Single Dose Intravesical Apaziquone Postoperative in Patients Undergoing TURBT for Noninvasive Bladder Cancer (SPI-611)

• Sponsor: Spectrum Pharmaceuticals, Inc (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00461591
• Collaborator: (none)
• Enrollment: 802
• Locations: 74
• Arms: 2
• Actual Duration (Months): 57
• Patients Per Site: 10.8
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The purpose of this study was to evaluate the 2-Year Recurrence Rate of bladder cancer in randomized patients with tumor histology Ta, G1-G2 who received TransUrethral Resection of Bladder Tumor (TURBT) plus apaziquone versus those who received TURBT plus placebo.

Condition or Disease	Intervention/Treatment	Phase
Bladder Cancer	Drug: Apaziquone; Drug: Placebo; Procedure: TURBT	Phase 3

Detailed Description

This was a Phase 3, multicenter, randomized, double-blind, placebo-controlled study. Within 14 days of Screening, eligible patients underwent a TURBT during Visit 1 (Day 0) following which they were immediately randomized in a 1:1 ratio to receive either placebo or 4 mg apaziquone, instilled in a volume of 40 mL into the bladder within 6 hours from the end of the TURBT procedure. After a 60-minute retention period, study drug was drained from the bladder.

A postoperative follow-up examination and review of the local pathology report were performed at Visit 2, which occurred 21 days (±10 days) after the TURBT (Week 3).

• If the histology of the patient's tumor was confirmed as Ta, G1-G2 (ie, low grade according to World Health Organization [WHO]/International Society of Urologic Pathology [ISUP] classification), no further treatment was given and the patient was observed cystoscopically every 3 months through Year 2 for tumor recurrence (Visit 3 through Visit 10).

• If the histology of the patient's tumor was other than Ta, G1 or G2 (low grade [WHO/ISUP classification]), further treatment was given in accordance with current treatment guidelines, and the patient was followed up cystoscopically every 3 months through Year 2 for tumor recurrence (Visit 3 through Visit 10).

All patients were to be followed for 2 years.

Study Design

• Study Type: Interventional
• Actual Enrollment: 802 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Multicenter, Randomized, Placebo-Controlled, Double-Blind, Phase 3 Trial of Single Dose Intravesical Apaziquone (EOquin®) as a Surgical Adjuvant Instilled in the Early Postoperative Period in Patients Undergoing Transurethral Resection for Noninvasive Bladder Cancer (Protocol SPI-611)
• Actual Study Start Date: Apr 1, 2007
• Actual Primary Completion Date: Jan 1, 2012
• Actual Study Completion Date: Jan 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Apaziquone TURBT + a single intravesical dose of Apaziquone 4mg in 40ml instilled into the bladder post-TURBT	Drug: Apaziquone; A single intravesical dose of Apaziquone 4mg in 40ml instilled into the bladder post-TURBT; Other Names: EOquin®, Qapzola ; Procedure: TURBT; TransUrethral Resection of the Bladder Tumor
Placebo Comparator: Placebo TURBT + a single intravesical dose of placebo instilled into the bladder post-TURBT	Drug: Placebo; A single intravesical dose of placebo instilled into the bladder post-TURBT; Procedure: TURBT; TransUrethral Resection of the Bladder Tumor

Outcome Measures

Primary Outcome Measures

1. Recurrence Rate at 2 Years [2 years]

   The percentage of participants with histologically confirmed recurrence of the bladder tumor at any time after randomization and on or before year 2.

Secondary Outcome Measures

1. Time to Recurrence [2 years]

   The number of months from randomization to histologically confirmed recurrence of the patient's bladder tumor.

2. Progression Rate at 2 Years [2 years]

   The percentage of participants that progress to either a higher stage or grade from the histologically confirmed stage and grade at time of randomization.

3. Time to Progression [2 years]

   The number of months from randomization to progression to either a higher stage or grade of the patient's bladder tumor.

4. Number of Recurrences Per Patient [2 years]

   The number of histologically confirmed recurrences during the course of the study.

5. Disease Free Interval [2 years]

   The number of months from randomization to histologically confirmed progression of the patient's bladder tumor or death from any cause

6. Disease Free Survival [2 years]

   The number of months from randomization to histologically confirmed recurrence of the patient's bladder tumor or death from any cause

7. Overall Survival [2 years]

   The number of months from randomization to death from any cause.

Eligibility Criteria

Criteria

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

Inclusion Criteria: (All questions must be answered YES)

• Has the patient given written informed consent?

• Is the patient at least 18 years old?

• Does the patient have transitional cell carcinoma of the bladder with clinically apparent stage Ta, grade G1-G2?

• If the patient is a female of childbearing potential, is she using an acceptable/effective method of contraception?

