REAL 2: A Trial to Compare the Safety of Once Weekly Dosing of Somapacitan With Daily Norditropin® FlexPro® for 26 Weeks in Previously Human Growth Hormone Treated Adults With Growth Hormone Deficiency

• Sponsor: Novo Nordisk A/S (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02382939
• Collaborator: (none)
• Enrollment: 92
• Locations: 28
• Arms: 2
• Actual Duration (Months): 10.7
• Patients Per Site: 3.3
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

This trial is conducted in Europe and Asia. The aim of the trial is to compare the safety of once weekly dosing of somapacitan (administered with an investigational pen) with daily Norditropin® FlexPro® (somatropin delivered within a prefilled pen) for 26 weeks in previously human growth hormone (hGH) treated adults with growth hormone deficiency.

Condition or Disease	Intervention/Treatment	Phase
Adult Growth Hormone Deficiency; Growth Hormone Disorder	Drug: somapacitan; Drug: somatropin	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 92 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Multicentre, Multinational, Randomised, Open-labelled, Parallel-group, Active-controlled Trial to Compare the Safety of Once Weekly Dosing of Somapacitan With Daily Norditropin® FlexPro® for 26 Weeks in Previously Human Growth Hormone Treated Adults With Growth Hormone Deficiency
• Actual Study Start Date: Feb 12, 2015
• Actual Primary Completion Date: Jan 4, 2016
• Actual Study Completion Date: Jan 4, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: somapacitan	Drug: somapacitan; Administered subcutaneously (s.c., under the skin) with an investigational pen once weekly for a 26 week period (8 weeks' dose titration, 18 weeks' fixed dose treatment) followed by 1 week washout.
Active Comparator: hGH (somatropin)	Drug: somatropin; Administered subcutaneously (s.c., under the skin) with a prefilled pen (Norditropin® FlexPro®) daily for a 26 week period (8 weeks' dose titration, 18 weeks' fixed dose treatment) followed by 1 week washout.

Outcome Measures

Primary Outcome Measures

1. Incidence of Adverse Events [Weeks 0 - 26]

   An adverse event can be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom or disease temporally associated with the use of a product, whether or not considered related to the product. Presented results are event rate per 100 patient years of exposure.

2. Incidence of Injection Site Reactions [Weeks 0- 26]

   Presented results are event (injection site reaction) rate per 100 patient years of exposure.

Secondary Outcome Measures

1. Occurrence of Anti-NNC0195-0092 Antibodies [At week 0 (baseline), and at week 2, 4, 8, 16, 25 and 27]

   Number of participants with anti-somapacitan (NNC0195-0092) antibodies are presented.

2. Change in Treatment Satisfaction Questionnaire for Medication (TSQM) Scores (Effectiveness,Convenience, and Global Satisfaction Scores) [Baseline (week 0), week 26]

   The Treatment Satisfaction Questionnaire for Medication (TSQM-9) is a psychometric measure of a patient's satisfaction with medication. It consists of 3 subscales: effectiveness, convenience and global satisfaction. Items are rated on a 5 or 7-point scale according to participants' experience with the medication. Each domain score can vary from 0 to 100 with higher scores indicating higher effectiveness of treatment, more convenient use of medication and overall greater satisfaction with the treatment.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 79 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria: - Male or female of at least 18 years of age and not more than 79 years of age at the time of signing informed consent - Adult growth hormone deficiency diagnosed for 6 months or longer (defined as 180 days) prior to screening - Treatment with hGH (human growth hormone) for at least 6 months at screening - If applicable, hormone replacement therapies for any other hormone deficiencies, adequate and stable for at least 90 days prior to randomisation as judged by the investigator Exclusion Criteria: - Active malignant disease or history of malignancy. Exceptions to this exclusion criterion: Resected in situ carcinoma of the cervix and squamous cell or basal cell carcinoma of the skin with complete local excision. / Subjects with GHD (growth hormone deficiency) attributed to treatment of intracranial malignant tumours or leukaemia, provided that a recurrence-free survival period of at least 5 years is documented in the subject's file - For patients with surgical removal or debulking of pituitary adenoma or other benign intracranial tumour within the last 5 years: Evidence of growth of pituitary adenoma or other benign intracranial tumour within the last 12 months (defined as below or equal to 365 days) before randomisation. Absence of growth must be documented by two post-surgery MRI or CT scans. The most recent MRI or CT scan must be performed below or equal to 9 months (defined as below or equal to 270 days) prior to randomisation

