Small for Gestational Age
Conditions
Brief summary
The objective of this surveillance is to collect information about 1) adverse drug reaction not expected from the LPD (unknown adverse drug reaction), 2) the incidence of adverse drug reactions in this surveillance, and 3)factors considered to affect the safety and/or efficacy of this drug.
Detailed description
All the patients whom an investigator prescribes the first Genotropin® should be registered consecutively until the number of subjects reaches target number in order to extract patients enrolled into the investigation at random.
Interventions
DRUGSomatropin
Genotropin® 5.3mg, Genotropin®inj.12mg, Genotropin®MiniQuick s.c. inj.0.6mg・1.0mg・1.4mg, depending on the Investigator prescription. Frequency and duration are according to Package Insert as follows. Normally, the dosage is 0.021 mg/kg/week as somatropin (genetical recombination) in 6-7 divided doses by s.c. route. If efficacy is insufficient, the dose may be increased up to 0.47 mg/kg/week in 6-7 divided doses in a week by s.c. route.
Sponsors
Pfizer
Study design
Observational model
CASE_ONLY
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
* Patients need to be administered Somatropin (Genotropin®) in order to be enrolled in the surveillance.
Exclusion criteria
* Patients not administered Somatropin (Genotropin®).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment Related Adverse Events. | Up to 3 years | Adverse events mean all unfavorable events that occur in participants after administration of somatropin, irrespective of causal relationship to somatropin (including clinically problematic abnormal changes in laboratory test values). Treatment related adverse events were evaluated in company with the causal relationship to somatropin. |
| Number of Unlisted Treatment Related Adverse Events According to Japanese Package Insert. | Up to 3 years | Adverse events mean all unfavorable events that occur in participants after administration of somatropin, irrespective of causal relationship to somatropin (including clinically problematic abnormal changes in laboratory test values). Treatment related adverse events were evaluated in company with the causal relationship to somatropin. Unlisted treatment related adverse events were confirmed with listed adverse drug reaction according to Japanese package insert. |
| Number of Participants With Treatment Related Adverse Events of Somatropin: <15 Years of Age vs. >=15 Years of Age. | Up to 3 years | To determine whether age is a significant risk factor in the frequency of treatment related adverse events. |
| Number of Participants With Treatment Related Adverse Events of Somatropin by Gender. | Up to 3 years | To determine whether gender is a significant risk factor in the frequency of treatment related adverse events. |
| Number of Participants With Treatment Related Adverse Events of Somatropin Based on SGA Severity. | Up to 3 years | To determine whether severity of SGA is a significant risk factor in the frequency of treatment related adverse events. The severity of SGA was comprehensively evaluated on the basis of information including height and weight at birth and height measured one year before the start of administration. |
| Number of Participants With Treatment Related Adverse Events of Somatropin: With Past History of Any Disease vs. Without Past History of Any Disease. | Up to 3 years | To determine whether past history of any disease is a significant risk factor in the frequency of treatment related adverse events. |
| Number of Participants With Treatment Related Adverse Events of Somatropin: With Complications vs. Without Complications | Up to 3 years | To determine whether having complication(s) is a significant risk factor in the frequency of treatment related adverse events. |
| Number of Participants With Treatment Related Adverse Events of Somatropin: With Hepatic Function Disorder vs. Without Hepatic Function Disorder. | Up to 3 years | To determine whether hepatic function disorder is a significant risk factor in the frequency of treatment related adverse events. |
| Number of Participants With Treatment Related Adverse Events of Somatropin: With Renal Impairment vs. Without Renal Impairment. | Up to 3 years | To determine whether renal impairment is a significant risk factor in the frequency of treatment related adverse events. |
| Number of Participants With Treatment Related Adverse Events of Somatropin: With Concomitant Drug(s) vs. Without Concomitant Drug(s). | Up to 3 years | To determine whether taking concomitant drug(s) is a significant risk factor in the frequency of treatment related adverse events. |
| Change in the Growth Rate Standard Deviation (SD) Score for Calendar Age. | Up to 3 years | Growth rate SD score = (Growth rate - Average growth rate for calendar age of gender) / SD score for growth rate for each calendar age of gender). An SD score indicates how far a participant's score deviates from the mean of the reference population; an SD score higher than the mean gives a positive SD score whereas an SD score lower than the mean gives a negative SD score. In addition, when the bone age was described, it was to be read as the calendar age for men who were 11 years or older and women who were 9 years or older, as necessary. |
| Change in Height SD Score for Calendar Age. | Up to 3 years | The change in height standard SD for calendar age = (Height SD score for each calendar age - Height SD score for calendar age of the previous year) / (the date on which the height was measured - the date of the previous year on which the height was measured) × 365.25. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Somatropin for Small-for-gestational Age Participants taking somatropin for small-for-gestational age according to Japanese package insert. | 890 |
| Total | 890 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lost to Follow-up | 1 |
| Overall Study | Protocol Violation | 18 |
Baseline characteristics
| Characteristic | Somatropin for Small-for-gestational Age |
|---|---|
| Age, Customized <15 years | 884 participants |
| Age, Customized >=15 years | 6 participants |
| Sex: Female, Male Female | 423 Participants |
| Sex: Female, Male Male | 467 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 36 / 890 |
| serious Total, serious adverse events | 8 / 890 |
Outcome results
Primary
Change in Height SD Score for Calendar Age.
