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Absorption, Metabolism, Excretion and Absolute Bioavailability

2017年12月19日 更新者:Pfizer

A Phase 1, Open-label, Non-randomized, 2-period, Fixed Sequence Study To Investigate The Absorption, Metabolism And Excretion Of [14c-pf-04965842] And To Assess The Absolute Bioavailability And Fraction Absorbed Of Pf-04965842 In Healthy Male Subjects Using A 14c-microtracer Approach

This study will investigate the absorption, metabolism and excretion of 14C-PF 04965842 and characterize plasma, fecal and urinary radioactivity and identify any metabolites, if possible, of 14C PF-04965842 in humans. In addition, this study will provide a better understanding of the pharmacokinetic disposition of PF-04965842 by obtaining intravenous (IV) clearance and delineating the extent of oral absorption (absolute bioavailability (F) and fraction absorbed (Fa)).

調査の概要

研究の種類

介入

入学 (実際)

6

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

      • Groningen、オランダ、9713 GZ
        • PRA Health Sciences
      • Groningen、オランダ、9728 NZ
        • PRA Health Sciences

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

説明

Inclusion Criteria:

  1. Healthy male subjects who, at the time of screening, are between the ages of 18 and 55 years, inclusive. Healthy is defined as no clinically relevant abnormalities identified by a detailed medical history, full physical examination, including blood pressure and pulse rate measurement, 12 lead electrocardiogram (ECG), or clinical laboratory tests.
  2. Body Mass Index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight >50 kg (110 lbs).
  3. Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study.
  4. Subjects who are willing and able to comply with study confinement period, scheduled visits, treatment plan, laboratory tests, contraceptive requirements and other study procedures.

Exclusion Criteria

Subjects with any of the following characteristics/conditions will not be included in the study:

  1. 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).
  2. Any clinically significant malabsorption condition (eg, gastrectomy, bowel resection).
  3. A positive urine drug screen for drugs of abuse or recreational drugs.
  4. History of human immunodeficiency virus (HIV), hepatitis B, or hepatitis C; positive testing for HIV, hepatitis B surface antigen (HepBsAg), hepatitis B core antibody (HepBcAb), or hepatitis C antibody (HCVAb).
  5. History of abuse of alcohol or binge drinking and/or any other illicit drug use or dependence within 6 months of Screening. Binge drinking is defined as a pattern of 5 or more alcoholic drinks (male) in about 2 hours. As a general rule, alcohol intake should not exceed 21 units per week (1 unit = ½ pint beer, 25 mL of 40% spirit or a 125 mL glass of wine).
  6. Use of tobacco/nicotine containing products in excess of 5 cigarettes/day.
  7. Treatment with an investigational drug within 60 days.
  8. Total 14C radioactivity measured in plasma exceeding 11 mBq/mL.
  9. Screening supine blood pressure >=140 mm Hg (systolic) or >=90 mm Hg (diastolic), following at least 5 minutes of supine rest. If blood pressure is >=140 mm Hg (systolic) or >=90 mm Hg (diastolic), the blood pressure measurement should be repeated two more times and the average of the three measurements should be used to assess the subject's eligibility.
  10. Supine 12 lead ECG demonstrating QTcF >450 msec or a QRS interval >120 msec at screening. If QTcF exceeds 450 msec, or QRS exceeds 120 msec, the ECG should be repeated two more times and the average of the three QTcF or QRS values should be used to determine the subject's eligibility.
  11. Use of prescription or nonprescription drugs (including vitamins and dietary supplements) within 7 days or 5 half lives (whichever is longer) prior to the first dose of study medication. As an exception, acetaminophen may be used at doses of =<1 g/day. Limited use of non prescription medications that are not believed to affect subject safety or the overall results of the study may be permitted on a case by case basis following approval by Pfizer.
  12. Use of herbal supplements within 28 days prior to the first dose of study medication.
  13. Blood donation (excluding plasma donations) of no more than 100 mL or more within 56 days prior to dosing.
  14. An estimated glomerular filtration rate of <90 mL/min/1.73 m2 based on the four variable Modification of Diet in Renal Disease (MDRD) equation.
  15. History of tuberculosis or active or latent or inadequately treated infection, positive QuantiFERON TB Gold test.
  16. Any medical history of disease (ie, Gilbert's disease) that has the potential to cause a rise in total bilirubin over the upper limit of normal (ULN).
  17. Subjects with ANY of the following abnormalities in clinical laboratory tests at Screening, as assessed by the study specific laboratory and confirmed by a single repeat, if deemed necessary:

