Study of Silodosin to Facilitate Passage of Urinary Stones

• Sponsor: Watson Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01144949
• Collaborator: (none)
• Enrollment: 239
• Locations: 27
• Arms: 2
• Duration (Months): 25
• Patients Per Site: 8.9
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

The purpose of this study is to assess if patients treated with silodosin will have a higher spontaneous passage rate of their ureteral stone than those treated with placebo.

Condition or Disease	Intervention/Treatment	Phase
Ureteral Calculi; Kidney Stones; Urolithiasis	Drug: silodosin; Drug: placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 239 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Double-Blind, Placebo-Controlled Study of Silodosin to Facilitate Urinary Stone Passage
• Study Start Date: Jun 1, 2010
• Actual Primary Completion Date: Jul 1, 2012
• Actual Study Completion Date: Jul 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: silodsosin	Drug: silodosin; one silodosin 8 mg capsule orally, once daily, with food for up to 4 weeks
Placebo Comparator: placebo	Drug: placebo; one placebo capsule orally, once daily, with food for up to 4 weeks

Outcome Measures

Primary Outcome Measures

1. Spontaneous Stone Passage (Distal Stones) Without Need for Emergency Department Visits, Hospital Admissions, Surgical Intervention, or Other Interventional Procedures. [4 weeks]

   The primary efficacy variable is the occurrence of spontaneous distal stone passage within 4 weeks, as determined by radiography. For this outcome measure, analysis includes only those stones located in the distal ureter.

2. Spontaneous Stone Passage (All Stones) Without Need for Emergency Department Visits, Hospital Admissions, Surgical Intervention, or Other Interventional Procedures. [4 weeks]

   The primary efficacy variable is the occurrence of spontaneous stone passage within 4 weeks, as determined by radiography. For this outcome measure, analysis includes all ureteral stones, regardless of location in the ureter.

Secondary Outcome Measures

1. Time to Spontaneous Stone Passage (Distal Stones) [4 weeks]

   Time to stone passage for distally-located stones is assessed by entries in subject diaries.

2. Outpatient Narcotic Analgesic Use for Pain Relief [4 weeks]

   Narcotic analgesic use was assessed through a subject diary. Analysis was performed on the number of days with analgesic use.

3. Change From Baseline in Average Score on the Brief Pain Inventory (Distal Stones) [4 weeks]

   At each study visit, subjects were given a Brief Pain Inventory (BPI) Questionnaire to complete. The BPI collects subject-reported pain severity scores and assesses impact of pain upon the subject's daily life, on a 10-point scale (with 10 being the greatest severity/impact). Analysis was change from baseline to week 4.

4. Time to Spontaneous Stone Passage (All Stones) [4 weeks]

   Time to stone passage for all ureteral stones (regardless of location) is assessed by entries in subject diaries.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• At least 18 years of age or older

• Male or a non-pregnant, non-lactating female using adequate means of birth control, if not menopausal

• Have radiopaque unilateral ureteral calculus ≥4mm and ≤10mm in any location of the ureter

Exclusion Criteria:

• Multiple ureteral calculi, or a solitary kidney, or refractory renal colic, or a non-opaque calculus, or active urinary tract infection, or severe hydronephrosis

• History of previous ureteral surgery or ureteral stricture on affected side

• History of any of the following conditions: myasthenia gravis, myopathy, spina bifida, spinal cord injury, autonomic nervous system disorder, fibromyalgia, breast cancer

• Moderate to severe renal impairment or severe liver insufficiency

• History of significant postural hypotension

• Is receiving medication(s) which preclude safe participation in the study or that may produce a confounding effect on the variables under study

