Trial Outcomes & Findings for Vitamin D Supplementation in Cutaneous Malignant Melanoma Outcome (NCT NCT01748448)

NCT ID: NCT01748448

Last Updated: 2025-02-17

Results Overview

Disease free survival will be the primary endpoint of this phase III trial. Study duration for one patient is maximum 9 years and 7 months. Patients are supplemented with studymedication (Vitamin D or placebo) for maximum 3.5 years. This is the treatment period. After the treatment period (in which the patients take study medication, placebo or Vitamin D), there is the follow-up period, no more study medication is taken, the study is still double blind, and the patients are followed at the clinical department for relapse and/or death.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 436 participants
• Primary outcome timeframe: study duration maximum 9 years and 7 months or until relapse
• Results posted on: 2025-02-17

Participant Flow

Participant milestones

Measure	Vitamin D Every month 100 000 units of Vitamin D in syringe oral dispenser is taken . Study duration is maximum 3,5 years or until relapse occurs Vitamin D: - prospective interventional randomized double blind placebo controlled trail * clinical setting (tertiary university hospital) * investigator driven, no pharmaceutical sponsor * cutaneous malignant melanoma patients * add- on study (placebo or vitamin D) on top of optimal standard care * 1:1 inclusion ratio (placebo:Vitamin D) * randomisation after informed consent and screening	Placebo: Oil Every month 100 000 units of vitamin D in syringe Oral dispenser is taken. Study duration is maximum of 3.5 years or until relapse occurs Oil
Treatment Period STARTED	218	218
Treatment Period COMPLETED	216	217
Treatment Period NOT COMPLETED	2	1
Follow-up Period STARTED	216	217
Follow-up Period COMPLETED	216	217
Follow-up Period NOT COMPLETED	0	0

Reasons for withdrawal

Measure	Vitamin D Every month 100 000 units of Vitamin D in syringe oral dispenser is taken . Study duration is maximum 3,5 years or until relapse occurs Vitamin D: - prospective interventional randomized double blind placebo controlled trail * clinical setting (tertiary university hospital) * investigator driven, no pharmaceutical sponsor * cutaneous malignant melanoma patients * add- on study (placebo or vitamin D) on top of optimal standard care * 1:1 inclusion ratio (placebo:Vitamin D) * randomisation after informed consent and screening	Placebo: Oil Every month 100 000 units of vitamin D in syringe Oral dispenser is taken. Study duration is maximum of 3.5 years or until relapse occurs Oil
Treatment Period Consent withdrawn by subject	1	0
Treatment Period Adverse Event	1	0
Treatment Period Personal	0	1

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Measure	Vitamin D n=218 Participants Every month 100 000 units of Vitamin D in syringe oral dispenser is taken . Study duration is maximum 3,5 years or until relapse occurs Vitamin D: - prospective interventional randomized double blind placebo controlled trail * clinical setting (tertiary university hospital) * investigator driven, no pharmaceutical sponsor * cutaneous malignant melanoma patients * add- on study (placebo or vitamin D) on top of optimal standard care * 1:1 inclusion ratio (placebo:Vitamin D) * randomisation after informed consent and screening	Placebo: Oil n=218 Participants Every month 100 000 units of vitamin D in syringe Oral dispenser is taken. Study duration is maximum of 3.5 years or until relapse occurs oil	Total n=436 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=218 Participants	0 Participants n=218 Participants	0 Participants n=436 Participants
Age, Categorical Between 18 and 65 years	157 Participants n=218 Participants	164 Participants n=218 Participants	321 Participants n=436 Participants
Age, Categorical >=65 years	61 Participants n=218 Participants	54 Participants n=218 Participants	115 Participants n=436 Participants
Sex: Female, Male Female	112 Participants n=218 Participants	125 Participants n=218 Participants	237 Participants n=436 Participants
Sex: Female, Male Male	106 Participants n=218 Participants	93 Participants n=218 Participants	199 Participants n=436 Participants
Race and Ethnicity Not Collected	—	—	0 Participants Race and Ethnicity were not collected from any participant.
Education (highest level) Primary	9 Participants n=218 Participants	8 Participants n=218 Participants	17 Participants n=436 Participants
Education (highest level) Secondary school	75 Participants n=218 Participants	68 Participants n=218 Participants	143 Participants n=436 Participants
Education (highest level) Vocational training	43 Participants n=218 Participants	40 Participants n=218 Participants	83 Participants n=436 Participants
Education (highest level) Vocational university	62 Participants n=218 Participants	59 Participants n=218 Participants	121 Participants n=436 Participants
Education (highest level) University graduated	27 Participants n=218 Participants	42 Participants n=218 Participants	69 Participants n=436 Participants
Education (highest level) Other	1 Participants n=218 Participants	1 Participants n=218 Participants	2 Participants n=436 Participants
Education (highest level) Unknown	1 Participants n=218 Participants	0 Participants n=218 Participants	1 Participants n=436 Participants
Current smoking No	99 Participants n=218 Participants	76 Participants n=218 Participants	175 Participants n=436 Participants
Current smoking Yes	33 Participants n=218 Participants	37 Participants n=218 Participants	70 Participants n=436 Participants
Current smoking Never Smoked	85 Participants n=218 Participants	105 Participants n=218 Participants	190 Participants n=436 Participants
Current smoking Unknown	1 Participants n=218 Participants	0 Participants n=218 Participants	1 Participants n=436 Participants

PRIMARY outcome

Timeframe: study duration maximum 9 years and 7 months or until relapse

Disease free survival will be the primary endpoint of this phase III trial. Study duration for one patient is maximum 9 years and 7 months. Patients are supplemented with studymedication (Vitamin D or placebo) for maximum 3.5 years. This is the treatment period. After the treatment period (in which the patients take study medication, placebo or Vitamin D), there is the follow-up period, no more study medication is taken, the study is still double blind, and the patients are followed at the clinical department for relapse and/or death.

Outcome measures

Measure	Vitamin D n=218 Participants Every month 100 000 units of Vitamin D in syringe oral dispenser is taken . Study duration is maximum 3,5 years or until relapse occurs Vitamin D: - prospective interventional randomized double blind placebo controlled trail * clinical setting (tertiary university hospital) * investigator driven, no pharmaceutical sponsor * cutaneous malignant melanoma patients * add- on study (placebo or vitamin D) on top of optimal standard care * 1:1 inclusion ratio (placebo:Vitamin D) * randomisation after informed consent and screening	Placebo: Oil n=218 Participants Every month 100 000 units of vitamin D in syringe Oral dispenser is taken. Study duration is maximum of 3.5 years or until relapse occurs Oil
Relapse Free Survival	41 Participants	32 Participants

SECONDARY outcome

Timeframe: Time at diagnosis

Vitamin D levels at diagnosis will be correlated with melanoma subtype, as assessed clinically and histologically.

