Risedronate to Prevent Skeletal Related Events in Patients With Metastatic Prostate Cancer Commencing Hormonal Therapy

• Sponsor: Christopher Sweeney, MBBS (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00216060
• Collaborator: Sanofi (Industry), Walther Cancer Institute (Other), Hoosier Cancer Research Network (Other)
• Enrollment: 63
• Locations: 45
• Arms: 2
• Duration (Months): 53
• Patients Per Site: 1.4
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

Risedronate is an orally administered pyridinyl bisphosphonate that is 36 times more potent than pamidronate and 72 times more potent than clodronate. Four randomized, double-blind trials have been carried out in patients with postmenopausal osteoporosis. In 2 of these studies, vertebral fracture incidence was reduced by a daily dose of 5 mg risedronate by up to 65% and 49% relative to placebo after 1 and 3 years, respectively. In these trials, risedronate improved lumbar spine, femoral neck, and femoral trochanter bone mineral density (BMD) at 6 months. In addition, preclinical studies have shown that risedronate is more potent than pamidronate and clodronate in inhibiting adhesion of prostate cancer cells to bone and preventing tumor cell invasion. The incidence of osteoporosis in prostate cancer patients has been well established; therefore, it is advantageous to assess the efficacy of oral bisphosphonate therapy.

Condition or Disease	Intervention/Treatment	Phase
Metastatic Prostate Cancer	Drug: Risedronate; Drug: Placebo	Phase 3

Detailed Description

OUTLINE: This is a randomized, placebo-controlled, double-blind, multicenter, 2 arm study.

The study population will consist of prostate cancer patients with metastatic bone disease for whom androgen-deprivation therapy is planned. After stratification based on the patient's age, performance status, and severity of metastatic disease, the patients will be randomized at a 1:1 ratio to the following treatment arms:

• Daily oral risedronate combined with androgen deprivation

• Daily oral placebo combined with androgen deprivation

Initial clinical evaluation will be performed during the 2-week screening period. While patients receive per-protocol treatment, study assessments will be performed every 4 weeks during the first 3 months, and every 12 weeks thereafter.

Performance Status: Eastern Cooperative Oncology Group (ECOG) 0 to 2

Life Expectancy: At least 12 weeks

Hematopoietic:

• Absolute neutrophil count (ANC) > 1,000/mm3

• Platelet count > 100,000/mm3

• international normalized ratio (INR) < 1.5 x upper limit of normal unless on therapeutic anticoagulation

• Partial thromboplastin time (PTT) < 1.5 x upper limit of normal unless on therapeutic anticoagulation

Hepatic:

• Bilirubin < 1.5 mg/dL

• Alanine transaminase (ALT) < 2.5 x upper limit of normal

Renal:

• Creatinine clearance of > 30 mL/min (by Cockcroft-Gault)

Cardiovascular:

• No significant history of uncontrolled cardiac disease (i.e., uncontrolled hypertension, unstable angina, and congestive heart failure).

Pulmonary:

• Not specified

Calcium:

• Corrected serum calcium = (4.0 g/dL - actual albumin g/dL)x 0.8 + serum calcium

Study Design

• Study Type: Interventional
• Actual Enrollment: 63 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Prevention
• Official Title: A Phase III, Randomized, Double-Blind, Placebo-Controlled Trial Evaluating the Ability of Risedronate to Prevent Skeletal Related Events in Patients With Metastatic Prostate Cancer Commencing Hormonal Therapy: Hoosier Oncology Group GU02-41
• Study Start Date: Oct 1, 2003
• Actual Primary Completion Date: Feb 1, 2008
• Actual Study Completion Date: Mar 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Experimental Arm Daily oral risedronate combined with androgen deprivation	Drug: Risedronate; Daily oral risedronate combined with androgen deprivation
Placebo Comparator: Placebo Arm daily oral placebo combined with androgen deprivation	Drug: Placebo; Daily oral placebo combined with androgen deprivation

Outcome Measures

Primary Outcome Measures

1. Numbers of SRE or Death Occurred Cumulatively [36 months]

   Number of participants experiencing a SRE(skeletal-related event) or death occurred, cumulative from each arm ( a daily oral dose of 30 mg risedronate, or placebo)

Secondary Outcome Measures

1. Rate of Patients Archiving a PSA (Prostate Specific Antigen) Nadir < 0.2 ng/mL [36 months]

2. Time to Development of Hormone Refractory Disease [36 months]

3. Bone Turnover Marker Changes -- Urine Total Deoxypyridinoline (DPD) [24 weeks]

   Urine total DPD median in response to treatment on both study arms at week 24. compare median from baseline and week 24. Deoxypyridinoline (DPD) is measured in hydrolyzed urine samples using high-performance liquid chromatography technique. After extraction of the cross-links and elimination of the urine impurities by a Bio-Rad SPE cartridge (Bio-Rad Laboratories, Hercules, CA), total DPD is eluted from reverse-phase high-performance liquid chromatography by ion pair chromatography with isocratic elution. The compounds are detected as a result of their natural fluorescence with a fluorescence detector

4. Three- Year Survival Rate [36 months]

5. Bone Turnover Marker Changes-- Urine N-telopeptide (NTX) Median [24 week]

   Urine N-telopeptide (NTX) median changes between baseline and week 24. The assays are performed with the NTx Reagent Pack kit from Ortho-Clinical Diagnostics (Ortho-Clinical Diagnostics/Johnson & Johnson, Amersham, UK), which is a kit designed for the quantitative determination of N-terminal telopeptide (NTx) in human urine on the automated Vitros Immunodiagnostic System ECi (Ortho-Clinical Diagnostics/Johnson & Johnson, Amersham, UK). A competitive immunoassay technique is used. This depends on competition between NTx present in the sample and a synthetic NTx peptide coated on the wells for binding by a horseradish peroxidase (HRP)-labeled antibody conjugate (mouse monoclonal anti-NTx). The conjugate is captured by the peptide coated on the wells; unbound materials are removed by washing. The bound HRP conjugate is measured by a luminescent reaction.

