Study of Abiraterone Acetate in Participants With Metastatic Castration-Resistant Prostate Cancer (mCRPC), Chemo-Naive, Who Received a Prior Diethylstilbestrol Therapy

• Sponsor: Janssen Research & Development, LLC (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02217566
• Collaborator: (none)
• Enrollment: 46
• Locations: 5
• Arm: 1
• Actual Duration (Months): 49.1
• Patients Per Site: 9.2
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the efficacy, based on prostate-specific antigen (PSA) progression, of abiraterone acetate in participants with metastatic (spread of cancer cells from one part of the body to another) castration (any action, surgical, chemical, or otherwise, by which a male loses the functions of the testes) resistant prostate cancer (cancer in prostrate; a gland that makes fluid that aids movement of sperm) (mCRPC), chemo-naive (treatment of cancer is not done using drugs), who received a prior diethylstilbestrol therapy (DES).

Condition or Disease	Intervention/Treatment	Phase
Prostatic Neoplasms	Drug: Abiraterone acetate; Drug: Prednisone; Drug: Androgen deprivation therapy (ADT)	Phase 2

Detailed Description

This is a Phase 2, multinational (when medical research study takes place in more than one country), multicenter (when more than one hospital or medical school team work on a medical research study), open-label (all people know the identity of the intervention), and single arm study to determine benefits of abiraterone acetate and low-dose prednisone to androgen deprivation therapy (ADT) in mCRPC participants who failed to prior DES therapy. The study will consist of a Screening Phase of up to 28 days before enrollment; a PSA Evaluation Phase; and a Follow-up Phase of up to 24 months. Each cycle of abiraterone therapy will be of 28 days. Participants will receive 1000 milligram (mg) abiraterone acetate orally once daily plus prednisone 5 mg orally once daily plus stable regimen of ADT (luteinizing hormone-releasing hormone [LHRH] agonists) as per Investigator's discretion. Treatment will continue until PSA progression, clinical progression, consent withdrawal, or the occurrence of unacceptable toxicity. Efficacy will primarily be assessed by time to PSA progression. Participants' safety will be monitored throughout the study.

Study Design

• Study Type: Interventional
• Actual Enrollment: 46 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Abiraterone Acetate in Patients With Metastatic Castration-Resistant Prostate Cancer, Chemo-Naive, Who Received a Prior Diethylstilbestrol Therapy
• Actual Study Start Date: Sep 23, 2014
• Actual Primary Completion Date: Oct 26, 2018
• Actual Study Completion Date: Oct 26, 2018

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Abiraterone Acetate Participants will receive abiraterone acetate 1000 milligram (mg) orally once daily along with prednisone 5 mg orally once daily and androgen deprivation therapy (ADT) as per Investigator's discretion until prostate-specific Antigen (PSA) progression, clinical progression, consent withdrawal, or the occurrence of unacceptable toxicity.

Drug: Abiraterone acetate; Participants will receive abiraterone acetate 1000 mg (4*250 mg tablets) orally once daily until PSA progression, clinical progression, consent withdrawal, or the occurrence of unacceptable toxicity.; Other Names: ZYTIGA® JNJ-212082 ; Drug: Prednisone; Participants will prednisone 5 mg orally once daily from Day 1 of Cycle 1 and continues until PSA progression, clinical progression, consent withdrawal, or the occurrence of unacceptable toxicity.; Drug: Androgen deprivation therapy (ADT); Participants will remain on a stable regimen of ADT, that is, luteinizing hormone-releasing hormone (LHRH) agonists including leuprolide acetate and goserelin acetate as per Investigator's discretion.

