Efficacy Evaluation Sample Clauses
Efficacy Evaluation. As indicated in Section 7.1, the primary efficacy variable is the change in the weekly number of UI episodes from Baseline (Day 1) to Week 6 after the first treatment. Secondary efficacy variables are: • weekly number of UI episodes • MCC • MDP during storage • Vol@1stIDC • proportion of subjects with no episodes of UI • proportion of subjects with no IDCs on urodynamic assessment • I-QoL total summary score (as well as individual domain scores i.e. avoidance and limiting behaviour, psychosocial impact, and social embarrassment) • urinary frequency (total, spontaneous only, CIC only) • 24-hour voided volume (total, spontaneous only, CIC only) • volume per void (total, spontaneous only, CIC only) • PdetMax@1stIDC • EFP • DC • EQ-5D-5L score • mPGI-I score • proportion of subjects with UI response at several levels (i.e. ≥30% improvement, ≥50% improvement, ≥75% improvement, etc.) • time to retreatment request • time to eligibility for retreatment • time between treatments. Full details of these assessments and timings are given in Section 7.2. The study Baseline value will be defined as the last value available prior to the first study IMP treatment administration. The aetiology of NDO (SCI or MS) and prior intradetrusor BTX-A usage for UI (BTX-naive and BTX-non-naive) will be used as covariates in the primary model. The results of the treatment effect will be presented for each subgroup formed by the covariates (see Section 9.5 for further details). In order to assess the impact of missing data on the conclusion of the primary analysis, a sensitivity analysis of the primary efficacy endpoint will be performed using a multiple imputation approach. If the parametric assumptions of the analysis are not satisfied, then a suitable transformation or a nonparametric procedure will be sought. Secondary efficacy endpoints will be assessed according to their scale (categorical or continuous), using a logistic regression model, mixed model, or survival analysis-type methods (e.g. ▇▇▇▇▇▇-▇▇▇▇▇ plots, log-rank statistics). Time to event data will be analysed by using survival methods. The results will be presented both in summary tables and graphically in ▇▇▇▇▇▇-▇▇▇▇▇ plots. Responders defined as subjects having an improvement in UI will be presented at several levels (i.e. ≥30% of improvement, ≥50% of improvement, ≥75% of improvement, etc.) for exploratory purposes.
Efficacy Evaluation. Primary Endpoint The primary endpoint is the change from baseline in mean average pain intensity following 12 weeks of treatment as measured by the NRS. Key Secondary Endpoints • Change in mean average pain intensity from baseline to Week 4 as measured by the NRS. • Change in non-pain neuropathic signs after 12 weeks in patients as assessed by change in the UENS. Secondary Endpoints • Change in weekly mean worst pain from baseline to week12 and week 4 as measured by the NRS. • Proportion of patients achieving ≥ 30% and ≥ 50% improvement in mean NRS score from baseline to Week 4 and to Week 12. • Change in mean brief pain inventory – short form (BPI-SF) pain interference score from Pre-Treatment/Day 1 to Week 12. • Change in mean BPI-SF pain interference score from Pre-Treatment/Day 1 to Week 4. • Change from baseline to Week 12 in the Neuropathy Total Symptom Score – 6 (NTSS-6). • Change from baseline to Week 12 in Norfolk Diabetic Quality of Life-Diabetic Neuropathy (QOL-DN). • Patient global impression of change (PGIC) at Week 4 and Week 12. • Rescue medication (acetaminophen) use. Exploratory Endpoints • Change in epidermal nerve fiber density in a subset of patients with painful DPN and reduced intraepidermal nerve fiber density (IENFD) at baseline after 24 weeks of treatment with ricolinostat. • Other exploratory endpoints may be identified at the time of analysis of the study data. Safety Evaluations: Safety evaluations will include assessment of adverse events (AEs), vital signs, physical examination, 12-lead electrocardiogram (ECG), and laboratory measures. An independent Data Monitoring Committee (DMC) will review safety after a vanguard cohort of at least 30 patients has had the opportunity to complete 4 weeks of treatment, and again after this cohort has had the opportunity to complete 12 weeks of treatment. The DMC will have another planned meeting to review safety when approximately 50% of the planned number of patients have been enrolled. The DMC may also meet for unplanned meetings should safety observations during the study warrant such meetings.