6. Bone Turnover Marker Changes-- Serum BAP [24 week]

   Serum BAP median changes between baseline and week 24. The Ostase assays are performed with an access immunoassay system, which is an assay of serum samples that provides a quantitative measurement of bone alkaline phosphatase (BAP). A mouse monoclonal antibody specific to BAP is added to a re-action vessel with paramagnetic particles coated with goat antimouse polyclonalantibody.Calibrators,controls,andsamplescontainingBAP are added to the coated particles and bind to the anti-BAP monoclonal antibody. After the formation of a solid phase/capture antibody/BAP complex, separation in a magnetic field and washing remove materials not bound to the solid phase. A chemiluminescent substrate, LumiPhos 530, is added to the reaction vessel, and light generated by the reaction is measured with a luminometer. The light production is directly proportional to the concentration of BAP in the sample. The amount of analyte in thesample is determined from a stored multipoint calibration curve

7. Bone Turnover Marker Changes-- Serum Osteocalcin (OC) [24 week]

   Serum Osteocalcin (OC) medians between baseline and 24 weeks areperformed with the Elecsys 2010 automated analyzer, which uses an electrochemiluminescence immunoassay technique for the in vitro quantitative determination of serum total osteocalcin in humanserum. The assay uses a sandwich test principle in which afirst biotinylated monoclonal antibody recognizing N-MID osteocalcin and a second monoclonal antibody against N-MID osteocalcin labeled with ruthenium are incubated with 20mL of serum. After a first incubation, streptavidin-coated microparticles are added for a second incubation, and the complex becomes bound to the solid phase by interaction of biotin and streptavidin.These microparticles are then magnetically captured onto the surface of an electrode. Application of a voltage on this electrode induces chemiluminescent emission, which is measured by a photomultiplierand compared with a calibration curve that is generated in aninstrument-specific manner by 2-point calibration.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Histologically or cytologically confirmed adenocarcinoma of the prostate with metastatic bone disease (by CT, MRI or bone scan) with plans to start or be < 30 days from beginning androgen deprivation therapy. Patients with lymph node or visceral metastases only are not eligible

• Patients may receive palliative radiation therapy at the investigators discretion during the first 4 weeks of beginning protocol therapy.

Exclusion Criteria:

• No neuroendocrine, small cell or transitional cell cancer of the prostate No abnormal bone metabolism (i.e., Paget's disease, untreated hyperthyroidism, untreated hyperprolactinemia, untreated Cushing's disease).

• No use of calcitonin within 14 days before being registered for protocol therapy or any previous use of bisphosphonates.

• No major surgery within 4 weeks of registration to protocol therapy.

• No adjuvant chemotherapy within 6 months of registration to protocol therapy.

• No previous chemotherapy for metastatic disease.

• No hormonal therapy in the adjuvant setting within 12 months of registration to protocol therapy; previous hormonal therapy must not have exceeded 6 months.

• No prior history of malignancy in the past 5 years with the exception of basal cell and squamous cell carcinoma of the skin.

• No history of allergy or drug reactions to bisphosphonates.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Center for Urological Research	La Mesa	California	United States	91942
2	San Bernadino Urological Associates	San Bernardino	California	United States	92404
3	Grove Hill Medical Center Urology	New Britain	Connecticut	United States	06052
4	Innovative Surgical Resources	Tampa	Florida	United States	33607
5	Medical & Surgical Specialists, LLC	Galesburg	Illinois	United States	61401
6	Peoria Urological Associates	Peoria	Illinois	United States	61614
7	Oncology Hematology Associates of SW Indiana	Evansville	Indiana	United States	47714
8	Center for Cancer Care at Goshen Health System	Goshen	Indiana	United States	46527
9	Indiana University Cancer Center	Indianapolis	Indiana	United States	46202
10	Quality Cancer Center (MCGOP)	Indianapolis	Indiana	United States	46202
11	Urology of Indiana, LLC	Indianapolis	Indiana	United States	46202
12	Urology Associates	Muncie	Indiana	United States	47303
13	Northern Indiana Cancer Research Consortium	South Bend	Indiana	United States	46601
14	Urologic Surgery Associates	Baltimore	Maryland	United States	21201
15	Drs. Werner, Murdock and Francis PA Urology Associates	Greenbelt	Maryland	United States	20770
16	Mayo Clinic Rochester	Rochester	Minnesota	United States	55905
17	Kansas City Urology Care	Kansas City	Missouri	United States	64131
18	Siteman Cancer Center	St. Louis	Missouri	United States	63110
19	Nevada Urology	Reno	Nevada	United States	89511
20	Cancer Institute of New Jersey	New Brunswick	New Jersey	United States	08903
21	Lawrenceville Urology	Trenton	New Jersey	United States	08648
22	Accumed Research Associates	Garden City	New York	United States	11530
23	Staten Island Urological Research, P.C.	Staten Island	New York	United States	10304
24	Cleveland Clinic Foundation	Cleveland	Ohio	United States	44195
25	Oregon Urology Specialists	Springfield	Oregon	United States	97477
26	Urological Associates of Lancaster	Lancaster	Pennsylvania	United States	17604
27	Triangle Urological Group	Pittsburgh	Pennsylvania	United States	15212
28	Salt Lake Research	Salt Lake City	Utah	United States	84124
29	David Reed, M.D.	Seattle	Washington	United States	98166
30	Madigan Army Medical Center Urology Service	Tacoma	Washington	United States	98431
31	Gundersen Lutheran Medical Center	LaCrosse	Wisconsin	United States	54601
32	Southern Interior Medical Research, Inc.	Kelowna	British Columbia	Canada	V1Y 2H4
33	Andreou Research	Surrey	British Columbia	Canada	V3W 1N1
34	Dr. G. Steinhoff Clinical Research	Victoria	British Columbia	Canada	V8V 3N1
35	Dr. Allan Patrick Professional Corporation	Fredericton	New Brunswick	Canada	E3B 5B8
36	Male/Female Health and Research	Barrie	Ontario	Canada	L4M 7G1
37	Burlington Professional Centre	Burlington	Ontario	Canada	L7N 3V2
38	Urology Resource Centre	Burlington	Ontario	Canada	L7S 1V2
39	Hamilton District Urology Research Center	Hamilton	Ontario	Canada	L8N 4A6
40	Centre for Advanced Urological Research	Kingston	Ontario	Canada	K7L-2V7
41	London Region Cancer Program	London	Ontario	Canada	N6A 4L6
42	MOR Urology, Inc.	New Market	Ontario	Canada	L3X 1W1
43	Male Health Centres	Oakville	Ontario	Canada	L6H 3P1
44	Scarborough General Hospital, Medical Mall	Scarborough	Ontario	Canada	M1P 2T7
45	University Health Network - Princess Margaret Division	Toronto	Ontario	Canada	M5G 2M9

