Overactive Bladder With Urinary Incontinence, Urinary Incontinence
Conditions
Brief summary
This study will evaluate the efficacy and safety of BOTOX® intravesical instillation in participants with overactive bladder and urinary incontinence.
Interventions
DRUGOnabotulinumtoxinA and Hydrogel admixture
BOTOX® (onabotulinumtoxinA) and Hydrogel admixture administered as a single intravesical instillation
DRUGPlacebo and Hydrogel admixture
Placebo and Hydrogel admixture administered as a single intravesical instillation
Sponsors
Allergan
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Symptoms of OAB (frequency/urgency) with urinary incontinence for at least 6 months * Inadequate response or limiting side effects with pharmacotherapy for the treatment of OAB
Exclusion criteria
* Overactive Bladder caused by neurological condition * Patient has predominance of stress incontinence * History or evidence of pelvic or urological abnormality * Prior use of BOTOX for any urological condition
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Stage 2: Change From Baseline in the Average Number of Urinary Incontinence Episodes (UIEs) Per Day | Baseline (3 consecutive days during Day -14 to Day -1) to 3 consecutive days in the Week prior to Week 12 | The participant recorded urinary incontinence (lack of voluntary control over urination) in a 3-day bladder diary. The average number of UIEs per day is the average of the 3-day diary entries. A negative change from Baseline indicates improvement. Baseline is defined as the last non-missing assessment before the first dose of study treatment. An analysis of covariance (ANCOVA) model was used for analyses. |
| Number of Participants With at Least One Treatment-Emergent Adverse Event (TEAEs) in the Treatment Period | Up to End of Study (Stage 1: Up to 114 days and Stage 2: Up to 35.1 weeks) | An adverse event (AE) is any untoward medical occurrence in a participants or clinical study investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not related to the medicinal product. A TEAE is an AE that occurs or worsens after receiving study drug. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Stage 2: Change From Baseline in the Average Number of Micturition Episodes Per Day | Baseline (3 consecutive days during Days -14 to Day -1) to 3 consecutive days in the Week prior to Week 12 | The participant recorded the number of micturition (urination in toilet or catherization) episodes per day in a 3-day bladder diary. The average number of micturition episodes per day is the average of the 3-day diary entries. A negative change from Baseline indicates improvement. Baseline is defined as the last non-missing assessment before the first dose of study treatment. ANCOVA model was used for analyses. |
| Stage 2: Change From Baseline in the Average Volume Voided Per Micturition | Baseline (3 consecutive days during Days -14 to Day -1) to 3 consecutive days in the Week prior to Week 12 | Volume voided per micturition was recorded over one 24-hour period during the 3-day bladder diary. The volume voided during each 24-hour period was divided by the number of micturitions during the period. The average volume voided per micturition is the average of the 3-day diary entries. A negative change from Baseline indicates improvement. Baseline is defined as the last non-missing assessment before the first dose of study treatment. ANCOVA model was used for analyses. |
Countries
Canada, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Stage 1: Placebo + Hydrogel Admixture BOTOX® matching-placebo and hydrogel admixture administered as a single intravesical instillation on Day 1. | 18 |
