Trial Outcomes & Findings for A Study to Assess the Safety and Efficacy of Leuprorelin in Central Precocious Puberty in Chinese Participants (NCT NCT02427958)

NCT ID: NCT02427958

Last Updated: 2022-03-16

Results Overview

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 307 participants
• Primary outcome timeframe: Day 1 up to Week 100
• Results posted on: 2022-03-16

Participant Flow

Participants took part in the study at 11 investigative sites in China from 07 August 2015 to 23 November 2018.

Chinese participants with central precocious puberty (CPP) were enrolled to receive leuprorelin as per body weight.

Participant milestones

Measure	Leuprorelin Participants with body weight greater than or equal to (\>=) 20 kilogram (kg) received the recommended initial dose of leuprorelin 3.75 milligram (mg), injection, subcutaneously, once every 4 weeks for 96 weeks. Participants with body weight less than (\<) 20 kg received leuprorelin 1.88 mg, injection, subcutaneously, once every 4 weeks for 96 weeks. The dose was adjusted based on participant's condition and investigator's judgment in alignment with the product label in China.
Overall Study STARTED	307
Overall Study COMPLETED	283
Overall Study NOT COMPLETED	24

Reasons for withdrawal

Measure	Leuprorelin Participants with body weight greater than or equal to (\>=) 20 kilogram (kg) received the recommended initial dose of leuprorelin 3.75 milligram (mg), injection, subcutaneously, once every 4 weeks for 96 weeks. Participants with body weight less than (\<) 20 kg received leuprorelin 1.88 mg, injection, subcutaneously, once every 4 weeks for 96 weeks. The dose was adjusted based on participant's condition and investigator's judgment in alignment with the product label in China.
Overall Study Pretreatment Event (PTE) or AE	3
Overall Study Lost to Follow-up	6
Overall Study Withdrawal by Subject	14
Overall Study Lack of Efficacy	1

Baseline Characteristics

Number of participants for whom Age at date of diagnosis of CPP data was available in baseline characteristics was 296.

Baseline characteristics by cohort

Measure	Leuprorelin n=307 Participants Participants with body weight greater than or equal to (\>=) 20 kilogram (kg) received the recommended initial dose of leuprorelin 3.75 milligram (mg), injection, subcutaneously, once every 4 weeks for 96 weeks. Participants with body weight less than (\<) 20 kg received leuprorelin 1.88 mg, injection, subcutaneously, once every 4 weeks for 96 weeks. The dose was adjusted based on participant's condition and investigator's judgment in alignment with the product label in China.
Age, Continuous	8.03 years STANDARD_DEVIATION 0.935 • n=307 Participants
Sex: Female, Male Female	305 Participants n=307 Participants
Sex: Female, Male Male	2 Participants n=307 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=307 Participants
Race (NIH/OMB) Asian	307 Participants n=307 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=307 Participants
Race (NIH/OMB) Black or African American	0 Participants n=307 Participants
Race (NIH/OMB) White	0 Participants n=307 Participants
Race (NIH/OMB) More than one race	0 Participants n=307 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=307 Participants
Region of Enrollment China	307 Participants n=307 Participants
Height	133.68 centimeter (cm) STANDARD_DEVIATION 7.108 • n=307 Participants
Weight	30.44 kilogram (kg) STANDARD_DEVIATION 5.346 • n=307 Participants
Weight Categories <20 kg	5 Participants n=307 Participants
Weight Categories >=20 kg	302 Participants n=307 Participants
Age at date of diagnosis of CPP	7.95 years STANDARD_DEVIATION 0.982 • n=296 Participants • Number of participants for whom Age at date of diagnosis of CPP data was available in baseline characteristics was 296.
Tanner Staging Evaluation: Breast (Female) and Genitals (Male) Stage 1	3 Participants n=307 Participants
Tanner Staging Evaluation: Breast (Female) and Genitals (Male) Stage 2	172 Participants n=307 Participants
Tanner Staging Evaluation: Breast (Female) and Genitals (Male) Stage 3	120 Participants n=307 Participants
Tanner Staging Evaluation: Breast (Female) and Genitals (Male) Stage 4	11 Participants n=307 Participants
Tanner Staging Evaluation: Breast (Female) and Genitals (Male) Stage 5	1 Participants n=307 Participants
Tanner Staging Evaluation: Pubic Hair Stage 1	266 Participants n=307 Participants
Tanner Staging Evaluation: Pubic Hair Stage 2	31 Participants n=307 Participants
Tanner Staging Evaluation: Pubic Hair Stage 3	9 Participants n=307 Participants
Tanner Staging Evaluation: Pubic Hair Stage 4	0 Participants n=307 Participants
Tanner Staging Evaluation: Pubic Hair Stage 5	1 Participants n=307 Participants
Peak Stimulated Luteinizing Hormone (LH)	20.664 unit per liter (U/L) STANDARD_DEVIATION 18.1982 • n=307 Participants
Peak Stimulated Follicle-stimulating Hormone (FSH)	14.992 U/L STANDARD_DEVIATION 6.7343 • n=307 Participants
Bone Age/Chronological Age	1.26 ratio STANDARD_DEVIATION 0.139 • n=304 Participants • Number of participants for whom bone age/chronological age data was available in baseline characteristics was 304.
Bone Mineral Density	0.4791 gram per square centimeter (g/cm^2) STANDARD_DEVIATION 0.2142 • n=182 Participants • Number of participants for whom bone mineral density data was available in baseline characteristics was 182.

