Trial Outcomes & Findings for Efficacy, Safety, and Pharmacokinetics (PK) of Triptorelin 6-month Formulation in Patients With Central Precocious Puberty (NCT NCT01467882)

NCT ID: NCT01467882

Last Updated: 2017-07-28

Results Overview

This is a lab test to see what percentage of participants were returned to normal before-puberty levels at Month 6.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 44 participants
• Primary outcome timeframe: Month 6
• Results posted on: 2017-07-28

Participant Flow

Intention to treat, defined as all participants enrolled

Participant milestones

Measure	Children All children enrolled who received triptorelin 22.5 mg, intramuscular (IM), at Day 1 and Day 169
Overall Study STARTED	44
Overall Study COMPLETED	44
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Efficacy, Safety, and Pharmacokinetics (PK) of Triptorelin 6-month Formulation in Patients With Central Precocious Puberty

Baseline characteristics by cohort

Measure	Children n=44 Participants All children enrolled who received triptorelin 22.5 mg, intramuscular (IM), at Day 1 and Day 169
Age, Categorical <=18 years	44 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Age, Continuous	7.41 years STANDARD_DEVIATION 1.28 • n=5 Participants
Sex: Female, Male Female	39 Participants n=5 Participants
Sex: Female, Male Male	5 Participants n=5 Participants
Region of Enrollment United States	28 participants n=5 Participants
Region of Enrollment Mexico	1 participants n=5 Participants
Region of Enrollment Chile	15 participants n=5 Participants

PRIMARY outcome

Timeframe: Month 6

Population: Intention to treat, defined as all participants enrolled

This is a lab test to see what percentage of participants were returned to normal before-puberty levels at Month 6.

Outcome measures

Measure	Children n=44 Participants All children enrolled who received triptorelin 22.5 mg, intramuscular (IM), at Day 1 and Day 169	All Children Follicle Stimulating Hormone All children enrolled who received triptorelin 22.5 mg, intramuscular (IM), at Day 1 and Day 169	Boys All boys enrolled who received triptorelin 22.5 mg, intramuscular (IM), at Day 1 and Day 169
Percentage of Children With Luteinizing Hormone (LH) Suppression to Prepubertal Levels 30 Minutes After Leuprolide Stimulation at Month 6	93.18 percentage of participants Interval 81.34 to 98.57	—	—

SECONDARY outcome

Timeframe: at Months 1, 2, 3, 9 and 12

Population: Intention to treat, defined as all participants enrolled

This is a lab test to see what percentage of children were returned to normal before-puberty levels by the drug at each time point.

Outcome measures

Measure	Children n=44 Participants All children enrolled who received triptorelin 22.5 mg, intramuscular (IM), at Day 1 and Day 169	All Children Follicle Stimulating Hormone All children enrolled who received triptorelin 22.5 mg, intramuscular (IM), at Day 1 and Day 169	Boys All boys enrolled who received triptorelin 22.5 mg, intramuscular (IM), at Day 1 and Day 169
Percentage of Children With LH Suppression to Prepubertal Levels 30 Minutes After Leuprolide Stimulation at Months 1, 2, 3, 9 and 12 Month 1	95.45 percentage of participants	—	—
Percentage of Children With LH Suppression to Prepubertal Levels 30 Minutes After Leuprolide Stimulation at Months 1, 2, 3, 9 and 12 Month 2	95.45 percentage of participants	—	—
Percentage of Children With LH Suppression to Prepubertal Levels 30 Minutes After Leuprolide Stimulation at Months 1, 2, 3, 9 and 12 Month 3	95.45 percentage of participants	—	—
Percentage of Children With LH Suppression to Prepubertal Levels 30 Minutes After Leuprolide Stimulation at Months 1, 2, 3, 9 and 12 Month 9	95.45 percentage of participants	—	—
Percentage of Children With LH Suppression to Prepubertal Levels 30 Minutes After Leuprolide Stimulation at Months 1, 2, 3, 9 and 12 Month 12	97.73 percentage of participants	—	—

SECONDARY outcome

Timeframe: from Month 6 to 12

Population: Intention to treat, defined as all participants enrolled

This is a lab test to see what percentage of children stayed at the normal before-puberty level from month 6 to month 12.

