A Relative Bioavailability Study of a Fixed Dose Combination (FDC) Tablets of GSK587323
2017年5月12日 更新者:GlaxoSmithKline
An Open-Label, Randomised, Single Dose, Two-Way Crossover Pilot Study to Determine the Relative Bioavailability of a Fixed Dose Combination Tablet Formulation of GSK587323 (16mg Candesartan Cilexetil/12.5mg Hydrochlorothiazide) Relative to Respective Reference Dosage Atacand D in Healthy Adult Human Subjects Under Fasting Conditions
This study is required to confirm the suitability of a candidate FDC of 16mg candesartan cilexetil/12.5mg
HCTZ (GSK587323) formulation for further development and provide data to allow the design of a future pivotal bioequivalence study.
This study aims to determine the relative bioavailability of a FDC tablet formulation of 16mg candesartan cilexetil/12.5mg
HCTZ relative to the reference product of same fixed dose combination (16mg candesartan cilexetil/12.5mg
HCTZ) in healthy adult humans.
This will be an open-label, randomised, single dose, two-way crossover study.
Each subject will participate in two treatment periods and will be randomized to one of two sequences and administered one of the two treatments, A or B, as per the randomization schedule.
The two treatment periods will be separated by a washout period of 7 to 14 days to ensure the candesartan and HCTZ have been effectively eliminated from the subject between dosing occasions.
The study will enroll 16 healthy subjects to ensure that 14 subjects complete the study as planned.
調査の概要
研究の種類
介入
入学 (実際)
16
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
-
-
-
Hyderabad、インド、500 013
- GSK Investigational Site
-
-
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~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
全て
説明
Inclusion Criteria:
- Subjects Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form
- Male and females aged between 18 and 65 years of age inclusive, at the time of signing the informed consent.
- Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring. A subject with a clinical abnormality or laboratory parameter(s) which is/are not specifically listed in the inclusion or exclusion criteria, outside the reference range for the population being studied may be included only if the Investigator in consultation with the GlaxoSmithKline (GSK) Medical Monitor if required agree and document that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
- Body weight >=50kilograms (kg) and Body Mass Index (BMI) within the range 19 - 24.9kg / meter^2 (m^2) (inclusive).
- A female subject is eligible to participate if she is of: non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy for this definition, "documented" refers to the outcome of the investigator's/designee's review of the subject's medical history for study eligibility, as obtained via a verbal interview with the subject or from the subject's medical records; or postmenopausal defined as 12 months of spontaneous amenorrhea in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) > 40 milli international units per millilitre (MlU/mL) and estradiol < 40 picograms per millilitre (pg/mL) (<147 picomol per litre (pmol/L)) is confirmatory. Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the contraception methods if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrolment. For most forms of HRT, at least 2-4 weeks will elapse between the cessation of therapy and the blood draw; this interval depends on the type and dosage of HRT. Following confirmation of their post-menopausal status, they can resume use of HRT during the study without use of a contraceptive method.
- A female subject is eligible to participate if she is of child-bearing potential with negative pregnancy test as determined by serum or urine Human Chorionic Gonadotropin (hCG) test at screening or prior to dosing AND agrees to use one of the contraception methods for an appropriate period of time (as determined by the product label or investigator) prior to the start of dosing to sufficiently minimize the risk of pregnancy at that point. Female subjects must agree to use contraception until the follow-up contact visit.
- A female subject is eligible to participate if she has only same-sex partners, when this is her preferred and usual lifestyle.
- Male subjects with female partners of child-bearing potential must agree to use one of the contraception methods. This criterion must be followed from the time of the first dose of study medication until the follow-up contact visit.
- Alanine aminotransferase (ALT), alkaline phosphatase and bilirubin 1.5x Upper limit of normal (ULN) (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
- Based on single or averaged QT duration corrected for heart rate (QTc) of triplicate Electrocardiograms (ECGs) obtained over a brief recording period: QT duration corrected for heart rate by Fridericia's Formula (QTcF) < 450 millisecond (msec).
Exclusion Criteria:
- Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
- History of regular alcohol consumption within 6 months of the study defined as: An average weekly intake of >21 units for males or >14 units for females. One unit is equivalent to 8 grams (g) of alcohol: a half-pint (approximately 240 mL) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits.
- History of sensitivity to heparin or heparin-induced thrombocytopenia.
- History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or GSK Medical Monitor, contraindicates their participation.
- Gastrointestinal disease or with gastrointestinal surgical history which can affect the absorption of the investigational drug.
- Any subject with a systolic blood pressure (BP)<95 millimetre of Mercury (mmHg) or with a recent history of postural symptoms
- A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening
- Urinary cotinine levels indicative of smoking or history or regular use of tobacco- or nicotine-containing products within 6 months prior to screening.
- A positive pre-study drug/alcohol screen.
- A positive test for Human Immunodeficiency Virus (HIV) antibody.
- Pregnant females as determined by positive serum or urine hCG test at screening or prior to dosing.
- Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period.
- Lactating females.