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novo Nordisk Investigational Site	København Ø		Denmark	2100
2	Novo Nordisk Investigational Site	Odense		Denmark	5000
3	Novo Nordisk Investigational Site	Århus C		Denmark	8000
4	Novo Nordisk Investigational Site	Angers		France	49000
5	Novo Nordisk Investigational Site	Brest		France	29609
6	Novo Nordisk Investigational Site	Bron		France	69677
7	Novo Nordisk Investigational Site	DIJON cedex		France	21079
8	Novo Nordisk Investigational Site	Saint Herblain		France	44800
9	Novo Nordisk Investigational Site	Aachen		Germany	52074
10	Novo Nordisk Investigational Site	Berlin		Germany	10117
11	Novo Nordisk Investigational Site	Frankfurt		Germany	60596
12	Novo Nordisk Investigational Site	Bunkyo-ku, Tokyo		Japan	113-8603
13	Novo Nordisk Investigational Site	Itabashi-ku, Tokyo		Japan	173-8606
14	Novo Nordisk Investigational Site	Izumo, Shimane		Japan	691-8501
15	Novo Nordisk Investigational Site	Kobe, Hyogo		Japan	650-0017
16	Novo Nordisk Investigational Site	Kobe-shi, Hyogo		Japan	657-0846
17	Novo Nordisk Investigational Site	Kyoto-shi Kyoto		Japan	612-8555
18	Novo Nordisk Investigational Site	Okayama, Okayama		Japan	700-8558
19	Novo Nordisk Investigational Site	Sagamihara-shi, Kanagawa		Japan	252-0375
20	Novo Nordisk Investigational Site	Göteborg		Sweden	413 45
21	Novo Nordisk Investigational Site	Lund		Sweden	221 85
22	Novo Nordisk Investigational Site	Stockholm		Sweden	171 76
23	Novo Nordisk Investigational Site	Birmingham		United Kingdom	B15 2TH
24	Novo Nordisk Investigational Site	Exeter		United Kingdom	EX2 5DW
25	Novo Nordisk Investigational Site	Leeds		United Kingdom	LS9 7TF
26	Novo Nordisk Investigational Site	London		United Kingdom	EC1A 7BE
27	Novo Nordisk Investigational Site	London		United Kingdom	SE5 9RS
28	Novo Nordisk Investigational Site	Manchester		United Kingdom	M20 4BX

Sponsors and Collaborators

• Novo Nordisk A/S

Investigators

• Study Director: Global Clinical Registry (GCR, 1452), Novo Nordisk A/S

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Clinical Trials at Novo Nordisk

Publications

None provided.

• Responsible Party: Novo Nordisk A/S
• ClinicalTrials.gov Identifier: NCT02382939
• Other Study ID Numbers: NN8640-4043; 2014-000290-39; U1111-1152-3664; JapicCTI-152850
• First Posted: Mar 9, 2015
• Last Update Posted: Jul 9, 2020
• Last Verified: Jun 1, 2020

• Additional relevant MeSH terms: Dwarfism, Pituitary; Endocrine System Diseases

Study Results

Participant Flow

Recruitment Details	The trial was conducted at 26 sites in 6 countries. All 26 sites screened and randomised/ assigned patients to treatment. Denmark: 3 sites; France: 5 sites; Germany: 3 sites; Sweden: 3 sites; United Kingdom: 5 sites; Japan: 7 sites.
Pre-assignment Detail	Participants, who were diagnosed with adults with growth hormone deficiency ≥ 6 months (defined as 180 days) prior to screening and receiving treatment with human growth hormone at least 6 months (defined as 180 days) at screening, were enrolled.

