Bioavailability of [14C]-SK-1404 ADME & IV Microtracer Study
2016年10月12日 更新者：Sanwa Kagaku Kenkyusho Co., Ltd.
An Open-Label, 2-Part Sequential Dose Study Designed to Assess the Absolute Bioavailability, Mass Balance Recovery, Metabolite Profile and Metabolite Identification of [14C]-SK-1404 Administered to Healthy Male Subjects
The primary objectives of the study are:
- To determine the absolute bioavailability of SK-1404
- To assess the mass balance recovery after a single oral (PO) dose of carbon-14 (14C)-SK-1404
- To provide plasma, urine and faecal samples for metabolite profiling and structural identification
The secondary objectives of the study are:
- To determine the routes and rates of elimination of [14C]-SK-1404
- To identify the chemical structure of each metabolite with an exposure (AUC) of more than 10% of circulating total radioactivity
- To explore the intravenous (IV) pharmacokinetics (PK) of [14C]-SK-1404
- To further explore the PO PK of SK-1404
- To provide additional safety and tolerability information for SK-1404
調査の概要
詳細な説明
This is a single-centre, 2-part, open-label, non-randomised, sequential, single dose study in healthy male subjects. It is planned to enrol a single cohort of 6 healthy male subjects who will participate in Parts 1 and Part 2 of the study.
In Part 1, each subject will receive a single PO dose of SK-1404 followed by an IV microtracer dose of [14C]-SK-1404.
In Part 2, each subject will receive a single PO dose of [14C]-SK-1404.
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
-
-
Nottingham
-
Ruddington、Nottingham、イギリス、NG11 6JS
- Quotient Clinical
-
-
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
30年～65年 (大人、高齢者)
健康ボランティアの受け入れ
はい
受講資格のある性別
男
説明
Inclusion Criteria:
- Healthy males
- Age 30 to 65 years of age
- Body mass index of 18.0 to 35.0 kg/m2 or, if outside the range, considered not clinically significant by the investigator
- Must be willing and able to communicate and participate in the whole study
- Must provide written informed consent
- Must have regular bowel movements (ie average stool production of ≥1 and ≤3 stools per day)
- Must agree to use an adequate method of contraception
Exclusion Criteria:
- Males with pregnant partners
- Participation in a clinical research study within the 3 months prior to IMP dose
- Subjects who are study site employees, or immediate family members of a study site or sponsor employee
- Subjects who have previously been enrolled in this study
- Subjects who have previously been dosed with SK-1404
- History of any drug or alcohol abuse in the past 2 years
- Regular alcohol consumption in males >21 units per week (1 unit = ½ pint beer, 25 mL of 40% spirit or a 125 mL glass of wine) in the past year
- Current smokers and those who have smoked within the last 12 months; this includes cigarettes, e-cigarettes and nicotine replacement products. A breath carbon monoxide reading of greater than 10 ppm at screening or admission
- Radiation exposure, including that from the present study, excluding background radiation but including diagnostic x-rays and other medical exposures, exceeding 5 mSv in the last 12 months or 10 mSv in the last 5 years. No occupationally exposed worker, as defined in the Ionising Radiation Regulations 1999, shall participate in the study
- Subjects who have been enrolled in an ADME study in the last 12 months
- Subjects who do not have suitable veins for multiple venepunctures/cannulation as assessed by the investigator at screening
- Clinically significant abnormal biochemistry, haematology or urinalysis as judged by the investigator (laboratory parameters are listed in Appendix 1)
- Aspartate aminotransferase, alanine aminotransferase or alkaline phosphatase >1.5 × upper limit of normal confirmed by repeat testing
- Serum sodium below the lower limit of normal
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：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 |
|---|---|
|
実験的：[14C]-SK-1404
|
In Part 1, each subject will receive a single PO dose of SK-1404 followed by an IV microtracer dose of [14C]-SK-1404.
