Long-Term Safety and Tolerability of Degarelix One-Month Dosing Regimen in Korean Patients

• Sponsor: Ferring Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01215513
• Collaborator: Ferring Pharmaceuticals Korea, Ltd. (Other)
• Enrollment: 127
• Locations: 11
• Arm: 1
• Duration (Months): 19
• Patients Per Site: 11.5
• Patients Per Site Per Month: 0.6

Study Details

Study Description

Brief Summary

This is an open-label, multi-centre single arm trial to investigate long-term safety and tolerability of degarelix in Korean patients with prostate cancer.

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 127 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-Label, Multi-Centre, Extension Trial, Evaluating the Long-Term Safety and Tolerability of Degarelix One-Month Dosing Regimen in Korean Patients Requiring Androgen Ablation Therapy
• Study Start Date: Sep 1, 2010
• Actual Primary Completion Date: Apr 1, 2012
• Actual Study Completion Date: Apr 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Degarelix	Drug: Degarelix

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Markedly Abnormal Values in Safety Laboratory Variables [From baseline (day 0) to end of treatment (up to day 364)]

   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 participant with abnormal value are presented, more variables were included in the study. ULN=upper limit of normal

2. Number of Participants With Markedly Abnormal Values in Vital Signs and Body Weight [From baseline (day 0) to end of treatment (up to day 364)]

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

3. Number of Participants With Markedly Abnormal Values in ECG Variables [From baseline (day 0) to end of treatment (up to day 364)]

   This outcome measure included incidence of markedly abnormal changes in ECG variables (PR, QRS, and QT interval, QTcF, and ventricular rate). The figures present the number of participants with normal baseline and at least one post-baseline markedly abnormal value.

Secondary Outcome Measures

1. Serum Levels of Prostate Specific Antigen (PSA) Over Time [Day 0, day 196, day 280, and day 364]

   PSA levels were measured over time. The figures present the median level at day 0 (n=155 participants), day 196 (n=148), day 280 (n=115), and day 364 (n=109).

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. A trial-related activity is defined as any procedure that would not have been performed during the normal management of the patient

• Has completed the 7-month main trial, FE200486 CS42

Exclusion Criteria:

• Has been withdrawn/discontinued from the FE200486 CS42 trial

• A patient may also not be entered into the CS42A trial at the discretion of the investigator due to safety or lack of efficacy concerns (LH or PSA response) in the CS42 trial.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Korea University Hospital	Seoul	Anam-dong, Seongbuk-gu	Korea, Republic of
2	Seoul St. Mary's Hospital	Seoul	Banpo-dong, Seocho-gu	Korea, Republic of
3	Yonsei University Health System Gangnam Sevrance	Seoul	Eonguro, Gangnam-gu	Korea, Republic of
4	Seoul National University Bundang Hospital	Seongnam	Gyeonggi	Korea, Republic of
5	Hallym University Sacred Heart Hospital	Pyungchon	Gyunggi-do	Korea, Republic of
6	Pusan National University Yangsan Hospital	Mulgeum-eup	Gyungnam	Korea, Republic of
7	Samsung Medical Center	Seoul	Ilwon-dong, Kangnam-gu	Korea, Republic of
8	Asan Medical Center	Seoul	Pungnap-2-dong, Songpa-gu	Korea, Republic of
9	Yonsei University Health System (Sevrance Hospital)	Seoul	Seongsanno, Seodaemun-gu	Korea, Republic of
10	Seoul National University Hospital	Seoul	Yeongeon-dong, Chongno-gu	Korea, Republic of
11	Kyoungbuk National University Hospital	Daegu		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: NCT01215513
• Other Study ID Numbers: FE200486 CS42A
• First Posted: Oct 6, 2010
• Last Update Posted: May 22, 2013
• Last Verified: Apr 1, 2013

• Additional relevant MeSH terms: Prostatic Neoplasms

Study Results

Participant Flow

Recruitment Details	The participants were recruited from 9 sites in Korea. All participants had completed the 7-month main study (CS42, NCT01071915) prior to enrollment into this extension study (CS42A). The CS42A study was conducted between 20 September 2010 (FPFV) and 25 April 2012 (LPLV).

