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. 1. Evaluate the toxicity of the combination of paricalcitol plus pembrolizumab versus pembrolizumab alone.
2. Evaluate the difference in overall survival (OS) in patients administered the combination of paricalcitol plus pembrolizumab versus pembrolizumab alone.
3. Define the impact of the combination of paricalcitol and pembrolizumab on tumor mutational landscape and transcriptional programs.
4. Identify cellular VDR targets in the immune microenvironment with PD1 blockade.
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)
2. To evaluate liver function after mobilization of stem cells in patients with chronic liver function.
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.
1.3.2 To determine the tolerability and safety of the study drug regimens. To evaluate the effect of prior NVP exposure on virologic failure through the assessment of genetic relatedness of HIV minority variants present at baseline with HIV variants selected at virologic failure in participants receiving NNRTI and/or PI-based regimens. To evaluate virologic response to a second regimen after NVP or LPV/RTV is changed due to virologic failure as defined above. To evaluate factors (e.g. HIV-1 subtype, disease status) in diverse geographical locations that are associated with risk of virologic failure and antiretroviral drug resistance. To compare changes in CD4+ cell counts and HIV-related disease progression and mortality in each treatment arm. To determine if NVP drug exposure (parent drug) as estimated by pharmacokinetic measurements correlates with development of NVP-associated rash and/or hepatitis. To evaluate adherence to study drug regimens by participant self-report and pill count. To compare resource utilization and quality of life in participants randomized to Arm 1A versus Arm 1B.
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.
Secondary Objectives. Secondary efficacy objectives will evaluate the effect of levosimendan compared with placebo when administered in addition to standard therapies on the: ● Duration of ICU/CCU LOS during the index hospitalization. ● Incidence of LCOS defined as cardiac index £ 2.0 L/min/m2 for ³ 30 minutes despite optimal fluid balance and maximal inotropic support (dobutamine, milrinone, epinephrine, norepinephrine), with the fluid balance and maximal inotropic dose at the investigator’s discretion. ● Postoperative use of secondary inotrope dobutamine, milrinone, and epinephrine, associated with the index surgical procedure. Safety objectives will evaluate the effect of levosimendan compared with placebo, when administered in addition to standard of care therapies on the: ● Occurrence of all-cause mortality from randomization through Day 90. ● Postoperative atrial fibrillation. Other exploratory objectives will be: ● The effect of levosimendan compared with placebo when administered in addition to standard therapies on extended health resource utilization surmised from hospitalization for any cause and duration of rehospitalization up to 30 days.
Secondary Objectives. Secondary objectives are: • To determine if treatment with SAGE-217 reduces anxiety symptoms compared to placebo • To assess self-report of depressive symptoms • To evaluate the safety and tolerability of SAGE-217 •
Secondary Objectives. The first secondary objective of this study is to demonstrate superiority of the TFNT00 IOL versus the 839MP IOL in mean photopic binocular uncorrected intermediate (60 m) visual acuity (UCIVA) at Visit 4A (120-180 days post 2nd eye implantation). The second secondary objective of this study is to demonstrate noninferiority of the TFNT00 IOL versus the 839MP IOL in mean photopic binocular uncorrected distance (4 m) visual acuity (UCDVA) at Visit 4A (120-180 days post 2nd eye implantation). The third secondary objective of this study is to demonstrate noninferiority of the TFNT00 IOL versus the 839MP IOL in mean photopic binocular uncorrected near (40 cm) visual acuity (UCNVA) at Visit 4A (120-180 days post 2nd eye implantation). The fourth secondary objective of this study is to demonstrate superiority of the TFNT00 IOL versus the 839MP IOL in mean photopic binocular uncorrected near (40 cm) visual acuity (UCNVA) at Visit 4A (120-180 days post 2nd eye implantation). The fifth secondary objective of this study is to demonstrate superiority of the TFNT00 IOL versus the 839MP IOL in mean photopic binocular uncorrected distance (4 m) visual acuity (UCDVA) at Visit 4A (120-180 days post 2nd eye implantation). The sixth secondary objective of this study is to characterize the Binocular Defocus Curve profiles, contrast sensitivity and patient satisfaction with the TFNT00 IOL versus the 839MP IOL at Visit 4A (120-180 days post 2nd eye implantation).
Secondary Objectives. The secondary analysis of the change from baseline in SNOT-22 will estimate the mean difference in SNOT-22 from baseline to 1-, 3-, and 6-months and will use mixed effects models for repeated measures when appropriate (similar approach as the one used for the primary objective). The change from baseline in VAS score for smell dysfunction will estimate the mean difference in VAS score for smell dysfunction at 1-, 3-, 6-, and 12-months and will use mixed effects models for repeated measures when appropriate (similar approach as the one used for the primary objective). The change from baseline in VAS score for nasal obstruction will estimate the mean difference in VAS score for nasal obstruction at 1-, 3-, 6-, and 12-months and will use mixed effects models for repeated measures when appropriate (similar approach as the one used for the primary objective). The change from baseline in NP score will estimate the mean difference in NP score per nasal endoscopy and/or CT scan at 1-, 3-, 6-, and 12-months and will use mixed effects models for repeated measures when appropriate (similar approach as the one used for the primary objective). The annualised rate of clinically significant asthma exacerbations 12-month pre- and 12-months post-mepolizumab treatment periods will be computed and described by using the information below. The definition for clinically significant asthma exacerbations according to the European Respiratory Society/American Thoracic Society consensus (and in order of decreasing severity) is: • Hospitalisation: any asthma-related referral or hospitalisation with a discharge diagnosis of asthma; • ER visits: any record of an ER visit related to an asthma diagnosis code; • OCS-defined: treatment with OCS burst for ≥3 days, but ≤28 days (or 4 weeks) with an asthma or CRSwNP exacerbation code recorded within ±2 weeks. For maintenance OCS users, increase of the prescribed dose by at least 2 times, for ≥3 days, but ≤28 days (or 4 weeks) with asthma or CRSwNP exacerbation code recorded within ±2 weeks. All other OCS therapy use is considered maintenance therapy or non-asthma-related. Asthma exacerbations occurring within 7 days of each other will be considered a single episode. All these categories of asthma exacerbations are considered as clinically significant for the patient. To assess the annualised rate of asthma exacerbations, sites will collect the following information: • Number of asthma exacerbations in 12 months prior to treatment initiation ...
