Efficacy and Safety of Degarelix One Month Dosing Regimen in Korean Patients With Prostate Cancer

• Sponsor: Ferring Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01071915
• Collaborator: Ferring Pharmaceuticals Korea, Ltd. (Other)
• Enrollment: 157
• Locations: 11
• Arm: 1
• Duration (Months): 20
• Patients Per Site: 14.3
• Patients Per Site Per Month: 0.7

Study Details

Study Description

Brief Summary

This is an open-label, multi-centre single arm trial to investigate efficacy and safety of degarelix in Korean patients with prostate cancer for bridging between CS21 trial (NCT00295750) results.

Condition or Disease	Intervention/Treatment	Phase
Prostate Cancer	Drug: Degarelix 240/80 mg	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 157 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-label, Multi-Centre Trial, Bridging Efficacy and Safety of Degarelix One-Month Dosing Regimen in Korean Patients With Prostate Cancer Requiring Androgen Ablation Therapy
• Study Start Date: Mar 1, 2010
• Actual Primary Completion Date: Nov 1, 2011
• Actual Study Completion Date: Nov 1, 2011

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Degarelix 240/80 mg The degarelix doses were administered into the abdominal wall every 28 days. A starting dose of 240 mg (40 mg/mL) degarelix was administered on Day 0 as two 3 mL subcutaneous (s.c.) injections. The subsequent maintenace of 80 mg (20 mg/mL) degarelix were administered as single 4 mL s.c. injections at 28 day intervals from day 28 to day 168.

Drug: Degarelix 240/80 mg; The degarelix doses were administered into the abdominal wall every 28 days. A starting dose of 240 mg (40 mg/mL) degarelix was administered on Day 0 as two 3 mL subcutaneous (s.c.) injections. The subsequent maintenance doses of 80 mg (20 mg/mL) degarelix were administered as single 4 mL s.c. injections at 28 day intervals from day 28 to day 168.; Other Names: FE200486 FIRMAGON

Outcome Measures

Primary Outcome Measures

1. Cumulative Probability of Testosterone at Castrate Level (≤0.5 ng/mL) From Day 28 to Day 196 [Day 28 to Day 196]

Secondary Outcome Measures

1. Proportion of Patients With Testosterone Level ≤0.5 ng/mL at Day 3 [At day 3]

2. Percentage Change in Prostate-specific Antigen (PSA) From Baseline to Day 28 [To Day 28]

3. Cumulative Probability of Testosterone at Castrate Level (≤0.5 ng/mL)From Day 56 to Day 196 [Day 56 to Day 196]

4. Cumulative Probability of no PSA Failure From Day 28 to Day 196 [To Day 196]

   PSA failure was defined as two consecutive increases of 50%, and at least 5 ng/mL, compared to nadir.

5. Number of Participants With Markedly Abnormal Values in Safety Laboratory Variables [To Day 196]

   The figures present the number of participants who had markedly abnormal levels of safety laboratory variables. Only the laboratory variables that had at least one percentage of participants in either group with abnormal value are presented, more variables were included in the study.

6. Number of Participants With Markedly Abnormal Values in Vital Signs and Body Weight [To Day 196]

   This outcome measure included incidence of markedly abnormal changes in blood pressure (systolic and diastolic), pulse, and body weight. The table presents the number of participants with normal baseline and at least one post-baseline markedly abnormal value.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Has given written informed consent before any trial-related activity is performed.

• Has a histologically confirmed (Gleason graded) adenocarcinoma of the prostate (all stages) (except for neoadjuvant hormonal therapy/ includes patients with rising PSA after prostatectomy or radiotherapy)

• Is a male patient aged 18 years or older

• Has a screening serum testosterone level >1.5 ng/mL

• Has an ECOG (Eastern Cooperative Oncology Group) score of ≤ 2

• Has a screening PSA value of ≥2 ng/mL

• Has a life expectancy of at least 12 months

Exclusion Criteria:

