Dose Finding Study of Once or Twice Weekly IMMU-130 in Metastatic Colorectal Cancer
Ontology highlight
ABSTRACT:
DISEASE(S): Metastatic Colorectal Cancer,Rectal Neoplasms,Colon Cancer,Colorectal Neoplasms,Rectal Cancer,Colonic Neoplasms
PROVIDER: 2125871 | ecrin-mdr-crc |
REPOSITORIES: ECRIN MDR
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Project description:A 48-week, multicenter, randomized, double-blind, double-dummy, active-controlled, non-inferiority trial (the TWICE study) conducted in Japanese primary osteoporosis patients with a high risk of fractures demonstrated that a 28.2-?g twice-weekly regimen of teriparatide can provide comparable efficacy to a 56.5-?g once-weekly regimen of teriparatide, while also improving safety.IntroductionWhile a 56.5-?g once-weekly regimen of teriparatide has high efficacy for osteoporosis, treatment continuation rates are low, with one of the major causes being adverse drug reactions such as nausea or vomiting. The TWICE study was therefore conducted to investigate whether a twice-weekly regimen with 28.2-?g teriparatide can provide comparable efficacy to the 56.5-?g once-weekly regimen while improving safety.MethodsA 48-week, multicenter, randomized, double-blind, double-dummy, active-controlled, non-inferiority trial was conducted in Japan. Patients with primary osteoporosis aged ??65 years at high risk of fractures (n?=?553) were randomly allocated to the 28.2-?g twice-weekly group (n?=?277) or the 56.5-?g once-weekly group (n?=?276). The primary endpoint was the percentage change in lumbar spine (L2-L4) bone mineral density (BMD) at final follow-up.ResultsThe percentage changes in lumbar spine (L2-L4) BMD at final follow-up in the 28.2-?g twice-weekly and 56.5-?g once-weekly groups were 7.3% and 5.9%, respectively; the difference (95% confidence interval [CI]) in percentage change was 1.3% (0.400-2.283%). Since the lower limit of the 95% CI was above the pre-specified non-inferiority margin (-?1.6%), non-inferiority of the 28.2-?g twice-weekly group was demonstrated. Adverse drug reactions were significantly less frequent in the 28.2-?g twice-weekly group (39.7% vs 56.2%; p?<?0.01); the incidence of major adverse drug reactions was lower, and the number of subjects who discontinued due to adverse drug reactions was less in the 28.2-?g twice-weekly group.ConclusionsA 28.2-?g twice-weekly regimen of teriparatide can provide comparable efficacy to a 56.5-?g once-weekly regimen while improving safety.Clinical trial registrationJapicCTI-163477 .
| S-EPMC6811384 | biostudies-literature
Project description:Anaemia is a common complication of chronic kidney disease and prevalence increases with declining renal function. Renal anaemia has significant implications for the well-being and quality of life of patients and impacts on morbidity and mortality. Anaemia can be well managed by therapy with erythropoiesis-stimulating agents (ESAs). Previous clinical trials have shown that the only human cell-line-derived ESA, epoetin delta, is well tolerated and effective in maintaining haemoglobin levels in anaemic patients with chronic kidney disease. The half-life of epoetin delta suggests that administration of this agent is feasible once weekly and once every two weeks. We report on the design and rationale of a trial to compare once weekly vs. twice weekly, and once weekly vs. once every two weeks dosing of epoetin delta.This is a randomized, open-label, multicentre trial. Patients aged 18 years or above with chronic kidney disease (Stages 3-5) are eligible to enter this trial. Two groups of patients form the trial population, those naïve to ESA therapy and those previously stable on ESA therapy. There are two primary objectives of this trial: 1) to demonstrate non-inferiority between twice weekly and once weekly dosing of epoetin delta in previously naïve patients (assessed by haemoglobin at Week 24); 2) to demonstrate non-inferiority between once weekly and once every two weeks dosing in previously stable patients (assessed by average haemoglobin over Weeks 16-24). Among the secondary analyses will be assessments of haematocrit, number(%) of patients meeting predefined targets for haemoglobin and haematocrit levels, and comparisons of average dose. All patients will receive study medication for 24 weeks and dose will be adjusted according to a predefined algorithm to achieve and maintain haemoglobin >or= 11 g/dL. All patients completing this trial are eligible to enter a 2-year follow-up study to enable monitoring of emergent adverse events, anti-erythropoietin antibody responses, maintenance of efficacy and changes in diabetic retinopathy status.To our knowledge, this trial is the first to randomize ESA-naïve patients to different dosing regimens of the same ESA. Data generated will help in guiding the most appropriate dosing frequency for epoetin delta, particularly in those patients new to epoetin delta therapy.ClinicalTrials.gov: NCT00450333.
