Pharmaceutical Division Research Articles

Best of both worlds: An expansion of the state of the art pKa model with data from three industrial partners.

In a unique collaboration between Simulations Plus and several industrial partners, we were able to develop a new version 11.0 of the previously published in silico pKa model, S+pKa, with considerably improved prediction accuracy. The model's training set was vastly expanded by large amounts of experimental data obtained from F. Hoffmann-La Roche AG, Genentech Inc., and the Crop Science division of Bayer AG. The previous v7.0 of S+pKa was trained on data from public sources and the Pharmaceutical division of Bayer AG. The model has shown dramatic improvements in predictive accuracy when externally validated on three new contributor compound sets. Less expected was v11.0's improvement in prediction on new compounds developed at Bayer Pharma after v7.0 was released (2013-2023), even without contributing additional data to v11.0. We illustrate chemical space coverage by chemistries encountered in the five domains, public and industrial, outline model construction, and discuss factors contributing to model's success.

Drug shortages in Israel, revisited: a bitter pill to swallow.

In 2017, we published an article addressing drug shortages (DS) in Israel, exploring regulatory perspectives, challenges, and potential solutions. Since then, DS remain a significant concern for patients, healthcare providers, and policymakers globally. In this updated article, we revisit the topic, providing new insights, data, and analysis on the current DS landscape in Israel, efforts to mitigate them, and propose strategies to combat this escalating issue. We conducted a comprehensive search of the Israeli Ministry of Health (MOH) DS database, spanning from 2014 to the present. We extracted DS numbers and theirreasons. Further searches on the Israeli MOH website, pharmaceutical division archives, and the internet yielded official MOH publications and correspondence regarding regulatory responses to DS from 2017 onwards. Additionally, two specific cases of DS were examined to analyze their handling. Recent activities and publications from the Israeli MOH aimed at reducing DS were also reviewed. Between 2014 and 2022, DS surged 2.66-fold. Total DS were 3228; 672 due to commercial reasons, and 2556 to operational reasons (20.5% and 79.5% respectively). The average duration of intermittent DS increased 1.56-fold, from 85 to 133days. Manufacturers informed the MOH 22days prior to actual shortage on average. Analyzing 2022's DS (640) by ATC groups, prominent categories included nervous system drugs (18%), drugs acting on the alimentary tract and metabolism (14%), and dermatologicals (11%). Operational DS in 2022 (n = 564) were primarily due to stock delivery delays (38%), stock over-utilization (12%), and raw material shortages (9%). Sixteen official MOH publications on DS were identified from 2017 onwards. Moreover, two high-impact DS case studies were examined. Despite routine monitoring by the Israeli MOH and updating the DS policy throughout this period, DS persist, intensifying annually and posing serious health risks. This trend mirrors international patterns, affecting countries globally. In Israel's uniquely structured healthcare system, with its swift stakeholder cooperation and implementation capabilities, more effective DS management is conceivable. We propose ten universally applicable rules to address DS challenges.

Perancangan Engine Decision Support System untuk Aplikasi Kefarmasian dengan Penggunaan Metode Analytical Hierarchy Process

This study aims to increase effectiveness in the selection of drug suppliers in the Tangerang public hospital pharmacy. Tangerang General Hospital is an agency engaged in the health and pharmaceutical services sector. This pharmaceutical division has an internal pharmaceutical application that has been implemented with various features used for recording transaction data both drug sales and drug purchases. Currently there is more than one supplier that supplies the same drug. Therefore the main focus of this research is to design an engine to feature a decision support system by utilizing the analytical hierarchy process approach for selecting the best specific medicine supplier. A decision support system (DSS) is an information system designed to assist decision makers in processing complex information and providing relevant data to support these decisions. The approach that used in this research is analytical hierarchy process with the criteria as needed. The conclusion of this research is to design a prototype engine that is able to provide information and recommendations about the best drug suppliers.