PRIMARY outcome

Timeframe: Day 1 up to Week 100

Population: The safety analysis set included all enrolled participants who received at least 1 dose of study drug.

Outcome measures

Measure

Leuprorelin n=307 Participants Participants with body weight greater than or equal to (\>=) 20 kilogram (kg) received the recommended initial dose of leuprorelin 3.75 milligram (mg), injection, subcutaneously, once every 4 weeks for 96 weeks. Participants with body weight less than (\<) 20 kg received leuprorelin 1.88 mg, injection, subcutaneously, once every 4 weeks for 96 weeks. The dose was adjusted based on participant's condition and investigator's judgment in alignment with the product label in China.

Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs)

252 participants

SECONDARY outcome

Timeframe: Week 96

Population: The full analysis set included all enrolled participants who received at least 1 dose of study drug. The full analysis set where data at specified time points was available.

Tanner assessment score was used to document the stage of development of puberty through the assessment of secondary sexual characteristics. Female pubertal development staged by pubic hair development and breast size; male pubertal development staged by size of the genitalia and development of pubic hair. Rated in 5 stages: stage 1 (no development) to 5 (adult-like development in quantity and size). Regression or no progression was defined as negative change (improvement) or no change in Tanner score at Week 96 compared to baseline.

Outcome measures

Measure	Leuprorelin n=307 Participants Participants with body weight greater than or equal to (\>=) 20 kilogram (kg) received the recommended initial dose of leuprorelin 3.75 milligram (mg), injection, subcutaneously, once every 4 weeks for 96 weeks. Participants with body weight less than (\<) 20 kg received leuprorelin 1.88 mg, injection, subcutaneously, once every 4 weeks for 96 weeks. The dose was adjusted based on participant's condition and investigator's judgment in alignment with the product label in China.
Percentage of Participants With Regression or no Progression in Tanner Staging at Week 96 Female	83.5 percentage of participants Interval 78.68 to 87.62
Percentage of Participants With Regression or no Progression in Tanner Staging at Week 96 Male	0 percentage of participants Interval 0.0 to 84.19