| S-EPMC2216039 | biostudies-literature
Project description:Doravirine (DOR) is a non-nucleoside reverse transcriptase inhibitor indicated for the treatment of HIV-1. Its use in combination with rifapentine (RPT), an antituberculosis (TB) antibiotic, may reduce the exposure of DOR compromising viral suppression in those living with HIV-1 co-infected with TB. We conducted a prospective, phase I, open label, two-period, fixed sequence, drug interaction study to evaluate the effect of once-weekly RPT and isoniazid (INH) on the pharmacokinetics (PKs) of DOR in healthy volunteers. DOR 100 mg was administered alone twice-daily for 4 days in period 1. In period 2, once-weekly RPT + INH were co-administered with multiple doses of DOR 100 mg twice-daily for study days 7, 14, and 21. Plasma was obtained for DOR PKs when given alone and co-administered with RPT + INH. Eleven healthy volunteers enrolled and completed the study. The geometric mean ratios and 90% confidence intervals for DOR area under the concentration-time curve from zero to 12 hours (AUC0-12 ) and C12 in the presence of RPT + INH compared with DOR alone were 0.71 (0.60-0.85) and 0.69 (0.54-0.89), respectively. Although exposures were moderately reduced in the presence of RPT + INH, trough DOR values were within the concentration range associated with virological suppression. These results demonstrate that a modest decrease in DOR exposure would unlikely be clinically relevant in a virally suppressed patient co-administered once-weekly RPT + INH.
| S-EPMC7719366 | biostudies-literature
Project description:Despite standard of care for glioblastoma, including gross total resection, high-dose radiation, and dose-limited chemotherapy, this tumor remains one of the most aggressive and therapeutically challenging. The relatively small number of patients with this diagnosis compared with more common solid tumors in clinical trials commits new glioblastoma therapies to testing in small, underpowered, nonrandomized settings. Among approximately 200 registered glioblastoma trials identified between 2005 and 2015, nearly half were single-arm studies with sample sizes not exceeding 50 patients. These constraints have made demonstrating efficacy for novel therapies difficult in glioblastoma and other rare and aggressive cancers. Novel immunotherapies for glioblastoma such as vaccination with dendritic cells (DC) have yielded mixed results in clinical trials. To address limited numbers, we sequentially conducted three separate clinical trials utilizing cytomegalovirus (CMV)-specific DC vaccines in patients with newly diagnosed glioblastoma whereby each follow-up study had nearly doubled in sample size. Follow-up data from the first blinded, randomized phase II clinical trial (NCT00639639) revealed that nearly one third of this cohort is without tumor recurrence at 5 years from diagnosis. A second clinical trial (NCT00639639) resulted in a 36% survival rate at 5 years from diagnosis. Results of the first two-arm trial (NCT00639639) showed increased migration of the DC vaccine to draining lymph nodes, and this increased migration has been recapitulated in our larger confirmatory clinical study (NCT02366728). We have now observed that nearly one third of the glioblastoma study patient population receiving CMV-specific DC vaccines results in exceptional long-term survivors.
| S-EPMC9832384 | biostudies-literature
Project description:Aims/introductionTo evaluate the efficacy and safety of once-weekly (q.w.) extended-release exenatide after switching from twice-daily (b.i.d.) exenatide in patients with type 2 diabetes.Materials and methodsThis was an investigator-initiated, prospective, single-arm, multicenter study. Individuals with type 2 diabetes who had been treated with exenatide b.i.d. for at least 3 months were enrolled and switched to exenatide q.w. for 24 weeks. The primary end-point was change in HbA1c at week 24 to test the glucose-lowering effect of exenatide q.w. versus exenatide b.i.d.ResultsA total of 58 Japanese individuals with type 2 diabetes completed the study. Glycated hemoglobin was reduced by 0.2% at week 24 (7.2 ± 1.2% vs 7.0 ± 1.2% [56 ± 13 vs 53 ± 13 mmol/mol], 95% confidence interval -0.4 to -0.03%, P < 0.005 for non-inferiority, P = 0.01 for superiority). Fasting plasma glucose was reduced by 12 mg/dL at week 24 (154 ± 46 vs 142 ± 46 mg/dL, P = 0.02). ?-Cell function assessed by homeostasis model assessment of ?-cell function and C-peptide index was significantly improved at week 24. The incidence of self-reported hypoglycemia was reduced, and treatment satisfaction assessed by the Diabetes Treatment Satisfaction Questionnaire and Diabetes Medication Satisfaction Questionnaire was improved at week 24, with no change in body weight. There was no serious adverse event related to the study drug.ConclusionsSwitching from exenatide b.i.d. to exenatide q.w. resulted in a reduction in glycated hemoglobin, fasting plasma glucose and the incidence of hypoglycemia, and improvement in ?-cell function and treatment satisfaction in patients with type 2 diabetes. These findings will be useful for selecting optimal treatment in individuals with type 2 diabetes.