Sponsors and Collaborators

• Christopher Sweeney, MBBS
• Sanofi
• Walther Cancer Institute
• Hoosier Cancer Research Network

Investigators

• Study Chair: Christopher Sweeney, M.B.B.S., Hoosier Oncology Group, LLC

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Christopher Sweeney, MBBS, Sponsor-Investigator, Hoosier Cancer Research Network
• ClinicalTrials.gov Identifier: NCT00216060
• Other Study ID Numbers: HOG GU02-41
• First Posted: Sep 22, 2005
• Last Update Posted: May 26, 2016
• Last Verified: May 1, 2016

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Additional relevant MeSH terms: Prostatic Neoplasms; Risedronic Acid

Study Results

Participant Flow

Recruitment Details	Target patients were men with castrate resistant prostate cancer for whom androgen-deprivation therapy was planned. Patients were enrolled at multiple outpatient oncology clinics and urological practices in the United States and Canada. Recruitment period was December 2003 and August 2005.
Pre-assignment Detail	1:1 stratification was based on patient's age, performance status and severity of metastatic disease. Initial clinical evaluation was performed during the 2-week screening period. Both arms received at least 500 mg/day oral calcium carbonate and 400 IU of vitamin D.

Arm/Group Title	Risedronate	Placebo
Arm/Group Description	Daily oral risedronate combined with androgen deprivation	daily oral placebo combined with androgen deprivation
Period Title: Overall Study
STARTED	32	31
COMPLETED	32	31
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Risedronate	Placebo	Total
Arm/Group Description	Daily oral risedronate combined with androgen deprivation	daily oral placebo combined with androgen deprivation	Total of all reporting groups
Overall Participants	32	31	63
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	8 25%	8 25.8%	16 25.4%
>=65 years	24 75%	23 74.2%	47 74.6%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	70.2 (9.5)	70.2 (8.4)	70.2 (8.95)
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%
Male	32 100%	31 100%	63 100%
Previous Adjuvant Hormone Therapy (participants) [Number]
Yes	2 6.3%	5 16.1%	7 11.1%
No	30 93.8%	26 83.9%	56 88.9%
Eastern Cooperative Oncology Group (ECOG) Performance Status (participants) [Number]
ECOG 0	26 81.3%	19 61.3%	45 71.4%
ECOG 1	4 12.5%	10 32.3%	14 22.2%
ECOG 2	2 6.3%	2 6.5%	4 6.3%
Disease Extent (participants) [Number]
Minimal Disease	11 34.4%	11 35.5%	22 34.9%
Extensive Disease	21 65.6%	20 64.5%	41 65.1%
Comorbidity Score (participants) [Number]
None	6 18.8%	3 9.7%	9 14.3%
Mild	7 21.9%	11 35.5%	18 28.6%
Moderate	12 37.5%	11 35.5%	23 36.5%
Severe	3 9.4%	5 16.1%	8 12.7%

