Genetic Disorder, Noonan Syndrome
Conditions
Brief summary
This trial is conducted in Asia. The aim of the trial is to investigate the long-term efficacy and safety of two doses of NN-220 (somatropin) in short stature due to Noonan syndrome.
Interventions
DRUGsomatropin
Administered subcutaneously (s.c., under the skin) in a daily regimen for at least 104 weeks. Subject will be offered to continue treatment for another 104 weeks.
Sponsors
Novo Nordisk A/S
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
3 Years to 10 Years
Healthy volunteers
No
Inclusion criteria
* Japanese children with Noonan syndrome clinically diagnosed in one of the following ways: 1. Clinically diagnosed by at least two medical experts using van der Burgt score list, 2. Clinically diagnosed by one medical expert using van der Burgt score list and diagnosed by result of genetic testing for Noonan syndrome, 3. Clinically diagnosed by one medical expert using van der Burgt score list and diagnosed by the same medical expert based on the results of centralised evaluation of facial change using van der Burgt score list * Height SDS (standard deviation score): -2 SDS or below (according to the Japanese reference data) * Age: boys 3 to below 11 years, girls 3 to below 10 years * Height records must be available within the period between 40 and 64 weeks prior to Visit 1 (screening) * Prepubertal children (definition for girls breast and pubes of Tanner stage is I, and none of menses, and for boys testicular volume below 4 mL, and pubes and penis of Tanner stage is I)
Exclusion criteria
* Children with known or suspected hypersensitivity against human growth hormone (hGH) or related products (including any components of the trial products) * Children with diabetic type diagnosed with the Japanese Diabetes Society Classification * Children with history or presence of active malignancy * Children who have received GH (growth hormone) treatment * Children who have received systemic administration of the following medications within two years prior to Visit 1 (screening): Thyroid hormone (except replacement therapy), antithyroid hormone, androgen, oestrogen, progesterone, anabolic steroid, adrenocortical steroid treatment period for at least 13 weeks), derivative of gonadotropin releasing hormone and somatomedin C (IGF-I)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Height SDS (Japanese National Reference Data) | Baseline, week 104 | Height SDS was calculated using the formula: SDS = (height - mean)/SD, where height was the height variable measured, mean and SD of height by sex and age for the reference population. The scores were centered around zero. Positive SDS indicated greater height and negative SDS indicated lesser height than the mean of the reference population. The change from baseline (week 0) in the height SDS after 104 weeks of treatment was analysed using an analysis of covariance (ANCOVA) model with treatment as a fixed effect and baseline height SDS as a covariate. Positive value in change from baseline indicated that SDS was better than baseline SDS. Missing values were imputed using the last observation carried forward (LOCF) method. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Height Velocity | Baseline to week 52 | Height velocity is change in height per year. The height velocity was calculated as the difference between current height (week 52) and height at baseline (week 0) divided by time between those measurement time points and multiplied by 365 days. |
| Incidence of Treatment Emergent Adverse Events | During 104 weeks of treatment | A treatment emergent adverse event (TEAE; for the pivotal phase) was defined as an event that had onset date on or after the date of visit 2 (week 0; start of treatment) and no later than the date of visit 12 (104 weeks; end of pivotal phase). For withdrawal participants (if any), an adverse event with onset date no later than 7 days after the last day of NN-220 treatment was included. |
| Change in IGF-I (Insulin-like Growth Factor-I) | Baseline, week 104 | Change from baseline (within 4 weeks prior to week 0) in IGF-I was evaluated after 104 weeks of treatment. Missing values were imputed using the LOCF method. |
| Change in HbA1c (Glycosylated Haemoglobin) | Baseline, week 104 | Change from baseline (within 4 weeks prior to week 0) in HbA1c was evaluated after 104 weeks of treatment. |
| Change in Clinical Laboratory Tests (Haematology: Erythrocytes) | Baseline, week 104 | Change from baseline (within 4 weeks prior to week 0) in haematological parameter - erythrocytes. Missing values were imputed using the LOCF method. |
| Change in Clinical Laboratory Tests (Haematology: Leukocytes and Thrombocytes) | Baseline, week 104 | Change from baseline (within 4 weeks prior to week 0) in haematological parameter - leukocytes and thrombocytes. Missing values were imputed using the LOCF method. |
| Change in Clinical Laboratory Tests (Haematology: Haemoglobin) | Baseline, week 104 | Change from baseline (within 4 weeks prior to week 0) in haematological parameter - haemoglobin. Missing values were imputed using the LOCF method. |
| Change in Clinical Laboratory Tests (Haematology: Haematocrit) | Baseline, week 104 | Change from baseline (within 4 weeks prior to week 0) in haematological parameter - haematocrit. Missing values were imputed using the LOCF method. |
| Change in Clinical Laboratory Tests (Haematology: Neutrophils) | Baseline, week 104 | Change from baseline (within 4 weeks prior to week 0) in haematological parameter - neutrophils. Missing values were imputed using the LOCF method. |
| Change in Clinical Laboratory Tests (Haematology: Lymphocytes) | Baseline, week 104 | Change from baseline (within 4 weeks prior to week 0) in haematological parameter - lymphocytes. Missing values were imputed using the LOCF method. |
| Change in Clinical Laboratory Tests (Haematology: Monocytes) | Baseline, week 104 | Change from baseline (within 4 weeks prior to week 0) in haematological parameter - monocytes. Missing values were imputed using the LOCF method. |
| Change in Clinical Laboratory Tests (Haematology: Eosinophils) | Baseline, week 104 | Change from baseline (within 4 weeks prior to week 0) in haematological parameter - eosinophils. Missing values were imputed using the LOCF method. |
| Change in Clinical Laboratory Tests (Haematology: Basophils) | Baseline, week 104 | Change from baseline (within 4 weeks prior to week 0) in haematological parameter - basophils. Missing values were imputed using the LOCF method. |
| Change in Clinical Laboratory Tests (Lipids: Total Cholesterol, LDL Cholesterol and HDL Cholesterol) | Baseline, week 104 | Change from baseline (within 4 weeks prior to week 0) in lipids: total cholesterol, LDL (low-density lipoprotein) cholesterol and HDL (high-density lipoprotein) cholesterol. Missing values were imputed using the LOCF method. |
| Change in Clinical Laboratory Tests (Biochemistry: AST, ALT, r-GTP and Alkaline Phosphatase) | Baseline, week 104 | Change from baseline (within 4 weeks prior to week 0) in biochemical parameters - aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transpeptidase (r-GTP) and alkaline phosphatase. Missing values were imputed using the LOCF method. |
| Change in Clinical Laboratory Tests (Biochemistry: Total Protein) | Baseline, week 104 | Change from baseline (within 4 weeks prior to week 0) in biochemical parameter - total protein. Missing values were imputed using the LOCF method. |
| Height Velocity SDS | Baseline to week 52 | Height velocity is change in height per year. The height velocity was calculated as the difference between current height (week 52) and height at baseline (week 0) divided by time between those measurement time points and multiplied by 365 days. Height velocity SDS was calculated using the formula: SDS = (height velocity - mean)/SD, where height velocity was the height velocity variable measured, mean and SD of height velocity by sex and age for the reference population. The scores were centered around zero. Positive SDS indicated greater height velocity and negative SDS indicated lesser height velocity than the mean of the reference population. |
| Change in Clinical Laboratory Tests (Biochemistry: Creatinine) | Baseline, Week 104 | Change from baseline (within 4 weeks prior to week 0) in biochemical parameter - creatinine. Missing values were imputed using the LOCF method. |
| Change in Glucose Tolerance (AUC of Glucose) Based on the OGTT | Baseline, week 104 | AUC (area under the curve) of glucose was calculated by the trapezoidal method. Change from baseline (within 4 weeks prior to week 0) in glucose tolerance (AUC of glucose: 30, 60, 90 and 120 min after oral glucose load) at week 104 was evaluated based on the oral glucose tolerance test (OGTT). Change from baseline results are presented as 'ratio to baseline'. |
| Change in Glucose Tolerance (AUC of Insulin) Based on the OGTT | Baseline, week 104 | AUC of insulin was calculated by the trapezoidal method. Change from baseline (within 4 weeks prior to week 0) in glucose tolerance (AUC of insulin: 30, 60, 90 and 120 min after oral glucose load) at week 104 was evaluated based on the OGTT. Change from baseline results are presented as 'ratio to baseline'. |
| Change in Bone Age | Baseline, week 104 | X-ray picture of carpal bones of left hand was taken for bone age determination. Centralised evaluation of bone age was done by the radius, ulna and short bones (RUS) score method of Tanner-Whitehouse II (TW2). Change from baseline (week 0) in bone age. |
| Change in Bone Age/Chronological Age | Baseline, week 104 | X-ray picture of carpal bones of left hand was taken for bone age determination. Centralised evaluation of bone age was done by the RUS score method of Tanner-Whitehouse II (TW2). Change from baseline (week 0) in bone age/chronological age. |
| Yearly Change in Bone Age/Change in Chronological Age | Baseline, week 52 | X-ray picture of carpal bones of left hand was taken for bone age determination. Centralised evaluation of bone age was done by the RUS score method of Tanner-Whitehouse II (TW2). Yearly change from baseline (week 0) in bone age/change in chronological age was presented. |
| Change in Vital Signs (Diastolic Blood Pressure and Systolic Blood Pressure) | Baseline, week 104 | Systolic and diastolic blood pressure were measured after a 5-minute rest in sitting position. Change from baseline (week 0) in systolic blood pressure and diastolic blood pressure. |
| Change in Vital Signs (Pulse) | Baseline, week 104 | Pulse was measured after a 5-minute rest in sitting position. Change from baseline (week 0) in pulse. |
| Change in Urinalysis (Protein, Glucose and Occult Blood) | Baseline, week 104 | The urinalysis was the measurements of protein, glucose, and occult blood at baseline (within 4 weeks prior to week 0) and week 104 and categorised as negative, trace, 1+, 2+ and 3+. Missing values were imputed using the LOCF method. Number of participants in each category at baseline and week 104 are presented. |
| Change in Blood Coagulation Test (Prothrombin Time and APTT) | Baseline, week 104 | Change from baseline (within 4 weeks prior to week 0) in blood coagulation test parameters: Prothrombin time and APTT (activated partial thromboplastin time). Missing values were imputed using the LOCF method. |
| Change in ECG | Baseline, week 104 | The ECG was recorded after a 3-minute rest in supine position at baseline (within 4 weeks prior to week 0) and week 104 and categorised as normal, abnormal NCS (not clinically significant) or abnormal CS (clinically significant). Number of participants in each ECG category at baseline and week 104 are presented. Missing values were imputed using the LOCF method. |
| Change in Height SDS (Japanese National Reference Data) | Baseline, week 208 | Height SDS was calculated using the formula: SDS = (height - mean)/SD, where height was the height variable measured, mean and SD of height by sex and age for the reference population. The scores were centered around zero. Positive SDS indicated greater height and negative SDS indicated lesser height than the mean of the reference population. The change from baseline (week 0) in the height SDS after 208 weeks of treatment was analysed. Positive value in change from baseline indicated that SDS was better than baseline SDS. Missing values were imputed using the LOCF method. |
| Change in Height SDS (Noonan Syndrome Reference Data in Japanese) | Baseline, week 208 | Height SDS was calculated using the formula: Z=\[(value/M)\^L-1\]/(S\*L); where L, M and S are skewness (L), median (M) and coefficient of variation (S) of Japanese Noonan syndrome' height provided for each sex and age. For each participant, a standard deviation score Z (SDS) was calculated based on age and sex referring to the values L, M and S. The scores were centered around zero. Positive SDS indicated greater height and negative SDS indicated lesser height than the mean of the reference population. The change from baseline (week 0) in the height SDS after 208 weeks of treatment was analysed. Positive value in change from baseline indicated that SDS was better than baseline SDS. Missing values were imputed using the LOCF method. |
| Incidence of Treatment Emergent AEs | Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period) | A treatment emergent AE (TEAE) was defined as an event that had onset date on or after the date of visit 2 (week 0; start of treatment) and no later than 7 days after the last day of NN-220 treatment. |
| Change in IGF-I | Baseline, week 208 | Change from baseline (within 4 weeks prior to week 0) in IGF-I was evaluated after 208 weeks of treatment. Missing values were imputed using the LOCF method. |
| Change in HbA1c | Baseline, week 208 | Change from baseline (within 4 weeks prior to week 0) in HbA1c was evaluated after 208 weeks of treatment. |
| Change in Clinical Laboratory Tests (Biochemistry: Blood Urea Nitrogen, Sodium, Potassium, Chloride, Total Calcium and Phosphorus) | Baseline, week 104 | Change from baseline (within 4 weeks prior to week 0) in biochemical parameters - blood urea nitrogen, sodium, potassium, chloride, total calcium and phosphorus. Missing values were imputed using the LOCF method. |
Countries
Japan
Participant flow
Recruitment details
The trial was conducted at 26 sites in Japan.