Outcome Measures

Primary Outcome Measures

1. Time to Prostate-specific Antigen (PSA) Progression [Up to 2 years]

   Time to PSA progression was calculated from date of enrollment to the date of first documentation of PSA progression. As per Prostate Cancer Clinical Trials Working Group (PCWG2) criteria, PSA progression was defined as greater than or equal to (>=) 25 percent (%) and >=2 nanogram/milliliter (ng/mL) after 12 weeks (in case of no decline in PSA from Baseline), or first PSA increase that is >=25% and >=2 ng/mL above the nadir, and which was confirmed by a second value 3 or more weeks later (in case of decline of PSA from Baseline).

Secondary Outcome Measures

1. Percentage of Participants Who Achieved Prostate-Specific Antigen (PSA) Response [Week 12 to any time up to 2 years]

   The PSA response according to Prostate Specific Antigen Working Group 3 criteria was defined as at least 50% decrease in PSA level from Baseline.

2. Overall Survival [Up to 4 years]

   Overall survival was defined as the time from date of the first dose of abiraterone acetate to the date of death due to any cause. For participants who did not die until the time of analysis, survival time was censored at the time of last contact alive.

3. Percentage of Participants With Pain Progression as Assessed by Brief Pain Inventory - Short Form (BPI-SF) - Pain Severity Score [Up to 2 years]

   The BPI-SF is a publicly available instrument to assess the pain and includes severity and interference scores. BPI-SF is an 11-item self-report questionnaire that is designed to assess the severity and impact of pain on daily functions of a participant. Pain severity score is a mean value for BPI-SF questions 3, 4, 5 and 6 (questions inquiring about the extent of pain, where the extent is ranked from 0 [no pain] to 10 [pain as bad as you can imagine]). Pain severity progression was defined as an increase in score of 30% or greater from baseline without decrease in analgesic use.

4. Percentage of Participants With Pain Progression as Assessed by Brief Pain Inventory - Short Form (BPI-SF) - Pain Interference Score [Up to 2 years]

   The BPI-SF is a publicly available instrument to assess the pain and includes severity and interference scores. BPI-SF is an 11-item self-report questionnaire that is designed to assess the severity and impact of pain on daily functions of a participant. Pain interference score is mean value for the 7 BPI-SF questions (questions inquiring about the extent of interference with activities by pain) where the extent is ranked from 0 (does not interfere) to 10 (completely interferes). Pain interference progression was defined as an increase in score of 50% or greater from baseline without decrease in analgesic use.

5. Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Up to 4 years]

   An AE is any untoward medical occurrence in a participant who will receive study drug without regard to possibility of causal relationship. An SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; or congenital anomaly.

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 without neuroendocrine differentiation or small cell histology

• Prior therapy with diethylstilbestrol (DES) for castration resistant prostate cancer. Participants should demonstrate evidence of progression on DES or evidence of grades 3/4 toxicities on DES

• Metastatic disease documented by positive bone scan or metastatic lesions on computerized tomography (CT) or magnetic resonance imaging (MRI)

• May have received prior androgen blockage (bicalutamide or flutamide) but must have been discontinued for least 28 days

• Ongoing androgen deprivation therapy (ADT) (luteinizing hormone-releasing hormone [LHRH] agonist or orchiectomy), with serum testosterone level of less than 50 nanogram per deciliter (1.7 nanomole per liter) and eligible participants must maintain ADT

Exclusion Criteria:

• Active infection or other medical condition that would make prednisone use contraindicated

• Any chronic medical condition requiring a higher systemic dose of corticosteroid than 5 milligram (mg) prednisone per day

• Pathological finding consistent with small cell carcinoma of the prostate

• Known brain metastasis

• Has had prior cytotoxic chemotherapy or biologic therapy for the treatment of metastatic castration-resistant prostate cancer (mCRPC)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Porto Alegre		Brazil
2		Rio De Janeiro		Brazil
3		Santo Andre		Brazil
4		Sao Paulo		Brazil
5		São Paulo		Brazil

Sponsors and Collaborators

• Janssen Research & Development, LLC

Investigators

• Study Director: Janssen Research & Development, LLC Clinical Trial, Janssen Research & Development, LLC

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Feb 19, 2018

More Information

Publications

None provided.

