Active Control Patients Research Articles

(393) Pooled Safety Analysis of Ten Clinical Studies Evaluating Fixed-Dose Oral Testosterone Undecanoate in Male Patients With Testosterone Deficiency

Abstract Introduction Oral testosterone undecanoate (TU) was approved outside the United States 50 years ago and is currently used in several countries for the treatment of men with testosterone deficiency. The efficacy of prior oral TU is limited by a short half-life, requiring frequent dosing and administration with meals. A novel formulation of fixed-dose TU is now indicated for the treatment of testosterone deficiency (FDA approved March 2022). In a phase 3 study (NCT03242590: 1021-16-002) evaluating the efficacy and safety of fixed-dose oral TU 225 mg twice daily in adult men with testosterone deficiency, oral TU was well tolerated and restored testosterone levels to eugonadal ranges in most patients. Objective The objective of this pooled analysis of ten clinical studies (LPCN 1021-09-001, S361.1.001, M12-778, M13-298, 1021-14-001, LPCN 1021-16-002, LPCN 1021-16-003, LPCN 1021-13-001, LPCN 1021-18-001, LPCN 1021-18-003) was to further evaluate the safety of fixed-dose TU administered to adult men with testosterone deficiency. Methods This pooled analysis included men with testosterone deficiency who were enrolled or randomized in one of ten clinical studies and received at least one dose of study drug, which included fixed-dose TU, dose-adjusted TU, or topical testosterone gel. Data from separate studies were allocated to defined treatment groups, and these data were pooled to present a safety summary of patients treated with fixed-dose TU. Treatment groups were defined as follows: all fixed-dose TU patients, active control patients (dose-adjusted TU or topical testosterone gel), and placebo patients. Participants in a crossover study of various fixed-dose TU doses were counted once overall for analysis, and data relating to the highest dose were used. Results Overall, 777 patients were included in this pooled analysis: 654 received fixed-dose TU, 104 received topical testosterone gel, 34 received dose-adjusted TU, and 18 received placebo. Baseline characteristics are available on Table 1. Among 654 patients who received fixed-dose TU, 549 (83.9%) patients completed their respective study, and 15 (2.3%) patients discontinued because of an AE. The most frequently occurring treatment-emergent related adverse events (AEs) for patients treated with fixed-dose TU included headache (10 [1.5]), hematocrit increase (8 [1.2]), and acne (6 [0.9]) (Table 2). Three (0.5%) patients receiving fixed-dose TU experienced a blood pressure increase and 13 (2.0%) exhibited hypertension. No patients receiving fixed-dose TU experienced an increase in hepatic enzymes. The mean change from baseline (SD) in hematocrit (HCT) for patients receiving fixed-dose TU was 0.003% (0.029); three patients receiving fixed-dose TU discontinued because of HCT >54%. No patients in this pooled analysis experienced a serious AE (SAE) related to study treatment, and no deaths occurred. Conclusions In this pooled analysis of ten clinical studies in male patients with testosterone deficiency, fixed-dose TU was well tolerated with no hepatic adverse events, no drug-related SAEs, and no deaths. Disclosure Yes, this is sponsored by industry/sponsor: Halozyme (previously Antares) Clarification Industry initiated, executed and funded study Any of the authors act as a consultant, employee or shareholder of an industry for: Halozyme (previously Antares)

Write to recover: The impact of group led creative writing on behavioral health outcomes in cancer patients.

11536 Background: The diagnosis of cancer can adversely affect mental wellbeing. In addition to treating cancer, the emotional wellbeing of patients must simultaneously be addressed. A previous pilot exploring the feasibility of creative writing workshop (CWW) in cancer patients showed apositive effect on patients’ mental health. Methods: To longitudinally evaluate the efficacy of CWW on mood, we conducted a phase II study with cancer patients (any stage, any cancer type); randomized 2:1 to CWW vs. active control (AC). Patients in the CWW arm attended at least 4, 1.5-hour bi-monthly CWW x 8 wks, whereas AC patients completed independent writing at home with the help of a book (bi-monthly x 8wks). We used validated tools, [Emotional Thermometer Scales (ETS), PHQ-9, GAD-7] to assess changes in overall mood, depression, and anxiety. Primary end point: a) ETS scores before and after intervention b) Changes in depression and anxiety based on PHQ-9 and GAD-7 scores. We present results from ETS scores. Descriptive statistics were generated for these quantitative scales measured in each group, pre and post intervention. Comparisons between groups (gp) were made using Wilcoxon Rank-sum tests. All tests were two sided and the statistical significance level used was 0.05. Results: Amongst evaluable patients, N of 50 (demographics in table below), twenty-six patients in the CWW gp attended at least one class and 19 attended at least 4 classes. Patients in CWW showed significant mood improvement vs. AC when comparing the final overall ETS (p=0.0063). Three of the five sub-scale ETS scores were significantly lower for the CWW vs. AC gp: anxiety (p=0.0027), depression (p=0.0009), and anger (p=0.0027). Conclusions: Group led CWW have a positive effect on mood. Our results suggest potential therapeutic benefit of this intervention on the emotional wellbeing of cancer patients. Larger studies are needed to evaluate the effect of CWW in cancer patients. Clinical trial information: NCT03536702. [Table: see text]

