Kidney Stones, Ureteral Calculi, Urolithiasis
Conditions
Keywords
ureteral calculi, renal colic, ureteral stones, kidney stones, medical expulsive therapy
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.
Interventions
DRUGsilodosin
one silodosin 8 mg capsule orally, once daily, with food for up to 4 weeks
DRUGplacebo
one placebo capsule orally, once daily, with food for up to 4 weeks
Sponsors
Watson Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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
| Measure | Time frame | Description |
|---|---|---|
| Time to Spontaneous Stone Passage (Distal Stones) | 4 weeks | Time to stone passage for distally-located stones is assessed by entries in subject diaries. |
| 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. |
| 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. |
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Silodsosin silodosin: one silodosin 8 mg capsule orally, once daily, with food for up to 4 weeks | 119 |
| Placebo placebo: one placebo capsule orally, once daily, with food for up to 4 weeks | 120 |
| Total | 239 |
Baseline characteristics
| Characteristic | Silodsosin | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 47.4 years STANDARD_DEVIATION 12.5 | 46.7 years STANDARD_DEVIATION 15.2 | 47.0 years STANDARD_DEVIATION 13.9 |
| Sex: Female, Male Female | 47 Participants | 36 Participants | 83 Participants |
| Sex: Female, Male Male | 72 Participants | 84 Participants | 156 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 27 / 119 | 8 / 120 |
| serious Total, serious adverse events | 2 / 119 | 2 / 120 |
Outcome results
Primary
Spontaneous Stone Passage (All Stones) Without Need for Emergency Department Visits, Hospital Admissions, Surgical Intervention, or Other Interventional Procedures.
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
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| Silodsosin | Spontaneous Stone Passage (All Stones) Without Need for Emergency Department Visits, Hospital Admissions, Surgical Intervention, or Other Interventional Procedures. | 60 participants |
| Placebo | Spontaneous Stone Passage (All Stones) Without Need for Emergency Department Visits, Hospital Admissions, Surgical Intervention, or Other Interventional Procedures. | 52 participants |
Primary
Spontaneous Stone Passage (Distal Stones) Without Need for Emergency Department Visits, Hospital Admissions, Surgical Intervention, or Other Interventional Procedures.
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
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| Silodsosin | Spontaneous Stone Passage (Distal Stones) Without Need for Emergency Department Visits, Hospital Admissions, Surgical Intervention, or Other Interventional Procedures. | 36 participants |
| Placebo | Spontaneous Stone Passage (Distal Stones) Without Need for Emergency Department Visits, Hospital Admissions, Surgical Intervention, or Other Interventional Procedures. | 27 participants |
Secondary
Change From Baseline in Average Score on the Brief Pain Inventory (Distal Stones)
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
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Silodsosin | Change From Baseline in Average Score on the Brief Pain Inventory (Distal Stones) | -2.6 units on a scale | Standard Deviation 2.5 |
| Placebo | Change From Baseline in Average Score on the Brief Pain Inventory (Distal Stones) | -1.9 units on a scale | Standard Deviation 3.1 |
Secondary
Outpatient Narcotic Analgesic Use for Pain Relief
Narcotic analgesic use was assessed through a subject diary. Analysis was performed on the number of days with analgesic use.
Time frame: 4 weeks
Population: ITT population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Silodsosin | Outpatient Narcotic Analgesic Use for Pain Relief | 5.8 Days | Standard Deviation 8 |
| Placebo | Outpatient Narcotic Analgesic Use for Pain Relief | 5.5 Days | Standard Deviation 6.8 |
Secondary
Time to Spontaneous Stone Passage (All Stones)
Time to stone passage for all ureteral stones (regardless of location) is assessed by entries in subject diaries.
Time frame: 4 weeks
Population: ITT population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Silodsosin | Time to Spontaneous Stone Passage (All Stones) | 22.3 days | Standard Error 1.02 |
| Placebo | Time to Spontaneous Stone Passage (All Stones) | 22.9 days | Standard Error 1 |
Secondary
Time to Spontaneous Stone Passage (Distal Stones)
Time to stone passage for distally-located stones is assessed by entries in subject diaries.
Time frame: 4 weeks
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Silodsosin | Time to Spontaneous Stone Passage (Distal Stones) | 19.6 days | Standard Error 1.61 |
| Placebo | Time to Spontaneous Stone Passage (Distal Stones) | 22.0 days | Standard Error 1.47 |