Trial Outcomes & Findings for Long Term Use of Somatropin in Patients Small for Gestational Age (NCT NCT00793325)

NCT ID: NCT00793325

Last Updated: 2014-02-06

Results Overview

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.

• Recruitment status: COMPLETED
• Target enrollment: 920 participants
• Primary outcome timeframe: Up to 3 years
• Results posted on: 2014-02-06

Participant Flow

Participant milestones

Measure	Somatropin for Small-for-gestational Age Participants taking somatropin for small-for-gestational age according to Japanese package insert.
Overall Study STARTED	909
Overall Study COMPLETED	890
Overall Study NOT COMPLETED	19

Reasons for withdrawal

Measure	Somatropin for Small-for-gestational Age Participants taking somatropin for small-for-gestational age according to Japanese package insert.
Overall Study Protocol Violation	18
Overall Study Lost to Follow-up	1

Baseline Characteristics

Long Term Use of Somatropin in Patients Small for Gestational Age

Baseline characteristics by cohort

Measure	Somatropin for Small-for-gestational Age n=890 Participants Participants taking somatropin for small-for-gestational age according to Japanese package insert.
Age, Customized <15 years	884 participants n=5 Participants
Age, Customized >=15 years	6 participants n=5 Participants
Sex: Female, Male Female	423 Participants n=5 Participants
Sex: Female, Male Male	467 Participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Somatropin for Small-for-gestational Age n=890 Participants Participants taking somatropin for small-for-gestational age according to Japanese package insert.	>=15 Years Participants 15 years of age or older when taking somatropin for SGA according to Japanese package insert.	Severe SGA Participants with severe SGA taking somatropin for SGA according to Japanese package insert.
Number of Participants With Treatment Related Adverse Events.	44 participants	—	—

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Somatropin for Small-for-gestational Age n=890 Participants Participants taking somatropin for small-for-gestational age according to Japanese package insert.	>=15 Years Participants 15 years of age or older when taking somatropin for SGA according to Japanese package insert.	Severe SGA Participants with severe SGA taking somatropin for SGA according to Japanese package insert.
Number of Unlisted Treatment Related Adverse Events According to Japanese Package Insert.	26 events	—	—

PRIMARY outcome

Timeframe: 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.

To determine whether age is a significant risk factor in the frequency of treatment related adverse events.

Outcome measures

Measure	Somatropin for Small-for-gestational Age n=884 Participants Participants taking somatropin for small-for-gestational age according to Japanese package insert.	>=15 Years n=6 Participants Participants 15 years of age or older when taking somatropin for SGA according to Japanese package insert.	Severe SGA Participants with severe SGA taking somatropin for SGA according to Japanese package insert.
Number of Participants With Treatment Related Adverse Events of Somatropin: <15 Years of Age vs. >=15 Years of Age.	44 participants	0 participants	—

PRIMARY outcome

Timeframe: 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.

To determine whether gender is a significant risk factor in the frequency of treatment related adverse events.

Outcome measures

Measure	Somatropin for Small-for-gestational Age n=467 Participants Participants taking somatropin for small-for-gestational age according to Japanese package insert.	>=15 Years n=423 Participants Participants 15 years of age or older when taking somatropin for SGA according to Japanese package insert.	Severe SGA Participants with severe SGA taking somatropin for SGA according to Japanese package insert.
Number of Participants With Treatment Related Adverse Events of Somatropin by Gender.	19 participants	25 participants	—

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Somatropin for Small-for-gestational Age n=180 Participants Participants taking somatropin for small-for-gestational age according to Japanese package insert.	>=15 Years n=479 Participants Participants 15 years of age or older when taking somatropin for SGA according to Japanese package insert.	Severe SGA n=230 Participants Participants with severe SGA taking somatropin for SGA according to Japanese package insert.
Number of Participants With Treatment Related Adverse Events of Somatropin Based on SGA Severity.	10 participants	16 participants	18 participants

PRIMARY outcome

Timeframe: 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.

To determine whether past history of any disease is a significant risk factor in the frequency of treatment related adverse events.

Outcome measures

Measure	Somatropin for Small-for-gestational Age n=223 Participants Participants taking somatropin for small-for-gestational age according to Japanese package insert.	>=15 Years n=667 Participants Participants 15 years of age or older when taking somatropin for SGA according to Japanese package insert.	Severe SGA Participants with severe SGA taking somatropin for SGA according to Japanese package insert.
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	26 participants	—

PRIMARY outcome

Timeframe: 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.

To determine whether having complication(s) is a significant risk factor in the frequency of treatment related adverse events.