Arm/Group Title	Norditropin	Somapacitan
Arm/Group Description	Participants received subcutaneous (s.c.) injections of Norditropin daily for 26 weeks (8 weeks dose titration followed by 18 weeks fixed dose treatment) followed by 1 week washout. The starting dose of Norditropin was 0.2 mg/day (except females on oral oestrogen: 0.3 mg/day; participants older than 60 years: 0.1 mg/day). An individualised dose titration regimen was used. Adjustment of dose was performed at weeks 2, 4, 6 and 8 based on insulin-like growth factor-I standard deviation score (IGF-I SDS) values: IGF-I SDS > 3: dose reduction by 0.1 mg/day 2 < IGF-I SDS ≤ 3: dose reduction by 0.05 mg/day 0 < IGF-I SDS ≤ 2: No need of dose adjustment 2 < IGF-I SDS ≤ 0: Dose increment by 0.1 mg/day IGF-I SDS ≤ -2: Dose increment by 0.2 mg/day After the last dose adjustment (if any) at week 8, the individual dose level was fixed. The minimum and maximum daily dose was set to 0.05 mg and 1.1 mg (Japan: maximum daily dose was 1.0 mg).	Participants received s.c. injections of somapacitan once-weekly for 26 weeks (8 weeks dose titration followed by 18 weeks fixed dose treatment) followed by 1 week washout. The starting dose of somapacitan was 1.5 mg/week (except females on oral oestrogen 2.0 mg/week; participants older than 60 years 1.0 mg/week). An individualised dose titration regimen was used. Adjustment of dose was performed at weeks 2, 4, 6 and 8 based on IGF-I SDS values: IGF-I SDS > 3: dose reduction by 1 mg 2 < IGF-I SDS ≤ 3: dose reduction by 0.5 mg 0 < IGF-I SDS ≤ 2: No need for dose adjustment 2 < IGF-I SDS ≤ 0: Dose Increment by 0.7 mg IGF-I SDS ≤ -2: Dose Increment by 1.5 mg After the last dose adjustment (if any) at week 8, the individual dose level was fixed. The minimum and maximum weekly dose was set to 0.1 mg and 8 mg.
Period Title: Overall Study
STARTED	31	61
Exposed	31	61
COMPLETED	28	58
NOT COMPLETED	3	3

Baseline Characteristics

Arm/Group Title	Norditropin	Somapacitan	Total
Arm/Group Description	Participants received s.c. injections of Norditropin daily for 26 weeks (8 weeks dose titration followed by 18 weeks fixed dose treatment) followed by 1 week washout. The starting dose of Norditropin was 0.2 mg/day (except females on oral oestrogen: 0.3 mg/day; participants older than 60 years: 0.1 mg/day). An individualised dose titration regimen was used. Adjustment of dose was performed at weeks 2, 4, 6 and 8 based on IGF-I SDS values: IGF-I SDS > 3: dose reduction by 0.1 mg/day 2 < IGF-I SDS ≤ 3: dose reduction by 0.05 mg/day 0 < IGF-I SDS ≤ 2: No need of dose adjustment 2 < IGF-I SDS ≤ 0: Dose increment by 0.1 mg/day IGF-I SDS ≤ -2: Dose increment by 0.2 mg/day After the last dose adjustment (if any) at week 8, the individual dose level was fixed. The minimum and maximum daily dose was set to 0.05 mg and 1.1 mg (Japan: maximum daily dose was 1.0 mg).	Participants received s.c. injections of somapacitan once-weekly for 26 weeks (8 weeks dose titration followed by 18 weeks fixed dose treatment) followed by 1 week washout. The starting dose of somapacitan was 1.5 mg/week (except females on oral oestrogen 2.0 mg/week; participants older than 60 years 1.0 mg/week). An individualised dose titration regimen was used. Adjustment of dose was performed at weeks 2, 4, 6 and 8 based on IGF-I SDS values: IGF-I SDS > 3: dose reduction by 1 mg 2 < IGF-I SDS ≤ 3: dose reduction by 0.5 mg 0 < IGF-I SDS ≤ 2: No need for dose adjustment 2 < IGF-I SDS ≤ 0: Dose Increment by 0.7 mg IGF-I SDS ≤ -2: Dose Increment by 1.5 mg After the last dose adjustment (if any) at week 8, the individual dose level was fixed. The minimum and maximum weekly dose was set to 0.1 mg and 8 mg.	Total of all reporting groups
Overall Participants	31	61	92
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	51.7 (17.1)	48.1 (16.2)	49.3 (16.5)
Age, Customized (Count of Participants)
18-64 years	23 74.2%	50 82%	73 79.3%
≥65 years	8 25.8%	11 18%	19 20.7%
Sex: Female, Male (Count of Participants)
Female	14 45.2%	28 45.9%	42 45.7%
Male	17 54.8%	33 54.1%	50 54.3%