• Responsible Party: Janssen Research & Development, LLC
• ClinicalTrials.gov Identifier: NCT02217566
• Other Study ID Numbers: CR103352; 212082PCR2036
• First Posted: Aug 15, 2014
• Last Update Posted: Jan 13, 2020
• Last Verified: Jan 1, 2020

• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Janssen Research & Development, LLC: Prostatic neoplasms; Diethylstilbestrol therapy; Abiraterone acetate; Prednisone; Androgen deprivation therapy
• Additional relevant MeSH terms: Prostatic Neoplasms; Prednisone; Abiraterone Acetate; Androgens

Study Results

Participant Flow

Recruitment Details	A total of 46 participants were enrolled into the study and were treated with abiraterone acetate and prednisone. Out of 46 participants, 6 did not fulfill all eligibility criteria and included in the safety population. Thirty-five (35) participants completed the study.

Arm/Group Title	Abiraterone Acetate
Arm/Group Description	Participants received abiraterone acetate 1000 milligram (mg) orally once daily along with prednisone 5 mg orally once daily and androgen deprivation therapy (ADT) as per Investigator's discretion until prostate-specific Antigen (PSA) progression, clinical progression, consent withdrawal, or the occurrence of unacceptable toxicity.
Period Title: Overall Study
STARTED	46
COMPLETED	35
NOT COMPLETED	11

Baseline Characteristics

Arm/Group Title	Abiraterone Acetate
Arm/Group Description	Participants received abiraterone acetate 1000 milligram (mg) orally once daily along with prednisone 5 mg orally once daily and androgen deprivation therapy (ADT) as per Investigator's discretion until prostate-specific Antigen (PSA) progression, clinical progression, consent withdrawal, or the occurrence of unacceptable toxicity.
Overall Participants	46
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	68.8 (7.71)
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	46 100%
Race/Ethnicity, Customized (Count of Participants)
Asian/Pacific Islander	1 2.2%
Black or African/South American	7 15.2%
Other	1 2.2%
White/Caucasian	37 80.4%
Region of Enrollment (Count of Participants)
BRAZIL	46 100%

Outcome Measures

1. Primary Outcome

Title	Time to Prostate-specific Antigen (PSA) Progression
Description	Time to PSA progression was calculated from date of enrollment to the date of first documentation of PSA progression. As per Prostate Cancer Clinical Trials Working Group (PCWG2) criteria, PSA progression was defined as greater than or equal to (>=) 25 percent (%) and >=2 nanogram/milliliter (ng/mL) after 12 weeks (in case of no decline in PSA from Baseline), or first PSA increase that is >=25% and >=2 ng/mL above the nadir, and which was confirmed by a second value 3 or more weeks later (in case of decline of PSA from Baseline).
Time Frame	Up to 2 years

Outcome Measure Data

Analysis Population Description

The efficacy population included all eligible participants who received at least one dose of any study drug.

Arm/Group Title	Abiraterone Acetate
Arm/Group Description	Participants received abiraterone acetate 1000 milligram (mg) orally once daily along with prednisone 5 mg orally once daily and androgen deprivation therapy (ADT) as per Investigator's discretion until prostate-specific Antigen (PSA) progression, clinical progression, consent withdrawal, or the occurrence of unacceptable toxicity.
Measure Participants	40
Median (95% Confidence Interval) [Months]	7.3

2. Secondary Outcome

Title	Percentage of Participants Who Achieved Prostate-Specific Antigen (PSA) Response
Description	The PSA response according to Prostate Specific Antigen Working Group 3 criteria was defined as at least 50% decrease in PSA level from Baseline.
Time Frame	Week 12 to any time up to 2 years

Outcome Measure Data

Analysis Population Description

The efficacy population included all eligible participants who received at least one dose of any study drug.

