Dose-Finding of Retinoid 9cUAB30 in Healthy Volunteers
A Randomized, Double-Blind, Single-dose and Multi-dose Study of the Novel Retinoid, 9cUAB30, to Determine Pharmacokinetics and Safety
調査の概要
状態
条件
詳細な説明
PRIMARY OBJECTIVES:
I. The primary objective is to determine the toxicities and recommended phase II dose of 9cUAB30. The co- primary objective is to characterize the urine and plasma single dose and steady state pharmacokinetics of 9cUAB30 in normal volunteers.
SECONDARY OBJECTIVES:
I. To correlate the pharmacokinetics of 9cUAB30 with toxicity. II. To compare observed toxicity between placebo controls and each dose level. III. To assess for any change in single dose PK after repeat dosing (Day 1 vs. Day 36).
IV. To assess the following potential biomarkers of UAB30:
- Telomerase activity (measurement of telomeric repeats) in PBMCs.
- Gene expression of DNA methyltransferase in PBMCs.
- Gene expression of CYP2B6 in PBMCs.
OUTLINE: This is a dose-escalation study. Participants are randomized to 1 of 2 treatment arms.
ARM I: Participants receive retinoid 9cUAB30* orally (PO) on days 1-28.
ARM II: Participants receive placebo* PO on days 1-28.
Courses repeat every 28 days in the absence of unacceptable toxicity.
*NOTE: Participants receive doses on days 8, 15, 22 and 29 after they have fasted for 12 hours.
After completion of study treatment, patients are followed up on days 7 and 30.
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
-
-
Wisconsin
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Madison、Wisconsin、アメリカ、53792
- University of Wisconsin Hospital and Clinics
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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:
- ECOG performance status =< 1 (Karnofsky >= 70%)
- WBC >= 3000/mm^3
- Platelets >= 100,000mm^3
- Bilirubin =< upper limit of institutional normal
- AST =< upper limit of institutional normal
- Creatinine within institutional normal limits
- Sodium =< upper limit of institutional normal
- Potassium =< upper limit of institutional normal
- Chloride =< upper limit of institutional normal
- Bicarbonate =< upper limit of institutional normal
- Fasting triglycerides =<1.5 x ULN
- Fasting cholesterol =< 1.5 x ULN
- Participants must agree to discontinue all vitamin supplements while taking study medication and for thirty days past the last dose of study medication
The effects of 9cUAB30 on the developing human fetus are unknown; for this reason, women must agree to use TWO effective forms of birth control for the duration of study participation and for 30 days following the last dose of study medication
The following persons are not considered to be able to father or bear children and therefore are eligible to participate without the use of concurrent birth control:
- Female with bilateral oophorectomy and/or hysterectomy
- Female with fallopian tubes cut, tied, or sealed
- Female with sterilization implant (e.g. Adiana, Essure) placed > 3 months prior to randomization
- Female post-menopausal (> 1 year since last menses)
- Male with vasectomy > 3 months prior to randomization
One of the following methods of birth control must be used by women of childbearing potential:
- Combined oral contraceptive pill in continuous use for > 30 days prior to study entry
- Vaginal ring (e.g. NuvaRing) in continuous use for > 30 days prior to study entry
- Skin patch (e.g. Ortho Evra) in continuous use for > 30 days prior to study entry
- Injection (e.g. Depo-Provera, Noristerat®) in continuous use for > 30 days prior to study entry
- Copper IUD (e.g. ParaGard)
Note: because of the decreased effectiveness of low dose progesterone-only contraceptive methods when used with retinoids, the following hormonal methods are NOT acceptable:
- Low dose progesterone only oral contraceptive pill ("mini pills" e.g. Micronor®, Nor-Q.D., Ovrette)
- Norplant subdermal implant
- Mirena® Hormonal Implanted Uterine Device (IUD)
In addition to the above method of contraception, one of the following methods of contraception will ALSO be used for the duration of study participation and for 30 days following the last dose of study medication:
- Diaphragm, cervical cap, or cervical shield with spermicide
- Contraceptive sponge (e.g. Today Sponge)
- Condom (male or female type) plus spermicide
- Females of child-bearing potential must have a negative pregnancy test within the current menstrual cycle and within 7 days before starting drug
- Participants must have the ability to understand, and the willingness to sign, a written informed consent document
Exclusion Criteria:
- Participants may not be taking medications that might interact with 9cUAB30; detailed list of potentially interacting medications
- Participants may not be taking lipid lowering agents
- Participants may not be receiving any other investigational agents
- Participants with a history of allergic reactions attributed to compounds of similar chemical or biologic composition of retinoids
- Participants with an uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with 9cUAB30, breastfeeding must be discontinued for the duration of study participation and for one month after the last dose of the study agent if the mother is treated with 9cUAB30
- Individuals known to be HIV-positive may not participate in this study; the uncertain immune status of HIV-positive people and the potential risks of taking part in this study are too great to justify this non-treatment therapy
- Individuals with a history of cancer diagnosis or reoccurrence < 5 years from study entry may not participate; however, individuals with a history of squamous or basal cell carcinoma of the skin < 5 years from study entry will not be excluded from this study; the effects of this study agent on the immune system of people at risk for recurring cancer are unknown
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:処理
- 割り当て:ランダム化
- 介入モデル:並列代入
- マスキング:トリプル
武器と介入
参加者グループ / アーム |
介入・治療 |
---|---|
実験的:Arm I (retinoid 9cUAB30)
Participants receive retinoid 9cUAB30* PO on days 1-28.
|
相関研究
相関研究
他の名前:
Given PO
Disease prevention
他の名前:
|
プラセボコンパレーター:Arm II (placebo)
Participants receive placebo* PO on days 1-28.
|
相関研究
相関研究
他の名前:
与えられたPO
他の名前:
Disease prevention
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 |
---|---|---|
Recommended phase II dose of 9cUAB30 based on the MTD
時間枠:28 days
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28 days
|
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Pharmacokinetics of 9cUAB30 in normal volunteers
時間枠:Baseline, days 1, 8, 15, 22, 36, and 43
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Using one-sample t-tests, or Wilcoxon signed-rank tests as appropriate in order to evaluate the single vs. steady state levels.
An appropriate regression model will be used to explore the relationship of dose with change in PK.
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Baseline, days 1, 8, 15, 22, 36, and 43
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
---|---|---|
Correlation between pharmacokinetic and toxicity as assessed by CTCAE
時間枠:Up to 36 days
|
Up to 36 days
|
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Comparison of toxicity between placebo and controls as assessed by CTCAE
時間枠:Up to 36 days
|
To compare toxicities at each dose level to placebo, the Chi-square test will be used for the presence or absence of toxicities, and Wilcoxon rank-sum tests will be used for CTCAE grade and investigator defined relationship data.
|
Up to 36 days
|
協力者と研究者
捜査官
- 主任研究者:Jill Kolesar、University of Wisconsin, Madison
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 (見積もり)
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
本研究に関する用語
その他の研究ID番号
- NCI-2013-00468
- N01CN35153 (米国 NIH グラント/契約)
- CO10311
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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