An open-label phase 2 trial to assess the efficacy, safety and pharmacokinetics of lanthanum carbonate in hyperphosphatemic children and adolescents with chronic kidney disease undergoing dialysis.

BACKGROUND: This study assessed the efficacy, tolerability and pharmacokinetics (PK) of lanthanum carbonate (LC) in hyperphosphatemic children and adolescents with chronic kidney disease (CKD) undergoing dialysis. METHODS: This was a three-part, multicenter, open-label study of LC (oral powder formulation) in patients 10 to < 18 years old with CKD undergoing dialysis. In part 1, the single-dose PK of LC (500 mg, ≤12 years old; 1000 mg, > 12 years old) were summarized. In part 2, patients received calcium carbonate (CC [chewable tablet formulation]) (1500-6500 mg [total daily dose]) followed by LC (powder formulation) (1500-3000 mg [total daily dose]), or LC only (1500-3000 mg [total daily dose]), each for 8 weeks. During part 3, patients received LC (1500-3000 mg [total daily dose]) for up to 6 months. The primary efficacy endpoint was the proportion of LC-treated patients achieving serum phosphorus control after 8 weeks during parts 2 and/or 3, defined as: ≤1.94 mmol/L, < 12 years old; ≤1.78 mmol/L, ≥12 years old. Secondary efficacy endpoints included: the proportion of patients who achieved serum phosphorus control after 8 weeks of treatment with CC followed by 8 weeks of treatment with LC (with a washout period between treatments). The safety of LC and CC was also evaluated. RESULTS: In part 1, 20 patients received a single dose of LC. In part 2, 53 and 51 patients were treated with CC and LC for 8 weeks, respectively. During part 3, 42 patients received LC for up to 6 months. Most patients were white and male. For the primary efficacy endpoint, 50% (17/34) of patients who received LC for 8 weeks during parts 2 and/or 3 achieved serum phosphorus control. After 8 weeks of treatment with CC, 58.8% of patients achieved serum phosphorus control; after a subsequent washout period and 8 weeks of treatment with LC, 70.6% of patients achieved serum phosphorus control. Tmax and t1/2 occurred within 3-8 h and ~ 19 h, respectively; however, variability was observed. LC and CC were generally well tolerated. CONCLUSIONS: These data support the use of LC to manage hyperphosphatemia in pediatric patients with CKD undergoing dialysis. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01696279; EudraCT identifier: 2012-000171-17. Date of registration: 01/10/2012.

Definitions of Resistant and Refractory Cytomegalovirus Infection and Disease in Transplant Recipients for Use in Clinical Trials.

Despite advances in preventive strategies, cytomegalovirus (CMV) infection remains a major complication in solid organ and hematopoietic cell transplant recipients. CMV infection may fail to respond to commercially available antiviral therapies, with or without demonstrating genotypic mutation(s) known to be associated with resistance to these therapies. This lack of response has been termed "resistant/refractory CMV" and is a key focus of clinical trials of some investigational antiviral agents. To provide consistent criteria for future clinical trials and outcomes research, the CMV Resistance Working Group of the CMV Drug Development Forum (consisting of scientists, clinicians, regulatory officials, and industry representatives from the United States, Canada, and Europe) has undertaken establishing standardized consensus definitions of "resistant" and "refractory" CMV. These definitions have emerged from the Working Group's review of the available virologic and clinical literature and will be subject to reassessment and modification based on results of future studies.

Sex differences in lopinavir and ritonavir pharmacokinetics among HIV-infected women and men.

The authors compared the pharmacokinetics of lopinavir (LPV) and ritonavir (RTV) between women and men. This 2-step, multicenter, pharmacokinetic study enrolled human immunodeficiency virus (HIV)-infected adults on lopinavir/ritonavir (LPV/r) capsules (400/100 mg bid) plus 1 or more nucleoside reverse transcriptase inhibitors. All participants underwent 12-hour pharmacokinetic sampling. The pharmacokinetic sampling was repeated in participants receiving the LPV/r tablet formulation. Step 1 enrolled 37 women and 40 men; step 2 included 42 participants from step 1 plus 35 new participants (39 women and 38 men). LPV pharmacokinetics in women and men were not significantly different with either formulation. Women had significantly higher median RTV AUC(0-12 h) with both the soft-gel capsule (SGC) and tablet formulations (SGC: 5395 vs 4119 ng·h/mL, P = .026; tablet: 5310 vs 3941 ng·h/mL, P = .012), higher median C(max) (SGC: 802 vs 635 ng/mL, P = .032; tablet: 773 vs 570 ng/mL, P = .006), and lower median CL/F (SGC: 18.54 vs 24.31 L/h, P = .026; tablet: 18.83 vs 25.37 L/h, P = .012). RTV CL/F was slower in women after weight adjustment with both formulations. The pharmacokinetics of LPV in the SGC and tablet formulations are comparable in HIV-infected patients. Women had higher RTV AUC(0-12 h) and lower CL/F with both formulations. The mechanism of the sex difference in RTV CL/F warrants elucidation.