Outcome measures

Measure	Vitamin D n=217 Participants Every month 100 000 units of Vitamin D in syringe oral dispenser is taken . Study duration is maximum 3,5 years or until relapse occurs Vitamin D: - prospective interventional randomized double blind placebo controlled trail * clinical setting (tertiary university hospital) * investigator driven, no pharmaceutical sponsor * cutaneous malignant melanoma patients * add- on study (placebo or vitamin D) on top of optimal standard care * 1:1 inclusion ratio (placebo:Vitamin D) * randomisation after informed consent and screening	Placebo: Oil n=218 Participants Every month 100 000 units of vitamin D in syringe Oral dispenser is taken. Study duration is maximum of 3.5 years or until relapse occurs Oil
Melanoma Subtype, as Assessed Clinically and Histologically Nodular melanoma	38 Participants	29 Participants
Melanoma Subtype, as Assessed Clinically and Histologically Superficial spreading melanoma	115 Participants	142 Participants
Melanoma Subtype, as Assessed Clinically and Histologically Acrolentigineus melanoma	8 Participants	6 Participants
Melanoma Subtype, as Assessed Clinically and Histologically Lentigo maligna melanoma	7 Participants	5 Participants
Melanoma Subtype, as Assessed Clinically and Histologically Unknown	22 Participants	21 Participants
Melanoma Subtype, as Assessed Clinically and Histologically Other	27 Participants	15 Participants

SECONDARY outcome

Timeframe: Time at diagnosis

Vitamin D levels at diagnosis will be correlated with melanoma site, as clinically recorded.

Outcome measures

Measure	Vitamin D n=217 Participants Every month 100 000 units of Vitamin D in syringe oral dispenser is taken . Study duration is maximum 3,5 years or until relapse occurs Vitamin D: - prospective interventional randomized double blind placebo controlled trail * clinical setting (tertiary university hospital) * investigator driven, no pharmaceutical sponsor * cutaneous malignant melanoma patients * add- on study (placebo or vitamin D) on top of optimal standard care * 1:1 inclusion ratio (placebo:Vitamin D) * randomisation after informed consent and screening	Placebo: Oil n=218 Participants Every month 100 000 units of vitamin D in syringe Oral dispenser is taken. Study duration is maximum of 3.5 years or until relapse occurs Oil
Melanoma Site, as Clinically Recorded Abdomen- chest	18 Participants	26 Participants
Melanoma Site, as Clinically Recorded Arm - hand	45 Participants	37 Participants
Melanoma Site, as Clinically Recorded Foot	12 Participants	12 Participants
Melanoma Site, as Clinically Recorded Genitals	1 Participants	2 Participants
Melanoma Site, as Clinically Recorded Head-neck	31 Participants	27 Participants
Melanoma Site, as Clinically Recorded Leg	55 Participants	61 Participants
Melanoma Site, as Clinically Recorded Back	55 Participants	53 Participants

SECONDARY outcome

Timeframe: study duration maximum 3.5 years (Treatment period) or until relapse

Population: The number of patients differs from baseline with the other time points for different reasons: patient was already End of study, no sample taken because of various reasons,...

25(OH)D3 serum levels will be recorded at diagnosis and at 6 months intervals up to final study visit.

Outcome measures

Measure	Vitamin D n=214 Participants Every month 100 000 units of Vitamin D in syringe oral dispenser is taken . Study duration is maximum 3,5 years or until relapse occurs Vitamin D: - prospective interventional randomized double blind placebo controlled trail * clinical setting (tertiary university hospital) * investigator driven, no pharmaceutical sponsor * cutaneous malignant melanoma patients * add- on study (placebo or vitamin D) on top of optimal standard care * 1:1 inclusion ratio (placebo:Vitamin D) * randomisation after informed consent and screening	Placebo: Oil n=218 Participants Every month 100 000 units of vitamin D in syringe Oral dispenser is taken. Study duration is maximum of 3.5 years or until relapse occurs Oil
25(OH)D3 Serum Levels At Month 30	44 ng/ml Standard Deviation 12	27 ng/ml Standard Deviation 8
25(OH)D3 Serum Levels Baseline	24 ng/ml Standard Deviation 9	23 ng/ml Standard Deviation 9
25(OH)D3 Serum Levels At Month 6	43 ng/ml Standard Deviation 11	23 ng/ml Standard Deviation 9
25(OH)D3 Serum Levels At Month 12	44 ng/ml Standard Deviation 11	24 ng/ml Standard Deviation 9
25(OH)D3 Serum Levels At Month 18	44 ng/ml Standard Deviation 11	24 ng/ml Standard Deviation 11
25(OH)D3 Serum Levels At Month 24	42 ng/ml Standard Deviation 11	24 ng/ml Standard Deviation 9
25(OH)D3 Serum Levels At Month 36	40 ng/ml Standard Deviation 12	25 ng/ml Standard Deviation 7
25(OH)D3 Serum Levels End of study (end of study medication)	43 ng/ml Standard Deviation 12	27 ng/ml Standard Deviation 9

SECONDARY outcome

Timeframe: Time at diagnosis

Stage of melanoma patient at diagnosis according to the 8th American Joint Committee of Cancer (AJCC) Melanoma staging and classification.

The eighth edition of the AJCC staging system is currently the most widely accepted and standardized approach to melanoma staging and classification at initial diagnosis. Melanoma staging is based on the American Joint Committee on Cancer (AJCC) staging system that uses three key pieces of information for assigning Tumor-Node-Metastasis (TNM) classifications. AJCC staging ifacilitates accurate risk stratification and is essential to guide patient treatment.

The higher the stage, the more severe the melanoma.

Outcome measures

Measure	Vitamin D n=218 Participants Every month 100 000 units of Vitamin D in syringe oral dispenser is taken . Study duration is maximum 3,5 years or until relapse occurs Vitamin D: - prospective interventional randomized double blind placebo controlled trail * clinical setting (tertiary university hospital) * investigator driven, no pharmaceutical sponsor * cutaneous malignant melanoma patients * add- on study (placebo or vitamin D) on top of optimal standard care * 1:1 inclusion ratio (placebo:Vitamin D) * randomisation after informed consent and screening	Placebo: Oil n=218 Participants Every month 100 000 units of vitamin D in syringe Oral dispenser is taken. Study duration is maximum of 3.5 years or until relapse occurs Oil
Stage of Melanoma Patient IA	24 Participants	26 Participants
Stage of Melanoma Patient IB	101 Participants	108 Participants
Stage of Melanoma Patient IIA	29 Participants	30 Participants
Stage of Melanoma Patient IIB	18 Participants	14 Participants
Stage of Melanoma Patient IIC	10 Participants	6 Participants
Stage of Melanoma Patient IIIA	14 Participants	10 Participants
Stage of Melanoma Patient IIIB	9 Participants	8 Participants
Stage of Melanoma Patient IIIC	10 Participants	14 Participants
Stage of Melanoma Patient IIID	0 Participants	1 Participants
Stage of Melanoma Patient Unkown	3 Participants	1 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: study duration maximum 3.5 years (Treatment period) or until relapse

Incidence and severity of adverse events will be recorded every 3 months up to final study visit (from the treatment period).