| S-EPMC7078076 | biostudies-literature
Project description:The range of glycated haemoglobin (HbA1c) responses and characteristics associated with above-average response to exenatide twice daily and once weekly were examined. Data were pooled from 8 exenatide-twice-daily and 5 exenatide-once-weekly studies. A baseline HbA1c-corrected measure of change in HbA1c after 24 weeks identified high, average and low responses. Multiple linear regression and multivariate generalized estimating equation models identified factors associated with high response. Among 2355 participants (exenatide twice daily, n = 1414; exenatide once weekly, n = 941), baseline HbA1c correlated with change in HbA1c (P < .0001). Across baseline HbA1c levels, the 25th to 75th percentile of HbA1c change ranged from -0.3% to -3.2% with exenatide twice daily and from -0.5% to -3.6% with exenatide once weekly. Asian ethnicity and older age were significantly associated with high response to exenatide twice daily; no factors were significantly associated with response to exenatide once weekly. These data provide clinically useful information for estimating the likelihood that, depending on baseline HbA1c, an individual can achieve HbA1c goals. The association between Asian ethnicity, age and high response to exenatide twice daily may relate to the specific effects of exenatide twice daily on postprandial glucose.
| S-EPMC5697639 | biostudies-literature
Project description:BackgroundCyslipidemia and type 2 diabetes are two of the most significant risk factors for the development of cardiovascular disease. Measurement of lipoprotein subclasses provides important information about derangements in lipid metabolism and helps refine cardiovascular risk assessment. Exenatide, a glucagon-like peptide 1 receptor agonist, improved glycemic control, obesity, hypertension, and dyslipidemia in patients with type 2 diabetes in clinical trials.MethodsIn the DURATION-1 trial, patients with type 2 diabetes were treated with exenatide once weekly or twice daily for 30 weeks. This post hoc analysis evaluated the impact of exenatide on lipoprotein subclasses in 211 DURATION-1 patients using vertical auto profile methodology and the Statistical Package for the Social Sciences general linear model adjusted for glycosylated hemoglobin (HbA(1c)) and weight.ResultsBaseline lipids and high sensitivity C-reactive protein were normal overall based on the standard lipid panel. Once-weekly exenatide reduced apolipoprotein B and the apolipoprotein B to apolipoprotein A1 ratio (P < 0.05), independent of glycemic improvement and weight loss. A significant shift in lipoprotein pattern away from small, dense low-density lipoprotein-4 cholesterol was also observed (P < 0.05). Exenatide once weekly increased high-density lipoprotein-2 cholesterol, even after adjustment for changes in HbA(1c) and weight (P < 0.05). Triglycerides, very low-density lipoprotein cholesterol, and high sensitivity C-reactive protein were reduced with both the once-weekly and twice-daily exenatide regimens (P < 0.05).ConclusionIn this post hoc analysis, exenatide significantly improved a number of cardiovascular risk markers. Continuous exenatide exposure with exenatide once weekly elicited a greater response than did immediate-release exenatide twice daily, generally independent of glycemic improvement and weight loss. Thus, in addition to improving glycemic control, exenatide induced favorable changes in lipid and lipoprotein metabolism and decreased systemic inflammation.