| Stage 1: BOTOX® 100U + Hydrogel Admixture BOTOX® 100 units (U) (onabotulinumtoxinA; botulinum toxin Type A) and hydrogel admixture administered as a single intravesical instillation on Day 1. | 12 |
| Stage 1: BOTOX® 300U + Hydrogel Admixture BOTOX® 300U (onabotulinumtoxinA) and hydrogel admixture administered as a single intravesical instillation on Day 1. | 18 |
| Stage 1: BOTOX® 400U + Hydrogel Admixture BOTOX® 400U (onabotulinumtoxinA) and hydrogel admixture administered as a single intravesical instillation on Day 1. | 22 |
| Stage 1: BOTOX® 500U + Hydrogel Admixture BOTOX® 500U (onabotulinumtoxinA) and hydrogel admixture administered as a single intravesical instillation on Day 1. | 19 |
| Stage 2: Placebo + Hydrogel Admixture BOTOX® matching-placebo and hydrogel admixture administered as a single intravesical instillation on Day 1. | 58 |
| Stage 2: BOTOX® 100U + Hydrogel Admixture BOTOX® 100U (onabotulinumtoxinA) and hydrogel admixture administered as a single intravesical instillation on Day 1. | 57 |
| Stage 2: BOTOX® 300U + Hydrogel Admixture BOTOX® 300U (onabotulinumtoxinA) and hydrogel admixture administered as a single intravesical instillation on Day 1. | 60 |
| Stage 2: BOTOX® 400U + Hydrogel Admixture BOTOX® 400U (onabotulinumtoxinA) and hydrogel admixture administered as a single intravesical instillation on Day 1. | 60 |
| Stage 2: BOTOX® 500U + Hydrogel Admixture BOTOX® 500U (onabotulinumtoxinA) and hydrogel admixture administered as a single intravesical instillation on Day 1. | 59 |
| Total | 383 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 0 | 0 | 0 | 2 | 1 | 0 | 2 | 0 |
| Overall Study | Failure to Meet Randomization Criteria | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Lack of Efficacy | 0 | 0 | 0 | 1 | 0 | 1 | 0 | 2 | 0 | 3 |
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 0 | 1 | 2 | 2 | 0 | 6 | 4 |
| Overall Study | Reason Not Specified | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 0 | 1 | 2 | 4 | 5 | 2 | 1 |
Baseline characteristics
| Characteristic | Stage 1: BOTOX® 100U + Hydrogel Admixture | Stage 1: Placebo + Hydrogel Admixture | Stage 1: BOTOX® 300U + Hydrogel Admixture | Stage 1: BOTOX® 400U + Hydrogel Admixture | Stage 1: BOTOX® 500U + Hydrogel Admixture | Total | Stage 2: Placebo + Hydrogel Admixture | Stage 2: BOTOX® 100U + Hydrogel Admixture | Stage 2: BOTOX® 300U + Hydrogel Admixture | Stage 2: BOTOX® 400U + Hydrogel Admixture | Stage 2: BOTOX® 500U + Hydrogel Admixture |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 54.7 years STANDARD_DEVIATION 13 | 55.7 years STANDARD_DEVIATION 13.8 | 56.2 years STANDARD_DEVIATION 12.1 | 62.4 years STANDARD_DEVIATION 8.6 | 55.3 years STANDARD_DEVIATION 13.2 | 59.6 years STANDARD_DEVIATION 10.2 | 57.9 years STANDARD_DEVIATION 11.17 | 60.4 years STANDARD_DEVIATION 9.93 | 59.1 years STANDARD_DEVIATION 11.33 | 59.8 years STANDARD_DEVIATION 9.1 | 60.7 years STANDARD_DEVIATION 9.38 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 2 Participants | 3 Participants | 1 Participants | 0 Participants | 45 Participants | 5 Participants | 9 Participants | 5 Participants | 11 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 10 Participants | 16 Participants | 15 Participants | 21 Participants | 19 Participants | 338 Participants | 53 Participants | 48 Participants | 55 Participants | 49 Participants | 52 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 3 Participants | 1 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 4 Participants | 4 Participants | 1 Participants | 7 Participants | 80 Participants | 12 Participants | 13 Participants | 10 Participants | 9 Participants | 16 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 3 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 8 Participants | 13 Participants | 14 Participants | 20 Participants | 11 Participants | 294 Participants | 44 Participants | 44 Participants | 48 Participants | 49 Participants | 43 Participants |
