Efficacy and safety of the selective progesterone receptor modulator (PRM) vilaprisan - 24-week outcomes from asteroid 2

Abstract

each: group (A) received 5 mg LE daily & CE 0.5 mg once weekly from first day of menstrual cycle for 6 weeks. Those in group (B) were prescribed only CE for the same dose & duration of trial. Regular follow-up visits were arranged, and changes in uterine & myoma size, volume and number were recorded at each visit for all patients. Adverse effects were recorded if any. Data analyzed and P-value considered to be significant if < 0.05. All analyses were performed using SPSS software. RESULTS: Treatments well tolerated in both groups with minor side effects. Five patients lost during follow-up period, three from (A) & two from (B) groups. Compared with baseline values, mean uterine volume was reduced significantly (P <0.05) in both groups and with significant difference between groups, more in group (A) than (B) (P <0.016). Total number of myomas was reduced significantly in both groups (P < 0.023). Group (A) patients expressed more myoma shrinkage in comparison to those in group (B) (P < 0.05). Reduction rate of tumor nodule varied from 43-78% in (A) group, while that in group (B) was between 38 to 58%. One patient in (A) group discontinued treatment because of headache, none in the other group. CONCLUSIONS: Combination of LE and CE in management of uterine myomas is safe and more effective than CE alone, leading to symptomatic improvements, and might be considered for short term treatments before surgery along with the opportunity to preserve fertility. References: A.M. Elbareg et al: (Effectiveness of dopamine agonist, Cabergoline (Dostinex), treatment on uterine myoma regression in comparison to effect of gonadotrophin-releasing hormone analogue (Zoladex). Fertility and Sterility,

Effect of hepatic impairment on the pharmacokinetics of vilaprisan: An open‐label, single‐dose, parallel‐group study

“…In this study, a single oral dose of vilaprisan 2 mg was well tolerated by participants of both sexes with mild or moderate hepatic impairment, and in participants with normal hepatic function. Safety findings in this study were comparable with observations from previous phase 1 and phase 2 studies in which vilaprisan was well tolerated, with no drug‐related serious AEs even at the maximal daily doses used in females . Here, the most frequently observed TEAEs were headache and nausea, which were also among the most common drug‐related AEs reported alongside ovarian and cervical cyst (identified at ultrasound), fatigue, abdominal or pelvic pain, other gastrointestinal disorders (flatulence, constipation), hot flushes, and dizziness in previous studies …”

“…In 2 phase 2 clinical studies in women with UF, treatment with vilaprisan resulted in effective bleeding control and reductions in fibroid volume, and demonstrated a favourable safety profile . Based on these promising results, vilaprisan is currently being investigated in phase 3 studies in patients for long‐term treatment of UF…”

“…Safety findings in this study were comparable with observations from previous phase 1 and phase 2 studies in which vilaprisan was well tolerated, with no drug-related serious AEs even at the maximal daily doses used in females. 4,5,7,21,23 Here, the most frequently observed TEAEs were headache and nausea, which were also among the most common drug-related AEs reported alongside ovarian and cervical cyst (identified at ultrasound), fatigue, abdominal or pelvic pain, other gastrointestinal disorders (flatulence, constipation), hot flushes, and dizziness in previous studies. 4,5,7,21,23 A limitation of this study, which is inherent in the primary objective to investigate the pharmacokinetics of vilaprisan, is that safety data were only collected in a small participant population and after single oral dosing (n = 36).…”

“…2,3 In 2 phase 2 clinical studies in women with UF, treatment with vilaprisan resulted in effective bleeding control and reductions in fibroid volume, and demonstrated a favourable safety profile. 4,5 Based on these promising results, vilaprisan is currently being investigated in phase 3 studies in patients for long-term treatment of UF. 6 Previous clinical drug-drug interaction studies with the potent cytochrome P450 3A4 (CYP3A4) inhibitor itraconazole and the potent CYP3A4 inducer rifampicin showed a mean increase by 6.2-fold and a reduction by 96% of the vilaprisan exposure, respectively, confirming preclinical investigations that vilaprisan is extensively metabolised by CYP3A4.…”

Pharmacokinetics and Safety of the Novel Selective Progesterone Receptor Modulator Vilaprisan in Participants With Renal Impairment

“…2 Previous phase 2 studies showed that a dose of 2 mg/day resulted in effective bleeding control and reductions in fibroid volume and demonstrated a favorable safety profile. 3,4 Based on these promising results, vilaprisan is currently being investigated in phase 3 studies. 5 Vilaprisan is predominantly cleared from plasma by hepatic cytochrome P450 (CYP) 3A metabolism and only marginally excreted unchanged with urine, 6 suggesting a minor effect of renal function on the PK of vilaprisan.…”