Outcome measures

Measure	Vitamin D n=218 Participants Every month 100 000 units of Vitamin D in syringe oral dispenser is taken . Study duration is maximum 3,5 years or until relapse occurs Vitamin D: - prospective interventional randomized double blind placebo controlled trail * clinical setting (tertiary university hospital) * investigator driven, no pharmaceutical sponsor * cutaneous malignant melanoma patients * add- on study (placebo or vitamin D) on top of optimal standard care * 1:1 inclusion ratio (placebo:Vitamin D) * randomisation after informed consent and screening	Placebo: Oil n=218 Participants Every month 100 000 units of vitamin D in syringe Oral dispenser is taken. Study duration is maximum of 3.5 years or until relapse occurs Oil
Safety Endpoints:Incidence and Severity of Adverse Events	44 Events	36 Events

Adverse Events

Vitamin D

Serious events: 28 serious events

Other events: 180 other events

Deaths: 13 deaths

Placebo: Oil

Serious events: 33 serious events

Other events: 178 other events

Deaths: 13 deaths

Serious adverse events

Measure	Vitamin D n=218 participants at risk Every month 100 000 units of Vitamin D in syringe oral dispenser is taken . Study duration is maximum 3,5 years or until relapse occurs Vitamin D: - prospective interventional randomized double blind placebo controlled trail * clinical setting (tertiary university hospital) * investigator driven, no pharmaceutical sponsor * cutaneous malignant melanoma patients * add- on study (placebo or vitamin D) on top of optimal standard care * 1:1 inclusion ratio (placebo:Vitamin D) * randomisation after informed consent and screening	Placebo: Oil n=218 participants at risk Every month 100 000 units of vitamin D in syringe Oral dispenser is taken. Study duration is maximum of 3.5 years or until relapse occurs Oil
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasms benign, malignant and unspecified (incl cysts and polyps)	2.8% 6/218 • In this study, the collection period for adverse events and serious Adverse events starts at the randomisation and ends when the patient completes the Treatment period of the study, serious and/or other adverse events were assessed up to 3.5 years. All-Cause Mortality was monitored for maximum 9 years and 7 months. The investigator will use the following terms te assess the severity of the adverse event: mild, moderate severe. The investigator will use the follwing causality terms to assess the relationship of teh adverse event or clinical efficacy to the use of the investigational medicinal product: reasonable causal relationship or not.	2.3% 5/218 • In this study, the collection period for adverse events and serious Adverse events starts at the randomisation and ends when the patient completes the Treatment period of the study, serious and/or other adverse events were assessed up to 3.5 years. All-Cause Mortality was monitored for maximum 9 years and 7 months. The investigator will use the following terms te assess the severity of the adverse event: mild, moderate severe. The investigator will use the follwing causality terms to assess the relationship of teh adverse event or clinical efficacy to the use of the investigational medicinal product: reasonable causal relationship or not.
Vascular disorders Vascular disorders	0.00% 0/218 • In this study, the collection period for adverse events and serious Adverse events starts at the randomisation and ends when the patient completes the Treatment period of the study, serious and/or other adverse events were assessed up to 3.5 years. All-Cause Mortality was monitored for maximum 9 years and 7 months. The investigator will use the following terms te assess the severity of the adverse event: mild, moderate severe. The investigator will use the follwing causality terms to assess the relationship of teh adverse event or clinical efficacy to the use of the investigational medicinal product: reasonable causal relationship or not.	0.46% 1/218 • In this study, the collection period for adverse events and serious Adverse events starts at the randomisation and ends when the patient completes the Treatment period of the study, serious and/or other adverse events were assessed up to 3.5 years. All-Cause Mortality was monitored for maximum 9 years and 7 months. The investigator will use the following terms te assess the severity of the adverse event: mild, moderate severe. The investigator will use the follwing causality terms to assess the relationship of teh adverse event or clinical efficacy to the use of the investigational medicinal product: reasonable causal relationship or not.
Surgical and medical procedures Surgical and medical procedures	2.8% 6/218 • In this study, the collection period for adverse events and serious Adverse events starts at the randomisation and ends when the patient completes the Treatment period of the study, serious and/or other adverse events were assessed up to 3.5 years. All-Cause Mortality was monitored for maximum 9 years and 7 months. The investigator will use the following terms te assess the severity of the adverse event: mild, moderate severe. The investigator will use the follwing causality terms to assess the relationship of teh adverse event or clinical efficacy to the use of the investigational medicinal product: reasonable causal relationship or not.	2.8% 6/218 • In this study, the collection period for adverse events and serious Adverse events starts at the randomisation and ends when the patient completes the Treatment period of the study, serious and/or other adverse events were assessed up to 3.5 years. All-Cause Mortality was monitored for maximum 9 years and 7 months. The investigator will use the following terms te assess the severity of the adverse event: mild, moderate severe. The investigator will use the follwing causality terms to assess the relationship of teh adverse event or clinical efficacy to the use of the investigational medicinal product: reasonable causal relationship or not.
General disorders General disorders and administration site conditions	0.46% 1/218 • In this study, the collection period for adverse events and serious Adverse events starts at the randomisation and ends when the patient completes the Treatment period of the study, serious and/or other adverse events were assessed up to 3.5 years. All-Cause Mortality was monitored for maximum 9 years and 7 months. The investigator will use the following terms te assess the severity of the adverse event: mild, moderate severe. The investigator will use the follwing causality terms to assess the relationship of teh adverse event or clinical efficacy to the use of the investigational medicinal product: reasonable causal relationship or not.	1.4% 3/218 • In this study, the collection period for adverse events and serious Adverse events starts at the randomisation and ends when the patient completes the Treatment period of the study, serious and/or other adverse events were assessed up to 3.5 years. All-Cause Mortality was monitored for maximum 9 years and 7 months. The investigator will use the following terms te assess the severity of the adverse event: mild, moderate severe. The investigator will use the follwing causality terms to assess the relationship of teh adverse event or clinical efficacy to the use of the investigational medicinal product: reasonable causal relationship or not.
Reproductive system and breast disorders Reproductive system and breast disorders	0.46% 1/218 • In this study, the collection period for adverse events and serious Adverse events starts at the randomisation and ends when the patient completes the Treatment period of the study, serious and/or other adverse events were assessed up to 3.5 years. All-Cause Mortality was monitored for maximum 9 years and 7 months. The investigator will use the following terms te assess the severity of the adverse event: mild, moderate severe. The investigator will use the follwing causality terms to assess the relationship of teh adverse event or clinical efficacy to the use of the investigational medicinal product: reasonable causal relationship or not.	0.46% 1/218 • In this study, the collection period for adverse events and serious Adverse events starts at the randomisation and ends when the patient completes the Treatment period of the study, serious and/or other adverse events were assessed up to 3.5 years. All-Cause Mortality was monitored for maximum 9 years and 7 months. The investigator will use the following terms te assess the severity of the adverse event: mild, moderate severe. The investigator will use the follwing causality terms to assess the relationship of teh adverse event or clinical efficacy to the use of the investigational medicinal product: reasonable causal relationship or not.