| Sex: Female, Male Female | 12 Participants | 17 Participants | 15 Participants | 18 Participants | 17 Participants | 347 Participants | 53 Participants | 53 Participants | 54 Participants | 54 Participants | 54 Participants |
| Sex: Female, Male Male | 0 Participants | 1 Participants | 3 Participants | 4 Participants | 2 Participants | 36 Participants | 5 Participants | 4 Participants | 6 Participants | 6 Participants | 5 Participants |
| Stage 1: Average Number of Micturition Episodes per Day | 10.9 episodes per day STANDARD_DEVIATION 3.5 | 10.6 episodes per day STANDARD_DEVIATION 2.4 | 10.0 episodes per day STANDARD_DEVIATION 1.6 | 11.3 episodes per day STANDARD_DEVIATION 2.4 | 11.8 episodes per day STANDARD_DEVIATION 2.9 | 10.9 episodes per day STANDARD_DEVIATION 2.6 | — | — | — | — | — |
| Stage 1: Average Number of Urinary Incontinence Episodes (UIE) | 4.7 episodes per day STANDARD_DEVIATION 2.5 | 7.1 episodes per day STANDARD_DEVIATION 3.4 | 5.8 episodes per day STANDARD_DEVIATION 2.7 | 4.4 episodes per day STANDARD_DEVIATION 2.7 | 5.3 episodes per day STANDARD_DEVIATION 3 | 5.5 episodes per day STANDARD_DEVIATION 3 | — | — | — | — | — |
| Stage 1: Average Volume Voided per Micturition | 189.8 milliliter (mL) STANDARD_DEVIATION 94 | 189.2 milliliter (mL) STANDARD_DEVIATION 64.1 | 182.5 milliliter (mL) STANDARD_DEVIATION 79.3 | 150.0 milliliter (mL) STANDARD_DEVIATION 54.7 | 199.4 milliliter (mL) STANDARD_DEVIATION 70 | 180.4 milliliter (mL) STANDARD_DEVIATION 71.9 | — | — | — | — | — |
| Stage 2: Average Number of Micturition Episodes per Day | — | — | — | — | — | 10.71 episodes per day STANDARD_DEVIATION 2.738 | 11.12 episodes per day STANDARD_DEVIATION 3.049 | 10.97 episodes per day STANDARD_DEVIATION 2.938 | 10.91 episodes per day STANDARD_DEVIATION 2.678 | 9.88 episodes per day STANDARD_DEVIATION 2.03 | 10.70 episodes per day STANDARD_DEVIATION 2.822 |
| Stage 2: Average Number of Urinary Incontinence Episodes | — | — | — | — | — | 5.30 episodes per day STANDARD_DEVIATION 3.386 | 6.06 episodes per day STANDARD_DEVIATION 3.162 | 5.60 episodes per day STANDARD_DEVIATION 4.267 | 4.46 episodes per day STANDARD_DEVIATION 2.738 | 4.56 episodes per day STANDARD_DEVIATION 3.073 | 5.92 episodes per day STANDARD_DEVIATION 3.302 |
| Stage 2: Average Volume Voided per Micturition | — | — | — | — | — | 182.79 mL STANDARD_DEVIATION 68.025 | 179.10 mL STANDARD_DEVIATION 59.421 | 173.28 mL STANDARD_DEVIATION 66.615 | 167.10 mL STANDARD_DEVIATION 67.94 | 194.50 mL STANDARD_DEVIATION 67.414 | 199.58 mL STANDARD_DEVIATION 74.154 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 18 | 0 / 12 | 0 / 18 | 0 / 22 | 0 / 19 | 0 / 58 | 0 / 57 | 0 / 60 | 0 / 60 | 0 / 59 |
| other Total, other adverse events | 6 / 18 | 4 / 12 | 4 / 18 | 4 / 22 | 6 / 19 | 10 / 57 | 17 / 57 | 17 / 60 | 16 / 60 | 19 / 58 |
| serious Total, serious adverse events | 0 / 18 | 0 / 12 | 0 / 18 | 0 / 22 | 0 / 19 | 1 / 57 | 3 / 57 | 1 / 60 | 2 / 60 | 0 / 58 |
Outcome results
Primary
Number of Participants With at Least One Treatment-Emergent Adverse Event (TEAEs) in the Treatment Period
An adverse event (AE) is any untoward medical occurrence in a participants or clinical study investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not related to the medicinal product. A TEAE is an AE that occurs or worsens after receiving study drug.