• If the patient is a female of childbearing potential, has she had a negative serum pregnancy test within the past 14 days?

• Is the patient willing and able to abide by the protocol?

Exclusion Criteria: (All questions must be answered NO)

• Does the patient have more than 4 bladder tumors?

• Does any single bladder tumor exceed 3.5 cm in diameter?

• Does the patient have a single, primary (no previous diagnosis of TCC) bladder tumor <0.5 cm?

• Has the patient ever received Apaziquone?

• Does the patient have, or has the patient ever had, any bladder tumor known to be other than stage Ta or grade G1 or G2 (low grade [WHO/ISUP classification])?

• Does the patient have, or has the patient ever had any bladder tumor with histology other than transitional cell carcinoma?

• Does the patient have, or has the patient ever had, carcinoma in situ (CIS)?

• Does the patient have an active urinary tract infection?

• Does the patient have a bleeding disorder or a screening platelet count < 100 x 10^9/L?

• Does the patient have any unstable medical condition that would make it unsafe for him/her to undergo TURBT under general or spinal anesthesia?

• Does the patient have a screening hemoglobin < 10 mg/dL, a screening absolute neutrophil count < 1.5 x 10^9/L or a screening creatinine > 2 mg/dL?

• Does the patient have a known immunodeficiency disorder?

• Has the patient received any investigational treatment within the past 30 days?

• Is the patient breast feeding?

• Does the patient have a history of interstitial cystitis?

• Does the patient have a history of allergy to red color food dye?

• Has the patient had transitional cell carcinoma of the bladder within the past 4 months?

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Alaska Clinical Research Center, LLC	Anchorage	Alaska	United States	99508
2	BCG Oncology	Phoenix	Arizona	United States	85032
3	Sun Health Research Institute	Sun City	Arizona	United States	85032
4	Urology Associates Medical Group	Burbank	California	United States	91505
5	Urology Associates of Central CA	Fresno	California	United States	93720
6	South Orange County Medical Research Center	Laguna Woods	California	United States	92653
7	Kaiser Permanente Los Angeles Medical Center	Los Angeles	California	United States	90027
8	Cancer Research Dept/St. Joseph Hospital	Orange	California	United States	92868
9	San Bernardino Urologic Association	San Bernardino	California	United States	92404
10	VA Medical Center	San Francisco	California	United States	94121
11	The Urology Center of Colorado	Denver	Colorado	United States	80211
12	Connecticut Clinical Research Center	Middlebury	Connecticut	United States	06762
13	Urologic Surgeons of Washington	Washington	District of Columbia	United States	20006
14	Lakeland Regional Cancer Center	Lakeland	Florida	United States	33805
15	Urology Consultants	Longwood	Florida	United States	32750
16	University of Miami	Miami	Florida	United States	33136
17	Advanced Research Institute	New Port Richey	Florida	United States	34652
18	Advanced Research Institute	New Port Richey	Florida	United States	34655
19	Florida Foundation for Healthcare Research	Ocala	Florida	United States	34474
20	Florida Urology Specialists	Sarasota	Florida	United States	34237
21	Southeastern Research Group, Inc.	Tallahassee	Florida	United States	32308
22	Gainesville Urology, PC	Gainesville	Georgia	United States	30501
23	Urological Professional Association	Macon	Georgia	United States	31217
24	North Idaho Urology	Coeur d'Alene	Idaho	United States	83814
25	Idaho Urologic Institute, P.A.	Meridian	Idaho	United States	83642
26	University of Chicago	Chicago	Illinois	United States	60637
27	Urology Associates, SC	Mattoon	Illinois	United States	61938
28	Speciality Care Research	Peoria	Illinois	United States	61614
29	Northeast Indiana Research, LLC	Fort Wayne	Indiana	United States	46825
30	Metropolitan Urology	Jeffersonville	Indiana	United States	47130
31	Kansas City Urology Care, P.A.	Overland Park	Kansas	United States	66211
32	Regional Urology, LLC	Shreveport	Louisiana	United States	71106
33	Anne Arundel Urology	Annapolis	Maryland	United States	21401
34	Myron Murdock, MD, LLC	Greenbelt	Maryland	United States	20770
35	MMPC Urology	Grand Rapids	Michigan	United States	49546
36	Lakeside Urology, PC	Saint Joseph	Michigan	United States	49085
37	Michigan Institute of Urology, PC	Troy	Michigan	United States	48084
38	Five Valleys Urology	Missoula	Montana	United States	59802
39	Coastal Urological Associates, PA	Brick	New Jersey	United States	08724
40	AdvanceMed Research	Lawrenceville	New Jersey	United States	08648
41	Delaware Valley Urology, LLC-Marlton	Marlton	New Jersey	United States	08053
42	Deleware Valley Urology, LLC-Washington Township	Sewell	New Jersey	United States	08080
43	Delaware Valley Urology, LLC - Voorhees	Voorhees	New Jersey	United States	08043
44	Delaware Valley Urology, LLC-Westampton	Westampton	New Jersey	United States	08060
45	Urology Group of New Mexico	Albuquerque	New Mexico	United States	87109
46	Capital Region Urological Surgeons	Albany	New York	United States	12208
47	The Urological Institute of NE NY	Albany	New York	United States	12208
48	Adult and Pediatric Urology	Carmel	New York	United States	10512
49	Accumed Research Associates	Garden City	New York	United States	11530
50	Urological Surgeons of Long Island, P.C.	Garden City	New York	United States	11530
51	Hudson Valley Urology, PC	Kingston	New York	United States	12401
52	University Urology Associates	New York	New York	United States	10016
53	CNY Urology, PC	Oneida	New York	United States	13421
54	Hudson Valley Urology	Poughkeepsie	New York	United States	12601
55	Urology Associates of Rochester, LLC	Rochester	New York	United States	14618
56	Center for Urologic Research of WNY, LLC	Williamsville	New York	United States	14221
57	TriState Urologic Services PSC, Inc.	Cincinnati	Ohio	United States	45212
58	Columbus Urology Research, LLC	Columbus	Ohio	United States	43220
59	Oregon Urology Institute	Springfield	Oregon	United States	97477
60	Urologic Consultants of South Eastern Pennsylvania	Bala-Cynwyd	Pennsylvania	United States	19026
61	Urological Associates of Lancaster	Lancaster	Pennsylvania	United States	17604
62	Fox Chase Cancer Center	Philadelphia	Pennsylvania	United States	19111-2497
63	Triangle Urology Group	Pittsburgh	Pennsylvania	United States	15212
64	Susquehenna Urology	Williamsport	Pennsylvania	United States	17701
65	Carolina Urologic Research Center	Myrtle Beach	South Carolina	United States	29572
66	The Conrad Pearson Clinic	Germantown	Tennessee	United States	38138
67	Corpus Christi Urology Group LLC	Corpus Christi	Texas	United States	78404
68	Urology Clinics of North Texas	Dallas	Texas	United States	75231
69	Urology San Antonio Research	San Antonio	Texas	United States	78229
70	Mary Washington Hospital and Urology Associates of Fredericksburg	Fredericksburg	Virginia	United States	22401
71	Urology of Virginia, PC	Norfolk	Virginia	United States	23502
72	Urology of Virginia, PC	Virginia Beach	Virginia	United States	23454
73	Integrity Medical Research, LLC	Mountlake Terrace	Washington	United States	98043
74	Seattle Urological Associates	Seattle	Washington	United States	98104