• Has had previous or is currently under hormonal management of prostate cancer. However, prostatectomy or radiotherapy with curative intention, neoadjuvant/adjuvant hormonal therapy are accepted for a maximum duration of 6 months, at least 6 months prior to Screening Visit

• Is currently treated with a 5-α-reductase inhibitor

• Is considered to be candidate for curative therapy, i.e. radical prostatectomy or radiotherapy

• Has a history of severe untreated asthma, anaphylactic reactions or severe urticaria and/or angioedema

• Has hypersensitivity towards any component of the investigational medicinal product

• A marked baseline prolongation of QT/QTcF interval

• A history of additional risk factors for Torsade de Pointes ventricular arrhythmias

• Has had cancer within the last five years except prostate cancer and surgically removed basal or squamous cell carcinoma of the skin

• Has a known or suspect hepatic, symptomatic biliary disease

• Has elevated serum ALT level more than the upper limit of normal or serum total bilirubin level above the upper level of normal range at the Screening Visit and confirmed with a second measurement within 21 days

• Has other clinically significant laboratory abnormalities

• Has a clinically significant disorder (other than prostate cancer) or any other condition, including alcohol or drug abuse

• Has a mental incapacity or language barriers precluding adequate understanding or co- operation

• Has received an investigational drug within the last 28 days preceding Screening Visit or longer if considered to possibly influence the outcome of the current trial

• Has previously participated in any degarelix trial

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hallym University Sacred Heart Hospital	Pyungchon	Gyunggi-do	Korea, Republic of
2	Pusan National University Yangsan Hospital	Mulgeum-eup	Gyungnam	Korea, Republic of
3	Kyoungbuk National University Hospital	Daegu		Korea, Republic of
4	Seoul National University Bundang Hospital	Seongnam		Korea, Republic of
5	Asan Medical Center	Seoul		Korea, Republic of
6	Korea University Hospital	Seoul		Korea, Republic of
7	Samsung Medical Center	Seoul		Korea, Republic of
8	Seoul National University Hospital	Seoul		Korea, Republic of
9	Seoul St. Mary's Hospital	Seoul		Korea, Republic of
10	Yonsei University Health System (Sevrance Hospital)	Seoul		Korea, Republic of
11	Yonsei University Health System Gangnam Sevrance	Seoul		Korea, Republic of

Sponsors and Collaborators

• Ferring Pharmaceuticals
• Ferring Pharmaceuticals Korea, Ltd.

Investigators

• Study Director: Clinical Development Support, Ferring Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Ferring Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT01071915
• Other Study ID Numbers: FE200486 CS42
• First Posted: Feb 19, 2010
• Last Update Posted: Feb 12, 2013
• Last Verified: Jan 1, 2013

• Additional relevant MeSH terms: Prostatic Neoplasms

Study Results

Participant Flow

Recruitment Details	The patients were recruited from 11 sites in Korea. The study was conducted between 08 March 2010 (FPFV) and 07 November 2011 (LPLV).

Arm/Group Title	Degarelix 240/80 mg
Arm/Group Description	The degarelix doses were administered into the abdominal wall every 28 days. A starting dose of 240 mg (40 mg/mL) degarelix was administered on Day 0 as two 3 mL subcutaneous (s.c.) injections. The subsequent maintenace of 80 mg (20 mg/mL) degarelix were administered as single 4 mL s.c. injections at 28 day intervals from day 28 to day 168.
Period Title: Overall Study
STARTED	157
Full Analysis Set (FAS)	155
Safety Analysis Set	156
COMPLETED	148
NOT COMPLETED	9

