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GSK1349572 Drug Interaction Study With Fosamprenavir/Ritonavir

2017年1月17日 更新者:ViiV Healthcare

Phase I, Open Label, Two Period Study to Evaluate the Effects of Fosamprenavir/Ritonavir on GSK1349572 Pharmacokinetics and a Phase I, Randomized, Three-Way Crossover Study to Evaluate the Relative Bioavailability of Three Tablet Variants Made Using Micronized, Unmicronized and Intermediate Particle Sizes of GSK1349572 in Healthy Adult Subjects

GSK1349572 is an integrase inhibitor being developed for the treatment of human immunodeficiency virus (HIV)-1 infection by GlaxoSmithKline (GSK) on behalf of Shionogi-ViiV HealthcareLLC. In HIV-infected patients where combination antiretroviral therapy is the standard of care, it is likely that it will be dosed with boosted protease inhibitors (PIs) including fosamprenavir/ritonavir (FPV/RTV or FPV/r). As FPV and RTV are modulators (induction as well as inhibition) of Uridine diphosphate glucuronosyltransferase (UGT) and Cytochrome P450 (CYP)3A which are the primary and secondary metabolic pathways of GKS1349572, it is likely that FPV/RTV will affect the pharmacokinetics (PK) of GSK1349572, therefore a drug interaction study is warranted and will be evaluated in Part A of this study. Part B will evaluate the effect of particle size of tablet variants on the PK of GSK1349572.

In Part A, approximately 12 subjects will receive GSK1349572 50mg every 24 hours (q24h) for 5 days (Treatment A). Subjects will then be administered GSK1349572 50mg q24h in combination with FPV/RTV 700/100 mg every 12 hours (q12h) (Treatment B) for 10 days. There will be no washout between treatments. In Part B 15 subjects will receive a single 50 mg dose (2 x 25mg tablet) in 3 different tablet variants of the same formulation, differing only in particle sizes of GSK1349572, under fasted conditions in a three-way crossover design. Safety evaluations and serial PK samples will be collected during each treatment period. A follow-up visit will occur 7-14 days after the last dose of study drug.

調査の概要

詳細な説明

Official Study Title: Phase I, open label, two period, study to evaluate the effects of fosamprenavir/ritonavir on GSK1349572 pharmacokinetics and a phase I, randomized, three-way crossover study to evaluate the relative bioavailability of three tablet variants made using micronized, unmicronized and intermediate particle sizes of GSK1349572 in healthy adult subjects (ING113068).

ViiV Healthcare is the new sponsor of this study, and GlaxoSmithKline is in the process of updating systems to reflect the change in sponsorship

研究の種類

介入

入学 (実際)

27

段階

  • フェーズ 1

連絡先と場所

このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。

研究場所

    • New York
      • Buffalo、New York、アメリカ、14202
        • GSK Investigational Site

参加基準

研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。

適格基準

就学可能な年齢

18年~65年 (大人、高齢者)

健康ボランティアの受け入れ

はい

受講資格のある性別

全て

説明

Inclusion Criteria:

  • Aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase and bilirubin less than 1.5x upper limit of normal (ULN) (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
  • Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring.
  • Male or female between 18 and 65 years of age inclusive, at the time of signing the informed consent.
  • A female subject is eligible to participate if she is of: Non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea [in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) > 40 MlU/ml and estradiol < 40 pg/ml (<146.8 pmol/L) is confirmatory]. or Child-bearing potential with a negative pregnancy test at both Screening and Day -1 and agrees to use one of the contraception methods listed in the protocol for an appropriate period of time (as determined by the product label or investigator) prior to the start of dosing to sufficiently minimize the risk of pregnancy at that point. Female subjects must agree to use contraception until the follow-up visit.
  • Body weight greater than 50 kg for males and 45 kg for females and BMI within the range 18.5- 31.0 kg/m2 (inclusive).
  • Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.

Exclusion Criteria:

  • The subject has a positive pre-study drug/alcohol screen. A minimum list of drugs that will be screened for include amphetamines, barbiturates, cocaine, opiates, cannabinoids and benzodiazepines.
  • The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
  • History of sensitivity to any of the study medications, or components thereof, or a history of drug (including sulfa drugs) or other allergy that, in the opinion of the investigator or GSK Medical Monitor, contraindicates their participation. History of sulphonamide allergy (FPV includes a sulphonamide moiety)
  • Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John's Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study medication, unless in the opinion of the Investigator and Medical Monitor the medication will not interfere with the study procedures or compromise subject safety.
  • If heparin is used during PK sampling, subjects with a history of sensitivity to heparin or heparin-induced thrombocytopenia should not be enrolled.
  • History of regular alcohol consumption within 6 months of the study defined as: An average weekly intake of >14 drinks/week for men or >7 drinks/week for women. One drink is equivalent to (12 g alcohol) = 5 ounces (150 ml) of wine or 12 ounces (360 ml) of beer or 1.5 ounces (45 ml) of 80 proof distilled spirits.
  • Consumption of red wine, seville oranges, grapefruit or grapefruit juice from 7 days prior to the first dose of study medication.
  • Pregnant females as determined by positive serum or urine human chorionic gonadotrophin (hCG) test at screening or prior to dosing.
  • Lactating females.
  • Unwillingness or inability to follow the procedures outlined in the protocol.
  • Subjects with a pre-existing condition interfering with normal gastrointestinal anatomy or motility, hepatic and/or renal function, that could interfere with the absorption, metabolism, and/or excretion of the study drugs. Subjects with a history of cholecystectomy, peptic ulceration, lower or upper gastrointestinal bleed, inflammatory bowel disease or pancreatitis should be excluded.
  • A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening.
  • A positive test for HIV antibody.
  • History of Gilbert's disease.
  • Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period.
  • The subject's systolic blood pressure is outside the range of 90-140mmHg, or diastolic blood pressure is outside the range of 45-90mmHg or heart rate is outside the range of 50-100bpm for female subjects or 45-100 bpm for male subjects.
  • Exclusion criteria for screening electrocardiogram as listed in the protocol.