Respiratory, thoracic and mediastinal disorders Respiratory, thoracic and mediastinal disorders	0.00% 0/218 • In this study, the collection period for adverse events and serious Adverse events starts at the randomisation and ends when the patient completes the Treatment period of the study, serious and/or other adverse events were assessed up to 3.5 years. All-Cause Mortality was monitored for maximum 9 years and 7 months. The investigator will use the following terms te assess the severity of the adverse event: mild, moderate severe. The investigator will use the follwing causality terms to assess the relationship of teh adverse event or clinical efficacy to the use of the investigational medicinal product: reasonable causal relationship or not.	0.92% 2/218 • In this study, the collection period for adverse events and serious Adverse events starts at the randomisation and ends when the patient completes the Treatment period of the study, serious and/or other adverse events were assessed up to 3.5 years. All-Cause Mortality was monitored for maximum 9 years and 7 months. The investigator will use the following terms te assess the severity of the adverse event: mild, moderate severe. The investigator will use the follwing causality terms to assess the relationship of teh adverse event or clinical efficacy to the use of the investigational medicinal product: reasonable causal relationship or not.
Psychiatric disorders Psychiatric disorders	0.00% 0/218 • In this study, the collection period for adverse events and serious Adverse events starts at the randomisation and ends when the patient completes the Treatment period of the study, serious and/or other adverse events were assessed up to 3.5 years. All-Cause Mortality was monitored for maximum 9 years and 7 months. The investigator will use the following terms te assess the severity of the adverse event: mild, moderate severe. The investigator will use the follwing causality terms to assess the relationship of teh adverse event or clinical efficacy to the use of the investigational medicinal product: reasonable causal relationship or not.	0.46% 1/218 • In this study, the collection period for adverse events and serious Adverse events starts at the randomisation and ends when the patient completes the Treatment period of the study, serious and/or other adverse events were assessed up to 3.5 years. All-Cause Mortality was monitored for maximum 9 years and 7 months. The investigator will use the following terms te assess the severity of the adverse event: mild, moderate severe. The investigator will use the follwing causality terms to assess the relationship of teh adverse event or clinical efficacy to the use of the investigational medicinal product: reasonable causal relationship or not.
Cardiac disorders Cardiac disorders	1.8% 4/218 • In this study, the collection period for adverse events and serious Adverse events starts at the randomisation and ends when the patient completes the Treatment period of the study, serious and/or other adverse events were assessed up to 3.5 years. All-Cause Mortality was monitored for maximum 9 years and 7 months. The investigator will use the following terms te assess the severity of the adverse event: mild, moderate severe. The investigator will use the follwing causality terms to assess the relationship of teh adverse event or clinical efficacy to the use of the investigational medicinal product: reasonable causal relationship or not.	0.92% 2/218 • In this study, the collection period for adverse events and serious Adverse events starts at the randomisation and ends when the patient completes the Treatment period of the study, serious and/or other adverse events were assessed up to 3.5 years. All-Cause Mortality was monitored for maximum 9 years and 7 months. The investigator will use the following terms te assess the severity of the adverse event: mild, moderate severe. The investigator will use the follwing causality terms to assess the relationship of teh adverse event or clinical efficacy to the use of the investigational medicinal product: reasonable causal relationship or not.
Nervous system disorders Nervous system disorders	0.46% 1/218 • In this study, the collection period for adverse events and serious Adverse events starts at the randomisation and ends when the patient completes the Treatment period of the study, serious and/or other adverse events were assessed up to 3.5 years. All-Cause Mortality was monitored for maximum 9 years and 7 months. The investigator will use the following terms te assess the severity of the adverse event: mild, moderate severe. The investigator will use the follwing causality terms to assess the relationship of teh adverse event or clinical efficacy to the use of the investigational medicinal product: reasonable causal relationship or not.	0.00% 0/218 • In this study, the collection period for adverse events and serious Adverse events starts at the randomisation and ends when the patient completes the Treatment period of the study, serious and/or other adverse events were assessed up to 3.5 years. All-Cause Mortality was monitored for maximum 9 years and 7 months. The investigator will use the following terms te assess the severity of the adverse event: mild, moderate severe. The investigator will use the follwing causality terms to assess the relationship of teh adverse event or clinical efficacy to the use of the investigational medicinal product: reasonable causal relationship or not.
Ear and labyrinth disorders Ear and labyrinth disorders	0.46% 1/218 • In this study, the collection period for adverse events and serious Adverse events starts at the randomisation and ends when the patient completes the Treatment period of the study, serious and/or other adverse events were assessed up to 3.5 years. All-Cause Mortality was monitored for maximum 9 years and 7 months. The investigator will use the following terms te assess the severity of the adverse event: mild, moderate severe. The investigator will use the follwing causality terms to assess the relationship of teh adverse event or clinical efficacy to the use of the investigational medicinal product: reasonable causal relationship or not.	0.00% 0/218 • In this study, the collection period for adverse events and serious Adverse events starts at the randomisation and ends when the patient completes the Treatment period of the study, serious and/or other adverse events were assessed up to 3.5 years. All-Cause Mortality was monitored for maximum 9 years and 7 months. The investigator will use the following terms te assess the severity of the adverse event: mild, moderate severe. The investigator will use the follwing causality terms to assess the relationship of teh adverse event or clinical efficacy to the use of the investigational medicinal product: reasonable causal relationship or not.
Eye disorders Eye disorders	0.46% 1/218 • In this study, the collection period for adverse events and serious Adverse events starts at the randomisation and ends when the patient completes the Treatment period of the study, serious and/or other adverse events were assessed up to 3.5 years. All-Cause Mortality was monitored for maximum 9 years and 7 months. The investigator will use the following terms te assess the severity of the adverse event: mild, moderate severe. The investigator will use the follwing causality terms to assess the relationship of teh adverse event or clinical efficacy to the use of the investigational medicinal product: reasonable causal relationship or not.	0.00% 0/218 • In this study, the collection period for adverse events and serious Adverse events starts at the randomisation and ends when the patient completes the Treatment period of the study, serious and/or other adverse events were assessed up to 3.5 years. All-Cause Mortality was monitored for maximum 9 years and 7 months. The investigator will use the following terms te assess the severity of the adverse event: mild, moderate severe. The investigator will use the follwing causality terms to assess the relationship of teh adverse event or clinical efficacy to the use of the investigational medicinal product: reasonable causal relationship or not.
Gastrointestinal disorders Gastrointestinal disorders	1.4% 3/218 • In this study, the collection period for adverse events and serious Adverse events starts at the randomisation and ends when the patient completes the Treatment period of the study, serious and/or other adverse events were assessed up to 3.5 years. All-Cause Mortality was monitored for maximum 9 years and 7 months. The investigator will use the following terms te assess the severity of the adverse event: mild, moderate severe. The investigator will use the follwing causality terms to assess the relationship of teh adverse event or clinical efficacy to the use of the investigational medicinal product: reasonable causal relationship or not.	2.3% 5/218 • In this study, the collection period for adverse events and serious Adverse events starts at the randomisation and ends when the patient completes the Treatment period of the study, serious and/or other adverse events were assessed up to 3.5 years. All-Cause Mortality was monitored for maximum 9 years and 7 months. The investigator will use the following terms te assess the severity of the adverse event: mild, moderate severe. The investigator will use the follwing causality terms to assess the relationship of teh adverse event or clinical efficacy to the use of the investigational medicinal product: reasonable causal relationship or not.