Baseline Characteristics

Arm/Group Title	Degarelix 240/80 mg
Arm/Group Description	The degarelix doses were administered into the abdominal wall every 28 days. A starting dose of 240 mg (40 mg/mL) degarelix was administered on Day 0 as two 3 mL subcutaneous (s.c.) injections. The subsequent maintenace of 80 mg (20 mg/mL) degarelix were administered as single 4 mL s.c. injections at 28 day intervals from day 28 to day 168.
Overall Participants	155
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	72.6 (8.08)
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	155 100%
Region of Enrollment (participants) [Number]
Korea, Republic of	155 100%
Body Mass Index (BMI) (kilogram per square meter) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kilogram per square meter]	23.8 (2.98)
Gleason Score (Number) [Number]
Gleason Score 2-4	0 0%
Gleason Score 5-6	24 15.5%
Gleason Score 7-10	130 83.9%
Stage of Prostate Cancer (Number) [Number]
Localized	43 27.7%
Locally Advanced	60 38.7%
Metastatic	39 25.2%
Not Classifiable	13 8.4%
Serum Testosterone Level (nanograms per milliliter (ng/mL)) [Median (Full Range) ]
Median (Full Range) [nanograms per milliliter (ng/mL)]	4.03
Serum Protsate-Specific Antigen (PSA) Levels (ng/mL) [Median (Full Range) ]
Median (Full Range) [ng/mL]	19.2

Outcome Measures

1. Primary Outcome

Title	Cumulative Probability of Testosterone at Castrate Level (≤0.5 ng/mL) From Day 28 to Day 196
Time Frame	Day 28 to Day 196

Outcome Measure Data

Analysis Population Description

152 participants for this outcome measure is the analysis population from day 28 to day 196

Arm/Group Title	Degarelix 240/80 mg
Arm/Group Description	The degarelix doses were administered into the abdominal wall every 28 days. A starting dose of 240 mg (40 mg/mL) degarelix was administered on Day 0 as two 3 mL subcutaneous (s.c.) injections. The subsequent maintenace of 80 mg (20 mg/mL) degarelix were administered as single 4 mL s.c. injections at 28 day intervals from day 28 to day 168.
Measure Participants	152
Mean (95% Confidence Interval) [percent probability]	96.7

2. Secondary Outcome

Title	Proportion of Patients With Testosterone Level ≤0.5 ng/mL at Day 3
Time Frame	At day 3

Outcome Measure Data

Analysis Population Description

Observed cases

Arm/Group Title	Degarelix 240/80 mg
Arm/Group Description	The degarelix doses were administered into the abdominal wall every 28 days. A starting dose of 240 mg (40 mg/mL) degarelix was administered on Day 0 as two 3 mL subcutaneous (s.c.) injections. The subsequent maintenace of 80 mg (20 mg/mL) degarelix were administered as single 4 mL s.c. injections at 28 day intervals from day 28 to day 168.
Measure Participants	154
Number (95% Confidence Interval) [percent]	97.4

3. Secondary Outcome

Title	Percentage Change in Prostate-specific Antigen (PSA) From Baseline to Day 28
Time Frame	To Day 28

Outcome Measure Data

Analysis Population Description

152 participants for this outcome measure is the analysis population from day 0 to day 28

Arm/Group Title	Degarelix 240/80 mg
Arm/Group Description	The degarelix doses were administered into the abdominal wall every 28 days. A starting dose of 240 mg (40 mg/mL) degarelix was administered on Day 0 as two 3 mL subcutaneous (s.c.) injections. The subsequent maintenace of 80 mg (20 mg/mL) degarelix were administered as single 4 mL s.c. injections at 28 day intervals from day 28 to day 168.
Measure Participants	152
Median (Inter-Quartile Range) [percent]	-79.7

4. Secondary Outcome

Title	Cumulative Probability of Testosterone at Castrate Level (≤0.5 ng/mL)From Day 56 to Day 196
Time Frame	Day 56 to Day 196

Outcome Measure Data

Analysis Population Description

152 participants for this outcome measure is the analysis population from day 56 to day 196

Arm/Group Title	Degarelix 240/80 mg
Arm/Group Description	The degarelix doses were administered into the abdominal wall every 28 days. A starting dose of 240 mg (40 mg/mL) degarelix was administered on Day 0 as two 3 mL subcutaneous (s.c.) injections. The subsequent maintenace of 80 mg (20 mg/mL) degarelix were administered as single 4 mL s.c. injections at 28 day intervals from day 28 to day 168.
Measure Participants	152
Mean (95% Confidence Interval) [percent probability]	96.7