Arm/Group Title	Abiraterone Acetate
Arm/Group Description	Participants received abiraterone acetate 1000 milligram (mg) orally once daily along with prednisone 5 mg orally once daily and androgen deprivation therapy (ADT) as per Investigator's discretion until prostate-specific Antigen (PSA) progression, clinical progression, consent withdrawal, or the occurrence of unacceptable toxicity.
Measure Participants	40
Number (95% Confidence Interval) [Percentage of participants]	57.50 125%

3. Secondary Outcome

Title	Overall Survival
Description	Overall survival was defined as the time from date of the first dose of abiraterone acetate to the date of death due to any cause. For participants who did not die until the time of analysis, survival time was censored at the time of last contact alive.
Time Frame	Up to 4 years

Outcome Measure Data

Analysis Population Description

The efficacy population included all eligible participants who received at least one dose of any study drug.

Arm/Group Title	Abiraterone Acetate
Arm/Group Description	Participants received abiraterone acetate 1000 milligram (mg) orally once daily along with prednisone 5 mg orally once daily and androgen deprivation therapy (ADT) as per Investigator's discretion until prostate-specific Antigen (PSA) progression, clinical progression, consent withdrawal, or the occurrence of unacceptable toxicity.
Measure Participants	40
Median (95% Confidence Interval) [Months]	29.6

4. Secondary Outcome

Title	Percentage of Participants With Pain Progression as Assessed by Brief Pain Inventory - Short Form (BPI-SF) - Pain Severity Score
Description	The BPI-SF is a publicly available instrument to assess the pain and includes severity and interference scores. BPI-SF is an 11-item self-report questionnaire that is designed to assess the severity and impact of pain on daily functions of a participant. Pain severity score is a mean value for BPI-SF questions 3, 4, 5 and 6 (questions inquiring about the extent of pain, where the extent is ranked from 0 [no pain] to 10 [pain as bad as you can imagine]). Pain severity progression was defined as an increase in score of 30% or greater from baseline without decrease in analgesic use.
Time Frame	Up to 2 years

Outcome Measure Data

Analysis Population Description

The efficacy population included all eligible participants who received at least one dose of any study drug and with at least 2 BPI-SF assessments after baseline.

Arm/Group Title	Abiraterone Acetate
Arm/Group Description	Participants received abiraterone acetate 1000 milligram (mg) orally once daily along with prednisone 5 mg orally once daily and androgen deprivation therapy (ADT) as per Investigator's discretion until prostate-specific Antigen (PSA) progression, clinical progression, consent withdrawal, or the occurrence of unacceptable toxicity.
Measure Participants	36
Number [Percentage of participants]	19.44 42.3%

5. Secondary Outcome

Title	Percentage of Participants With Pain Progression as Assessed by Brief Pain Inventory - Short Form (BPI-SF) - Pain Interference Score
Description	The BPI-SF is a publicly available instrument to assess the pain and includes severity and interference scores. BPI-SF is an 11-item self-report questionnaire that is designed to assess the severity and impact of pain on daily functions of a participant. Pain interference score is mean value for the 7 BPI-SF questions (questions inquiring about the extent of interference with activities by pain) where the extent is ranked from 0 (does not interfere) to 10 (completely interferes). Pain interference progression was defined as an increase in score of 50% or greater from baseline without decrease in analgesic use.
Time Frame	Up to 2 years

Outcome Measure Data

Analysis Population Description

The efficacy population included all eligible participants who received at least one dose of any study drug and with at least 2 BPI-SF assessments after baseline.