Adverse Events

Leuprorelin

Serious events: 12 serious events

Other events: 189 other events

Deaths: 0 deaths

Serious adverse events

Measure	Leuprorelin n=307 participants at risk Participants with body weight greater than or equal to (\>=) 20 kilogram (kg) received the recommended initial dose of leuprorelin 3.75 milligram (mg), injection, subcutaneously, once every 4 weeks for 96 weeks. Participants with body weight less than (\<) 20 kg received leuprorelin 1.88 mg, injection, subcutaneously, once every 4 weeks for 96 weeks. The dose was adjusted based on participant's condition and investigator's judgment in alignment with the product label in China.
Infections and infestations Pneumonia	1.3% 4/307 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days (Week 100) after the last dose of study drug At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Infections and infestations Pneumonia mycoplasmal	0.65% 2/307 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days (Week 100) after the last dose of study drug At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Infections and infestations Tonsillitis	0.65% 2/307 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days (Week 100) after the last dose of study drug At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Infections and infestations Appendicitis	0.33% 1/307 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days (Week 100) after the last dose of study drug At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Infections and infestations Bronchitis	0.33% 1/307 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days (Week 100) after the last dose of study drug At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Infections and infestations Chronic tonsillitis	0.33% 1/307 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days (Week 100) after the last dose of study drug At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Infections and infestations Otitis media	0.33% 1/307 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days (Week 100) after the last dose of study drug At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Injury, poisoning and procedural complications Comminuted fracture	0.33% 1/307 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days (Week 100) after the last dose of study drug At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Injury, poisoning and procedural complications Epiphyseal injury	0.33% 1/307 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days (Week 100) after the last dose of study drug At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Injury, poisoning and procedural complications Peripheral nerve injury	0.33% 1/307 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days (Week 100) after the last dose of study drug At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Injury, poisoning and procedural complications Post procedural haemorrhage	0.33% 1/307 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days (Week 100) after the last dose of study drug At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Injury, poisoning and procedural complications Skin abrasion	0.33% 1/307 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days (Week 100) after the last dose of study drug At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Injury, poisoning and procedural complications Tibia fracture	0.33% 1/307 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days (Week 100) after the last dose of study drug At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Respiratory, thoracic and mediastinal disorders Tonsillar hypertrophy	0.33% 1/307 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days (Week 100) after the last dose of study drug At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Skin and subcutaneous tissue disorders Dermatitis allergic	0.33% 1/307 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days (Week 100) after the last dose of study drug At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.

Other adverse events

Measure	Leuprorelin n=307 participants at risk Participants with body weight greater than or equal to (\>=) 20 kilogram (kg) received the recommended initial dose of leuprorelin 3.75 milligram (mg), injection, subcutaneously, once every 4 weeks for 96 weeks. Participants with body weight less than (\<) 20 kg received leuprorelin 1.88 mg, injection, subcutaneously, once every 4 weeks for 96 weeks. The dose was adjusted based on participant's condition and investigator's judgment in alignment with the product label in China.
Infections and infestations Upper respiratory tract infection	38.4% 118/307 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days (Week 100) after the last dose of study drug At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Respiratory, thoracic and mediastinal disorders Cough	16.6% 51/307 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days (Week 100) after the last dose of study drug At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
General disorders Pyrexia	14.7% 45/307 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days (Week 100) after the last dose of study drug At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Infections and infestations Nasopharyngitis	11.4% 35/307 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days (Week 100) after the last dose of study drug At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Infections and infestations Bronchitis	11.1% 34/307 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days (Week 100) after the last dose of study drug At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Infections and infestations Tonsillitis	6.2% 19/307 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days (Week 100) after the last dose of study drug At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Infections and infestations Pharyngitis	5.2% 16/307 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days (Week 100) after the last dose of study drug At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.

Additional Information

Medical Director

Takeda

Phone: +1-877-825-3327

Email: trialdisclosures@takeda.com

Results disclosure agreements

• Principal investigator is a sponsor employee The first study related publication will be a multi-center publication submitted within 24 months after conclusion or termination of a study at all sites. After such multi site publication, all proposed site publications and presentations will be submitted to sponsor for review 60 days in advance of publication. Site will remove Sponsor confidential information unrelated to study results. Sponsor can delay a proposed publication for another 60 days to preserve intellectual property.
• Publication restrictions are in place

Restriction type: OTHER