A Study to Evaluate Leuprolide Acetate 45 mg 6-Month Form... | NCT03695237

Label	Type	Description	Intervention Names
Leuprolide Acetate (LA)	Experimental	Participants received leuprolide acetate (LA) 45 mg every 6 months administered as an intramuscular injection for up to 144 weeks.	Drug: Leuprolide Acetate (LA)

Name	Type	Description	Arm Group Labels	Other Names
Leuprolide Acetate (LA)	Drug	Administered intramuscularly as an injection	Leuprolide Acetate (LA)

Measure	Description	Time Frame
Percentage of Participants With Suppression of Peak Gonadotropin-releasing Hormone Agonist (GnRHa)-Stimulated Luteinizing Hormone (LH) to Less Than 4 mlU/mL at Week 24	Suppression of GnRHa-stimulated luteinizing hormone (LH) was measured using a peak GnRHa stimulation test, performed using subcutaneous injection with an aqueous formulation of leuprolide acetate at 20 µg/kg. Peak stimulated LH was calculated by taking the maximum LH concentrations measured from blood samples taken at 30 or 60 min following the GnRHa stimulation test. Suppression of GnRHa-stimulated luteinizing hormone is defined as peak stimulated LH less than 4 mIU/mL.	Week 24 (prior to the Week 24 dose); samples for LH measurement were taken 30 and 60 minutes after the stimulation test injection.

Measure	Description	Time Frame
Part 1: Percentage of Participants With Suppression of Peak GnRHa-stimulated LH to Less Than 4 mlU/mL at Weeks 12, 20, 44, and 48	Suppression of GnRHa-stimulated luteinizing hormone (LH) was measured using a peak GnRHa stimulation test, performed using subcutaneous injection with an aqueous formulation of leuprolide acetate at 20 µg/kg. Peak stimulated LH was calculated by taking the maximum LH concentrations measured from blood samples taken at 30 or 60 min following the GnRHa stimulation test. Suppression of GnRHa-stimulated luteinizing hormone is defined as peak stimulated LH less than 4 mIU/mL.

Name	Affiliation	Role
ABBVIE INC.	AbbVie	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Pediatric Endocrinology Associates /ID# 200629		Long Beach	California	90806-1651	United States
Rady Children's Hospital San Diego /ID# 202491

Label	URL
Related Info	View source

ID	Title	Description
FG000	Leuprolide Acetate - Previously Treated	Participants who had been previously treated with a GnRHa for at least 6 months prior to enrollment received leuprolide acetate (LA) 45 mg every 6 months administered as an intramuscular injection for up to 48 weeks in Part 1 and for up to an additional 96 weeks in Part 2.
FG001

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Aug 5, 2020	Apr 18, 2023

ID	Title	Description
BG000	Leuprolide Acetate - Previously Treated	Participants who had been previously treated with a GnRHa for at least 6 months prior to enrollment received leuprolide acetate (LA) 45 mg every 6 months administered as an intramuscular injection for up to 48 weeks in Part 1.
BG001	Leuprolide Acetate - Treament Naïve	Participants without previous GnRHa treatment prior to enrollment (treatment naïve) received leuprolide acetate 45 mg every 6 months administered as an intramuscular injection for up to 48 weeks in Part 1.
BG002	Total	Total of all reporting groups

Units	Counts
Participants	BG00018 BG00127 BG00245

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Percentage of Participants With Suppression of Peak Gonadotropin-releasing Hormone Agonist (GnRHa)-Stimulated Luteinizing Hormone (LH) to Less Than 4 mlU/mL at Week 24

Suppression of GnRHa-stimulated luteinizing hormone (LH) was measured using a peak GnRHa stimulation test, performed using subcutaneous injection with an aqueous formulation of leuprolide acetate at 20 µg/kg.

Peak stimulated LH was calculated by taking the maximum LH concentrations measured from blood samples taken at 30 or 60 min following the GnRHa stimulation test.

Suppression of GnRHa-stimulated luteinizing hormone is defined as peak stimulated LH less than 4 mIU/mL.

The Full Analysis Set (FAS) consists of all participants who received at least 1 dose of study drug. Participants with missing GnRHa-stimulated LH results at Week 24 were counted as not achieving suppression.

