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A Randomized, Double Blind, Placebo Controlled, Incomplete Block, Crossover, Dose Ranging Study to Evaluate the Dose Response of GSK573719 Administered Once or Twice Daily Over 7 Days in Patients With Chronic Obstructive Pulmonary Disease (COPD) (AC4115321)

2017年10月9日 更新者:GlaxoSmithKline
The purpose of this study is to further characterize the dose response of GSK573719 at doses of 15.6 micrograms (mcg) to 125 mcg once daily in patients with chronic obstructive pulmonary disease (COPD). Treatment with doses of GSK573719 dosed twice daily will also be included to further evaluate dosing frequency. Treatment with tiotropium (18 mcg) once daily via the Handihaler will be included as an active control. A placebo treatment will be included in order to evaluate absolute treatment effect of the different doses of GSK573719.

調査の概要

詳細な説明

Inhaled bronchodilators, such as beta 2 agonists and anticholinergics, and inhaled corticosteroids are the mainstays of therapy in patients diagnosed with COPD. Anticholinergic bronchodilators or long acting muscarinic receptor antagonists function by blocking endogenous airway smooth muscle cholinergic tone. Treatment with anticholinergics has been shown to significantly improve forced expiratory volume in 1 second (FEV1), resting and dynamic lung hyperinflation, symptoms, and exercise capacity in patients with COPD. Currently tiotropium is the only approved long acting muscarinic antagonist available for treatment of COPD.

This is a multicenter, randomized, double-blind, placebo controlled, three way crossover, incomplete block study to evaluate 4 doses of GSK573719 inhaled once daily and 2 doses of GSK573719 inhaled twice daily over 7 days in patients with COPD. Tiotropium will be included as an open label active comparator. A placebo treatment will be included to evaluate treatment effect of each GSK573719 dose. Pharmacokinetic profiles of GSK573719 will also be determined. Each eligible subject will receive a sequence of 3 of 8 potential treatments for a total of 3 treatment periods per subject. There will be 7 clinic visits, during three of which 24 hour serial spirometry will be performed. The total duration of subject participation is approximately 9 weeks.

研究の種類

介入

入学 (実際)

163

段階

  • フェーズ2

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

    • California
      • Costa Mesa、California、アメリカ、92626
        • GSK Investigational Site
    • Georgia
      • Atlanta、Georgia、アメリカ、30342
        • GSK Investigational Site
      • Duluth、Georgia、アメリカ、30096
        • GSK Investigational Site
    • Minnesota
      • Edina、Minnesota、アメリカ、55438
        • GSK Investigational Site
    • North Carolina
      • Charlotte、North Carolina、アメリカ、28207
        • GSK Investigational Site
      • Raleigh、North Carolina、アメリカ、27607
        • GSK Investigational Site
    • Oklahoma
      • Oklahoma City、Oklahoma、アメリカ、73103
        • GSK Investigational Site
    • South Carolina
      • Easley、South Carolina、アメリカ、29640
        • GSK Investigational Site
      • Gaffney、South Carolina、アメリカ、29340
        • GSK Investigational Site
      • Greenville、South Carolina、アメリカ、29615
        • GSK Investigational Site
      • Orangeburg、South Carolina、アメリカ、29118
        • GSK Investigational Site
      • Spartanburg、South Carolina、アメリカ、29303
        • GSK Investigational Site
      • Union、South Carolina、アメリカ、29379
        • 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

40年~80年 (大人、高齢者)

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:

  • Outpatient
  • A signed and dated written informed consent prior to study participation.
  • Male or female adults.
  • 40 to 80 years of age at Visit 1
  • Diagnosis of COPD
  • Current or former cigarette smokers with a history of cigarette smoking of greater than or equal to 10 pack-years
  • Post-albuterol forced expiratory volume in 1 second (FEV1)/ forced vital capacity (FVC)<0.70 and post albuterol FEV1 of greater than or equal to 35% and less than or equal to 70% of predicted normal values

Exclusion Criteria:

