Safety of Tenofovir Disoproxil Fumarate (TDF) and Emtricitabine/TDF in HIV Infected Pregnant Women and Their Infants
A Phase I Study of the Safety, Tolerance, and Pharmacokinetics of Tenofovir Disoproxil Fumarate (TDF) and the Combination of TDF Plus Emtricitabine in HIV-1 Infected Pregnant Women and Their Infants
調査の概要
詳細な説明
The majority of perinatally infected infants are infected during the labor and delivery process, but recent studies suggest that additional factors, such as postexposure prophylaxis, are likely to be involved in the prevention of MTCT of HIV. It is possible that antiretroviral dosing only during labor and short-term dosing to newly born infants would be sufficiently effective to prevent MTCT of HIV. TDF is a nucleoside reverse transcriptase inhibitor that has demonstrated significant effectiveness in preventing MTCT of simian immunodeficiency virus (SIV) in a primate model of HIV. FTC/TDF is a combination of two NRTIs being studied because this combination has the potential to prevent MTCT, while protecting the mother from developing resistance that may develop with single drug therapy. This study will evaluate the safety, tolerance, and pharmacokinetics (PK) of single doses of TDF and FTC/TDF in both HIV infected pregnant women and their newborn infants.
Cohort 1 is now closed. Each participant in Cohort 1 received a single 600 mg oral dose of TDF at the start of active labor or 4 hours prior to C-section, with concurrent administration of standard intravenous zidovudine (ZDV) prophylaxis and/or other antiretrovirals prescribed by her physician. The infants from Cohort 1 received only the standard 6 weeks of oral ZDV prophylaxis postpartum. PK blood samples were taken from mothers at predose and 1, 2, 4, 8, 12, and 24 hours postdose and at the time of delivery; PK blood samples were taken from infants at 12, 24, and 36 hours after birth.
Pregnant women with HIV infection entering this study will be assigned to Cohort 2, as all infants in Cohort 1 have completed the 6 to 8 week study visit and all Cohort 1 data have been reviewed. Mothers in Cohort 2 will receive a single dose of 900 mg of TDF combined with 600 mg emtricitabine, along with standard ZDV prophylaxis and/or other antiretrovirals prescribed by her physician. Infants will receive a single dose of TDF at 4 mg/kg combined with 3 mg/kg emtricitabine as soon as possible after delivery and within 6 hours of age as well as the standard 6 weeks of oral ZDV prophylaxis after birth. Blood samples from mothers and infants will be taken as for Cohort 1.
Mothers will be followed for 12 weeks postpartum or for 2 years after giving birth if viral resistance to TDF or FTC/TDF is demonstrated at Weeks 1, 6, or 12. In addition to the PK studies, blood collection will occur around the time of delivery, at screening, study entry, at delivery, and after delivery at various times up to Week 12. Physical exams will be done at screening, study entry, at delivery, and after delivery at various times up to Week 8. Infants will be followed until age 2. Blood will be collected and physical exams will be done at birth and at various times up to Week 96. Mothers are encouraged to coenroll in PACTG P1025, Pharmacokinetic Study of Anti-HIV Drugs During Pregnancy.
研究の種類
入学 (実際)
段階
- フェーズ 1
連絡先と場所
研究場所
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District of Columbia
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Washington、District of Columbia、アメリカ、20010
- Children's National Med. Ctr. Washington DC NICHD CRS
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Washington、District of Columbia、アメリカ、20010
- Washington Hosp. Ctr. NICHD CRS
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Florida
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Miami、Florida、アメリカ、33136
- Univ. of Miami Ped. Perinatal HIV/AIDS CRS
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Illinois
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Chicago、Illinois、アメリカ、60608
- Mt. Sinai Hosp. Med. Ctr. - Chicago, Womens & Childrens HIV Program
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Michigan
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Detroit、Michigan、アメリカ、48201
- Children's Hospital of Michigan NICHD CRS
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New Jersey
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Newark、New Jersey、アメリカ、07101-1709
- NJ Med. School CRS
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New York
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Bronx、New York、アメリカ、10457
- Bronx-Lebanon Hosp. IMPAACT CRS
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New York、New York、アメリカ、10016
- Nyu Ny Nichd Crs
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Pennsylvania
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Philadelphia、Pennsylvania、アメリカ、19102-1192
- Hahnemann Univ. Hosp.
