (0.86%) 
Tooth extraction * 1  1/113 (0.88%)  0/116 (0.00%) 
Wisdom teeth removal * 1  0/113 (0.00%)  1/116 (0.86%) 
Vascular disorders     
Circulatory collapse * 1  0/113 (0.00%)  1/116 (0.86%) 
Haematoma * 1  1/113 (0.88%)  0/116 (0.00%) 
Haemorrhage * 1  0/113 (0.00%)  1/116 (0.86%) 
Hypertension * 1  6/113 (5.31%)  4/116 (3.45%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 13.1
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.
 
Results Point of Contact
Name/Title: Merck KGaA Communication Center
Organization: Merck KGaA
Phone: +49-6151-72-5200
Responsible Party: Merck KGaA, Darmstadt, Germany
ClinicalTrials.gov Identifier: NCT01285401     History of Changes
Other Study ID Numbers: EMR 200136-532
2010-020328-23 ( EudraCT Number )
First Submitted: January 26, 2011
First Posted: January 28, 2011
Results First Submitted: May 31, 2016
Results First Posted: July 11, 2016
Last Update Posted: November 28, 2016