Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Subcutaneous Rivipansel With rHuPH20 in Healthy Subjects
2020年6月16日 更新者：GlycoMimetics Incorporated
A Phase 1, Randomized, Double Blind, Sponsor Open, Placebo Controlled, Single And Multiple Ascending Dose Study To Evaluate The Safety, Tolerability, And Pharmacokinetics Of Rivipansel (pf 06460031) Following Subcutaneous Administration With Rhuph20 (pf 06744547) In Healthy Subjects
This is a 2 part study designed to provide an initial assessment on the safety, tolerability, and PK of rivipansel, following single ascending (Part 1) and multiple ascending dosing (Part 2) given subcutaneously with rHuPH20, in healthy subjects.
Part 1 of the study will be conducted using a cross-over design while Part 2 of the study will be conducted using a parallel design.
調査の概要
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
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Brussels、ベルギー、B-1070
- Pfizer Clinical Research Unit
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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
18年～55年 (大人)
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
Inclusion Criteria:
- Healthy male and/or female subjects of non-childbearing potential between the ages of 18 and 55 years, inclusive.
- Body Mass Index 17.5 - 30.5 kg/m2 and body weight >50 kg at Screening.
- Normal skin without potentially obscuring features in the area intended for infusion.
- Subjects willing to defer receiving prophylactic immunizations (eg, influenza or pneumococcal vaccines) during the study.
- Evidence of a personally signed and dated informed consent document indicating that the subject or a legally acceptable representative has been informed of all pertinent aspects of the study
Exclusion Criteria:
- Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at time of dosing).
- History of a recent major surgery (within 3 months of screening).
- Serious infection within 1 month of screening.
- Subjects with chronic skin condition that may interfere in the assessment of emergent safety data.
- A positive urine drug screen.
- Known sensitivity to hyaluronidases.
- History of hepatitis or positive testing for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb) or hepatitis C antibodies (HCV).
- Unwilling or unable to comply with the Lifestyle Guidelines described in this protocol.
- Subjects who are investigational site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the Investigator, or subjects who are Pfizer employees directly involved in the conduct of the study.
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：基礎科学
- 割り当て：ランダム化
- 介入モデル：順次割り当て
- マスキング：ダブル
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：Cohort 1
Single ascending dose in 3 period cross-over design (with optional 4th period)
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Rivipansel administered as a single dose subcutaneously with rHuPH20 in cross-over fashion.
Each subject may receive up to 4 study treatments (placebo and up to 3 doses of rivipansel).
The planned dose levels are 350 mg, 1210 mg, and 4200 mg (these are subject to change based on emerging data).
Matched Placebo administered as single dose subcutaneously with rHuPH20.
Rivipansel administered q12h for 7 days (a total of 13 doses) subcutaneously with rHuPH20.
Planned doses are 1400 mg loading and 700 mg maintenance for 12 doses (these are subject to change based on emerging data).
Rivipansel administered q12h for 7 days (a total of 13 doses) subcutaneously with rHuPH20.
Planned doses are 2800 mg loading and 1400 mg maintenance for 12 doses (these are subject to change based on emerging data).
Matched Placebo administered q12h for 7 days (a total of 13 doses) subcutaneously with rHuPH20.
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実験的：Cohort 2
Multiple ascending dose
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Rivipansel administered as a single dose subcutaneously with rHuPH20 in cross-over fashion.
Each subject may receive up to 4 study treatments (placebo and up to 3 doses of rivipansel).
The planned dose levels are 350 mg, 1210 mg, and 4200 mg (these are subject to change based on emerging data).
Matched Placebo administered as single dose subcutaneously with rHuPH20.
Rivipansel administered q12h for 7 days (a total of 13 doses) subcutaneously with rHuPH20.
Planned doses are 1400 mg loading and 700 mg maintenance for 12 doses (these are subject to change based on emerging data).
Rivipansel administered q12h for 7 days (a total of 13 doses) subcutaneously with rHuPH20.
Planned doses are 2800 mg loading and 1400 mg maintenance for 12 doses (these are subject to change based on emerging data).
Matched Placebo administered q12h for 7 days (a total of 13 doses) subcutaneously with rHuPH20.
|
|
実験的：Cohort 3
Multiple ascending dose
|
Rivipansel administered as a single dose subcutaneously with rHuPH20 in cross-over fashion.
Each subject may receive up to 4 study treatments (placebo and up to 3 doses of rivipansel).
The planned dose levels are 350 mg, 1210 mg, and 4200 mg (these are subject to change based on emerging data).
Matched Placebo administered as single dose subcutaneously with rHuPH20.
Rivipansel administered q12h for 7 days (a total of 13 doses) subcutaneously with rHuPH20.
Planned doses are 1400 mg loading and 700 mg maintenance for 12 doses (these are subject to change based on emerging data).
Rivipansel administered q12h for 7 days (a total of 13 doses) subcutaneously with rHuPH20.