Analisis Rasio Laporan Keuangan dalam Mengukur Kinerja Perusahaan PT. Kalbe Farma Tbk Tahun 2018-2021

The purpose of the study was to specify the increase in financial performance for the pandemic in pharmaceutical division. PT. Kalbe Farma Tbk registed on Indonesian Stock Exchange (IDX). The approach method used is the quantitative descriptive approach. The species of data used is secondary data facile from the Indonesia Stock Exchange, ie financial statements of PT. Kalbe Farma Tbk from 2018 to 2021. The ratio analysis used in this study includes analysis of liquidity, solvency, activity and profitability ratios. As a result, the liquidity and solvency ratios over the past four years have been in good shape for the company as it has been competent to meet all its obligations, but the profitability and activity ratios have fluctuated and are trending downward. It was shown that there was Researchers say PT. Kalbe Farma Tbk uses ratio analysis to measure financial performance, and the results generally increase percentages, but not significantly.

Croda signs vaccine adjuvant partnerships

Croda’s pharmaceutical division has signed two deals to shore up the supply chain for vaccine adjuvants, which are ingredients that enhance medicines’ performance. The synthetic biology firm Amyris will supply Croda with fermentation-derived squalene, which boosts immune response. Croda will also work with the tissue culture specialist Botanical Solution to make an immune-system-stimulating triterpene glycoside called QS-21. Botanical’s method avoids the destruction of soapbark ( Quillaja saponaria ), a rare Chilean evergreen tree.

의약분업 정책 결정 이후 약사법 개정과정의 법정책적 고찰

의약분업 정책 결정 이후 약사법 개정과정의 법정책적 고찰

LOGISTIC DEVELOPMENT STRATEGY FOR PHARMACEUTICAL INDUSTRY FOLLOWING LEAN PERSPECTIVE: THE CASE STUDY OF PAKISTAN

Pharmaceutical strategies are typically unseen to patients but have a direct impact on how well healthcare is managed. This study focuses on creating a new strategy to further develop the coordinated elements supporting the pharmaceutical divisions. The study focuses on the administration and network of stores for pharmaceutical materials used in this sector in Pakistan. This study investigates previous studies to develop an improvement strategy to computerise the systems used in the distribution center and outbuildings. The study explores the impact of the disagreements between pharmaceutical organizations on the business and their commitment to the development of strategies along with recognizing the best-known strategies of pharmaceutical development and their benefits. It also offers best practices and develops a structure of understanding with respect to the pharmaceutical companies in Pakistan. The study finds that the pharmaceuticaldevelopment and its situation in Pakistan is exceptionally unique and rapidly evolving. The study formulates new strategic proposals within the broader political context of Pakistan and its pharmaceutical industry.

Pharmacodynamic Study of Copanlisib in Patients with Non-Hodgkin's Lymphoma and Advanced Solid Tumors: Confirmation of on-Target PI3K Inhibitory Activity