- The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
- Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
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:処理
- 割り当て: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:Sequence 1
Participants in this arm will receive treatment A in period 1 and treatment B in period 2. Subjects will receive a single reference FDC tablet of 16mg candesartan cilexetil/12.5mg
HCTZ as Treatment A administered orally with 240mL of water and a single 16mg candesartan cilexetil/12.5mg
HCTZ FDC tablet (GSK587323) as Treatment B.
|
Single dose of FDC tablet formulation to be taken orally.
Single dose of FDC tablet formulation to be taken orally
|
|
実験的:Sequence 2
Participants in this arm will receive treatment B in period 1 and treatment A in period 2. Subjects will receive a single reference FDC tablet of 16mg candesartan cilexetil/12.5mg
HCTZ as Treatment A administered orally with 240mL of water and a single 16mg candesartan cilexetil/12.5mg
HCTZ FDC tablet (GSK587323) as Treatment B.
|
Single dose of FDC tablet formulation to be taken orally.
Single dose of FDC tablet formulation to be taken orally
|
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 |
|---|---|---|
|
Composite of PK parameters for candesartan and HCTZ to assess relative bioavailability.
時間枠:Pre dose, 0.33, 0.67, 1, 1.33, 1.67, 2.0, 2.33, 2.67, 3, 3.5, 4, 4.5, 5, 5.5, 6, 7, 8, 10, 12, 16, 24, 36, and 48hours post dose in each treatment period.
|
PK parameters include: maximum observed plasma concentration (Cmax), area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time (AUC [0-infinite]) and area under the concentration-time curve from time zero (pre-dose) to last time of quantifiable concentration within a subject across all treatments (AUC [0-t]).
Twenty four blood samples (1x 5mililiter (mL)) will be collected at the specified time points for PK analysis of candesartan and HCTZ.
|
Pre dose, 0.33, 0.67, 1, 1.33, 1.67, 2.0, 2.33, 2.67, 3, 3.5, 4, 4.5, 5, 5.5, 6, 7, 8, 10, 12, 16, 24, 36, and 48hours post dose in each treatment period.
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
PK profile of candesartan and HCTZ.
時間枠:Pre dose, 0.33, 0.67, 1, 1.33, 1.67, 2.0, 2.33, 2.67, 3, 3.5, 4, 4.5, 5, 5.5, 6, 7, 8, 10, 12, 16, 24, 36, and 48hours post dose in each treatment period.
|
PK parameters included: time to Cmax (tmax), Percentage of AUC (0-infinite) obtained by extrapolation, and apparent terminal phase half-life (t1/2).
PK blood samples (1x 5mL)) will be collected at the specified time points for PK analysis of candesartan and HCTZ.
|
Pre dose, 0.33, 0.67, 1, 1.33, 1.67, 2.0, 2.33, 2.67, 3, 3.5, 4, 4.5, 5, 5.5, 6, 7, 8, 10, 12, 16, 24, 36, and 48hours post dose in each treatment period.
|
|
Vital sign assessment as a measure of safety and tolerability.
時間枠:Up to 39 days
|
Vital sign parameters include: systolic blood pressure, diastolic blood pressure, and pulse rate.
At Baseline the average of the last two blood pressures and pulse readings will be recorded.
All measurements will be measured in supine position after 5 minutes rest.
|
Up to 39 days
|
|
Review of adverse events (AEs) as a measure of safety and tolerability.
時間枠:Up to 39 days
|
An AE is any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
All AEs and serious AEs (SAEs) will be collected from the start of dosing with Investigational Product and until the follow-up visit.
However, any SAEs related to study participation or concomitant
|
Up to 39 days
|
|
Clinical laboratory data assessment as measure of safety and tolerability.
時間枠:Up to 39 days
|
All subjects for all treatments will be evaluated for any abnormal laboratory test results (haematology, clinical chemistry, or urinalysis).
|
Up to 39 days
|
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)
2014年4月17日
一次修了 (実際)
2014年5月23日
研究の完了 (実際)
2014年5月23日
試験登録日
最初に提出
2014年3月20日
QC基準を満たした最初の提出物
2014年3月20日
最初の投稿 (見積もり)
2014年3月24日
学習記録の更新
投稿された最後の更新 (実際)
2017年5月15日
QC基準を満たした最後の更新が送信されました
2017年5月12日
最終確認日
2017年5月1日
詳しくは
本研究に関する用語
追加の関連 MeSH 用語
その他の研究ID番号
- 200957
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?
はい
IPD プランの説明
Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
試験データ・資料
-
研究プロトコル
情報識別子:200957情報コメント:For additional information about this study please refer to the GSK Clinical Study Register
-
臨床研究報告書
情報識別子:200957情報コメント:For additional information about this study please refer to the GSK Clinical Study Register
-
データセット仕様
情報識別子:200957情報コメント:For additional information about this study please refer to the GSK Clinical Study Register
-
インフォームド コンセント フォーム
情報識別子:200957情報コメント:For additional information about this study please refer to the GSK Clinical Study Register
-
統計分析計画
情報識別子:200957情報コメント:For additional information about this study please refer to the GSK Clinical Study Register
-
個人参加者データセット
情報識別子:200957情報コメント:For additional information about this study please refer to the GSK Clinical Study Register
-
注釈付き症例報告書
情報識別子:200957情報コメント:For additional information about this study please refer to the GSK Clinical Study Register
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。