Arm/Group Title	Degarelix
Arm/Group Description	80 mg degarelix at a concentration of 20 mg/mL were administered as a single 4 mL subcutaneous injection at monthly intervals.
Period Title: Overall Study
STARTED	157
CS42 and CS42A Safety Analysis Set	156
CS42 and CS42A Full Analysis Set	155
CS42A Safety Analysis Set	127
COMPLETED	112
NOT COMPLETED	45

Baseline Characteristics

Arm/Group Title	Degarelix
Arm/Group Description	80 mg degarelix at a concentration of 20 mg/mL were administered as a single 4 mL subcutaneous injection at monthly intervals
Overall Participants	156
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	72.6 (8.06)
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	156 100%
Region of Enrollment (participants) [Number]
Korea, Republic of	156 100%

Outcome Measures

1. Primary 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 participant with abnormal value are presented, more variables were included in the study. ULN=upper limit of normal
Time Frame	From baseline (day 0) to end of treatment (up to day 364)

Outcome Measure Data

Analysis Population Description

Descriptive statistics provided a view of the 1-year safety of degarelix (CS42 and CS42A safety analysis set).

Arm/Group Title	Degarelix
Arm/Group Description	80 mg degarelix at a concentration of 20 mg/mL were administered as a single 4 mL subcutaneous injection at monthly intervals.
Measure Participants	156
S-Alanine aminotransferase (IU/L) >3xULN	1 0.6%
S-Cholesterol (mmol/L) >=8.0	1 0.6%
S-Potassium (mmol/L) >=5.8	10 6.4%
S-Sodium (mmol/L) <=130	2 1.3%
S-Total bilirubin (micromol/L) >1.5xULN	1 0.6%
S-Urea nitrogen (mmol/L) >=10.7	10 6.4%
B-Basophils (%) >=5	1 0.6%
B-Eosinophils (%) >=10	7 4.5%
B-Haematocrit (ratio) <=0.37	83 53.2%
B-Haemoglobin (g/L) <=115	9 5.8%
B-Lymphocytes (%) <=10	4 2.6%
B-Neutrophils (%) >=90	1 0.6%
B-Red blood cell count (10^12/L) <=3.5	25 16%
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%

2. Primary 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 figures present the number of participants with normal baseline and at least one post-baseline markedly abnormal value.
Time Frame	From baseline (day 0) to end of treatment (up to day 364)

Outcome Measure Data

Analysis Population Description

Descriptive statistics provided a view of the 1-year safety of degarelix (CS42 and CS42A safety analysis set).

Arm/Group Title	Degarelix
Arm/Group Description	80 mg degarelix at a concentration of 20 mg/mL were administered as a single 4 mL subcutaneous injection at monthly intervals.
Measure Participants	156
Diastolic blood pressure <=50 and decrease >=15	13 8.3%
Diastolic blood pressure >=105 and increase >=15	0 0%
Systolic blood pressure <=90 and decrease >=20	20 12.8%
Systolic blood pressure >=180 and increase >=20	1 0.6%
Pulse rate <=50 and decrease >=15	10 6.4%
Pulse rate >=120 and increase >=15	0 0%
Body weight decrease of >=7% from baseline	4 2.6%
Body weight increase of >=7% from baseline	12 7.7%

3. Secondary Outcome

Title	Serum Levels of Prostate Specific Antigen (PSA) Over Time
Description	PSA levels were measured over time. The figures present the median level at day 0 (n=155 participants), day 196 (n=148), day 280 (n=115), and day 364 (n=109).
Time Frame	Day 0, day 196, day 280, and day 364

Outcome Measure Data

Analysis Population Description

CS42 and CS42A full analysis set (data of all participants who received at least one dose of degarelix and had at least one efficacy assessment after dosing). The figures present the median of the absolute values at day 0 (n=155 participants), day 196 (n=148), day 280 (n=115), and day 364 (n=109).

Arm/Group Title	Degarelix
Arm/Group Description	80 mg degarelix at a concentration of 20 mg/mL were administered as a single 4 mL subcutaneous injection at monthly intervals.
Measure Participants	155
Baseline (Day 0)	19.2
Day 196	0.67
Day 280	0.52
Day 364	0.46

4. Primary Outcome

Title	Number of Participants With Markedly Abnormal Values in ECG Variables
Description	This outcome measure included incidence of markedly abnormal changes in ECG variables (PR, QRS, and QT interval, QTcF, and ventricular rate). The figures present the number of participants with normal baseline and at least one post-baseline markedly abnormal value.
Time Frame	From baseline (day 0) to end of treatment (up to day 364)

Outcome Measure Data

Analysis Population Description

Descriptive statistics provided a view of the 1-year safety of degarelix (CS42 and CS42A safety analysis set).