Abstract Introduction: Inhibition of phosphatidylinositol 3-kinase (PI3K) has been shown to be an effective therapeutic strategy for patients with indolent malignant B-cell lymphoma who have relapsed or are refractory to standard therapies. Copanlisib is a novel, potent, intravenous, pan-class I PI3K inhibitor with predominant activity against PI3K-α and PI3K-δ isoforms and has demonstrated robust objective tumor responses of 59.15%, including 12% CR, in patients with indolent non-Hodgkin lymphoma (NHL) treated at a fixed dose of 60 mg (0.8 mg/kg) (Dreyling et al., AACR 2017, CT149). Here we explore the dose-dependent pharmacodynamic (PD) effects of copanlisib relative to plasma exposure in subjects with NHL and solid tumors (ST) (NCT02155582). Methods: Patients with NHL or advanced/or refractory ST received copanlisib as a 1-hr IV infusion in 28 day cycles on an intermittent weekly schedule (3 weeks on /1 week off) at a dose of 0.8 mg/kg or 0.4 mg/kg. PD measurements comprised biomarkers related to PI3K signaling, including pAKT in platelet rich plasma (PRP), pAKT Ser473 or Thr308 and pS6 ribosomal protein Ser235/236 in paired tumor tissues, tumor glucose metabolism using FDG-PET imaging, and glucose metabolism markers (plasma glucose, insulin, and C-peptide). In addition, tumor/lymphoma lesions were evaluated based on RECIST 1.1 (for ST) and modified Cheson 2007 criteria (for NHL). Pharmacokinetic plasma exposure (Cmax and Cav) was calculated to assess the relationship with the PD markers. Adverse events were reported using NCI CTCAE v4.03. Results: Sixty-three patients received treatment: 33 patients with NHL (20 patients at 0.4 mg/kg and 13 patients at 0.8 mg/kg), 28 patients with ST (14 patients at 0.4 mg/kg and 14 patients at 0.8 mg/kg). Treatment with copanlisib resulted in ≥50% reduction in pAKT in PRP during the first two cycles at both 0.4 and 0.8 mg/kg dose levels within 24 hours. The decrease in pAKT in PRP was pronounced at 1.5 and at 3 hours post infusion and was sustained for ~24 hours. In paired tumor biopsies, copanlisib inhibited tumor pAKT (S473) and pS6 more effectively at 0.8 mg/kg (p Conclusions: This study provides PD evidence of target modulation with copanlisib including the inhibition of pAKT-S473 and pS6 in tumor tissue, inhibition of pAKT in PRP, reduction of FDG-PET tracer uptake, as well as increase in plasma glucose, insulin and C-peptide levels. A dose-dependency was observed for all PD parameters, except for pAKT in surrogate tissue. Treatment with copanlisib at 0.8 mg/kg was more effective at reducing tumor pAKT-S473 and pS6 levels compared to 0.4 mg/kg, consistent with more objective tumor responses seen here at 0.8 mg/kg. The safety profile was similar to previous reports. These results extend previous in vitro/in vivo observations and strongly support the on-target PI3K inhibitory activity for copanlisib in the clinical setting. Download : Download high-res image (182KB) Download : Download full-size image Disclosures Morschhauser: Roche: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Servier: Consultancy; Janssen: Consultancy, Honoraria; Gilead: Consultancy; Bristol-Myers Squibb: Consultancy, Honoraria. Machiels: Janssen: Research Funding; Bayer: Research Funding; Novartis: Research Funding; MSD: Membership on an entity's Board of Directors or advisory committees; Astrazeneca: Membership on an entity's Board of Directors or advisory committees; Innate: Membership on an entity's Board of Directors or advisory committees; Debiopharm: Membership on an entity's Board of Directors or advisory committees; Nanobiotik: Membership on an entity's Board of Directors or advisory committees. Salles: Servier: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; MSD: Consultancy, Honoraria; Kite: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Roche: Consultancy, Honoraria, Research Funding; BMS: Consultancy; morphosys: Consultancy, Honoraria. Rule: Roche: Consultancy, Honoraria, Other: Travel, Accommodations, Expenses, Research Funding; Astra-Zeneca: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Other: Travel, Accommodations, Expenses, Research Funding; Pharmacyclics: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Sunesis: Consultancy, Honoraria; TG Therapeutics: Consultancy, Honoraria; Napp: Consultancy; Kite: Consultancy. Cunningham: AstraZeneca: Research Funding; Bayer: Research Funding; Celgene: Research Funding; Merrimack: Research Funding; Mediummune: Research Funding; Merck Serono: Research Funding; Amgen: Research Funding; Sanofi: Research Funding. Genvresse: Bayer AG, Pharmaceuticals Division: Employment. Liu: Bayer HealthCare Pharmaceuticals: Employment. Kneip: Bayer AG, Pharmaceuticals Division: Employment. Pena: Bayer HealthCare Pharmaceuticals: Employment. Grevel: Bayer AG, Pharmaceuticals Division: Employment. Zhang: Bayer HealthCare Pharmaceuticals: Employment. Cisternas: Bayer AG, Pharmaceuticals Division: Employment. Reschke: Bayer AG, Pharmaceuticals Division: Employment. Granvil: Bayer HealthCare Pharmaceuticals: Employment.

