Trial Outcomes & Findings for Efficacy and Safety of Leuprolide Acetate 22.5 mg Depot in Treatment of Prostate Cancer (NCT NCT01415960)
NCT ID: NCT01415960
Last Updated: 2017-03-03
Results Overview
The primary endpoint was testosterone ≤ 0.5 ng/mL assessed on Days 28, 84, and 168. Thereby, maintenance of castration was to be demonstrated through Day 168 with no missing data at these key time points, unless the missing data were due to an event unrelated to the study drug (ITT patients).
COMPLETED
PHASE3
163 participants
168 days
2017-03-03
Participant Flow
Participant milestones
| Measure |
Leuprolide Acetate 22.5 mg Depot
Leuprolide acetate 22.5 mg depot administered twice, 3 months apart
Leuprolide acetate 22.5 mg depot, GP-Pharm SA: Administered by im injection, twice during the study, three months apart
|
|---|---|
|
Overall Study
STARTED
|
163
|
|
Overall Study
ITT
|
161
|
|
Overall Study
PK Subgroup
|
30
|
|
Overall Study
COMPLETED
|
151
|
|
Overall Study
NOT COMPLETED
|
12
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Efficacy and Safety of Leuprolide Acetate 22.5 mg Depot in Treatment of Prostate Cancer
Baseline characteristics by cohort
| Measure |
Leuprolide Acetate 22.5 mg Depot
n=161 Participants
Leuprolide acetate 22.5 mg depot administered twice, 3 months apart
Leuprolide acetate 22.5 mg depot, GP-Pharm SA: Administered by im injection, twice during the study, three months apart
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=93 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
42 Participants
n=93 Participants
|
|
Age, Categorical
>=65 years
|
119 Participants
n=93 Participants
|
|
Age, Continuous
|
71 years
STANDARD_DEVIATION 9.02 • n=93 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=93 Participants
|
|
Sex: Female, Male
Male
|
161 Participants
n=93 Participants
|
|
Region of Enrollment
United States
|
161 participants
n=93 Participants
|
PRIMARY outcome
Timeframe: 168 daysThe primary endpoint was testosterone ≤ 0.5 ng/mL assessed on Days 28, 84, and 168. Thereby, maintenance of castration was to be demonstrated through Day 168 with no missing data at these key time points, unless the missing data were due to an event unrelated to the study drug (ITT patients).
Outcome measures
| Measure |
Leuprolide Acetate 22.5 mg Depot
n=161 Participants
Leuprolide acetate 22.5 mg depot administered twice, 3 months apart.
Leuprolide acetate 22.5 mg depot, GP-Pharm SA: Administered by im (intramuscular) injection, twice during the study, three months apart.
|
|---|---|
|
Percentage of Participants Achieving Chemical Castration (Defined as Testosterone Levels ≤ 0.5 ng/mL) at Days 28, 84, and 168.
|
98.1 percentage of participants
Interval 94.7 to 99.6
|
SECONDARY outcome
Timeframe: 168 daysFor purposes of calculating summary statistics, any concentration values Below Limit of Quantification (BLQ) were to be assigned ½ the Low Limit of Quantification (LLOQ) (LLOQ=2.00). If the calculated mean, median or minimum value at a time point was less than LLOQ, "BLQ" is presented. In addition, since a high proportion of BLQ values may affect the Standard Deviation (SD); if more than 50% of values were imputed, then no mean or median was calculated for that time point.
Outcome measures
| Measure |
Leuprolide Acetate 22.5 mg Depot
n=161 Participants
Leuprolide acetate 22.5 mg depot administered twice, 3 months apart.
Leuprolide acetate 22.5 mg depot, GP-Pharm SA: Administered by im (intramuscular) injection, twice during the study, three months apart.
|
|---|---|
|
Determination of Serum Luteinizing Hormone (LH)
Baseline
|
7.24 mIU/mL
Standard Deviation 6.48
|
|
Determination of Serum Luteinizing Hormone (LH)
Day 28
|
1 mIU/mL
Standard Deviation 2.79
|
|
Determination of Serum Luteinizing Hormone (LH)
Day 168
|
1 mIU/mL
Standard Deviation 0.92
|
SECONDARY outcome
Timeframe: 168 daysFor purposes of calculating summary statistics, any concentration values Below Limit of Quantification (BLQ) were to be assigned ½ the Low Limit of Quantification (LLOQ) (LLOQ=3.66). If the calculated mean, median or minimum value at a time point was less than LLOQ, "BLQ" is presented. In addition, since a high proportion of BLQ values may affect the Standard Deviation (SD); if more than 50% of values were imputed, then no mean or median was to be calculated for that time point.