Arm/Group Title	Degarelix
Arm/Group Description	80 mg degarelix at a concentration of 20 mg/mL were administered as a single 4 mL subcutaneous injection at monthly intervals
Measure Participants	156
PR interval (msec) <=120	1 0.6%
PR interval (msec) >=220	3 1.9%
QRS interval (msec) >=120	3 1.9%
QT interval (msec) >=450	27 17.3%
QT interval (msec) >=480	6 3.8%
QT interval (msec) >=500	2 1.3%
QT interval increase of >=30 from baseline	69 44.2%
QT interval increase of >=60 from baseline	20 12.8%
QTcF (msec) >=450	25 16%
QTcF (msec) >=480	3 1.9%
QTcF (msec) >=500	1 0.6%
QTcF increase of >=30 from baseline	39 25%
QTcF increase of >=60 from baseline	8 5.1%
Ventricular rate (beats/min) <=50	1 0.6%
Ventricular rate (beats/min) >=120	2 1.3%

Adverse Events

Time Frame	From baseline (day 0) to end of treatment (up to day 364)
Adverse Event Reporting Description	The investigator monitored the condition of each participant throughout the study from the time the participant signed the informed consent form until the end of study visit or the end of follow-up period.
Arm/Group Title	Degarelix
Arm/Group Description	80 mg degarelix at a concentration of 20 mg/mL were administered as a single 4 mL subcutaneous injection at monthly intervals.
All Cause Mortality
	Degarelix
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Degarelix
	Affected / at Risk (%)	# Events
Total	25/156 (16%)
Cardiac disorders
Angina pectoris	1/156 (0.6%)	1
Angina unstable	1/156 (0.6%)	1
Atrial fibrillation	1/156 (0.6%)	1
Coronary artery occlusion	1/156 (0.6%)	1
Myocardial ischaemia	1/156 (0.6%)	1
Eye disorders
Diabetic retinopathy	1/156 (0.6%)	1
Hypermetropia	1/156 (0.6%)	1
Gastrointestinal disorders
Constipation	1/156 (0.6%)	1
Inguinal hernia	1/156 (0.6%)	1
General disorders
Asthenia	1/156 (0.6%)	1
Disease progression	1/156 (0.6%)	1
Sudden death	1/156 (0.6%)	1
Infections and infestations
Appendicitis	1/156 (0.6%)	1
Herpes zoster	1/156 (0.6%)	1
Influenza	1/156 (0.6%)	1
Upper respiratory tract infection	1/156 (0.6%)	1
Injury, poisoning and procedural complications
Spinal compression fracture	2/156 (1.3%)	2
Drug toxicity	1/156 (0.6%)	1
Metabolism and nutrition disorders
Anorexia	1/156 (0.6%)	1
Diabetes mellitus inadequate control	1/156 (0.6%)	1
Hyperglycaemia	1/156 (0.6%)	1
Musculoskeletal and connective tissue disorders
Back pain	1/156 (0.6%)	1
Flank pain	1/156 (0.6%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to prostate	1/156 (0.6%)	1
Metastatic pain	1/156 (0.6%)	1
Nervous system disorders
Dizziness	1/156 (0.6%)	2
Paraplegia	1/156 (0.6%)	1
Spinal cord compression	1/156 (0.6%)	1
Renal and urinary disorders
Dysuria	1/156 (0.6%)	1
Haematuria	1/156 (0.6%)	1
Urinary retention	1/156 (0.6%)	1
Reproductive system and breast disorders
Benign prostatic hyperplasia	1/156 (0.6%)	1
Pelvic pain	1/156 (0.6%)	1
Penile pain	1/156 (0.6%)	1
Perineal pain	1/156 (0.6%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnoea	1/156 (0.6%)	1
Surgical and medical procedures
Removal of internal fixation	1/156 (0.6%)	1
Ureteral stent removal	1/156 (0.6%)	1
Other (Not Including Serious) Adverse Events
	Degarelix
	Affected / at Risk (%)	# Events
Total	88/156 (56.4%)
Gastrointestinal disorders
Constipation	13/156 (8.3%)	13
Diarrhoea	11/156 (7.1%)	15
General disorders
Injection site pain	39/156 (25%)	55
Injection site erythema	13/156 (8.3%)	13
Infections and infestations
Upper respiratory tract infection	14/156 (9%)	16
Musculoskeletal and connective tissue disorders
Back pain	8/156 (5.1%)	10
Nervous system disorders
Dizziness	11/156 (7.1%)	13
Headache	10/156 (6.4%)	13
Psychiatric disorders
Insomnia	8/156 (5.1%)	9
Renal and urinary disorders
Nocturia	11/156 (7.1%)	11
Pollakiuria	9/156 (5.8%)	10
Skin and subcutaneous tissue disorders
Hyperhidrosis	19/156 (12.2%)	21

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.