Safety after extended repeated use of ulipristal acetate for uterine fibroids

Bart C J M Fauser; Jacques Donnez; Philippe Bouchard; David H Barlow; Francisco Vázquez; Pablo Arriagada; Sven O Skouby; Santiago Palacios; Janusz Tomaszewski; Boguslaw Lemieszczuk; Alistair R W William

doi:10.1371/journal.pone.0173523

Safety after extended repeated use of ulipristal acetate for uterine fibroids

Bart C J M Fauser, Jacques Donnez, Philippe Bouchard, David H Barlow, Francisco Vázquez, Pablo Arriagada, Sven O Skouby, Santiago Palacios, Janusz Tomaszewski, Boguslaw Lemieszczuk, Alistair R W William

Department of Clinical Medicine

40 Citations (Scopus)

58 Downloads (Pure)

Abstract

OBJECTIVE: To assess long term safety of extended repeated 3-month courses of ulipristal acetate (UPA) 10 mg/day, for up to 8 courses, with focus on endometrial and laboratory safety parameters.

METHODS: This long-term, multi-center, open-label cohort, follow up study consisted of up to 8 consecutive 3-month courses of daily UPA 10 mg, each separated by a drug free period of 2 spontaneous menstrual bleeds. Sixty-four pre-menopausal women, with moderate to severe symptomatic uterine myoma(s) and heavy bleeding were enrolled and were studied for approximately 4 years. The main outcome measures were endometrial histology, laboratory parameters and general safety.

RESULTS: All data was reported in a descriptive manner with no formal statistical comparisons. In the 64 women, non-physiological changes (mostly cyst formation, epithelial and vascular changes) in endometrial histology at screening and after treatment courses 4 and 8 were observed in 18.0%, 21.4% and 16.3% of biopsies, respectively. After treatment cessation, such changes were observed in 9.1% of biopsies. All endometrial biopsies were benign after course 8. The median endometrial thickness was 7.0 mm, 10-18 days after the start of menses following treatment courses 5-8, compared to 9.0 mm at screening (before UPA treatment). No changes in the number and type of laboratory results outside the normal ranges were observed with the increasing treatment courses. In total, adverse events were reported in 10 (16%), 12 (19%), 8 (14%) and 5 (9%) subjects, during treatment courses 5, 6, 7 and 8, respectively of which the most frequent adverse events were headache and hot flush.

CONCLUSION: The results of this study further support the safety profile of extended repeated 3 months treatment of symptomatic fibroids with ulipristal acetate 10 mg/day. Repeated UPA treatment courses did not result in any changes of concern in endometrial histology, endometrial thickness, or laboratory safety measures.

Original language	English
Article number	e0173523
Journal	PLOS ONE
Volume	12
Issue number	3
Number of pages	11
ISSN	1932-6203
DOIs	https://doi.org/10.1371/journal.pone.0173523
Publication status	Published - Mar 2017

Keywords

Adult
Biopsy
Clinical Trials, Phase III as Topic
Contraceptive Agents
Endometrium
Female
Follow-Up Studies
Humans
Leiomyoma
Middle Aged
Norpregnadienes
Journal Article
Multicenter Study

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10.1371/journal.pone.0173523Licence: CC BY

Safety after extended repeated use of ulipristal acetate for uterine fibroidsFinal published version, 1.27 MBLicence: CC BY

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title = "Safety after extended repeated use of ulipristal acetate for uterine fibroids",

abstract = "OBJECTIVE: To assess long term safety of extended repeated 3-month courses of ulipristal acetate (UPA) 10 mg/day, for up to 8 courses, with focus on endometrial and laboratory safety parameters.METHODS: This long-term, multi-center, open-label cohort, follow up study consisted of up to 8 consecutive 3-month courses of daily UPA 10 mg, each separated by a drug free period of 2 spontaneous menstrual bleeds. Sixty-four pre-menopausal women, with moderate to severe symptomatic uterine myoma(s) and heavy bleeding were enrolled and were studied for approximately 4 years. The main outcome measures were endometrial histology, laboratory parameters and general safety.RESULTS: All data was reported in a descriptive manner with no formal statistical comparisons. In the 64 women, non-physiological changes (mostly cyst formation, epithelial and vascular changes) in endometrial histology at screening and after treatment courses 4 and 8 were observed in 18.0%, 21.4% and 16.3% of biopsies, respectively. After treatment cessation, such changes were observed in 9.1% of biopsies. All endometrial biopsies were benign after course 8. The median endometrial thickness was 7.0 mm, 10-18 days after the start of menses following treatment courses 5-8, compared to 9.0 mm at screening (before UPA treatment). No changes in the number and type of laboratory results outside the normal ranges were observed with the increasing treatment courses. In total, adverse events were reported in 10 (16%), 12 (19%), 8 (14%) and 5 (9%) subjects, during treatment courses 5, 6, 7 and 8, respectively of which the most frequent adverse events were headache and hot flush.CONCLUSION: The results of this study further support the safety profile of extended repeated 3 months treatment of symptomatic fibroids with ulipristal acetate 10 mg/day. Repeated UPA treatment courses did not result in any changes of concern in endometrial histology, endometrial thickness, or laboratory safety measures.",

keywords = "Adult, Biopsy, Clinical Trials, Phase III as Topic, Contraceptive Agents, Endometrium, Female, Follow-Up Studies, Humans, Leiomyoma, Middle Aged, Norpregnadienes, Journal Article, Multicenter Study",

author = "Fauser, {Bart C J M} and Jacques Donnez and Philippe Bouchard and Barlow, {David H} and Francisco V{\'a}zquez and Pablo Arriagada and Skouby, {Sven O} and Santiago Palacios and Janusz Tomaszewski and Boguslaw Lemieszczuk and William, {Alistair R W}",