Sponsors and Collaborators

• Spectrum Pharmaceuticals, Inc

Investigators

• Study Director: Shanta Chawla, MD, Spectrum Pharmaceuticals, Inc

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Spectrum Pharmaceuticals, Inc
• ClinicalTrials.gov Identifier: NCT00461591
• Other Study ID Numbers: SPI-611
• First Posted: Apr 18, 2007
• Last Update Posted: Mar 30, 2021
• Last Verified: Mar 1, 2021

• Keywords provided by Spectrum Pharmaceuticals, Inc: Noninvasive Bladder Cancer
• Additional relevant MeSH terms: Urinary Bladder Neoplasms; Apaziquone

Study Results

Participant Flow

Arm/Group Title	Apaziquone	Placebo
Arm/Group Description	Apaziquone: TURBT + a single intravesical dose of Apaziquone 4mg in 40ml instilled into the bladder post-TURBT	Placebo: TURBT + a single intravesical dose of placebo instilled into the bladder post-TURBT
Period Title: Overall Study
STARTED	406	396
COMPLETED	317	311
NOT COMPLETED	89	85

Baseline Characteristics

Arm/Group Title	Apaziquone	Placebo	Total
Arm/Group Description	Apaziquone: TURBT + a single intravesical dose of Apaziquone 4mg in 40ml instilled into the bladder post-TURBT	Placebo: TURBT + a single intravesical dose of placebo instilled into the bladder post-TURBT	Total of all reporting groups
Overall Participants	406	396	802
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	67.5 (10.92)	68.2 (10.72)	67.8 (10.82)
Age, Customized (Count of Participants)
<65	159 39.2%	146 36.9%	305 38%
65-75	140 34.5%	139 35.1%	279 34.8%
>75	107 26.4%	111 28%	218 27.2%
Sex: Female, Male (Count of Participants)
Female	108 26.6%	102 25.8%	210 26.2%
Male	298 73.4%	294 74.2%	592 73.8%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	13 3.2%	17 4.3%	30 3.7%
Not Hispanic or Latino	393 96.8%	379 95.7%	772 96.3%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	1 0.2%	3 0.8%	4 0.5%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	11 2.7%	9 2.3%	20 2.5%
White	392 96.6%	383 96.7%	775 96.6%
More than one race	2 0.5%	1 0.3%	3 0.4%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	381 93.8%	375 94.7%	756 94.3%
Poland	25 6.2%	21 5.3%	46 5.7%