Pooled Safety Analysis from Phase I and II Studies for Patients with Relapsed Indolent Non-Hodgkin's Lymphoma Treated with Intravenous Copanlisib

Pooled Safety Analysis from Phase I and II Studies for Patients with Relapsed Indolent Non-Hodgkin's Lymphoma Treated with Intravenous Copanlisib

Efficacy of Copanlisib Monotherapy in Patients with Relapsed or Refractory Marginal Zone Lymphoma: Subset Analysis from the CHRONOS-1 Trial

Efficacy of Copanlisib Monotherapy in Patients with Relapsed or Refractory Marginal Zone Lymphoma: Subset Analysis from the CHRONOS-1 Trial

Updated Safety and Efficacy from the Copanlisib CHRONOS-1 Trial in Patients with Relapsed or Refractory Indolent B-Cell Lymphoma: Low Incidence of Late-Onset Severe Toxicities

Updated Safety and Efficacy from the Copanlisib CHRONOS-1 Trial in Patients with Relapsed or Refractory Indolent B-Cell Lymphoma: Low Incidence of Late-Onset Severe Toxicities

Serendipity in the search for “morning-after pills” led to clomiphene for the induction of ovulation

The approval of the oral contraceptive on June 23, 1960, by the United States Food and Drug Administration (FDA), changed society forever. For the first time, a pill designed and tested by men, supported by influential women, allowed women to control their fertility. For the first time, the FDA approved a medicine to be taken by humans without a disease. The chance discovery of a new group of medicines called nonsteroidal antiestrogens, created an opportunity for the pharmaceutical industry. These compounds were shown to be postcoital antifertility agents in rats and mice. In the 1960s, the development of a "morning-after pill" would have had an enormous market. Numerous companies focused discovery efforts to evaluate the development of their patented nonsteroidal antiestrogens: Merrell (clomiphene), Upjohn (U-11,100A), and ICI Pharmaceutical Division (ICI46,474). However, the antifertility effects of antiestrogens in rats and mice does not mean that the new medicine would be an antifertility agent in women. In this case, clomiphene did exactly the opposite of what it was predicted to prevent. Clomiphene became the first medicine to induce ovulation in subfertile women. This article describes the twists and turns of drug discovery and development over the past half century. The conclusion emphasizes the evolution of drug development over decades, based on fashions in medical research and discoveries in clinical pharmacology. As a result, new uses for old molecules, that started life as "nonsteroidal antiestrogens," have revolutionized women's health as members of the new group of medicines called selective estrogen receptor modulators.

History of risedronate.

Herein we review the discovery, development, commercial history and legacy of risedronate or NE-58095, a potent N-containing bisphosphonate developed by scientists at the Cincinnati Miami Valley Laboratories and the Norwich Eaton Laboratories of Procter and Gamble. It is characterized by a hydroxyl substituent (R1) and a pyridyl-methylene substituent (R2) at the carbon bridging two phosphonate moieties. It was shown to have greater potency than alendronate in cell-based systems while binding affinity to bone matrix was lower than alendronate, accounting for the relatively rapid offset of bone turnover inhibition when therapy is discontinued. Risedronate was shown to significantly reduce serum alkaline phosphatase and clinical features in patients with Paget's disease and was approved for this indication, at a dose of 30mg daily for 2months, in 1998. Formal dose response testing for treatment of osteoporosis was not performed. In large Phase 3 studies, 5mg risedronate daily increased bone mineral density more than did the 2.5mg dose. As a result, the 2.5mg dose was dropped from most of the Phase 3 studies after 12months. The 5mg daily dose was approved for treating and preventing postmenopausal osteoporosis and glucocorticoid-induced osteoporosis in 2000. The drug was subsequently approved for treating men with osteoporosis. Following the leads of other companies, weekly and monthly preparations were developed and approved, based on non-inferiority BMD studies vs the 5mg daily oral dose as was a unique dosing regimen of 75mg given on 2 consecutive days each month. Finally, to overcome the effect of food on limiting the already poor gastrointestinal absorption of the drug, a once-weekly oral preparation containing the chelating agent EDTA and with an enteric coating delaying dissolution until the tablet was in the small intestine was approved in 2010 to be administered after breakfast. The Alliance for Better Bone Health, a collaboration between Procter & Gamble Pharmaceuticals and sanofi-aventis U.S. was formed to market risedronate as Actonel® and, subsequently, Actonel-EC® or Atelvia®. These drugs are still marketed by sanofi-aventis in some countries. The sale of the pharmaceutical division of Procter & Gamble to Warner Chilcott (US) was based, in large part, on the perceived value and marketability of the risedronate drugs. When marketing targets of Warner-Chilcott were not met, the rights of risedronate were sold to Allergan USA, Inc. which never actively promoted the drug. Generic forms of risedronate were introduced into the United States in 2015 but are rarely used, although several generic forms are actively marketed in other countries.

