BackgroundThe primary objective of the present trial was to assess the endometrial safety of a new oral contraceptive containing 4 mg drospirenone for a total duration of 13 cycles of 28 days each: 24 days of active treatment followed by 4 days placebo treatment per treatment cycle.Materials and methodsThis was a single-center, open-label, multiple-dose study on healthy female subjects at risk of pregnancy. Twenty one (= safety population set) pre-menopausal female Caucasian subjects started treatment with the study medication. The mean age was 29.0 years (range 19.0–36.0 years). Four subjects terminated the trial prematurely for the following reasons: on the subject’s request (n = 2), due to an adverse event (n = 1) and due to loss of contact (n = 1). Seventeen subjects completed the planned duration of 13 cycles of open treatment with the test product (each cycle of 28 days).ResultsAt visit 1 (pre-treatment), the biopsy result in the safety population set was proliferative in 14 cases and secretory in seven cases. At visit 7, four cases showed an inadequate result (insufficient tissue for diagnosis), 12 as proliferative and three as secretory. The number of biopsies with proliferative and secretory results reduced under treatment (safety population). The pre-post treatment changes in the endometrial biopsy results in the treatment completers set (n = 17) showed almost no differences. At visit 1 (pre-treatment), the biopsy result was proliferative in 12 cases and secretory in five cases. At visit 7 (after 13 cycles of 28 days), four cases showed an inadequate result (insufficient tissue for diagnosis), 11 as proliferative, and two as secretory.The mean endometrial thickness in the safety population was reduced from 8.3 mm at visit 1 to 6.0 mm at visit 7. When comparing the endometrial thickness in the 21 subjects (safety population), the endometrial thickness showed a pre-post difference of 2.1 mm, whereas the endometrial thickness in the 17 study completers showed a pre-post difference of 2.5 mm (8.2 mm at visit 1–5.6 mm at visit 7).ConclusionsDrospirenone 4 mg film-coated tablet in a dosage regime of 24/4 days is, regarding endometrial histology, a safe drug. Trial registration: EudraCT Register number: 2013-002300-13.
OBJECTIVE Finerenone significantly improved cardiorenal outcomes in patients with chronic kidney disease (CKD) and type 2 diabetes (T2D) in the Finerenone in Reducing Kidney Failure and Disease Progression in Diabetic Kidney Disease trial. We explored whether baseline HbA1c level and insulin treatment influenced outcomes. RESEARCH DESIGN AND METHODS Patients with T2D, urine albumin-to-creatinine ratio (UACR) of 30–5,000 mg/g, estimated glomerular filtration rate (eGFR) of 25 to <75 mL/min/1.73 m2, and treated with optimized renin–angiotensin system blockade were randomly assigned to receive finerenone or placebo. Efficacy outcomes included kidney (kidney failure, sustained decrease ≥40% in eGFR from baseline, or renal death) and cardiovascular (cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure) composite endpoints. Patients were analyzed by baseline insulin use and by baseline HbA1c <7.5% (58 mmol/mol) or ≥7.5%. RESULTS Of 5,674 patients, 3,637 (64.1%) received insulin at baseline. Overall, 5,663 patients were included in the analysis for HbA1c; 2,794 (49.3%) had baseline HbA1c <7.5% (58 mmol/mol). Finerenone significantly reduced risk of the kidney composite outcome independent of baseline HbA1c level and insulin use (Pinteraction = 0.41 and 0.56, respectively). Cardiovascular composite outcome incidence was reduced with finerenone irrespective of baseline HbA1c level and insulin use (Pinteraction = 0.70 and 0.33, respectively). Although baseline HbA1c level did not affect kidney event risk, cardiovascular risk increased with higher HbA1c level. UACR reduction was consistent across subgroups. Adverse events were similar between groups regardless of baseline HbA1c level and insulin use; few finerenone-treated patients discontinued treatment because of hyperkalemia. CONCLUSIONS Finerenone reduces kidney and cardiovascular outcome risk in patients with CKD and T2D, and risks appear consistent irrespective of HbA1c levels or insulin use.
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