Posted

Number

95% Confidence Interval

percentage of participants

Week 24 (prior to the Week 24 dose); samples for LH measurement were taken 30 and 60 minutes after the stimulation test injection.

ID	Title	Description
OG000	Leuprolide Acetate - Previously Treated	Participants who had been previously treated with a GnRHa for at least 6 months prior to enrollment received leuprolide acetate 45 mg every 6 months administered as an intramuscular injection for up to 48 weeks in Part 1.
OG001	Leuprolide Acetate - Treament Naïve	Participants without previous GnRHa treatment prior to enrollment (treatment naïve) received leuprolide acetate 45 mg every 6 months administered as an intramuscular injection for up to 48 weeks in Part 1.
OG002	Leuprolide Acetate - Overall	Participants received leuprolide acetate 45 mg every 6 months administered as an intramuscular injection for up to 48 weeks in Part 1.

Units	Counts
Participants	OG00018 OG00127 OG00245

Title

Denominators

Categories

Title	Measurements
	OG00094.4(72.7 to 99.9) OG00181.5(61.9 to 93.7) OG00286.7(73.2 to 95.0)

Secondary

Part 1: Percentage of Participants With Suppression of Peak GnRHa-stimulated LH to Less Than 4 mlU/mL at Weeks 12, 20, 44, and 48

Peak stimulated LH was calculated by taking the maximum LH concentrations measured from blood samples taken at 30 or 60 min following the GnRHa stimulation test.

Suppression of GnRHa-stimulated luteinizing hormone is defined as peak stimulated LH less than 4 mIU/mL.

The Full Analysis Set (FAS) consists of all participants who received at least 1 dose of study drug. Participants with missing GnRHa-stimulated LH results at a specific visit were counted as not achieving suppression for that visit.

Posted

Number

95% Confidence Interval

percentage of participants

Weeks 12, 20, 44, and 48 (prior to Week 48 dose); samples for LH measurement were taken 30 and 60 minutes after the stimulation test injection.

ID	Title	Description
OG000	Leuprolide Acetate - Previously Treated	Participants who had been previously treated with a GnRHa for at least 6 months prior to enrollment received leuprolide acetate 45 mg every 6 months administered as an intramuscular injection for up to 48 weeks in Part 1.
OG001	Leuprolide Acetate - Treament Naïve	Participants without previous GnRHa treatment prior to enrollment (treatment naïve) received leuprolide acetate 45 mg every 6 months administered as an intramuscular injection for up to 48 weeks in Part 1.

Secondary

Part 1: Percentage of Female Participants With Suppression of Basal Estradiol to < 20 pg/mL at Weeks 12, 20, 24, 44, and 48

Estradiol concentrations were measured from blood samples taken at each study visit prior to stimulation testing (and prior to study drug administration at Weeks 24 and 48).

Full analysis set; female participants with available data at each time point

Posted

Number

95% Confidence Interval

percentage of participants

Weeks 12, 20, 24, 44, and 48

ID	Title	Description
OG000	Leuprolide Acetate - Previously Treated	Participants who had been previously treated with a GnRHa for at least 6 months prior to enrollment received leuprolide acetate 45 mg every 6 months administered as an intramuscular injection for up to 48 weeks in Part 1.
OG001	Leuprolide Acetate - Treament Naïve	Participants without previous GnRHa treatment prior to enrollment (treatment naïve) received leuprolide acetate 45 mg every 6 months administered as an intramuscular injection for up to 48 weeks in Part 1.
OG002	Leuprolide Acetate - Overall	Participants received leuprolide acetate 45 mg every 6 months administered as an intramuscular injection for up to 48 weeks in Part 1.

Secondary

Part 1: Percentage of Male Participants With Suppression of Basal Testosterone to < 30 ng/dL at Weeks 12, 20, 24, 44, and 48

Testosterone concentrations were measured from blood samples taken at each study visit prior to stimulation testing (and prior to study drug administration for Weeks 24 and 48).