Outcome Measures

1. Primary Outcome

Title	Recurrence Rate at 2 Years
Description	The percentage of participants with histologically confirmed recurrence of the bladder tumor at any time after randomization and on or before year 2.
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

Target Ta, G1-G2 Population: patients who had 4 or fewer tumors that were ≤ 3.5 cm each at the time of randomization and who had subsequent histological confirmation from the central pathology lab that the tumors resected at the time of randomization were Ta, Grade 1 or 2.

Arm/Group Title	Apaziquone	Placebo
Arm/Group Description	Apaziquone: TURBT + a single intravesical dose of Apaziquone 4mg in 40ml instilled into the bladder post-TURBT	Placebo: TURBT + a single intravesical dose of placebo instilled into the bladder post-TURBT
Measure Participants	295	271
Recurrence	112 27.6%	121 30.6%
Non-Recurrence	183 45.1%	150 37.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Apaziquone, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1068
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.76
	Confidence Interval	(2-Sided) 95%; 0.54 to 1.06
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Time to Recurrence
Description	The number of months from randomization to histologically confirmed recurrence of the patient's bladder tumor.
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

Target Ta, G1-G2 Population: patients who had 4 or fewer tumors that were ≤ 3.5 cm each at the time of randomization and who had subsequent histological confirmation from the central pathology lab that the tumors resected at the time of randomization were Ta, Grade 1 or 2.

Arm/Group Title	Apaziquone	Placebo
Arm/Group Description	Apaziquone: TURBT + a single intravesical dose of Apaziquone 4mg in 40ml instilled into the bladder post-TURBT	Placebo: TURBT + a single intravesical dose of placebo instilled into the bladder post-TURBT
Measure Participants	295	271
Mean (Standard Error) [months]	18.3 (0.47)	16.7 (0.55)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Apaziquone, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0412
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.77
	Confidence Interval	(2-Sided) 95%; 0.59 to 0.99
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Progression Rate at 2 Years
Description	The percentage of participants that progress to either a higher stage or grade from the histologically confirmed stage and grade at time of randomization.
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

Target Ta, G1-G2 Population: patients who had 4 or fewer tumors that were ≤ 3.5 cm each at the time of randomization and who had subsequent histological confirmation from the central pathology lab that the tumors resected at the time of randomization were Ta, Grade 1 or 2.

Arm/Group Title	Apaziquone	Placebo
Arm/Group Description	Apaziquone: TURBT + a single intravesical dose of Apaziquone 4mg in 40ml instilled into the bladder post-TURBT	Placebo: TURBT + a single intravesical dose of placebo instilled into the bladder post-TURBT
Measure Participants	295	271
Progression	30 7.4%	39 9.8%
Non-Progression	265 65.3%	232 58.6%

4. Secondary Outcome

Title	Time to Progression
Description	The number of months from randomization to progression to either a higher stage or grade of the patient's bladder tumor.
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

Target Ta, G1-G2 Population: patients who had 4 or fewer tumors that were ≤ 3.5 cm each at the time of randomization and who had subsequent histological confirmation from the central pathology lab that the tumors resected at the time of randomization were Ta, Grade 1 or 2.

Arm/Group Title	Apaziquone	Placebo
Arm/Group Description	Apaziquone: TURBT + a single intravesical dose of Apaziquone 4mg in 40ml instilled into the bladder post-TURBT	Placebo: TURBT + a single intravesical dose of placebo instilled into the bladder post-TURBT
Measure Participants	295	271
Mean (Standard Error) [months]	22.9 (0.26)	22.0 (0.34)

5. Secondary Outcome

Title	Number of Recurrences Per Patient
Description	The number of histologically confirmed recurrences during the course of the study.
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

Target Ta, G1-G2 Population: patients who had 4 or fewer tumors that were ≤ 3.5 cm each at the time of randomization and who had subsequent histological confirmation from the central pathology lab that the tumors resected at the time of randomization were Ta, Grade 1 or 2.