研究計画

このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。

研究はどのように設計されていますか?

デザインの詳細

  • 主な目的:処理
  • 割り当て:ランダム化
  • 介入モデル:単一グループの割り当て
  • マスキング:なし(オープンラベル)

武器と介入

参加者グループ / アーム
介入・治療
実験的:Part A
Approximately 12 subjects will be enrolled. In the first treatment period, all subjects will receive GSK1349572 50 mg every 24 hours for 5 days. In Period 2, subjects will receive GSK1349572 50 mg every 24 hours in combination with fosamprenavir 700 mg plus ritonavir 100 mg every 12 hours for 10 days. Day 1 of Period 2 will be the day after Day 5 of Period 1. Subjects will have a screening visit within 30 days prior to the first dose of study drug, two treatment periods, and a follow-up visit 7-14 days after the last dose of study drug.
GSK1349572 is an integrase inhibitor being developed for the treatment of human immunodeficiency virus -1 infection by ViiV Healthcare. This drug is experimental and has not been approved by the Food and Drug Administration (FDA).
Fosamprenavir is a drug in the protease inhibitor class that is approved by the FDA for the treatment of HIV infection.
他の名前:
  • TELZIR
  • LEXIVA
  • GW433908
Ritonavir is a drug in the protease inhibitor class that is approved by the FDA for the treatment of HIV infection.
他の名前:
  • ノルビア
実験的:Part B
Approximately 15 subjects will be enrolled and receive three single doses of GSK1349572 approximately one week apart. One will be the current tablet formulation containing micronized drug substance and 2 will be new tablet versions, one containing unmicronized drug substance and one containing an intermediate particle size drug substance. Subjects will have a screening visit within 30 days prior to the first dose of study drug, three treatment periods, and a follow-up visit 7-14 days after the last dose of study drug.
GSK1349572 is an integrase inhibitor being developed for the treatment of human immunodeficiency virus -1 infection by ViiV Healthcare. This drug is experimental and has not been approved by the Food and Drug Administration (FDA).

この研究は何を測定していますか?

主要な結果の測定

結果測定
時間枠
Plasma GSK1349572 steady-state AUC(0-tau), Cmax, C0, Ctau, and Cmin following administration of GSK1349572 50 mg q24h for 5 days and following co-administration with FPV/RTV 700/100 mg q12h for 10 days
時間枠:15 days
15 days
Plasma GSK1349572 AUC(0-infinity), AUC(0-t), and Cmax following a single dose of GSK1349572 50 mg
時間枠:48 hours
48 hours

二次結果の測定

結果測定
時間枠
Safety and tolerability parameters, including adverse events, concurrent medication, clinical laboratory tests, ECG, and vital signs assessments
時間枠:15 days
15 days
Plasma amprenavir (APV) steady-state AUC(0-tau), Cmax, C0, Ctau, t½, and CL/F following administration of GSK1349572 50 mg q24h co-administered with FPV/RTV 700/100 mg q12h for 10 days
時間枠:15 days
15 days
Plasma GSK1349572 steady-state tmin, t1/2 and CL/F following administration of GSK1349572 50 mg q24h for 5 days and following co-administration with FPV/RTV 700/100 mg q12h for 10 days
時間枠:15 days
15 days
Plasma GSK1349572 C24, t1/2, tlag, tmax, CL/F and Vz/F following a single dose of GSK1349572 50 mg
時間枠:48 hours
48 hours

協力者と研究者

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スポンサー

協力者

出版物と役立つリンク

研究に関する情報を入力する責任者は、自発的にこれらの出版物を提供します。これらは、研究に関連するあらゆるものに関するものである可能性があります。

研究記録日

これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。

主要日程の研究

研究開始

2010年9月1日

一次修了 (実際)

2010年11月1日

研究の完了 (実際)

2010年11月1日

試験登録日

最初に提出

2010年8月30日

QC基準を満たした最初の提出物

2010年9月23日

最初の投稿 (見積もり)

2010年9月24日

学習記録の更新

投稿された最後の更新 (見積もり)

2017年1月19日

QC基準を満たした最後の更新が送信されました

2017年1月17日

最終確認日

2017年1月1日

詳しくは

この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。

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