Hepatobiliary disorders Hepatobiliary disorders	0.92% 2/218 • In this study, the collection period for adverse events and serious Adverse events starts at the randomisation and ends when the patient completes the Treatment period of the study, serious and/or other adverse events were assessed up to 3.5 years. All-Cause Mortality was monitored for maximum 9 years and 7 months. The investigator will use the following terms te assess the severity of the adverse event: mild, moderate severe. The investigator will use the follwing causality terms to assess the relationship of teh adverse event or clinical efficacy to the use of the investigational medicinal product: reasonable causal relationship or not.	0.46% 1/218 • In this study, the collection period for adverse events and serious Adverse events starts at the randomisation and ends when the patient completes the Treatment period of the study, serious and/or other adverse events were assessed up to 3.5 years. All-Cause Mortality was monitored for maximum 9 years and 7 months. The investigator will use the following terms te assess the severity of the adverse event: mild, moderate severe. The investigator will use the follwing causality terms to assess the relationship of teh adverse event or clinical efficacy to the use of the investigational medicinal product: reasonable causal relationship or not.
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders	0.46% 1/218 • In this study, the collection period for adverse events and serious Adverse events starts at the randomisation and ends when the patient completes the Treatment period of the study, serious and/or other adverse events were assessed up to 3.5 years. All-Cause Mortality was monitored for maximum 9 years and 7 months. The investigator will use the following terms te assess the severity of the adverse event: mild, moderate severe. The investigator will use the follwing causality terms to assess the relationship of teh adverse event or clinical efficacy to the use of the investigational medicinal product: reasonable causal relationship or not.	0.92% 2/218 • In this study, the collection period for adverse events and serious Adverse events starts at the randomisation and ends when the patient completes the Treatment period of the study, serious and/or other adverse events were assessed up to 3.5 years. All-Cause Mortality was monitored for maximum 9 years and 7 months. The investigator will use the following terms te assess the severity of the adverse event: mild, moderate severe. The investigator will use the follwing causality terms to assess the relationship of teh adverse event or clinical efficacy to the use of the investigational medicinal product: reasonable causal relationship or not.
Renal and urinary disorders Renal and urinary disorders	1.4% 3/218 • In this study, the collection period for adverse events and serious Adverse events starts at the randomisation and ends when the patient completes the Treatment period of the study, serious and/or other adverse events were assessed up to 3.5 years. All-Cause Mortality was monitored for maximum 9 years and 7 months. The investigator will use the following terms te assess the severity of the adverse event: mild, moderate severe. The investigator will use the follwing causality terms to assess the relationship of teh adverse event or clinical efficacy to the use of the investigational medicinal product: reasonable causal relationship or not.	0.92% 2/218 • In this study, the collection period for adverse events and serious Adverse events starts at the randomisation and ends when the patient completes the Treatment period of the study, serious and/or other adverse events were assessed up to 3.5 years. All-Cause Mortality was monitored for maximum 9 years and 7 months. The investigator will use the following terms te assess the severity of the adverse event: mild, moderate severe. The investigator will use the follwing causality terms to assess the relationship of teh adverse event or clinical efficacy to the use of the investigational medicinal product: reasonable causal relationship or not.
Endocrine disorders Endocrine disorders	0.92% 2/218 • In this study, the collection period for adverse events and serious Adverse events starts at the randomisation and ends when the patient completes the Treatment period of the study, serious and/or other adverse events were assessed up to 3.5 years. All-Cause Mortality was monitored for maximum 9 years and 7 months. The investigator will use the following terms te assess the severity of the adverse event: mild, moderate severe. The investigator will use the follwing causality terms to assess the relationship of teh adverse event or clinical efficacy to the use of the investigational medicinal product: reasonable causal relationship or not.	0.00% 0/218 • In this study, the collection period for adverse events and serious Adverse events starts at the randomisation and ends when the patient completes the Treatment period of the study, serious and/or other adverse events were assessed up to 3.5 years. All-Cause Mortality was monitored for maximum 9 years and 7 months. The investigator will use the following terms te assess the severity of the adverse event: mild, moderate severe. The investigator will use the follwing causality terms to assess the relationship of teh adverse event or clinical efficacy to the use of the investigational medicinal product: reasonable causal relationship or not.
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tissue disorders	1.8% 4/218 • In this study, the collection period for adverse events and serious Adverse events starts at the randomisation and ends when the patient completes the Treatment period of the study, serious and/or other adverse events were assessed up to 3.5 years. All-Cause Mortality was monitored for maximum 9 years and 7 months. The investigator will use the following terms te assess the severity of the adverse event: mild, moderate severe. The investigator will use the follwing causality terms to assess the relationship of teh adverse event or clinical efficacy to the use of the investigational medicinal product: reasonable causal relationship or not.	1.8% 4/218 • In this study, the collection period for adverse events and serious Adverse events starts at the randomisation and ends when the patient completes the Treatment period of the study, serious and/or other adverse events were assessed up to 3.5 years. All-Cause Mortality was monitored for maximum 9 years and 7 months. The investigator will use the following terms te assess the severity of the adverse event: mild, moderate severe. The investigator will use the follwing causality terms to assess the relationship of teh adverse event or clinical efficacy to the use of the investigational medicinal product: reasonable causal relationship or not.
Infections and infestations Infections and infestations	1.4% 3/218 • In this study, the collection period for adverse events and serious Adverse events starts at the randomisation and ends when the patient completes the Treatment period of the study, serious and/or other adverse events were assessed up to 3.5 years. All-Cause Mortality was monitored for maximum 9 years and 7 months. The investigator will use the following terms te assess the severity of the adverse event: mild, moderate severe. The investigator will use the follwing causality terms to assess the relationship of teh adverse event or clinical efficacy to the use of the investigational medicinal product: reasonable causal relationship or not.	0.46% 1/218 • In this study, the collection period for adverse events and serious Adverse events starts at the randomisation and ends when the patient completes the Treatment period of the study, serious and/or other adverse events were assessed up to 3.5 years. All-Cause Mortality was monitored for maximum 9 years and 7 months. The investigator will use the following terms te assess the severity of the adverse event: mild, moderate severe. The investigator will use the follwing causality terms to assess the relationship of teh adverse event or clinical efficacy to the use of the investigational medicinal product: reasonable causal relationship or not.

