Study to Determine Pharmacodynamic Effects and Pharmacokinetics of KUC 7483 CL in Patients With Spinal Cord Injury and Neurogenic Detrusor Overactivity
Primary Purpose
Spinal Cord Injuries
Status
Completed
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
KUC 7483 CL
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Spinal Cord Injuries
Eligibility Criteria
Inclusion Criteria:
- Male patients with acquired suprasacral spinal cord injury practicing intermittent catheterization under stable condition as determined by the investigator
- Recovery from spinal shock in posttraumatic patients
- Aged 18 - 70 years
- BMI range ≥ 18.5 and < 29.9 kg/m2
- Documented neurogenic detrusor overactivity as shown by urodynamics within the last 12 months prior to study start and confirmation by the baseline urodynamics (day 2). Detrusor overactivity is defined as a non-volitional increase in detrusor pressure of > 6 cm H2O. Detrusor sphincter dyssynergia may be facultative
- Written informed consent consistent with International committee on harmonization (ICH)/ Good Clinical Practice (GCP) and local legislation given prior to any study procedures
- Ability and willingness to comply with study treatment regimen and to attend study
Exclusion Criteria:
- A total daily volume of urine > 3000 ml as verified in the micturition diary before randomization
- Treatment with drugs with known anticholinergic effect on the detrusor and/or alpha-blockers, 7 days prior to inclusion visit 2
- Treatment with botulinus toxin, capsaicin or resiniferatoxin in the last 6 months prior to the study
- Unstable dosage of any drug or the expectation of initiation of such a treatment during the trial
- Use of agonists or antagonists at beta-adrenoceptors (The following drugs may nevertheless be used since they do not act upon beta-3 adrenoceptors in therapeutic doses: atenolol, bisoprolol, carvedilol, metoprolol, propranolol, salbutamol and salmeterol)
- Neurological diseases other than suprasacral spinal cord injury, affecting urinary bladder function
- Significant stress incontinence as determined by the investigator
- Non-functional bladder outlet obstruction as determined by the investigator
- Dilatation of the upper urinary tract
- Low compliance bladder (Compliance < 20 mL/cm H2O)
- Detrusor hyporeflexia/areflexia and bradykinesia/tremor of the external urethral sphincter
- Prostatic or bladder carcinoma
- Acute urinary tract infection during the run-in period or during study period
- History of interstitial cystitis
- Surgery of the prostate, the urinary bladder, the urethra, and thermotherapy, ultrasound or laser therapy of the prostate for 12 months prior to enrolment to the study
- Pelvic radiation therapy
- Use of indwelling catheter
- Any electro stimulation therapy within the 14 days prior to inclusion visit 2
- Significant hepatic or renal disease defined as twice the upper limit of the reference range, regarding serum concentrations of Aspartate transaminase ((SGOT) (AST)), Alanine transaminase ((SGPT) ALT)), Alkaline phosphatase (ALP), and/or creatinine > 1.4 mg/dl
- Diseases or any condition, in which treatment with ß3-adrenoceptors agonists is contraindicated
- Participation in another clinical trail 8 weeks preceding to enrolment in this study or during study period
- Patients with any severe medical or any other condition which in the opinion of the investigator makes the patient unsuitable for inclusion
- Allergic to KUC-7483 or its excipients
- Patients with Diabetes mellitus type 1 or 2 treated with oral antidiabetic drugs or insulin (any formulation)
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
KUC 7483 CL
Placebo
Arm Description
Outcomes
Primary Outcome Measures
Change from baseline in "volume at first contraction"
Change from baseline in "volume at first contraction"
Secondary Outcome Measures
Change from baseline in Detrusor pressure at first contraction
Change from baseline in Maximum amplitude of involuntary detrusor contraction
Change from baseline in Volume at first incontinence episode
Change from baseline in compliance
Change from baseline in Maximum cystometric capacity
Change from baseline in Detrusor pressure at maximum flow induced by triggering
Change from baseline in Post-triggering residual urinary volume
AUC0-∞ (area under the concentration time curve of KUC 7322 ZW in plasma over the time interval from 0 extrapolated to infinity)
Cmax (maximum concentration of KUC 7322 ZW in plasma)
AUC0-tz (area under the concentration-time curve of KUC 7322 ZW in plasma over the time interval from 0 to the time of the last quantifiable data point)