Outcome Measures

1. Primary Outcome

Title	Numbers of SRE or Death Occurred Cumulatively
Description	Number of participants experiencing a SRE(skeletal-related event) or death occurred, cumulative from each arm ( a daily oral dose of 30 mg risedronate, or placebo)
Time Frame	36 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Risedronate Arm	Placebo Arm
Arm/Group Description	Daily oral risedronate combined with androgen deprivation Risedronate: Daily oral risedronate combined with androgen deprivation	daily oral placebo combined with androgen deprivation Placebo: Daily oral placebo combined with androgen deprivation
Measure Participants	32	31
Number [participants]	11 34.4%	13 41.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Risedronate Arm, Placebo Arm
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3
	Comments
	Method	Regression, Cox
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	2.08
	Confidence Interval	(2-Sided) 95%; 0.51 to 8.40
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Rate of Patients Archiving a PSA (Prostate Specific Antigen) Nadir < 0.2 ng/mL
Time Frame	36 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Risedronate Arm	Placebo Arm
Arm/Group Description	Daily oral risedronate combined with androgen deprivation Risedronate: Daily oral risedronate combined with androgen deprivation	daily oral placebo combined with androgen deprivation Placebo: Daily oral placebo combined with androgen deprivation
Measure Participants	32	31
Number [percentage of participants]	50 156.3%	29 93.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Risedronate Arm, Placebo Arm
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.12
	Comments
	Method	univariate analysis
	Comments

3. Secondary Outcome

Title	Time to Development of Hormone Refractory Disease
Time Frame	36 months

Outcome Measure Data

Analysis Population Description

No data were collected for this Outcome Measure due to low accrual and subsequent study termination.

Arm/Group Title	Risedronate Arm	Placebo Arm
Arm/Group Description	Daily oral risedronate combined with androgen deprivation Risedronate: Daily oral risedronate combined with androgen deprivation	daily oral placebo combined with androgen deprivation Placebo: Daily oral placebo combined with androgen deprivation
Measure Participants	0	0

4. Secondary Outcome

Title	Bone Turnover Marker Changes -- Urine Total Deoxypyridinoline (DPD)
Description	Urine total DPD median in response to treatment on both study arms at week 24. compare median from baseline and week 24. Deoxypyridinoline (DPD) is measured in hydrolyzed urine samples using high-performance liquid chromatography technique. After extraction of the cross-links and elimination of the urine impurities by a Bio-Rad SPE cartridge (Bio-Rad Laboratories, Hercules, CA), total DPD is eluted from reverse-phase high-performance liquid chromatography by ion pair chromatography with isocratic elution. The compounds are detected as a result of their natural fluorescence with a fluorescence detector
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

Number of Participants Analyzed reflects participants who had data available prior to study termination.

Arm/Group Title	Risedronate Arm	Placebo Arm
Arm/Group Description	Daily oral risedronate combined with androgen deprivation Risedronate: Daily oral risedronate combined with androgen deprivation	daily oral placebo combined with androgen deprivation Placebo: Daily oral placebo combined with androgen deprivation
Measure Participants	22	22
week 24	6.91 (4.17)	12.62 (13.59)
baseline	8.83 (20.53)	10.12 (31.83)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Risedronate Arm, Placebo Arm
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Kruskal-Wallis
	Comments

5. Secondary Outcome

Title	Three- Year Survival Rate
Time Frame	36 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Risedronate	Placebo
Arm/Group Description	Daily oral risedronate combined with androgen deprivation	daily oral placebo combined with androgen deprivation
Measure Participants	32	31
Number (95% Confidence Interval) [percentage of participants]	72.5 226.6%	71.5 230.6%

6. Secondary Outcome

Title	Bone Turnover Marker Changes-- Urine N-telopeptide (NTX) Median
Description	Urine N-telopeptide (NTX) median changes between baseline and week 24. The assays are performed with the NTx Reagent Pack kit from Ortho-Clinical Diagnostics (Ortho-Clinical Diagnostics/Johnson & Johnson, Amersham, UK), which is a kit designed for the quantitative determination of N-terminal telopeptide (NTx) in human urine on the automated Vitros Immunodiagnostic System ECi (Ortho-Clinical Diagnostics/Johnson & Johnson, Amersham, UK). A competitive immunoassay technique is used. This depends on competition between NTx present in the sample and a synthetic NTx peptide coated on the wells for binding by a horseradish peroxidase (HRP)-labeled antibody conjugate (mouse monoclonal anti-NTx). The conjugate is captured by the peptide coated on the wells; unbound materials are removed by washing. The bound HRP conjugate is measured by a luminescent reaction.
Time Frame	24 week

Outcome Measure Data

Analysis Population Description

Number of Participants Analyzed reflects participants who had data available prior to study termination.

Arm/Group Title	Risedronate Arm	Placebo Arm
Arm/Group Description	Daily oral risedronate combined with androgen deprivation Risedronate: Daily oral risedronate combined with androgen deprivation	daily oral placebo combined with androgen deprivation Placebo: Daily oral placebo combined with androgen deprivation
Measure Participants	20	19
at 24 week	20.63 (9.15)	62.95 (151.67)
baseline	41.33 (325.87)	48.08 (691.70)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Risedronate Arm, Placebo Arm
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Kruskal-Wallis
	Comments

7. Secondary Outcome

Title	Bone Turnover Marker Changes-- Serum BAP
Description	Serum BAP median changes between baseline and week 24. The Ostase assays are performed with an access immunoassay system, which is an assay of serum samples that provides a quantitative measurement of bone alkaline phosphatase (BAP). A mouse monoclonal antibody specific to BAP is added to a re-action vessel with paramagnetic particles coated with goat antimouse polyclonalantibody.Calibrators,controls,andsamplescontainingBAP are added to the coated particles and bind to the anti-BAP monoclonal antibody. After the formation of a solid phase/capture antibody/BAP complex, separation in a magnetic field and washing remove materials not bound to the solid phase. A chemiluminescent substrate, LumiPhos 530, is added to the reaction vessel, and light generated by the reaction is measured with a luminometer. The light production is directly proportional to the concentration of BAP in the sample. The amount of analyte in thesample is determined from a stored multipoint calibration curve
Time Frame	24 week

Outcome Measure Data

Analysis Population Description

Number of Participants Analyzed reflects participants who had data available prior to study termination.