Arm/Group Title	Apaziquone	Placebo
Arm/Group Description	Apaziquone: TURBT + a single intravesical dose of Apaziquone 4mg in 40ml instilled into the bladder post-TURBT	Placebo: TURBT + a single intravesical dose of placebo instilled into the bladder post-TURBT
Measure Participants	295	271
Mean (Standard Deviation) [times]	0.6 (1.03)	0.9 (1.21)

6. Secondary Outcome

Title	Disease Free Interval
Description	The number of months from randomization to histologically confirmed progression of the patient's bladder tumor or death from any cause
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

Target Ta, G1-G2 Population: patients who had 4 or fewer tumors that were ≤ 3.5 cm each at the time of randomization and who had subsequent histological confirmation from the central pathology lab that the tumors resected at the time of randomization were Ta, Grade 1 or 2.

Arm/Group Title	Apaziquone	Placebo
Arm/Group Description	Apaziquone: TURBT + a single intravesical dose of Apaziquone 4mg in 40ml instilled into the bladder post-TURBT	Placebo: TURBT + a single intravesical dose of placebo instilled into the bladder post-TURBT
Measure Participants	295	271
Mean (Standard Error) [months]	22.9 (0.26)	22.0 (0.34)

7. Secondary Outcome

Title	Disease Free Survival
Description	The number of months from randomization to histologically confirmed recurrence of the patient's bladder tumor or death from any cause
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

Target Ta, G1-G2 Population: patients who had 4 or fewer tumors that were ≤ 3.5 cm each at the time of randomization and who had subsequent histological confirmation from the central pathology lab that the tumors resected at the time of randomization were Ta, Grade 1 or 2.

Arm/Group Title	Apaziquone	Placebo
Arm/Group Description	Apaziquone: TURBT + a single intravesical dose of Apaziquone 4mg in 40ml instilled into the bladder post-TURBT	Placebo: TURBT + a single intravesical dose of placebo instilled into the bladder post-TURBT
Measure Participants	295	271
Mean (Standard Error) [months]	18.0 (0.48)	16.4 (0.55)

8. Secondary Outcome

Title	Overall Survival
Description	The number of months from randomization to death from any cause.
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

Target Ta, G1-G2 Population: patients who had 4 or fewer tumors that were ≤ 3.5 cm each at the time of randomization and who had subsequent histological confirmation from the central pathology lab that the tumors resected at the time of randomization were Ta, Grade 1 or 2.

Arm/Group Title	Apaziquone	Placebo
Arm/Group Description	Apaziquone: TURBT + a single intravesical dose of Apaziquone 4mg in 40ml instilled into the bladder post-TURBT	Placebo: TURBT + a single intravesical dose of placebo instilled into the bladder post-TURBT
Measure Participants	295	271
Mean (Standard Error) [months]	20.3 (0.13)	23.7 (0.14)

