Pharmacokinetics, Safety, and Efficacy of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Disoproxil Fumarate Single Tablet Regimen (STR) in Adolescents
2018年7月20日 更新者：Gilead Sciences
A Phase 2/3, Open-Label Study of the Pharmacokinetics, Safety, and Antiviral Activity of the Elvitegravir/ Cobicistat/Emtricitabine/Tenofovir Disoproxil Fumarate Single Tablet Regimen (STR) in HIV-1 Infected Antiretroviral Treatment-Naive Adolescents
The primary objectives of this study are to evaluate the steady-state pharmacokinetics (PK) and confirm the dose of the elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (EVG/COBI/FTC/TDF) single-tablet regimen (STR) (Part A) and to evaluate the safety and tolerability of EVG/COBI/FTC/TDF STR through Week 48 (Part B) in HIV-1 infected, antiretroviral (ARV) treatment-naive adolescents.
A total of 50 adolescent participants (12 to < 18 years of age) will be enrolled to receive EVG/COBI/FTC/TDF as follows:
- Part A: Twelve to 16 eligible participants will be enrolled to evaluate steady-state PK, and confirm the dose, with the intent to enroll at least 4 participants 12 to < 15 and at least 4 participants 15 to < 18 years of age.
- Part B: Following confirmation of EVG exposure in at least 12 participants from Part A, 34 to 38 participants in addition to those enrolled in Part A will be enrolled to evaluate the safety, tolerability, and antiviral activity of EVG/COBI/FTC/TDF STR.
調査の概要
研究の種類
介入
入学 (実際)
50
段階
- フェーズ2
- フェーズ 3
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
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California
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Oakland、California、アメリカ、94609
- East Bay AIDS Center Medical Group
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Florida
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Tampa、Florida、アメリカ、33606
- University of South Florida - Department of Pediatrics
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Illinois
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Chicago、Illinois、アメリカ、60637
- University of Chicago
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New York
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Bronx、New York、アメリカ、10467
- Montefiore Medical Center
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New York、New York、アメリカ、10016
- New York University School of Medicine
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Pennsylvania
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Philadelphia、Pennsylvania、アメリカ、19134
- St. Christopher's Hospital for Children
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Tennessee
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Memphis、Tennessee、アメリカ、38105
- St. Jude Children's Research Hospital
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Bangkok、タイ、10330
- The HIV Netherlands Australia Thailand Research collaboration (HIV-NAT)
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Bangkok、タイ、10700
- Siriraj Hospital, Mahidol University
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Chon Buri、タイ、20110
- Queen Savang Vadhana Memorial Hospital
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Khon Kaen、タイ、40002
- Srinakarind Hospital
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Cape Town、南アフリカ、7925
- Desmond Tutu HIV Research Centre
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Dundee、南アフリカ、3000
- Mpati Medical Center
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Johannesburg、南アフリカ、2092
- Clinical HIV Research Unit
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Soweto、南アフリカ、2013
- Perinatal HIV Research Unit
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Stellenbosch、南アフリカ、7602
- University of Stellenbosch
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Gauteng
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Johannesburg、Gauteng、南アフリカ、2112
- Rahima Moosa Mother and Child Hospital (Wits)
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Kwazulu-Natal
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Durban、Kwazulu-Natal、南アフリカ、4001
- Dr Latiff Private Practice
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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
12年～17年 (子)
健康ボランティアの受け入れ
いいえ
受講資格のある性別
全て
説明
Key Inclusion Criteria:
- 12 years to < 18 years of age at baseline
- Able to give written assent prior to any screening evaluations
- Parent or guardian able to give written informed consent prior to any screening evaluations and willing to comply with study requirements
- Plasma HIV-1 RNA levels of ≥ 1,000 copies/mL
- CD4+ cell count > 100 cells/µL
- Weight ≥ 35 kg (77 lbs)
- Screening genotype report must show sensitivity to FTC and TDF
- Able to swallow oral tablets
- Adequate renal function
- Clinically normal ECG
- Documented screening for active pulmonary tuberculosis per local standard of care within 6 months of a screening visit
- Hepatic transaminases ≤ 5 x upper limit of normal
- Total bilirubin ≤ 1.5 mg/dL, or normal direct bilirubin