Outcome measures

Measure	Children n=44 Participants All children enrolled who received triptorelin 22.5 mg, intramuscular (IM), at Day 1 and Day 169	All Children Follicle Stimulating Hormone All children enrolled who received triptorelin 22.5 mg, intramuscular (IM), at Day 1 and Day 169	Boys All boys enrolled who received triptorelin 22.5 mg, intramuscular (IM), at Day 1 and Day 169
Percentage of Children Maintaining LH Suppression at Prepubertal Levels 30 Minutes After Leuprolide Stimulation From Month 6 to 12	93.18 percentage of participants	—	—

SECONDARY outcome

Timeframe: at Months 1, 2, 3, 6, 9 and 12

Population: Intention to treat, defined as all participants enrolled

This is a lab test to see what percentage of children were returned to lower than normal before-puberty levels by the drug at each time point.

Outcome measures

Measure	Children n=44 Participants All children enrolled who received triptorelin 22.5 mg, intramuscular (IM), at Day 1 and Day 169	All Children Follicle Stimulating Hormone All children enrolled who received triptorelin 22.5 mg, intramuscular (IM), at Day 1 and Day 169	Boys All boys enrolled who received triptorelin 22.5 mg, intramuscular (IM), at Day 1 and Day 169
Percentage of Children With LH Suppression (LH ≤ 4 IU/L)30 Minutes After Leuprolide Stimulation at Months 1, 2, 3, 6, 9 and 12 Month 1	95.45 percentage of participants	—	—
Percentage of Children With LH Suppression (LH ≤ 4 IU/L)30 Minutes After Leuprolide Stimulation at Months 1, 2, 3, 6, 9 and 12 Month 2	95.45 percentage of participants	—	—
Percentage of Children With LH Suppression (LH ≤ 4 IU/L)30 Minutes After Leuprolide Stimulation at Months 1, 2, 3, 6, 9 and 12 Month 3	93.18 percentage of participants	—	—
Percentage of Children With LH Suppression (LH ≤ 4 IU/L)30 Minutes After Leuprolide Stimulation at Months 1, 2, 3, 6, 9 and 12 Month 6	90.91 percentage of participants	—	—
Percentage of Children With LH Suppression (LH ≤ 4 IU/L)30 Minutes After Leuprolide Stimulation at Months 1, 2, 3, 6, 9 and 12 Month 9	93.18 percentage of participants	—	—
Percentage of Children With LH Suppression (LH ≤ 4 IU/L)30 Minutes After Leuprolide Stimulation at Months 1, 2, 3, 6, 9 and 12 Month 12	97.73 percentage of participants	—	—

SECONDARY outcome

Timeframe: from Month 6 to 12

Population: Intention to treat, defined as all participants enrolled

This is a lab test to see what percentage of children stayed at the lower than normal before-puberty level from month 6 to month 12.

Outcome measures

Measure	Children n=44 Participants All children enrolled who received triptorelin 22.5 mg, intramuscular (IM), at Day 1 and Day 169	All Children Follicle Stimulating Hormone All children enrolled who received triptorelin 22.5 mg, intramuscular (IM), at Day 1 and Day 169	Boys All boys enrolled who received triptorelin 22.5 mg, intramuscular (IM), at Day 1 and Day 169
Percentage of Children Maintaining LH Suppression at </= 4 IU/L 30 Minutes After Leuprolide Stimulation From Month 6 to 12	90.91 percentage of participants	—	—