Adverse Events

Time Frame	Treatment-emergent Adverse Events (ie, AEs that occurred or worsened following the TURBT procedure) were recorded from the time of randomization to Month 6; after Month 6 until Month 24 (end of study), only genitourinary AEs and Serious AEs (SAEs) were recorded.
Arm/Group Title	Apaziquone		Placebo
Arm/Group Description	Apaziquone: TURBT + a single intravesical dose of Apaziquone 4mg in 40ml instilled into the bladder post-TURBT		Placebo: TURBT + a single intravesical dose of placebo instilled into the bladder post-TURBT
All Cause Mortality
	Apaziquone		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	11/406 (2.7%)		13/396 (3.3%)
Serious Adverse Events
	Apaziquone		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	93/406 (22.9%)		98/396 (24.7%)
Blood and lymphatic system disorders
Iron deficiency anemia	1/406 (0.2%)		1/396 (0.3%)
Anemia of chronic disease	1/406 (0.2%)		0/396 (0%)
Anemia	0/406 (0%)		1/396 (0.3%)
Cardiac disorders
Atrial Fibrillation	6/406 (1.5%)		0/396 (0%)
Cardiac Failure Congestive	5/406 (1.2%)		6/396 (1.5%)
Coronary Artery Disease	3/406 (0.7%)		6/396 (1.5%)
Myocardial Infarction	3/406 (0.7%)		3/396 (0.8%)
Acute Myocardial Infarction	2/406 (0.5%)		1/396 (0.3%)
Acute Coronary Syndrome	2/406 (0.5%)		0/396 (0%)
Atrioventricular block complete	1/406 (0.2%)		1/396 (0.3%)
Bradycardia	1/406 (0.2%)		0/396 (0%)
Cardiac arrest	1/406 (0.2%)		0/396 (0%)
Cardiac tamponade	1/406 (0.2%)		0/396 (0%)
Coronary artery stenosis	1/406 (0.2%)		0/396 (0%)
Sinus bradycardia	1/406 (0.2%)		0/396 (0%)
Ventricular fibrillation	1/406 (0.2%)		0/396 (0%)
Arteriosclerosis coronary artery	0/406 (0%)		1/396 (0.3%)
Atrial tachycardia	0/406 (0%)		1/396 (0.3%)
Cardiac perforation	0/406 (0%)		1/396 (0.3%)
Cardiopulmonary failure	0/406 (0%)		1/396 (0.3%)
Palpitations	0/406 (0%)		1/396 (0.3%)
Ventricular tachycardia	0/406 (0%)		1/396 (0.3%)
Eye disorders
Cataract	0/406 (0%)		1/396 (0.3%)
Gastrointestinal disorders
Small Intestinal Obstruction	1/406 (0.2%)		2/396 (0.5%)
Pancreatitis acute	0/406 (0%)		2/396 (0.5%)
Abdominal pain	1/406 (0.2%)		0/396 (0%)
Diarrhea	1/406 (0.2%)		0/396 (0%)
Duodenal ulcer	1/406 (0.2%)		0/396 (0%)
Ileus	1/406 (0.2%)		0/396 (0%)
Intestinal perforation	1/406 (0.2%)		0/396 (0%)
Intra-abdominal hemorrhage	1/406 (0.2%)		0/396 (0%)
Large intestine polyp	1/406 (0.2%)		0/396 (0%)
Nausea	1/406 (0.2%)		0/396 (0%)
Upper gastrointestinal hemorrhage	1/406 (0.2%)		0/396 (0%)
Vomiting	1/406 (0.2%)		0/396 (0%)
Colitis ischemic	0/406 (0%)		1/396 (0.3%)
Colitis ulcerative	0/406 (0%)		1/396 (0.3%)
Duodenal ulcer hemorrhage	0/406 (0%)		1/396 (0.3%)
Gallstone ileus	0/406 (0%)		1/396 (0.3%)
Gastrointestinal hemorrhage	0/406 (0%)		1/396 (0.3%)
Inguinal hernia, obstructive	0/406 (0%)		1/396 (0.3%)
Pancreatic mass	0/406 (0%)		1/396 (0.3%)
Rectal prolapse	0/406 (0%)		1/396 (0.3%)
Retroperitoneal hemorrhage	0/406 (0%)		1/396 (0.3%)
General disorders
Chest Pain	5/406 (1.2%)		4/396 (1%)
Death	2/406 (0.5%)		0/396 (0%)
Asthenia	1/406 (0.2%)		0/396 (0%)
Ischemic ulcer	1/406 (0.2%)		0/396 (0%)
Generalised oedema	0/406 (0%)		1/396 (0.3%)
Hepatobiliary disorders
Cholecystitis Acute	2/406 (0.5%)		0/396 (0%)
Cholecystitis	1/406 (0.2%)		0/396 (0%)
Immune system disorders
Anaphylactic reaction	1/406 (0.2%)		0/396 (0%)
Infections and infestations
Pneumonia	5/406 (1.2%)		7/396 (1.8%)
Cellulitis	5/406 (1.2%)		3/396 (0.8%)
Urinary Tract Infection	2/406 (0.5%)		5/396 (1.3%)
Sepsis	2/406 (0.5%)		3/396 (0.8%)
Abdominal wall abscess	1/406 (0.2%)		0/396 (0%)
Appendicitis	1/406 (0.2%)		0/396 (0%)