Arm/Group Title	Risedronate Arm	Placebo Arm
Arm/Group Description	Daily oral risedronate combined with androgen deprivation Risedronate: Daily oral risedronate combined with androgen deprivation	daily oral placebo combined with androgen deprivation Placebo: Daily oral placebo combined with androgen deprivation
Measure Participants	19	17
24 week	9.5 (4.59)	13.16 (54.62)
baseline	20.95 (229.68)	19.50 (272.98)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Risedronate Arm, Placebo Arm
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.010
	Comments
	Method	Kruskal-Wallis
	Comments

8. Secondary Outcome

Title	Bone Turnover Marker Changes-- Serum Osteocalcin (OC)
Description	Serum Osteocalcin (OC) medians between baseline and 24 weeks areperformed with the Elecsys 2010 automated analyzer, which uses an electrochemiluminescence immunoassay technique for the in vitro quantitative determination of serum total osteocalcin in humanserum. The assay uses a sandwich test principle in which afirst biotinylated monoclonal antibody recognizing N-MID osteocalcin and a second monoclonal antibody against N-MID osteocalcin labeled with ruthenium are incubated with 20mL of serum. After a first incubation, streptavidin-coated microparticles are added for a second incubation, and the complex becomes bound to the solid phase by interaction of biotin and streptavidin.These microparticles are then magnetically captured onto the surface of an electrode. Application of a voltage on this electrode induces chemiluminescent emission, which is measured by a photomultiplierand compared with a calibration curve that is generated in aninstrument-specific manner by 2-point calibration.
Time Frame	24 week

Outcome Measure Data

Analysis Population Description

Number of Participants Analyzed reflects participants who had data available prior to study termination.

Arm/Group Title	Risedronate Arm	Placebo Arm
Arm/Group Description	Daily oral risedronate combined with androgen deprivation Risedronate: Daily oral risedronate combined with androgen deprivation	daily oral placebo combined with androgen deprivation Placebo: Daily oral placebo combined with androgen deprivation
Measure Participants	19	18
at 24 week	11.88 (14.94)	27.35 (57.43)
baseline	20.08 (38.36)	18.24 (43.06)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Risedronate Arm, Placebo Arm
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Kruskal-Wallis
	Comments