Arm/Group Title	Abiraterone Acetate
Arm/Group Description	Participants received abiraterone acetate 1000 milligram (mg) orally once daily along with prednisone 5 mg orally once daily and androgen deprivation therapy (ADT) as per Investigator's discretion until prostate-specific Antigen (PSA) progression, clinical progression, consent withdrawal, or the occurrence of unacceptable toxicity.
Measure Participants	33
Number [Percentage of participants]	15.15 32.9%

6. Secondary Outcome

Title	Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Description	An AE is any untoward medical occurrence in a participant who will receive study drug without regard to possibility of causal relationship. An SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; or congenital anomaly.
Time Frame	Up to 4 years

Outcome Measure Data

Analysis Population Description

The safety population included all participants who received at least 1 dose of any study drug.

Arm/Group Title	Abiraterone Acetate
Arm/Group Description	Participants received abiraterone acetate 1000 milligram (mg) orally once daily along with prednisone 5 mg orally once daily and androgen deprivation therapy (ADT) as per Investigator's discretion until prostate-specific Antigen (PSA) progression, clinical progression, consent withdrawal, or the occurrence of unacceptable toxicity.
Measure Participants	46
Participants with AEs	45 97.8%
Participants with SAEs	11 23.9%

Adverse Events

Time Frame	Up to 4 years
Adverse Event Reporting Description	Safety population included all participants who received at least 1 dose of any study drug.
Arm/Group Title	Abiraterone Acetate
Arm/Group Description	Participants received abiraterone acetate 1000 milligram (mg) orally once daily along with prednisone 5 mg orally once daily and androgen deprivation therapy (ADT) as per Investigator's discretion until prostate-specific Antigen (PSA) progression, clinical progression, consent withdrawal, or the occurrence of unacceptable toxicity.
All Cause Mortality
	Abiraterone Acetate
	Affected / at Risk (%)	# Events
Total	3/46 (6.5%)
Serious Adverse Events
	Abiraterone Acetate
	Affected / at Risk (%)	# Events
Total	11/46 (23.9%)
Blood and lymphatic system disorders
Anaemia	1/46 (2.2%)
Cardiac disorders
Cardiac Failure	2/46 (4.3%)
Cardio-Respiratory Arrest	1/46 (2.2%)
Eye disorders
Amaurosis	1/46 (2.2%)
Gastrointestinal disorders
Gastrointestinal Obstruction	1/46 (2.2%)
Rectal Haemorrhage	1/46 (2.2%)
General disorders
Asthenia	1/46 (2.2%)
Infections and infestations
Cystitis	1/46 (2.2%)
Pneumonia	2/46 (4.3%)
Sepsis	1/46 (2.2%)
Urinary Tract Infection	1/46 (2.2%)
Injury, poisoning and procedural complications
Fall	1/46 (2.2%)
Femur Fracture	1/46 (2.2%)
Ulna Fracture	1/46 (2.2%)
Metabolism and nutrition disorders
Hyperkalaemia	1/46 (2.2%)