Other adverse events

Measure	Vitamin D n=218 participants at risk Every month 100 000 units of Vitamin D in syringe oral dispenser is taken . Study duration is maximum 3,5 years or until relapse occurs Vitamin D: - prospective interventional randomized double blind placebo controlled trail * clinical setting (tertiary university hospital) * investigator driven, no pharmaceutical sponsor * cutaneous malignant melanoma patients * add- on study (placebo or vitamin D) on top of optimal standard care * 1:1 inclusion ratio (placebo:Vitamin D) * randomisation after informed consent and screening	Placebo: Oil n=218 participants at risk Every month 100 000 units of vitamin D in syringe Oral dispenser is taken. Study duration is maximum of 3.5 years or until relapse occurs Oil
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasms benign, malignant and unspecified (incl cysts and polyps)	8.3% 18/218 • In this study, the collection period for adverse events and serious Adverse events starts at the randomisation and ends when the patient completes the Treatment period of the study, serious and/or other adverse events were assessed up to 3.5 years. All-Cause Mortality was monitored for maximum 9 years and 7 months. The investigator will use the following terms te assess the severity of the adverse event: mild, moderate severe. The investigator will use the follwing causality terms to assess the relationship of teh adverse event or clinical efficacy to the use of the investigational medicinal product: reasonable causal relationship or not.	5.0% 11/218 • In this study, the collection period for adverse events and serious Adverse events starts at the randomisation and ends when the patient completes the Treatment period of the study, serious and/or other adverse events were assessed up to 3.5 years. All-Cause Mortality was monitored for maximum 9 years and 7 months. The investigator will use the following terms te assess the severity of the adverse event: mild, moderate severe. The investigator will use the follwing causality terms to assess the relationship of teh adverse event or clinical efficacy to the use of the investigational medicinal product: reasonable causal relationship or not.
Vascular disorders Vascular disorders	0.92% 2/218 • In this study, the collection period for adverse events and serious Adverse events starts at the randomisation and ends when the patient completes the Treatment period of the study, serious and/or other adverse events were assessed up to 3.5 years. All-Cause Mortality was monitored for maximum 9 years and 7 months. The investigator will use the following terms te assess the severity of the adverse event: mild, moderate severe. The investigator will use the follwing causality terms to assess the relationship of teh adverse event or clinical efficacy to the use of the investigational medicinal product: reasonable causal relationship or not.	0.46% 1/218 • In this study, the collection period for adverse events and serious Adverse events starts at the randomisation and ends when the patient completes the Treatment period of the study, serious and/or other adverse events were assessed up to 3.5 years. All-Cause Mortality was monitored for maximum 9 years and 7 months. The investigator will use the following terms te assess the severity of the adverse event: mild, moderate severe. The investigator will use the follwing causality terms to assess the relationship of teh adverse event or clinical efficacy to the use of the investigational medicinal product: reasonable causal relationship or not.
Surgical and medical procedures Surgical and medical procedures	6.4% 14/218 • In this study, the collection period for adverse events and serious Adverse events starts at the randomisation and ends when the patient completes the Treatment period of the study, serious and/or other adverse events were assessed up to 3.5 years. All-Cause Mortality was monitored for maximum 9 years and 7 months. The investigator will use the following terms te assess the severity of the adverse event: mild, moderate severe. The investigator will use the follwing causality terms to assess the relationship of teh adverse event or clinical efficacy to the use of the investigational medicinal product: reasonable causal relationship or not.	7.3% 16/218 • In this study, the collection period for adverse events and serious Adverse events starts at the randomisation and ends when the patient completes the Treatment period of the study, serious and/or other adverse events were assessed up to 3.5 years. All-Cause Mortality was monitored for maximum 9 years and 7 months. The investigator will use the following terms te assess the severity of the adverse event: mild, moderate severe. The investigator will use the follwing causality terms to assess the relationship of teh adverse event or clinical efficacy to the use of the investigational medicinal product: reasonable causal relationship or not.
Pregnancy, puerperium and perinatal conditions Pregnancy, puerperium and perinatal conditions	0.00% 0/218 • In this study, the collection period for adverse events and serious Adverse events starts at the randomisation and ends when the patient completes the Treatment period of the study, serious and/or other adverse events were assessed up to 3.5 years. All-Cause Mortality was monitored for maximum 9 years and 7 months. The investigator will use the following terms te assess the severity of the adverse event: mild, moderate severe. The investigator will use the follwing causality terms to assess the relationship of teh adverse event or clinical efficacy to the use of the investigational medicinal product: reasonable causal relationship or not.	0.46% 1/218 • In this study, the collection period for adverse events and serious Adverse events starts at the randomisation and ends when the patient completes the Treatment period of the study, serious and/or other adverse events were assessed up to 3.5 years. All-Cause Mortality was monitored for maximum 9 years and 7 months. The investigator will use the following terms te assess the severity of the adverse event: mild, moderate severe. The investigator will use the follwing causality terms to assess the relationship of teh adverse event or clinical efficacy to the use of the investigational medicinal product: reasonable causal relationship or not.
General disorders General disorders and administration site conditions	16.5% 36/218 • In this study, the collection period for adverse events and serious Adverse events starts at the randomisation and ends when the patient completes the Treatment period of the study, serious and/or other adverse events were assessed up to 3.5 years. All-Cause Mortality was monitored for maximum 9 years and 7 months. The investigator will use the following terms te assess the severity of the adverse event: mild, moderate severe. The investigator will use the follwing causality terms to assess the relationship of teh adverse event or clinical efficacy to the use of the investigational medicinal product: reasonable causal relationship or not.	14.7% 32/218 • In this study, the collection period for adverse events and serious Adverse events starts at the randomisation and ends when the patient completes the Treatment period of the study, serious and/or other adverse events were assessed up to 3.5 years. All-Cause Mortality was monitored for maximum 9 years and 7 months. The investigator will use the following terms te assess the severity of the adverse event: mild, moderate severe. The investigator will use the follwing causality terms to assess the relationship of teh adverse event or clinical efficacy to the use of the investigational medicinal product: reasonable causal relationship or not.
Reproductive system and breast disorders Reproductive system and breast disorders	2.8% 6/218 • In this study, the collection period for adverse events and serious Adverse events starts at the randomisation and ends when the patient completes the Treatment period of the study, serious and/or other adverse events were assessed up to 3.5 years. All-Cause Mortality was monitored for maximum 9 years and 7 months. The investigator will use the following terms te assess the severity of the adverse event: mild, moderate severe. The investigator will use the follwing causality terms to assess the relationship of teh adverse event or clinical efficacy to the use of the investigational medicinal product: reasonable causal relationship or not.	2.8% 6/218 • In this study, the collection period for adverse events and serious Adverse events starts at the randomisation and ends when the patient completes the Treatment period of the study, serious and/or other adverse events were assessed up to 3.5 years. All-Cause Mortality was monitored for maximum 9 years and 7 months. The investigator will use the following terms te assess the severity of the adverse event: mild, moderate severe. The investigator will use the follwing causality terms to assess the relationship of teh adverse event or clinical efficacy to the use of the investigational medicinal product: reasonable causal relationship or not.
Respiratory, thoracic and mediastinal disorders Respiratory, thoracic and mediastinal disorders	13.3% 29/218 • In this study, the collection period for adverse events and serious Adverse events starts at the randomisation and ends when the patient completes the Treatment period of the study, serious and/or other adverse events were assessed up to 3.5 years. All-Cause Mortality was monitored for maximum 9 years and 7 months. The investigator will use the following terms te assess the severity of the adverse event: mild, moderate severe. The investigator will use the follwing causality terms to assess the relationship of teh adverse event or clinical efficacy to the use of the investigational medicinal product: reasonable causal relationship or not.	21.1% 46/218 • In this study, the collection period for adverse events and serious Adverse events starts at the randomisation and ends when the patient completes the Treatment period of the study, serious and/or other adverse events were assessed up to 3.5 years. All-Cause Mortality was monitored for maximum 9 years and 7 months. The investigator will use the following terms te assess the severity of the adverse event: mild, moderate severe. The investigator will use the follwing causality terms to assess the relationship of teh adverse event or clinical efficacy to the use of the investigational medicinal product: reasonable causal relationship or not.