5. Secondary Outcome

Title	Cumulative Probability of no PSA Failure From Day 28 to Day 196
Description	PSA failure was defined as two consecutive increases of 50%, and at least 5 ng/mL, compared to nadir.
Time Frame	To Day 196

Outcome Measure Data

Analysis Population Description

152 participants for this outcome measure is the analysis population from day 28 to day 196

Arm/Group Title	Degarelix 240/80 mg
Arm/Group Description	The degarelix doses were administered into the abdominal wall every 28 days. A starting dose of 240 mg (40 mg/mL) degarelix was administered on Day 0 as two 3 mL subcutaneous (s.c.) injections. The subsequent maintenace of 80 mg (20 mg/mL) degarelix were administered as single 4 mL s.c. injections at 28 day intervals from day 28 to day 168.
Measure Participants	152
Mean (95% Confidence Interval) [percent probability]	97.3

6. Secondary Outcome

Title	Number of Participants With Markedly Abnormal Values in Safety Laboratory Variables
Description	The figures present the number of participants who had markedly abnormal levels of safety laboratory variables. Only the laboratory variables that had at least one percentage of participants in either group with abnormal value are presented, more variables were included in the study.
Time Frame	To Day 196

Outcome Measure Data

Analysis Population Description

Safety analysis population

Arm/Group Title	Degarelix 240/80 mg
Arm/Group Description	The degarelix doses were administered into the abdominal wall every 28 days. A starting dose of 240 mg (40 mg/mL) degarelix was administered on Day 0 as two 3 mL subcutaneous (s.c.) injections. The subsequent maintenace of 80 mg (20 mg/mL) degarelix were administered as single 4 mL s.c. injections at 28 day intervals from day 28 to day 168.
Measure Participants	156
B-Haematocrit (Ratio) <=0.37	73 47.1%
B-Haemoglobin (g/L) <=115	5 3.2%
B-White blood cell count (10^9/L) <=2.8	1 0.6%
B-White blood cell count (10^9/L) >=16.0	1 0.6%
B-Red blood cell count (10^12/L) <=3.5	19 12.3%
S-Alanine aminotransferase (IU/L) >3xULN	1 0.6%
S-Potassium (mmol/L) >=5.8	10 6.5%
S-Sodium (mmol/L) <=130	2 1.3%
S-Urea nitrogen (mmol/L) >=10.7	8 5.2%
B-Lymphocytes (%) <=10	4 2.6%
B-Eosinophils (%) >=10	7 4.5%

7. Secondary Outcome

Title	Number of Participants With Markedly Abnormal Values in Vital Signs and Body Weight
Description	This outcome measure included incidence of markedly abnormal changes in blood pressure (systolic and diastolic), pulse, and body weight. The table presents the number of participants with normal baseline and at least one post-baseline markedly abnormal value.
Time Frame	To Day 196

Outcome Measure Data

Analysis Population Description

Safety analyis population

Arm/Group Title	Degarelix 240/80 mg
Arm/Group Description	The degarelix doses were administered into the abdominal wall every 28 days. A starting dose of 240 mg (40 mg/mL) degarelix was administered on Day 0 as two 3 mL subcutaneous (s.c.) injections. The subsequent maintenace of 80 mg (20 mg/mL) degarelix were administered as single 4 mL s.c. injections at 28 day intervals from day 28 to day 168.
Measure Participants	156
Diastolic blood pressure <=50 and decrease >=15	6 3.9%
Diastolic blood pressure >=105 and increase >=15	0 0%
Systolic blood pressure <=90 and decrease >=20	12 7.7%
Systolic blood pressure >=180 and increase >=20	1 0.6%
Heart rate <=50 and decrease >=15	4 2.6%
Heart rate >=120 and increase >=15	0 0%
Body weight decrease of >=7 percent	4 2.6%
Body weight increase of >=7 percent	12 7.7%