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Tennessee
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Memphis、Tennessee、アメリカ
- Regional Med. Ctr. at Memphis
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Memphis、Tennessee、アメリカ
- St. Jude/UTHSC CRS
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San Juan、プエルトリコ
- San Juan City Hosp. PR NICHD CRS
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参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
説明
Inclusion Criteria for Mothers:
- HIV infected
- 34 weeks or more (third trimester) into pregnancy at study screening
- Have access to a participating AIDS clinical trial unit (ACTU) and are willing to be followed at location for the duration of the study
Exclusion Criteria for Mothers:
- Prior treatment with TDF, including coformulated drugs that contain TDF, during current pregnancy
- Active opportunistic infection and/or serious bacterial infection at time of study entry
- Certain abnormal laboratory values at study screening
- Chronic malabsorption or chronic diarrhea
- Certain medical or obstetrical complications during the current pregnancy
- Fetal abnormalities as measured by ultrasound screening performed at 18 weeks into pregnancy or later
- Intend to breastfeed
- Current alcohol abuse or use of illicit substances
- Participation in any other therapeutic or vaccine perinatal treatment trial during the current pregnancy, unless given permission by the protocol chairs
- Require certain medications
研究計画
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：防止
- 割り当て：非ランダム化
- 介入モデル：並列代入
- 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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アクティブコンパレータ：1
Each participant in Cohort 1 received a single 600 mg oral dose of TDF at the start of active labor or 4 hours prior to C-section, with concurrent administration of standard intravenous zidovudine (ZDV) prophylaxis and/or other antiretrovirals prescribed by her physician.
The infants from Cohort 1 received only the standard 6 weeks of oral ZDV prophylaxis postpartum.
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900 mg of TDF combined with 600 mg emtricitabine
600 mg oral dose of TDF
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アクティブコンパレータ：2
Mothers in Cohort 2 will receive a single dose of 900 mg of TDF combined with 600 mg emtricitabine, along with standard ZDV prophylaxis and/or other antiretrovirals prescribed by her physician.
Infants will receive a single dose of TDF at 4 mg/kg combined with 3 mg/kg emtricitabine as soon as possible after delivery and within 6 hours of age as well as the standard 6 weeks of oral ZDV prophylaxis after birth.
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900 mg of TDF combined with 600 mg emtricitabine
600 mg oral dose of TDF
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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 |
時間枠 |
|---|---|
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Adverse experiences with a severity of Grade 3 or 4 and adverse pregnancy outcomes that cannot be directly attributed to a cause besides study treatment
時間枠：Throughout study
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Throughout study
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二次結果の測定
結果測定 |
時間枠 |
|---|---|
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Maternal viral load
時間枠：during active labor and 24 to 48 hours, 7 days, 6 to 8 weeks, and 12 weeks postpartum
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during active labor and 24 to 48 hours, 7 days, 6 to 8 weeks, and 12 weeks postpartum
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viral resistance to emtricitabine/tenofovir disoproxil fumarate using bulk sequencing
時間枠：at Weeks 1, 6, and 12 postpartum
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at Weeks 1, 6, and 12 postpartum
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infant HIV DNA PCR
時間枠：at 24 to 48 hours, 6 to 8 weeks, 4 months, and 6 months of life
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at 24 to 48 hours, 6 to 8 weeks, 4 months, and 6 months of life
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協力者と研究者
協力者
捜査官
- スタディチェア：Patricia M. Flynn, MD、Department of Infectious Disease, St. Jude's Children's Research Hospital
- スタディチェア：Arlene D. Bardeguez, MD, MPH, FACOG、Obstetrics, Gynecology, and Women's Health, University of Medicine and Dentistry of New Jersey
出版物と役立つリンク
一般刊行物
- Abrams EJ. Prevention of mother-to-child transmission of HIV--successes, controversies and critical questions. AIDS Rev. 2004 Jul-Sep;6(3):131-43.
- Antoniou T, Park-Wyllie LY, Tseng AL. Tenofovir: a nucleotide analog for the management of human immunodeficiency virus infection. Pharmacotherapy. 2003 Jan;23(1):29-43. doi: 10.1592/phco.23.1.29.31915.
- Kourtis AP, Duerr A. Prevention of perinatal HIV transmission: a review of novel strategies. Expert Opin Investig Drugs. 2003 Sep;12(9):1535-44. doi: 10.1517/13543784.12.9.1535.
- Moodley J, Moodley D. Management of human immunodeficiency virus infection in pregnancy. Best Pract Res Clin Obstet Gynaecol. 2005 Apr;19(2):169-83. doi: 10.1016/j.bpobgyn.2004.10.007. Epub 2004 Dec 15.
- Thorne C, Newell ML. The safety of antiretroviral drugs in pregnancy. Expert Opin Drug Saf. 2005 Mar;4(2):323-35. doi: 10.1517/14740338.4.2.323.
研究記録日
主要日程の研究
研究開始
一次修了 (実際)
研究の完了 (実際)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (見積もり)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
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