Adverse Events

Time Frame	36 Months
Arm/Group Title	Placebo		Risedronate
Arm/Group Description	daily oral placebo combined with androgen deprivation		Daily oral risedronate combined with androgen deprivation
All Cause Mortality
	Placebo		Risedronate
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		Risedronate
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/31 (16.1%)		8/32 (25%)
Blood and lymphatic system disorders
HEMOLYSIS (E.G., IMMUNE HEMOLYTIC ANEMIA, DRUG-RELATED HEMOLYSIS)	0/31 (0%)	0	1/32 (3.1%)	1
PLATELETS	0/31 (0%)	0	1/32 (3.1%)	1
Cardiac disorders
CARDIAC GENERAL - OTHER	0/31 (0%)	0	1/32 (3.1%)	1
CARDIAC ISCHEMIA/INFARCTION	2/31 (6.5%)	2	0/32 (0%)	0
CONDUCTION ABNORMALITY/ATRIOVENTRICULAR HEART BLOCK / AV BLOCK-THIRD DEGREE (COMPLETE AV BLOCK)	0/31 (0%)	0	1/32 (3.1%)	1
LEFT VENTRICULAR SYSTOLIC DYSFUNCTION	1/31 (3.2%)	1	0/32 (0%)	0
SUPRAVENTRICULAR AND NODAL ARRHYTHMIA / ATRIAL FIBRILLATION	0/31 (0%)	0	1/32 (3.1%)	1
Gastrointestinal disorders
DEHYDRATION	0/31 (0%)	0	2/32 (6.3%)	2
PAIN / ABDOMEN NOS	1/31 (3.2%)	1	0/32 (0%)	0
STRICTURE/STENOSIS (INCLUDING ANASTOMOTIC), GI / BILIARY TREE	1/31 (3.2%)	1	0/32 (0%)	0
General disorders
PAIN / PAIN NOS	0/31 (0%)	0	1/32 (3.1%)	1
Infections and infestations
INFECTION WITH UNKNOWN ANC / LUNG (PNEUMONIA)	1/31 (3.2%)	1	0/32 (0%)	0
INFECTION WITH UNKNOWN ANC / URINARY TRACT NOS	1/31 (3.2%)	1	0/32 (0%)	0
Investigations
SODIUM, SERUM-LOW (HYPONATREMIA)	0/31 (0%)	0	1/32 (3.1%)	1
Musculoskeletal and connective tissue disorders
MUSCLE WEAKNESS, GENERALIZED OR SPECIFIC AREA (NOT DUE TO NEUROPATHY) / WHOLE BODY/GENERALIZED	1/31 (3.2%)	1	0/32 (0%)	0
Renal and urinary disorders
CYSTITIS	0/31 (0%)	0	1/32 (3.1%)	1
PERFORATION, GU / KIDNEY	1/31 (3.2%)	1	0/32 (0%)	0
RENAL FAILURE	1/31 (3.2%)	1	0/32 (0%)	0
Respiratory, thoracic and mediastinal disorders
PULMONARY FIBROSIS (RADIOGRAPHIC CHANGES)	0/31 (0%)	0	1/32 (3.1%)	1
Surgical and medical procedures
INR (INTERNATIONAL NORMALIZED RATIO OF PROTHROMBIN TIME)	0/31 (0%)	0	1/32 (3.1%)	1
Vascular disorders
THROMBOSIS/THROMBUS/EMBOLISM	2/31 (6.5%)	2	0/32 (0%)	0
VESSEL INJURY-ARTERY / AORTA	1/31 (3.2%)	1	0/32 (0%)	0
Other (Not Including Serious) Adverse Events
	Placebo		Risedronate
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	26/31 (83.9%)		29/32 (90.6%)
Blood and lymphatic system disorders
EDEMA: LIMB	5/31 (16.1%)	6	5/32 (15.6%)	6
HEMOGLOBIN	3/31 (9.7%)	3	2/32 (6.3%)	2
HEMOLYSIS (E.G., IMMUNE HEMOLYTIC ANEMIA, DRUG-RELATED HEMOLYSIS)	1/31 (3.2%)	1	0/32 (0%)	0
PLATELETS	1/31 (3.2%)	1	0/32 (0%)	0
Cardiac disorders
CARDIAC GENERAL - OTHER	1/31 (3.2%)	1	0/32 (0%)	0
HYPERTENSION	5/31 (16.1%)	6	1/32 (3.1%)	1
HYPOTENSION	0/31 (0%)	0	1/32 (3.1%)	1
RESTRICTIVE CARDIOMYOPATHY	0/31 (0%)	0	1/32 (3.1%)	2
SUPRAVENTRICULAR AND NODAL ARRHYTHMIA / SINUS BRADYCARDIA	1/31 (3.2%)	1	0/32 (0%)	0
Ear and labyrinth disorders
OTITIS, MIDDLE EAR (NON-INFECTIOUS)	0/31 (0%)	0	1/32 (3.1%)	1
Endocrine disorders
ENDOCRINE - OTHER	1/31 (3.2%)	1	0/32 (0%)	0
HOT FLASHES/FLUSHES	16/31 (51.6%)	17	16/32 (50%)	20
Eye disorders
CATARACT	0/31 (0%)	0	1/32 (3.1%)	1
OCULAR/VISUAL - OTHER	1/31 (3.2%)	1	1/32 (3.1%)	1
WATERY EYE (EPIPHORA, TEARING)	0/31 (0%)	0	1/32 (3.1%)	1
Gastrointestinal disorders
ANOREXIA	1/31 (3.2%)	1	3/32 (9.4%)	3
CONSTIPATION	8/31 (25.8%)	8	8/32 (25%)	9
DIARRHEA	3/31 (9.7%)	3	5/32 (15.6%)	8
DISTENSION/BLOATING, ABDOMINAL	1/31 (3.2%)	1	1/32 (3.1%)	1
DRY MOUTH/SALIVARY GLAND (XEROSTOMIA)	3/31 (9.7%)	3	0/32 (0%)	0
