Trial Outcomes & Findings for Aromatase Inhibitors, Alone And In Combination With Growth Hormone In Adolescent Boys With Idiopathic Short Stature (NCT NCT01248416)

NCT ID: NCT01248416

Last Updated: 2018-08-07

Results Overview

Differences in height gains

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 76 participants
• Primary outcome timeframe: 0 to 24 months
• Results posted on: 2018-08-07

Participant Flow

Participant milestones

Measure	Aromatase Inhibitor Anastrozole 1mg or Letrozole 2.5mg daily orally for 2 to 3 years Aromatase Inhibitor	Growth Hormone Somatropin 0.3mg/kg/week divided daily subcutaneously for 2 to 3 years Growth Hormone	Aromatase Inhibitor and Growth Hormone Anastrozole 1mg or Letrozole 2.5mg orally daily for 2 to 3 years and Somatropin 0.3mg/kg/week divided daily subcutaneously for 2 to 3 years Aromatase Inhibitor Growth Hormone Aromatase Inhibitor and Growth Hormone
Overall Study STARTED	25	25	26
Overall Study COMPLETED	21	25	25
Overall Study NOT COMPLETED	4	0	1

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Aromatase Inhibitors, Alone And In Combination With Growth Hormone In Adolescent Boys With Idiopathic Short Stature

Baseline characteristics by cohort

Measure	Aromatase Inhibitor n=25 Participants Anastrozole 1mg or Letrozole 2.5mg daily orally for 2 to 3 years Aromatase Inhibitor	Growth Hormone n=25 Participants Somatropin 0.3mg/kg/week divided daily subcutaneously for 2 to 3 years Growth Hormone	Aromatase Inhibitor and Growth Hormone n=26 Participants Anastrozole 1mg or Letrozole 2.5mg orally daily for 2 to 3 years and Somatropin 0.3mg/kg/week divided daily subcutaneously for 2 to 3 years Aromatase Inhibitor Growth Hormone Aromatase Inhibitor and Growth Hormone	Total n=76 Participants Total of all reporting groups
Age, Continuous	14.2 years STANDARD_DEVIATION 1.0 • n=5 Participants	14.1 years STANDARD_DEVIATION 1.2 • n=7 Participants	14.0 years STANDARD_DEVIATION 1.1 • n=5 Participants	14.1 years STANDARD_DEVIATION 1.1 • n=4 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Sex: Female, Male Male	25 Participants n=5 Participants	25 Participants n=7 Participants	26 Participants n=5 Participants	76 Participants n=4 Participants

PRIMARY outcome

Timeframe: 0 to 24 months

Population: Differences in height gains from 0 to 24 months; Of the 76 Subjects, 65 completed all procedures at 24 months.

Differences in height gains

Outcome measures

Measure	Aromatase Inhibitor n=18 Participants Anastrozole 1mg or Letrozole 2.5mg daily orally for 2 to 3 years Aromatase Inhibitor	Growth Hormone n=24 Participants Somatropin 0.3mg/kg/week divided daily subcutaneously for 2 to 3 years Growth Hormone	Aromatase Inhibitor and Growth Hormone n=23 Participants Anastrozole 1mg or Letrozole 2.5mg orally daily for 2 to 3 years and Somatropin 0.3mg/kg/week divided daily subcutaneously for 2 to 3 years Aromatase Inhibitor Growth Hormone Aromatase Inhibitor and Growth Hormone
Change in Height	14 Centimeters Standard Error 0.8	17.1 Centimeters Standard Error 0.9	18.9 Centimeters Standard Error 0.8

PRIMARY outcome

Timeframe: 0 to 24 months

Population: Of the 76 Subjects, 65 completed all procedures at 24 months.

Primary efficacy end point: change in predicted height (cm) from baseline at 24 months based on change in bone age (years)

Outcome measures

Measure	Aromatase Inhibitor n=18 Participants Anastrozole 1mg or Letrozole 2.5mg daily orally for 2 to 3 years Aromatase Inhibitor	Growth Hormone n=24 Participants Somatropin 0.3mg/kg/week divided daily subcutaneously for 2 to 3 years Growth Hormone	Aromatase Inhibitor and Growth Hormone n=23 Participants Anastrozole 1mg or Letrozole 2.5mg orally daily for 2 to 3 years and Somatropin 0.3mg/kg/week divided daily subcutaneously for 2 to 3 years Aromatase Inhibitor Growth Hormone Aromatase Inhibitor and Growth Hormone
Change in Predicted Height	0.5 centimeters Standard Error 1.0	4.9 centimeters Standard Error 0.9	7.4 centimeters Standard Error 0.9

SECONDARY outcome

Timeframe: 0 to 24 months

Population: Of the 76 Subjects, 65 completed all procedures at 24 months, however, 2 Subjects had a screw/pin in their leg/hip at the 24 month visit, and therefore, could not have a DEXA scan performed (N=63).