Outcome Measures

1. Primary Outcome

Title	Incidence of Adverse Events
Description	An adverse event can be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom or disease temporally associated with the use of a product, whether or not considered related to the product. Presented results are event rate per 100 patient years of exposure.
Time Frame	Weeks 0 - 26

Outcome Measure Data

Analysis Population Description

Safety analysis set: all randomised participants that received at least one dose of randomised treatment.

Arm/Group Title	Norditropin	Somapacitan
Arm/Group Description	Participants received s.c. injections of Norditropin daily for 26 weeks (8 weeks dose titration followed by 18 weeks fixed dose treatment) followed by 1 week washout. The starting dose of Norditropin was 0.2 mg/day (except females on oral oestrogen: 0.3 mg/day; participants older than 60 years: 0.1 mg/day). An individualised dose titration regimen was used. Adjustment of dose was performed at weeks 2, 4, 6 and 8 based on IGF-I SDS values: IGF-I SDS > 3: dose reduction by 0.1 mg/day 2 < IGF-I SDS ≤ 3: dose reduction by 0.05 mg/day 0 < IGF-I SDS ≤ 2: No need of dose adjustment 2 < IGF-I SDS ≤ 0: Dose increment by 0.1 mg/day IGF-I SDS ≤ -2: Dose increment by 0.2 mg/day After the last dose adjustment (if any) at week 8, the individual dose level was fixed. The minimum and maximum daily dose was set to 0.05 mg and 1.1 mg (Japan: maximum daily dose was 1.0 mg).	Participants received s.c. injections of somapacitan once-weekly for 26 weeks (8 weeks dose titration followed by 18 weeks fixed dose treatment) followed by 1 week washout. The starting dose of somapacitan was 1.5 mg/week (except females on oral oestrogen 2.0 mg/week; participants older than 60 years 1.0 mg/week). An individualised dose titration regimen was used. Adjustment of dose was performed at weeks 2, 4, 6 and 8 based on IGF-I SDS values: IGF-I SDS > 3: dose reduction by 1 mg 2 < IGF-I SDS ≤ 3: dose reduction by 0.5 mg 0 < IGF-I SDS ≤ 2: No need for dose adjustment 2 < IGF-I SDS ≤ 0: Dose Increment by 0.7 mg IGF-I SDS ≤ -2: Dose Increment by 1.5 mg After the last dose adjustment (if any) at week 8, the individual dose level was fixed. The minimum and maximum weekly dose was set to 0.1 mg and 8 mg.
Measure Participants	31	61
Number [Events per 100 patient years]	530.8	514.2

2. Primary Outcome

Title	Incidence of Injection Site Reactions
Description	Presented results are event (injection site reaction) rate per 100 patient years of exposure.
Time Frame	Weeks 0- 26

Outcome Measure Data

Analysis Population Description

Safety analysis set: all randomised participants that received at least one dose of randomised treatment.