|
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 |
|---|---|---|
|
Absolute bioavailability (F) calculated with the AUC values of IV administration in Part 1 and PO administration in Part 2
時間枠：Predose to 96hr
|
Predose to 96hr
|
|
|
Mass balance recovery of total radioactivity in urine, faeces and all excreta
時間枠：Predose to 168hr
|
Amount excreted (Ae), and Ae as a percentage of the administered dose (%Ae), cumulative recovery (Cum Ae) and cumulative recovery expressed as a percentage of the dose (Cum %Ae)
|
Predose to 168hr
|
|
Number and structural identification of known and unknown metabolites of SK-1404 in the plasma, urine and faeces samples
時間枠：Predose to 168hr
|
Predose to 168hr
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Ae total radioactivity in plasma by metabolite profiling and structural identification to estimate the routes and rates of elimination of [14C]-SK-1404
時間枠：Predose to 168hr
|
Predose to 168hr
|
|
|
%Ae total radioactivity in plasma by metabolite profiling and structural identification to estimate the routes and rates of elimination of [14C]-SK-1404
時間枠：Predose to 168hr
|
Predose to 168hr
|
|
|
Cum Ae (total) for urine by metabolite profiling and structural identification to estimate the routes and rates of elimination of [14C]-SK-1404
時間枠：Predose to 168hr
|
Predose to 168hr
|
|
|
Cum %Ae (total) for urine by metabolite profiling and structural identification to estimate the routes and rates of elimination of [14C]-SK-1404
時間枠：Predose to 168hr
|
Predose to 168hr
|
|
|
Cum Ae (total) for faeces by metabolite profiling and structural identification to estimate the routes and rates of elimination of [14C]-SK-1404
時間枠：Predose to 168hr
|
Predose to 168hr
|
|
|
Cum %Ae (total) for faeces by metabolite profiling and structural identification to estimate the routes and rates of elimination of [14C]-SK-1404
時間枠：Predose to 168hr
|
Predose to 168hr
|
|
|
Number and structural identification of unknown metabolites of SK-1404 with an AUC of more than 10% of circulating total radioactivity
時間枠：Predose to 168hr
|
Predose to 168hr
|
|
|
The peak plasma concentration (Cmax) of SK-1404F and its active metabolites M-1, M-7 and M-9) after IV SK-1404
時間枠：Predose to 96hr
|
Metabolite:parent ratios will be calculated for SK-1404F, M-1, M-7 and M-9
|
Predose to 96hr
|
|
The time from dosing at which Cmax was apparent (Tmax) of SK-1404F and its active metabolites M-1, M-7 and M-9) after IV SK-1404
時間枠：Predose to 96hr
|
Metabolite:parent ratios will be calculated for SK-1404F, M-1, M-7 and M-9
|
Predose to 96hr
|
|
The elapsed time from dosing at which the analyte was first quantifiable in a concentration vs time profile (Tlag) of SK-1404F and its active metabolites M-1, M-7 and M-9) after IV SK-1404
時間枠：Predose to 96hr
|
Metabolite:parent ratios will be calculated for SK-1404F, M-1, M-7 and M-9
|
Predose to 96hr
|
|
The area under the concentration-time curve from dosing to the last measurable concentration (AUC(0-last)) of SK-1404F and its active metabolites M-1, M-7 and M-9) after IV SK-1404
時間枠：Predose to 96hr
|
Metabolite:parent ratios will be calculated for SK-1404F, M-1, M-7 and M-9
|
Predose to 96hr
|
|
The area under the concentration-time curve from dosing extrapolated to infinity (AUC(0-inf)) of SK-1404F and its active metabolites M-1, M-7 and M-9) after IV SK-1404
時間枠：Predose to 96hr
|
Metabolite:parent ratios will be calculated for SK-1404F, M-1, M-7 and M-9
|
Predose to 96hr
|
|
The percentage of AUC(0-inf) extrapolated beyond the last measured time point (AUC%extrap) of SK-1404F and its active metabolites M-1, M-7 and M-9) after IV SK-1404
時間枠：Predose to 96hr
|
Metabolite:parent ratios will be calculated for SK-1404F, M-1, M-7 and M-9
|
Predose to 96hr
|
|
The terminal elimination rate constant calculated from the slope of the apparent elimination phase (lambda-z) of SK-1404F and its active metabolites M-1, M-7 and M-9) after IV SK-1404
時間枠：Predose to 96hr
|
Metabolite:parent ratios will be calculated for SK-1404F, M-1, M-7 and M-9
|
Predose to 96hr
|
|
The apparent terminal elimination half-life (T1/2) of SK-1404F and its active metabolites M-1, M-7 and M-9) after IV SK-1404
時間枠：Predose to 96hr
|
Metabolite:parent ratios will be calculated for SK-1404F, M-1, M-7 and M-9
|
Predose to 96hr
|
|
The apparent total clearance (CL/F) of SK-1404F and its active metabolites M-1, M-7 and M-9) after IV SK-1404
時間枠：Predose to 96hr
|
Metabolite:parent ratios will be calculated for SK-1404F, M-1, M-7 and M-9
|
Predose to 96hr
|
|