Outcome measures

Measure	Aromatase Inhibitor n=18 Participants Anastrozole 1mg or Letrozole 2.5mg daily orally for 2 to 3 years Aromatase Inhibitor	Growth Hormone n=24 Participants Somatropin 0.3mg/kg/week divided daily subcutaneously for 2 to 3 years Growth Hormone	Aromatase Inhibitor and Growth Hormone n=23 Participants Anastrozole 1mg or Letrozole 2.5mg orally daily for 2 to 3 years and Somatropin 0.3mg/kg/week divided daily subcutaneously for 2 to 3 years Aromatase Inhibitor Growth Hormone Aromatase Inhibitor and Growth Hormone
Change in Bone Density z Score Adjusted for Height	-1.061 z-score Standard Error 0.313	-0.586 z-score Standard Error 0.244	-0.605 z-score Standard Error 0.257

SECONDARY outcome

Timeframe: 0 to 24 months

Population: Of the 76 Subjects, 65 completed all procedures at 24 months, however, 2 Subjects had a screw/pin in their leg/hip at the 24 month visit, and therefore, could not have a DEXA scan performed (N=63).

Outcome measures

Measure	Aromatase Inhibitor n=18 Participants Anastrozole 1mg or Letrozole 2.5mg daily orally for 2 to 3 years Aromatase Inhibitor	Growth Hormone n=23 Participants Somatropin 0.3mg/kg/week divided daily subcutaneously for 2 to 3 years Growth Hormone	Aromatase Inhibitor and Growth Hormone n=22 Participants Anastrozole 1mg or Letrozole 2.5mg orally daily for 2 to 3 years and Somatropin 0.3mg/kg/week divided daily subcutaneously for 2 to 3 years Aromatase Inhibitor Growth Hormone Aromatase Inhibitor and Growth Hormone
Change in Lean Body Mass	42.2 kg Standard Error 1.6	42.0 kg Standard Error 1.3	46.5 kg Standard Error 1.2

SECONDARY outcome

Timeframe: 0 to 24 months

Population: Of the 76 Subjects, 65 completed all procedures at 24 months.

Outcome measures

Measure	Aromatase Inhibitor n=18 Participants Anastrozole 1mg or Letrozole 2.5mg daily orally for 2 to 3 years Aromatase Inhibitor	Growth Hormone n=24 Participants Somatropin 0.3mg/kg/week divided daily subcutaneously for 2 to 3 years Growth Hormone	Aromatase Inhibitor and Growth Hormone n=23 Participants Anastrozole 1mg or Letrozole 2.5mg orally daily for 2 to 3 years and Somatropin 0.3mg/kg/week divided daily subcutaneously for 2 to 3 years Aromatase Inhibitor Growth Hormone Aromatase Inhibitor and Growth Hormone
Change in Body Mass Index	2.5 kg/m^2 Standard Error 0.3	1.7 kg/m^2 Standard Error 0.4	2.5 kg/m^2 Standard Error 0.4

SECONDARY outcome

Timeframe: 0 to 24 months

Population: Of the 76 Subjects, 65 completed all procedures at 24 months, however, 1 Subject, did not have IGF-1 results available for the 24 month visit (N=64).

Outcome measures

Measure	Aromatase Inhibitor n=17 Participants Anastrozole 1mg or Letrozole 2.5mg daily orally for 2 to 3 years Aromatase Inhibitor	Growth Hormone n=24 Participants Somatropin 0.3mg/kg/week divided daily subcutaneously for 2 to 3 years Growth Hormone	Aromatase Inhibitor and Growth Hormone n=23 Participants Anastrozole 1mg or Letrozole 2.5mg orally daily for 2 to 3 years and Somatropin 0.3mg/kg/week divided daily subcutaneously for 2 to 3 years Aromatase Inhibitor Growth Hormone Aromatase Inhibitor and Growth Hormone
Change in IGF-I Concentrations	158 ng/mL Standard Error 14	280 ng/mL Standard Error 16	303 ng/mL Standard Error 27

SECONDARY outcome

Timeframe: 0 to 24 months

Population: Of the 76 Subjects, 65 completed all procedures at 24 months.

