Large, comparative, randomized double-blind trial confirming noninferiority of pregnancy rates for corifollitropin alfa compared with recombinant follicle-stimulating hormone in a gonadotropin-releasing hormone antagonist controlled ovarian stimulation protocol in older patients undergoing in vitro fertilization

Rosenwaks, Zev; Witjes, Han; Stegmann, B.; Elbers, Jolanda; Gordon, Keith; Mannaerts, Bernadette; Barmat, Larry I.; Bayer, Steven R.; Boostanfar, R.; Carson, Samantha; Crain, J.L.; DeVane, Gary W.; Dokras, Anuja; Doody, Kevin J.; Frattarelli, John L.; Givens, C.; Jacobs, M.; Karande, Vishvanath; Kenigsberg, O.; Kim, A.; Kort, Hilton I.; Slayden, S.M.; Kutteh, W.H.; Levy, Michael J.; Lifchez, A.; Beltsos, Angeline; Nulsen, John; Oehninger, Sergio; Pang, Samuel C.; Sauer, Mark V.; Scheiber, Michael D.; Schnell, Vicki L.; Schoolcraft, William B.; Shapiro, B.S.; Slater, Cristin C.; Stelling, J.; Werlin, L.B.; Westphal, Lynn M.; Yee, Woon Chee; Yeko, T.

doi:10.1016/j.fertnstert.2015.04.018

Cited by 52 publications

(73 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Dose selection for the phase III clinical programme was based on an extensive modelling and simulation analysis. The selected doses were evaluated prospectively after completion of the phase III trials, and resulted in an acceptable safety profile, favourable pharmacodynamics, a low risk of cycle cancellation and a desirable number of follicles and oocytes retrieved . The recommended dose of corifollitropin alfa is dependent on body weight in women ≤ 36 years of age: 100 μg for women with a body weight ≤ 60 kg and 150 μg for women with a body weight > 60 kg.…”

Section: Discussionmentioning

confidence: 99%

“…From day 8 onward, additional doses of rFSH may be needed until the criteria for hCG trigger (three follicles at ≥ 17 mm) have been met. This profile for follicular recruitment and oocyte development has been supported by clinical trials which have demonstrated equivalency between the treatments [4][5][6].…”

Section: Introductionmentioning

confidence: 91%

“…AUC = area under the curve Figure 6 Comparison of area under the curve (AUC) across the pivotal phase III trials. Data are limited to Caucasian subjects only retrieved [4][5][6]. The recommended dose of corifollitropin alfa is dependent on body weight in women ≤ 36 years of age: 100 μg for women with a body weight ≤ 60 kg and 150 μg for women with a body weight > 60 kg.…”

Section: Figurementioning

confidence: 99%

See 2 more Smart Citations

Impact of patient characteristics on the pharmacokinetics of corifollitropin alfa during controlled ovarian stimulation

Zandvliet

Prohn

Greef

et al. 2016

Brit J Clinical Pharma

Self Cite

View full text Add to dashboard Cite

AIMThe aim of the present study was to characterize the pharmacokinetic profile of corifollitropin alfa and examine the relationships between dose, intrinsic factors [body weight, body mass index (BMI), age and race] and corifollitropin alfa pharmacokinetics. METHODSData from five phase II and III clinical trials of corifollitropin alfa were evaluated. All subjects included in the analysis received 60 -180 μg corifollitropin alfa for controlled ovarian stimulation in a gonadotrophin-releasing hormone antagonist protocol followed by daily recombinant follicle stimulating hormone (rFSH) from day 8 onwards. Serum corifollitropin alfa levels (across the entire range of treatment) and total follicle stimulating hormone immunoreactivity levels (up to the start of rFSH treatment) were indicators of drug exposure. The analyses were performed using a nonlinear mixed-effects modelling approach. RESULTSA total of 2630 subjects were treated with corifollitropin alfa, and 2557 subjects were evaluable for analysis. Body weight, BMI and race (Asian and Black vs. Caucasian) were significant determinants of corifollitropin alfa exposure. Dose-normalized corifollitropin alfa exposure was~89% higher in women with a body weight of 50 kg vs. 90 kg (in subjects with a similar BMI of 24 kg m À2 ); 14% higher in women with a BMI of 18 kg m À2 vs. 32 kg m À2 (provided they were of similar body weight); and~15.7% lower in Asian subjects and 13% higher in Black subjects vs. Caucasian subjects. CONCLUSIONSBody weight was the major determinant of corifollitropin alfa exposure; BMI and race (Asian and Black) were also determinants but to a lesser extent and without associated effects on clinical outcomes. Corifollitropin alfa dose adjustment is indicated, based on body weight but not for BMI or race. These recommendations are consistent with the product label. WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• Corifollitropin alfa is a recombinant gonadotrophin.• A single injection of corifollitropin alfa initiates and sustains multiple follicular growth over the first 7 days of ovarian stimulation.• Body weight is a major determinant of exposure to corifollitropin alfa and treatment outcome. WHAT THIS STUDY ADDS• Body mass index and race are also determinants of corifollitropin alfa exposure but to a lesser extent than body weight.• Ovarian response is similar, irrespective of BMI and race; thus, dose adjustments based on these factors are not necessary. British Journal of Clinical PharmacologyBr J Clin Pharmacol (2016) 82 74-82 74

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 91%

Section: Figurementioning

confidence: 99%

See 1 more Smart Citation

Impact of patient characteristics on the pharmacokinetics of corifollitropin alfa during controlled ovarian stimulation

