Contact information
Type
Scientific
Primary contact
Miss Sheryl Caswell
ORCID ID
Contact details
Plethora Solutions
11-13 Macklin Street
London
WC2B 5NH
United Kingdom
+44 (0)207 269 8630
sheryl.caswell@plethorasolutions.co.uk
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
PSD506-OAB-002
Study information
Scientific title
An open-label, escalating dose, proof of concept study to determine the effects of single oral doses of PSD506 on unstable urinary bladder contractions induced by volume provocation in subjects with detrusor hyper-reflexia secondary to spinal injuries above T12
Acronym
Study hypothesis
This study aims to establish the volume provocation test as a surrogate endpoint for demonstrating the efficacy of PSD506 on urinary bladder contractions. This study will also assess the safety of PSD506 in subjects with neurogenic detrusor overactivity due to a spinal cord injury, and will investigate the effect on detrusor instability and function in this patient group.
Ethics approval
Wandsworth Research Ethics Committee, 17/10/06,ref: 06/Q0803/161
Study design
This is an open-label, single-centre, escalating dose, proof of concept study of the effects of single doses of PSD506 on volume provocation tests in subjects with stable spinal injuries above T12.
Primary study design
Interventional
Secondary study design
Single-centre
Trial setting
Not specified
Trial type
Treatment
Patient information sheet
Condition
Detrusor hyper-reflexia secondary to spinal injury (mid-thoracic or cervical level)
Intervention
Single oral administration of PSD506 capsules 5 mg to 40 mg
Intervention type
Drug
Phase
Not Specified
Drug names
PSD506
Primary outcome measures
To determine the effects of single oral doses of PSD506 (anti-muscarinic antagonist) on the reduction of unstable urinary bladder detrusor contractions induced by volume provocation testing in patients with hyper-reflexia secondary to spinal injury.
Secondary outcome measures
1. To assess the safety of PSD06 in this population
2. To determine the dose-response of different doses of PSD506 on the reduction of unstable urinary bladder detrusor contractions
Overall trial start date
01/09/2006
Overall trial end date
30/04/2007
Reason abandoned
Eligibility
Participant inclusion criteria
1. Male or female subjects, aged 18 years or over
2. Spinal lesion above T12, which has been stable for at least 6 months prior to screening.
3. Detrusor hyper- reflexia secondary to spinal injury (mid-thoracic or cervical level) present for at least 12 months
4. If female, must either be surgically sterile or post-menopausal for the past year confirmed by a negative hormone panel (luteinizing hormone [LH], follicle stimulating hormone [FSH], 17β estradiol), or if of child-bearing potential be on adequate non-hormonal contraception (not oral or injectable) i.e. double barrier method or intrauterine contraceptive device [IUCD]. If male must also use adequate contraception (hormonal methods permitted)
5. Anti-muscarinic-naïve or treated subjects completing the 5 day wash-out period.
6. Written informed consent
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
15 to 18 subjects
Participant exclusion criteria
1. If female, has a positive urine pregnancy test
2. History of drug or alcohol abuse
3. Use of anti-muscarinic agents with a long-half life e.g. solifenacin.
4. Body Mass Index (BMI) greater than 28 or less than 16
5. Mean sitting BP greater than 150/85 or less than 100/60 mmHg
6. Mean HR greater than 90 bpm or less than 50 bpm
7. Clinically significant orthostatic hypotension present at screening
8. History of clinically significant hypotensive episodes or symptoms of fainting, dizziness, or lightheadedness
9. History or symptoms of cardiovascular disease, particularly coronary artery disease, arrhythmias, atrial tachycardia, or congestive heart failure
10. History of significant central nervous system disease, including: transient ischemic attack, stroke, seizure disorder, depression, or behavioral disturbances
11. History of peripheral vascular or cerebrovascular disease
12. History of narrow angle glaucoma or increased ocular pressure
13. Clinically significant bladder pathology, including urinary tract infection within 6 weeks of Day 0
14. History of diabetes
15. Clinically significant GI disorder which would, in the opinion of the investigator, pose an unacceptable risk to the subject in this study
16. History of clinically significant liver disease, e.g., hepatitis B
17. Prohibited medications taken within 2 weeks
18. Concomitant use of any agent that has a significant interaction with CYP3A4 or P glycoprotein (Pgp)
19. Clinically significant abnormalities in laboratory test results at screening (including hepatic and renal, full blood count, biochemistry and urinalysis)
20. Participation in an investigational drug or device study within 30 days prior to study.
21. Known hypersensitivity to anticholinergic agents
22. Concomitant disease or condition which could interfere with, or for which the treatment of might interfere with, the conduct of the study, or which would, in the opinion of the investigator, pose an unacceptable risk to the subject in this study. This would include, but is not limited to, cancer, alcoholism, drug dependency or abuse, or psychiatric disease
23. Unwillingness or inability to comply with the study protocol for any other reason.
24. Any clinically significant abnormality on 12-lead ECG
Recruitment start date
01/09/2006
Recruitment end date
30/04/2007
Locations
Countries of recruitment
United Kingdom
Trial participating centre
Plethora Solutions
London
WC2B 5NH
United Kingdom
Sponsor information
Organisation
Plethora Solutions Ltd (UK)
Sponsor details
Lupus House
11-13 Macklin Street
London
WC2B 5NH
United Kingdom
+44 (0)207 269 8630
mail@plethorasolutions.co.uk
Sponsor type
Industry
Website
Funders
Funder type
Industry
Funder name
Plethora Solutions Ltd (UK)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Results - basic reporting
Publication summary