The change in height standard SD for calendar age = (Height SD score for each calendar age - Height SD score for calendar age of the previous year) / (the date on which the height was measured - the date of the previous year on which the height was measured) × 365.25.
Time frame: Up to 3 years
Population: The efficacy analysis population basically consists of the evaluable participants in whom the changes in the growth rate SD score for calendar age and in the height SD score for calendar age were assessed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Somatropin for Small-for-gestational Age | Change in Height SD Score for Calendar Age. | At one year | 0.6 standard deviation (SD) score | Standard Deviation 0.49 |
| Somatropin for Small-for-gestational Age | Change in Height SD Score for Calendar Age. | At two years | 0.3 standard deviation (SD) score | Standard Deviation 0.41 |
| Somatropin for Small-for-gestational Age | Change in Height SD Score for Calendar Age. | At three years | 0.3 standard deviation (SD) score | Standard Deviation 0.4 |
Comparison: The null hypothesis is that there is no difference in the mean value of the change in the height SD score for calendar age between SGA at one year and SGA at baseline.p-value: <0.001t-test, 1 sided
Comparison: The null hypothesis is that there is no difference in the mean value of the change in the height SD score for calendar age between SGA at two years and SGA at baseline.p-value: <0.001t-test, 1 sided
Comparison: The null hypothesis is that there is no difference in the mean value of the change in the height SD score for calendar age between SGA at three years and SGA at baseline.p-value: <0.001t-test, 1 sided
Primary
Change in the Growth Rate Standard Deviation (SD) Score for Calendar Age.
Growth rate SD score = (Growth rate - Average growth rate for calendar age of gender) / SD score for growth rate for each calendar age of gender). An SD score indicates how far a participant's score deviates from the mean of the reference population; an SD score higher than the mean gives a positive SD score whereas an SD score lower than the mean gives a negative SD score. In addition, when the bone age was described, it was to be read as the calendar age for men who were 11 years or older and women who were 9 years or older, as necessary.
Time frame: Up to 3 years
Population: The efficacy analysis population basically consists of the evaluable participants in whom the changes in the growth rate SD score for calendar age and in the height SD score for calendar age were assessed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Somatropin for Small-for-gestational Age | Change in the Growth Rate Standard Deviation (SD) Score for Calendar Age. | At one year | 3.9 standard deviation (SD) score | Standard Deviation 2.6 |
| Somatropin for Small-for-gestational Age | Change in the Growth Rate Standard Deviation (SD) Score for Calendar Age. | At two years | 3.1 standard deviation (SD) score | Standard Deviation 2.54 |
| Somatropin for Small-for-gestational Age | Change in the Growth Rate Standard Deviation (SD) Score for Calendar Age. | At three years | 2.9 standard deviation (SD) score | Standard Deviation 3.03 |
Comparison: The null hypothesis is that there is no difference in the mean value of the change in the growth rate SD score for calendar age between SGA at one year and SGA at baseline.p-value: <0.001t-test, 1 sided
Comparison: The null hypothesis is that there is no difference in the mean value of the change in the growth rate SD score for calendar age between SGA at two years and SGA at baseline.p-value: <0.001t-test, 1 sided
Comparison: The null hypothesis is that there is no difference in the mean value of the change in the growth rate SD score for calendar age between SGA at three years and SGA at baseline.p-value: <0.001t-test, 1 sided
Primary
Number of Participants With Treatment Related Adverse Events.