SECONDARY outcome

Timeframe: Baseline to Months 1, 2, 3, 6, 9, and 12

Population: Intention to treat, defined as all participants enrolled

Outcome measures

Measure	Children n=44 Participants All children enrolled who received triptorelin 22.5 mg, intramuscular (IM), at Day 1 and Day 169	All Children Follicle Stimulating Hormone n=44 Participants All children enrolled who received triptorelin 22.5 mg, intramuscular (IM), at Day 1 and Day 169	Boys All boys enrolled who received triptorelin 22.5 mg, intramuscular (IM), at Day 1 and Day 169
Change From Baseline in Luteinizing Hormone (LH) and Follicle Stimulating Hormone (FSH) at Months 1, 2, 3, 6, 9, and 12 at Month 1	-25.21 IU/L Standard Deviation 20.28	-8.85 IU/L Standard Deviation 4.15	—
Change From Baseline in Luteinizing Hormone (LH) and Follicle Stimulating Hormone (FSH) at Months 1, 2, 3, 6, 9, and 12 at Month 2	-25.25 IU/L Standard Deviation 20.41	-8.80 IU/L Standard Deviation 4.20	—
Change From Baseline in Luteinizing Hormone (LH) and Follicle Stimulating Hormone (FSH) at Months 1, 2, 3, 6, 9, and 12 at Month 3	-25.17 IU/L Standard Deviation 20.53	-8.13 IU/L Standard Deviation 4.26	—
Change From Baseline in Luteinizing Hormone (LH) and Follicle Stimulating Hormone (FSH) at Months 1, 2, 3, 6, 9, and 12 at Month 6	-23.06 IU/L Standard Deviation 22.17	-6.66 IU/L Standard Deviation 4.61	—
Change From Baseline in Luteinizing Hormone (LH) and Follicle Stimulating Hormone (FSH) at Months 1, 2, 3, 6, 9, and 12 at Month 9	-25.24 IU/L Standard Deviation 20.49	-7.87 IU/L Standard Deviation 4.27	—
Change From Baseline in Luteinizing Hormone (LH) and Follicle Stimulating Hormone (FSH) at Months 1, 2, 3, 6, 9, and 12 at Month 12	-25.15 IU/L Standard Deviation 20.50	-6.99 IU/L Standard Deviation 4.63	—

SECONDARY outcome

Timeframe: Baseline to Months 1, 2, 3, 6, 9, and 12

Population: Intention to treat girls, defined as all girls enrolled

Outcome measures

Measure	Children n=39 Participants All children enrolled who received triptorelin 22.5 mg, intramuscular (IM), at Day 1 and Day 169	All Children Follicle Stimulating Hormone All children enrolled who received triptorelin 22.5 mg, intramuscular (IM), at Day 1 and Day 169	Boys All boys enrolled who received triptorelin 22.5 mg, intramuscular (IM), at Day 1 and Day 169
Change From Baseline in Estradiol Levels at Months 1, 2, 3, 6, 9, and 12 at Month 1	-31.87 ng/L Standard Deviation 27.82	—	—
Change From Baseline in Estradiol Levels at Months 1, 2, 3, 6, 9, and 12 at Month 2	-31.24 ng/L Standard Deviation 31.80	—	—
Change From Baseline in Estradiol Levels at Months 1, 2, 3, 6, 9, and 12 at Month 3	-32.15 ng/L Standard Deviation 28.65	—	—
Change From Baseline in Estradiol Levels at Months 1, 2, 3, 6, 9, and 12 at Month 6	-28.18 ng/L Standard Deviation 31.26	—	—
Change From Baseline in Estradiol Levels at Months 1, 2, 3, 6, 9, and 12 at Month 9	-30.08 ng/L Standard Deviation 27.44	—	—
Change From Baseline in Estradiol Levels at Months 1, 2, 3, 6, 9, and 12 at Month 12	-29.74 ng/L Standard Deviation 28.24	—	—