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T1 - Safety after extended repeated use of ulipristal acetate for uterine fibroids

AU - Fauser, Bart C J M

AU - Donnez, Jacques

AU - Bouchard, Philippe

AU - Barlow, David H

AU - Vázquez, Francisco

AU - Arriagada, Pablo

AU - Skouby, Sven O

AU - Palacios, Santiago

AU - Tomaszewski, Janusz

AU - Lemieszczuk, Boguslaw

AU - William, Alistair R W

PY - 2017/3

Y1 - 2017/3

N2 - OBJECTIVE: To assess long term safety of extended repeated 3-month courses of ulipristal acetate (UPA) 10 mg/day, for up to 8 courses, with focus on endometrial and laboratory safety parameters.METHODS: This long-term, multi-center, open-label cohort, follow up study consisted of up to 8 consecutive 3-month courses of daily UPA 10 mg, each separated by a drug free period of 2 spontaneous menstrual bleeds. Sixty-four pre-menopausal women, with moderate to severe symptomatic uterine myoma(s) and heavy bleeding were enrolled and were studied for approximately 4 years. The main outcome measures were endometrial histology, laboratory parameters and general safety.RESULTS: All data was reported in a descriptive manner with no formal statistical comparisons. In the 64 women, non-physiological changes (mostly cyst formation, epithelial and vascular changes) in endometrial histology at screening and after treatment courses 4 and 8 were observed in 18.0%, 21.4% and 16.3% of biopsies, respectively. After treatment cessation, such changes were observed in 9.1% of biopsies. All endometrial biopsies were benign after course 8. The median endometrial thickness was 7.0 mm, 10-18 days after the start of menses following treatment courses 5-8, compared to 9.0 mm at screening (before UPA treatment). No changes in the number and type of laboratory results outside the normal ranges were observed with the increasing treatment courses. In total, adverse events were reported in 10 (16%), 12 (19%), 8 (14%) and 5 (9%) subjects, during treatment courses 5, 6, 7 and 8, respectively of which the most frequent adverse events were headache and hot flush.CONCLUSION: The results of this study further support the safety profile of extended repeated 3 months treatment of symptomatic fibroids with ulipristal acetate 10 mg/day. Repeated UPA treatment courses did not result in any changes of concern in endometrial histology, endometrial thickness, or laboratory safety measures.

AB - OBJECTIVE: To assess long term safety of extended repeated 3-month courses of ulipristal acetate (UPA) 10 mg/day, for up to 8 courses, with focus on endometrial and laboratory safety parameters.METHODS: This long-term, multi-center, open-label cohort, follow up study consisted of up to 8 consecutive 3-month courses of daily UPA 10 mg, each separated by a drug free period of 2 spontaneous menstrual bleeds. Sixty-four pre-menopausal women, with moderate to severe symptomatic uterine myoma(s) and heavy bleeding were enrolled and were studied for approximately 4 years. The main outcome measures were endometrial histology, laboratory parameters and general safety.RESULTS: All data was reported in a descriptive manner with no formal statistical comparisons. In the 64 women, non-physiological changes (mostly cyst formation, epithelial and vascular changes) in endometrial histology at screening and after treatment courses 4 and 8 were observed in 18.0%, 21.4% and 16.3% of biopsies, respectively. After treatment cessation, such changes were observed in 9.1% of biopsies. All endometrial biopsies were benign after course 8. The median endometrial thickness was 7.0 mm, 10-18 days after the start of menses following treatment courses 5-8, compared to 9.0 mm at screening (before UPA treatment). No changes in the number and type of laboratory results outside the normal ranges were observed with the increasing treatment courses. In total, adverse events were reported in 10 (16%), 12 (19%), 8 (14%) and 5 (9%) subjects, during treatment courses 5, 6, 7 and 8, respectively of which the most frequent adverse events were headache and hot flush.CONCLUSION: The results of this study further support the safety profile of extended repeated 3 months treatment of symptomatic fibroids with ulipristal acetate 10 mg/day. Repeated UPA treatment courses did not result in any changes of concern in endometrial histology, endometrial thickness, or laboratory safety measures.

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KW - Biopsy

KW - Clinical Trials, Phase III as Topic

KW - Contraceptive Agents

KW - Endometrium

KW - Female

KW - Follow-Up Studies

KW - Humans

KW - Leiomyoma

KW - Middle Aged

KW - Norpregnadienes

KW - Journal Article

KW - Multicenter Study

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DO - 10.1371/journal.pone.0173523

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SN - 1932-6203

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JO - PLOS ONE

JF - PLOS ONE

IS - 3

M1 - e0173523

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Safety after extended repeated use of ulipristal acetate for uterine fibroids

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Keywords

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