Pre-assignment details
Participants were assigned to treatment for 104 weeks in the pivotal phase and for further 104 weeks in the extension phase and were offered to continue treatment in the extended treatment phase for 26 weeks.
Participants by arm
| Arm | Count |
|---|---|
| NN-220 0.033 mg/kg/Day Participants received s.c. injection of NN-220, 0.033 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase). | 25 |
| NN-220 0.066 mg/kg/Day Participants received s.c. injection of NN-220, 0.066 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase). | 26 |
| Total | 51 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Extension Phase (104 Weeks) | Adverse Event | 0 | 2 |
| Extension Phase (104 Weeks) | Unclassified | 0 | 1 |
Baseline characteristics
| Characteristic | NN-220 0.033 mg/kg/Day | NN-220 0.066 mg/kg/Day | Total |
|---|---|---|---|
| Age, Continuous | 6.57 years STANDARD_DEVIATION 2.42 | 6.06 years STANDARD_DEVIATION 2.25 | 6.31 years STANDARD_DEVIATION 2.32 |
| Height standard deviation score (SDS) (Japanese national reference data) | -3.24 Standard deviation score STANDARD_DEVIATION 0.76 | -3.25 Standard deviation score STANDARD_DEVIATION 0.71 | -3.24 Standard deviation score STANDARD_DEVIATION 0.73 |
| Race and Ethnicity Not Collected | — | — | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 25 Participants | 26 Participants | 51 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 11 Participants | 8 Participants | 19 Participants |
| Sex: Female, Male Male | 14 Participants | 18 Participants | 32 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 25 | 0 / 26 |
| other Total, other adverse events | 24 / 25 | 26 / 26 |
| serious Total, serious adverse events | 9 / 25 | 10 / 26 |
Outcome results
Primary
Change in Height SDS (Japanese National Reference Data)
Height SDS was calculated using the formula: SDS = (height - mean)/SD, where height was the height variable measured, mean and SD of height by sex and age for the reference population. The scores were centered around zero. Positive SDS indicated greater height and negative SDS indicated lesser height than the mean of the reference population. The change from baseline (week 0) in the height SDS after 104 weeks of treatment was analysed using an analysis of covariance (ANCOVA) model with treatment as a fixed effect and baseline height SDS as a covariate. Positive value in change from baseline indicated that SDS was better than baseline SDS. Missing values were imputed using the last observation carried forward (LOCF) method.
Time frame: Baseline, week 104
Population: FAS.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| NN-220 0.033 mg/kg/Day | Change in Height SDS (Japanese National Reference Data) | 0.84 Standard deviation score | Standard Error 0.09 |
| NN-220 0.066 mg/kg/Day | Change in Height SDS (Japanese National Reference Data) | 1.47 Standard deviation score | Standard Error 0.09 |
Comparison: The change from baseline (week 0) in the height SDS after 104 weeks of treatment was analysed using an ANCOVA model with treatment as a fixed effect and baseline height SDS as a covariate.p-value: <0.000195% CI: [0.38, 0.88]ANCOVA
Secondary
Change in Blood Coagulation Test (Prothrombin Time and APTT)
Change from baseline (within 4 weeks prior to week 0) in blood coagulation test parameters: prothrombin time and APTT. Missing values were imputed using the LOCF method.
Time frame: Baseline, week 208
Population: SAS.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| NN-220 0.033 mg/kg/Day | Change in Blood Coagulation Test (Prothrombin Time and APTT) | Prothrombin time | 0.70 sec |
| NN-220 0.033 mg/kg/Day | Change in Blood Coagulation Test (Prothrombin Time and APTT) | APTT | 0.70 sec |
| NN-220 0.066 mg/kg/Day | Change in Blood Coagulation Test (Prothrombin Time and APTT) | APTT | 0.80 sec |
| NN-220 0.066 mg/kg/Day | Change in Blood Coagulation Test (Prothrombin Time and APTT) | Prothrombin time | 1.20 sec |
Secondary
Change in Blood Coagulation Test (Prothrombin Time and APTT)
Change from baseline (within 4 weeks prior to week 0) in blood coagulation test parameters: Prothrombin time and APTT (activated partial thromboplastin time). Missing values were imputed using the LOCF method.
Time frame: Baseline, week 104
Population: SAS.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| NN-220 0.033 mg/kg/Day | Change in Blood Coagulation Test (Prothrombin Time and APTT) | Prothrombin time | 0.50 Second (sec) |
| NN-220 0.033 mg/kg/Day | Change in Blood Coagulation Test (Prothrombin Time and APTT) | APTT | 0.60 Second (sec) |
| NN-220 0.066 mg/kg/Day | Change in Blood Coagulation Test (Prothrombin Time and APTT) | Prothrombin time | 0.80 Second (sec) |
| NN-220 0.066 mg/kg/Day | Change in Blood Coagulation Test (Prothrombin Time and APTT) | APTT | 0.25 Second (sec) |
Secondary
Change in Bone Age
X-ray picture of carpal bones of left hand was taken for bone age determination. Centralised evaluation of bone age was done by the RUS score method of Tanner-Whitehouse II (TW2). Change from baseline (week 0) in bone age.
Time frame: Baseline, week 208
Population: SAS. Number analyzed = participants with available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NN-220 0.033 mg/kg/Day | Change in Bone Age | 3.89 Years | Standard Deviation 1.35 |
| NN-220 0.066 mg/kg/Day | Change in Bone Age | 4.68 Years | Standard Deviation 1.11 |
Secondary
Change in Bone Age
X-ray picture of carpal bones of left hand was taken for bone age determination. Centralised evaluation of bone age was done by the radius, ulna and short bones (RUS) score method of Tanner-Whitehouse II (TW2). Change from baseline (week 0) in bone age.
Time frame: Baseline, week 104
Population: SAS.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NN-220 0.033 mg/kg/Day | Change in Bone Age | 2.07 Years | Standard Deviation 0.8 |
| NN-220 0.066 mg/kg/Day | Change in Bone Age | 2.63 Years | Standard Deviation 0.94 |
Secondary
Change in Bone Age/Chronological Age
X-ray picture of carpal bones of left hand was taken for bone age determination. Centralised evaluation of bone age was done by the RUS score method of Tanner-Whitehouse II (TW2). Change from baseline (week 0) in bone age/chronological age.
Time frame: Baseline, week 208
Population: SAS. Number analyzed = participants with available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NN-220 0.033 mg/kg/Day | Change in Bone Age/Chronological Age | 0.049 Ratio (bone age/chronological age) | Standard Deviation 0.159 |
| NN-220 0.066 mg/kg/Day | Change in Bone Age/Chronological Age | 0.149 Ratio (bone age/chronological age) | Standard Deviation 0.151 |
Secondary
Change in Bone Age/Chronological Age
X-ray picture of carpal bones of left hand was taken for bone age determination. Centralised evaluation of bone age was done by the RUS score method of Tanner-Whitehouse II (TW2). Change from baseline (week 0) in bone age/chronological age.
Time frame: Baseline, week 104
Population: SAS.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NN-220 0.033 mg/kg/Day | Change in Bone Age/Chronological Age | 0.047 Ratio (bone age/chronological age) | Standard Deviation 0.127 |
| NN-220 0.066 mg/kg/Day | Change in Bone Age/Chronological Age | 0.133 Ratio (bone age/chronological age) | Standard Deviation 0.127 |
Secondary
Change in Clinical Laboratory Tests (Biochemistry: AST, ALT, r-GTP and Alkaline Phosphatase)
Change from baseline (within 4 weeks prior to week 0) in biochemical parameters - aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transpeptidase (r-GTP) and alkaline phosphatase. Missing values were imputed using the LOCF method.
Time frame: Baseline, week 104
Population: SAS. Number analyzed = participants with available data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| NN-220 0.033 mg/kg/Day | Change in Clinical Laboratory Tests (Biochemistry: AST, ALT, r-GTP and Alkaline Phosphatase) | AST | -3.6 Units per liter (U/L) | Standard Deviation 2.9 |
| NN-220 0.033 mg/kg/Day | Change in Clinical Laboratory Tests (Biochemistry: AST, ALT, r-GTP and Alkaline Phosphatase) | r-GTP | 0.4 Units per liter (U/L) | Standard Deviation 1.6 |
| NN-220 0.033 mg/kg/Day | Change in Clinical Laboratory Tests (Biochemistry: AST, ALT, r-GTP and Alkaline Phosphatase) | ALT | -1.04 Units per liter (U/L) | Standard Deviation 3.1 |
| NN-220 0.033 mg/kg/Day | Change in Clinical Laboratory Tests (Biochemistry: AST, ALT, r-GTP and Alkaline Phosphatase) | Alkaline phosphatase | 73.8 Units per liter (U/L) | Standard Deviation 76.3 |
| NN-220 0.066 mg/kg/Day | Change in Clinical Laboratory Tests (Biochemistry: AST, ALT, r-GTP and Alkaline Phosphatase) | ALT | -1.73 Units per liter (U/L) | Standard Deviation 4.2 |
| NN-220 0.066 mg/kg/Day | Change in Clinical Laboratory Tests (Biochemistry: AST, ALT, r-GTP and Alkaline Phosphatase) | AST | -6.0 Units per liter (U/L) | Standard Deviation 4.3 |
| NN-220 0.066 mg/kg/Day | Change in Clinical Laboratory Tests (Biochemistry: AST, ALT, r-GTP and Alkaline Phosphatase) | Alkaline phosphatase | 124.3 Units per liter (U/L) | Standard Deviation 124 |
| NN-220 0.066 mg/kg/Day | Change in Clinical Laboratory Tests (Biochemistry: AST, ALT, r-GTP and Alkaline Phosphatase) | r-GTP | -3.7 Units per liter (U/L) | Standard Deviation 19.4 |
Secondary
Change in Clinical Laboratory Tests (Biochemistry: AST, ALT, r-GTP and Alkaline Phosphatase)
Change from baseline (within 4 weeks prior to week 0) in biochemical parameters - AST, ALT, r-GTP and alkaline phosphatase. Missing values were imputed using the LOCF method.
Time frame: Baseline, week 208
Population: SAS. Number analyzed = participants with available data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| NN-220 0.033 mg/kg/Day | Change in Clinical Laboratory Tests (Biochemistry: AST, ALT, r-GTP and Alkaline Phosphatase) | AST | -5.4 U/L | Standard Deviation 2.4 |
| NN-220 0.033 mg/kg/Day | Change in Clinical Laboratory Tests (Biochemistry: AST, ALT, r-GTP and Alkaline Phosphatase) | ALT | -1.28 U/L | Standard Deviation 2.65 |
| NN-220 0.033 mg/kg/Day | Change in Clinical Laboratory Tests (Biochemistry: AST, ALT, r-GTP and Alkaline Phosphatase) | r-GTP | 1.0 U/L | Standard Deviation 1.6 |
| NN-220 0.033 mg/kg/Day | Change in Clinical Laboratory Tests (Biochemistry: AST, ALT, r-GTP and Alkaline Phosphatase) | Alkaline phosphatase | 113.9 U/L | Standard Deviation 126.4 |
| NN-220 0.066 mg/kg/Day | Change in Clinical Laboratory Tests (Biochemistry: AST, ALT, r-GTP and Alkaline Phosphatase) | Alkaline phosphatase | 84.8 U/L | Standard Deviation 140.9 |
| NN-220 0.066 mg/kg/Day | Change in Clinical Laboratory Tests (Biochemistry: AST, ALT, r-GTP and Alkaline Phosphatase) | AST | -7.4 U/L | Standard Deviation 5.2 |
| NN-220 0.066 mg/kg/Day | Change in Clinical Laboratory Tests (Biochemistry: AST, ALT, r-GTP and Alkaline Phosphatase) | r-GTP | -3.5 U/L | Standard Deviation 22.8 |
| NN-220 0.066 mg/kg/Day | Change in Clinical Laboratory Tests (Biochemistry: AST, ALT, r-GTP and Alkaline Phosphatase) | ALT | -1.81 U/L | Standard Deviation 4.42 |
Secondary
Change in Clinical Laboratory Tests (Biochemistry: Blood Urea Nitrogen, Sodium, Potassium, Chloride, Total Calcium and Phosphorus)
Change from baseline (within 4 weeks prior to week 0) in biochemical parameters - blood urea nitrogen, sodium, potassium, chloride, total calcium and phosphorus. Missing values were imputed using the LOCF method.