Adverse Events

Time Frame	7 months (196 days)
Adverse Event Reporting Description	Each participant's condition was monitored throughout the trial from the time of signing the informed consent until the end of the follow-up period. The investigator was to record all adverse events (AEs) in the AE log of the participant's Case Report Form.
Arm/Group Title	Degarelix 240/80 mg
Arm/Group Description	The degarelix doses were administered into the abdominal wall every 28 days. A starting dose of 240 mg (40 mg/mL) degarelix was administered on Day 0 as two 3 mL subcutaneous (s.c.) injections. The subsequent maintenace of 80 mg (20 mg/mL) degarelix were administered as single 4 mL s.c. injections at 28 day intervals from day 28 to day 168.
All Cause Mortality
	Degarelix 240/80 mg
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Degarelix 240/80 mg
	Affected / at Risk (%)	# Events
Total	18/156 (11.5%)
Cardiac disorders
Angina pectoris	1/156 (0.6%)
Angina unstable	1/156 (0.6%)
Atrial fibrillation	1/156 (0.6%)
Coronary artery occlusion	1/156 (0.6%)
Myocardial ischaemia	1/156 (0.6%)
Gastrointestinal disorders
Constipation	1/156 (0.6%)
Inguinal hernia	1/156 (0.6%)
General disorders
Asthenia	1/156 (0.6%)
Disease progression	1/156 (0.6%)
Infections and infestations
Appendicitis	1/156 (0.6%)
Herpes zoster	1/156 (0.6%)
Influenza	1/156 (0.6%)
Upper respiratory tract infection	1/156 (0.6%)
Injury, poisoning and procedural complications
Drug toxicity	1/156 (0.6%)
Spinal compression fracture	1/156 (0.6%)
Metabolism and nutrition disorders
Anorexia	1/156 (0.6%)
Hyperglycaemia	1/156 (0.6%)
Musculoskeletal and connective tissue disorders
Back pain	1/156 (0.6%)
Flank pain	1/156 (0.6%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to prostate	1/156 (0.6%)
Metastatic pain	1/156 (0.6%)
Nervous system disorders
Paraplegia	1/156 (0.6%)
Spinal cord compression	1/156 (0.6%)
Renal and urinary disorders
Dysuria	1/156 (0.6%)
Haematuria	1/156 (0.6%)
Urinary retention	1/156 (0.6%)
Reproductive system and breast disorders
Pelvic pain	1/156 (0.6%)
Penile pain	1/156 (0.6%)
Perineal pain	1/156 (0.6%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	1/156 (0.6%)
Surgical and medical procedures
Ureteral stent removal	1/156 (0.6%)
Other (Not Including Serious) Adverse Events
	Degarelix 240/80 mg
	Affected / at Risk (%)	# Events
Total	113/156 (72.4%)
Gastrointestinal disorders
Constipation	13/156 (8.3%)
Diarrhoea	7/156 (4.5%)
Dyspepsia	5/156 (3.2%)
General disorders
Injection site pain	34/156 (21.8%)
Injection site erythema	13/156 (8.3%)
Injection site induration	6/156 (3.8%)
Oedema peripheral	6/156 (3.8%)
Fatigue	5/156 (3.2%)
Infections and infestations
Upper respiratory tract	12/156 (7.7%)
Musculoskeletal and connective tissue disorders
Back pain	5/156 (3.2%)
Nervous system disorders
Headache	7/156 (4.5%)
Dizziness	6/156 (3.8%)
Insomnia	7/156 (4.5%)
Renal and urinary disorders
Nocturia	10/156 (6.4%)
Dysuria	6/156 (3.8%)
Haematuria	5/156 (3.2%)
Skin and subcutaneous tissue disorders
Hyperhidrosis	14/156 (9%)
Vascular disorders
Hot flush	5/156 (3.2%)
Flushing	5/156 (3.2%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review the draft manuscript prior to publication and can request delay of publication where any contents are deemed patentable by the sponsor or confidential to the sponsor. Comments will be given within four weeks from receipt of the draft manuscript. Additional time may be required to allow Ferring to seek patent protection of the invention.