Psychiatric disorders Psychiatric disorders	0.46% 1/218 • In this study, the collection period for adverse events and serious Adverse events starts at the randomisation and ends when the patient completes the Treatment period of the study, serious and/or other adverse events were assessed up to 3.5 years. All-Cause Mortality was monitored for maximum 9 years and 7 months. The investigator will use the following terms te assess the severity of the adverse event: mild, moderate severe. The investigator will use the follwing causality terms to assess the relationship of teh adverse event or clinical efficacy to the use of the investigational medicinal product: reasonable causal relationship or not.	0.92% 2/218 • In this study, the collection period for adverse events and serious Adverse events starts at the randomisation and ends when the patient completes the Treatment period of the study, serious and/or other adverse events were assessed up to 3.5 years. All-Cause Mortality was monitored for maximum 9 years and 7 months. The investigator will use the following terms te assess the severity of the adverse event: mild, moderate severe. The investigator will use the follwing causality terms to assess the relationship of teh adverse event or clinical efficacy to the use of the investigational medicinal product: reasonable causal relationship or not.
Product Issues Product issues	19.3% 42/218 • In this study, the collection period for adverse events and serious Adverse events starts at the randomisation and ends when the patient completes the Treatment period of the study, serious and/or other adverse events were assessed up to 3.5 years. All-Cause Mortality was monitored for maximum 9 years and 7 months. The investigator will use the following terms te assess the severity of the adverse event: mild, moderate severe. The investigator will use the follwing causality terms to assess the relationship of teh adverse event or clinical efficacy to the use of the investigational medicinal product: reasonable causal relationship or not.	0.46% 1/218 • In this study, the collection period for adverse events and serious Adverse events starts at the randomisation and ends when the patient completes the Treatment period of the study, serious and/or other adverse events were assessed up to 3.5 years. All-Cause Mortality was monitored for maximum 9 years and 7 months. The investigator will use the following terms te assess the severity of the adverse event: mild, moderate severe. The investigator will use the follwing causality terms to assess the relationship of teh adverse event or clinical efficacy to the use of the investigational medicinal product: reasonable causal relationship or not.
Cardiac disorders Cardiac disorders	4.1% 9/218 • In this study, the collection period for adverse events and serious Adverse events starts at the randomisation and ends when the patient completes the Treatment period of the study, serious and/or other adverse events were assessed up to 3.5 years. All-Cause Mortality was monitored for maximum 9 years and 7 months. The investigator will use the following terms te assess the severity of the adverse event: mild, moderate severe. The investigator will use the follwing causality terms to assess the relationship of teh adverse event or clinical efficacy to the use of the investigational medicinal product: reasonable causal relationship or not.	3.2% 7/218 • In this study, the collection period for adverse events and serious Adverse events starts at the randomisation and ends when the patient completes the Treatment period of the study, serious and/or other adverse events were assessed up to 3.5 years. All-Cause Mortality was monitored for maximum 9 years and 7 months. The investigator will use the following terms te assess the severity of the adverse event: mild, moderate severe. The investigator will use the follwing causality terms to assess the relationship of teh adverse event or clinical efficacy to the use of the investigational medicinal product: reasonable causal relationship or not.
Nervous system disorders Nervous system disorders	6.9% 15/218 • In this study, the collection period for adverse events and serious Adverse events starts at the randomisation and ends when the patient completes the Treatment period of the study, serious and/or other adverse events were assessed up to 3.5 years. All-Cause Mortality was monitored for maximum 9 years and 7 months. The investigator will use the following terms te assess the severity of the adverse event: mild, moderate severe. The investigator will use the follwing causality terms to assess the relationship of teh adverse event or clinical efficacy to the use of the investigational medicinal product: reasonable causal relationship or not.	3.2% 7/218 • In this study, the collection period for adverse events and serious Adverse events starts at the randomisation and ends when the patient completes the Treatment period of the study, serious and/or other adverse events were assessed up to 3.5 years. All-Cause Mortality was monitored for maximum 9 years and 7 months. The investigator will use the following terms te assess the severity of the adverse event: mild, moderate severe. The investigator will use the follwing causality terms to assess the relationship of teh adverse event or clinical efficacy to the use of the investigational medicinal product: reasonable causal relationship or not.
Blood and lymphatic system disorders Blood and lymphatic system disorders	3.7% 8/218 • In this study, the collection period for adverse events and serious Adverse events starts at the randomisation and ends when the patient completes the Treatment period of the study, serious and/or other adverse events were assessed up to 3.5 years. All-Cause Mortality was monitored for maximum 9 years and 7 months. The investigator will use the following terms te assess the severity of the adverse event: mild, moderate severe. The investigator will use the follwing causality terms to assess the relationship of teh adverse event or clinical efficacy to the use of the investigational medicinal product: reasonable causal relationship or not.	1.4% 3/218 • In this study, the collection period for adverse events and serious Adverse events starts at the randomisation and ends when the patient completes the Treatment period of the study, serious and/or other adverse events were assessed up to 3.5 years. All-Cause Mortality was monitored for maximum 9 years and 7 months. The investigator will use the following terms te assess the severity of the adverse event: mild, moderate severe. The investigator will use the follwing causality terms to assess the relationship of teh adverse event or clinical efficacy to the use of the investigational medicinal product: reasonable causal relationship or not.
Ear and labyrinth disorders Ear and labyrinth disorders	3.2% 7/218 • In this study, the collection period for adverse events and serious Adverse events starts at the randomisation and ends when the patient completes the Treatment period of the study, serious and/or other adverse events were assessed up to 3.5 years. All-Cause Mortality was monitored for maximum 9 years and 7 months. The investigator will use the following terms te assess the severity of the adverse event: mild, moderate severe. The investigator will use the follwing causality terms to assess the relationship of teh adverse event or clinical efficacy to the use of the investigational medicinal product: reasonable causal relationship or not.	1.8% 4/218 • In this study, the collection period for adverse events and serious Adverse events starts at the randomisation and ends when the patient completes the Treatment period of the study, serious and/or other adverse events were assessed up to 3.5 years. All-Cause Mortality was monitored for maximum 9 years and 7 months. The investigator will use the following terms te assess the severity of the adverse event: mild, moderate severe. The investigator will use the follwing causality terms to assess the relationship of teh adverse event or clinical efficacy to the use of the investigational medicinal product: reasonable causal relationship or not.
Eye disorders Eye disorders	4.1% 9/218 • In this study, the collection period for adverse events and serious Adverse events starts at the randomisation and ends when the patient completes the Treatment period of the study, serious and/or other adverse events were assessed up to 3.5 years. All-Cause Mortality was monitored for maximum 9 years and 7 months. The investigator will use the following terms te assess the severity of the adverse event: mild, moderate severe. The investigator will use the follwing causality terms to assess the relationship of teh adverse event or clinical efficacy to the use of the investigational medicinal product: reasonable causal relationship or not.	2.3% 5/218 • In this study, the collection period for adverse events and serious Adverse events starts at the randomisation and ends when the patient completes the Treatment period of the study, serious and/or other adverse events were assessed up to 3.5 years. All-Cause Mortality was monitored for maximum 9 years and 7 months. The investigator will use the following terms te assess the severity of the adverse event: mild, moderate severe. The investigator will use the follwing causality terms to assess the relationship of teh adverse event or clinical efficacy to the use of the investigational medicinal product: reasonable causal relationship or not.
Gastrointestinal disorders Gastrointestinal disorders	16.5% 36/218 • In this study, the collection period for adverse events and serious Adverse events starts at the randomisation and ends when the patient completes the Treatment period of the study, serious and/or other adverse events were assessed up to 3.5 years. All-Cause Mortality was monitored for maximum 9 years and 7 months. The investigator will use the following terms te assess the severity of the adverse event: mild, moderate severe. The investigator will use the follwing causality terms to assess the relationship of teh adverse event or clinical efficacy to the use of the investigational medicinal product: reasonable causal relationship or not.	17.4% 38/218 • In this study, the collection period for adverse events and serious Adverse events starts at the randomisation and ends when the patient completes the Treatment period of the study, serious and/or other adverse events were assessed up to 3.5 years. All-Cause Mortality was monitored for maximum 9 years and 7 months. The investigator will use the following terms te assess the severity of the adverse event: mild, moderate severe. The investigator will use the follwing causality terms to assess the relationship of teh adverse event or clinical efficacy to the use of the investigational medicinal product: reasonable causal relationship or not.
