Vera Halpern , Angie Wheeless , Vivian Brache , Anja Lendvay , Leila Cochón , Douglas Taylor , Laneta J. Dorflinger
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We assessed local tolerability by occurrence of injection site reactions (ISRs), as well as injection site pain and overall safety for at least 9 months postinjections.</p></div><div><h3>Results</h3><p>Of a total of 108 study injections, three injections were partial due to needle blockage. We observed a total of 30 ISRs following 105 full-dose injections, including hypopigmentation (<em>n</em> = 24), bruising (<em>n</em> = 4), and atrophy/dimple (<em>n</em> = 2). Eleven cases of hypopigmentation occurred following 25 full-dose injections of undiluted TV-46046 (44.0%), six following 27 full-dose injections of diluted TV-46046 (22.2%), and seven following 26 full-dose injections of Depo-subQ 104 (26.9%). Hypopigmentations occurred on average 8 months postinjection. Injection pain was minimal and dissipated quickly after all four injections.</p></div><div><h3>Conclusions</h3><p>Subcutaneous administration of MPA in a suspension formulation is associated with the delayed onset of hypopigmentation at the site of injection. Although not statistically significant, the rate of ISRs was over 60% higher for undiluted TV-46046 compared to Depo-subQ 104. This difference bears careful monitoring in future studies of TV-46046.</p></div><div><h3>Implications</h3><p>From a safety standpoint, investigational drug TV-46046 is appropriate for further clinical testing as a 6-month contraceptive injectable. The previously underreported hypopigmentation associated with subcutaneous administration of MPA warrants further investigation and acceptability assessment among users of existing Depo-subQ 104 as well as careful monitoring of local tolerability of TV-46046 in future clinical trials.</p></div><div><h3>Trial registration</h3><p>Registered at clinicaltrials.gov no: NCT02817464</p></div>","PeriodicalId":10655,"journal":{"name":"Contraception: X","volume":"5 ","pages":"Article 100100"},"PeriodicalIF":0.0000,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10562734/pdf/","citationCount":"0","resultStr":"{\"title\":\"A randomized crossover study to evaluate local tolerability following subcutaneous administration of a new depot medroxyprogesterone acetate contraceptive formulation\",\"authors\":\"Vera Halpern , Angie Wheeless , Vivian Brache , Anja Lendvay , Leila Cochón , Douglas Taylor , Laneta J. Dorflinger\",\"doi\":\"10.1016/j.conx.2023.100100\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Objectives</h3><p>This study aimed to evaluate and compare local tolerability of investigational drug TV-46046 and reference drug Depo-subQ Provera 104, both containing medroxyprogesterone acetate (MPA) as an active ingredient.</p></div><div><h3>Study design</h3><p>We conducted a randomized, crossover, single-center study. Twenty-seven healthy women aged 25 to 47 years at low risk of pregnancy received a subcutaneous injection of each of the four study drugs (120 mg/0.3 mL of TV-46046, 60 mg/0.3 mL of diluted TV-46046, 0.3 mL of TV-46046 placebo, and 104 mg/0.65 mL of Depo-subQ 104) in different quadrants of the abdomen. We assessed local tolerability by occurrence of injection site reactions (ISRs), as well as injection site pain and overall safety for at least 9 months postinjections.</p></div><div><h3>Results</h3><p>Of a total of 108 study injections, three injections were partial due to needle blockage. We observed a total of 30 ISRs following 105 full-dose injections, including hypopigmentation (<em>n</em> = 24), bruising (<em>n</em> = 4), and atrophy/dimple (<em>n</em> = 2). Eleven cases of hypopigmentation occurred following 25 full-dose injections of undiluted TV-46046 (44.0%), six following 27 full-dose injections of diluted TV-46046 (22.2%), and seven following 26 full-dose injections of Depo-subQ 104 (26.9%). Hypopigmentations occurred on average 8 months postinjection. 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The previously underreported hypopigmentation associated with subcutaneous administration of MPA warrants further investigation and acceptability assessment among users of existing Depo-subQ 104 as well as careful monitoring of local tolerability of TV-46046 in future clinical trials.