Time frame: Baseline, week 208
Population: SAS. Number analyzed = participants with available data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| NN-220 0.033 mg/kg/Day | Change in Clinical Laboratory Tests (Biochemistry: Blood Urea Nitrogen, Sodium, Potassium, Chloride, Total Calcium and Phosphorus) | Blood urea nitrogen | -0.10 mmol/L | Standard Deviation 0.52 |
| NN-220 0.033 mg/kg/Day | Change in Clinical Laboratory Tests (Biochemistry: Blood Urea Nitrogen, Sodium, Potassium, Chloride, Total Calcium and Phosphorus) | Sodium | 0.9 mmol/L | Standard Deviation 2.1 |
| NN-220 0.033 mg/kg/Day | Change in Clinical Laboratory Tests (Biochemistry: Blood Urea Nitrogen, Sodium, Potassium, Chloride, Total Calcium and Phosphorus) | Potassium | -0.13 mmol/L | Standard Deviation 0.28 |
| NN-220 0.033 mg/kg/Day | Change in Clinical Laboratory Tests (Biochemistry: Blood Urea Nitrogen, Sodium, Potassium, Chloride, Total Calcium and Phosphorus) | Chloride | -0.3 mmol/L | Standard Deviation 2.2 |
| NN-220 0.033 mg/kg/Day | Change in Clinical Laboratory Tests (Biochemistry: Blood Urea Nitrogen, Sodium, Potassium, Chloride, Total Calcium and Phosphorus) | Total calcium | -0.02 mmol/L | Standard Deviation 0.07 |
| NN-220 0.033 mg/kg/Day | Change in Clinical Laboratory Tests (Biochemistry: Blood Urea Nitrogen, Sodium, Potassium, Chloride, Total Calcium and Phosphorus) | Phosphorus | 0.036 mmol/L | Standard Deviation 0.111 |
| NN-220 0.066 mg/kg/Day | Change in Clinical Laboratory Tests (Biochemistry: Blood Urea Nitrogen, Sodium, Potassium, Chloride, Total Calcium and Phosphorus) | Total calcium | -0.00 mmol/L | Standard Deviation 0.08 |
| NN-220 0.066 mg/kg/Day | Change in Clinical Laboratory Tests (Biochemistry: Blood Urea Nitrogen, Sodium, Potassium, Chloride, Total Calcium and Phosphorus) | Blood urea nitrogen | -0.15 mmol/L | Standard Deviation 0.53 |
| NN-220 0.066 mg/kg/Day | Change in Clinical Laboratory Tests (Biochemistry: Blood Urea Nitrogen, Sodium, Potassium, Chloride, Total Calcium and Phosphorus) | Chloride | -0.2 mmol/L | Standard Deviation 2.2 |
| NN-220 0.066 mg/kg/Day | Change in Clinical Laboratory Tests (Biochemistry: Blood Urea Nitrogen, Sodium, Potassium, Chloride, Total Calcium and Phosphorus) | Sodium | 1.4 mmol/L | Standard Deviation 2.5 |
| NN-220 0.066 mg/kg/Day | Change in Clinical Laboratory Tests (Biochemistry: Blood Urea Nitrogen, Sodium, Potassium, Chloride, Total Calcium and Phosphorus) | Phosphorus | 0.111 mmol/L | Standard Deviation 0.103 |
| NN-220 0.066 mg/kg/Day | Change in Clinical Laboratory Tests (Biochemistry: Blood Urea Nitrogen, Sodium, Potassium, Chloride, Total Calcium and Phosphorus) | Potassium | -0.09 mmol/L | Standard Deviation 0.38 |
Secondary
Change in Clinical Laboratory Tests (Biochemistry: Blood Urea Nitrogen, Sodium, Potassium, Chloride, Total Calcium and Phosphorus)
Change from baseline (within 4 weeks prior to week 0) in biochemical parameters - blood urea nitrogen, sodium, potassium, chloride, total calcium and phosphorus. Missing values were imputed using the LOCF method.
Time frame: Baseline, week 104
Population: SAS. Number analyzed = participants with available data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| NN-220 0.033 mg/kg/Day | Change in Clinical Laboratory Tests (Biochemistry: Blood Urea Nitrogen, Sodium, Potassium, Chloride, Total Calcium and Phosphorus) | Blood urea nitrogen | -0.17 mmol/L | Standard Deviation 0.38 |
| NN-220 0.033 mg/kg/Day | Change in Clinical Laboratory Tests (Biochemistry: Blood Urea Nitrogen, Sodium, Potassium, Chloride, Total Calcium and Phosphorus) | Sodium | -0.3 mmol/L | Standard Deviation 2.4 |
| NN-220 0.033 mg/kg/Day | Change in Clinical Laboratory Tests (Biochemistry: Blood Urea Nitrogen, Sodium, Potassium, Chloride, Total Calcium and Phosphorus) | Potassium | -0.03 mmol/L | Standard Deviation 0.32 |
| NN-220 0.033 mg/kg/Day | Change in Clinical Laboratory Tests (Biochemistry: Blood Urea Nitrogen, Sodium, Potassium, Chloride, Total Calcium and Phosphorus) | Chloride | -0.8 mmol/L | Standard Deviation 2.3 |
| NN-220 0.033 mg/kg/Day | Change in Clinical Laboratory Tests (Biochemistry: Blood Urea Nitrogen, Sodium, Potassium, Chloride, Total Calcium and Phosphorus) | Total calcium | 0.00 mmol/L | Standard Deviation 0.08 |
| NN-220 0.033 mg/kg/Day | Change in Clinical Laboratory Tests (Biochemistry: Blood Urea Nitrogen, Sodium, Potassium, Chloride, Total Calcium and Phosphorus) | Phosphorus | 0.124 mmol/L | Standard Deviation 0.125 |
| NN-220 0.066 mg/kg/Day | Change in Clinical Laboratory Tests (Biochemistry: Blood Urea Nitrogen, Sodium, Potassium, Chloride, Total Calcium and Phosphorus) | Total calcium | 0.01 mmol/L | Standard Deviation 0.07 |
| NN-220 0.066 mg/kg/Day | Change in Clinical Laboratory Tests (Biochemistry: Blood Urea Nitrogen, Sodium, Potassium, Chloride, Total Calcium and Phosphorus) | Blood urea nitrogen | -0.21 mmol/L | Standard Deviation 0.44 |
| NN-220 0.066 mg/kg/Day | Change in Clinical Laboratory Tests (Biochemistry: Blood Urea Nitrogen, Sodium, Potassium, Chloride, Total Calcium and Phosphorus) | Chloride | -1.3 mmol/L | Standard Deviation 1.9 |
| NN-220 0.066 mg/kg/Day | Change in Clinical Laboratory Tests (Biochemistry: Blood Urea Nitrogen, Sodium, Potassium, Chloride, Total Calcium and Phosphorus) | Sodium | -0.2 mmol/L | Standard Deviation 2.6 |
| NN-220 0.066 mg/kg/Day | Change in Clinical Laboratory Tests (Biochemistry: Blood Urea Nitrogen, Sodium, Potassium, Chloride, Total Calcium and Phosphorus) | Phosphorus | 0.129 mmol/L | Standard Deviation 0.141 |
| NN-220 0.066 mg/kg/Day | Change in Clinical Laboratory Tests (Biochemistry: Blood Urea Nitrogen, Sodium, Potassium, Chloride, Total Calcium and Phosphorus) | Potassium | -0.15 mmol/L | Standard Deviation 0.41 |
Secondary
Change in Clinical Laboratory Tests (Biochemistry: Creatinine)
Change from baseline (within 4 weeks prior to week 0) in biochemical parameter - creatinine. Missing values were imputed using the LOCF method.
Time frame: Baseline, Week 104
Population: SAS.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NN-220 0.033 mg/kg/Day | Change in Clinical Laboratory Tests (Biochemistry: Creatinine) | 1.8 Micromoles per liter (umol/L) | Standard Deviation 3.5 |
| NN-220 0.066 mg/kg/Day | Change in Clinical Laboratory Tests (Biochemistry: Creatinine) | 2.5 Micromoles per liter (umol/L) | Standard Deviation 3.4 |
Secondary
Change in Clinical Laboratory Tests (Biochemistry: Creatinine)
Change from baseline (within 4 weeks prior to week 0) in biochemical parameters - creatinine. Missing values were imputed using the LOCF method.
Time frame: Baseline, week 208
Population: SAS.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NN-220 0.033 mg/kg/Day | Change in Clinical Laboratory Tests (Biochemistry: Creatinine) | 5.5 umol/L | Standard Deviation 4.4 |
| NN-220 0.066 mg/kg/Day | Change in Clinical Laboratory Tests (Biochemistry: Creatinine) | 6.7 umol/L | Standard Deviation 4.1 |
Secondary
Change in Clinical Laboratory Tests (Biochemistry: Total Protein)
Change from baseline (within 4 weeks prior to week 0) in biochemical parameter - total protein. Missing values were imputed using the LOCF method.
Time frame: Baseline, week 208
Population: SAS. Number analyzed = participants with available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NN-220 0.033 mg/kg/Day | Change in Clinical Laboratory Tests (Biochemistry: Total Protein) | 0.02 g/dL | Standard Deviation 0.33 |
| NN-220 0.066 mg/kg/Day | Change in Clinical Laboratory Tests (Biochemistry: Total Protein) | 0.05 g/dL | Standard Deviation 0.37 |
Secondary
Change in Clinical Laboratory Tests (Biochemistry: Total Protein)
Change from baseline (within 4 weeks prior to week 0) in biochemical parameter - total protein. Missing values were imputed using the LOCF method.
Time frame: Baseline, week 104
Population: SAS. Number analyzed = participants with available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NN-220 0.033 mg/kg/Day | Change in Clinical Laboratory Tests (Biochemistry: Total Protein) | 0.02 Grams per deciliter (g/dL) | Standard Deviation 0.38 |
| NN-220 0.066 mg/kg/Day | Change in Clinical Laboratory Tests (Biochemistry: Total Protein) | -0.05 Grams per deciliter (g/dL) | Standard Deviation 0.27 |
Secondary
Change in Clinical Laboratory Tests (Haematology: Basophils)
Change from baseline (within 4 weeks prior to week 0) in haematological parameter - basophils. Missing values were imputed using the LOCF method.
Time frame: Baseline, week 104
Population: SAS.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NN-220 0.033 mg/kg/Day | Change in Clinical Laboratory Tests (Haematology: Basophils) | 0.10 Percentage of basophils | Standard Deviation 0.36 |
| NN-220 0.066 mg/kg/Day | Change in Clinical Laboratory Tests (Haematology: Basophils) | -0.07 Percentage of basophils | Standard Deviation 0.27 |
Secondary
Change in Clinical Laboratory Tests (Haematology: Basophils)
Change from baseline (within 4 weeks prior to week 0) in haematological parameter - basophils. Missing values were imputed using the LOCF method.
Time frame: Baseline, week 208
Population: SAS.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NN-220 0.033 mg/kg/Day | Change in Clinical Laboratory Tests (Haematology: Basophils) | -0.01 Percentage of basophils | Standard Deviation 0.26 |
| NN-220 0.066 mg/kg/Day | Change in Clinical Laboratory Tests (Haematology: Basophils) | -0.12 Percentage of basophils | Standard Deviation 0.26 |
Secondary
Change in Clinical Laboratory Tests (Haematology: Eosinophils)
Change from baseline (within 4 weeks prior to week 0) in haematological parameter - eosinophils. Missing values were imputed using the LOCF method.