Intensive Structured Self-Monitoring of Blood Glucose and Glycemic Control in Noninsulin-Treated Type 2 Diabetes

OBJECTIVEWe aimed to evaluate the added value of intensive self-monitoring of blood glucose (SMBG), structured in timing and frequency, in noninsulin-treated patients with type 2 diabetes.RESEARCH DESIGN AND METHODSThe 12-month, randomized, clinical trial enrolled 1,024 patients with noninsulin-treated type 2 diabetes (median baseline HbA1c, 7.3% [IQR, 6.9–7.8%]) at 39 diabetes clinics in Italy. After standardized education, 501 patients were randomized to intensive structured monitoring (ISM) with 4-point glycemic profiles (fasting, preprandial, 2-h postprandial, and postabsorptive measurements) performed 3 days/week; 523 patients were randomized to active control (AC) with 4-point glycemic profiles performed at baseline and at 6 and 12 months. Two primary end points were tested in hierarchical order: HbA1c change at 12 months and percentage of patients at risk target for low and high blood glucose index.RESULTSIntent-to-treat analysis showed greater HbA1c reductions over 12 months in ISM (−0.39%) than in AC patients (−0.27%), with a between-group difference of −0.12% (95% CI, −0.210 to −0.024; P = 0.013). In the per-protocol analysis, the between-group difference was −0.21% (−0.331 to −0.089; P = 0.0007). More ISM than AC patients achieved clinically meaningful reductions in HbA1c (>0.3, >0.4, or >0.5%) at study end (P < 0.025). The proportion of patients reaching/maintaining the risk target at month 12 was similar in ISM (74.6%) and AC (70.1%) patients (P = 0.131). At visits 2, 3, and 4, diabetes medications were changed more often in ISM than in AC patients (P < 0.001).CONCLUSIONSUse of structured SMBG improves glycemic control and provides guidance in prescribing diabetes medications in patients with relatively well-controlled noninsulin-treated type 2 diabetes.

A phase 3, randomized, double-blinded, active-controlled, unblinded standard of care study assessing the efficacy and safety of intramyocardial autologous CD34+ cell administration in patients with refractory angina: Design of the RENEW study

Preclinical trials indicate that CD34+ cells represent an effective angiogenic stem cell component. Early-phase clinical trials suggest that intramyocardial administration of autologous CD34+ cells may improve functional capacity and symptoms of angina. RENEW is a pivotal phase 3 trial designed to determine the efficacy of granulocyte colony-stimulating factor (G-CSF)-mobilized CD34+ stem cells for the treatment for patients with refractory angina and chronic myocardial ischemia. Patients (n = 444) receiving maximally tolerated antianginal therapies and lacking conventional revascularization options with Canadian Cardiovascular Society class III or IV angina and ischemia on stress testing will be randomized 2:1:1 to cell therapy (G-CSF-mediated stem cell mobilization, apheresis, and intramyocardial injection of 1 × 10(5) autologous CD34(+) cells/kg), active control (G-CSF-mediated stem cell mobilization, apheresis, and intramyocardial placebo injection), or open-label standard of care. The primary efficacy end point is change in exercise treadmill time in the treated vs active control patients, with 90% power to detect a 60-second difference in exercise time between cell-treated (n = 200) and active control (n = 100) patients. Key secondary end points include total number of anginal episodes per week and the incidence of independently adjudicated major adverse cardiac events and serious adverse events. RENEW will be the first adequately powered study aimed at definitively determining the efficacy of a cell therapy (intramyocardially delivered autologous CD34+ cells) for improvement of functional capacity in patients with refractory angina.

NovoTTF-100A versus physician’s choice chemotherapy in recurrent glioblastoma: A randomised phase III trial of a novel treatment modality

PurposeNovoTTF-100A is a portable device delivering low-intensity, intermediate frequency electric fields via non-invasive, transducer arrays. Tumour Treatment Fields (TTF), a completely new therapeutic modality in cancer treatment, physically interfere with cell division. MethodsPhase III trial of chemotherapy-free treatment of NovoTTF (20–24h/day) versus active chemotherapy in the treatment of patients with recurrent glioblastoma. Primary end-point was improvement of overall survival. ResultsPatients (median age 54years (range 23–80), Karnofsky performance status 80% (range 50–100) were randomised to TTF alone (n=120) or active chemotherapy control (n=117). Number of prior treatments was two (range 1–6). Median survival was 6.6 versus 6.0months (hazard ratio 0.86 [95% CI 0.66–1.12]; p=0.27), 1-year survival rate was 20% and 20%, progression-free survival rate at 6months was 21.4% and 15.1% (p=0.13), respectively in TTF and active control patients. Responses were more common in the TTF arm (14% versus 9.6%, p=0.19). The TTF-related adverse events were mild (14%) to moderate (2%) skin rash beneath the transducer arrays. Severe adverse events occurred in 6% and 16% (p=0.022) of patients treated with TTF and chemotherapy, respectively. Quality of life analyses favoured TTF therapy in most domains. ConclusionsThis is the first controlled trial evaluating an entirely novel cancer treatment modality delivering electric fields rather than chemotherapy. No improvement in overall survival was demonstrated, however efficacy and activity with this chemotherapy-free treatment device appears comparable to chemotherapy regimens that are commonly used for recurrent glioblastoma. Toxicity and quality of life clearly favoured TTF.