Outcome measures

Measure	Somatropin for Small-for-gestational Age n=268 Participants Participants taking somatropin for small-for-gestational age according to Japanese package insert.	>=15 Years n=622 Participants Participants 15 years of age or older when taking somatropin for SGA according to Japanese package insert.	Severe SGA Participants with severe SGA taking somatropin for SGA according to Japanese package insert.
Number of Participants With Treatment Related Adverse Events of Somatropin: With Complications vs. Without Complications	21 participants	23 participants	—

PRIMARY outcome

Timeframe: 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.

To determine whether hepatic function disorder is a significant risk factor in the frequency of treatment related adverse events.

Outcome measures

Measure	Somatropin for Small-for-gestational Age n=4 Participants Participants taking somatropin for small-for-gestational age according to Japanese package insert.	>=15 Years n=879 Participants Participants 15 years of age or older when taking somatropin for SGA according to Japanese package insert.	Severe SGA Participants with severe SGA taking somatropin for SGA according to Japanese package insert.
Number of Participants With Treatment Related Adverse Events of Somatropin: With Hepatic Function Disorder vs. Without Hepatic Function Disorder.	3 Participants	40 Participants	—

PRIMARY outcome

Timeframe: 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.

To determine whether renal impairment is a significant risk factor in the frequency of treatment related adverse events.

Outcome measures

Measure	Somatropin for Small-for-gestational Age n=9 Participants Participants taking somatropin for small-for-gestational age according to Japanese package insert.	>=15 Years n=874 Participants Participants 15 years of age or older when taking somatropin for SGA according to Japanese package insert.	Severe SGA Participants with severe SGA taking somatropin for SGA according to Japanese package insert.
Number of Participants With Treatment Related Adverse Events of Somatropin: With Renal Impairment vs. Without Renal Impairment.	3 Participants	40 Participants	—

PRIMARY outcome

Timeframe: 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.

To determine whether taking concomitant drug(s) is a significant risk factor in the frequency of treatment related adverse events.

Outcome measures

Measure	Somatropin for Small-for-gestational Age n=250 Participants Participants taking somatropin for small-for-gestational age according to Japanese package insert.	>=15 Years n=640 Participants Participants 15 years of age or older when taking somatropin for SGA according to Japanese package insert.	Severe SGA Participants with severe SGA taking somatropin for SGA according to Japanese package insert.
Number of Participants With Treatment Related Adverse Events of Somatropin: With Concomitant Drug(s) vs. Without Concomitant Drug(s).	21 Participants	23 Participants	—

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Somatropin for Small-for-gestational Age n=855 Participants Participants taking somatropin for small-for-gestational age according to Japanese package insert.	>=15 Years Participants 15 years of age or older when taking somatropin for SGA according to Japanese package insert.	Severe SGA Participants with severe SGA taking somatropin for SGA according to Japanese package insert.
Change in the Growth Rate Standard Deviation (SD) Score for Calendar Age. At one year	3.9 standard deviation (SD) score Standard Deviation 2.60	—	—
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	—	—
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	—	—

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Somatropin for Small-for-gestational Age n=855 Participants Participants taking somatropin for small-for-gestational age according to Japanese package insert.	>=15 Years Participants 15 years of age or older when taking somatropin for SGA according to Japanese package insert.	Severe SGA Participants with severe SGA taking somatropin for SGA according to Japanese package insert.
Change in Height SD Score for Calendar Age. At one year	0.6 standard deviation (SD) score Standard Deviation 0.49	—	—
Change in Height SD Score for Calendar Age. At two years	0.3 standard deviation (SD) score Standard Deviation 0.41	—	—
Change in Height SD Score for Calendar Age. At three years	0.3 standard deviation (SD) score Standard Deviation 0.40	—	—

Adverse Events

Somatropin for Small-for-gestational Age

Serious events: 8 serious events

Other events: 36 other events

Deaths: 0 deaths

Serious adverse events

Measure	Somatropin for Small-for-gestational Age n=890 participants at risk Participants taking somatropin for small-for-gestational age according to Japanese package insert.
Nervous system disorders Febrile convulsion	0.11% 1/890 • Number of events 1 The frequency of treatment related adverse events.
Respiratory, thoracic and mediastinal disorders Adenoidal hypertrophy	0.11% 1/890 • Number of events 1 The frequency of treatment related adverse events.
Respiratory, thoracic and mediastinal disorders Sleep apnoea syndrome	0.11% 1/890 • Number of events 1 The frequency of treatment related adverse events.
Hepatobiliary disorders Hepatic function abnormal	0.11% 1/890 • Number of events 1 The frequency of treatment related adverse events.
Musculoskeletal and connective tissue disorders Synovial disorder	0.11% 1/890 • Number of events 1 The frequency of treatment related adverse events.
Musculoskeletal and connective tissue disorders Scoliosis	0.22% 2/890 • Number of events 2 The frequency of treatment related adverse events.
Renal and urinary disorders Glomerulonephritis membranous	0.11% 1/890 • Number of events 1 The frequency of treatment related adverse events.