Outcome measures

Measure	Aromatase Inhibitor n=18 Participants Anastrozole 1mg or Letrozole 2.5mg daily orally for 2 to 3 years Aromatase Inhibitor	Growth Hormone n=24 Participants Somatropin 0.3mg/kg/week divided daily subcutaneously for 2 to 3 years Growth Hormone	Aromatase Inhibitor and Growth Hormone n=23 Participants Anastrozole 1mg or Letrozole 2.5mg orally daily for 2 to 3 years and Somatropin 0.3mg/kg/week divided daily subcutaneously for 2 to 3 years Aromatase Inhibitor Growth Hormone Aromatase Inhibitor and Growth Hormone
Change in Testosterone	737 ng/dL Standard Error 79	372 ng/dL Standard Error 33	668 ng/dL Standard Error 37

SECONDARY outcome

Timeframe: 0 to 24 months

Population: Of the 51 AI alone or AI/GH combined Subjects, 41 completed all procedures at 24 months, however, 1 Subject did not have Estrone results available for the 24 month visit (N=40).

Those taking AI alone or AI/GH combined were grouped by type, either anastrozole or letrozole.

Outcome measures

Measure	Aromatase Inhibitor n=18 Participants Anastrozole 1mg or Letrozole 2.5mg daily orally for 2 to 3 years Aromatase Inhibitor	Growth Hormone n=22 Participants Somatropin 0.3mg/kg/week divided daily subcutaneously for 2 to 3 years Growth Hormone	Aromatase Inhibitor and Growth Hormone Anastrozole 1mg or Letrozole 2.5mg orally daily for 2 to 3 years and Somatropin 0.3mg/kg/week divided daily subcutaneously for 2 to 3 years Aromatase Inhibitor Growth Hormone Aromatase Inhibitor and Growth Hormone
Change in Estradiol	8 pg/mL Standard Error 1	4 pg/mL Standard Error 1	—

SECONDARY outcome

Timeframe: 0 to 24 months

Population: Of the 76 Subjects, 65 completed all procedures at 24 months, however, 1 Subject, did not have Estrone results available for the 24 month visit (N=64).

Outcome measures

Measure	Aromatase Inhibitor n=18 Participants Anastrozole 1mg or Letrozole 2.5mg daily orally for 2 to 3 years Aromatase Inhibitor	Growth Hormone n=24 Participants Somatropin 0.3mg/kg/week divided daily subcutaneously for 2 to 3 years Growth Hormone	Aromatase Inhibitor and Growth Hormone n=22 Participants Anastrozole 1mg or Letrozole 2.5mg orally daily for 2 to 3 years and Somatropin 0.3mg/kg/week divided daily subcutaneously for 2 to 3 years Aromatase Inhibitor Growth Hormone Aromatase Inhibitor and Growth Hormone
Change in Estrone	0.0 pg/mL Standard Error 1.7	6.1 pg/mL Standard Error 0.9	-0.9 pg/mL Standard Error 1.3

Adverse Events

Aromatase Inhibitor

Serious events: 4 serious events

Other events: 0 other events

Deaths: 0 deaths

Growth Hormone

Serious events: 2 serious events

Other events: 0 other events

Deaths: 0 deaths

Aromatase Inhibitor and Growth Hormone

Serious events: 2 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Measure	Aromatase Inhibitor n=25 participants at risk Anastrozole 1mg or Letrozole 2.5mg daily orally for 2 to 3 years Aromatase Inhibitor	Growth Hormone n=25 participants at risk Somatropin 0.3mg/kg/week divided daily subcutaneously for 2 to 3 years Growth Hormone	Aromatase Inhibitor and Growth Hormone n=26 participants at risk Anastrozole 1mg or Letrozole 2.5mg orally daily for 2 to 3 years and Somatropin 0.3mg/kg/week divided daily subcutaneously for 2 to 3 years Aromatase Inhibitor Growth Hormone Aromatase Inhibitor and Growth Hormone
Musculoskeletal and connective tissue disorders Slipped capital femoral epiphysis (SCFE)	0.00% 0/25	0.00% 0/25	3.8% 1/26 • Number of events 1
Nervous system disorders Headache	4.0% 1/25 • Number of events 1	0.00% 0/25	0.00% 0/26
Respiratory, thoracic and mediastinal disorders Pneumonia	0.00% 0/25	4.0% 1/25 • Number of events 1	0.00% 0/26
Psychiatric disorders Self Injury	0.00% 0/25	4.0% 1/25 • Number of events 1	0.00% 0/26
Nervous system disorders Concussion	4.0% 1/25 • Number of events 1	0.00% 0/25	0.00% 0/26
Renal and urinary disorders Testicular Torsion	4.0% 1/25 • Number of events 1	0.00% 0/25	0.00% 0/26
Musculoskeletal and connective tissue disorders Tibial Fracture and Torn Meniscus	0.00% 0/25	0.00% 0/25	3.8% 1/26 • Number of events 1
Musculoskeletal and connective tissue disorders Back Injury	4.0% 1/25 • Number of events 1	0.00% 0/25	0.00% 0/26

Other adverse events

Adverse event data not reported

Additional Information

Dr. Nelly Mauras

Nemours Children's Clinic

Phone: 904-697-3674

Email: nmauras@nemours.org

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place