Nervous system disorders
Cerebrovascular Accident	1/46 (2.2%)
Dysarthria	1/46 (2.2%)
Spinal Cord Compression	1/46 (2.2%)
Tremor	1/46 (2.2%)
Psychiatric disorders
Delirium	1/46 (2.2%)
Renal and urinary disorders
Haematuria	2/46 (4.3%)
Nephrolithiasis	1/46 (2.2%)
Respiratory, thoracic and mediastinal disorders
Aspiration	1/46 (2.2%)
Chronic Obstructive Pulmonary Disease	1/46 (2.2%)
Dyspnoea	1/46 (2.2%)
Other (Not Including Serious) Adverse Events
	Abiraterone Acetate
	Affected / at Risk (%)	# Events
Total	45/46 (97.8%)
Blood and lymphatic system disorders
Anaemia	13/46 (28.3%)
Eosinophilia	1/46 (2.2%)
Lymphopenia	2/46 (4.3%)
Neutropenia	2/46 (4.3%)
Thrombocytopenia	3/46 (6.5%)
Cardiac disorders
Atrial Fibrillation	1/46 (2.2%)
Atrioventricular Block	1/46 (2.2%)
Bundle Branch Block Left	1/46 (2.2%)
Cardiac Failure	1/46 (2.2%)
Cardiac Failure Congestive	1/46 (2.2%)
Sinus Tachycardia	1/46 (2.2%)
Endocrine disorders
Hypothyroidism	1/46 (2.2%)
Eye disorders
Conjunctival Haemorrhage	1/46 (2.2%)
Eye Pain	1/46 (2.2%)
Glaucoma	1/46 (2.2%)
Ocular Hyperaemia	1/46 (2.2%)
Papilloedema	1/46 (2.2%)
Vision Blurred	1/46 (2.2%)
Gastrointestinal disorders
Abdominal Discomfort	1/46 (2.2%)
Abdominal Pain	3/46 (6.5%)
Abdominal Pain Lower	1/46 (2.2%)
Abdominal Pain Upper	8/46 (17.4%)
Abdominal Wall Haematoma	1/46 (2.2%)
Anal Incontinence	1/46 (2.2%)
Anorectal Discomfort	1/46 (2.2%)
Aphthous Ulcer	1/46 (2.2%)
Constipation	10/46 (21.7%)
Diarrhoea	9/46 (19.6%)
Diverticulum	1/46 (2.2%)
Dry Mouth	2/46 (4.3%)
Dyspepsia	4/46 (8.7%)
Flatulence	2/46 (4.3%)
Haematochezia	1/46 (2.2%)
Haemorrhoidal Haemorrhage	1/46 (2.2%)
Nausea	11/46 (23.9%)
Odynophagia	2/46 (4.3%)
Proctalgia	1/46 (2.2%)
Vomiting	12/46 (26.1%)
General disorders
Asthenia	8/46 (17.4%)
Chest Pain	4/46 (8.7%)
Face Oedema	1/46 (2.2%)
Fatigue	15/46 (32.6%)
Influenza Like Illness	4/46 (8.7%)
Localised Oedema	1/46 (2.2%)
Malaise	3/46 (6.5%)
Mucosal Inflammation	1/46 (2.2%)
Oedema Peripheral	9/46 (19.6%)
Pyrexia	4/46 (8.7%)
Hepatobiliary disorders
Hyperbilirubinaemia	1/46 (2.2%)
Infections and infestations
Anal Abscess	1/46 (2.2%)
Gastroenteritis	1/46 (2.2%)
Influenza	7/46 (15.2%)
Nasopharyngitis	1/46 (2.2%)
Paronychia	1/46 (2.2%)
Pneumonia	2/46 (4.3%)
Rhinitis	1/46 (2.2%)
Sinusitis	2/46 (4.3%)
Strongyloidiasis	1/46 (2.2%)
Subcutaneous Abscess	1/46 (2.2%)
Upper Respiratory Tract Infection	2/46 (4.3%)
Urinary Tract Infection	7/46 (15.2%)
Injury, poisoning and procedural complications
Eye Injury	1/46 (2.2%)
Fall	4/46 (8.7%)
Infusion Related Reaction	1/46 (2.2%)
Joint Injury	1/46 (2.2%)
Sciatic Nerve Injury	1/46 (2.2%)
Tooth Fracture	1/46 (2.2%)
Investigations
Alanine Aminotransferase Increased	1/46 (2.2%)
Aspartate Aminotransferase Increased	2/46 (4.3%)
Blood Alkaline Phosphatase Increased	3/46 (6.5%)
Blood Bilirubin Increased	2/46 (4.3%)