Full analysis set; male participants with available data at each time point

Posted

Number

95% Confidence Interval

percentage of participants

Weeks 12, 20, 24, 44, and 48

ID	Title	Description
OG000	Leuprolide Acetate - Previously Treated	Participants who had been previously treated with a GnRHa for at least 6 months prior to enrollment received leuprolide acetate 45 mg every 6 months administered as an intramuscular injection for up to 48 weeks in Part 1.
OG001	Leuprolide Acetate - Treament Naïve	Participants without previous GnRHa treatment prior to enrollment (treatment naïve) received leuprolide acetate 45 mg every 6 months administered as an intramuscular injection for up to 48 weeks in Part 1.
OG002	Leuprolide Acetate - Overall	Participants received leuprolide acetate 45 mg every 6 months administered as an intramuscular injection for up to 48 weeks in Part 1.

Secondary

Parts 1 and 2: Percentage of Participants With Suppression of the Physical Signs of Puberty

Breast development in females and testicular volume or genital development in males was assessed using modified Tanner staging, on a scale from Stage 1 (prepubertal) to Stage 5 (adult characteristics).

Females: Suppression is defined as regression or no progression of breast development according to modified Tanner staging.

Males: Suppression is defined as regression or no progression in testicular volume and genital staging according to modified Tanner staging.

Full analysis set; results for males and females (with an assessment at each time point) are reported separately.

Posted

Number

percentage of participants

Part 1: Weeks 24 and 48; Part 2: Weeks 72, 96, 120, and 144

ID	Title	Description
OG000	Leuprolide Acetate - Previously Treated	Participants who had been previously treated with a GnRHa for at least 6 months prior to enrollment received leuprolide acetate 45 mg every 6 months administered as an intramuscular injection for up to 48 weeks in Part 1 and for up to an additional 96 weeks in Part 2.
OG001	Leuprolide Acetate - Treament Naïve	Participants without previous GnRHa treatment prior to enrollment (treatment naïve) received leuprolide acetate 45 mg every 6 months administered as an intramuscular injection for up to 48 weeks in Part 1 and for up to an additional 96 weeks in Part 2.

Secondary

Parts 1 and 2: Change From Baseline in Incremental Growth Rate

Growth rate (height in centimeter/year) was calculated both prior to treatment in the study and during the study. For Baseline calculation a historical measurement of height at least 6 months prior to Screening and the Screening value was used.

Full analysis set; participants with available data at Baseline (43 participants) and each time point.

Posted

Mean

Standard Deviation

cm/year

Part 1: Baseline and Weeks 4, 12, 20, 24, 44, and 48; Part 2: Weeks 72, 96, 120, and 144

ID	Title	Description
OG000	Leuprolide Acetate - Previously Treated	Participants who had been previously treated with a GnRHa for at least 6 months prior to enrollment received leuprolide acetate 45 mg every 6 months administered as an intramuscular injection for up to 48 weeks in Part 1 and for up to an additional 96 weeks in Part 2.
OG001	Leuprolide Acetate - Treament Naïve	Participants without previous GnRHa treatment prior to enrollment (treatment naïve) received leuprolide acetate 45 mg every 6 months administered as an intramuscular injection for up to 48 weeks in Part 1 and for up to an additional 96 weeks in Part 2.
OG002	Leuprolide Acetate - Overall

Secondary

Parts 1 and 2: Ratio of Change From Baseline in Bone Age to Change From Baseline in Chronological Age

Bone age was assessed from radiographs of the hand and wrist by a central imaging vendor using the BoneXpert automated system.

A ratio less than 1 indicates less advancement of bone age compared to chronological age.

Full analysis set; based on non missing observations.

Posted

Mean

Standard Deviation

ratio

Part 1: Baseline and Weeks 24 and 48; Part 2: Weeks 72, 96, 120, and 144

ID	Title	Description
OG000	Leuprolide Acetate - Previously Treated	Participants who had been previously treated with a GnRHa for at least 6 months prior to enrollment received leuprolide acetate 45 mg every 6 months administered as an intramuscular injection for up to 48 weeks in Part 1 and for up to an additional 96 weeks in Part 2.
OG001	Leuprolide Acetate - Treament Naïve	Participants without previous GnRHa treatment prior to enrollment (treatment naïve) received leuprolide acetate 45 mg every 6 months administered as an intramuscular injection for up to 48 weeks in Part 1 and for up to an additional 96 weeks in Part 2.
OG002	Leuprolide Acetate - Overall	Participants received leuprolide acetate 45 mg every 6 months administered as an intramuscular injection for up to 48 weeks in Part 1 and for up to an additional 96 weeks in Part 2.