Arm/Group Title	Norditropin	Somapacitan
Arm/Group Description	Participants received s.c. injections of Norditropin daily for 26 weeks (8 weeks dose titration followed by 18 weeks fixed dose treatment) followed by 1 week washout. The starting dose of Norditropin was 0.2 mg/day (except females on oral oestrogen: 0.3 mg/day; participants older than 60 years: 0.1 mg/day). An individualised dose titration regimen was used. Adjustment of dose was performed at weeks 2, 4, 6 and 8 based on IGF-I SDS values: IGF-I SDS > 3: dose reduction by 0.1 mg/day 2 < IGF-I SDS ≤ 3: dose reduction by 0.05 mg/day 0 < IGF-I SDS ≤ 2: No need of dose adjustment 2 < IGF-I SDS ≤ 0: Dose increment by 0.1 mg/day IGF-I SDS ≤ -2: Dose increment by 0.2 mg/day After the last dose adjustment (if any) at week 8, the individual dose level was fixed. The minimum and maximum daily dose was set to 0.05 mg and 1.1 mg (Japan: maximum daily dose was 1.0 mg).	Participants received s.c. injections of somapacitan once-weekly for 26 weeks (8 weeks dose titration followed by 18 weeks fixed dose treatment) followed by 1 week washout. The starting dose of somapacitan was 1.5 mg/week (except females on oral oestrogen 2.0 mg/week; participants older than 60 years 1.0 mg/week). An individualised dose titration regimen was used. Adjustment of dose was performed at weeks 2, 4, 6 and 8 based on IGF-I SDS values: IGF-I SDS > 3: dose reduction by 1 mg 2 < IGF-I SDS ≤ 3: dose reduction by 0.5 mg 0 < IGF-I SDS ≤ 2: No need for dose adjustment 2 < IGF-I SDS ≤ 0: Dose Increment by 0.7 mg IGF-I SDS ≤ -2: Dose Increment by 1.5 mg After the last dose adjustment (if any) at week 8, the individual dose level was fixed. The minimum and maximum weekly dose was set to 0.1 mg and 8 mg.
Measure Participants	31	61
Number [Events per 100 patient years]	0	6.5

3. Secondary Outcome

Title	Occurrence of Anti-NNC0195-0092 Antibodies
Description	Number of participants with anti-somapacitan (NNC0195-0092) antibodies are presented.
Time Frame	At week 0 (baseline), and at week 2, 4, 8, 16, 25 and 27

Outcome Measure Data

Analysis Population Description

Overall Number of Participants Analyzed = safety analysis set which included all randomised participants that received at least one dose of randomised treatment. Number Analyzed = number of participants with available data. This outcome measure is applicable only for the somapacitan treatment arm.

Arm/Group Title	Somapacitan
Arm/Group Description	Participants received s.c. injections of somapacitan once-weekly for 26 weeks (8 weeks dose titration followed by 18 weeks fixed dose treatment) followed by 1 week washout. The starting dose of somapacitan was 1.5 mg/week (except females on oral oestrogen 2.0 mg/week; participants older than 60 years 1.0 mg/week). An individualised dose titration regimen was used. Adjustment of dose was performed at weeks 2, 4, 6 and 8 based on IGF-I SDS values: IGF-I SDS > 3: dose reduction by 1 mg 2 < IGF-I SDS ≤ 3: dose reduction by 0.5 mg 0 < IGF-I SDS ≤ 2: No need for dose adjustment 2 < IGF-I SDS ≤ 0: Dose Increment by 0.7 mg IGF-I SDS ≤ -2: Dose Increment by 1.5 mg After the last dose adjustment (if any) at week 8, the individual dose level was fixed. The minimum and maximum weekly dose was set to 0.1 mg and 8 mg.
Measure Participants	61
Week 0:	0 0%
Week 2:	0 0%
Week 4:	0 0%
Week 8:	0 0%
Week 16:	0 0%
Week 25:	0 0%
Week 27:	0 0%

