Post Marketing Surveillance on Long-term Use With Norditropin® (Short Stature Due to Noonan Syndrome)

Study Overview
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Brief Summary
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The purpose of this study is to collect information about safety and effectiveness for long term use of Norditropin®. Participants will attend the medical institution according to usual practice and receive medical care, as agreed with the study doctor.

Official Title
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Post Marketing Surveillance on Long-term Use With Norditropin® (Short Stature Due to Noonan Syndrome)

Conditions
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Genetic Disorder, Noonan Syndrome

Intervention / Treatment
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* Drug: Somatropin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent obtained before any study-related activities (study-related activities are any procedure related to recording of data according to the protocol). The decision to initiate treatment with commercially available Norditropin® has been made by the patient/Legally Acceptable Representative (LAR) and the treating physician before and independently from the decision to include the patient in this study. For non-naïve patients; patients who were previously enrolled in study: GHLIQUID-4020. For naïve patients; short stature due to Noonan syndrome diagnosed by the physician and a decision to initiate treatment with Norditropin® has been made by the patient/parent and the physician. At study sites, all patients will be registered consecutively from the first patient after approval date (consecutively registered system). Male or female, 3 years old or over, bone age: less than 17 years old for male / less than 15 years old for female. Exclusion Criteria: Previous participation in this study. Participation is defined as having given informed consent in this study. Known or suspected allergy to study products or related products. In case of naïve patients, patients who have received growth hormone (GH) products for treatment of indication other than short stature due to Noonan syndrome before approval date of Noonan indication.