- Individuals with a positive Hepatitis B surface antigen screening test can participate in the study, providing that alternate therapy (other than TDF) for chronic Hepatitis B infection is available as a part of local standard of care
- Adequate hematologic function
- Negative serum pregnancy test for all females
- Males and females of childbearing potential must agree to utilize highly effective contraception methods while on study treatment or agree to abstain from heterosexual intercourse throughout the study period and for 30 days following the last dose of study drug
- Males must agree to utilize a highly effective method of contraception during heterosexual intercourse throughout the study period and for 30 days following discontinuation of investigational medicinal product
- Must be willing and able to comply with all study requirements
- Life expectancy ≥ 1 year
Key Exclusion Criteria:
- A new AIDS-defining condition diagnosed within the 30 days prior to screening
- Prior treatment with any approved or investigational or experimental anti HIV-1 drug for any length of time (other than that given for prevention of mother-to-child transmission)
- Evidence of active pulmonary or extra-pulmonary tuberculosis disease within 3 months of the screening visit
- Anticipated to require rifamycin treatment for mycobacterial infection while participating in the study. Note: prophylactic Isoniazid (INH) therapy for latent tuberculosis (TB) treatment is allowed.
- Individuals experiencing decompensated cirrhosis
- Pregnant or lactating females
- Have any serious or active medical or psychiatric illness which would interfere with treatment, assessment, or compliance with the protocol. This would include uncontrolled renal, cardiac, hematological, hepatic, pulmonary, endocrine, central nervous, gastrointestinal, vascular, metabolic, immunodeficiency disorders, active infection, or malignancy that are clinically significant or requiring treatment within 30 days prior to the study dosing.
- Current alcohol or substance abuse that will potentially interfere with compliance
- Have history of significant drug sensitivity or drug allergy
- Known hypersensitivity to the study drugs, the metabolites or formulation excipients
- Have been treated with immunosuppressant therapies or chemotherapeutic agents within 3 months of study screening or expected to receive these agents during the study
- A history of malignancy within the past 5 years or ongoing malignancy other than cutaneous Kaposi's sarcoma, basal cell carcinoma, or resected, non-invasive cutaneous squamous carcinoma
- Have previously participated in an investigational trial involving administration of any investigational agent within 30 days prior to the study dosing
- Participation in any other clinical trial without prior approval from sponsor is prohibited while participating in this trial
- Receiving ongoing therapy with any disallowed medications, including drugs not to be used with EVG, COBI, FTC, TDF or individuals with any known allergies to the excipients of EVG/COBI/FTC/TDF STR tablets
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
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：なし
- 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 |
|---|---|
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実験的：EVG/COBI/FTC/TDF
Participants will receive treatment for 48 weeks and then had the option to enter an Extension Phase to receive EVG/COBI/FTC/TDF until 1) the age of 18, 2) EVG/COBI/FTC/TDF becomes commercially available in the country the participant is enrolled, or 3) Gilead elects to terminate the development of EVG/COBI/FTC/TDF in that country.
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150/150/200/300 mg STR administered orally once daily with food
他の名前：
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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 |
メジャーの説明 |
時間枠 |
|---|---|---|
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For Part A, Pharmacokinetic (PK) Parameter: AUCtau of EVG
時間枠：Predose, 2, 4, 4.5, 5, 8, and 12 hours postdose on Day 10
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AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).
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Predose, 2, 4, 4.5, 5, 8, and 12 hours postdose on Day 10
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Incidence of Treatment-Emergent Serious Adverse Events (SAEs) and All Treatment-Emergent Adverse Events (AEs)
時間枠：Up to Week 48 plus 30 days
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Up to Week 48 plus 30 days
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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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For Part A, PK Parameter: Ctau of EVG, FTC, Tenofovir (TFV), and COBI
時間枠：Predose, 2, 4, 4.5, 5, 8, and 12 hours postdose on Day 10
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Ctau is defined as the observed drug concentration at the end of the dosing interval.