Zandvliet

Prohn

Greef

et al. 2016

Brit J Clinical Pharma

Self Cite

View full text Add to dashboard Cite

show abstract

“…In women seeking infertility care, treatment with corifollitropin alfa produced a similar therapeutic response compared with that of recFSH [7–9]. Corifollitropin alfa has the same pharmacodynamic (PD) profile as recFSH, but an approximately two-fold longer elimination half-life (t 1/2 ) and an almost four-fold extended time interval to peak serum levels relative to that of recFSH [10].…”

Section: Introductionmentioning

confidence: 99%

An open-label clinical trial to investigate the efficacy and safety of corifollitropin alfa combined with hCG in adult men with hypogonadotropic hypogonadism

Nieschlag

Bouloux

Stegmann

et al. 2017

Reprod Biol Endocrinol

Self Cite

View full text Add to dashboard Cite

BackgroundHypogonadotropic hypogonadism (HH) in men results in insufficient testicular function and deficiencies in testosterone and spermatogenesis. Combinations of human chorionic gonadotropin (hCG) and recombinant follicle-stimulating hormone (recFSH) have been successful in the treatment of HH. Corifollitropin alfa is a long-acting FSH-analog with demonstrated action in women seeking infertility care. The aim of this study was to investigate the efficacy and safety of corifollitropin alfa combined with hCG to increase testicular volume and induce spermatogenesis in men with HH.MethodsThis was a Phase III, multi-center, open-label, single-arm trial of corifollitropin alfa in azoospermic men aged 18 to 50 years with HH. After 16 weeks of pretreatment of 23 subjects with hCG alone, 18 subjects with normalized testosterone (T) levels who remained azoospermic entered the 52-week combined treatment phase with hCG twice-weekly and 150 μg corifollitropin alfa every other week. The increase in testicular volume (primary efficacy endpoint) and induction of spermatogenesis resulting in a sperm count ≥1 × 106/mL (key secondary efficacy endpoint) during 52 weeks of combined treatment were assessed. Safety was evaluated by the presence of anti-corifollitropin alfa antibodies and the occurrence of adverse events (AEs).ResultsMean (±SD) testicular volume increased from 8.6 (±6.09) mL to 17.8 (±8.93) mL (geometric mean fold increase, 2.30 [95% CI: 2.03, 2.62]); 14 (77.8%) subjects reached a sperm count ≥1 × 106/mL. No subject developed confirmed anti-corifollitropin alfa antibodies during the trial. Treatment was generally well tolerated.ConclusionsCorifollitropin alfa 150 μg administrated every other week combined with twice-weekly hCG for 52 weeks increased testicular volume significantly, and induced spermatogenesis in >75% of men with HH who had remained azoospermic after hCG treatment alone.Trial registrationClinicalTrials.gov: NCT01709331.Electronic supplementary materialThe online version of this article (doi:10.1186/s12958-017-0232-y) contains supplementary material, which is available to authorized users.

show abstract

“…The FSH‐CTP introduction reduces the number of injections needed for ovarian stimulation and permits a simpler approach. FSH‐CTP has been used successfully in women, cattle and rabbits (Boostanfar et al, ; Carvalho et al, ; Devroey et al, ; Fauser et al, ; Vicente, Viudes‐de‐Castro, Cedano‐Castro, & Marco‐Jiménez, ; Viudes‐de‐Castro et al, ). Although FSH is the main regulator of ovarian follicle growth and maturation, LH induces key changes in both oocyte and follicular cells, that contribute to suitable oocyte competence acquisition, with a prominent role in the process of ovulation and in subsequent fertilization and implantation process.…”

Section: Discussionmentioning

confidence: 99%

A single injection of corifollitropin alfa supplemented with human chorionic gonadotropin increases follicular recruitment and transferable embryos in the rabbit

Viudes-de-Castro

Marco‐Jiménez

Pellicer

et al. 2019

Reprod Domestic Animals

View full text Add to dashboard Cite

| INTRODUC TI ONSuperovulation protocols are designed to ensure the maximum number of transferable embryos per donor. Most of the embryos produced by superovulation are cryopreserved until they are subsequently used, which allows saving embryos for an unlimited time. The human gonadotropins, follicle-stimulating hormone (FSH), luteinizing hormone (LH) and human chorionic gonadotropin (hCG) are commonly used for superovulation in humans and animals. The effectiveness of superovulation treatments with gonadotropins is dependent on the maintenance of adequate daily levels of FSH throughout the process. The short elimination half-life and rapid metabolic clearance of the traditional FSH require twice daily treatments, which increases the donor handling and the possibility of errors in giving the treatments. The introduction of corifollitropin alfa (FSH-CTP), a long-acting recombinant FSH, has given an opportunity to simplify superstimulation protocols, reducing the number of injections and consequently improving the overall donor management. On the other hand, results of superovulation treatments vary, and one of the reasons for this may be the variable LH:FSH ratio. Although LH has essential and well-established roles in ovarian steroid synthesis and ovulation (

show abstract

Cited by 52 publications

References 18 publications

Impact of patient characteristics on the pharmacokinetics of corifollitropin alfa during controlled ovarian stimulation

Impact of patient characteristics on the pharmacokinetics of corifollitropin alfa during controlled ovarian stimulation

An open-label clinical trial to investigate the efficacy and safety of corifollitropin alfa combined with hCG in adult men with hypogonadotropic hypogonadism

A single injection of corifollitropin alfa supplemented with human chorionic gonadotropin increases follicular recruitment and transferable embryos in the rabbit

Contact Info

Product

Resources

About