Time frame: Baseline, week 208
Population: SAS.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NN-220 0.033 mg/kg/Day | Change in Clinical Laboratory Tests (Haematology: Eosinophils) | 1.30 Percentage of eosinophils | Standard Deviation 3.57 |
| NN-220 0.066 mg/kg/Day | Change in Clinical Laboratory Tests (Haematology: Eosinophils) | 0.42 Percentage of eosinophils | Standard Deviation 1.44 |
Secondary
Change in Clinical Laboratory Tests (Haematology: Eosinophils)
Change from baseline (within 4 weeks prior to week 0) in haematological parameter - eosinophils. Missing values were imputed using the LOCF method.
Time frame: Baseline, week 104
Population: SAS.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NN-220 0.033 mg/kg/Day | Change in Clinical Laboratory Tests (Haematology: Eosinophils) | 0.99 Percentage of eosinophils | Standard Deviation 2.95 |
| NN-220 0.066 mg/kg/Day | Change in Clinical Laboratory Tests (Haematology: Eosinophils) | -0.05 Percentage of eosinophils | Standard Deviation 1.33 |
Secondary
Change in Clinical Laboratory Tests (Haematology: Erythrocytes)
Change from baseline (within 4 weeks prior to week 0) in haematological parameter - erythrocytes. Missing values were imputed using the LOCF method.
Time frame: Baseline, week 104
Population: SAS.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NN-220 0.033 mg/kg/Day | Change in Clinical Laboratory Tests (Haematology: Erythrocytes) | 0.106 10^12 cells per liter (10^12 cells/L) | Standard Deviation 0.3 |
| NN-220 0.066 mg/kg/Day | Change in Clinical Laboratory Tests (Haematology: Erythrocytes) | 0.165 10^12 cells per liter (10^12 cells/L) | Standard Deviation 0.234 |
Secondary
Change in Clinical Laboratory Tests (Haematology: Erythrocytes)
Change from baseline (within 4 weeks prior to week 0) in haematological parameter - erythrocytes. Missing values were imputed using the LOCF method.
Time frame: Baseline, week 208
Population: SAS.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NN-220 0.033 mg/kg/Day | Change in Clinical Laboratory Tests (Haematology: Erythrocytes) | 0.121 10^12 cells/L | Standard Deviation 0.328 |
| NN-220 0.066 mg/kg/Day | Change in Clinical Laboratory Tests (Haematology: Erythrocytes) | 0.095 10^12 cells/L | Standard Deviation 0.204 |
Secondary
Change in Clinical Laboratory Tests (Haematology: Haematocrit)
Change from baseline (within 4 weeks prior to week 0) in haematological parameter - haematocrit. Missing values were imputed using the LOCF method.
Time frame: Baseline, week 208
Population: SAS.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NN-220 0.033 mg/kg/Day | Change in Clinical Laboratory Tests (Haematology: Haematocrit) | 1.24 Percentage of red blood cells | Standard Deviation 2.45 |
| NN-220 0.066 mg/kg/Day | Change in Clinical Laboratory Tests (Haematology: Haematocrit) | 1.26 Percentage of red blood cells | Standard Deviation 1.63 |
Secondary
Change in Clinical Laboratory Tests (Haematology: Haematocrit)
Change from baseline (within 4 weeks prior to week 0) in haematological parameter - haematocrit. Missing values were imputed using the LOCF method.
Time frame: Baseline, week 104
Population: SAS.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NN-220 0.033 mg/kg/Day | Change in Clinical Laboratory Tests (Haematology: Haematocrit) | 0.85 Percentage of red blood cells | Standard Deviation 2.11 |
| NN-220 0.066 mg/kg/Day | Change in Clinical Laboratory Tests (Haematology: Haematocrit) | 0.94 Percentage of red blood cells | Standard Deviation 1.93 |
Secondary
Change in Clinical Laboratory Tests (Haematology: Haemoglobin)
Change from baseline (within 4 weeks prior to week 0) in haematological parameter - haemoglobin. Missing values were imputed using the LOCF method.
Time frame: Baseline, week 208
Population: SAS.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NN-220 0.033 mg/kg/Day | Change in Clinical Laboratory Tests (Haematology: Haemoglobin) | 0.46 mmol/L | Standard Deviation 0.58 |
| NN-220 0.066 mg/kg/Day | Change in Clinical Laboratory Tests (Haematology: Haemoglobin) | 0.46 mmol/L | Standard Deviation 0.35 |
Secondary
Change in Clinical Laboratory Tests (Haematology: Haemoglobin)
Change from baseline (within 4 weeks prior to week 0) in haematological parameter - haemoglobin. Missing values were imputed using the LOCF method.
Time frame: Baseline, week 104
Population: SAS.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NN-220 0.033 mg/kg/Day | Change in Clinical Laboratory Tests (Haematology: Haemoglobin) | 0.26 Millimoles per liter (mmol/L) | Standard Deviation 0.46 |
| NN-220 0.066 mg/kg/Day | Change in Clinical Laboratory Tests (Haematology: Haemoglobin) | 0.32 Millimoles per liter (mmol/L) | Standard Deviation 0.55 |
Secondary
Change in Clinical Laboratory Tests (Haematology: Leukocytes and Thrombocytes)
Change from baseline (within 4 weeks prior to week 0) in haematological parameter - leukocytes and thrombocytes. Missing values were imputed using the LOCF method.
Time frame: Baseline, Week 208
Population: SAS. Number analyzed = participants with available data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| NN-220 0.033 mg/kg/Day | Change in Clinical Laboratory Tests (Haematology: Leukocytes and Thrombocytes) | Leukocytes | -1.50 10^9 cells/L | Standard Deviation 2.22 |
| NN-220 0.033 mg/kg/Day | Change in Clinical Laboratory Tests (Haematology: Leukocytes and Thrombocytes) | Thrombocytes | -27.5 10^9 cells/L | Standard Deviation 55.5 |
| NN-220 0.066 mg/kg/Day | Change in Clinical Laboratory Tests (Haematology: Leukocytes and Thrombocytes) | Leukocytes | -1.50 10^9 cells/L | Standard Deviation 1.57 |
| NN-220 0.066 mg/kg/Day | Change in Clinical Laboratory Tests (Haematology: Leukocytes and Thrombocytes) | Thrombocytes | -56.6 10^9 cells/L | Standard Deviation 58.5 |
Secondary
Change in Clinical Laboratory Tests (Haematology: Leukocytes and Thrombocytes)
Change from baseline (within 4 weeks prior to week 0) in haematological parameter - leukocytes and thrombocytes. Missing values were imputed using the LOCF method.
Time frame: Baseline, week 104
Population: SAS. Number analyzed = participants with available data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| NN-220 0.033 mg/kg/Day | Change in Clinical Laboratory Tests (Haematology: Leukocytes and Thrombocytes) | Leukocytes | -0.69 10^9 cells per liter (10^9 cells/L) | Standard Deviation 2.28 |
| NN-220 0.033 mg/kg/Day | Change in Clinical Laboratory Tests (Haematology: Leukocytes and Thrombocytes) | Thrombocytes | -6.9 10^9 cells per liter (10^9 cells/L) | Standard Deviation 60.2 |
| NN-220 0.066 mg/kg/Day | Change in Clinical Laboratory Tests (Haematology: Leukocytes and Thrombocytes) | Leukocytes | -1.01 10^9 cells per liter (10^9 cells/L) | Standard Deviation 1.77 |
| NN-220 0.066 mg/kg/Day | Change in Clinical Laboratory Tests (Haematology: Leukocytes and Thrombocytes) | Thrombocytes | -29.0 10^9 cells per liter (10^9 cells/L) | Standard Deviation 63.2 |
Secondary
Change in Clinical Laboratory Tests (Haematology: Lymphocytes)
Change from baseline (within 4 weeks prior to week 0) in haematological parameter - lymphocytes. Missing values were imputed using the LOCF method.
Time frame: Baseline, week 104
Population: SAS.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NN-220 0.033 mg/kg/Day | Change in Clinical Laboratory Tests (Haematology: Lymphocytes) | 2.80 Percentage of lymphocytes | Standard Deviation 9.07 |
| NN-220 0.066 mg/kg/Day | Change in Clinical Laboratory Tests (Haematology: Lymphocytes) | -4.73 Percentage of lymphocytes | Standard Deviation 8.73 |
Secondary
Change in Clinical Laboratory Tests (Haematology: Lymphocytes)
Change from baseline (within 4 weeks prior to week 0) in haematological parameter - lymphocytes. Missing values were imputed using the LOCF method.
Time frame: Baseline, week 208
Population: SAS.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NN-220 0.033 mg/kg/Day | Change in Clinical Laboratory Tests (Haematology: Lymphocytes) | -0.14 Percentage of lymphocytes | Standard Deviation 8.88 |
| NN-220 0.066 mg/kg/Day | Change in Clinical Laboratory Tests (Haematology: Lymphocytes) | -5.70 Percentage of lymphocytes | Standard Deviation 8.86 |
Secondary
Change in Clinical Laboratory Tests (Haematology: Monocytes)
Change from baseline (within 4 weeks prior to week 0) in haematological parameter - monocytes. Missing values were imputed using the LOCF method.
Time frame: Baseline, week 104
Population: SAS.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NN-220 0.033 mg/kg/Day | Change in Clinical Laboratory Tests (Haematology: Monocytes) | 0.38 Percentage of monocytes | Standard Deviation 1.41 |
| NN-220 0.066 mg/kg/Day | Change in Clinical Laboratory Tests (Haematology: Monocytes) | 0.39 Percentage of monocytes | Standard Deviation 1.35 |
Secondary
Change in Clinical Laboratory Tests (Haematology: Monocytes)
Change from baseline (within 4 weeks prior to week 0) in haematological parameter - monocytes. Missing values were imputed using the LOCF method.
Time frame: Baseline, week 208
Population: SAS.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NN-220 0.033 mg/kg/Day | Change in Clinical Laboratory Tests (Haematology: Monocytes) | 0.08 Percentage of monocytes | Standard Deviation 1.21 |
| NN-220 0.066 mg/kg/Day | Change in Clinical Laboratory Tests (Haematology: Monocytes) | 0.56 Percentage of monocytes | Standard Deviation 1.18 |
Secondary
Change in Clinical Laboratory Tests (Haematology: Neutrophils)
Change from baseline (within 4 weeks prior to week 0) in haematological parameter - neutrophils. Missing values were imputed using the LOCF method.
Time frame: Baseline, week 208
Population: SAS.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NN-220 0.033 mg/kg/Day | Change in Clinical Laboratory Tests (Haematology: Neutrophils) | -1.23 Percentage of neutrophils | Standard Deviation 10.8 |
| NN-220 0.066 mg/kg/Day | Change in Clinical Laboratory Tests (Haematology: Neutrophils) | 4.88 Percentage of neutrophils | Standard Deviation 9.41 |
Secondary
Change in Clinical Laboratory Tests (Haematology: Neutrophils)
Change from baseline (within 4 weeks prior to week 0) in haematological parameter - neutrophils. Missing values were imputed using the LOCF method.
Time frame: Baseline, week 104
Population: SAS.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NN-220 0.033 mg/kg/Day | Change in Clinical Laboratory Tests (Haematology: Neutrophils) | -4.28 Percentage of neutrophils | Standard Deviation 11.44 |
| NN-220 0.066 mg/kg/Day | Change in Clinical Laboratory Tests (Haematology: Neutrophils) | 4.50 Percentage of neutrophils | Standard Deviation 9.01 |
Secondary
Change in Clinical Laboratory Tests (Lipids: Total Cholesterol, LDL Cholesterol and HDL Cholesterol)
Change from baseline (within 4 weeks prior to week 0) in lipids: total cholesterol, LDL (low-density lipoprotein) cholesterol and HDL (high-density lipoprotein) cholesterol. Missing values were imputed using the LOCF method.