A REVIEW ON LIQUID CRYSTALLINE NANOPARTICLES (CUBOSOMES): EMERGING NANOPARTICULATE DRUG CARRIER

Cubosomes are novel biocompatible drug delivery system and have honeycombed (cavernous) structures whose diameter size range from 10–500 nm. They appear like dots, which are likely to be spherical structures. Each dot corresponds to the presence of a pore containing aqueous cubic phase in the lipid water system. Cubosomes posse’s great significance in the field of cosmeceuticals and Pharmaceuticals due to its unique features and become an attractive choice of vehicle for in vivo drug delivery due to their low cost, safety, efficacy and versatility for controlled release application and functionalization. Cubosomes have a very simple method of preparation; biodegradability of selected lipids has the capability to encapsulate hydrophobic and hydrophilic substances. Cubosomes are considered to be versatile systems, and prepared cubosomes can be administrated by different ways such as oral, percutaneous and parenteral routes. On the whole, cubosomes offer high consequence in nano-based drug preparations for melanoma (skin cancer) treatment, targeted drug delivery systems and comprise a wide range of applications in many areas and are characterized by various parameters. Consequently, cubosomes are in progress forward of awareness in the Pharmaceutical division. This review article mainly focuses on the methods of preparation, advantages, and applications of cubosomes.

Ibuprofen Safety at the Golden Anniversary: Are all NSAIDs the Same? A Narrative Review.

Ibuprofen first came to market about 50years ago and rapidly moved to over-the-counter (OTC) sales. In April 2019, the National Agency for the Safety of Medicines and Health Products (ANSM) of France issued a warning for NSAID uses by patients with infectious diseases based on an analysis of 20years of real-world safety data on ibuprofen and ketoprofen. Nevertheless, ibuprofen remains a mainstay in the analgesic armamentarium and with numerous randomized clinical trials, head-to-head studies, and decades of clinical experience. The authors offer a review of the safety of ibuprofen and how it may differ from other NSAIDs. Ibuprofen is associated with certain well-known gastrointestinal adverse effects that are related to dose and patient population. Among nonsteroidal anti-inflammatory drugs (NSAIDs), ibuprofen has a comparatively low risk of cardiovascular adverse effects. It has been associated with renal and hepatic adverse effects, which appear to depend on dose, concomitant medications, and patient population. The association of ibuprofen with infections is more complex in that it confers risk in some situations but benefits in others, the latter in cystic fibrosis. Emerging interest in the literature is providing evidence of the role of ibuprofen as a possible endocrine disrupter as well as its potential antiproliferative effects for cancer cells. Taken altogether, ibuprofen has a favorable safety profile and is an effective analgesic for many acute and chronic pain conditions, although it-like other NSAIDs-is not without risk. After 50years, evidence is still emerging about ibuprofen and its unique safety profile among NSAIDs. FUNDING: The Rapid Service Fee was funded by Abbott Established Pharmaceuticals Division (EPD).