• History of allergy to alpha-blockers or oxycodone

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Watson Investigational Site	Birmingham	Alabama	United States
2	Watson Investigational Site	Anchorage	Alaska	United States
3	Watson Investigative Site	Mission Hills	California	United States
4	Watson Investigational Site	Murrieta	California	United States
5	Watson Investigational Site	San Diego	California	United States
6	Watson Investigational Site	Daytona Beach	Florida	United States
7	Watson Investigational Site	Gainesville	Florida	United States
8	Watson Investigational Site	Orange City	Florida	United States
9	Watson Investigative Site	Overland Park	Kansas	United States
10	Watson Investigative Site	North Kansas City	Missouri	United States
11	Watson Investigational Site	Hackensack	New Jersey	United States
12	Watson Investigational Site	Mt Laurel	New Jersey	United States
13	Watson Investigational Site	Sewell	New Jersey	United States
14	Watson Investigational Site	Voorhees	New Jersey	United States
15	Watson Investigational Site	Albany	New York	United States
16	Watson Investigational Site	Garden City	New York	United States
17	Watson Investigational Site	New York	New York	United States
18	Watson Investigational Site	Plainview	New York	United States
19	Watson Investigational Site	Syracuse	New York	United States
20	Watson Investigational Site	Cincinnati	Ohio	United States
21	Watson Investigational Site	Columbus	Ohio	United States
22	Watson Investigational Site	Bala Cynwyd	Pennsylvania	United States
23	Watson Investigational Site	Lancaster	Pennsylvania	United States
24	Watson Investigational Site	Myrtle Beach	South Carolina	United States
25	Watson Investigational Site	Dallas	Texas	United States
26	Watson Investigational Site	San Antonio	Texas	United States
27	Watson Investigational Site	Virginia Beach	Virginia	United States

Sponsors and Collaborators

• Watson Pharmaceuticals

Investigators

• Study Director: Scott Olsen, MPH, Watson Pharmaceuticals, Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Watson Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT01144949
• Other Study ID Numbers: SIL1001
• First Posted: Jun 16, 2010
• Last Update Posted: Aug 11, 2014
• Last Verified: Jul 1, 2014

• Keywords provided by Watson Pharmaceuticals: ureteral calculi; renal colic; ureteral stones; kidney stones; medical expulsive therapy
• Additional relevant MeSH terms: Kidney Calculi; Nephrolithiasis; Urolithiasis; Urinary Calculi; Ureteral Calculi; Ureterolithiasis; Calculi; Silodosin

Study Results

Participant Flow

Arm/Group Title	Silodsosin	Placebo
Arm/Group Description	silodosin: one silodosin 8 mg capsule orally, once daily, with food for up to 4 weeks	placebo: one placebo capsule orally, once daily, with food for up to 4 weeks
Period Title: Overall Study
STARTED	119	120
COMPLETED	108	106
NOT COMPLETED	11	14

Baseline Characteristics

Arm/Group Title	Silodsosin	Placebo	Total
Arm/Group Description	silodosin: one silodosin 8 mg capsule orally, once daily, with food for up to 4 weeks	placebo: one placebo capsule orally, once daily, with food for up to 4 weeks	Total of all reporting groups
Overall Participants	119	120	239
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	47.4 (12.5)	46.7 (15.2)	47.0 (13.9)
Sex: Female, Male (Count of Participants)
Female	47 39.5%	36 30%	83 34.7%
Male	72 60.5%	84 70%	156 65.3%

Outcome Measures

1. Primary Outcome

Title	Spontaneous Stone Passage (Distal Stones) Without Need for Emergency Department Visits, Hospital Admissions, Surgical Intervention, or Other Interventional Procedures.
Description	The primary efficacy variable is the occurrence of spontaneous distal stone passage within 4 weeks, as determined by radiography. For this outcome measure, analysis includes only those stones located in the distal ureter.
Time Frame	4 weeks

Outcome Measure Data

Analysis Population Description

Those subjects in the ITT population (defined as randomized and received at least one dose of study drug) with stones located in the distal ureter (determined by radiography) were included in this analysis. The number of ITT subjects with distal stones was 52/115 in the 8 mg silodosin treatment arm and 59/117 in the placebo treatment arm.

Arm/Group Title	Silodsosin	Placebo
Arm/Group Description	silodosin: one silodosin 8 mg capsule orally, once daily, with food for up to 4 weeks	placebo: one placebo capsule orally, once daily, with food for up to 4 weeks
Measure Participants	52	59
Number [participants]	36 30.3%	27 22.5%

2. Secondary Outcome

Title	Time to Spontaneous Stone Passage (Distal Stones)
Description	Time to stone passage for distally-located stones is assessed by entries in subject diaries.
Time Frame	4 weeks

Outcome Measure Data

Analysis Population Description

Those subjects in the ITT population (defined as randomized and received at least one dose of study drug) with stones located in the distal ureter (determined by radiography) were included in this analysis. The number of ITT subjects with distal stones was 52/115 in the 8 mg silodosin treatment arm and 59/117 in the placebo treatment arm.