The apparent volume of distribution (Vd) of SK-1404F and its active metabolites M-1, M-7 and M-9) after IV SK-1404
時間枠：Predose to 96hr
|
Metabolite:parent ratios will be calculated for SK-1404F, M-1, M-7 and M-9
|
Predose to 96hr
|
|
The apparent volume of distribution (Vss) of SK-1404F and its active metabolites M-1, M-7 and M-9) after IV SK-1404
時間枠：Predose to 96hr
|
Metabolite:parent ratios will be calculated for SK-1404F, M-1, M-7 and M-9
|
Predose to 96hr
|
|
The mean residence time (MRT) of SK-1404F and its active metabolites M-1, M-7 and M-9) after IV SK-1404
時間枠：Predose to 96hr
|
Metabolite:parent ratios will be calculated for SK-1404F, M-1, M-7 and M-9
|
Predose to 96hr
|
|
The peak plasma concentration (Cmax) of SK-1404F and its active metabolites M-1, M-7 and M-9) after PO SK-1404
時間枠：Predose to 168hr
|
Metabolite:parent ratios will be calculated for SK-1404F, M-1, M-7 and M-9
|
Predose to 168hr
|
|
The time from dosing at which Cmax was apparent (Tmax) of SK-1404F and its active metabolites M-1, M-7 and M-9) after PO SK-1404
時間枠：Predose to 168hr
|
Metabolite:parent ratios will be calculated for SK-1404F, M-1, M-7 and M-9
|
Predose to 168hr
|
|
The elapsed time from dosing at which the analyte was first quantifiable in a concentration vs time profile (Tlag) of SK-1404F and its active metabolites M-1, M-7 and M-9) after PO SK-1404
時間枠：Predose to 168hr
|
Metabolite:parent ratios will be calculated for SK-1404F, M-1, M-7 and M-9
|
Predose to 168hr
|
|
The area under the concentration-time curve from dosing to the last measurable concentration (AUC(0-last)) of SK-1404F and its active metabolites M-1, M-7 and M-9) after PO SK-1404
時間枠：Predose to 168hr
|
Metabolite:parent ratios will be calculated for SK-1404F, M-1, M-7 and M-9
|
Predose to 168hr
|
|
The area under the concentration-time curve from dosing extrapolated to infinity (AUC(0-inf)) of SK-1404F and its active metabolites M-1, M-7 and M-9) after PO SK-1404
時間枠：Predose to 168hr
|
Metabolite:parent ratios will be calculated for SK-1404F, M-1, M-7 and M-9
|
Predose to 168hr
|
|
The percentage of AUC(0-inf) extrapolated beyond the last measured time point (AUC%extrap) of SK-1404F and its active metabolites M-1, M-7 and M-9) after PO SK-1404
時間枠：Predose to 168hr
|
Metabolite:parent ratios will be calculated for SK-1404F, M-1, M-7 and M-9
|
Predose to 168hr
|
|
The terminal elimination rate constant calculated from the slope of the apparent elimination phase (lambda-z) of SK-1404F and its active metabolites M-1, M-7 and M-9) after PO SK-1404
時間枠：Predose to 168hr
|
Metabolite:parent ratios will be calculated for SK-1404F, M-1, M-7 and M-9
|
Predose to 168hr
|
|
The apparent terminal elimination half-life (T1/2) of SK-1404F and its active metabolites M-1, M-7 and M-9) after PO SK-1404
時間枠：Predose to 168hr
|
Metabolite:parent ratios will be calculated for SK-1404F, M-1, M-7 and M-9
|
Predose to 168hr
|
|
The absolute bioavailability (F, PO vs IV from Part 1) of SK-1404F and its active metabolites M-1, M-7 and M-9) after PO SK-1404
時間枠：Predose to 168hr
|
Metabolite:parent ratios will be calculated for SK-1404F, M-1, M-7 and M-9
|
Predose to 168hr
|
|
The apparent total clearance (CL/F) of SK-1404F and its active metabolites M-1, M-7 and M-9) after PO SK-1404
時間枠：Predose to 168hr
|
Metabolite:parent ratios will be calculated for SK-1404F, M-1, M-7 and M-9
|
Predose to 168hr
|
|
The apparent volume of distribution (Vd/F) of SK-1404F and its active metabolites M-1, M-7 and M-9) after PO SK-1404
時間枠：Predose to 168hr
|
Metabolite:parent ratios will be calculated for SK-1404F, M-1, M-7 and M-9
|
Predose to 168hr
|
|
The mean residence time (MRT) of SK-1404F and its active metabolites M-1, M-7 and M-9) after PO SK-1404
時間枠：Predose to 168hr
|
Metabolite:parent ratios will be calculated for SK-1404F, M-1, M-7 and M-9
|
Predose to 168hr
|
|
To collect further information about the safety and tolerability of IMP
時間枠：Predose to 168hr
|
By assessing physical examination, safety laboratory tests, vital signs, electrocardiograms (ECGs) and AEs.
|
Predose to 168hr
|
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。
捜査官
- 主任研究者：Litza McKenzie, MBChB BScMedSci、Quotient Clinical
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
2016年7月1日
一次修了 (実際)
2016年8月1日
研究の完了 (実際)
2016年8月1日
試験登録日
最初に提出
2016年8月5日
QC基準を満たした最初の提出物
2016年8月19日
最初の投稿 (見積もり)
2016年8月25日
学習記録の更新
投稿された最後の更新 (見積もり)
2016年10月14日
QC基準を満たした最後の更新が送信されました
2016年10月12日
最終確認日
2016年10月1日
詳しくは
本研究に関する用語
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
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。