Ages Eligible for Study
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Minimum Age: 3 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Norditropin® (naïve participants)<br>The treatment period of Norditropin® for naïve participants will be up to 208 weeks. | Drug: Somatropin<br>* Participants will be treated with commercially available Norditropin® (somatropin) according to routine clinical practice at the discretion of the treating physician.<br>|
| Norditropin® (non-naïve participants)<br>The treatment period of Norditropin® for non-naïve participants will be up to 442 weeks. | Drug: Somatropin<br>* Participants will be treated with commercially available Norditropin® (somatropin) according to routine clinical practice at the discretion of the treating physician.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of adverse drug reactions (ADR) | Count of events | Weeks 0-208 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of serious adverse drug reaction (SADR) | Count of events | Week 0-208 | 
| Number of serious adverse event (SAE) | Count of events | Week 0-208 | 
| Number of cardiac adverse event (AE) | Count of events | Week 0-208 | 
| Change in insulin like growth factor I (IGF-I) for non-naïve patients | Measured in ng/mL | Weeks 0, 52, 104, 156, 208, 260, 312, 364, 416, and 442 weeks | 
| Change in insulin like growth factor I (IGF-I) for naïve patients | Measured in ng/mL | Weeks 0, 52, 104, 156, and 208 weeks | 
| Change in insulin like growth factor I standard deviation score (IGF-I SDS) for non-naïve patients | Presented as standard deviation (SD) score | Weeks 0, 52, 104, 156, 208, 260, 312, 364, 416, and 442 weeks | 
| Change in insulin like growth factor I standard deviation score (IGF-I SDS) for naïve patients | Presented as SD score | Weeks 0, 52, 104, 156, and 208 weeks | 
| Change in haemoglobin A1c (HbA1c) for non-naïve patients | Measured in % | Weeks 0, 52, 104, 156, 208, 260, 312, 364, 416, and 442 weeks | 
| Change in haemoglobin A1c (HbA1c) for naïve patients | Measured in % | Weeks 0, 52, 104, 156, and 208 weeks | 
| Change in aspartate aminotransferase (AST) for non-naïve patients | Measured in IU/L | Weeks 0, 52, 104, 156, 208, 260, 312, 364, 416, and 442 weeks | 
| Change in aspartate aminotransferase (AST) for naïve patients | Measured in IU/L | Weeks 0, 52, 104, 156, and 208 weeks | 
| Change in alanine aminotransferase (ALT) for non-naïve patients | Measured in IU/L | Weeks 0, 52, 104, 156, 208, 260, 312, 364, 416, and 442 weeks | 
| Change in alanine aminotransferase (ALT) for naïve patients | Measured in IU/L | Weeks 0, 52, 104, 156, and 208 weeks | 
| Change in total cholesterol (T-CHO) for non-naïve patients | Measured in mg/dL | Weeks 0, 52, 104, 156, 208, 260, 312, 364, 416, and 442 weeks | 
| Change in total cholesterol (T-CHO) for naïve patients | Measured in mg/dL | Weeks 0, 52, 104, 156, and 208 weeks | 
| Change in high-density lipoprotein cholesterol (HDL-C) for non-naïve patients | Measured in mg/dL | Weeks 0, 52, 104, 156, 208, 260, 312, 364, 416, and 442 weeks | 
| Change in high-density lipoprotein cholesterol (HDL-C) for naïve patients | Measured in mg/dL | Weeks 0, 52, 104, 156, and 208 weeks | 
| Change in Low-density lipoprotein cholesterol (LDL-C) for non-naïve patients | Measured in mg/dL | Weeks 0, 52, 104, 156, 208, 260, 312, 364, 416, and 442 weeks | 
| Change in Low-density lipoprotein cholesterol (LDL-C) for naïve patients | Measured in mg/dL | Weeks 0, 52, 104, 156, and 208 weeks | 
| Change in triglyceride (TG) for non-naïve patients | Measured in mg/dL | Weeks 0, 52, 104, 156, 208, 260, 312, 364, 416, and 442 weeks | 
| Change in triglyceride (TG) for naïve patients | Measured in mg/dL | Weeks 0, 52, 104, 156, and 208 weeks | 
| Change in thyroid stimulation hormone(TSH) for non-naïve patients | Measured in μU/mL | Weeks 0, 52, 104, 156, 208, 260, 312, 364, 416, and 442 weeks | 
| Change in thyroid stimulation hormone(TSH) for naïve patients | Measured in μU/mL | Weeks 0, 52, 104, 156, and 208 weeks | 
| Change in free triiodothyronine (FT-3) for non-naïve patients | Measured in pg/mL | Weeks 0, 52, 104, 156, 208, 260, 312, 364, 416, and 442 weeks | 
| Change in free triiodothyronine (FT-3) for naïve patients | Measured in pg/mL | Weeks 0, 52, 104, 156, and 208 weeks | 
| Change in free thyroxine (FT-4) for non-naïve patients | Measured in ng/mL | Weeks 0, 52, 104, 156, 208, 260, 312, 364, 416, and 442 weeks | 
| Change in free thyroxine (FT-4) for naïve patients | Measured in ng/mL | Weeks 0, 52, 104, 156, and 208 weeks | 
| Change in white blood cell (WBC) for non-naïve patients | Measured in μ/L | Weeks 0, 52, 104, 156, 208, 260, 312, 364, 416, and 442 weeks | 
| Change in white blood cell (WBC) for naïve patients | Measured in μ/L | Weeks 0, 52, 104, 156, and 208 weeks | 
| Change in platelet (PLT) for non-naïve patients | Measured in 10^4/μL | Weeks 0, 52, 104, 156, 208, 260, 312, 364, 416, and 442 weeks | 
| Change in platelet (PLT) for naïve patients | Measured in 10^4/μL | Weeks 0, 52, 104, 156, and 208 weeks | 
| Change in bone age (BA) for non-naïve patients | Measured in year | Weeks 0, 52, 104, 156, 208, 260, 312, 364, 416, and 442 weeks | 
| Change in bone age (BA) for naïve patients | Measured in year | Weeks 0, 52, 104, 156, and 208 weeks | 
| Change in bone age/chronological age (BA/CA) for non-naïve patients | Presented as ratio | Weeks 0, 52, 104, 156, 208, 260, 312, 364, 416, and 442 weeks | 
| Change in bone age/chronological age (BA/CA) for naïve patients | Presented as ratio | Weeks 0, 52, 104, 156, and 208 weeks | 
| Change in electrocardiogram (ECG) for non-naïve patients | Assessment of change in ECG is measured by categories recorded in case report forms (CRFs): normal, abnormal not clinically significant and abnormal clinically significant. | Weeks 0, 52, 104, 156, 208, 260, 312, 364, 416, and 442 weeks | 
| Change in electrocardiogram (ECG) for naïve patients | Assessment of change in ECG is measured by categories recorded in CRFs: normal, abnormal not clinically significant and abnormal clinically significant. | Weeks 0, 52, 104, 156, and 208 weeks | 
| Change in height standard deviation score (HSDS) for non-naïve patients | Presented as SD score | Weeks 0, 52, 104, 156, 208, 260, 312, 364, 416, and 442 weeks | 
| Change in height standard deviation score (HSDS) for naïve patients | Presented as SD score | Weeks 0, 52, 104, 156, and 208 weeks | 
| Height velocity standard deviation score (HVSDS) for non-naïve patients | Presented as SD score | Weeks 0, 52, 104, 156, 208, 260, 312, 364, 416, and 442 weeks | 
| Height velocity standard deviation score (HVSDS) for naïve patients | Presented as SD score | Weeks 0, 52, 104, 156, and 208 weeks | 
| Height velocity (HV) for non-naïve patients | Measured in cm/year | Weeks 0, 52, 104, 156, 208, 260, 312, 364, 416, and 442 weeks | 
| Height velocity (HV) for naïve patients | Measured in cm/year | Weeks 0, 52, 104, 156, and 208 weeks |