Study to Determine Pharmacodynamic Effects and Pharmacokinetics of KUC 7483 CL in Patients With Spinal Cord Injury and Neurogenic Detrusor Overactivity

Spinal Cord Injuries Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02259751
• Other study ID #: 1207.4
• Status: Completed
• Phase: Phase 1
• First received: October 6, 2014
• Last updated: October 6, 2014
• Start date: February 2004

Study information

• Verified date: October 2014
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical DevicesSwitzerland: SwissmedicRussia: Ministry of Health of the Russian Federation
• Study type: Interventional

Clinical Trial Summary

Study to investigate pharmacodynamic effects and pharmacokinetics of KUC 7483

Recruitment information / eligibility

• Status: Completed
• Enrollment: 26
• Est. primary completion date: February 2005
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

1. Male patients with acquired suprasacral spinal cord injury practicing intermittent catheterization under stable condition as determined by the investigator

2. Recovery from spinal shock in posttraumatic patients

3. Aged 18 - 70 years

4. BMI range = 18.5 and < 29.9 kg/m2

5. 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

6. Written informed consent consistent with International committee on harmonization (ICH)/ Good Clinical Practice (GCP) and local legislation given prior to any study procedures

7. Ability and willingness to comply with study treatment regimen and to attend study

Exclusion Criteria:

1. A total daily volume of urine > 3000 ml as verified in the micturition diary before randomization

2. Treatment with drugs with known anticholinergic effect on the detrusor and/or alpha-blockers, 7 days prior to inclusion visit 2

3. Treatment with botulinus toxin, capsaicin or resiniferatoxin in the last 6 months prior to the study

4. Unstable dosage of any drug or the expectation of initiation of such a treatment during the trial

5. 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)

6. Neurological diseases other than suprasacral spinal cord injury, affecting urinary bladder function

7. Significant stress incontinence as determined by the investigator

8. Non-functional bladder outlet obstruction as determined by the investigator

9. Dilatation of the upper urinary tract

10. Low compliance bladder (Compliance < 20 mL/cm H2O)

11. Detrusor hyporeflexia/areflexia and bradykinesia/tremor of the external urethral sphincter

12. Prostatic or bladder carcinoma

13. Acute urinary tract infection during the run-in period or during study period

14. History of interstitial cystitis

15. 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

16. Pelvic radiation therapy

17. Use of indwelling catheter

18. Any electro stimulation therapy within the 14 days prior to inclusion visit 2

19. 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

20. Diseases or any condition, in which treatment with ß3-adrenoceptors agonists is contraindicated

21. Participation in another clinical trail 8 weeks preceding to enrolment in this study or during study period

22. Patients with any severe medical or any other condition which in the opinion of the investigator makes the patient unsuitable for inclusion

23. Allergic to KUC-7483 or its excipients

24. Patients with Diabetes mellitus type 1 or 2 treated with oral antidiabetic drugs or insulin (any formulation)

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Spinal Cord Injuries

Intervention

Drug:
• KUC 7483 CL

• Placebo

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from baseline in "volume at first contraction"		2 hours post dosing	No
Primary	Change from baseline in "volume at first contraction"		6 hours post dosing	No
Secondary	Change from baseline in Detrusor pressure at first contraction		2 and 6 hours post dosing	No
Secondary	Change from baseline in Maximum amplitude of involuntary detrusor contraction		2 and 6 hours post dosing	No
Secondary	Change from baseline in Volume at first incontinence episode		2 and 6 hours post dosing	No
Secondary	Change from baseline in compliance		2 and 6 hours post dosing	No
Secondary	Change from baseline in Maximum cystometric capacity		2 and 6 hours post dosing	No
Secondary	Change from baseline in Detrusor pressure at maximum flow induced by triggering		2 and 6 hours post dosing	No
Secondary	Change from baseline in Post-triggering residual urinary volume		2 and 6 hours post dosing	No
Secondary	AUC0-8 (area under the concentration time curve of KUC 7322 ZW in plasma over the time interval from 0 extrapolated to infinity)		up to 24 hours post dosing	No
Secondary	Cmax (maximum concentration of KUC 7322 ZW in plasma)		up to 24 hours post dosing	No
Secondary	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)		up to 24 hours post dosing	No
Secondary	AUC0-24 (Area under the concentration time curve of KUC 7322 ZW in plasma over the time interval 0 to 24 hours)		up to 24 hours post dosing	No
Secondary	tmax (time from dosing to the maximum concentration of KUC 7322 ZW in plasma)		up to 24 hours post dosing	No
Secondary	?z (terminal rate constant of KUC 7322 ZW in plasma)		up to 24 hours post dosing	No
Secondary	t1/2 (terminal half-life of KUC 7322 ZW in plasma)		up to 24 hours post dosing	No
Secondary	MRTpo (mean residence time of KUC 7322 ZW in the body after po administration)		up to 24 hours post dosing	No
Secondary	CL/F (apparent clearance of KUC 7322 ZW in the plasma after extravascular administration)		up to 24 hours post dosing	No
Secondary	Vz/F (apparent volume of distribution during the terminal phase ?z following an extravascular dose)		up to 24 hours post dosing	No
Secondary	Aet1-t2 (amount of KUC 7322 ZW that is eliminated in urine from the time interval t1 to t2)		up to 24 hours post dosing	No
Secondary	fet1-t2 (fraction of administered drug excreted unchanged in urine from time point t1 to t2)		up to 24 hours post dosing	No
Secondary	CLR,t1-t2 (renal clearance of KUC 7322 ZW in plasma from the time point t1 until the time point t2)		up to 24 hours post dosing	No
Secondary	Number of patients with adverse events		up to 26 days	No
Secondary	Number of patients with clinically significant changes in vital signs	Blood Pressure	up to 24 hours post dosing	No
Secondary	Assessment of tolerability by investigator on a 4-point scale		10 days post dosing	No
Secondary	Assessment of tolerability by patient on a 4-point scale		10 days post dosing	No

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