Secondary

Part 2: Percentage of Participants With Maintenance of Suppression of GnRHa-stimulated LH (< 4 mlU/mL)

Peak stimulated LH was calculated by taking the maximum LH concentrations measured from blood samples taken at 30 or 60 min following the GnRHa stimulation test.

Suppression of GnRHa-stimulated luteinizing hormone is defined as peak stimulated LH less than 4 mIU/mL.

Full analysis set; observed cases.

Posted

Number

95% Confidence Interval

percentage of participants

Weeks 72, 96, 120, and 144

ID	Title	Description
OG000	Leuprolide Acetate - Previously Treated	Participants who had been previously treated with a GnRHa for at least 6 months prior to enrollment received leuprolide acetate 45 mg every 6 months administered as an intramuscular injection for up to 48 weeks in Part 1 and for up to an additional 96 weeks in Part 2.
OG001	Leuprolide Acetate - Treament Naïve	Participants without previous GnRHa treatment prior to enrollment (treatment naïve) received leuprolide acetate 45 mg every 6 months administered as an intramuscular injection for up to 48 weeks in Part 1 and for up to an additional 96 weeks in Part 2.
OG002

Secondary

Part 2: Percentage of Female Participants With Maintenance of Suppression of Basal Estradiol to < 20 pg/mL

Estradiol concentrations were measured from blood samples taken at each study visit prior to stimulation testing.

Full analysis set; participants with non-missing observations.

Posted

Number

95% Confidence Interval

percentage of participants

Weeks 72, 96, 120, and 144

ID	Title	Description
OG000	Leuprolide Acetate - Previously Treated	Participants who had been previously treated with a GnRHa for at least 6 months prior to enrollment received leuprolide acetate 45 mg every 6 months administered as an intramuscular injection for up to 48 weeks in Part 1 and for up to an additional 96 weeks in Part 2.
OG001	Leuprolide Acetate - Treament Naïve	Participants without previous GnRHa treatment prior to enrollment (treatment naïve) received leuprolide acetate 45 mg every 6 months administered as an intramuscular injection for up to 48 weeks in Part 1 and for up to an additional 96 weeks in Part 2.
OG002	Leuprolide Acetate - Overall	Participants received leuprolide acetate 45 mg every 6 months administered as an intramuscular injection for up to 48 weeks in Part 1 and for up to an additional 96 weeks in Part 2.

Secondary

Part 2: Percentage of Male Participants With Maintenance of Suppression of Basal Testosterone to < 30 ng/dL

Male participants with maintenance of suppression of testosterone to < 30 ng/dL are assessed

Full analysis set; participants with non-missing observations.

Posted

Number

95% Confidence Interval

percentage of participants

Weeks 72, 96, 120, and 144

ID	Title	Description
OG000	Leuprolide Acetate - Previously Treated	Participants who had been previously treated with a GnRHa for at least 6 months prior to enrollment received leuprolide acetate 45 mg every 6 months administered as an intramuscular injection for up to 48 weeks in Part 1 and for up to an additional 96 weeks in Part 2.
OG001	Leuprolide Acetate - Treament Naïve	Participants without previous GnRHa treatment prior to enrollment (treatment naïve) received leuprolide acetate 45 mg every 6 months administered as an intramuscular injection for up to 48 weeks in Part 1 and for up to an additional 96 weeks in Part 2.
OG002	Leuprolide Acetate - Overall	Participants received leuprolide acetate 45 mg every 6 months administered as an intramuscular injection for up to 48 weeks in Part 1 and for up to an additional 96 weeks in Part 2.

