A Randomized, Double-Blind, Placebo-Controlled, Multicenter Phase 3 Study to Evaluate the Efficacy and Safety of Alvimopan 0.5mg Once Daily and 0.5mg Twice Daily for 12 Weeks for the Treatment of Opioid-Induced Bowel Dysfunction in Adults taking Opioid Therapy for Persistent Non-Cancer Pain
Ontology highlight
ABSTRACT:
DISEASE(S): Opioid-induced Bowel Dysfunction
PROVIDER: 2517462 | ecrin-mdr-crc |
REPOSITORIES: ECRIN MDR
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Project description:Primary objectives: To compare alvimopan with placebo for efficacy in the treatment of OBD
Primary endpoints: Proportion of subjects responding on spontaneous BM frequency
| 2517463 | ecrin-mdr-crc
Project description:Primary objectives: To compare alvimopan with placebo for long-term safety and tolerability
Primary endpoints: Incidence of reported clinical adverse events, including serious and non-serious adverse events as well as treatment-limiting adverse events
| 2517464 | ecrin-mdr-crc
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:This open-label study aimed to compare once-daily and twice-daily pramipexole extended release (PER) treatment in Parkinson's disease (PD). PD patients on dopamine agonist therapy, but with unsatisfactory control, were enrolled. Existing agonist doses were switched into equivalent PER doses. Subjects were consecutively enrolled into either once-daily-first or twice-daily-first groups and received the prescribed amount in one or two, respectively, daily doses for 8 weeks. For the second period, subjects switched regimens in a crossover manner. The forty-four patients completed a questionnaire requesting preference during their last visit. We measured the UPDRS-III, Hoehn and Yahr stages (H&Y) in medication-on state, Parkinson's disease sleep scale (PDSS), and Epworth Sleepiness Scale. Eighteen patients preferred a twice-daily regimen, 12 preferred a once-daily regimen, and 14 had no preference. After the trial, 14 subjects wanted to be on a once-daily regimen, 25 chose a twice-daily regimen, and 5 wanted to maintain the prestudy regimen. Main reasons for choosing the twice-daily regimen were decreased off-duration, more tolerable off-symptoms, and psychological stability. The mean UPDRS-III, H&Y, and PDSS were not different. Daytime sleepiness was significantly high in the once-daily regimen, whereas nocturnal hallucinations were more common in the twice-daily. Multiple dosing should be considered if once-daily dosing is unsatisfactory. This study is registered as NCT01515774 at ClinicalTrials.gov.
| S-EPMC5318624 | biostudies-literature
Project description:BackgroundInhaled corticosteroids are the recommended first-line treatment for asthma but adherence to therapy is suboptimal. The objectives of this study were to compare the efficacy and safety of once-daily (OD) evening and twice-daily (BD) regimens of the novel inhaled corticosteroid fluticasone furoate (FF) in asthma patients.MethodsPatients with moderate asthma (age ≥ 12 years; pre-bronchodilator forced expiratory volume in 1 second (FEV1) 40-85% predicted; FEV1 reversibility of ≥ 12% and ≥ 200 ml) were randomized to FF or fluticasone propionate (FP) regimens in a double-blind, crossover study. Patients were not permitted to have used any ICS for ≥ 8 weeks prior to enrolment and subsequently received doses of FF or FP 200 μg OD, FF or FP 100 μg BD and matching placebo by inhalation for 28 days each. Primary endpoint was Day 28 evening pre-dose (trough) FEV1; non-inferiority of FF 200 μg OD and FF 100 μg BD was assessed, as was superiority of all active treatment relative to placebo. Adverse events (AEs) and 24-hour urinary cortisol excretion were assessed.ResultsThe intent-to-treat population comprised 147 (FF) and 43 (FP) patients. On Day 28, pre-dose FEV1 showed FF 200 μg OD to be non-inferior (pre-defined limit -110 ml) to FF 100 μg BD (mean treatment difference 11 ml; 95% CI: -35 to +56 ml); all FF and FP regimens were significantly superior to placebo (p ≤ 0.02). AEs were similar to placebo; no serious AEs were reported. Urinary cortisol excretion at Day 28 for FF was lower than placebo (ratios: 200 μg OD, 0.75; 100 μg BD, 0.84; p ≤ 0.02).ConclusionsFF 200 μg OD in the evening is an efficacious and well tolerated treatment for asthma patients and is not inferior to the same total BD dose.Trial registrationClinicaltrials.gov; NCT00766090.
| S-EPMC3282675 | biostudies-literature
Project description:BackgroundAntiretroviral therapy (ART) adherence is critical for successful HIV treatment outcomes. Once-daily dosing could improve adherence. Plasma concentrations of once-daily vs twice-daily abacavir + lamivudine are bioequivalent in children, but no randomized trial has compared virological outcomes.MethodsChildren taking abacavir + lamivudine-containing first-line regimens twice daily for more than 36 weeks in the ARROW trial (NCT02028676, ISRCTN24791884) were randomized to continue twice-daily vs move to once-daily abacavir + lamivudine (open-label). Co-primary outcomes were viral load suppression at week 48 (12% noninferiority margin, measured retrospectively) and lamivudine or abacavir-related grade 3/4 adverse events.ResultsSix hundred and sixty-nine children (median 5 years, range 1-16) were randomized to twice daily (n = 333) vs once daily (n = 336) after median 1.8 years on twice-daily abacavir + lamivudine-containing first-line ART. Children were followed for median 114 weeks. At week 48, 242/331 (73%) twice daily vs 236/330 (72%) once daily had viral load less than 80 copies/ml [difference -1.6% (95% confidence interval -8.4,+5.2%) P = 0.65]; 79% twice daily vs 78% once daily had viral load less than 400 copies/ml (P = 0.76) (week 96 results similar). One grade 3/4 adverse event was judged uncertainly related to abacavir + lamivudine (hepatitis; once daily). At week 48, 9% twice daily vs 10% once daily reported missing one or more ART pills in the last 4 weeks (P = 0.74) and 8 vs 8% at week 96 (P = 0.90). Carers strongly preferred once-daily dosing. There was no difference between randomized groups in postbaseline drug-resistance mutations or drug-susceptibility; WHO 3/4 events; ART-modifying, grade 3/4 or serious adverse events; CD4% or weight-for-age/height-for-age (all P > 0.15).ConclusionOnce-daily abacavir + lamivudine was noninferior to twice daily in viral load suppression, with similar resistance, adherence, clinical, immunological and safety outcomes. Abacavir + lamivudine provides the first once-daily nucleoside backbone across childhood that can be used to simplify ART.