DYSPHAGIA (DIFFICULTY SWALLOWING)	0/31 (0%)	0	1/32 (3.1%)	1
GASTRITIS (INCLUDING BILE REFLUX GASTRITIS)	0/31 (0%)	0	1/32 (3.1%)	1
GASTROINTESTINAL - OTHER	2/31 (6.5%)	2	4/32 (12.5%)	6
HEARTBURN/DYSPEPSIA	4/31 (12.9%)	4	6/32 (18.8%)	6
NAUSEA	4/31 (12.9%)	5	5/32 (15.6%)	6
PAIN / ABDOMEN NOS	1/31 (3.2%)	1	0/32 (0%)	0
VOMITING	2/31 (6.5%)	3	2/32 (6.3%)	2
General disorders
CONSTITUTIONAL SYMPTOMS - OTHER	6/31 (19.4%)	6	4/32 (12.5%)	9
FATIGUE (ASTHENIA, LETHARGY, MALAISE)	13/31 (41.9%)	19	12/32 (37.5%)	15
FEVER (IN THE ABSENCE OF NEUTROPENIA, WHERE NEUTROPENIA IS DEFINED AS ANC <1.0 X 10E9/L)	1/31 (3.2%)	1	0/32 (0%)	0
INSOMNIA	6/31 (19.4%)	7	5/32 (15.6%)	5
OBESITY	1/31 (3.2%)	1	0/32 (0%)	0
PAIN / BACK	6/31 (19.4%)	7	10/32 (31.3%)	12
PAIN / HEAD/HEADACHE	1/31 (3.2%)	1	2/32 (6.3%)	2
PAIN / NECK	2/31 (6.5%)	2	3/32 (9.4%)	3
PAIN / PAIN NOS	0/31 (0%)	0	2/32 (6.3%)	3
PAIN - OTHER	1/31 (3.2%)	1	3/32 (9.4%)	6
SWEATING (DIAPHORESIS)	3/31 (9.7%)	4	1/32 (3.1%)	1
WEIGHT GAIN	1/31 (3.2%)	3	0/32 (0%)	0
WEIGHT LOSS	1/31 (3.2%)	1	2/32 (6.3%)	2
Infections and infestations
INFECTION WITH GRADE 3 OR 4 NEUTROPHILS (ANC <1.0 X 10E9/L) / MIDDLE EAR (OTITIS MEDIA)	0/31 (0%)	0	1/32 (3.1%)	1
INFECTION - OTHER	1/31 (3.2%)	1	2/32 (6.3%)	2
INFECTION WITH NORMAL ANC OR GRADE 1 OR 2 NEUTROPHILS / BLADDER (URINARY)	0/31 (0%)	0	1/32 (3.1%)	1
INFECTION WITH NORMAL ANC OR GRADE 1 OR 2 NEUTROPHILS / JOINT	1/31 (3.2%)	1	0/32 (0%)	0
INFECTION WITH NORMAL ANC OR GRADE 1 OR 2 NEUTROPHILS / LUNG (PNEUMONIA)	1/31 (3.2%)	1	0/32 (0%)	0
INFECTION WITH NORMAL ANC OR GRADE 1 OR 2 NEUTROPHILS / NERVE-PERIPHERAL	1/31 (3.2%)	1	0/32 (0%)	0
INFECTION WITH NORMAL ANC OR GRADE 1 OR 2 NEUTROPHILS / PENIS	1/31 (3.2%)	1	0/32 (0%)	0
INFECTION WITH NORMAL ANC OR GRADE 1 OR 2 NEUTROPHILS / SKIN (CELLULITIS)	1/31 (3.2%)	1	0/32 (0%)	0
INFECTION WITH NORMAL ANC OR GRADE 1 OR 2 NEUTROPHILS / UPPER AIRWAY NOS	1/31 (3.2%)	1	0/32 (0%)	0
INFECTION WITH NORMAL ANC OR GRADE 1 OR 2 NEUTROPHILS / URINARY TRACT NOS	0/31 (0%)	0	1/32 (3.1%)	1
INFECTION WITH UNKNOWN ANC / LUNG (PNEUMONIA)	1/31 (3.2%)	1	1/32 (3.1%)	1
INFECTION WITH UNKNOWN ANC / UNGUAL (NAILS)	1/31 (3.2%)	1	0/32 (0%)	0
INFECTION WITH UNKNOWN ANC / URINARY TRACT NOS	0/31 (0%)	0	1/32 (3.1%)	1
INFECTION WITH UNKNOWN ANC / WOUND	1/31 (3.2%)	1	0/32 (0%)	0
UPPER RESPIRATORY INFECTION	1/31 (3.2%)	1	1/32 (3.1%)	1
Investigations
ALT, SGPT (SERUM GLUTAMIC PYRUVIC TRANSAMINASE)	2/31 (6.5%)	3	0/32 (0%)	0
AST, SGOT(SERUM GLUTAMIC OXALOACETIC TRANSAMINASE)	1/31 (3.2%)	2	0/32 (0%)	0
BILIRUBIN (HYPERBILIRUBINEMIA)	1/31 (3.2%)	2	0/32 (0%)	0
CHOLESTEROL, SERUM-HIGH (HYPERCHOLESTREMIA)	1/31 (3.2%)	1	1/32 (3.1%)	1
CREATININE	1/31 (3.2%)	1	0/32 (0%)	0
GLUCOSE, SERUM-HIGH (HYPERGLYCEMIA)	3/31 (9.7%)	6	0/32 (0%)	0
SODIUM, SERUM-LOW (HYPONATREMIA)	1/31 (3.2%)	1	0/32 (0%)	0
Musculoskeletal and connective tissue disorders
ARTHRITIS (NON-SEPTIC)	0/31 (0%)	0	2/32 (6.3%)	2
CERVICAL SPINE-RANGE OF MOTION	0/31 (0%)	0	1/32 (3.1%)	1
EXTREMITY-LOWER (GAIT/WALKING)	1/31 (3.2%)	1	1/32 (3.1%)	1
EXTREMITY-UPPER (FUNCTION)	2/31 (6.5%)	2	0/32 (0%)	0
FRACTURE	2/31 (6.5%)	2	0/32 (0%)	0
JOINT-EFFUSION	1/31 (3.2%)	1	1/32 (3.1%)	1
JOINT-FUNCTION	3/31 (9.7%)	4	1/32 (3.1%)	1
LUMBAR SPINE-RANGE OF MOTION	1/31 (3.2%)	2	0/32 (0%)	0
MUSCLE WEAKNESS, GENERALIZED OR SPECIFIC AREA (NOT DUE TO NEUROPATHY) / EXTREMITY-LOWER	3/31 (9.7%)	3	2/32 (6.3%)	2
MUSCLE WEAKNESS, GENERALIZED OR SPECIFIC AREA (NOT DUE TO NEUROPATHY) / EXTREMITY-UPPER	0/31 (0%)	0	1/32 (3.1%)	1