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
ANAEMIA	Blood and lymphatic system disorders	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected18 at risk EG0010 events0 affected27 at risk
IRON DEFICIENCY ANAEMIA	Blood and lymphatic system disorders	MedDRA 26.0	Systematic Assessment	EG0000 events0 affected18 at risk EG0012 events2 affected27 at risk
LYMPHADENOPATHY	Blood and lymphatic system disorders	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected18 at risk EG0010 events0 affected27 at risk
EAR PAIN	Ear and labyrinth disorders	MedDRA 26.0	Systematic Assessment	EG0002 events2 affected18 at risk EG0011 events1 affected27 at risk
EYE PAIN	Eye disorders	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected18 at risk EG0011 events1 affected27 at risk
PHOTOPSIA	Eye disorders	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected18 at risk EG0010 events0 affected27 at risk
ABDOMINAL PAIN	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected18 at risk EG0014 events3 affected27 at risk
ABDOMINAL PAIN LOWER	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment	EG0002 events2 affected18 at risk EG0010 events0 affected27 at risk
ABDOMINAL PAIN UPPER	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected18 at risk EG0016 events6 affected27 at risk
CONSTIPATION	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected18 at risk EG0011 events1 affected27 at risk
DIARRHOEA	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment	EG0002 events1 affected18 at risk EG0013 events3 affected27 at risk
HAEMATOCHEZIA	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected18 at risk EG0010 events0 affected27 at risk
LIP BLISTER	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment	EG0002 events1 affected18 at risk EG0010 events0 affected27 at risk
NAUSEA	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment	EG0002 events2 affected18 at risk EG0013 events3 affected27 at risk
ORAL PAIN	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected18 at risk EG0010 events0 affected27 at risk
TOOTH IMPACTED	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected18 at risk EG0010 events0 affected27 at risk
TOOTHACHE	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment	EG0000 events0 affected18 at risk EG0012 events2 affected27 at risk
VOMITING	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment	EG0003 events3 affected18 at risk EG0015 events3 affected27 at risk
CHEST PAIN	General disorders	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected18 at risk EG0011 events1 affected27 at risk
CRYING	General disorders	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected18 at risk EG0014 events4 affected27 at risk
FATIGUE	General disorders	MedDRA 26.0	Systematic Assessment	EG0003 events3 affected18 at risk EG0010 events0 affected27 at risk
FEELING HOT	General disorders	MedDRA 26.0	Systematic Assessment	EG0002 events2 affected18 at risk EG0011 events1 affected27 at risk
GAIT DISTURBANCE	General disorders	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected18 at risk EG0013 events2 affected27 at risk
INJECTED LIMB MOBILITY DECREASED	General disorders	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected18 at risk EG0010 events0 affected27 at risk
INJECTION SITE BRUISING	General disorders	MedDRA 26.0	Systematic Assessment	EG0002 events2 affected18 at risk EG0010 events0 affected27 at risk
INJECTION SITE DISCOMFORT	General disorders	MedDRA 26.0	Systematic Assessment	EG0002 events1 affected18 at risk EG0010 events0 affected27 at risk
INJECTION SITE ERYTHEMA	General disorders	MedDRA 26.0	Systematic Assessment	EG0003 events3 affected18 at risk EG0014 events4 affected27 at risk
INJECTION SITE PAIN	General disorders	MedDRA 26.0	Systematic Assessment	EG00039 events16 affected18 at risk EG00194 events26 affected27 at risk
INJECTION SITE PRURITUS	General disorders	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected18 at risk EG0010 events0 affected27 at risk
INJECTION SITE REACTION	General disorders	MedDRA 26.0	Systematic Assessment	EG0006 events4 affected18 at risk EG00118 events9 affected27 at risk
INJECTION SITE SWELLING	General disorders	MedDRA 26.0	Systematic Assessment	EG0005 events3 affected18 at risk EG0012 events1 affected27 at risk
INJECTION SITE WARMTH	General disorders	MedDRA 26.0	Systematic Assessment	EG0003 events3 affected18 at risk EG0013 events3 affected27 at risk