</p></div><div><h3>Trial registration</h3><p>Registered at clinicaltrials.gov no: NCT02817464</p></div>\",\"PeriodicalId\":10655,\"journal\":{\"name\":\"Contraception: X\",\"volume\":\"5 \",\"pages\":\"Article 100100\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2023-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10562734/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Contraception: X\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S2590151623000126\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"Medicine\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Contraception: X","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2590151623000126","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"Medicine","Score":null,"Total":0}
引用次数: 0
摘要
目的：本研究旨在评估和比较试验药物TV-46046和参考药物Depo subQ Provera 104的局部耐受性，这两种药物都含有醋酸甲羟孕酮（MPA）作为活性成分。研究设计：我们进行了一项随机、交叉、单中心的研究。27名年龄在25至47岁、妊娠风险较低的健康女性在腹部不同象限皮下注射四种研究药物（120 mg/0.3 mL TV-46046、60 mg/0.3 mL稀释的TV-46043、0.3 mL TV-46046安慰剂和104 mg/0.65 mL Depo subQ 104）。我们通过注射部位反应（ISRs）的发生、注射部位疼痛和注射后至少9个月的总体安全性来评估局部耐受性。结果：在总共108次研究注射中，有三次是由于针头堵塞而部分注射的。在105次全剂量注射后，我们共观察到30次ISR，包括色素沉着不足（n=24）、瘀伤（n=4）和萎缩/酒窝（n=2）。在25次全剂量注射未稀释的TV-46046（44.0%）后出现11例色素沉着不足，在27次全剂量注入稀释的TV-46046（22.2%）后出现6例，在26次全剂量注射剂Depo subQ 104（26.9%）后出现7例。注射疼痛很小，四次注射后很快就消失了。结论：MPA混悬剂皮下给药与注射部位色素沉着减退的延迟发作有关。尽管没有统计学意义，但与Depo subQ 104相比，未稀释的TV-46046的ISR发生率高出60%以上。这种差异在未来的TV-46046研究中需要仔细监测。提示：从安全性的角度来看，试验药物TV-4604六适合作为6个月的避孕注射药物进行进一步的临床测试。先前少报的与皮下注射MPA相关的色素沉着不足，需要在现有Depo subQ 104的使用者中进行进一步的调查和可接受性评估，并在未来的临床试验中仔细监测TV-46046的局部耐受性。试验注册：注册于clinicaltrials.gov，编号：NCT02817464。
A randomized crossover study to evaluate local tolerability following subcutaneous administration of a new depot medroxyprogesterone acetate contraceptive formulation
Objectives
This study aimed to evaluate and compare local tolerability of investigational drug TV-46046 and reference drug Depo-subQ Provera 104, both containing medroxyprogesterone acetate (MPA) as an active ingredient.
Study design
We conducted a randomized, crossover, single-center study. Twenty-seven healthy women aged 25 to 47 years at low risk of pregnancy received a subcutaneous injection of each of the four study drugs (120 mg/0.3 mL of TV-46046, 60 mg/0.3 mL of diluted TV-46046, 0.3 mL of TV-46046 placebo, and 104 mg/0.65 mL of Depo-subQ 104) in different quadrants of the abdomen. We assessed local tolerability by occurrence of injection site reactions (ISRs), as well as injection site pain and overall safety for at least 9 months postinjections.
Results
Of a total of 108 study injections, three injections were partial due to needle blockage. We observed a total of 30 ISRs following 105 full-dose injections, including hypopigmentation (n = 24), bruising (n = 4), and atrophy/dimple (n = 2). Eleven cases of hypopigmentation occurred following 25 full-dose injections of undiluted TV-46046 (44.0%), six following 27 full-dose injections of diluted TV-46046 (22.2%), and seven following 26 full-dose injections of Depo-subQ 104 (26.9%). Hypopigmentations occurred on average 8 months postinjection. Injection pain was minimal and dissipated quickly after all four injections.
Conclusions
Subcutaneous administration of MPA in a suspension formulation is associated with the delayed onset of hypopigmentation at the site of injection. Although not statistically significant, the rate of ISRs was over 60% higher for undiluted TV-46046 compared to Depo-subQ 104. This difference bears careful monitoring in future studies of TV-46046.
Implications
From a safety standpoint, investigational drug TV-46046 is appropriate for further clinical testing as a 6-month contraceptive injectable. The previously underreported hypopigmentation associated with subcutaneous administration of MPA warrants further investigation and acceptability assessment among users of existing Depo-subQ 104 as well as careful monitoring of local tolerability of TV-46046 in future clinical trials.
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