Outcome measures
| Measure |
Leuprolide Acetate 22.5 mg Depot
n=161 Participants
Leuprolide acetate 22.5 mg depot administered twice, 3 months apart.
Leuprolide acetate 22.5 mg depot, GP-Pharm SA: Administered by im (intramuscular) injection, twice during the study, three months apart.
|
|---|---|
|
Follicle-stimulating Hormone (FSH)
Baseline
|
15.14 mIU/mL
Standard Deviation 13.46
|
|
Follicle-stimulating Hormone (FSH)
Day 28
|
1 mIU/mL
Standard Deviation 1.44
|
|
Follicle-stimulating Hormone (FSH)
Day 168
|
5.80 mIU/mL
Standard Deviation 3.62
|
SECONDARY outcome
Timeframe: 168 daysFor purposes of calculating summary statistics, any concentration values Below Limit Quantification (BLQ) were to be assigned ½ the Low Limit Quantification (LLOQ) (LLOQ=0.36). If the calculated mean, median or minimum value at a time point was less than LLOQ, "BLQ" is presented. In addition, since a high proportion of BLQ values may affect the Standard Deviation (SD); if more than 50% of values were imputed, then no mean or median was calculated for that time point.
Outcome measures
| Measure |
Leuprolide Acetate 22.5 mg Depot
n=161 Participants
Leuprolide acetate 22.5 mg depot administered twice, 3 months apart.
Leuprolide acetate 22.5 mg depot, GP-Pharm SA: Administered by im (intramuscular) injection, twice during the study, three months apart.
|
|---|---|
|
Prostate-specific Antigen (PSA) Concentrations
Baseline
|
44.36 ng/mL
Standard Deviation 165.81
|
|
Prostate-specific Antigen (PSA) Concentrations
Day 168
|
2.37 ng/mL
Standard Deviation 10.30
|
SECONDARY outcome
Timeframe: Cmax1: 0, 1 and 4 hours post-dose on Day 0 and once on Days 2, 14, 28, 56; Cmax2: 0, 1 and 4 hours post-dose on Day 84 and once on Days 86, 112 and 168.Leuprolide Pharmacokinetic Parameters (PK Population).
Outcome measures
| Measure |
Leuprolide Acetate 22.5 mg Depot
n=30 Participants
Leuprolide acetate 22.5 mg depot administered twice, 3 months apart.
Leuprolide acetate 22.5 mg depot, GP-Pharm SA: Administered by im (intramuscular) injection, twice during the study, three months apart.
|
|---|---|
|
Determination of Leuprolide Cmax
Day 0/Dose 1 Cmax
|
46.79 ng/mL
Standard Deviation 18.008
|
|
Determination of Leuprolide Cmax
Day 84/Dose 2 Cmax
|
48.30 ng/mL
Standard Deviation 18.557
|
SECONDARY outcome
Timeframe: 168 DaysPopulation: Safety endpoints adverse events (AEs), local tolerability, vital signs, performance status, bone pain, urinary pain, and urinary symptoms, occurrence of hot flushes and clinical laboratory and electrocardiogram (ECG) results.
The WHO/ECOG, bone pain, urinary pain and urinary symptoms data reported are the most frequent percentage at the assessment time. * The WHO/ECOG performance status was summarized using the 0 to 4 WHO/ECOG performance status scale. (0= fully active, able to carry on all pre-disease performances without restriction). * Bone pain, urinary pain and urinary symptoms were determined using a 10-point scale (1= no pain/symptoms, 10= worst pain/symptom imaginable).
Outcome measures
| Measure |
Leuprolide Acetate 22.5 mg Depot
n=161 Participants
Leuprolide acetate 22.5 mg depot administered twice, 3 months apart.