Hepatobiliary disorders Hepatobiliary disorders	2.3% 5/218 • In this study, the collection period for adverse events and serious Adverse events starts at the randomisation and ends when the patient completes the Treatment period of the study, serious and/or other adverse events were assessed up to 3.5 years. All-Cause Mortality was monitored for maximum 9 years and 7 months. The investigator will use the following terms te assess the severity of the adverse event: mild, moderate severe. The investigator will use the follwing causality terms to assess the relationship of teh adverse event or clinical efficacy to the use of the investigational medicinal product: reasonable causal relationship or not.	0.92% 2/218 • In this study, the collection period for adverse events and serious Adverse events starts at the randomisation and ends when the patient completes the Treatment period of the study, serious and/or other adverse events were assessed up to 3.5 years. All-Cause Mortality was monitored for maximum 9 years and 7 months. The investigator will use the following terms te assess the severity of the adverse event: mild, moderate severe. The investigator will use the follwing causality terms to assess the relationship of teh adverse event or clinical efficacy to the use of the investigational medicinal product: reasonable causal relationship or not.
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders	16.1% 35/218 • In this study, the collection period for adverse events and serious Adverse events starts at the randomisation and ends when the patient completes the Treatment period of the study, serious and/or other adverse events were assessed up to 3.5 years. All-Cause Mortality was monitored for maximum 9 years and 7 months. The investigator will use the following terms te assess the severity of the adverse event: mild, moderate severe. The investigator will use the follwing causality terms to assess the relationship of teh adverse event or clinical efficacy to the use of the investigational medicinal product: reasonable causal relationship or not.	10.1% 22/218 • In this study, the collection period for adverse events and serious Adverse events starts at the randomisation and ends when the patient completes the Treatment period of the study, serious and/or other adverse events were assessed up to 3.5 years. All-Cause Mortality was monitored for maximum 9 years and 7 months. The investigator will use the following terms te assess the severity of the adverse event: mild, moderate severe. The investigator will use the follwing causality terms to assess the relationship of teh adverse event or clinical efficacy to the use of the investigational medicinal product: reasonable causal relationship or not.
Renal and urinary disorders Renal and urinary disorders	7.8% 17/218 • In this study, the collection period for adverse events and serious Adverse events starts at the randomisation and ends when the patient completes the Treatment period of the study, serious and/or other adverse events were assessed up to 3.5 years. All-Cause Mortality was monitored for maximum 9 years and 7 months. The investigator will use the following terms te assess the severity of the adverse event: mild, moderate severe. The investigator will use the follwing causality terms to assess the relationship of teh adverse event or clinical efficacy to the use of the investigational medicinal product: reasonable causal relationship or not.	6.0% 13/218 • In this study, the collection period for adverse events and serious Adverse events starts at the randomisation and ends when the patient completes the Treatment period of the study, serious and/or other adverse events were assessed up to 3.5 years. All-Cause Mortality was monitored for maximum 9 years and 7 months. The investigator will use the following terms te assess the severity of the adverse event: mild, moderate severe. The investigator will use the follwing causality terms to assess the relationship of teh adverse event or clinical efficacy to the use of the investigational medicinal product: reasonable causal relationship or not.
Endocrine disorders Endocrine disorders	20.2% 44/218 • In this study, the collection period for adverse events and serious Adverse events starts at the randomisation and ends when the patient completes the Treatment period of the study, serious and/or other adverse events were assessed up to 3.5 years. All-Cause Mortality was monitored for maximum 9 years and 7 months. The investigator will use the following terms te assess the severity of the adverse event: mild, moderate severe. The investigator will use the follwing causality terms to assess the relationship of teh adverse event or clinical efficacy to the use of the investigational medicinal product: reasonable causal relationship or not.	45.4% 99/218 • In this study, the collection period for adverse events and serious Adverse events starts at the randomisation and ends when the patient completes the Treatment period of the study, serious and/or other adverse events were assessed up to 3.5 years. All-Cause Mortality was monitored for maximum 9 years and 7 months. The investigator will use the following terms te assess the severity of the adverse event: mild, moderate severe. The investigator will use the follwing causality terms to assess the relationship of teh adverse event or clinical efficacy to the use of the investigational medicinal product: reasonable causal relationship or not.
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tissue disorders	17.9% 39/218 • In this study, the collection period for adverse events and serious Adverse events starts at the randomisation and ends when the patient completes the Treatment period of the study, serious and/or other adverse events were assessed up to 3.5 years. All-Cause Mortality was monitored for maximum 9 years and 7 months. The investigator will use the following terms te assess the severity of the adverse event: mild, moderate severe. The investigator will use the follwing causality terms to assess the relationship of teh adverse event or clinical efficacy to the use of the investigational medicinal product: reasonable causal relationship or not.	17.0% 37/218 • In this study, the collection period for adverse events and serious Adverse events starts at the randomisation and ends when the patient completes the Treatment period of the study, serious and/or other adverse events were assessed up to 3.5 years. All-Cause Mortality was monitored for maximum 9 years and 7 months. The investigator will use the following terms te assess the severity of the adverse event: mild, moderate severe. The investigator will use the follwing causality terms to assess the relationship of teh adverse event or clinical efficacy to the use of the investigational medicinal product: reasonable causal relationship or not.
Infections and infestations Infections and infestations	26.1% 57/218 • In this study, the collection period for adverse events and serious Adverse events starts at the randomisation and ends when the patient completes the Treatment period of the study, serious and/or other adverse events were assessed up to 3.5 years. All-Cause Mortality was monitored for maximum 9 years and 7 months. The investigator will use the following terms te assess the severity of the adverse event: mild, moderate severe. The investigator will use the follwing causality terms to assess the relationship of teh adverse event or clinical efficacy to the use of the investigational medicinal product: reasonable causal relationship or not.	25.2% 55/218 • In this study, the collection period for adverse events and serious Adverse events starts at the randomisation and ends when the patient completes the Treatment period of the study, serious and/or other adverse events were assessed up to 3.5 years. All-Cause Mortality was monitored for maximum 9 years and 7 months. The investigator will use the following terms te assess the severity of the adverse event: mild, moderate severe. The investigator will use the follwing causality terms to assess the relationship of teh adverse event or clinical efficacy to the use of the investigational medicinal product: reasonable causal relationship or not.
Metabolism and nutrition disorders Metabolism and nutrition disorders	0.92% 2/218 • In this study, the collection period for adverse events and serious Adverse events starts at the randomisation and ends when the patient completes the Treatment period of the study, serious and/or other adverse events were assessed up to 3.5 years. All-Cause Mortality was monitored for maximum 9 years and 7 months. The investigator will use the following terms te assess the severity of the adverse event: mild, moderate severe. The investigator will use the follwing causality terms to assess the relationship of teh adverse event or clinical efficacy to the use of the investigational medicinal product: reasonable causal relationship or not.	0.46% 1/218 • In this study, the collection period for adverse events and serious Adverse events starts at the randomisation and ends when the patient completes the Treatment period of the study, serious and/or other adverse events were assessed up to 3.5 years. All-Cause Mortality was monitored for maximum 9 years and 7 months. The investigator will use the following terms te assess the severity of the adverse event: mild, moderate severe. The investigator will use the follwing causality terms to assess the relationship of teh adverse event or clinical efficacy to the use of the investigational medicinal product: reasonable causal relationship or not.

Additional Information

Prof. Dr. M. Garmyn

UZLeuven

Phone: 0032 16 33 79 50

Email: marjan.garmyn@uzleuven.be

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place