Time frame: Up to End of Study (Stage 1: Up to 114 days and Stage 2: Up to 35.1 weeks)
Population: Safety Analysis Set included all randomized and treated participants in Stages 1 and 2.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Stage 2: Placebo + Hydrogel Admixture | Number of Participants With at Least One Treatment-Emergent Adverse Event (TEAEs) in the Treatment Period | 6 Participants |
| Stage 2: BOTOX® 100U + Hydrogel Admixture | Number of Participants With at Least One Treatment-Emergent Adverse Event (TEAEs) in the Treatment Period | 4 Participants |
| Stage 2: BOTOX® 300U + Hydrogel Admixture | Number of Participants With at Least One Treatment-Emergent Adverse Event (TEAEs) in the Treatment Period | 4 Participants |
| Stage 2: BOTOX® 400U + Hydrogel Admixture | Number of Participants With at Least One Treatment-Emergent Adverse Event (TEAEs) in the Treatment Period | 10 Participants |
| Stage 2: BOTOX® 500U + Hydrogel Admixture | Number of Participants With at Least One Treatment-Emergent Adverse Event (TEAEs) in the Treatment Period | 6 Participants |
| Stage 2: Placebo + Hydrogel Admixture | Number of Participants With at Least One Treatment-Emergent Adverse Event (TEAEs) in the Treatment Period | 25 Participants |
| Stage 2: BOTOX® 100U + Hydrogel Admixture | Number of Participants With at Least One Treatment-Emergent Adverse Event (TEAEs) in the Treatment Period | 30 Participants |
| Stage 2: BOTOX® 300U + Hydrogel Admixture | Number of Participants With at Least One Treatment-Emergent Adverse Event (TEAEs) in the Treatment Period | 30 Participants |
| Stage 2: BOTOX® 400U + Hydrogel Admixture | Number of Participants With at Least One Treatment-Emergent Adverse Event (TEAEs) in the Treatment Period | 38 Participants |
| Stage 2: BOTOX® 500U + Hydrogel Admixture | Number of Participants With at Least One Treatment-Emergent Adverse Event (TEAEs) in the Treatment Period | 25 Participants |
Primary
Stage 2: Change From Baseline in the Average Number of Urinary Incontinence Episodes (UIEs) Per Day
The participant recorded urinary incontinence (lack of voluntary control over urination) in a 3-day bladder diary. The average number of UIEs per day is the average of the 3-day diary entries. A negative change from Baseline indicates improvement. Baseline is defined as the last non-missing assessment before the first dose of study treatment. An analysis of covariance (ANCOVA) model was used for analyses.
Time frame: Baseline (3 consecutive days during Day -14 to Day -1) to 3 consecutive days in the Week prior to Week 12
Population: Participants from the Intent-to-treat (ITT) Analysis Set, all randomized participants in Stage 2, with data available for analysis at Baseline and Week 12. As per protocol, this endpoint is only applicable to the Stage 2 arms.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Stage 2: Placebo + Hydrogel Admixture | Stage 2: Change From Baseline in the Average Number of Urinary Incontinence Episodes (UIEs) Per Day | -2.72 episodes per day | Standard Error 0.534 |
| Stage 2: BOTOX® 100U + Hydrogel Admixture | Stage 2: Change From Baseline in the Average Number of Urinary Incontinence Episodes (UIEs) Per Day | -1.62 episodes per day | Standard Error 0.539 |
| Stage 2: BOTOX® 300U + Hydrogel Admixture | Stage 2: Change From Baseline in the Average Number of Urinary Incontinence Episodes (UIEs) Per Day | -0.89 episodes per day | Standard Error 0.521 |
| Stage 2: BOTOX® 400U + Hydrogel Admixture | Stage 2: Change From Baseline in the Average Number of Urinary Incontinence Episodes (UIEs) Per Day | -1.52 episodes per day | Standard Error 0.52 |
| Stage 2: BOTOX® 500U + Hydrogel Admixture | Stage 2: Change From Baseline in the Average Number of Urinary Incontinence Episodes (UIEs) Per Day | -1.85 episodes per day | Standard Error 0.53 |
Comparison: The null hypothesis is that there is no difference between each (BOTOX® and Hydrogel admixture group) and (placebo and Hydrogel admixture) in the mean change from Baseline in daily average number of UIEs at Week 12.p-value: 0.084595% CI: [-0.15, 2.35]ANCOVA
Comparison: The null hypothesis is that there is no difference between each (BOTOX® and Hydrogel admixture group) and (placebo and Hydrogel admixture) in the mean change from Baseline in daily average number of UIEs at Week 12.p-value: 0.004195% CI: [0.59, 3.08]ANCOVA
Comparison: The null hypothesis is that there is no difference between each (BOTOX® and Hydrogel admixture group) and (placebo and Hydrogel admixture) in the mean change from Baseline in daily average number of UIEs at Week 12.p-value: 0.0695% CI: [-0.05, 2.44]ANCOVA
Comparison: The null hypothesis is that there is no difference between each (BOTOX® and Hydrogel admixture group) and (placebo and Hydrogel admixture) in the mean change from Baseline in daily average number of UIEs at Week 12.p-value: 0.170295% CI: [-0.37, 2.11]ANCOVA
Secondary
Stage 2: Change From Baseline in the Average Number of Micturition Episodes Per Day
The participant recorded the number of micturition (urination in toilet or catherization) episodes per day in a 3-day bladder diary. The average number of micturition episodes per day is the average of the 3-day diary entries. A negative change from Baseline indicates improvement. Baseline is defined as the last non-missing assessment before the first dose of study treatment. ANCOVA model was used for analyses.