MALAISE	General disorders	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected18 at risk EG0010 events0 affected27 at risk
MEDICAL DEVICE PAIN	General disorders	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected18 at risk EG0010 events0 affected27 at risk
PAIN	General disorders	MedDRA 26.0	Systematic Assessment	EG0009 events5 affected18 at risk EG0017 events5 affected27 at risk
PYREXIA	General disorders	MedDRA 26.0	Systematic Assessment	EG0006 events6 affected18 at risk EG0016 events5 affected27 at risk
SWELLING	General disorders	MedDRA 26.0	Systematic Assessment	EG0003 events1 affected18 at risk EG0012 events2 affected27 at risk
TENDERNESS	General disorders	MedDRA 26.0	Systematic Assessment	EG0002 events2 affected18 at risk EG0013 events1 affected27 at risk
MULTIPLE ALLERGIES	Immune system disorders	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected18 at risk EG0012 events2 affected27 at risk
SEASONAL ALLERGY	Immune system disorders	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected18 at risk EG0012 events2 affected27 at risk
COVID-19	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0003 events3 affected18 at risk EG00110 events9 affected27 at risk
GASTROENTERITIS	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0003 events3 affected18 at risk EG0012 events2 affected27 at risk
GASTROENTERITIS VIRAL	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected18 at risk EG0011 events1 affected27 at risk
INFLUENZA	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0005 events4 affected18 at risk EG0013 events3 affected27 at risk
LICE INFESTATION	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected18 at risk EG0010 events0 affected27 at risk
NASOPHARYNGITIS	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0006 events4 affected18 at risk EG0017 events3 affected27 at risk
OTITIS EXTERNA	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected18 at risk EG0010 events0 affected27 at risk
PHARYNGITIS STREPTOCOCCAL	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0002 events2 affected18 at risk EG0016 events4 affected27 at risk
SINUSITIS	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected18 at risk EG0014 events3 affected27 at risk
TINEA VERSICOLOUR	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected18 at risk EG0011 events1 affected27 at risk
UPPER RESPIRATORY TRACT INFECTION	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0005 events5 affected18 at risk EG0018 events7 affected27 at risk
VIRAL UPPER RESPIRATORY TRACT INFECTION	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0000 events0 affected18 at risk EG0013 events2 affected27 at risk
CONTUSION	Injury, poisoning and procedural complications	MedDRA 26.0	Systematic Assessment	EG0002 events2 affected18 at risk EG0010 events0 affected27 at risk
FALL	Injury, poisoning and procedural complications	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected18 at risk EG0010 events0 affected27 at risk
FOOT FRACTURE	Injury, poisoning and procedural complications	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected18 at risk EG0010 events0 affected27 at risk
FRACTURED COCCYX	Injury, poisoning and procedural complications	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected18 at risk EG0010 events0 affected27 at risk
HAND FRACTURE	Injury, poisoning and procedural complications	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected18 at risk EG0010 events0 affected27 at risk
HUMAN BITE	Injury, poisoning and procedural complications	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected18 at risk EG0010 events0 affected27 at risk
LIGAMENT SPRAIN	Injury, poisoning and procedural complications	MedDRA 26.0	Systematic Assessment	EG0003 events3 affected18 at risk EG0013 events2 affected27 at risk
MUSCLE STRAIN	Injury, poisoning and procedural complications	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected18 at risk EG0011 events1 affected27 at risk
NAIL INJURY	Injury, poisoning and procedural complications	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected18 at risk EG0010 events0 affected27 at risk
TIBIA FRACTURE	Injury, poisoning and procedural complications	MedDRA 26.0	Systematic Assessment	EG0003 events3 affected18 at risk EG0010 events0 affected27 at risk