SECONDARY outcome

Timeframe: Baseline to Months 1, 2, 3, 6, 9, and 12

Population: Intention to treat boys, defined as all boys enrolled

Outcome measures

Measure	Children n=5 Participants All children enrolled who received triptorelin 22.5 mg, intramuscular (IM), at Day 1 and Day 169	All Children Follicle Stimulating Hormone All children enrolled who received triptorelin 22.5 mg, intramuscular (IM), at Day 1 and Day 169	Boys All boys enrolled who received triptorelin 22.5 mg, intramuscular (IM), at Day 1 and Day 169
Change From Baseline in Testosterone Levels at Months 1, 2, 3, 6, 9, and 12 at Month 1	-306.96 ng/dL Standard Deviation 184.06	—	—
Change From Baseline in Testosterone Levels at Months 1, 2, 3, 6, 9, and 12 at Month 2	-290.70 ng/dL Standard Deviation 214.81	—	—
Change From Baseline in Testosterone Levels at Months 1, 2, 3, 6, 9, and 12 at Month 3	-319.20 ng/dL Standard Deviation 177.04	—	—
Change From Baseline in Testosterone Levels at Months 1, 2, 3, 6, 9, and 12 at Month 6	-317.62 ng/dL Standard Deviation 178.11	—	—
Change From Baseline in Testosterone Levels at Months 1, 2, 3, 6, 9, and 12 at Month 9	-315.54 ng/dL Standard Deviation 183.98	—	—
Change From Baseline in Testosterone Levels at Months 1, 2, 3, 6, 9, and 12 at Month 12	-301.86 ng/dL Standard Deviation 205.29	—	—

SECONDARY outcome

Timeframe: at Months 1, 2, 3, 6, 9, and 12

Population: Intention to treat, defined as all participants enrolled

Outcome measures

Measure	Children n=44 Participants All children enrolled who received triptorelin 22.5 mg, intramuscular (IM), at Day 1 and Day 169	All Children Follicle Stimulating Hormone n=39 Participants All children enrolled who received triptorelin 22.5 mg, intramuscular (IM), at Day 1 and Day 169	Boys n=5 Participants All boys enrolled who received triptorelin 22.5 mg, intramuscular (IM), at Day 1 and Day 169
Percentage of Children With Prepubertal Estradiol or Testosterone Levels at Months 1, 2, 3, 6, 9, and 12 at Month 1	86.36 percentage of participants	87.18 percentage of participants	80.00 percentage of participants
Percentage of Children With Prepubertal Estradiol or Testosterone Levels at Months 1, 2, 3, 6, 9, and 12 at Month 2	88.37 percentage of participants	89.47 percentage of participants	80.00 percentage of participants
Percentage of Children With Prepubertal Estradiol or Testosterone Levels at Months 1, 2, 3, 6, 9, and 12 at Month 3	93.18 percentage of participants	92.31 percentage of participants	100.00 percentage of participants
Percentage of Children With Prepubertal Estradiol or Testosterone Levels at Months 1, 2, 3, 6, 9, and 12 at Month 6	81.82 percentage of participants	79.49 percentage of participants	100.00 percentage of participants
Percentage of Children With Prepubertal Estradiol or Testosterone Levels at Months 1, 2, 3, 6, 9, and 12 at Month 9	81.82 percentage of participants	82.05 percentage of participants	80.00 percentage of participants
Percentage of Children With Prepubertal Estradiol or Testosterone Levels at Months 1, 2, 3, 6, 9, and 12 at Month 12	79.55 percentage of participants	79.49 percentage of participants	80.00 percentage of participants

SECONDARY outcome

Timeframe: at 2 days after second triptorelin injection (Day 171)

