Secondary Objectives. The secondary objectives of each study are to evaluate: ▪ The safety of discontinuing vs. continuing hypertonic saline (Study A) or dornase alfa (Study B) ▪ The effect of discontinuing vs. continuing hypertonic saline (Study A) or dornase alfa (Study B) on lung clearance index (LCI) ▪ The effect of discontinuing vs. continuing hypertonic saline (Study A) or dornase alfa (Study B) on other clinical outcomes (e.g., antibiotic events, pulmonary exacerbations, and patient reported outcomes)
Secondary Objectives. The following objectives will compare full dose subjects to low dose subjects in Stage 1: • Assess changes in self-reported PTSD symptoms in participants receiving the full dose and low dose MDMA as measured with the PTSD Diagnostic Scale (PDS) at baseline, after each experimental session and/or the primary endpoint. • Assess depression symptoms with the Xxxx Depression Inventory- II (BDI-II) at baseline and the primary endpoint. • Assess quality of life with the Global Assessment of Functionality (GAF) at baseline and the primary endpoint. • Assess self-reported sleep quality with the Pittsburgh Sleep Quality Index (PSQI) at baseline and the primary endpoint. The following objectives will compare effects in specified subjects: • Assess PTSD symptoms via CAPS and PDS, depression symptoms via BDI-II, quality of life via GAF and sleep quality via PSQI throughout Stage 2 in comparison to Stage 1 in crossover subjects. • Assess long-term effects of MDMA-assisted psychotherapy on symptoms of PTSD, depression, sleep quality, and global function via CAPS and PDS, BDI-II, PSQI and GAF one year after the final experimental session for each subject. The following objectives will include exploratory analyses intended to inform protocol design: • Explore the effects of each experimental session upon self-reported changes in consciousness, as those associated with a transformational or mystical experience via the States of Consciousness Questionnaire (SOCQ). • Assess the effect of the third experimental session for full dose subjects in Stage 1 and Stage 2 using CAPS, PDS, BDI-II, GAF and PSQI. • Assess the ability of the investigators and subjects to accurately guess condition assignment in Stage 1. • Correlate adherence to the treatment manual with Global CAPS scores using adherence criteria ratings to assess videos of psychotherapy sessions. • Correlate development of therapeutic alliance with Global CAPS scores using the Segmented Working Alliance Inventory-Observer Form (S-WAI-O) to assess videos of psychotherapy sessions.
Secondary Objectives. The secondary objective of the First part (Part A) of this study is • To make a p reliminary assessment of the anti-tumour activity of AZD5363 when combined with paclitaxel by assessment of objective response rate (XXX), and the percentage of patients without progressive disease, at 12 weeks. • To assess the PK of AZD5363 when combined with paclitaxel • To assess the PK of paclitaxel alone and when combined with AZD5363 • To assess the pharmacokinetic/pharmacodynamic (PK/PD) relationship between plasma AZD5363 exposure and plasma concentrations of biomarkers (including phospo-PRAS40, total PRAS40, pAKT and pGSK3þ) anti-tumour activity (assessed by RECIST 1.1)
Secondary Objectives. The secondary objectives of the second part (Part B) of this study are: ! To assess the relative efficacy of AZD5363 when combined with weekly paclitaxel compared with weekly paclitaxel plus placebo by assessment of objective response rate (XXX) at 12 weeks, best objective response (BOR), durable response rate (DRR) and duration of response (DoR). ! To assess the relative anti-tumour activity of AZD5363 when combined with weekly paclitaxel vs. weekly paclitaxel plus placebo by comparison of change in tumour size at 12 weeks (target lesion assessment using Response Evaluation Criteria In Solid Tumours [RECIST 1.1]). ! To compare overall survival (OS) in patients treated with AZD5363 in combination with weekly paclitaxel compared with weekly paclitaxel plus placebo by assessment of time to death. ! To further assess the safety and tolerability of AZD5363 when combined with weekly paclitaxel compared with weekly paclitaxel plus placebo. ! To investigate the effect on patients’ quality of life (QoL) of AZD5363 when combined with weekly paclitaxel compared with weekly paclitaxel alone by change from baseline, utilising a patient-completed QoL questionnaire. ! To assess the pharmacokinetics (PK) of AZD5363 when combined with paclitaxel. ! To assess the PK of paclitaxel alone and when combined with AZD5363. ! To assess the Pharmacokinetic /Pharmacodynamic (PK/PDc) relationship between plasma AZD5363 exposure and plasma concentrations of biomarkers (including
Secondary Objectives. To assess the steady-state pharmacokinetics (PK) and pharmacodynamics (PD) of RP103. •
Secondary Objectives. The secondary objectives of this study are to: Evaluate changes on other clinical outcomes (growth, lung function, gastrointestinal symptoms, hospitalizations, antibiotic utilization and PEs) Evaluate changes in blood and fecal inflammatory markers
Secondary Objectives. 1. Evaluate the toxicity of the combination of paricalcitol plus pembrolizumab versus pembrolizumab alone.
Secondary Objectives. 1. To determine the levels of mesenchymal xxxxx cell mobilization (CD34, CD90 and CD 105 expressing cells in peripheral blood and CFU-F)
Secondary Objectives. 1.3.1 To compare the proportion of participants in each treatment arm with drug-resistant virus at entry and at virologic failure, as determined by bulk sequencing.
Secondary Objectives. A secondary objective for Part A is to determine if physiological and molecular profiles differ among those with mild versus severe lung disease in CF patients absent CFTR function (Cohort 3). A secondary objective of Part B of the study is to explore the impact of combination CFTR modulator therapy (lumacaftor/ivacaftor) on various experimental outcome measures directly and indirectly relevant to CFTR modulation in sub-sets of subjects. A secondary objective for both Parts A and B is to collect nasal epithelial cells from a sub- set of subjects to develop a cell culture bank of sustained primary nasal epithelium for in vitro analysis of disease mechanisms and response to experimental therapeutics.