Team work on hazardous drugs exposure handling measures and future prospects

Abstract In Japan, after the publication of guidelines for preventing Hazardous drug (HD) exposure in cancer treatment in 2015, much attention has been drawn to measures to prevent occupational exposure to HDs. However, sufficient HD measures have not been gained. A multi-institutional HD exposure survey was conducted from February 2016 to March 2018 as the National Hospital Organization (NHO) Hospital Network Research. In this survey, measures were taken by the exposure control team based on the actual HD exposure survey. As a result of repeated planning and implementation, the situation of HD exposure at each facility improved. Since the purpose of this study was to present a methodology for developing specific exposure measures, Ehime Prefecture Cancer cooperation council had started to establish a HD handling system based on this survey. A multicenter HD exposure survey was planned and implemented at 14 cancer hospitals. At 14 hospitals, we conducted HD exposure surveys using the sampling sheet method and the wipe method in the pharmaceutical division and the chemotherapeutic unit twice in 2018. Medical staff at each hospital organized a HD handling team and discussed specific measures to construct the safe handling system for HD exposure. In addition, a meeting was held to share information and discuss the two exposure survey results. At each facility, the actual condition of HD exposure improved in the second survey compared to the first. A third survey will be conducted this fall, including exposure surveys in wards, and plans are to be implemented based on continuous exposure monitoring. We established a system to create the practical HD exposure control system including doctors, nurses and pharmacists in Ehime prefecture, and promote continuous planning of measures by the team.

Balancing Tricks and Mini-pigs: Steps along the Road to Propofol

Balancing Tricks and Mini-pigs: Steps along the Road to Propofol

Effectiveness analysis and inspirations of rational administration of carbapenem

The hospital introduced a multi-department synergy in management of the rational use of carbapenems. Specifically, the medical affairs department conducts training and appraisal of doctors along with a monthly checkup of medical records. The pharmaceutical affairs division conducts prior prescriptions checkup and follow-up comment. The clinical microbiology laboratory and the hospital-acquired infection management department monitors and releases such infection and bacterial resistance information of the whole hospital in real time. The results showed increased prescriptions of imipenem and cilastatin sodium, and decreased prescriptions of biapenem for injection. Drug resistance analysis showed that carbapenem resistant strains increased by 28%, but the total number of patients reduced by 10% and total number of patients with multidrug resistance remained unchanged. It is proposed to further antimicrobial stewardship in the hospital to achieve rational drug use and curb bacterial resistance. Key words: Pharmacy administration; Carbapenem; Antibacterial agent; Rational use

Strategies for patient empowerment through the promotion of medicines in Israel: regulatory framework for the pharmaceutical industry

The correct and rational use of medications can have a positive direct impact on disease outcomes, as well on the utilization of the health system resources. Unfortunately, 50% of the patients do not take their medications as prescribed, largely due to lack of patients’ understanding of their medical condition, as well as the lack of reliable medicine information.There are multiple strategies implemented in many countries to tackle this challenge including: disease awareness campaigns (DAC) to raise the public awareness to specific diseases, direct-to-consumer advertisement (DTCA) to raise the public awareness to prescription medicines, specific treatments and over-the-counter (OTC) products to improve the accessibility of patients to specific medicines.Prior to 2013, the Israeli policy prohibited prescribing medication advertising and prevented the flow of information from pharmaceutical companies to the patient. In the last five years, the Pharmaceutical division in the Israeli Ministry of Health, as part of the “empowering the patient” agenda, has taken new innovative approaches to raise public awareness to diseases, medications and appropriate usage, as well as promotion of information to improve patient adherence to the prescribed medication.This paper elaborates on the aforementioned strategies implemented in developed countries, and specifically focuses on newly implemented strategies and regulations in Israel regarding pre- and post-prescription information, to improve patient appropriate utilization and adherence to medication.

A Phase III randomized controlled trial comparing the efficacy, safety and tolerability of oral dydrogesterone versus micronized vaginal progesterone for luteal support in in vitro fertilization.

