Dee-Dee Shiller, Betty B. Yao, Mong-Jen Chen, Amelia Orejudos, Nael M. Mostafa, John F. Marcinak, Margaret Burroughs, Craig Boyle
{"title":"含低剂量炔雌醇的口服避孕药联合格列卡普瑞韦/匹布特韦治疗对绝经前健康女性安全性和耐受性的 1 期研究。","authors":"Dee-Dee Shiller, Betty B. Yao, Mong-Jen Chen, Amelia Orejudos, Nael M. Mostafa, John F. Marcinak, Margaret Burroughs, Craig Boyle","doi":"10.1111/jvh.13946","DOIUrl":null,"url":null,"abstract":"<p>Glecaprevir/pibrentasvir (GLE/PIB) is an approved guideline-recommended chronic hepatitis C virus infection treatment. GLE/PIB coadministration with ethinyl oestradiol (EE) is not recommended in current labels owing to a Phase 1 study observing Grade ≥2 alanine aminotransferase (ALT) elevation in 2 out of 12 healthy women cotreated for 11 days with GLE/PIB and oral contraceptive (OC) containing 35 μg/250 μg EE/norgestimate. No Grade ≥2 elevation was observed with low-dose (20 μg) EE (<i>n</i> = 14). This Phase 1 study examined safety/tolerability of GLE/PIB coadministered with an OC containing low-dose EE using a larger sample size and longer treatment duration. Healthy premenopausal women were treated with EE/levonorgestrel alone (20/100 μg, Cycles 1–2), followed by coadministration with GLE/PIB (300/120 mg; Cycles 3–4). A safety criterion of special interest was a confirmed Grade ≥2 ALT elevation (>3× upper normal limit). Adverse events (AEs) and study drugs concentrations were examined. Of 85 enrolled women, 72 initiated combined GLE/PIB + EE/levonorgestrel treatment, 66 completed the study and 19 discontinued prematurely (non-safety reason, <i>n</i> = 16; AE [deemed unelated to GLE/PIB], <i>n</i> = 3). No participant met the safety criterion of special interest of confirmed Grade ≥2 ALT elevation. No serious/Grade ≥3 AEs were reported. Study drug concentrations were within the expected ranges. GLE/PIB in combination with an OC containing low-dose EE was generally well tolerated with no confirmed Grade ≥2 ALT elevation and no evidence of drug-induced liver injury. No pattern to the reported AEs and no new safety issues were identified. This was a Phase 1 study of healthy volunteers, not a registered clinical trial.</p>","PeriodicalId":17762,"journal":{"name":"Journal of Viral Hepatitis","volume":"31 7","pages":"409-415"},"PeriodicalIF":2.5000,"publicationDate":"2024-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jvh.13946","citationCount":"0","resultStr":"{\"title\":\"Phase 1 study of safety and tolerability of an oral contraceptive containing low-dose ethinyl oestradiol combined with glecaprevir/pibrentasvir treatment in healthy premenopausal women\",\"authors\":\"Dee-Dee Shiller, Betty B. Yao, Mong-Jen Chen, Amelia Orejudos, Nael M. Mostafa, John F. Marcinak, Margaret Burroughs, Craig Boyle\",\"doi\":\"10.1111/jvh.13946\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>Glecaprevir/pibrentasvir (GLE/PIB) is an approved guideline-recommended chronic hepatitis C virus infection treatment. GLE/PIB coadministration with ethinyl oestradiol (EE) is not recommended in current labels owing to a Phase 1 study observing Grade ≥2 alanine aminotransferase (ALT) elevation in 2 out of 12 healthy women cotreated for 11 days with GLE/PIB and oral contraceptive (OC) containing 35 μg/250 μg EE/norgestimate. No Grade ≥2 elevation was observed with low-dose (20 μg) EE (<i>n</i> = 14). This Phase 1 study examined safety/tolerability of GLE/PIB coadministered with an OC containing low-dose EE using a larger sample size and longer treatment duration. Healthy premenopausal women were treated with EE/levonorgestrel alone (20/100 μg, Cycles 1–2), followed by coadministration with GLE/PIB (300/120 mg; Cycles 3–4). A safety criterion of special interest was a confirmed Grade ≥2 ALT elevation (>3× upper normal limit). Adverse events (AEs) and study drugs concentrations were examined. Of 85 enrolled women, 72 initiated combined GLE/PIB + EE/levonorgestrel treatment, 66 completed the study and 19 discontinued prematurely (non-safety reason, <i>n</i> = 16; AE [deemed unelated to GLE/PIB], <i>n</i> = 3). No participant met the safety criterion of special interest of confirmed Grade ≥2 ALT elevation. No serious/Grade ≥3 AEs were reported. Study drug concentrations were within the expected ranges. GLE/PIB in combination with an OC containing low-dose EE was generally well tolerated with no confirmed Grade ≥2 ALT elevation and no evidence of drug-induced liver injury. No pattern to the reported AEs and no new safety issues were identified. 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Phase 1 study of safety and tolerability of an oral contraceptive containing low-dose ethinyl oestradiol combined with glecaprevir/pibrentasvir treatment in healthy premenopausal women
Glecaprevir/pibrentasvir (GLE/PIB) is an approved guideline-recommended chronic hepatitis C virus infection treatment. GLE/PIB coadministration with ethinyl oestradiol (EE) is not recommended in current labels owing to a Phase 1 study observing Grade ≥2 alanine aminotransferase (ALT) elevation in 2 out of 12 healthy women cotreated for 11 days with GLE/PIB and oral contraceptive (OC) containing 35 μg/250 μg EE/norgestimate. No Grade ≥2 elevation was observed with low-dose (20 μg) EE (n = 14). This Phase 1 study examined safety/tolerability of GLE/PIB coadministered with an OC containing low-dose EE using a larger sample size and longer treatment duration. Healthy premenopausal women were treated with EE/levonorgestrel alone (20/100 μg, Cycles 1–2), followed by coadministration with GLE/PIB (300/120 mg; Cycles 3–4). A safety criterion of special interest was a confirmed Grade ≥2 ALT elevation (>3× upper normal limit). Adverse events (AEs) and study drugs concentrations were examined. Of 85 enrolled women, 72 initiated combined GLE/PIB + EE/levonorgestrel treatment, 66 completed the study and 19 discontinued prematurely (non-safety reason, n = 16; AE [deemed unelated to GLE/PIB], n = 3). No participant met the safety criterion of special interest of confirmed Grade ≥2 ALT elevation. No serious/Grade ≥3 AEs were reported. Study drug concentrations were within the expected ranges. GLE/PIB in combination with an OC containing low-dose EE was generally well tolerated with no confirmed Grade ≥2 ALT elevation and no evidence of drug-induced liver injury. No pattern to the reported AEs and no new safety issues were identified. This was a Phase 1 study of healthy volunteers, not a registered clinical trial.
期刊介绍:
The Journal of Viral Hepatitis publishes reviews, original work (full papers) and short, rapid communications in the area of viral hepatitis. It solicits these articles from epidemiologists, clinicians, pathologists, virologists and specialists in transfusion medicine working in the field, thereby bringing together in a single journal the important issues in this expanding speciality.
The Journal of Viral Hepatitis is a monthly journal, publishing reviews, original work (full papers) and short rapid communications in the area of viral hepatitis. It brings together in a single journal important issues in this rapidly expanding speciality including articles from:
virologists;
epidemiologists;
clinicians;
pathologists;
specialists in transfusion medicine.