AUC0-24 (Area under the concentration time curve of KUC 7322 ZW in plasma over the time interval 0 to 24 hours)
tmax (time from dosing to the maximum concentration of KUC 7322 ZW in plasma)
λz (terminal rate constant of KUC 7322 ZW in plasma)
t1/2 (terminal half-life of KUC 7322 ZW in plasma)
MRTpo (mean residence time of KUC 7322 ZW in the body after po administration)
CL/F (apparent clearance of KUC 7322 ZW in the plasma after extravascular administration)
Vz/F (apparent volume of distribution during the terminal phase λz following an extravascular dose)
Aet1-t2 (amount of KUC 7322 ZW that is eliminated in urine from the time interval t1 to t2)
fet1-t2 (fraction of administered drug excreted unchanged in urine from time point t1 to t2)
CLR,t1-t2 (renal clearance of KUC 7322 ZW in plasma from the time point t1 until the time point t2)
Number of patients with adverse events
Number of patients with clinically significant changes in vital signs
Blood Pressure
Assessment of tolerability by investigator on a 4-point scale
Assessment of tolerability by patient on a 4-point scale
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02259751
Brief Title
Study to Determine Pharmacodynamic Effects and Pharmacokinetics of KUC 7483 CL in Patients With Spinal Cord Injury and Neurogenic Detrusor Overactivity
Official Title
A Phase I, Randomised, Double-blind, Placebo-controlled Study to Determine Pharmacodynamic Effects and Pharmacokinetics of a Single Oral Dose of 320 mg KUC 7483 CL in Patients With Spinal Cord Injury and Neurogenic Detrusor Overactivity
Study Type
Interventional
2. Study Status
Record Verification Date
October 2014
Overall Recruitment Status
Completed
Study Start Date
February 2004 (undefined)
Primary Completion Date
February 2005 (Actual)
Study Completion Date
undefined (undefined)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Boehringer Ingelheim
4. Oversight
5. Study Description
Brief Summary
Study to investigate pharmacodynamic effects and pharmacokinetics of KUC 7483
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Spinal Cord Injuries
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
Double
Allocation
Randomized
Enrollment
26 (Actual)
8. Arms, Groups, and Interventions
Arm Title
KUC 7483 CL
Arm Type
Experimental
Arm Title
Placebo
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
KUC 7483 CL
Intervention Type
Drug
Intervention Name(s)
Placebo
Primary Outcome Measure Information:
Title
Change from baseline in "volume at first contraction"
Time Frame
2 hours post dosing
Title
Change from baseline in "volume at first contraction"
Time Frame
6 hours post dosing
Secondary Outcome Measure Information:
Title
Change from baseline in Detrusor pressure at first contraction
Time Frame
2 and 6 hours post dosing
Title
Change from baseline in Maximum amplitude of involuntary detrusor contraction
Time Frame
2 and 6 hours post dosing
Title
Change from baseline in Volume at first incontinence episode
Time Frame
2 and 6 hours post dosing
Title
Change from baseline in compliance
Time Frame
2 and 6 hours post dosing
Title
Change from baseline in Maximum cystometric capacity
Time Frame
2 and 6 hours post dosing
Title
Change from baseline in Detrusor pressure at maximum flow induced by triggering
Time Frame
2 and 6 hours post dosing
Title
Change from baseline in Post-triggering residual urinary volume
Time Frame
2 and 6 hours post dosing
Title
AUC0-∞ (area under the concentration time curve of KUC 7322 ZW in plasma over the time interval from 0 extrapolated to infinity)
Time Frame
up to 24 hours post dosing
Title
Cmax (maximum concentration of KUC 7322 ZW in plasma)
Time Frame
up to 24 hours post dosing
Title
AUC0-tz (area under the concentration-time curve of KUC 7322 ZW in plasma over the time interval from 0 to the time of the last quantifiable data point)
Time Frame
up to 24 hours post dosing
Title
AUC0-24 (Area under the concentration time curve of KUC 7322 ZW in plasma over the time interval 0 to 24 hours)
Time Frame
up to 24 hours post dosing
Title
tmax (time from dosing to the maximum concentration of KUC 7322 ZW in plasma)
Time Frame
up to 24 hours post dosing
Title
λz (terminal rate constant of KUC 7322 ZW in plasma)
Time Frame
up to 24 hours post dosing
Title
t1/2 (terminal half-life of KUC 7322 ZW in plasma)
Time Frame
up to 24 hours post dosing
Title
MRTpo (mean residence time of KUC 7322 ZW in the body after po administration)
Time Frame
up to 24 hours post dosing
Title
CL/F (apparent clearance of KUC 7322 ZW in the plasma after extravascular administration)