STUDY QUESTION Is oral dydrogesterone 30 mg daily (10 mg three times daily [TID]) non-inferior to micronized vaginal progesterone (MVP) 600 mg daily (200 mg TID) for luteal support in in vitro fertilization (IVF), assessed by the presence of fetal heartbeats determined by transvaginal ultrasound at 12 weeks of gestation? SUMMARY ANSWER Non-inferiority of oral dydrogesterone versus MVP was demonstrated at 12 weeks of gestation, with a difference in pregnancy rate and an associated confidence interval (CI) that were both within the non-inferiority margin. WHAT IS KNOWN ALREADY MVP is routinely used in most clinics for luteal support in IVF, but it is associated with side effects, such as vaginal irritation and discharge, as well as poor patient acceptance. Dydrogesterone may be an alternative treatment due to its patient-friendly oral administration. STUDY DESIGN, SIZE, DURATION Lotus I was an international Phase III randomized controlled trial, performed across 38 sites, from August 2013 to March 2016. Subjects were premenopausal women (>18 to <42 years of age; body mass index (BMI) ≥18 to ≤30 kg/m2) with a documented history of infertility who were planning to undergo IVF. A centralized electronic system was used for randomization, and the study investigators, sponsor's study team, and subjects remained blinded throughout the study. PARTICIPANTS/MATERIALS, SETTING, METHODS In total, 1031 subjects were randomized to receive either oral dydrogesterone (n = 520) or MVP (n = 511). Luteal support was started on the day of oocyte retrieval and continued until 12 weeks of gestation (Week 10), if a positive pregnancy test was obtained at 2 weeks after embryo transfer. MAIN RESULTS AND THE ROLE OF CHANCE In the full analysis set (FAS), 497 and 477 subjects in the oral dydrogesterone and MVP groups, respectively, had an embryo transfer. Non-inferiority of oral dydrogesterone was demonstrated, with pregnancy rates at 12 weeks of gestation of 37.6% and 33.1% in the oral dydrogesterone and MVP treatment groups, respectively (difference 4.7%; 95% CI: -1.2-10.6%). Live birth rates of 34.6% (172 mothers with 213 newborns) and 29.8% (142 mothers with 158 newborns) were obtained in the dydrogesterone and MVP groups, respectively (difference 4.9%; 95% CI: -0.8-10.7%). Oral dydrogesterone was well tolerated and had a similar safety profile to MVP. LIMITATIONS, REASONS FOR CAUTION The analysis of the results was powered to consider the clinical pregnancy rate, but the live birth rate may be of greater clinical interest. Conclusions relating to the differences between treatments in live birth rate, observed in this study, should therefore be made with caution. WIDER IMPLICATIONS OF THE FINDINGS Oral dydrogesterone may replace MVP as the standard of care for luteal phase support in IVF, owing to the oral route being more patient-friendly than intravaginal administration, as well as it being a well tolerated and efficacious treatment. STUDY FUNDING/COMPETING INTEREST(S) Sponsored and supported by Abbott Established Pharmaceuticals Division. H.T.'s institution has received grants from Merck, MSD, Goodlife, Cook, Roche, Besins, Ferring and Mithra (now Allergan) and H.T. has received consultancy fees from Finox, Ferring, Abbott, ObsEva and Ovascience. G.S. has nothing to disclose. E.K. is an employee of Abbott GmbH. G.G. has received investigator fees from Abbott during the conduct of the study; outside of this submitted work, G.G. has received personal fees and non-financial support from MSD, Ferring, Merck-Serono, Finox, TEVA, Glycotope, as well as personal fees from VitroLife, NMC Healthcare LLC, ReprodWissen LLC and ZIVA LLC. TRIAL REGISTRATION NUMBER NCT01850030 (clinicaltrials.gov). TRIAL REGISTRATION DATE 19 April 2013. DATE OF FIRST PATIENT'S ENROLLMENT 23 August 2013.