WEIGHT INCREASED	Investigations	MedDRA 26.0	Systematic Assessment	EG0002 events2 affected18 at risk EG0010 events0 affected27 at risk
ABNORMAL WEIGHT GAIN	Metabolism and nutrition disorders	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected18 at risk EG0012 events2 affected27 at risk
IRON DEFICIENCY	Metabolism and nutrition disorders	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected18 at risk EG0010 events0 affected27 at risk
ARTHRALGIA	Musculoskeletal and connective tissue disorders	MedDRA 26.0	Systematic Assessment	EG0000 events0 affected18 at risk EG0013 events2 affected27 at risk
BACK PAIN	Musculoskeletal and connective tissue disorders	MedDRA 26.0	Systematic Assessment	EG0003 events3 affected18 at risk EG0011 events1 affected27 at risk
JOINT RANGE OF MOTION DECREASED	Musculoskeletal and connective tissue disorders	MedDRA 26.0	Systematic Assessment	EG0000 events0 affected18 at risk EG0012 events2 affected27 at risk
KNEE DEFORMITY	Musculoskeletal and connective tissue disorders	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected18 at risk EG0010 events0 affected27 at risk
MYALGIA	Musculoskeletal and connective tissue disorders	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected18 at risk EG0014 events3 affected27 at risk
PAIN IN EXTREMITY	Musculoskeletal and connective tissue disorders	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected18 at risk EG0014 events4 affected27 at risk
CLUSTER HEADACHE	Nervous system disorders	MedDRA 26.0	Systematic Assessment	EG0003 events1 affected18 at risk EG0010 events0 affected27 at risk
DIZZINESS	Nervous system disorders	MedDRA 26.0	Systematic Assessment	EG0000 events0 affected18 at risk EG0012 events2 affected27 at risk
HEADACHE	Nervous system disorders	MedDRA 26.0	Systematic Assessment	EG00014 events9 affected18 at risk EG00120 events9 affected27 at risk
AFFECTIVE DISORDER	Psychiatric disorders	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected18 at risk EG0010 events0 affected27 at risk
AGGRESSION	Psychiatric disorders	MedDRA 26.0	Systematic Assessment	EG0000 events0 affected18 at risk EG0012 events2 affected27 at risk
ANGER	Psychiatric disorders	MedDRA 26.0	Systematic Assessment	EG0000 events0 affected18 at risk EG0015 events3 affected27 at risk
ANXIETY	Psychiatric disorders	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected18 at risk EG0011 events1 affected27 at risk
ATTENTION DEFICIT HYPERACTIVITY DISORDER	Psychiatric disorders	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected18 at risk EG0011 events1 affected27 at risk
DEPRESSED MOOD	Psychiatric disorders	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected18 at risk EG0010 events0 affected27 at risk
EMOTIONAL DISORDER	Psychiatric disorders	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected18 at risk EG0017 events5 affected27 at risk
HALLUCINATION, AUDITORY	Psychiatric disorders	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected18 at risk EG0010 events0 affected27 at risk
INITIAL INSOMNIA	Psychiatric disorders	MedDRA 26.0	Systematic Assessment	EG0000 events0 affected18 at risk EG0012 events2 affected27 at risk
INSOMNIA	Psychiatric disorders	MedDRA 26.0	Systematic Assessment	EG0002 events2 affected18 at risk EG0011 events1 affected27 at risk
IRRITABILITY	Psychiatric disorders	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected18 at risk EG0012 events2 affected27 at risk
MOOD ALTERED	Psychiatric disorders	MedDRA 26.0	Systematic Assessment	EG0003 events1 affected18 at risk EG0017 events5 affected27 at risk
MOOD SWINGS	Psychiatric disorders	MedDRA 26.0	Systematic Assessment	EG0000 events0 affected18 at risk EG0012 events2 affected27 at risk
TEARFULNESS	Psychiatric disorders	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected18 at risk EG0010 events0 affected27 at risk
BREAST PAIN	Reproductive system and breast disorders	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected18 at risk EG0011 events1 affected27 at risk
BREAST TENDERNESS	Reproductive system and breast disorders	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected18 at risk EG0012 events1 affected27 at risk
NIPPLE PAIN	Reproductive system and breast disorders	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected18 at risk EG0010 events0 affected27 at risk
VAGINAL DISCHARGE	Reproductive system and breast disorders	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected18 at risk EG0011 events1 affected27 at risk