Bronchitis	1/406 (0.2%)		0/396 (0%)
Gastroenteritis viral	1/406 (0.2%)		0/396 (0%)
Influenza	1/406 (0.2%)		0/396 (0%)
Appendicitis perforated	0/406 (0%)		1/396 (0.3%)
Brain abscess	0/406 (0%)		1/396 (0.3%)
Cystitis	0/406 (0%)		1/396 (0.3%)
Herpes zoster	0/406 (0%)		1/396 (0.3%)
Osteomyelitis	0/406 (0%)		1/396 (0.3%)
Peritonitis	0/406 (0%)		1/396 (0.3%)
Urinary tract infection enterococcal	0/406 (0%)		1/396 (0.3%)
Injury, poisoning and procedural complications
Subdural hematoma	1/406 (0.2%)		1/396 (0.3%)
Toxicity to various agents	1/406 (0.2%)		1/396 (0.3%)
Hip fracture	0/406 (0%)		2/396 (0.5%)
Ankle fracture	1/406 (0.2%)		0/396 (0%)
Incisional hernia	1/406 (0.2%)		0/396 (0%)
Post procedural hematuria	1/406 (0.2%)		0/396 (0%)
Procedural nausea	1/406 (0.2%)		0/396 (0%)
Procedural pain	1/406 (0.2%)		0/396 (0%)
Spinal compression fracture	1/406 (0.2%)		0/396 (0%)
Cervical vertebral fracture	0/406 (0%)		1/396 (0.3%)
Fall	0/406 (0%)		1/396 (0.3%)
Femur fracture	0/406 (0%)		1/396 (0.3%)
Multiple injuries	0/406 (0%)		1/396 (0.3%)
Pneumothorax traumatic	0/406 (0%)		1/396 (0.3%)
Post procedural hemorrhage	0/406 (0%)		1/396 (0.3%)
Seroma	0/406 (0%)		1/396 (0.3%)
Investigations
Anticoagulation drug level above therapeutic	0/406 (0%)		1/396 (0.3%)
Metabolism and nutrition disorders
Dehydration	2/406 (0.5%)		1/396 (0.3%)
Electrolyte imbalance	1/406 (0.2%)		0/396 (0%)
Type 2 diabetes mellitus	1/406 (0.2%)		0/396 (0%)
Cachexia	0/406 (0%)		1/396 (0.3%)
Diabetes mellitus	0/406 (0%)		1/396 (0.3%)
Diabetes mellitus inadequate control	0/406 (0%)		1/396 (0.3%)
Hyponatremia	0/406 (0%)		1/396 (0.3%)
Metabolic acidosis	0/406 (0%)		1/396 (0.3%)
Musculoskeletal and connective tissue disorders
Back Pain	2/406 (0.5%)		1/396 (0.3%)
Intervertebral Disc Degeneration	2/406 (0.5%)		0/396 (0%)
Lumbar spinal stenosis	1/406 (0.2%)		1/396 (0.3%)
Osteoarthritis	1/406 (0.2%)		1/396 (0.3%)
Muscular weakness	1/406 (0.2%)		0/396 (0%)
Spinal osteoarthritis	1/406 (0.2%)		0/396 (0%)
Flank pain	0/406 (0%)		1/396 (0.3%)
Intervertebral disc protrusion	0/406 (0%)		1/396 (0.3%)
Osteonecrosis	0/406 (0%)		1/396 (0.3%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Gastrointestinal stromal tumor	1/406 (0.2%)		1/396 (0.3%)
Renal cell carcinoma	1/406 (0.2%)		1/396 (0.3%)
Adenocarcinoma of colon	1/406 (0.2%)		0/396 (0%)
Bladder cancer recurrent	1/406 (0.2%)		0/396 (0%)
Colon cancer	1/406 (0.2%)		0/396 (0%)
Lung adenocarcinoma stage I	1/406 (0.2%)		0/396 (0%)
Lung neoplasm malignant	1/406 (0.2%)		0/396 (0%)
Ureteric cancer	1/406 (0.2%)		0/396 (0%)
Brain cancer metastatic	0/406 (0%)		1/396 (0.3%)
Cholesteatoma	0/406 (0%)		1/396 (0.3%)
Lung neoplasm	0/406 (0%)		1/396 (0.3%)
Metastases to lung	0/406 (0%)		1/396 (0.3%)
Metastases to spine	0/406 (0%)		1/396 (0.3%)
Metastatic bronchial carcinoma	0/406 (0%)		1/396 (0.3%)
Neoplasm malignant	0/406 (0%)		1/396 (0.3%)
Non-small cell lung cancer metastatic	0/406 (0%)		1/396 (0.3%)
Prostate cancer	0/406 (0%)		1/396 (0.3%)
Prostate cancer metastatic	0/406 (0%)		1/396 (0.3%)
Urinary tract neoplasm	0/406 (0%)		1/396 (0.3%)
Nervous system disorders
Syncope	3/406 (0.7%)		2/396 (0.5%)
Transient Ischemic Attack	2/406 (0.5%)		1/396 (0.3%)
Cerebrovascular Accident	1/406 (0.2%)		2/396 (0.5%)
Carotid artery disease	1/406 (0.2%)		0/396 (0%)
Cerebrospinal fluid retention	1/406 (0.2%)		0/396 (0%)
Dementia Alzheimer's type	1/406 (0.2%)		0/396 (0%)
Dizziness	1/406 (0.2%)		0/396 (0%)
Encephalopathy	1/406 (0.2%)		0/396 (0%)
Hepatic encephalopathy	1/406 (0.2%)		0/396 (0%)
Partial seizures	1/406 (0.2%)		0/396 (0%)