Time frame: Baseline, week 104
Population: SAS.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| NN-220 0.033 mg/kg/Day | Change in Clinical Laboratory Tests (Lipids: Total Cholesterol, LDL Cholesterol and HDL Cholesterol) | Total cholesterol | 0.073 mmol/L | Standard Deviation 0.655 |
| NN-220 0.033 mg/kg/Day | Change in Clinical Laboratory Tests (Lipids: Total Cholesterol, LDL Cholesterol and HDL Cholesterol) | LDL cholesterol | 0.040 mmol/L | Standard Deviation 0.521 |
| NN-220 0.033 mg/kg/Day | Change in Clinical Laboratory Tests (Lipids: Total Cholesterol, LDL Cholesterol and HDL Cholesterol) | HDL cholesterol | -0.020 mmol/L | Standard Deviation 0.212 |
| NN-220 0.066 mg/kg/Day | Change in Clinical Laboratory Tests (Lipids: Total Cholesterol, LDL Cholesterol and HDL Cholesterol) | HDL cholesterol | -0.034 mmol/L | Standard Deviation 0.21 |
| NN-220 0.066 mg/kg/Day | Change in Clinical Laboratory Tests (Lipids: Total Cholesterol, LDL Cholesterol and HDL Cholesterol) | Total cholesterol | -0.110 mmol/L | Standard Deviation 0.371 |
| NN-220 0.066 mg/kg/Day | Change in Clinical Laboratory Tests (Lipids: Total Cholesterol, LDL Cholesterol and HDL Cholesterol) | LDL cholesterol | -0.120 mmol/L | Standard Deviation 0.323 |
Secondary
Change in Clinical Laboratory Tests (Lipids: Total Cholesterol, LDL Cholesterol and HDL Cholesterol)
Change from baseline (within 4 weeks prior to week 0) in lipids: total cholesterol, LDL cholesterol and HDL cholesterol. Missing values were imputed using the LOCF method.
Time frame: Baseline, week 208
Population: SAS.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| NN-220 0.033 mg/kg/Day | Change in Clinical Laboratory Tests (Lipids: Total Cholesterol, LDL Cholesterol and HDL Cholesterol) | Total cholesterol | 0.031 mmol/L | Standard Deviation 0.639 |
| NN-220 0.033 mg/kg/Day | Change in Clinical Laboratory Tests (Lipids: Total Cholesterol, LDL Cholesterol and HDL Cholesterol) | LDL cholesterol | -0.005 mmol/L | Standard Deviation 0.55 |
| NN-220 0.033 mg/kg/Day | Change in Clinical Laboratory Tests (Lipids: Total Cholesterol, LDL Cholesterol and HDL Cholesterol) | HDL cholesterol | 0.036 mmol/L | Standard Deviation 0.275 |
| NN-220 0.066 mg/kg/Day | Change in Clinical Laboratory Tests (Lipids: Total Cholesterol, LDL Cholesterol and HDL Cholesterol) | Total cholesterol | -0.110 mmol/L | Standard Deviation 0.609 |
| NN-220 0.066 mg/kg/Day | Change in Clinical Laboratory Tests (Lipids: Total Cholesterol, LDL Cholesterol and HDL Cholesterol) | LDL cholesterol | -0.173 mmol/L | Standard Deviation 0.523 |
| NN-220 0.066 mg/kg/Day | Change in Clinical Laboratory Tests (Lipids: Total Cholesterol, LDL Cholesterol and HDL Cholesterol) | HDL cholesterol | 0.056 mmol/L | Standard Deviation 0.173 |
Secondary
Change in ECG
The ECG was recorded after a 3-minute rest in supine position at baseline (within 4 weeks prior to week 0) and week 208 and categorised as normal, abnormal NCS or abnormal CS. Number of participants in each ECG category at baseline and week 208 are presented. Missing values were imputed using the LOCF method.
Time frame: Baseline, week 208
Population: SAS.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| NN-220 0.033 mg/kg/Day | Change in ECG | Normal (Baseline) | 15 Participants |
| NN-220 0.033 mg/kg/Day | Change in ECG | Abnormal NCS (Baseline) | 10 Participants |
| NN-220 0.033 mg/kg/Day | Change in ECG | Abnormal CS (Baseline) | 0 Participants |
| NN-220 0.033 mg/kg/Day | Change in ECG | Normal (Week 208) | 20 Participants |
| NN-220 0.033 mg/kg/Day | Change in ECG | Abnormal NCS (Week 208) | 5 Participants |
| NN-220 0.033 mg/kg/Day | Change in ECG | Abnormal CS (Week 208) | 0 Participants |
| NN-220 0.066 mg/kg/Day | Change in ECG | Abnormal NCS (Week 208) | 9 Participants |
| NN-220 0.066 mg/kg/Day | Change in ECG | Normal (Baseline) | 14 Participants |
| NN-220 0.066 mg/kg/Day | Change in ECG | Normal (Week 208) | 16 Participants |
| NN-220 0.066 mg/kg/Day | Change in ECG | Abnormal NCS (Baseline) | 12 Participants |
| NN-220 0.066 mg/kg/Day | Change in ECG | Abnormal CS (Week 208) | 1 Participants |
| NN-220 0.066 mg/kg/Day | Change in ECG | Abnormal CS (Baseline) | 0 Participants |
Secondary
Change in ECG
The ECG was recorded after a 3-minute rest in supine position at baseline (within 4 weeks prior to week 0) and week 104 and categorised as normal, abnormal NCS (not clinically significant) or abnormal CS (clinically significant). Number of participants in each ECG category at baseline and week 104 are presented. Missing values were imputed using the LOCF method.
Time frame: Baseline, week 104
Population: SAS.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| NN-220 0.033 mg/kg/Day | Change in ECG | Normal (Baseline) | 15 Participants |
| NN-220 0.033 mg/kg/Day | Change in ECG | Abnormal NCS (Baseline) | 10 Participants |
| NN-220 0.033 mg/kg/Day | Change in ECG | Abnormal CS (Baseline) | 0 Participants |
| NN-220 0.033 mg/kg/Day | Change in ECG | Normal (Week 104) | 16 Participants |
| NN-220 0.033 mg/kg/Day | Change in ECG | Abnormal NCS (Week 104) | 9 Participants |
| NN-220 0.033 mg/kg/Day | Change in ECG | Abnormal CS (Week 104) | 0 Participants |
| NN-220 0.066 mg/kg/Day | Change in ECG | Abnormal NCS (Week 104) | 13 Participants |
| NN-220 0.066 mg/kg/Day | Change in ECG | Normal (Baseline) | 14 Participants |
| NN-220 0.066 mg/kg/Day | Change in ECG | Normal (Week 104) | 13 Participants |
| NN-220 0.066 mg/kg/Day | Change in ECG | Abnormal NCS (Baseline) | 12 Participants |
| NN-220 0.066 mg/kg/Day | Change in ECG | Abnormal CS (Week 104) | 0 Participants |
| NN-220 0.066 mg/kg/Day | Change in ECG | Abnormal CS (Baseline) | 0 Participants |
Secondary
Change in Glucose Tolerance (AUC of Glucose) Based on the OGTT
AUC (area under the curve) of glucose was calculated by the trapezoidal method. Change from baseline (within 4 weeks prior to week 0) in glucose tolerance (AUC of glucose: 30, 60, 90 and 120 min after oral glucose load) at week 104 was evaluated based on the oral glucose tolerance test (OGTT). Change from baseline results are presented as 'ratio to baseline'.
Time frame: Baseline, week 104
Population: SAS.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| NN-220 0.033 mg/kg/Day | Change in Glucose Tolerance (AUC of Glucose) Based on the OGTT | 0.98 Ratio of AUC | Geometric Coefficient of Variation 12.19 |
| NN-220 0.066 mg/kg/Day | Change in Glucose Tolerance (AUC of Glucose) Based on the OGTT | 1.04 Ratio of AUC | Geometric Coefficient of Variation 17.75 |
Secondary
Change in Glucose Tolerance (AUC of Glucose) Based on the OGTT
AUC of glucose was calculated by the trapezoidal method. Change from baseline (within 4 weeks prior to week 0) in glucose tolerance (AUC of glucose: 30, 60, 90 and 120 min after oral glucose load) at week 208 was evaluated based on the OGTT. Change from baseline results are presented as 'ratio to baseline'.
Time frame: Baseline, week 208
Population: SAS. Number analyzed = participants with available data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| NN-220 0.033 mg/kg/Day | Change in Glucose Tolerance (AUC of Glucose) Based on the OGTT | 1.03 Ratio of AUC | Geometric Coefficient of Variation 12.34 |
| NN-220 0.066 mg/kg/Day | Change in Glucose Tolerance (AUC of Glucose) Based on the OGTT | 1.10 Ratio of AUC | Geometric Coefficient of Variation 14.55 |
Secondary
Change in Glucose Tolerance (AUC of Insulin) Based on the OGTT
AUC of insulin was calculated by the trapezoidal method. Change from baseline (within 4 weeks prior to week 0) in glucose tolerance (AUC of insulin: 30, 60, 90 and 120 min after oral glucose load) at week 208 was evaluated based on the OGTT. Change from baseline results are presented as 'ratio to baseline'.
Time frame: Baseline, week 208
Population: SAS. Number analyzed = participants with available data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| NN-220 0.033 mg/kg/Day | Change in Glucose Tolerance (AUC of Insulin) Based on the OGTT | 1.52 Ratio of AUC | Geometric Coefficient of Variation 49.97 |
| NN-220 0.066 mg/kg/Day | Change in Glucose Tolerance (AUC of Insulin) Based on the OGTT | 2.38 Ratio of AUC | Geometric Coefficient of Variation 47.04 |
Secondary
Change in Glucose Tolerance (AUC of Insulin) Based on the OGTT
AUC of insulin was calculated by the trapezoidal method. Change from baseline (within 4 weeks prior to week 0) in glucose tolerance (AUC of insulin: 30, 60, 90 and 120 min after oral glucose load) at week 104 was evaluated based on the OGTT. Change from baseline results are presented as 'ratio to baseline'.
Time frame: Baseline, week 104
Population: SAS. Number analyzed = participants with available data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| NN-220 0.033 mg/kg/Day | Change in Glucose Tolerance (AUC of Insulin) Based on the OGTT | 1.25 Ratio of AUC | Geometric Coefficient of Variation 45.08 |
| NN-220 0.066 mg/kg/Day | Change in Glucose Tolerance (AUC of Insulin) Based on the OGTT | 1.72 Ratio of AUC | Geometric Coefficient of Variation 85.78 |
Secondary
Change in HbA1c
Change from baseline (within 4 weeks prior to week 0) in HbA1c was evaluated after 208 weeks of treatment.
Time frame: Baseline, week 208
Population: SAS. Number analyzed = participants with available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NN-220 0.033 mg/kg/Day | Change in HbA1c | 0.19 Percentage of HbA1c | Standard Deviation 0.13 |
| NN-220 0.066 mg/kg/Day | Change in HbA1c | 0.20 Percentage of HbA1c | Standard Deviation 0.21 |
Secondary
Change in HbA1c (Glycosylated Haemoglobin)
Change from baseline (within 4 weeks prior to week 0) in HbA1c was evaluated after 104 weeks of treatment.
Time frame: Baseline, week 104
Population: SAS.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NN-220 0.033 mg/kg/Day | Change in HbA1c (Glycosylated Haemoglobin) | 0.14 Percentage of HbA1c | Standard Deviation 0.18 |
| NN-220 0.066 mg/kg/Day | Change in HbA1c (Glycosylated Haemoglobin) | 0.13 Percentage of HbA1c | Standard Deviation 0.2 |
Secondary
Change in Height SDS (Japanese National Reference Data)
Height SDS was calculated using the formula: SDS = (height - mean)/SD, where height was the height variable measured, mean and SD of height by sex and age for the reference population. The scores were centered around zero. Positive SDS indicated greater height and negative SDS indicated lesser height than the mean of the reference population. The change from baseline (week 0) in the height SDS after 208 weeks of treatment was analysed. Positive value in change from baseline indicated that SDS was better than baseline SDS. Missing values were imputed using the LOCF method.