    • Serum aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >=1.5 × ULN, total serum bilirubin >= 25.6 micromol/L;
    • Hemoglobin =<2.17 mmol/L (males).
  18. Known participation in a clinical trial for PF 04965842 within 60 days prior to the first dose of study medication.
  19. Serious adverse reaction or serious hypersensitivity to any drug or the formulation excipients.
  20. Unwilling or unable to comply with the Lifestyle Requirements described in this protocol.
  21. 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, including their family members, directly involved in the conduct of the study.
  22. Systemic therapy with any of the following medications that are CYP3A4 inhibitors within 7 days or 5 half lives (whichever is longer) or CYP3A inducers within 28 days prior to the first dose of the trial medication, or during the trial (Section 5.7).
  23. History of sensitivity to heparin or heparin induced thrombocytopenia.
  24. Other acute or chronic medical or psychiatric condition including recent (within the past year) or active suicidal ideation or behavior or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study.
  25. Subjects with conditions that affect their ability to taste ie, dysgeusia, respiratory infection, cold, etc.
  26. Male subjects who are unwilling or unable to use a highly effective method of contraception as outlined in this protocol for the duration of the study and for at least 90 days after the last dose of investigational product.

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:他の
  • 割り当て:非ランダム化
  • 介入モデル:クロスオーバー割り当て
  • 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:Mass Balance
Cumulative recovery of radioactivity in urine and feces
14C labeled PF-04965842
実験的:Absolute Bioavailability
Oral absolute bioavailability
Oral dose of unlabeled PF-04965842 and an IV dose of 14C labeled PF- 04965842

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
Cumulative recovery of radioactivity
時間枠:From predose to Day 14 day
Total radioactivity in urine and feces based on total administered dose.
From predose to Day 14 day

二次結果の測定

結果測定
メジャーの説明
時間枠
Cmax
時間枠:From predose to Day 5
Maximum plasma concentration
From predose to Day 5
Tmax
時間枠:From predose to Day 5
Time to maximum concentration
From predose to Day 5
AUClast
時間枠:From predose to Day 5
Area under the plasma concentration-time curve from time 0 to last quantifiable concentration
From predose to Day 5
AUCinf
時間枠:From predose to Day 5
Area under the plasma concentration-time curve from time zero to infinity
From predose to Day 5
t1/2
時間枠:From predose to Day 5
Apparent terminal elimination half-life
From predose to Day 5
CL/F
時間枠:From predose to Day 5
Apparent total body clearance
From predose to Day 5
Vz/F
時間枠:From predose to Day 5
Apparent volume of distribution
From predose to Day 5
Vss (IV)
時間枠:From predose to Day 5
Steady State Volume of distribution
From predose to Day 5
CL (IV)
時間枠:From predose to Day 5
Total Body Clearance
From predose to Day 5
F
時間枠:From predose to Day 5
Absolute bioavailability= ratio of the adjusted geometric means of dose normalized AUCinf for unlabeled PF-04965842 and IV labeled 14C-PF-04965842
From predose to Day 5
Fa
時間枠:Predose to Day Day 5
Fraction of PF 04965842 dose absorbed = Total 14C urine data following both IV and oral administration of 14C PF 04965842 (quantification by AMS).
Predose to Day Day 5

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。

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)

2017年7月10日

一次修了 (実際)

2017年9月15日

研究の完了 (実際)

2017年9月15日

試験登録日

最初に提出

2017年7月11日

QC基準を満たした最初の提出物

2017年8月10日

最初の投稿 (実際)

2017年8月15日

学習記録の更新

投稿された最後の更新 (実際)

2017年12月21日

QC基準を満たした最後の更新が送信されました

2017年12月19日

最終確認日

2017年12月1日

詳しくは

本研究に関する用語

その他の研究ID番号

  • B7451008
  • 2017-000461-73 (EudraCT番号)

個々の参加者データ (IPD) の計画

個々の参加者データ (IPD) を共有する予定はありますか?

いいえ

IPD プランの説明

Information relating to our policy on data sharing and the process for requesting data can be found at the following link: http://www.pfizer.com/research/clinical_trials/trial_data_and_results/data_requests

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

いいえ

米国FDA規制機器製品の研究

いいえ

米国で製造され、米国から輸出された製品。

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。

PF-04965842の臨床試験

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