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

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.

Study Overview

• Status: Completed
• Conditions: Noonan Syndrome; Genetic Disorder
• Intervention / Treatment: Drug: Somatropin

• Study Type: Observational
• Enrollment (Actual): 71

Contacts and Locations

Study Locations

• Japan
  • Asahikawa, Hokkaido, Japan, 078-8510
    • Novo Nordisk Investigational Site
  • Fukuoka, Japan, 830-0011
    • Novo Nordisk Investigational Site
  • Kanagawa, Japan, 216-8511
    • Novo Nordisk Investigational Site
  • Kanagawa, Japan, 232-8555
    • Novo Nordisk Investigational Site
  • Kyoto, Japan, 602-8566
    • Novo Nordisk Investigational Site
  • Kyoto, Japan, 629-2261
    • Novo Nordisk Investigational Site
  • Maebashi-shi, Gunma, Japan, 371-8511
    • Novo Nordisk Investigational Site
  • Miyazaki, Japan, 889-1692
    • Novo Nordisk Investigational Site
  • Nagoya, Aichi, Japan, 467-8602
    • Novo Nordisk Investigational Site
  • Niigata-shi, Niigata, Japan, 951 8520
    • Novo Nordisk Investigational Site
  • Oita, Japan, 879-5593
    • Novo Nordisk Investigational Site
  • Osaka, Japan, 534-0021
    • Novo Nordisk Investigational Site
  • Osaka, Japan, 594-1101
    • Novo Nordisk Investigational Site
  • Saitama-shi, Saitama, Japan, 330-8777
    • Novo Nordisk Investigational Site
  • Sapporo, Hokkaido, Japan, 065-8611
    • Novo Nordisk Investigational Site
  • Sendai-shi, Miyagi, Japan, 980 8574
    • Novo Nordisk Investigational Site
  • Shizuoka, Japan, 431-3192
    • Novo Nordisk Investigational Site
  • Tochigi, Japan, 329-0498
    • Novo Nordisk Investigational Site
  • Tokyo, Japan, 157 8535
    • Novo Nordisk Investigational Site
  • Tokyo, Japan, 160-8582
    • Novo Nordisk Investigational Site
  • Tokyo, Japan, 162-8666
    • Novo Nordisk Investigational Site
  • Tokyo, Japan, 183-8561
    • Novo Nordisk Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

A total of 60 patients (consisting of non-naïve patients who were previously enrolled in study: GHLIQUID-4020 and naïve patients enrolled after approval of the Noonan indication in Japan) are planned to be included in this study.

Description

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.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Novo Nordisk A/S

Study record dates

Study Major Dates

• Study Start (Actual): February 26, 2018
• Primary Completion (Actual): January 18, 2022
• Study Completion (Actual): January 18, 2022

Study Registration Dates

• First Submitted: January 31, 2018
• First Submitted That Met QC Criteria: February 9, 2018
• First Posted (Actual): February 19, 2018

Study Record Updates

• Last Update Posted (Actual): November 14, 2022
• Last Update Submitted That Met QC Criteria: November 10, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Endocrine System Diseases; Disease; Congenital Abnormalities; Musculoskeletal Diseases; Connective Tissue Diseases; Bone Diseases; Heart Defects, Congenital; Cardiovascular Abnormalities; Craniofacial Abnormalities; Musculoskeletal Abnormalities; Bone Diseases, Developmental; Syndrome; Genetic Diseases, Inborn; Noonan Syndrome; Dwarfism
• Other Study ID Numbers: GHLIQUID-4358; U1111-1191-3084 (Other Identifier: World Health Organization (WHO))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: According to the Novo Nordisk disclosure commitment on novonordisk-trials.com

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No