Time frame: Baseline, week 208
Population: FAS.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NN-220 0.033 mg/kg/Day | Change in Height SDS (Japanese National Reference Data) | 0.85 Standard deviation score | Standard Deviation 0.6 |
| NN-220 0.066 mg/kg/Day | Change in Height SDS (Japanese National Reference Data) | 1.84 Standard deviation score | Standard Deviation 0.7 |
Secondary
Change in Height SDS (Noonan Syndrome Reference Data in Japanese)
Height SDS was calculated using the formula: Z=\[(value/M)\^L-1\]/(S\*L); where L, M and S are skewness (L), median (M) and coefficient of variation (S) of Japanese Noonan syndrome' height provided for each sex and age. For each participant, a standard deviation score Z (SDS) was calculated based on age and sex referring to the values L, M and S. The scores were centered around zero. Positive SDS indicated greater height and negative SDS indicated lesser height than the mean of the reference population. The change from baseline (week 0) in the height SDS after 208 weeks of treatment was analysed. Positive value in change from baseline indicated that SDS was better than baseline SDS. Missing values were imputed using the LOCF method.
Time frame: Baseline, week 208
Population: FAS.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NN-220 0.033 mg/kg/Day | Change in Height SDS (Noonan Syndrome Reference Data in Japanese) | 0.96 Standard deviation score | Standard Deviation 0.47 |
| NN-220 0.066 mg/kg/Day | Change in Height SDS (Noonan Syndrome Reference Data in Japanese) | 1.92 Standard deviation score | Standard Deviation 0.6 |
Secondary
Change in IGF-I
Change from baseline (within 4 weeks prior to week 0) in IGF-I was evaluated after 208 weeks of treatment. Missing values were imputed using the LOCF method.
Time frame: Baseline, week 208
Population: SAS.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NN-220 0.033 mg/kg/Day | Change in IGF-I | 133.5 ng/mL | Standard Deviation 97.6 |
| NN-220 0.066 mg/kg/Day | Change in IGF-I | 217.2 ng/mL | Standard Deviation 91.1 |
Secondary
Change in IGF-I (Insulin-like Growth Factor-I)
Change from baseline (within 4 weeks prior to week 0) in IGF-I was evaluated after 104 weeks of treatment. Missing values were imputed using the LOCF method.
Time frame: Baseline, week 104
Population: SAS.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NN-220 0.033 mg/kg/Day | Change in IGF-I (Insulin-like Growth Factor-I) | 90.4 Nanograms per milliliter (ng/mL) | Standard Deviation 65.5 |
| NN-220 0.066 mg/kg/Day | Change in IGF-I (Insulin-like Growth Factor-I) | 159.1 Nanograms per milliliter (ng/mL) | Standard Deviation 88 |
Secondary
Change in Urinalysis (Protein, Glucose and Occult Blood)
The urinalysis was the measurements of protein, glucose, and occult blood at baseline (within 4 weeks prior to week 0) and week 104 and categorised as negative, trace, 1+, 2+ and 3+. Missing values were imputed using the LOCF method. Number of participants in each category at baseline and week 104 are presented.
Time frame: Baseline, week 104
Population: SAS.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| NN-220 0.033 mg/kg/Day | Change in Urinalysis (Protein, Glucose and Occult Blood) | Glucose: Negative (Week 104) | 25 Participants |
| NN-220 0.033 mg/kg/Day | Change in Urinalysis (Protein, Glucose and Occult Blood) | Protein: 2+ (Week 104) | 0 Participants |
| NN-220 0.033 mg/kg/Day | Change in Urinalysis (Protein, Glucose and Occult Blood) | Glucose: Trace (Week 104) | 0 Participants |
| NN-220 0.033 mg/kg/Day | Change in Urinalysis (Protein, Glucose and Occult Blood) | Protein: Trace (Baseline) | 2 Participants |
| NN-220 0.033 mg/kg/Day | Change in Urinalysis (Protein, Glucose and Occult Blood) | Glucose: 1+ (Week 104) | 0 Participants |
| NN-220 0.033 mg/kg/Day | Change in Urinalysis (Protein, Glucose and Occult Blood) | Protein: 3+ (Week 104) | 0 Participants |
| NN-220 0.033 mg/kg/Day | Change in Urinalysis (Protein, Glucose and Occult Blood) | Glucose: 2+ (Week 104) | 0 Participants |
| NN-220 0.033 mg/kg/Day | Change in Urinalysis (Protein, Glucose and Occult Blood) | Protein: Negative (Week 104) | 18 Participants |
| NN-220 0.033 mg/kg/Day | Change in Urinalysis (Protein, Glucose and Occult Blood) | Glucose: 3+ (Week 104) | 0 Participants |
| NN-220 0.033 mg/kg/Day | Change in Urinalysis (Protein, Glucose and Occult Blood) | Glucose: Negative (Baseline) | 25 Participants |
| NN-220 0.033 mg/kg/Day | Change in Urinalysis (Protein, Glucose and Occult Blood) | Occult blood: Negative (Baseline) | 24 Participants |
| NN-220 0.033 mg/kg/Day | Change in Urinalysis (Protein, Glucose and Occult Blood) | Protein: 2+ (Baseline) | 0 Participants |
| NN-220 0.033 mg/kg/Day | Change in Urinalysis (Protein, Glucose and Occult Blood) | Occult blood: Trace (Baseline) | 1 Participants |
| NN-220 0.033 mg/kg/Day | Change in Urinalysis (Protein, Glucose and Occult Blood) | Glucose: Trace (Baseline) | 0 Participants |
| NN-220 0.033 mg/kg/Day | Change in Urinalysis (Protein, Glucose and Occult Blood) | Occult blood: 1+ (Baseline) | 0 Participants |
| NN-220 0.033 mg/kg/Day | Change in Urinalysis (Protein, Glucose and Occult Blood) | Protein: Trace (Week 104) | 7 Participants |
| NN-220 0.033 mg/kg/Day | Change in Urinalysis (Protein, Glucose and Occult Blood) | Occult blood: 2+ (Baseline) | 0 Participants |
| NN-220 0.033 mg/kg/Day | Change in Urinalysis (Protein, Glucose and Occult Blood) | Glucose: 1+ (Baseline) | 0 Participants |
| NN-220 0.033 mg/kg/Day | Change in Urinalysis (Protein, Glucose and Occult Blood) | Occult blood: 3+ (Baseline) | 0 Participants |
| NN-220 0.033 mg/kg/Day | Change in Urinalysis (Protein, Glucose and Occult Blood) | Protein: 1+ (Baseline) | 0 Participants |
| NN-220 0.033 mg/kg/Day | Change in Urinalysis (Protein, Glucose and Occult Blood) | Occult blood: Negative (Week 104) | 25 Participants |
| NN-220 0.033 mg/kg/Day | Change in Urinalysis (Protein, Glucose and Occult Blood) | Glucose: 2+ (Baseline) | 0 Participants |
| NN-220 0.033 mg/kg/Day | Change in Urinalysis (Protein, Glucose and Occult Blood) | Occult blood: Trace (Week 104) | 0 Participants |
| NN-220 0.033 mg/kg/Day | Change in Urinalysis (Protein, Glucose and Occult Blood) | Protein: 1+ (Week 104) | 0 Participants |
| NN-220 0.033 mg/kg/Day | Change in Urinalysis (Protein, Glucose and Occult Blood) | Occult blood: 1+ (Week 104) | 0 Participants |
| NN-220 0.033 mg/kg/Day | Change in Urinalysis (Protein, Glucose and Occult Blood) | Glucose: 3+ (Baseline) | 0 Participants |
| NN-220 0.033 mg/kg/Day | Change in Urinalysis (Protein, Glucose and Occult Blood) | Occult blood: 2+ (Week 104) | 0 Participants |
| NN-220 0.033 mg/kg/Day | Change in Urinalysis (Protein, Glucose and Occult Blood) | Protein: 3+ (Baseline) | 0 Participants |
| NN-220 0.033 mg/kg/Day | Change in Urinalysis (Protein, Glucose and Occult Blood) | Occult blood: 3+ (Week 104) | 0 Participants |
| NN-220 0.033 mg/kg/Day | Change in Urinalysis (Protein, Glucose and Occult Blood) | Protein: Negative (Baseline) | 23 Participants |
| NN-220 0.066 mg/kg/Day | Change in Urinalysis (Protein, Glucose and Occult Blood) | Occult blood: 3+ (Week 104) | 0 Participants |
| NN-220 0.066 mg/kg/Day | Change in Urinalysis (Protein, Glucose and Occult Blood) | Protein: Negative (Baseline) | 22 Participants |
| NN-220 0.066 mg/kg/Day | Change in Urinalysis (Protein, Glucose and Occult Blood) | Protein: Trace (Baseline) | 4 Participants |
| NN-220 0.066 mg/kg/Day | Change in Urinalysis (Protein, Glucose and Occult Blood) | Protein: 1+ (Baseline) | 0 Participants |
| NN-220 0.066 mg/kg/Day | Change in Urinalysis (Protein, Glucose and Occult Blood) | Protein: 2+ (Baseline) | 0 Participants |
| NN-220 0.066 mg/kg/Day | Change in Urinalysis (Protein, Glucose and Occult Blood) | Protein: 3+ (Baseline) | 0 Participants |
| NN-220 0.066 mg/kg/Day | Change in Urinalysis (Protein, Glucose and Occult Blood) | Protein: Negative (Week 104) | 16 Participants |
| NN-220 0.066 mg/kg/Day | Change in Urinalysis (Protein, Glucose and Occult Blood) | Protein: Trace (Week 104) | 8 Participants |
| NN-220 0.066 mg/kg/Day | Change in Urinalysis (Protein, Glucose and Occult Blood) | Protein: 1+ (Week 104) | 2 Participants |
| NN-220 0.066 mg/kg/Day | Change in Urinalysis (Protein, Glucose and Occult Blood) | Protein: 2+ (Week 104) | 0 Participants |
| NN-220 0.066 mg/kg/Day | Change in Urinalysis (Protein, Glucose and Occult Blood) | Protein: 3+ (Week 104) | 0 Participants |
| NN-220 0.066 mg/kg/Day | Change in Urinalysis (Protein, Glucose and Occult Blood) | Glucose: Negative (Baseline) | 26 Participants |
| NN-220 0.066 mg/kg/Day | Change in Urinalysis (Protein, Glucose and Occult Blood) | Glucose: Trace (Baseline) | 0 Participants |
| NN-220 0.066 mg/kg/Day | Change in Urinalysis (Protein, Glucose and Occult Blood) | Glucose: 1+ (Baseline) | 0 Participants |
| NN-220 0.066 mg/kg/Day | Change in Urinalysis (Protein, Glucose and Occult Blood) | Glucose: 2+ (Baseline) | 0 Participants |
| NN-220 0.066 mg/kg/Day | Change in Urinalysis (Protein, Glucose and Occult Blood) | Glucose: 3+ (Baseline) | 0 Participants |
| NN-220 0.066 mg/kg/Day | Change in Urinalysis (Protein, Glucose and Occult Blood) | Glucose: Negative (Week 104) | 26 Participants |
| NN-220 0.066 mg/kg/Day | Change in Urinalysis (Protein, Glucose and Occult Blood) | Glucose: Trace (Week 104) | 0 Participants |
| NN-220 0.066 mg/kg/Day | Change in Urinalysis (Protein, Glucose and Occult Blood) | Glucose: 1+ (Week 104) | 0 Participants |
| NN-220 0.066 mg/kg/Day | Change in Urinalysis (Protein, Glucose and Occult Blood) | Glucose: 2+ (Week 104) | 0 Participants |
| NN-220 0.066 mg/kg/Day | Change in Urinalysis (Protein, Glucose and Occult Blood) | Glucose: 3+ (Week 104) | 0 Participants |
| NN-220 0.066 mg/kg/Day | Change in Urinalysis (Protein, Glucose and Occult Blood) | Occult blood: Negative (Baseline) | 25 Participants |
| NN-220 0.066 mg/kg/Day | Change in Urinalysis (Protein, Glucose and Occult Blood) | Occult blood: Trace (Baseline) | 1 Participants |
| NN-220 0.066 mg/kg/Day | Change in Urinalysis (Protein, Glucose and Occult Blood) | Occult blood: 1+ (Baseline) | 0 Participants |
| NN-220 0.066 mg/kg/Day | Change in Urinalysis (Protein, Glucose and Occult Blood) | Occult blood: 2+ (Baseline) | 0 Participants |
| NN-220 0.066 mg/kg/Day | Change in Urinalysis (Protein, Glucose and Occult Blood) | Occult blood: 3+ (Baseline) | 0 Participants |
| NN-220 0.066 mg/kg/Day | Change in Urinalysis (Protein, Glucose and Occult Blood) | Occult blood: Negative (Week 104) | 20 Participants |
| NN-220 0.066 mg/kg/Day | Change in Urinalysis (Protein, Glucose and Occult Blood) | Occult blood: Trace (Week 104) | 5 Participants |
| NN-220 0.066 mg/kg/Day | Change in Urinalysis (Protein, Glucose and Occult Blood) | Occult blood: 1+ (Week 104) | 0 Participants |
| NN-220 0.066 mg/kg/Day | Change in Urinalysis (Protein, Glucose and Occult Blood) | Occult blood: 2+ (Week 104) | 1 Participants |
Secondary
Change in Urinalysis (Protein, Glucose and Occult Blood)
The urinalysis was the measurements of protein, glucose, and occult blood at baseline (within 4 weeks prior to week 0) and week 208 and categorised as negative, trace, 1+, 2+ and 3+. Number of participants in each category at baseline and week 208 are presented. Missing values were imputed using the LOCF method.