4. Secondary Outcome

Title	Change in Treatment Satisfaction Questionnaire for Medication (TSQM) Scores (Effectiveness,Convenience, and Global Satisfaction Scores)
Description	The Treatment Satisfaction Questionnaire for Medication (TSQM-9) is a psychometric measure of a patient's satisfaction with medication. It consists of 3 subscales: effectiveness, convenience and global satisfaction. Items are rated on a 5 or 7-point scale according to participants' experience with the medication. Each domain score can vary from 0 to 100 with higher scores indicating higher effectiveness of treatment, more convenient use of medication and overall greater satisfaction with the treatment.
Time Frame	Baseline (week 0), week 26

Outcome Measure Data

Analysis Population Description

Overall Number of Participants Analyzed = full analysis set which included all randomised participants that received at least one dose of randomised treatment. Number Analyzed = number of participants with available data.

Arm/Group Title	Norditropin	Somapacitan
Arm/Group Description	Participants received s.c. injections of Norditropin daily for 26 weeks (8 weeks dose titration followed by 18 weeks fixed dose treatment) followed by 1 week washout. The starting dose of Norditropin was 0.2 mg/day (except females on oral oestrogen: 0.3 mg/day; participants older than 60 years: 0.1 mg/day). An individualised dose titration regimen was used. Adjustment of dose was performed at weeks 2, 4, 6 and 8 based on IGF-I SDS values: IGF-I SDS > 3: dose reduction by 0.1 mg/day 2 < IGF-I SDS ≤ 3: dose reduction by 0.05 mg/day 0 < IGF-I SDS ≤ 2: No need of dose adjustment 2 < IGF-I SDS ≤ 0: Dose increment by 0.1 mg/day IGF-I SDS ≤ -2: Dose increment by 0.2 mg/day After the last dose adjustment (if any) at week 8, the individual dose level was fixed. The minimum and maximum daily dose was set to 0.05 mg and 1.1 mg (Japan: maximum daily dose was 1.0 mg).	Participants received s.c. injections of somapacitan once-weekly for 26 weeks (8 weeks dose titration followed by 18 weeks fixed dose treatment) followed by 1 week washout. The starting dose of somapacitan was 1.5 mg/week (except females on oral oestrogen 2.0 mg/week; participants older than 60 years 1.0 mg/week). An individualised dose titration regimen was used. Adjustment of dose was performed at weeks 2, 4, 6 and 8 based on IGF-I SDS values: IGF-I SDS > 3: dose reduction by 1 mg 2 < IGF-I SDS ≤ 3: dose reduction by 0.5 mg 0 < IGF-I SDS ≤ 2: No need for dose adjustment 2 < IGF-I SDS ≤ 0: Dose Increment by 0.7 mg IGF-I SDS ≤ -2: Dose Increment by 1.5 mg After the last dose adjustment (if any) at week 8, the individual dose level was fixed. The minimum and maximum weekly dose was set to 0.1 mg and 8 mg.
Measure Participants	31	61
Effectiveness	3.8 (27.4)	9.7 (18.1)
Convenience	3.0 (16.5)	15.3 (20.9)
Global satisfaction	-1.2 (15.2)	5.4 (21.0)