Leuprolide acetate 22.5 mg depot, GP-Pharm SA: Administered by im (intramuscular) injection, twice during the study, three months apart.
|
|---|---|
|
Safety Endpoints
Baseline WHO/ECOG Score 0 (n=161)
|
83.9 percentage of participants
|
|
Safety Endpoints
Day 168 WHO/ECOG Scores 0 (n=152)
|
82.9 percentage of participants
|
|
Safety Endpoints
Baseline Bone Pain score 1 (n=161)
|
95.0 percentage of participants
|
|
Safety Endpoints
Day 168 Bone Pain score 1 (n=152)
|
94.1 percentage of participants
|
|
Safety Endpoints
Baseline Urinary Pain score 1 (n=161)
|
98.8 percentage of participants
|
|
Safety Endpoints
Day 168 Urinary Pain Score 1 (n=152)
|
97.4 percentage of participants
|
|
Safety Endpoints
Baseline Urinary Symptoms score 1 (n=161)
|
87.6 percentage of participants
|
|
Safety Endpoints
Day 168 Urinary Symptoms score 1 (n=152)
|
89.5 percentage of participants
|
SECONDARY outcome
Timeframe: 84 daysLeuprolide Pharmacokinetic Parameters (PK Population).
Outcome measures
| Measure |
Leuprolide Acetate 22.5 mg Depot
n=30 Participants
Leuprolide acetate 22.5 mg depot administered twice, 3 months apart.
Leuprolide acetate 22.5 mg depot, GP-Pharm SA: Administered by im (intramuscular) injection, twice during the study, three months apart.
|
|---|---|
|
Determination of Leuprolide Tmax
Day 0/Dose 1 Tmax
|
0.07 day
Standard Deviation 0.051
|
|
Determination of Leuprolide Tmax
Day 84/Dose 2 Tmax
|
0.08 day
Standard Deviation 0.056
|
Adverse Events
Leuprolide Acetate 22.5 mg Depot
Serious adverse events
| Measure |
Leuprolide Acetate 22.5 mg Depot
n=163 participants at risk
Leuprolide acetate 22.5 mg depot administered twice, 3 months apart
Leuprolide acetate 22.5 mg depot, GP-Pharm SA: Administered by im injection, twice during the study, three months apart
|
|---|---|
|
Cardiac disorders
CONGESTIVE HEART FAILURE
|
0.61%
1/163
|
|
Cardiac disorders
MYOCARDIAL INFARCTION
|
0.61%
1/163
|
|
Gastrointestinal disorders
DIARRHEA
|
0.61%
1/163
|
|
Gastrointestinal disorders
INCARCERATED INGUINAL HERNIA
|
0.61%
1/163
|
|
Gastrointestinal disorders
RECTAL BLEEDING
|
0.61%
1/163
|
|
General disorders
NON-CARDIAC CHEST PAIN
|
0.61%
1/163
|
|
Infections and infestations
PNEUMONIA
|
0.61%
1/163
|
|
Injury, poisoning and procedural complications
FALL
|
0.61%
1/163
|
|
Metabolism and nutrition disorders
DEHYDRATION
|
0.61%
1/163
|
|
Metabolism and nutrition disorders
DIABETIC KETOACIDOSIS
|
0.61%
1/163
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
BENIGN NEOPLASM OF BLADDER
|
0.61%
1/163
|
|
Nervous system disorders
SYNCOPE
|
1.8%
3/163
|
Other adverse events
| Measure |
Leuprolide Acetate 22.5 mg Depot
n=163 participants at risk
Leuprolide acetate 22.5 mg depot administered twice, 3 months apart
Leuprolide acetate 22.5 mg depot, GP-Pharm SA: Administered by im injection, twice during the study, three months apart
|
|---|---|
|
General disorders
TEAE Related Injection site pain
|
9.2%
15/163 • Number of events 16
|
|
General disorders
TEAE Related Fatigue
|
9.8%
16/163 • Number of events 19
|
|
Vascular disorders
TEAE Related Hot Flushes
|
77.3%
126/163 • Number of events 146
|
Additional Information
Dr. Neal Shore MD
Grand Strand Urology Carolina Urology Reseearch Centre
Results disclosure agreements
- Principal investigator is a sponsor employee All information from the trial is property of the Sponsor and the PI has no right on it except the prior writing authorization of the sponsor
- Publication restrictions are in place
Restriction type: OTHER