Time frame: Baseline, week 208
Population: SAS.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| NN-220 0.033 mg/kg/Day | Change in Urinalysis (Protein, Glucose and Occult Blood) | Protein: 1+ (Week 208) | 0 Participants |
| NN-220 0.033 mg/kg/Day | Change in Urinalysis (Protein, Glucose and Occult Blood) | Glucose: Negative (Week 208) | 25 Participants |
| NN-220 0.033 mg/kg/Day | Change in Urinalysis (Protein, Glucose and Occult Blood) | Glucose: Trace (Week 208) | 0 Participants |
| NN-220 0.033 mg/kg/Day | Change in Urinalysis (Protein, Glucose and Occult Blood) | Protein: Negative (Baseline) | 23 Participants |
| NN-220 0.033 mg/kg/Day | Change in Urinalysis (Protein, Glucose and Occult Blood) | Glucose: 1+ (Week 208) | 0 Participants |
| NN-220 0.033 mg/kg/Day | Change in Urinalysis (Protein, Glucose and Occult Blood) | Protein: 2+ (Week 208) | 0 Participants |
| NN-220 0.033 mg/kg/Day | Change in Urinalysis (Protein, Glucose and Occult Blood) | Glucose: 2+ (Week 208) | 0 Participants |
| NN-220 0.033 mg/kg/Day | Change in Urinalysis (Protein, Glucose and Occult Blood) | Protein: 3+ (Baseline) | 0 Participants |
| NN-220 0.033 mg/kg/Day | Change in Urinalysis (Protein, Glucose and Occult Blood) | Glucose: 3+ (Week 208) | 0 Participants |
| NN-220 0.033 mg/kg/Day | Change in Urinalysis (Protein, Glucose and Occult Blood) | Protein: 3+ (Week 208) | 0 Participants |
| NN-220 0.033 mg/kg/Day | Change in Urinalysis (Protein, Glucose and Occult Blood) | Occult blood: Negative (Baseline) | 24 Participants |
| NN-220 0.033 mg/kg/Day | Change in Urinalysis (Protein, Glucose and Occult Blood) | Protein: 1+ (Baseline) | 0 Participants |
| NN-220 0.033 mg/kg/Day | Change in Urinalysis (Protein, Glucose and Occult Blood) | Occult blood: Trace (Baseline) | 1 Participants |
| NN-220 0.033 mg/kg/Day | Change in Urinalysis (Protein, Glucose and Occult Blood) | Glucose: Negative (Baseline) | 25 Participants |
| NN-220 0.033 mg/kg/Day | Change in Urinalysis (Protein, Glucose and Occult Blood) | Occult blood: 1+ (Baseline) | 0 Participants |
| NN-220 0.033 mg/kg/Day | Change in Urinalysis (Protein, Glucose and Occult Blood) | Protein: Negative (Week 208) | 17 Participants |
| NN-220 0.033 mg/kg/Day | Change in Urinalysis (Protein, Glucose and Occult Blood) | Occult blood: 2+ (Baseline) | 0 Participants |
| NN-220 0.033 mg/kg/Day | Change in Urinalysis (Protein, Glucose and Occult Blood) | Glucose: Trace (Baseline) | 0 Participants |
| NN-220 0.033 mg/kg/Day | Change in Urinalysis (Protein, Glucose and Occult Blood) | Occult blood: 3+ (Baseline) | 0 Participants |
| NN-220 0.033 mg/kg/Day | Change in Urinalysis (Protein, Glucose and Occult Blood) | Protein: Trace (Baseline) | 2 Participants |
| NN-220 0.033 mg/kg/Day | Change in Urinalysis (Protein, Glucose and Occult Blood) | Occult blood: Negative (Week 208) | 24 Participants |
| NN-220 0.033 mg/kg/Day | Change in Urinalysis (Protein, Glucose and Occult Blood) | Glucose: 1+ (Baseline) | 0 Participants |
| NN-220 0.033 mg/kg/Day | Change in Urinalysis (Protein, Glucose and Occult Blood) | Occult blood: Trace (Week 208) | 1 Participants |
| NN-220 0.033 mg/kg/Day | Change in Urinalysis (Protein, Glucose and Occult Blood) | Protein: Trace (Week 208) | 8 Participants |
| NN-220 0.033 mg/kg/Day | Change in Urinalysis (Protein, Glucose and Occult Blood) | Occult blood: 1+ (Week 208) | 0 Participants |
| NN-220 0.033 mg/kg/Day | Change in Urinalysis (Protein, Glucose and Occult Blood) | Glucose: 2+ (Baseline) | 0 Participants |
| NN-220 0.033 mg/kg/Day | Change in Urinalysis (Protein, Glucose and Occult Blood) | Occult blood: 2+ (Week 208) | 0 Participants |
| NN-220 0.033 mg/kg/Day | Change in Urinalysis (Protein, Glucose and Occult Blood) | Protein: 2+ (Baseline) | 0 Participants |
| NN-220 0.033 mg/kg/Day | Change in Urinalysis (Protein, Glucose and Occult Blood) | Occult blood: 3+ (Week 208) | 0 Participants |
| NN-220 0.033 mg/kg/Day | Change in Urinalysis (Protein, Glucose and Occult Blood) | Glucose: 3+ (Baseline) | 0 Participants |
| NN-220 0.066 mg/kg/Day | Change in Urinalysis (Protein, Glucose and Occult Blood) | Occult blood: 3+ (Week 208) | 1 Participants |
| NN-220 0.066 mg/kg/Day | Change in Urinalysis (Protein, Glucose and Occult Blood) | Protein: Negative (Baseline) | 22 Participants |
| NN-220 0.066 mg/kg/Day | Change in Urinalysis (Protein, Glucose and Occult Blood) | Protein: Trace (Baseline) | 4 Participants |
| NN-220 0.066 mg/kg/Day | Change in Urinalysis (Protein, Glucose and Occult Blood) | Protein: 1+ (Baseline) | 0 Participants |
| NN-220 0.066 mg/kg/Day | Change in Urinalysis (Protein, Glucose and Occult Blood) | Protein: 2+ (Baseline) | 0 Participants |
| NN-220 0.066 mg/kg/Day | Change in Urinalysis (Protein, Glucose and Occult Blood) | Protein: 3+ (Baseline) | 0 Participants |
| NN-220 0.066 mg/kg/Day | Change in Urinalysis (Protein, Glucose and Occult Blood) | Protein: Negative (Week 208) | 18 Participants |
| NN-220 0.066 mg/kg/Day | Change in Urinalysis (Protein, Glucose and Occult Blood) | Protein: Trace (Week 208) | 7 Participants |
| NN-220 0.066 mg/kg/Day | Change in Urinalysis (Protein, Glucose and Occult Blood) | Protein: 1+ (Week 208) | 0 Participants |
| NN-220 0.066 mg/kg/Day | Change in Urinalysis (Protein, Glucose and Occult Blood) | Protein: 2+ (Week 208) | 1 Participants |
| NN-220 0.066 mg/kg/Day | Change in Urinalysis (Protein, Glucose and Occult Blood) | Protein: 3+ (Week 208) | 0 Participants |
| NN-220 0.066 mg/kg/Day | Change in Urinalysis (Protein, Glucose and Occult Blood) | Glucose: Negative (Baseline) | 26 Participants |
| NN-220 0.066 mg/kg/Day | Change in Urinalysis (Protein, Glucose and Occult Blood) | Glucose: Trace (Baseline) | 0 Participants |
| NN-220 0.066 mg/kg/Day | Change in Urinalysis (Protein, Glucose and Occult Blood) | Glucose: 1+ (Baseline) | 0 Participants |
| NN-220 0.066 mg/kg/Day | Change in Urinalysis (Protein, Glucose and Occult Blood) | Glucose: 2+ (Baseline) | 0 Participants |
| NN-220 0.066 mg/kg/Day | Change in Urinalysis (Protein, Glucose and Occult Blood) | Glucose: 3+ (Baseline) | 0 Participants |
| NN-220 0.066 mg/kg/Day | Change in Urinalysis (Protein, Glucose and Occult Blood) | Glucose: Trace (Week 208) | 0 Participants |
| NN-220 0.066 mg/kg/Day | Change in Urinalysis (Protein, Glucose and Occult Blood) | Glucose: 1+ (Week 208) | 0 Participants |
| NN-220 0.066 mg/kg/Day | Change in Urinalysis (Protein, Glucose and Occult Blood) | Glucose: 2+ (Week 208) | 0 Participants |
| NN-220 0.066 mg/kg/Day | Change in Urinalysis (Protein, Glucose and Occult Blood) | Glucose: 3+ (Week 208) | 0 Participants |
| NN-220 0.066 mg/kg/Day | Change in Urinalysis (Protein, Glucose and Occult Blood) | Occult blood: Negative (Baseline) | 25 Participants |
| NN-220 0.066 mg/kg/Day | Change in Urinalysis (Protein, Glucose and Occult Blood) | Occult blood: Trace (Baseline) | 1 Participants |
| NN-220 0.066 mg/kg/Day | Change in Urinalysis (Protein, Glucose and Occult Blood) | Occult blood: 1+ (Baseline) | 0 Participants |
| NN-220 0.066 mg/kg/Day | Change in Urinalysis (Protein, Glucose and Occult Blood) | Occult blood: 2+ (Baseline) | 0 Participants |
| NN-220 0.066 mg/kg/Day | Change in Urinalysis (Protein, Glucose and Occult Blood) | Occult blood: 3+ (Baseline) | 0 Participants |
| NN-220 0.066 mg/kg/Day | Change in Urinalysis (Protein, Glucose and Occult Blood) | Occult blood: Negative (Week 208) | 22 Participants |
| NN-220 0.066 mg/kg/Day | Change in Urinalysis (Protein, Glucose and Occult Blood) | Occult blood: Trace (Week 208) | 2 Participants |
| NN-220 0.066 mg/kg/Day | Change in Urinalysis (Protein, Glucose and Occult Blood) | Occult blood: 1+ (Week 208) | 1 Participants |
| NN-220 0.066 mg/kg/Day | Change in Urinalysis (Protein, Glucose and Occult Blood) | Occult blood: 2+ (Week 208) | 0 Participants |
| NN-220 0.066 mg/kg/Day | Change in Urinalysis (Protein, Glucose and Occult Blood) | Glucose: Negative (Week 208) | 26 Participants |
Secondary
Change in Vital Signs (Diastolic Blood Pressure and Systolic Blood Pressure)
Systolic and diastolic blood pressure were measured after a 5-minute rest in sitting position. Change from baseline (week 0) in systolic blood pressure and diastolic blood pressure.
Time frame: Baseline, week 104
Population: SAS. Number analyzed = participants with available data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| NN-220 0.033 mg/kg/Day | Change in Vital Signs (Diastolic Blood Pressure and Systolic Blood Pressure) | Diastolic blood pressure | 2.3 Millimeters of mercury (mmHg) | Standard Deviation 13.2 |
| NN-220 0.033 mg/kg/Day | Change in Vital Signs (Diastolic Blood Pressure and Systolic Blood Pressure) | Systolic blood pressure | 5.5 Millimeters of mercury (mmHg) | Standard Deviation 11.9 |
| NN-220 0.066 mg/kg/Day | Change in Vital Signs (Diastolic Blood Pressure and Systolic Blood Pressure) | Diastolic blood pressure | 6.3 Millimeters of mercury (mmHg) | Standard Deviation 15.8 |
| NN-220 0.066 mg/kg/Day | Change in Vital Signs (Diastolic Blood Pressure and Systolic Blood Pressure) | Systolic blood pressure | 4.1 Millimeters of mercury (mmHg) | Standard Deviation 12.1 |
Secondary
Change in Vital Signs (Diastolic Blood Pressure and Systolic Blood Pressure)
Systolic and diastolic blood pressure were measured after a 5-minute rest in sitting position. Change from baseline (week 0) in systolic blood pressure and diastolic blood pressure. Missing values were imputed using the LOCF method.