Time frame: Baseline (3 consecutive days during Days -14 to Day -1) to 3 consecutive days in the Week prior to Week 12
Population: Participants from the ITT Analysis Set, all randomized participants in Stage 2, with data available for analysis at Baseline and Week 12. As per protocol, this endpoint is only applicable to the Stage 2 arms.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Stage 2: Placebo + Hydrogel Admixture | Stage 2: Change From Baseline in the Average Number of Micturition Episodes Per Day | -1.64 episodes per day | Standard Error 0.519 |
| Stage 2: BOTOX® 100U + Hydrogel Admixture | Stage 2: Change From Baseline in the Average Number of Micturition Episodes Per Day | -0.91 episodes per day | Standard Error 0.514 |
| Stage 2: BOTOX® 300U + Hydrogel Admixture | Stage 2: Change From Baseline in the Average Number of Micturition Episodes Per Day | -0.86 episodes per day | Standard Error 0.486 |
| Stage 2: BOTOX® 400U + Hydrogel Admixture | Stage 2: Change From Baseline in the Average Number of Micturition Episodes Per Day | -1.00 episodes per day | Standard Error 0.48 |
| Stage 2: BOTOX® 500U + Hydrogel Admixture | Stage 2: Change From Baseline in the Average Number of Micturition Episodes Per Day | -1.11 episodes per day | Standard Error 0.492 |
p-value: 0.236195% CI: [-0.48, 1.95]ANCOVA
p-value: 0.198595% CI: [-0.41, 1.98]ANCOVA
p-value: 0.292395% CI: [-0.56, 1.84]ANCOVA
p-value: 0.376995% CI: [-0.66, 1.74]ANCOVA
Secondary
Stage 2: Change From Baseline in the Average Volume Voided Per Micturition
Volume voided per micturition was recorded over one 24-hour period during the 3-day bladder diary. The volume voided during each 24-hour period was divided by the number of micturitions during the period. The average volume voided per micturition is the average of the 3-day diary entries. A negative change from Baseline indicates improvement. Baseline is defined as the last non-missing assessment before the first dose of study treatment. ANCOVA model was used for analyses.
Time frame: Baseline (3 consecutive days during Days -14 to Day -1) to 3 consecutive days in the Week prior to Week 12
Population: Participants from the ITT Analysis Set, all randomized participants in Stage 2, with data available for analysis at Baseline and Week 12. As per protocol, this endpoint is only applicable to the Stage 2 arms.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Stage 2: Placebo + Hydrogel Admixture | Stage 2: Change From Baseline in the Average Volume Voided Per Micturition | 12.61 mL | Standard Error 11.251 |
| Stage 2: BOTOX® 100U + Hydrogel Admixture | Stage 2: Change From Baseline in the Average Volume Voided Per Micturition | 5.56 mL | Standard Error 11.214 |
| Stage 2: BOTOX® 300U + Hydrogel Admixture | Stage 2: Change From Baseline in the Average Volume Voided Per Micturition | 4.61 mL | Standard Error 10.576 |
| Stage 2: BOTOX® 400U + Hydrogel Admixture | Stage 2: Change From Baseline in the Average Volume Voided Per Micturition | 11.28 mL | Standard Error 10.349 |
| Stage 2: BOTOX® 500U + Hydrogel Admixture | Stage 2: Change From Baseline in the Average Volume Voided Per Micturition | 21.94 mL | Standard Error 10.779 |
p-value: 0.591195% CI: [-32.87, 18.77]ANCOVA
p-value: 0.537595% CI: [-33.52, 17.52]ANCOVA
p-value: 0.917395% CI: [-26.47, 23.81]ANCOVA
p-value: 0.47395% CI: [-16.24, 34.9]ANCOVA