Time Frame
up to 24 hours post dosing
Title
Vz/F (apparent volume of distribution during the terminal phase λz following an extravascular dose)
Time Frame
up to 24 hours post dosing
Title
Aet1-t2 (amount of KUC 7322 ZW that is eliminated in urine from the time interval t1 to t2)
Time Frame
up to 24 hours post dosing
Title
fet1-t2 (fraction of administered drug excreted unchanged in urine from time point t1 to t2)
Time Frame
up to 24 hours post dosing
Title
CLR,t1-t2 (renal clearance of KUC 7322 ZW in plasma from the time point t1 until the time point t2)
Time Frame
up to 24 hours post dosing
Title
Number of patients with adverse events
Time Frame
up to 26 days
Title
Number of patients with clinically significant changes in vital signs
Description
Blood Pressure
Time Frame
up to 24 hours post dosing
Title
Assessment of tolerability by investigator on a 4-point scale
Time Frame
10 days post dosing
Title
Assessment of tolerability by patient on a 4-point scale
Time Frame
10 days post dosing
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Male patients with acquired suprasacral spinal cord injury practicing intermittent catheterization under stable condition as determined by the investigator
Recovery from spinal shock in posttraumatic patients
Aged 18 - 70 years
BMI range ≥ 18.5 and < 29.9 kg/m2
Documented neurogenic detrusor overactivity as shown by urodynamics within the last 12 months prior to study start and confirmation by the baseline urodynamics (day 2). Detrusor overactivity is defined as a non-volitional increase in detrusor pressure of > 6 cm H2O. Detrusor sphincter dyssynergia may be facultative
Written informed consent consistent with International committee on harmonization (ICH)/ Good Clinical Practice (GCP) and local legislation given prior to any study procedures
Ability and willingness to comply with study treatment regimen and to attend study
Exclusion Criteria:
A total daily volume of urine > 3000 ml as verified in the micturition diary before randomization
Treatment with drugs with known anticholinergic effect on the detrusor and/or alpha-blockers, 7 days prior to inclusion visit 2
Treatment with botulinus toxin, capsaicin or resiniferatoxin in the last 6 months prior to the study
Unstable dosage of any drug or the expectation of initiation of such a treatment during the trial
Use of agonists or antagonists at beta-adrenoceptors (The following drugs may nevertheless be used since they do not act upon beta-3 adrenoceptors in therapeutic doses: atenolol, bisoprolol, carvedilol, metoprolol, propranolol, salbutamol and salmeterol)
Neurological diseases other than suprasacral spinal cord injury, affecting urinary bladder function
Significant stress incontinence as determined by the investigator
Non-functional bladder outlet obstruction as determined by the investigator
Dilatation of the upper urinary tract
Low compliance bladder (Compliance < 20 mL/cm H2O)
Detrusor hyporeflexia/areflexia and bradykinesia/tremor of the external urethral sphincter
Prostatic or bladder carcinoma
Acute urinary tract infection during the run-in period or during study period
History of interstitial cystitis
Surgery of the prostate, the urinary bladder, the urethra, and thermotherapy, ultrasound or laser therapy of the prostate for 12 months prior to enrolment to the study
Pelvic radiation therapy
Use of indwelling catheter
Any electro stimulation therapy within the 14 days prior to inclusion visit 2
Significant hepatic or renal disease defined as twice the upper limit of the reference range, regarding serum concentrations of Aspartate transaminase ((SGOT) (AST)), Alanine transaminase ((SGPT) ALT)), Alkaline phosphatase (ALP), and/or creatinine > 1.4 mg/dl
Diseases or any condition, in which treatment with ß3-adrenoceptors agonists is contraindicated
Participation in another clinical trail 8 weeks preceding to enrolment in this study or during study period
Patients with any severe medical or any other condition which in the opinion of the investigator makes the patient unsuitable for inclusion
Allergic to KUC-7483 or its excipients
Patients with Diabetes mellitus type 1 or 2 treated with oral antidiabetic drugs or insulin (any formulation)
12. IPD Sharing Statement
Links:
URL
http://trials.boehringer-ingelheim.com
Description
Related Info
Learn more about this trial
Study to Determine Pharmacodynamic Effects and Pharmacokinetics of KUC 7483 CL in Patients With Spinal Cord Injury and Neurogenic Detrusor Overactivity
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