Population: AOC Subset is defined as 50% of the population randomly assigned

Outcome measures

Measure	Children n=22 Participants All children enrolled who received triptorelin 22.5 mg, intramuscular (IM), at Day 1 and Day 169	All Children Follicle Stimulating Hormone All children enrolled who received triptorelin 22.5 mg, intramuscular (IM), at Day 1 and Day 169	Boys All boys enrolled who received triptorelin 22.5 mg, intramuscular (IM), at Day 1 and Day 169
Percentage of Children Without Higher Basal LH and Estradiol or Testosterone	13.64 percentage of participants	—	—

SECONDARY outcome

Timeframe: Baseline to Months 6 and 12

Population: Intention to treat, defined as all participants enrolled

Outcome measures

Measure	Children n=44 Participants All children enrolled who received triptorelin 22.5 mg, intramuscular (IM), at Day 1 and Day 169	All Children Follicle Stimulating Hormone All children enrolled who received triptorelin 22.5 mg, intramuscular (IM), at Day 1 and Day 169	Boys All boys enrolled who received triptorelin 22.5 mg, intramuscular (IM), at Day 1 and Day 169
Change From Baseline in Height-for-age Z-score Per 2000 CDC Growth Charts at Months 6 and 12 at Month 6	0.05 Z-score Standard Deviation 0.20	—	—
Change From Baseline in Height-for-age Z-score Per 2000 CDC Growth Charts at Months 6 and 12 at Month 12	0.00 Z-score Standard Deviation 0.27	—	—

SECONDARY outcome

Timeframe: Baseline to Months 6 and 12

Population: Intention to treat, defined as all participants enrolled

Outcome measures

Measure	Children n=44 Participants All children enrolled who received triptorelin 22.5 mg, intramuscular (IM), at Day 1 and Day 169	All Children Follicle Stimulating Hormone All children enrolled who received triptorelin 22.5 mg, intramuscular (IM), at Day 1 and Day 169	Boys All boys enrolled who received triptorelin 22.5 mg, intramuscular (IM), at Day 1 and Day 169
Change From Baseline in Height-for-age Percentile Per 2000 CDC Growth Charts at Months 6 and 12 at Month 6	1.01 percentile Standard Deviation 3.21	—	—
Change From Baseline in Height-for-age Percentile Per 2000 CDC Growth Charts at Months 6 and 12 at Month 12	0.91 percentile Standard Deviation 4.39	—	—

SECONDARY outcome

Timeframe: Baseline to Months 6 and 12

Population: Intention to treat, defined as all participants enrolled

Outcome measures

Measure	Children n=44 Participants All children enrolled who received triptorelin 22.5 mg, intramuscular (IM), at Day 1 and Day 169	All Children Follicle Stimulating Hormone All children enrolled who received triptorelin 22.5 mg, intramuscular (IM), at Day 1 and Day 169	Boys All boys enrolled who received triptorelin 22.5 mg, intramuscular (IM), at Day 1 and Day 169
Change From Baseline in Growth Velocity at Months 6 and 12 at Month 6	6.84 cm/year Standard Deviation 2.33	—	—
Change From Baseline in Growth Velocity at Months 6 and 12 at Month 12	6.05 cm/year Standard Deviation 1.7	—	—

SECONDARY outcome

Timeframe: Baseline to Months 6 and 12

Population: Intention to treat, defined as all participants enrolled

Outcome measures

Measure	Children n=44 Participants All children enrolled who received triptorelin 22.5 mg, intramuscular (IM), at Day 1 and Day 169	All Children Follicle Stimulating Hormone All children enrolled who received triptorelin 22.5 mg, intramuscular (IM), at Day 1 and Day 169	Boys All boys enrolled who received triptorelin 22.5 mg, intramuscular (IM), at Day 1 and Day 169
Percentage of Participants Without Bone Age / Chronological Age Ratio Increase From Baseline at Months 6 and 12 at Month 6	63.64 percentage of participants	—	—
Percentage of Participants Without Bone Age / Chronological Age Ratio Increase From Baseline at Months 6 and 12 at Month 12	95.45 percentage of participants	—	—