VAGINAL HAEMORRHAGE	Reproductive system and breast disorders	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected18 at risk EG0011 events1 affected27 at risk
VULVOVAGINAL DISCOMFORT	Reproductive system and breast disorders	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected18 at risk EG0010 events0 affected27 at risk
VULVOVAGINAL PRURITUS	Reproductive system and breast disorders	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected18 at risk EG0011 events1 affected27 at risk
BRONCHOSPASM	Respiratory, thoracic and mediastinal disorders	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected18 at risk EG0010 events0 affected27 at risk
COUGH	Respiratory, thoracic and mediastinal disorders	MedDRA 26.0	Systematic Assessment	EG0005 events3 affected18 at risk EG0017 events6 affected27 at risk
DYSPNOEA	Respiratory, thoracic and mediastinal disorders	MedDRA 26.0	Systematic Assessment	EG0000 events0 affected18 at risk EG0012 events2 affected27 at risk
NASAL CONGESTION	Respiratory, thoracic and mediastinal disorders	MedDRA 26.0	Systematic Assessment	EG0002 events2 affected18 at risk EG0013 events2 affected27 at risk
OROPHARYNGEAL PAIN	Respiratory, thoracic and mediastinal disorders	MedDRA 26.0	Systematic Assessment	EG0006 events5 affected18 at risk EG0013 events3 affected27 at risk
RHINORRHOEA	Respiratory, thoracic and mediastinal disorders	MedDRA 26.0	Systematic Assessment	EG0004 events2 affected18 at risk EG0013 events3 affected27 at risk
SINUS CONGESTION	Respiratory, thoracic and mediastinal disorders	MedDRA 26.0	Systematic Assessment	EG0000 events0 affected18 at risk EG0012 events2 affected27 at risk
SNEEZING	Respiratory, thoracic and mediastinal disorders	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected18 at risk EG0010 events0 affected27 at risk
WHEEZING	Respiratory, thoracic and mediastinal disorders	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected18 at risk EG0010 events0 affected27 at risk
ACNE	Skin and subcutaneous tissue disorders	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected18 at risk EG0010 events0 affected27 at risk
ECZEMA	Skin and subcutaneous tissue disorders	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected18 at risk EG0010 events0 affected27 at risk
ERYTHEMA	Skin and subcutaneous tissue disorders	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected18 at risk EG0013 events2 affected27 at risk
HYPERHIDROSIS	Skin and subcutaneous tissue disorders	MedDRA 26.0	Systematic Assessment	EG0000 events0 affected18 at risk EG0012 events2 affected27 at risk
PRURITUS	Skin and subcutaneous tissue disorders	MedDRA 26.0	Systematic Assessment	EG0000 events0 affected18 at risk EG0013 events3 affected27 at risk
RASH	Skin and subcutaneous tissue disorders	MedDRA 26.0	Systematic Assessment	EG0003 events2 affected18 at risk EG0013 events3 affected27 at risk
SKIN ODOUR ABNORMAL	Skin and subcutaneous tissue disorders	MedDRA 26.0	Systematic Assessment	EG0000 events0 affected18 at risk EG0012 events2 affected27 at risk
HOT FLUSH	Vascular disorders	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected18 at risk EG0010 events0 affected27 at risk

ID	Term
D006058	Gonadal Disorders
D004700	Endocrine System Diseases

ID	Term
D007987	Gonadotropin-Releasing Hormone
D010906	Pituitary Hormone-Releasing Hormones
D007028	Hypothalamic Hormones
D036361	Peptide Hormones
D006728	Hormones
D006730	Hormones, Hormone Substitutes, and Hormone Antagonists
D009479	Neuropeptides
D010455	Peptides
D000602	Amino Acids, Peptides, and Proteins
D009842	Oligopeptides
D009419	Nerve Tissue Proteins
D011506	Proteins

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Leuprolide Acetate - Previously Treated	Participants who had been previously treated with a GnRHa for at least 6 months prior to enrollment received leuprolide acetate (LA) 45 mg every 6 months administered as an intramuscular injection for up to 48 weeks in Part 1 and for up to an additional 96 weeks in Part 2.	0	18	0	18	18	18
EG001	Leuprolide Acetate - Treament Naïve	Participants without previous GnRHa treatment prior to enrollment (treatment naïve) received leuprolide acetate 45 mg every 6 months administered as an intramuscular injection for up to 48 weeks in Part 1 and for up to an additional 96 weeks in Part 2.	0	27	1	27	27	27