MUSCLE WEAKNESS, GENERALIZED OR SPECIFIC AREA (NOT DUE TO NEUROPATHY) / RIGHT-SIDED	0/31 (0%)	0	1/32 (3.1%)	1
MUSCLE WEAKNESS, GENERALIZED OR SPECIFIC AREA (NOT DUE TO NEUROPATHY) / WHOLE BODY/GENERALIZED	1/31 (3.2%)	1	1/32 (3.1%)	1
MUSCULOSKELETAL/SOFT TISSUE - OTHER	3/31 (9.7%)	4	6/32 (18.8%)	11
OSTEOPOROSIS	1/31 (3.2%)	1	0/32 (0%)	0
PAIN / BONE	4/31 (12.9%)	6	1/32 (3.1%)	1
PAIN / EXTREMITY-LIMB	4/31 (12.9%)	5	5/32 (15.6%)	8
PAIN / JOINT	6/31 (19.4%)	9	5/32 (15.6%)	10
PAIN / MUSCLE	0/31 (0%)	0	2/32 (6.3%)	2
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
SECONDARY MALIGNANCY - POSSIBLY RELATED TO CANCER TREATMENT (SPECIFY, __)	1/31 (3.2%)	1	1/32 (3.1%)	1
Nervous system disorders
CONFUSION	1/31 (3.2%)	1	0/32 (0%)	0
DIZZINESS	2/31 (6.5%)	2	2/32 (6.3%)	2
NEUROLOGY - OTHER	2/31 (6.5%)	2	0/32 (0%)	0
NEUROPATHY: CRANIAL / CN VII MOTOR-FACE; SENSORY-TASTE	1/31 (3.2%)	1	0/32 (0%)	0
NEUROPATHY: MOTOR	0/31 (0%)	0	1/32 (3.1%)	1
NEUROPATHY: SENSORY	6/31 (19.4%)	9	6/32 (18.8%)	8
SEIZURE	1/31 (3.2%)	1	0/32 (0%)	0
SYNCOPE (FAINTING)	1/31 (3.2%)	1	0/32 (0%)	0
Psychiatric disorders
MOOD ALTERATION / AGITATION	1/31 (3.2%)	1	0/32 (0%)	0
MOOD ALTERATION / ANXIETY	3/31 (9.7%)	3	0/32 (0%)	0
MOOD ALTERATION / DEPRESSION	5/31 (16.1%)	5	3/32 (9.4%)	3
Renal and urinary disorders
HEMORRHAGE, GU / URINARY NOS	1/31 (3.2%)	1	0/32 (0%)	0
INCONTINENCE, URINARY	0/31 (0%)	0	1/32 (3.1%)	1
LEAK (INCLUDING ANASTOMOTIC), GU / URETHRA	0/31 (0%)	0	1/32 (3.1%)	1
OBSTRUCTION, GU / URETER	1/31 (3.2%)	1	0/32 (0%)	0
RENAL/GENITOURINARY - OTHER	3/31 (9.7%)	6	3/32 (9.4%)	3
URINARY FREQUENCY/URGENCY	7/31 (22.6%)	8	7/32 (21.9%)	8
URINARY RETENTION (INCLUDING NEUROGENIC BLADDER)	1/31 (3.2%)	1	1/32 (3.1%)	1
Reproductive system and breast disorders
ERECTILE DYSFUNCTION	1/31 (3.2%)	1	0/32 (0%)	0
GYNECOMASTIA	1/31 (3.2%)	1	1/32 (3.1%)	1
PAIN / BREAST	0/31 (0%)	0	1/32 (3.1%)	1
PAIN / PENIS	0/31 (0%)	0	1/32 (3.1%)	1
PAIN / SCROTUM	1/31 (3.2%)	1	0/32 (0%)	0
PAIN / TESTICLE	2/31 (6.5%)	2	0/32 (0%)	0
Respiratory, thoracic and mediastinal disorders
BRONCHOSPASM, WHEEZING	2/31 (6.5%)	2	0/32 (0%)	0
COUGH	5/31 (16.1%)	7	4/32 (12.5%)	5
DYSPNEA (SHORTNESS OF BREATH)	4/31 (12.9%)	5	4/32 (12.5%)	4
HEMORRHAGE, PULMONARY/UPPER RESPIRATORY / NOSE	1/31 (3.2%)	1	0/32 (0%)	0
HYPOXIA	1/31 (3.2%)	1	0/32 (0%)	0
NASAL CAVITY/PARANASAL SINUS REACTIONS	2/31 (6.5%)	2	0/32 (0%)	0
PULMONARY/UPPER RESPIRATORY - OTHER	1/31 (3.2%)	1	3/32 (9.4%)	3
VOICE CHANGES/DYSARTHRIA (E.G., HOARSENESS, LOSS OR ALTERATION IN VOICE, LARYNGITIS)	0/31 (0%)	0	1/32 (3.1%)	1
Skin and subcutaneous tissue disorders
BRUISING (IN ABSENCE OF GRADE 3 OR 4 THROMBOCYTOPENIA)	0/31 (0%)	0	1/32 (3.1%)	1
BURN	1/31 (3.2%)	1	0/32 (0%)	0
DERMATOLOGY/SKIN - OTHER	5/31 (16.1%)	5	3/32 (9.4%)	5
DRY SKIN	0/31 (0%)	0	3/32 (9.4%)	3
FLUSHING	1/31 (3.2%)	1	1/32 (3.1%)	1
HAIR LOSS/ALOPECIA (SCALP OR BODY)	1/31 (3.2%)	2	2/32 (6.3%)	2
INJECTION SITE REACTION/EXTRAVASATION CHANGES	1/31 (3.2%)	1	0/32 (0%)	0
NAIL CHANGES	0/31 (0%)	0	2/32 (6.3%)	2
PRURITUS/ITCHING	5/31 (16.1%)	5	2/32 (6.3%)	3
RASH/DESQUAMATION	3/31 (9.7%)	4	2/32 (6.3%)	2
RASH: ACNE/ACNEIFORM	1/31 (3.2%)	1	2/32 (6.3%)	2
RIGHT FOREARM LESION	1/31 (3.2%)	1	0/32 (0%)	0
WOUND COMPLICATION, NON-INFECTIOUS	1/31 (3.2%)	1	0/32 (0%)	0
Vascular disorders
THROMBOSIS/EMBOLISM (VASCULAR ACCESS-RELATED)	1/31 (3.2%)	1	0/32 (0%)	0
THROMBOSIS/THROMBUS/EMBOLISM	0/31 (0%)	0	2/32 (6.3%)	2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.