Adverse Events

Time Frame	Baseline (week 0) to week 26.
Adverse Event Reporting Description	Participants in the safety analysis set contributed to the evaluation of adverse events.
Arm/Group Title	Norditropin		Somapacitan
Arm/Group Description	Participants received s.c. injections of Norditropin daily for 26 weeks (8 weeks dose titration followed by 18 weeks fixed dose treatment) followed by 1 week washout. The starting dose of Norditropin was 0.2 mg/day (except females on oral oestrogen: 0.3 mg/day; participants older than 60 years: 0.1 mg/day). An individualised dose titration regimen was used. Adjustment of dose was performed at weeks 2, 4, 6 and 8 based on IGF-I SDS values: IGF-I SDS > 3: dose reduction by 0.1 mg/day 2 < IGF-I SDS ≤ 3: dose reduction by 0.05 mg/day 0 < IGF-I SDS ≤ 2: No need of dose adjustment 2 < IGF-I SDS ≤ 0: Dose increment by 0.1 mg/day IGF-I SDS ≤ -2: Dose increment by 0.2 mg/day After the last dose adjustment (if any) at week 8, the individual dose level was fixed.		Participants received s.c. injections of somapacitan once-weekly for 26 weeks (8 weeks dose titration followed by 18 weeks fixed dose treatment) followed by 1 week washout. The starting dose of somapacitan was 1.5 mg/week (except females on oral oestrogen 2.0 mg/week; participants older than 60 years 1.0 mg/week). An individualised dose titration regimen was used. Adjustment of dose was performed at weeks 2, 4, 6 and 8 based on IGF-I SDS values: IGF-I SDS > 3: dose reduction by 1 mg 2 < IGF-I SDS ≤ 3: dose reduction by 0.5 mg 0 < IGF-I SDS ≤ 2: No need for dose adjustment 2 < IGF-I SDS ≤ 0: Dose Increment by 0.7 mg IGF-I SDS ≤ -2: Dose Increment by 1.5 mg After the last dose adjustment (if any) at week 8, the individual dose level was fixed. The minimum and maximum weekly dose was set to 0.1 mg and 8 mg.
All Cause Mortality
	Norditropin		Somapacitan
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Norditropin		Somapacitan
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/31 (6.5%)		4/61 (6.6%)
Gastrointestinal disorders
Intestinal ischaemia	1/31 (3.2%)	1	0/61 (0%)	0
Short-bowel syndrome	1/31 (3.2%)	1	0/61 (0%)	0
Hepatobiliary disorders
Cholelithiasis	0/31 (0%)	0	1/61 (1.6%)	1
Injury, poisoning and procedural complications
Patella fracture	0/31 (0%)	0	1/61 (1.6%)	1
Procedural complication	0/31 (0%)	0	1/61 (1.6%)	1
Renal and urinary disorders
Nephrolithiasis	1/31 (3.2%)	1	0/61 (0%)	0
Surgical and medical procedures
Mammoplasty	0/31 (0%)	0	1/61 (1.6%)	1
Other (Not Including Serious) Adverse Events
	Norditropin		Somapacitan
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	18/31 (58.1%)		30/61 (49.2%)
Endocrine disorders
Hypothyroidism	2/31 (6.5%)	2	1/61 (1.6%)	1
Gastrointestinal disorders
Abdominal pain	0/31 (0%)	0	4/61 (6.6%)	4
General disorders
Asthenia	1/31 (3.2%)	1	4/61 (6.6%)	5
Fatigue	5/31 (16.1%)	5	6/61 (9.8%)	7
Infections and infestations
Nasopharyngitis	8/31 (25.8%)	11	12/61 (19.7%)	13
Investigations
Gamma-glutamyltransferase increased	2/31 (6.5%)	2	0/61 (0%)	0
Musculoskeletal and connective tissue disorders
Arthralgia	2/31 (6.5%)	2	5/61 (8.2%)	5
Nervous system disorders
Dizziness	3/31 (9.7%)	3	1/61 (1.6%)	1
Headache	6/31 (19.4%)	10	7/61 (11.5%)	11
Sciatica	0/31 (0%)	0	4/61 (6.6%)	4
Psychiatric disorders
Depression	2/31 (6.5%)	2	0/61 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

At the end of the trial, one or more manuscripts for publication will be prepared collaboratively between Investigator(s) and Novo Nordisk. Novo Nordisk reserves the right to postpone publication and/or communication for less than 60 days to protect intellectual property.