SECONDARY outcome

Timeframe: at Months 6 and 12

Population: Intention to treat, defined as all participants enrolled

Outcome measures

Measure	Children n=44 Participants All children enrolled who received triptorelin 22.5 mg, intramuscular (IM), at Day 1 and Day 169	All Children Follicle Stimulating Hormone All children enrolled who received triptorelin 22.5 mg, intramuscular (IM), at Day 1 and Day 169	Boys All boys enrolled who received triptorelin 22.5 mg, intramuscular (IM), at Day 1 and Day 169
Percentage of Children Achieving Stabilization of Sexual Maturation at Months 6 and 12 at Month 6	90.91 percentage of participants	—	—
Percentage of Children Achieving Stabilization of Sexual Maturation at Months 6 and 12 at Month 12	88.64 percentage of participants	—	—

SECONDARY outcome

Timeframe: Baseline to Months 6 and 12

Population: Intention to treat girls, defined as all girls enrolled

Outcome measures

Measure	Children n=39 Participants All children enrolled who received triptorelin 22.5 mg, intramuscular (IM), at Day 1 and Day 169	All Children Follicle Stimulating Hormone All children enrolled who received triptorelin 22.5 mg, intramuscular (IM), at Day 1 and Day 169	Boys All boys enrolled who received triptorelin 22.5 mg, intramuscular (IM), at Day 1 and Day 169
Percentage of Girls With Regression of Uterine Length Compared to Baseline at Months 6 and 12 at Month 12	76.92 percentage of participants	—	—
Percentage of Girls With Regression of Uterine Length Compared to Baseline at Months 6 and 12 at Month 6	69.23 percentage of participants	—	—

SECONDARY outcome

Timeframe: Baseline to Months 6 and 12

Population: Intention to treat boys, defined as all boys enrolled

Outcome measures

Measure	Children n=5 Participants All children enrolled who received triptorelin 22.5 mg, intramuscular (IM), at Day 1 and Day 169	All Children Follicle Stimulating Hormone All children enrolled who received triptorelin 22.5 mg, intramuscular (IM), at Day 1 and Day 169	Boys All boys enrolled who received triptorelin 22.5 mg, intramuscular (IM), at Day 1 and Day 169
Percentage of Boys With Absence of Progression of Testis Volumes Compared to Baseline at Months 6 and 12 at Month 6	100.00 percentage of participants	—	—
Percentage of Boys With Absence of Progression of Testis Volumes Compared to Baseline at Months 6 and 12 at Month 12	100.00 percentage of participants	—	—

Adverse Events

Children

Serious events: 1 serious events

Other events: 20 other events

Deaths: 0 deaths

Serious adverse events

Measure	Children n=44 participants at risk All children enrolled who received triptorelin 22.5 mg, intramuscular (IM), at Day 1 and Day 169
Infections and infestations Device related infection	2.3% 1/44 • Number of events 1

Other adverse events

Measure	Children n=44 participants at risk All children enrolled who received triptorelin 22.5 mg, intramuscular (IM), at Day 1 and Day 169
Respiratory, thoracic and mediastinal disorders Cough	6.8% 3/44 • Number of events 4
Nervous system disorders Headache	13.6% 6/44 • Number of events 7
Infections and infestations Gastroenteritis	6.8% 3/44 • Number of events 3
Infections and infestations Nasopharyngitis	13.6% 6/44 • Number of events 6
Infections and infestations Upper respiratory tract infection	9.1% 4/44 • Number of events 5

Additional Information

Eija Lundström

Debiopharm International, S.A.

Phone: :+41 21 3210111

Email: eija.lundstrom@debiopharm.com

Results disclosure agreements

• Principal investigator is a sponsor employee Any publication or scientific communication related to this study can only take place once the agreement between the Sponsor and the Investigator has been reached.
• Publication restrictions are in place

Restriction type: OTHER