Blood Creatinine Increased	2/46 (4.3%)
Blood Lactate Dehydrogenase Increased	1/46 (2.2%)
Blood Pressure Increased	1/46 (2.2%)
ECG Electrically Inactive Area	1/46 (2.2%)
International Normalised Ratio	1/46 (2.2%)
Platelet Count Decreased	2/46 (4.3%)
Weight Decreased	6/46 (13%)
Weight Increased	1/46 (2.2%)
White Blood Cell Count Decreased	3/46 (6.5%)
Metabolism and nutrition disorders
Decreased Appetite	11/46 (23.9%)
Hypercholesterolaemia	1/46 (2.2%)
Hyperglycaemia	17/46 (37%)
Hyperkalaemia	1/46 (2.2%)
Hypokalaemia	2/46 (4.3%)
Metabolic Acidosis	1/46 (2.2%)
Vitamin B12 Deficiency	1/46 (2.2%)
Vitamin D Deficiency	2/46 (4.3%)
Musculoskeletal and connective tissue disorders
Arthralgia	12/46 (26.1%)
Back Pain	21/46 (45.7%)
Bone Pain	2/46 (4.3%)
Coccydynia	1/46 (2.2%)
Groin Pain	3/46 (6.5%)
Muscle Spasms	2/46 (4.3%)
Muscular Weakness	1/46 (2.2%)
Musculoskeletal Chest Pain	4/46 (8.7%)
Musculoskeletal Pain	5/46 (10.9%)
Myalgia	4/46 (8.7%)
Neck Pain	5/46 (10.9%)
Osteonecrosis of Jaw	1/46 (2.2%)
Osteopenia	1/46 (2.2%)
Osteoporosis	1/46 (2.2%)
Pain in Extremity	12/46 (26.1%)
Spinal Pain	2/46 (4.3%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer Pain	1/46 (2.2%)
Nervous system disorders
Cerebrovascular Accident	1/46 (2.2%)
Dizziness	4/46 (8.7%)
Headache	11/46 (23.9%)
Motor Dysfunction	1/46 (2.2%)
Neuropathy Peripheral	1/46 (2.2%)
Paraesthesia	4/46 (8.7%)
Syncope	3/46 (6.5%)
Tremor	1/46 (2.2%)
Psychiatric disorders
Anxiety	3/46 (6.5%)
Depression	1/46 (2.2%)
Insomnia	2/46 (4.3%)
Renal and urinary disorders
Dysuria	9/46 (19.6%)
Haematuria	6/46 (13%)
Lower Urinary Tract Symptoms	1/46 (2.2%)
Renal Failure	1/46 (2.2%)
Urethral Haemorrhage	1/46 (2.2%)
Urethral Pain	1/46 (2.2%)
Urinary Retention	2/46 (4.3%)
Reproductive system and breast disorders
Gynaecomastia	1/46 (2.2%)
Pelvic Pain	3/46 (6.5%)
Penile Burning Sensation	1/46 (2.2%)
Respiratory, thoracic and mediastinal disorders
Chronic Obstructive Pulmonary Disease	2/46 (4.3%)
Cough	10/46 (21.7%)
Dysphonia	1/46 (2.2%)
Dyspnoea	4/46 (8.7%)
Nasal Obstruction	1/46 (2.2%)
Oropharyngeal Pain	3/46 (6.5%)
Productive Cough	2/46 (4.3%)
Rhinorrhoea	2/46 (4.3%)
Tracheal Pain	1/46 (2.2%)
Upper Respiratory Tract Irritation	1/46 (2.2%)
Skin and subcutaneous tissue disorders
Alopecia	2/46 (4.3%)
Dry Skin	1/46 (2.2%)
Hyperhidrosis	3/46 (6.5%)
Petechiae	1/46 (2.2%)
Pruritus	1/46 (2.2%)
Rash	1/46 (2.2%)
Vascular disorders
Flushing	1/46 (2.2%)
Haematoma	1/46 (2.2%)
Hyperaemia	2/46 (4.3%)
Hypertension	19/46 (41.3%)
Hypotension	2/46 (4.3%)
Shock	1/46 (2.2%)
Varicose Vein	1/46 (2.2%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

A copy of the manuscript must be provided to the sponsor for review at least 60 days before submission for publication or presentation. If requested in writing, such publication will be withheld for up to an additional 60 days.