Time frame: Baseline, week 208
Population: SAS. Number analyzed = participants with available data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| NN-220 0.033 mg/kg/Day | Change in Vital Signs (Diastolic Blood Pressure and Systolic Blood Pressure) | Diastolic blood pressure | 5.8 mmHg | Standard Deviation 13.4 |
| NN-220 0.033 mg/kg/Day | Change in Vital Signs (Diastolic Blood Pressure and Systolic Blood Pressure) | Systolic blood pressure | 6.8 mmHg | Standard Deviation 11.9 |
| NN-220 0.066 mg/kg/Day | Change in Vital Signs (Diastolic Blood Pressure and Systolic Blood Pressure) | Diastolic blood pressure | 3.5 mmHg | Standard Deviation 8.4 |
| NN-220 0.066 mg/kg/Day | Change in Vital Signs (Diastolic Blood Pressure and Systolic Blood Pressure) | Systolic blood pressure | 5.8 mmHg | Standard Deviation 16.1 |
Secondary
Change in Vital Signs (Pulse)
Pulse was measured after a 5-minute rest in sitting position. Change from baseline (week 0) in pulse.
Time frame: Baseline, week 104
Population: SAS. Number analyzed = participants with available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NN-220 0.033 mg/kg/Day | Change in Vital Signs (Pulse) | -9.5 Beats per minute (beats/min) | Standard Deviation 15.7 |
| NN-220 0.066 mg/kg/Day | Change in Vital Signs (Pulse) | 1.8 Beats per minute (beats/min) | Standard Deviation 21.9 |
Secondary
Change in Vital Signs (Pulse)
Pulse was measured after a 5-minute rest in sitting position. Change from baseline (week 0) in pulse. Missing values were imputed using the LOCF method.
Time frame: Baseline, week 208
Population: SAS. Number analyzed = participants with available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NN-220 0.033 mg/kg/Day | Change in Vital Signs (Pulse) | -15.3 beats/min | Standard Deviation 14.2 |
| NN-220 0.066 mg/kg/Day | Change in Vital Signs (Pulse) | -3.8 beats/min | Standard Deviation 16.5 |
Secondary
Height Velocity
Height velocity is change in height per year. The height velocity was calculated as the difference between current height (week 156) and height at week 104 divided by time between those measurement time points and multiplied by 365 days. Missing values were imputed using the LOCF method.
Time frame: Week 104 to week 156
Population: FAS.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NN-220 0.033 mg/kg/Day | Height Velocity | 5.77 cm/year | Standard Deviation 1.26 |
| NN-220 0.066 mg/kg/Day | Height Velocity | 7.01 cm/year | Standard Deviation 1.12 |
Secondary
Height Velocity
Height velocity is change in height per year. The height velocity was calculated as the difference between current height (week 104) and height at week 52 divided by time between those measurement time points and multiplied by 365 days.
Time frame: Week 52 to week 104
Population: FAS.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NN-220 0.033 mg/kg/Day | Height Velocity | 6.20 cm/year | Standard Deviation 0.95 |
| NN-220 0.066 mg/kg/Day | Height Velocity | 7.99 cm/year | Standard Deviation 1.2 |
Secondary
Height Velocity
Height velocity is change in height per year. The height velocity was calculated as the difference between current height (week 208) and height at week 156 divided by time between those measurement time points and multiplied by 365 days. Missing values were imputed using the LOCF method.
Time frame: Week 156 to week 208
Population: FAS.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NN-220 0.033 mg/kg/Day | Height Velocity | 5.64 cm/year | Standard Deviation 1.23 |
| NN-220 0.066 mg/kg/Day | Height Velocity | 6.11 cm/year | Standard Deviation 1.28 |
Secondary
Height Velocity
Height velocity is change in height per year. The height velocity was calculated as the difference between current height (week 52) and height at baseline (week 0) divided by time between those measurement time points and multiplied by 365 days.
Time frame: Baseline to week 52
Population: FAS.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NN-220 0.033 mg/kg/Day | Height Velocity | 7.88 Centimeters per year (cm/year) | Standard Deviation 0.87 |
| NN-220 0.066 mg/kg/Day | Height Velocity | 9.90 Centimeters per year (cm/year) | Standard Deviation 1.49 |
Secondary
Height Velocity SDS
Height velocity is change in height per year. The height velocity was calculated as the difference between current height (week 208) and height at week 156 divided by time between those measurement time points and multiplied by 365 days. Height velocity SDS was calculated using the formula: SDS = (height velocity - mean)/SD, where height velocity was the height velocity variable measured, mean and SD of height velocity by sex and age for the reference population. The scores were centered around zero. Positive SDS indicated greater height velocity and negative SDS indicated lesser height velocity than the mean of the reference population.
Time frame: Week 156 to week 208
Population: FAS.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NN-220 0.033 mg/kg/Day | Height Velocity SDS | -0.73 Standard deviation score | Standard Deviation 1.52 |
| NN-220 0.066 mg/kg/Day | Height Velocity SDS | 0.92 Standard deviation score | Standard Deviation 1.69 |
Secondary
Height Velocity SDS
Height velocity is change in height per year. The height velocity was calculated as the difference between current height (week 52) and height at baseline (week 0) divided by time between those measurement time points and multiplied by 365 days. Height velocity SDS was calculated using the formula: SDS = (height velocity - mean)/SD, where height velocity was the height velocity variable measured, mean and SD of height velocity by sex and age for the reference population. The scores were centered around zero. Positive SDS indicated greater height velocity and negative SDS indicated lesser height velocity than the mean of the reference population.
Time frame: Baseline to week 52
Population: FAS.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NN-220 0.033 mg/kg/Day | Height Velocity SDS | 2.80 Standard deviation score | Standard Deviation 1.13 |
| NN-220 0.066 mg/kg/Day | Height Velocity SDS | 5.01 Standard deviation score | Standard Deviation 1.92 |
Secondary
Height Velocity SDS
Height velocity is change in height per year. The height velocity was calculated as the difference between current height (week 104) and height at week 52 divided by time between those measurement time points and multiplied by 365 days. Height velocity SDS was calculated using the formula: SDS = (height velocity - mean)/SD, where height velocity was the height velocity variable measured, mean and SD of height velocity by sex and age for the reference population. The scores were centered around zero. Positive SDS indicated greater height velocity and negative SDS indicated lesser height velocity than the mean of the reference population.
Time frame: Week 52 to week 104
Population: FAS.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NN-220 0.033 mg/kg/Day | Height Velocity SDS | 0.58 Standard deviation score | Standard Deviation 1.59 |
| NN-220 0.066 mg/kg/Day | Height Velocity SDS | 2.65 Standard deviation score | Standard Deviation 1.76 |
Secondary
Height Velocity SDS
Height velocity is change in height per year. The height velocity was calculated as the difference between current height (week 156) and height at week 104 divided by time between those measurement time points and multiplied by 365 days. Height velocity SDS was calculated using the formula: SDS = (height velocity - mean)/SD, where height velocity was the height velocity variable measured, mean and SD of height velocity by sex and age for the reference population. The scores were centered around zero. Positive SDS indicated greater height velocity and negative SDS indicated lesser height velocity than the mean of the reference population.
Time frame: Week 104 to week 156
Population: FAS.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NN-220 0.033 mg/kg/Day | Height Velocity SDS | -0.39 Standard deviation score | Standard Deviation 1.61 |
| NN-220 0.066 mg/kg/Day | Height Velocity SDS | 1.44 Standard deviation score | Standard Deviation 1.25 |
Secondary
Incidence of Treatment Emergent Adverse Events
A treatment emergent adverse event (TEAE; for the pivotal phase) was defined as an event that had onset date on or after the date of visit 2 (week 0; start of treatment) and no later than the date of visit 12 (104 weeks; end of pivotal phase). For withdrawal participants (if any), an adverse event with onset date no later than 7 days after the last day of NN-220 treatment was included.
Time frame: During 104 weeks of treatment
Population: Safety analysis set (SAS) which included all participants who received at least one dose of trial product (NN-220, 0.033 mg/kg/day or NN-220, 0.066 mg/kg/day).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| NN-220 0.033 mg/kg/Day | Incidence of Treatment Emergent Adverse Events | 265 Events |
| NN-220 0.066 mg/kg/Day | Incidence of Treatment Emergent Adverse Events | 306 Events |
Secondary
Incidence of Treatment Emergent AEs
A treatment emergent AE (TEAE) was defined as an event that had onset date on or after the date of visit 2 (week 0; start of treatment) and no later than 7 days after the last day of NN-220 treatment.
Time frame: Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period)
Population: SAS.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| NN-220 0.033 mg/kg/Day | Incidence of Treatment Emergent AEs | 507 Events |
| NN-220 0.066 mg/kg/Day | Incidence of Treatment Emergent AEs | 539 Events |
Secondary
Yearly Change in Bone Age/Change in Chronological Age
X-ray picture of carpal bones of left hand was taken for bone age determination. Centralised evaluation of bone age was done by the RUS score method of Tanner-Whitehouse II (TW2). Yearly change from week 156 in bone age/change in chronological age was presented.
Time frame: Week 156, week 208
Population: SAS. Number analyzed = participants with available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NN-220 0.033 mg/kg/Day | Yearly Change in Bone Age/Change in Chronological Age | 0.87 Ratio (bone age/chronological age) | Standard Deviation 0.55 |
| NN-220 0.066 mg/kg/Day | Yearly Change in Bone Age/Change in Chronological Age | 1.05 Ratio (bone age/chronological age) | Standard Deviation 0.51 |
Secondary
Yearly Change in Bone Age/Change in Chronological Age
X-ray picture of carpal bones of left hand was taken for bone age determination. Centralised evaluation of bone age was done by the RUS score method of Tanner-Whitehouse II (TW2). Yearly change from week 104 in bone age/change in chronological age was presented.
Time frame: Week 104, week 156
Population: SAS. Number analyzed = participants with available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NN-220 0.033 mg/kg/Day | Yearly Change in Bone Age/Change in Chronological Age | 0.94 Ratio (bone age/chronological age) | Standard Deviation 0.7 |
| NN-220 0.066 mg/kg/Day | Yearly Change in Bone Age/Change in Chronological Age | 0.97 Ratio (bone age/chronological age) | Standard Deviation 0.56 |
Secondary
Yearly Change in Bone Age/Change in Chronological Age
X-ray picture of carpal bones of left hand was taken for bone age determination. Centralised evaluation of bone age was done by the RUS score method of Tanner-Whitehouse II (TW2). Yearly change from baseline (week 0) in bone age/change in chronological age was presented.
Time frame: Baseline, week 52
Population: SAS.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NN-220 0.033 mg/kg/Day | Yearly Change in Bone Age/Change in Chronological Age | 0.93 Ratio (bone age/chronological age) | Standard Deviation 0.66 |
| NN-220 0.066 mg/kg/Day | Yearly Change in Bone Age/Change in Chronological Age | 1.28 Ratio (bone age/chronological age) | Standard Deviation 0.7 |
Secondary
Yearly Change in Bone Age/Change in Chronological Age
X-ray picture of carpal bones of left hand was taken for bone age determination. Centralised evaluation of bone age was done by the RUS score method of Tanner-Whitehouse II (TW2). Yearly change from week 52 in bone age/change in chronological age was presented.
Time frame: Week 52, week 104
Population: SAS.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NN-220 0.033 mg/kg/Day | Yearly Change in Bone Age/Change in Chronological Age | 1.15 Ratio (bone age/chronological age) | Standard Deviation 0.57 |
| NN-220 0.066 mg/kg/Day | Yearly Change in Bone Age/Change in Chronological Age | 1.38 Ratio (bone age/chronological age) | Standard Deviation 0.91 |