Adverse events mean all unfavorable events that occur in participants after administration of somatropin, irrespective of causal relationship to somatropin (including clinically problematic abnormal changes in laboratory test values). Treatment related adverse events were evaluated in company with the causal relationship to somatropin.
Time frame: Up to 3 years
Population: The safety analysis population consists of the participants who satisfy the case conditions and in whom administration of this drug was confirmed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Somatropin for Small-for-gestational Age | Number of Participants With Treatment Related Adverse Events. | 44 participants |
Primary
Number of Participants With Treatment Related Adverse Events of Somatropin: <15 Years of Age vs. >=15 Years of Age.
To determine whether age is a significant risk factor in the frequency of treatment related adverse events.
Time frame: Up to 3 years
Population: The safety analysis population consists of the participants who satisfy the case conditions and in whom administration of this drug was confirmed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Somatropin for Small-for-gestational Age | Number of Participants With Treatment Related Adverse Events of Somatropin: <15 Years of Age vs. >=15 Years of Age. | 44 participants |
| >=15 Years | Number of Participants With Treatment Related Adverse Events of Somatropin: <15 Years of Age vs. >=15 Years of Age. | 0 participants |
Comparison: The risk factor tested was Age. The null hypothesis is that there is no difference between \<15 years and \>=15 years in the frequency of treatment related adverse events.p-value: =0.575Chi-squared
Primary
Number of Participants With Treatment Related Adverse Events of Somatropin Based on SGA Severity.
To determine whether severity of SGA is a significant risk factor in the frequency of treatment related adverse events. The severity of SGA was comprehensively evaluated on the basis of information including height and weight at birth and height measured one year before the start of administration.
Time frame: Up to 3 years
Population: The safety analysis population consists of the participants who satisfy the case conditions and in whom administration of this drug was confirmed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Somatropin for Small-for-gestational Age | Number of Participants With Treatment Related Adverse Events of Somatropin Based on SGA Severity. | 10 participants |
| >=15 Years | Number of Participants With Treatment Related Adverse Events of Somatropin Based on SGA Severity. | 16 participants |
| Severe SGA | Number of Participants With Treatment Related Adverse Events of Somatropin Based on SGA Severity. | 18 participants |
Comparison: The risk factor tested was Severity. The null hypothesis is that there is no association between mild, moderate and severe in the frequency of treatment related adverse events.p-value: =0.033Chi-squared
Comparison: The risk factor tested was Severity. The null hypothesis is that there is no linear trend in the frequency of treatment related adverse events across increasing levels of severity.p-value: =0.207Cochran-Armitage Exact
Primary
Number of Participants With Treatment Related Adverse Events of Somatropin by Gender.
To determine whether gender is a significant risk factor in the frequency of treatment related adverse events.
Time frame: Up to 3 years
Population: The safety analysis population consists of the participants who satisfy the case conditions and in whom administration of this drug was confirmed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Somatropin for Small-for-gestational Age | Number of Participants With Treatment Related Adverse Events of Somatropin by Gender. | 19 participants |
| >=15 Years | Number of Participants With Treatment Related Adverse Events of Somatropin by Gender. | 25 participants |
Comparison: The risk factor tested was Gender. The null hypothesis is that there is no difference between Male and Female in the frequency of treatment related adverse events.p-value: =0.206Chi-squared
Primary
Number of Participants With Treatment Related Adverse Events of Somatropin: With Complications vs. Without Complications
To determine whether having complication(s) is a significant risk factor in the frequency of treatment related adverse events.
Time frame: Up to 3 years
Population: The safety analysis population consists of the participants who satisfy the case conditions and in whom administration of this drug was confirmed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Somatropin for Small-for-gestational Age | Number of Participants With Treatment Related Adverse Events of Somatropin: With Complications vs. Without Complications | 21 participants |
| >=15 Years | Number of Participants With Treatment Related Adverse Events of Somatropin: With Complications vs. Without Complications | 23 participants |
Comparison: The risk factor tested was Complication(s). The null hypothesis is that there is no difference between With complication(s) and Without complication(s)in the frequency of treatment related adverse events.p-value: =0.009Chi-squared
Primary
Number of Participants With Treatment Related Adverse Events of Somatropin: With Concomitant Drug(s) vs. Without Concomitant Drug(s).