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Predose, 2, 4, 4.5, 5, 8, and 12 hours postdose on Day 10
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For Part A, PK Parameter: Cmax of EVG, FTC, TFV, and COBI
時間枠：Predose, 2, 4, 4.5, 5, 8, and 12 hours postdose on Day 10
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Cmax is defined as the maximum concentration of drug.
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Predose, 2, 4, 4.5, 5, 8, and 12 hours postdose on Day 10
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For Part A, PK Parameter: AUCtau of FTC, TFV, and COBI
時間枠：Predose, 2, 4, 4.5, 5, 8, and 12 hours postdose on Day 10
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AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).
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Predose, 2, 4, 4.5, 5, 8, and 12 hours postdose on Day 10
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Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Weeks 24 and 48 as Defined by the FDA Snapshot Analysis
時間枠：Weeks 24 and 48
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Weeks 24 and 48
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Percentage of Participants With HIV-1 RNA < 400 Copies/mL at Weeks 24 and 48 as Defined by the FDA Snapshot Analysis
時間枠：Weeks 24 and 48
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Weeks 24 and 48
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Change From Baseline in Plasma log10 HIV-1 RNA at Weeks 24 and 48
時間枠：Baseline; Weeks 24 and 48
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Baseline; Weeks 24 and 48
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24 週および 48 週での CD4+ 細胞数のベースラインからの変化
時間枠：ベースライン; 24週目と48週目
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ベースライン; 24週目と48週目
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Change From Baseline in CD4 Percentage at Weeks 24 and 48
時間枠：Baseline; Weeks 24 and 48
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Baseline; Weeks 24 and 48
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協力者と研究者
ここでは、この調査に関係する人々や組織を見つけることができます。
スポンサー
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。
一般刊行物
- Gaur A, Fourie J, Chokephaibulkit K, Bekker L-G, Yin X, Custodio J, Bennett S, Cheng A, Quirk E. Pharmacokinetics, Efficacy and Safety of an Integrase Inhibitor-Based Single-Tablet Regimen in HIV-Infected Treatment-Naïve Adolescents. 21st Conference on Retroviruses and Opportunistic Infections (CROI). March 2014. Boston, MA, USA
- Chokephaibulkit K, Gaur A, Fourie J, Bekker L-G, Shao Y, Custodio J, Bennett S, Cheng A, Quirk E. Safety and Efficacy of the Integrase Inhibitor-Based Stribild Single-Tablet Regimen in HIV-Infected Adolescents Through 24 Weeks of Treatment. 20th International AIDS Conference. July 2014. Melbourne, Australia
- Porter DP, Bennett S, Quirk E, Miller MD, White KL. Lack of Emergent Resistance in HIV-1-Infected Adolescents on Elvitegravir-Based STRs. 22nd Conference on Retroviruses and Opportunistic Infections (CROI). February 2015. Seattle, WA, USA
- Kizito H, Gaur A, Prasitsuebsai W, Rakhmanina N, Chokephaibulkit K, Fourie J, Bekker LG, Shao Y, Bennett S, Quirk E. Changes in renal laboratory markers and bone mineral density in treatment-naïve HIV-1-infected adolescents initiating INSTI-based single-tablet regimens containing tenofovir alafenamide (TAF) or tenofovir disoproxil fumarate (TDF). 8th IAS Conference on HIV Pathogenesis, Treatment & Prevention. July 2015. Vancouver, Canada
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 (実際)
2012年12月6日
一次修了 (実際)
2015年10月22日
研究の完了 (実際)
2018年1月29日
試験登録日
最初に提出
2012年11月1日
QC基準を満たした最初の提出物
2012年11月1日
最初の投稿 (見積もり)
2012年11月4日
学習記録の更新
投稿された最後の更新 (実際)
2018年8月17日
QC基準を満たした最後の更新が送信されました
2018年7月20日
最終確認日
2018年7月1日
詳しくは
本研究に関する用語
追加の関連 MeSH 用語
その他の研究ID番号
- GS-US-236-0112
- 2015-000313-40 (EudraCT番号)
医薬品およびデバイス情報、研究文書
米国FDA規制医薬品の研究
はい
米国FDA規制機器製品の研究
いいえ
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。