  • Women who are pregnant or lactating or are planning on becoming pregnant during the study.
  • A current diagnosis of asthma
  • Known alpha-1 antitrypsin deficiency, active lung infections (such as tuberculosis), and lung cancer
  • Other significant respiratory conditions in addition to COPD
  • Other diseases that are uncontrolled including cancer in remission for less than 5 years
  • Chest x-ray or CT scan with clinically significant abnormalities not believed to be due to the presence of COPD
  • Hypersensitivity to any anticholinergic/muscarinic receptor antagonist, beta2-agonist, lactose/milk protein or magnesium stearate
  • A medical condition that contraindicates study participation or use of an inhaled anticholinergic
  • Hospitalization for COPD or pneumonia within 12 weeks of Visit 1
  • Any previous lung resection surgery
  • A body mass index (BMI) value of >35 kilogram (kg)/meter squared (m2)
  • An abnormal and significant electrocardiogram finding at Visit 1
  • Significantly abnormal finding from clinical chemistry or haematology tests at Visit 1.
  • A positive Hepatitis B surface antigen or positive Hepatitis C antibody
  • Medically unable to withhold albuterol (salbutamol) for the 6 hour period prior to study visits
  • Use of depot corticosteroids within 12 weeks of Visit 1
  • Use of oral or parenteral corticosteroids or antibiotics for lower respiratory tract infection within 6 weeks of Visit 1
  • Use of long-acting beta-agonist (LABA)/inhaled corticosteroid (ICS) product if LABA/ICS therapy is discontinued within 30 days of Visit 1
  • Use of ICS at a dose of >1000mcg/day of fluticasone propionate or equivalent within 30 days of Visit 1
  • Initiation or discontinuation of ICS within 30 days of Visit 1
  • Use of tiotropium or phosphodiesterase 4 inhibitors within 14 days of Visit 1
  • Use of theophyllines, oral leukotriene inhibitors, long-acting oral beta-agonists, or inhaled long-acting beta-agonists within 48 hours of Visit 1
  • Short-acting oral beta-agonists within 12 hours of Visit 1
  • Use of LABA/ICS combination products only if discontinuing LABA therapy and switching to ICS monotherapy within 48 hours of Visit 1 for the LABA component
  • Use of sodium cromoglycate or nedocromil sodium within 24 hours of Visit 1
  • Use of inhaled short-acting beta-agonists, inhaled short-acting anticholinergics, or inhaled short-acting anticholinergic/short-acting beta-agonist combination products within 6 hours of Visit 1
  • Use of any other investigational medication within 30 days or 5 drug half-lives (whichever is longer)
  • Oxygen therapy prescribed for greater than 12 hours a day
  • Regular use (prescribed for use every day, not for as-needed use) of short-acting bronchodilators
  • Use of continuous positive airway pressure (CPAP), nocturnal positive pressure or non-invasive positive pressure ventilation (NIPPV), including use for sleep apnea.
  • Acute phase of a pulmonary rehabilitation program within 4 weeks prior to Visit 1
  • A known or suspected history of alcohol or drug abuse within 2 years prior to Visit 1
  • Anyone affiliated with investigator site
  • Previous use of GSK573719 or GSK53719/GW642444

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:ダブル

武器と介入

参加者グループ / アーム
介入・治療
アクティブコンパレータ:Tiotropium
18 mcg, inhaled long acting muscarinic antagonist
18 mcg once daily
実験的:GSK573719
inhaled medication
125 mcg once daily
62.5 mcg once daily
31.25 mcg once daily
15.6 mcg once daily
31.25 mcg twice daily
15.6 mcg twice daily
プラセボコンパレーター:Placebo
inactive/excipients only
once or twice daily