| S-EPMC3500143 | biostudies-literature
Project description:AimsTo compare the safety and efficacy of a simpler titration algorithm for insulin degludec/liraglutide (IDegLira) with that used in previous DUAL trials in insulin-naïve patients with type 2 diabetes.Research design and methodsThis 32-week, open-label, non-inferiority trial randomized adults with type 2 diabetes uncontrolled on metformin ± pioglitazone to receive IDegLira, titrated either once weekly, based on the mean of 2 pre-breakfast plasma glucose (PG) readings (n = 210), or twice weekly, based on the mean of 3 pre-breakfast PG readings (n = 210).ResultsMean HbA1c decreased from 8.2% (65 mmol/mol) to 6.1% (43 mmol/mol) with once-weekly titration and from 8.1% (65 mmol/mol) to 6.0% (42 mmol/mol) with twice-weekly titration; non-inferiority was confirmed (estimated treatment difference: 0.12% [-0.04; 0.28]95%CI , 1.30 mmol/mol [-0.41; 3.01]95%CI ). Approximately 90% of patients achieved HbA1c < 7% in each arm. Mean fasting PG was similar after 32 weeks. Weight change was -1.0 kg vs -2.0 kg for once-weekly vs twice-weekly titration. Rates of severe or blood glucose-confirmed symptomatic hypoglycaemia were low in both arms: 0.16 events/patient-year of exposure (PYE) for once-weekly, 0.76 events/PYE for twice-weekly titration. Mean IDegLira dose at 32 weeks was 41 dose steps (41 U IDeg/1.48 mg Lira) for both arms. Overall adverse event rates were 207.8 and 241.3 events/100 PYE with once-weekly and twice-weekly titration, respectively.ConclusionA pragmatic titration algorithm with once-weekly adjustments based on 2 PG readings resulted in a safety and glycaemic efficacy profile similar to that with twice-weekly adjustments based on 3 preceding PG values in insulin-naïve patients.
| S-EPMC5484356 | biostudies-literature
Project description:Background. Previous studies have demonstrated that once-weekly yoga classes are effective for chronic low back pain (cLBP) in white adults with high socioeconomic status. The comparative effectiveness of twice-weekly classes and generalizability to racially diverse low income populations are unknown. Methods. We conducted a 12-week randomized, parallel-group, dosing trial for 95 adults recruited from an urban safety-net hospital and five community health centers comparing once-weekly (n = 49) versus twice-weekly (n = 46) standardized yoga classes supplemented by home practice. Primary outcomes were change from baseline to 12 weeks in pain (11-point scale) and back-related function (23-point modified Roland-Morris Disability Questionnaire). Results. 82% of participants were nonwhite; 77% had annual household incomes <$40,000. The sample's baseline mean pain intensity [6.9 (SD 1.6)] and function [13.7 (SD 5.0)] reflected moderate to severe back pain and impairment. Pain and back-related function improved within both groups (P < 0.001). However, there were no differences between once-weekly and twice-weekly groups for pain reduction [-2.1 (95% CI -2.9, -1.3) versus -2.4 (95% CI -3.1, -1.8), P = 0.62] or back-related function [-5.1 (95% CI -7.0, -3.2) versus -4.9 (95% CI -6.5, -3.3), P = 0.83]. Conclusions. Twelve weeks of once-weekly or twice-weekly yoga classes were similarly effective for predominantly low income minority adults with moderate to severe chronic low back pain. This trial is registered with ClinicalTrials.gov NCT01761617.
| S-EPMC3710634 | biostudies-literature
Project description:The phase 3 A.R.R.O.W. study demonstrated that treatment with once-weekly carfilzomib (70 mg/m2) and dexamethasone (once-weekly Kd70 mg/m2) improved progression-free survival compared with twice-weekly carfilzomib (27 mg/m2) and dexamethasone (twice-weekly Kd27 mg/m2) in patients with relapsed and refractory multiple myeloma (RRMM; median, 11.2 versus 7.6 months; hazard ratio [HR] = 0.69; 95% confidence interval, 0.54-0.88; P = 0.0029). Once-weekly dosing also improved response rates and depth of response. We performed a subgroup analysis from A.R.R.O.W. according to age (<65, 65-74, or ≥75 years), renal function (creatinine clearance <50, ≥50-<80, or ≥80 mL/min), number of prior therapies (2 or 3), and bortezomib-refractory status (yes or no). Compared with twice-weekly Kd27 mg/m2, once-weekly Kd70 mg/m2 reduced the risk of progression or death (HR = 0.60-0.85) and increased overall response rates in nearly all the examined subgroups, consistent with reports in the overall A.R.R.O.W. population. The safety profiles of once-weekly Kd70 mg/m2 across subgroups were also generally consistent with those in the overall population. Findings from this subgroup analysis generally demonstrate a favorable benefit-risk profile of once-weekly Kd70 mg/m2, further supporting once-weekly carfilzomib dosing as an appropriate treatment option for patients with RRMM, regardless of baseline patient and disease characteristics.
| S-EPMC7062899 | biostudies-literature