To determine whether taking concomitant drug(s) is a significant risk factor in the frequency of treatment related adverse events.
Time frame: Up to 3 years
Population: The safety analysis population consists of the participants who satisfy the case conditions and in whom administration of this drug was confirmed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Somatropin for Small-for-gestational Age | Number of Participants With Treatment Related Adverse Events of Somatropin: With Concomitant Drug(s) vs. Without Concomitant Drug(s). | 21 Participants |
| >=15 Years | Number of Participants With Treatment Related Adverse Events of Somatropin: With Concomitant Drug(s) vs. Without Concomitant Drug(s). | 23 Participants |
Comparison: The risk factor tested was Concomitant Drug(s). The null hypothesis is that there is no difference between With Concomitant Drug(s) and Without Concomitant Drug(s) in the frequency of treatment related adverse events.p-value: =0.003Chi-squared
Primary
Number of Participants With Treatment Related Adverse Events of Somatropin: With Hepatic Function Disorder vs. Without Hepatic Function Disorder.
To determine whether hepatic function disorder is a significant risk factor in the frequency of treatment related adverse events.
Time frame: Up to 3 years
Population: The safety analysis population consists of the participants who satisfy the case conditions and in whom administration of this drug was confirmed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Somatropin for Small-for-gestational Age | Number of Participants With Treatment Related Adverse Events of Somatropin: With Hepatic Function Disorder vs. Without Hepatic Function Disorder. | 3 Participants |
| >=15 Years | Number of Participants With Treatment Related Adverse Events of Somatropin: With Hepatic Function Disorder vs. Without Hepatic Function Disorder. | 40 Participants |
Comparison: The risk factor tested was Hepatic Function Disorder. The null hypothesis is that there is no difference between with Hepatic Function Disorder and without Hepatic Function Disorder in the frequency of treatment related adverse events.p-value: <0.001Chi-squared
Primary
Number of Participants With Treatment Related Adverse Events of Somatropin: With Past History of Any Disease vs. Without Past History of Any Disease.
To determine whether past history of any disease is a significant risk factor in the frequency of treatment related adverse events.
Time frame: Up to 3 years
Population: The safety analysis population consists of the participants who satisfy the case conditions and in whom administration of this drug was confirmed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Somatropin for Small-for-gestational Age | Number of Participants With Treatment Related Adverse Events of Somatropin: With Past History of Any Disease vs. Without Past History of Any Disease. | 18 participants |
| >=15 Years | Number of Participants With Treatment Related Adverse Events of Somatropin: With Past History of Any Disease vs. Without Past History of Any Disease. | 26 participants |
Comparison: The risk factor tested was Past history of any disease. The null hypothesis is that there is no difference between With past history of any disease and Without past history any disease in the frequency of treatment related adverse events.p-value: =0.013Chi-squared
Primary
Number of Participants With Treatment Related Adverse Events of Somatropin: With Renal Impairment vs. Without Renal Impairment.
To determine whether renal impairment is a significant risk factor in the frequency of treatment related adverse events.
Time frame: Up to 3 years
Population: The safety analysis population consists of the participants who satisfy the case conditions and in whom administration of this drug was confirmed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Somatropin for Small-for-gestational Age | Number of Participants With Treatment Related Adverse Events of Somatropin: With Renal Impairment vs. Without Renal Impairment. | 3 Participants |
| >=15 Years | Number of Participants With Treatment Related Adverse Events of Somatropin: With Renal Impairment vs. Without Renal Impairment. | 40 Participants |
Comparison: The risk factor tested was Renal Impairment. The null hypothesis is that there is no difference between With Renal Impairment and Without Renal Impairment in the frequency of treatment related adverse events.p-value: <0.001Chi-squared
Primary
Number of Unlisted Treatment Related Adverse Events According to Japanese Package Insert.
Adverse events mean all unfavorable events that occur in participants after administration of somatropin, irrespective of causal relationship to somatropin (including clinically problematic abnormal changes in laboratory test values). Treatment related adverse events were evaluated in company with the causal relationship to somatropin. Unlisted treatment related adverse events were confirmed with listed adverse drug reaction according to Japanese package insert.
Time frame: Up to 3 years
Population: The safety analysis population consists of the participants who satisfy the case conditions and in whom administration of this drug was confirmed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Somatropin for Small-for-gestational Age | Number of Unlisted Treatment Related Adverse Events According to Japanese Package Insert. | 26 events |