Arm/Group Title	Silodsosin	Placebo
Arm/Group Description	silodosin: one silodosin 8 mg capsule orally, once daily, with food for up to 4 weeks	placebo: one placebo capsule orally, once daily, with food for up to 4 weeks
Measure Participants	52	59
Mean (Standard Error) [days]	19.6 (1.61)	22.0 (1.47)

3. Secondary Outcome

Title	Outpatient Narcotic Analgesic Use for Pain Relief
Description	Narcotic analgesic use was assessed through a subject diary. Analysis was performed on the number of days with analgesic use.
Time Frame	4 weeks

Outcome Measure Data

Analysis Population Description

ITT population

Arm/Group Title	Silodsosin	Placebo
Arm/Group Description	silodosin: one silodosin 8 mg capsule orally, once daily, with food for up to 4 weeks	placebo: one placebo capsule orally, once daily, with food for up to 4 weeks
Measure Participants	95	104
Mean (Standard Deviation) [Days]	5.8 (8.0)	5.5 (6.8)

4. Secondary Outcome

Title	Change From Baseline in Average Score on the Brief Pain Inventory (Distal Stones)
Description	At each study visit, subjects were given a Brief Pain Inventory (BPI) Questionnaire to complete. The BPI collects subject-reported pain severity scores and assesses impact of pain upon the subject's daily life, on a 10-point scale (with 10 being the greatest severity/impact). Analysis was change from baseline to week 4.
Time Frame	4 weeks

Outcome Measure Data

Analysis Population Description

Those subjects in the ITT population (defined as randomized and received at least one dose of study drug) with stones located in the distal ureter (determined by radiography) were included in this analysis. The number of ITT subjects with distal stones was 52/115 in the 8 mg silodosin treatment arm and 59/117 in the placebo treatment arm.

Arm/Group Title	Silodsosin	Placebo
Arm/Group Description	silodosin: one silodosin 8 mg capsule orally, once daily, with food for up to 4 weeks	placebo: one placebo capsule orally, once daily, with food for up to 4 weeks
Measure Participants	52	59
Mean (Standard Deviation) [units on a scale]	-2.6 (2.5)	-1.9 (3.1)

5. Primary Outcome

Title	Spontaneous Stone Passage (All Stones) Without Need for Emergency Department Visits, Hospital Admissions, Surgical Intervention, or Other Interventional Procedures.
Description	The primary efficacy variable is the occurrence of spontaneous stone passage within 4 weeks, as determined by radiography. For this outcome measure, analysis includes all ureteral stones, regardless of location in the ureter.
Time Frame	4 weeks

Outcome Measure Data

Analysis Population Description

This endpoint analyzed all subjects in the ITT population, defined as randomized and received at least one dose of study drug (115 in the 8 mg silodosin arm, 117 in the placebo arm)

Arm/Group Title	Silodsosin	Placebo
Arm/Group Description	silodosin: one silodosin 8 mg capsule orally, once daily, with food for up to 4 weeks	placebo: one placebo capsule orally, once daily, with food for up to 4 weeks
Measure Participants	115	117
Number [participants]	60 50.4%	52 43.3%

6. Secondary Outcome

Title	Time to Spontaneous Stone Passage (All Stones)
Description	Time to stone passage for all ureteral stones (regardless of location) is assessed by entries in subject diaries.
Time Frame	4 weeks

Outcome Measure Data

Analysis Population Description

ITT population

Arm/Group Title	Silodsosin	Placebo
Arm/Group Description	silodosin: one silodosin 8 mg capsule orally, once daily, with food for up to 4 weeks	placebo: one placebo capsule orally, once daily, with food for up to 4 weeks
Measure Participants	115	117
Mean (Standard Error) [days]	22.3 (1.02)	22.9 (1.00)

Adverse Events

Arm/Group Title	Silodsosin		Placebo
Arm/Group Description	silodosin: one silodosin 8 mg capsule orally, once daily, with food for up to 4 weeks		placebo: one placebo capsule orally, once daily, with food for up to 4 weeks
All Cause Mortality
	Silodsosin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Silodsosin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/119 (1.7%)		2/120 (1.7%)
Renal and urinary disorders
Renal colic	2/119 (1.7%)	2	2/120 (1.7%)	2
Other (Not Including Serious) Adverse Events
	Silodsosin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	27/119 (22.7%)		8/120 (6.7%)
Gastrointestinal disorders
Nausea	9/119 (7.6%)		2/120 (1.7%)
Vomiting	4/119 (3.4%)		4/120 (3.3%)
Nervous system disorders
Dizziness	8/119 (6.7%)		2/120 (1.7%)
Headache	4/119 (3.4%)		0/120 (0%)
Reproductive system and breast disorders
Retrograde ejaculation	11/119 (9.2%)		1/120 (0.8%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.