Planned doses are 2800 mg loading and 1400 mg maintenance for 12 doses (these are subject to change based on emerging data).
Matched Placebo administered q12h for 7 days (a total of 13 doses) subcutaneously with rHuPH20.
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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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Assessment of adverse events (AEs)
時間枠：Baseline up to 7 days of dosing
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Baseline up to 7 days of dosing
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Assessment of cardiac conduction intervals as assessed via 12-lead electrocardiogram (ECG)
時間枠：Baseline up to 7 days of dosing
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Baseline up to 7 days of dosing
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Assessment of vital signs (including blood pressure and pulse rate)
時間枠：Baseline up to 7 days of dosing
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Baseline up to 7 days of dosing
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Assessment of clinical laboratory tests
時間枠：Baseline up to 7 days of dosing
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Baseline up to 7 days of dosing
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二次結果の測定
結果測定 |
時間枠 |
|---|---|
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Maximum Observed Plasma Concentration (Cmax) for rivipansel following single dose
時間枠：Samples are collected pre-dose and at 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72 H following single dose administration
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Samples are collected pre-dose and at 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72 H following single dose administration
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Time to Reach Maximum Observed Plasma Concentration (Tmax) for rivipansel following single dose
時間枠：Samples are collected pre-dose and at 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72 H following single dose administration
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Samples are collected pre-dose and at 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72 H following single dose administration
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Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for rivipansel following single dose
時間枠：Samples are collected pre-dose and at 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72 H following single dose administration
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Samples are collected pre-dose and at 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72 H following single dose administration
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Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) for rivipansel following single dose
時間枠：Samples are collected pre-dose and at 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72 H following single dose administration
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Samples are collected pre-dose and at 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72 H following single dose administration
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Dose-Normalized Cmax for rivipansel following single dose
時間枠：Samples are collected pre-dose and at 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72 H following single dose administration
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Samples are collected pre-dose and at 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72 H following single dose administration
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Dose-Normalized AUClast for rivipansel
時間枠：Samples are collected pre-dose and at 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72 H following single dose administration
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Samples are collected pre-dose and at 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72 H following single dose administration
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Dose-Normalized AUCinf for rivipansel
時間枠：Samples are collected pre-dose and at 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72 H following single dose administration
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Samples are collected pre-dose and at 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72 H following single dose administration
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Plasma Decay Half-Life (t1/2) for rivipansel following single dose
時間枠：Samples are collected pre-dose and at 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72 H following single dose administration
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Samples are collected pre-dose and at 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72 H following single dose administration
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Apparent Clearance (CL/F) for rivipansel following single dose
時間枠：Samples are collected pre-dose and at 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72 H following single dose administration
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Samples are collected pre-dose and at 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72 H following single dose administration
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Apparent Volume of Distribution (Vz/F) for rivipansel following single dose
時間枠：Samples are collected pre-dose and at 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72 H following single dose administration
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Samples are collected pre-dose and at 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72 H following single dose administration
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Maximum Observed Plasma Concentration (Cmax) for rivipansel following multiple dose
時間枠：Days 1, 7
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Days 1, 7
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Time to Reach Maximum Observed Plasma Concentration (Tmax) for rivipansel following multiple dose
時間枠：Days 1, 7
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Days 1, 7
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Area Under the Curve from Time Zero to end of dosing interval (AUCtau) for rivipansel following multiple dose administration, where tau is 12 hours
時間枠：Days 1, 7
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Days 1, 7
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Dose-Normalized Cmax for rivipansel following multiple dose administration
時間枠：Days 1, 7
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Days 1, 7
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Dose-Normalized AUCtau for rivipansel following multiple dose administration
時間枠：Days 1, 7
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Days 1, 7
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Plasma Decay Half-Life (t1/2) for rivipansel following multiple dose
時間枠：Day 7
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Day 7
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Minimum Observed Plasma Concentration (Cmin) for rivipansel following multiple dose
時間枠：Day 7
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Day 7
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Apparent Clearance (CL/F) for rivipansel following multiple dose
時間枠：Day 7
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Day 7
|
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Peak to Trough Ratio (PTR) of plasma concentration for rivipanselmultiple dose administration
時間枠：Day 7
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Day 7
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Accumulation ratio for Area Under the Curve during the dosing interval (Rac) for rivipansel
時間枠：Day 7
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Day 7
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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。
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
2015年10月1日
一次修了 (実際)
2016年4月1日
研究の完了 (実際)
2016年4月1日
試験登録日
最初に提出
2014年8月13日
QC基準を満たした最初の提出物
2014年8月13日
最初の投稿 (見積もり)
2014年8月15日
学習記録の更新
投稿された最後の更新 (実際)
2020年6月18日
QC基準を満たした最後の更新が送信されました
2020年6月16日
最終確認日
2020年6月1日
詳しくは
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