| S-EPMC6217915 | biostudies-literature
Project description:Primary objectives: To identify at least one alvimopan treatment regimen that improves spontaneous complete bowel movement (SCBM) frequency compared to placebo while maintaining an acceptable tolerability profile.
Primary endpoints: Changes in weekly spontaneous complete bowel movement (SCBM) frequency during the 3-week Treatment Period.
| 2517533 | ecrin-mdr-crc
Project description:BackgroundTraditional first line regimens containing a non-nucleoside reverse transcriptase inhibitor or protease inhibitor may not be suitable for a subset of antiretroviral-naïve patients such as those with certain co-morbidities, women of child-bearing potential, and intolerability to components of standard first line therapy. This study was conducted to determine if alternate treatment options may meet the needs of both general and special patient populations. The ACTION study was a randomized, open-label, multicenter, 48-week trial that compared the safety and efficacy of a triple nucleoside regimen versus a protease inhibitor plus a dual nucleoside regimen in HIV-1 treatment-naïve subjects.Results279 HIV-infected subjects with HIV-1 RNA (VL) >5000 but < 200,000 copies/mL (c/mL) and CD4+ count >/= 100 cells/mm3 were randomized (1:1) to receive abacavir sulfate/lamivudine/zidovudine (ABC/3TC/ZDV) twice-daily or atazanavir (ATV) once-daily plus lamivudine/zidovudine (3TC/ZDV) twice-daily. Protocol-defined virologic failure was based on multiple failure criteria.Non-inferiority of ABC/3TC/ZDV to ATV+3TC/ZDV was established with 62% vs. 59% of subjects achieving a VL < 50 c/mL at week 48, [ITT(E), M/S = F, 95% CI: -5.9, 10.4]. Similar results were observed in the 230 (82%) subjects with baseline VL<100,000 c/mL (ABC/3TC/ZDV vs. ATV+3TC/ZDV), 66% vs. 59%; 95% CI: -5.6, 19.5. However, ABC/3TC/ZDV did not meet the non-inferiority criterion compared to ATV+3TC/ZDV in the 48 subjects with baseline VL >/= 100,000 c/mL, 39% vs. 60%; 95% CI: -49.2, 7.4, respectively. Protocol-defined virologic failure was similar between groups.ConclusionABC/3TC/ZDV demonstrated comparable virologic efficacy to ATV+3TC/ZDV in this population over 48 weeks. In those with a baseline VL >/= 100,000 c/mL, subjects in the ATV+3TC/ZDV showed better virologic efficacy. Both regimens offer benefits in select therapy-naïve subjects.Trial registration[Clinical Trials Identifier, NCT00082394].
| S-EPMC2672933 | biostudies-literature
Project description:OBJECTIVES:To investigate the pharmacokinetics of darunavir/ritonavir and raltegravir, in HIV-infected subjects, in both plasma and at the intracellular (IC) site of action. METHODS:HIV-infected patients on antiretroviral therapy received raltegravir 400 mg twice daily for 21 days (period 1); darunavir/ritonavir 800/100 mg once daily was added for 14 days (period 2), and patients were randomized to continue raltegravir twice daily (group 1) or to switch to 800 mg once daily (group 2), then they all stopped raltegravir intake and continued darunavir/ritonavir once daily for 14 days (period 3). Drug concentrations in plasma and cells (peripheral blood mononuclear cell) were measured, and differences in geometric mean ratios (GMR) and 90% confidence intervals (CI) between period 2 versus period 3 and period 2 versus period 1 were assessed. RESULTS:Twenty-four patients completed the study. Group 1 GMR (90% CI) of darunavir area under the curve (AUC) with and without raltegravir was 1.24 (1.13 to 1.45) for plasma and 1.24 (1.07 to 1.73) for cells and for group 2 was 1.14 (1.07 to 1.24) and 1.03 (0.94 to 1.16). GMR (90% CI) of raltegravir AUC without and with darunavir/ritonavir (plasma and cells) for group 1 was 0.90 (0.73 to 1.44) and 1.02 (0.81 to 1.67) and for group 2 was 1.21 (1.03 to 1.77) and 1.27 (1.07 to 1.94). Geometric mean IC to plasma AUC ratios were 5.3 and 4.9 for darunavir in groups 1 and 2 when darunavir/ritonavir was given alone and 4.9 and 5.6 for raltegravir when given alone. These ratios were not altered by the coadministered drug. CONCLUSIONS:No remarkable interactions between darunavir/ritonavir and raltegravir in plasma or cells were seen. Raltegravir IC concentrations are higher than previously reported; the difference being due to modified cell isolation procedures that reduced drug loss caused by washing.
| S-EPMC3594701 | biostudies-literature