Status epilepticus	1/406 (0.2%)		0/396 (0%)
Subarachnoid hemorrhage	1/406 (0.2%)		0/396 (0%)
Cerebral hemorrhage	0/406 (0%)		1/396 (0.3%)
Nerve compression	0/406 (0%)		1/396 (0.3%)
Psychiatric disorders
Bipolar disorder	1/406 (0.2%)		0/396 (0%)
Completed suicide	1/406 (0.2%)		0/396 (0%)
Agitation	0/406 (0%)		1/396 (0.3%)
Anxiety	0/406 (0%)		1/396 (0.3%)
Suicide attempt	0/406 (0%)		1/396 (0.3%)
Renal and urinary disorders
Hematuria	6/406 (1.5%)		8/396 (2%)
Urinary Bladder Hemorrhage	3/406 (0.7%)		0/396 (0%)
Renal Failure Acute	2/406 (0.5%)		2/396 (0.5%)
Urinary retention	1/406 (0.2%)		1/396 (0.3%)
Calculus ureteric	0/406 (0%)		2/396 (0.5%)
Nephrolithiasis	1/406 (0.2%)		0/396 (0%)
Renal colic	1/406 (0.2%)		0/396 (0%)
Ureteric obstruction	1/406 (0.2%)		0/396 (0%)
Acute prerenal failure	0/406 (0%)		1/396 (0.3%)
Bladder perforation	0/406 (0%)		1/396 (0.3%)
Renal failure chronic	0/406 (0%)		1/396 (0.3%)
Renal impairment	0/406 (0%)		1/396 (0.3%)
Respiratory, thoracic and mediastinal disorders
Chronic Obstructive Pulmonary Disease	5/406 (1.2%)		4/396 (1%)
Respiratory Failure	3/406 (0.7%)		3/396 (0.8%)
Pulmonary Embolism	1/406 (0.2%)		3/396 (0.8%)
Acute Respiratory Failure	1/406 (0.2%)		2/396 (0.5%)
Status asthmaticus	0/406 (0%)		1/396 (0.3%)
Skin and subcutaneous tissue disorders
Diabetic foot	1/406 (0.2%)		0/396 (0%)
Psoriasis	1/406 (0.2%)		0/396 (0%)
Surgical and medical procedures
Hip Arthroplasty	4/406 (1%)		2/396 (0.5%)
Knee Arthroplasty	3/406 (0.7%)		4/396 (1%)
Cardiac rehabilitation therapy	1/406 (0.2%)		1/396 (0.3%)
Abdominal hernia repair	1/406 (0.2%)		0/396 (0%)
Angioplasty	1/406 (0.2%)		0/396 (0%)
Aortic aneurysm repair	1/406 (0.2%)		0/396 (0%)
Aortic valve replacement	1/406 (0.2%)		0/396 (0%)
Carotid endarterectomy	1/406 (0.2%)		0/396 (0%)
Coronary arterial stent insertion	1/406 (0.2%)		0/396 (0%)
Mitral valve replacement	1/406 (0.2%)		0/396 (0%)
Penile prosthesis insertion	1/406 (0.2%)		0/396 (0%)
Salpingo-oophorectomy	1/406 (0.2%)		0/396 (0%)
Spinal fusion surgery	1/406 (0.2%)		0/396 (0%)
Bladder neoplasm surgery	0/406 (0%)		1/396 (0.3%)
Implantable defibrillator insertion	0/406 (0%)		1/396 (0.3%)
Radical prostatectomy	0/406 (0%)		1/396 (0.3%)
Ventriculo-peritoneal shunt	0/406 (0%)		1/396 (0.3%)
Vascular disorders
Aortic aneurysm	1/406 (0.2%)		1/396 (0.3%)
Hypotension	0/406 (0%)		2/396 (0.5%)
Labile hypertension	1/406 (0.2%)		0/396 (0%)
Peripheral artery aneurysm	1/406 (0.2%)		0/396 (0%)
Thrombophlebitis	1/406 (0.2%)		0/396 (0%)
Hypertension	0/406 (0%)		1/396 (0.3%)
Other (Not Including Serious) Adverse Events
	Apaziquone		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	312/406 (76.8%)		285/396 (72%)
Gastrointestinal disorders
Nausea	16/406 (3.9%)		19/396 (4.8%)
Infections and infestations
Urinary tract infection	70/406 (17.2%)		58/396 (14.6%)
Injury, poisoning and procedural complications
Procedural pain	31/406 (7.6%)		27/396 (6.8%)
Renal and urinary disorders
Bladder pain	22/406 (5.4%)		18/396 (4.5%)
Bladder spasm	29/406 (7.1%)		23/396 (5.8%)
Dysuria	74/406 (18.2%)		67/396 (16.9%)
Haematuria	38/406 (9.4%)		57/396 (14.4%)
Micturition urgency	31/406 (7.6%)		37/396 (9.3%)
Pollakiuria	39/406 (9.6%)		46/396 (11.6%)
Urinary retention	17/406 (4.2%)		30/396 (7.6%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

First publication is the multi-center publication of Study results from all study sites. Other than the multi-center publication, site may publish an independent publication of data generated by site subject to Sponsor review rights (e.g., review for intellectual property, confidentiality).