Clinical Trial Result Information
Protocol number
NN16586
Title of Study
Open-label Extension for treatment of incontinent patients who have completed an Ro115-1240 study.
Sponsor
Hoffmann-La Roche Inc.
Company division
Pharmaceutical
Product name
Alpha 1A/1L agonist
Therapeutic area
Urinary Incontinence, Stress
Clinical study summary
This was an open-label extension study, which was terminated prematurely because of a decision to discontinue development of alpha 1A/1L agonist.
Study center(s)
57 centers in Australia, Brazil, Canada, Israel, South Africa, Spain and United States.
Phase of development
II
Objectives
To provide alpha 1A/1L agonist for a longer period of time to patients who derived benefit from the treatment and to ensure its safe use. To obtain safety information concerning extended use.
Methodology
Beginning at the baseline visit, all patients took 1.5 mg alpha 1A/1L agonist bid. Safety assessments were to be conducted at intervals up to week 52, and then quarterly.
Number of patients (planned/analyzed)
386 patients enrolled.
Diagnosis and main criteria for inclusion
Women 18 to 70 years of age with SUI or mixed urinary incontinence with a preponderance of SUI symptoms; completion of study NN16378 or NN16691 without a tolerability concern or a clinically significant safety concern.
Test product, dose and mode of administration or test procedure
Oral doses of 1A/1L agonist 1.5 mg twice daily (bid), at breakfast and lunch, with at least 5 hours between doses.
Duration of treatment
Until study termination or withdrawal.
Reference therapy, dose and mode of administration or reference procedure
N/A
Criteria for evaluation (efficacy, safety)
Adverse events, blood pressure (BP), heart rate (HR), clinical laboratory tests, ECGs.
Statistical methods
All safety data were summarized using descriptive statistics.
Summary (efficacy, safety, other results)
A majority of the patients, 61% (234), were treated for more than 90 days, and 49% (187) were treated for more than 180 days. The most frequent adverse event was scalp tingling, which was reported by 18% of the patients. The percentage of patients reporting scalp tingling in this extension study tended to be lower for patients who had been in the higher alpha 1A/1L agonist dose groups of their previous study. The incidence of other frequent adverse events (goose bumps, headache, sinusitis, chills, upper respiratory tract infection and nasopharyngitis, each reported in at least 5% of patients overall) was not related to the previous dose level of alpha 1A/1L agonist.
In general, adverse events tended to be reported most frequently during the first 90 days of treatment. This was true for adverse events known to be associated with alpha 1A/1L agonist: scalp tingling, goose bumps and chills. There was no evidence of a delayed increase in the frequency of any of the adverse events, although data for the later follow-up periods are limited to small numbers of patients.
Seven patients had serious adverse events. One serious adverse event, severe chest pain, was considered remotely related to study treatment.
Overall, 11% of the patients withdrew from treatment because of adverse events. Scalp tingling led to withdrawal in 7 patients, and chills led to withdrawal in 4 patients. Other adverse events each led to withdrawal in less than 1% of patients.
The mean changes from baseline in supine systolic BP were generally small increases. Mean supine HR was slightly lower at week 1 than at screening or baseline and was generally stable thereafter.
The mean changes in laboratory values from baseline were small and not indicative of a trend over time. The most frequent marked laboratory abnormality was 4+ hematuria.
The mean changes in PR and QTc intervals were generally small and variable over time. The percentage of patients with PR intervals ≥200 msec remained fairly constant, ranging from 1.6% to 2.6% during the first year of treatment.
Conclusions
Alpha 1A/1L agonist was generally well tolerated during long-term treatment (more than 90 days in the majority of patients). The drug had little or no effect on vital signs, clinical laboratory results, or ECGs.
Date of report
1/1/2006
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