Other adverse events

Measure	Somatropin for Small-for-gestational Age n=890 participants at risk Participants taking somatropin for small-for-gestational age according to Japanese package insert.
Endocrine disorders Hypothyroidism	0.22% 2/890 • Number of events 2 The frequency of treatment related adverse events.
Endocrine disorders Precocious puberty	0.11% 1/890 • Number of events 1 The frequency of treatment related adverse events.
Metabolism and nutrition disorders Hyperamylasaemia	0.11% 1/890 • Number of events 1 The frequency of treatment related adverse events.
Metabolism and nutrition disorders Hyperphosphatasaemia	0.11% 1/890 • Number of events 1 The frequency of treatment related adverse events.
Metabolism and nutrition disorders Hyperinsulinaemia	0.11% 1/890 • Number of events 1 The frequency of treatment related adverse events.
Metabolism and nutrition disorders Hyperglycaemia	0.22% 2/890 • Number of events 2 The frequency of treatment related adverse events.
Metabolism and nutrition disorders Polydipsia	0.11% 1/890 • Number of events 1 The frequency of treatment related adverse events.
Metabolism and nutrition disorders Glucose tolerance impaired	0.11% 1/890 • Number of events 1 The frequency of treatment related adverse events.
Nervous system disorders Headache	0.22% 2/890 • Number of events 2 The frequency of treatment related adverse events.
Vascular disorders Hypertension	0.11% 1/890 • Number of events 1 The frequency of treatment related adverse events.
Vascular disorders Pallor	0.11% 1/890 • Number of events 1 The frequency of treatment related adverse events.
Respiratory, thoracic and mediastinal disorders Adenoidal hypertrophy	0.22% 2/890 • Number of events 2 The frequency of treatment related adverse events.
Respiratory, thoracic and mediastinal disorders Sleep apnoea syndrome	0.11% 1/890 • Number of events 1 The frequency of treatment related adverse events.
Gastrointestinal disorders Pigmentation lip	0.11% 1/890 • Number of events 1 The frequency of treatment related adverse events.
Gastrointestinal disorders Malocclusion	0.11% 1/890 • Number of events 1 The frequency of treatment related adverse events.
Hepatobiliary disorders Hepatic function abnormal	0.22% 2/890 • Number of events 2 The frequency of treatment related adverse events.
Skin and subcutaneous tissue disorders Blister	0.11% 1/890 • Number of events 1 The frequency of treatment related adverse events.
Skin and subcutaneous tissue disorders Rash	0.22% 2/890 • Number of events 2 The frequency of treatment related adverse events.
Musculoskeletal and connective tissue disorders Arthralgia	0.11% 1/890 • Number of events 1 The frequency of treatment related adverse events.
Renal and urinary disorders Haematuria	0.22% 2/890 • Number of events 2 The frequency of treatment related adverse events.
Renal and urinary disorders Proteinuria	0.11% 1/890 • Number of events 1 The frequency of treatment related adverse events.
General disorders Thirst	0.11% 1/890 • Number of events 1 The frequency of treatment related adverse events.
General disorders Injection site haemorrhage	0.22% 2/890 • Number of events 2 The frequency of treatment related adverse events.
General disorders Injection site pain	0.11% 1/890 • Number of events 1 The frequency of treatment related adverse events.
General disorders Pyrexia	0.11% 1/890 • Number of events 1 The frequency of treatment related adverse events.
Investigations Insulin-like growth factor	0.11% 1/890 • Number of events 1 The frequency of treatment related adverse events.
Investigations Insulin-like growth factor increased	0.45% 4/890 • Number of events 4 The frequency of treatment related adverse events.
Investigations Blood alkaline phosphatase increased	0.11% 1/890 • Number of events 1 The frequency of treatment related adverse events.
Investigations Blood creatine phosphokinase increased	0.34% 3/890 • Number of events 3 The frequency of treatment related adverse events.
Investigations Blood glucose increased	0.11% 1/890 • Number of events 1 The frequency of treatment related adverse events.
Investigations Blood thyroid stimulating hormone increased	0.11% 1/890 • Number of events 1 The frequency of treatment related adverse events.
Investigations Blood urine present	0.11% 1/890 • Number of events 1 The frequency of treatment related adverse events.
Investigations Thyroxine free decreased	0.11% 1/890 • Number of events 1 The frequency of treatment related adverse events.

Additional Information

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Email: ClinicalTrials.gov_Inquiries@pfizer.com

Results disclosure agreements

• Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
• Publication restrictions are in place

Restriction type: OTHER