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
Final Dose-response Model for Trough Forced Expiratory Volume in One Second (FEV1)
時間枠:Day 7 and Day 8 of each treatment period (up to Study Day 50)
The trough FEV1 data for both the once-daily (QD) and twice-daily (BID) UMEC doses were included in a parametric analysis in order to evaluate trough FEV1dose response. The Day 8 dataset and a pooled dataset for Day 7 and Day 8 were analyzed separately and reported. The rationale for pooling Day 7 and Day 8 (post-hoc analysis) was to ensure informative interpretation of FEV1 response as a function of dose given the repeated measures for trough FEV1 response within each participant on different days. The fixed-effects parameters of the dose response model include Emax (the maximum predicted FEV1 response), ED50 (potency), and S0 (estimated Baseline FEV1). FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. Data for Emax and S0 are reported in this table. mITT=Modified Intent-to-Treat; par.=participants; BL=Baseline.
Day 7 and Day 8 of each treatment period (up to Study Day 50)
Final Dose-response Model for Trough FEV1 for ED50 (Potency) Parameter
時間枠:Day 7 and Day 8 of each treatment period (up to Study Day 50)
The trough FEV1 data for both the once-daily (QD) and twice-daily (BID) UMEC doses were included in a parametric analysis in order to evaluate dose response. Both a Day 8 dataset and a pooled dataset for Day 7 and Day 8 were analyzed and reported. The rationale for pooling Day 7 and Day 8 (post-hoc analysis) was to ensure informative interpretation of FEV1 response as a function of dose given the repeated measures for trough FEV1 response within each participant on different days. ED50 is defined as the potency and is the dose that yields 50% of Emax (maximum predicted FEV1 response). FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second.
Day 7 and Day 8 of each treatment period (up to Study Day 50)
Final Dose-response Model Parameter β-FEV1MB-S0 for Trough FEV1
時間枠:Day 7 and Day 8 of each treatment period (up to Study Day 50)
The trough FEV1 data for both the once-daily (QD) and twice-daily (BID) UMEC doses were included in a parametric analysis in order to evaluate dose response. Both a Day 8 dataset and a pooled dataset for Day 7 and Day 8 were analyzed and reported. The rationale for pooling Day 7 and Day 8 (post-hoc analysis) was to ensure informative interpretation of FEV1 response as a function of dose given the repeated measures for trough FEV1 response within each participant on different days. β-FEV1MB-S0 is defined as the covariate (Baseline trough FEV1) effect on the mean Baseline trough FEV1 estimate (S0). FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second.
Day 7 and Day 8 of each treatment period (up to Study Day 50)
Change From Baseline in Trough Forced Expiratory Volume in One Second (FEV1) on Day 8 of Each Treatment Period
時間枠:Baseline and Day 8 of each treatment period (up to Study Day 50)
FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. Trough FEV1 on Treatment Day 8 is defined as the value obtained 24 hours after the morning dose administered on Day 7. Analysis was performed using a mixed model with covariates of mean Baseline, period Baseline, treatment, and period as fixed effects and participant as a random effect. Baseline is the FEV1 value recorded pre-dose on Day 1 of each treatment period, mean Baseline is the mean of the Baselines for each participant, and period Baseline is the difference between the Baseline and the mean Baseline in each treatment period for each particiapant. Change from Baseline for each treatment period is the trough FEV1 at Day 8 minus the Baseline value for that treatment period.
Baseline and Day 8 of each treatment period (up to Study Day 50)

二次結果の測定

結果測定
メジャーの説明
時間枠
Change From Baseline (BL) in Serial FEV1 Over Time on Day 7 of Each Treatment Period
時間枠:Baseline and Day 7 of each treatment period (TP; up to Study Day 49)
Serial FEV1 for once daily dosing is recorded at the pre-AM dose (AMD; time 0 hour [h]) and at 1, 3, 6, 9, 12,13, 15, 23, and 24 hours after the AMD on Day 7. For twice daily dosing, the 12 h AMD corresponds to the pre-PM dose (PMD), the 13 h AMD corresponds to the 1 h PMD, the 15 h AMD corresponds to the 3 h PMD, the 23 h AMD corresponds to the 11 h PMD, and the 24 h AMD corresponds to the 12 h PMD in this table. Analysis was performed using a mixed model with covariates of mean BL, period BL, treatment, period, time, time by period BL interaction, time by mean BL interaction, and time by treatment interaction as fixed effects and participant as a random effect. BL is the value recorded pre-dose on Day 1 of each TP, mean BLis the mean of the BLs for each participant, and period BL is the difference between the BL and the mean BL in each TP for each participant. Change from BL for each timepoint within a TP is the serial FEV1 measure at that timepoint minus the BL value for that TP.
Baseline and Day 7 of each treatment period (TP; up to Study Day 49)
Change From Baseline (BL) in Weighted Mean FEV1 Over 0 to 24 Hours After the Morning Dosing on Day 7 of Each Treatment Period
時間枠:Baseline and Day 7 of each treatment period (TP; up to Study Day 49)
FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. The weighted mean FEV1 was derived by calculating the area under the FEV1/time curve (AUC) using the trapezoidal rule, and then dividing the value by the time interval over which the AUC was calculated. The weighted mean FEV1 was calculated using 0-24 hour post-dose measurements at Day 7 of each treatment period, which included pre-dose and post-dose 1, 3, 6, 9, 12, 13, 15, 23, and 24 hours. Analysis was performed using a mixed model with covariates of mean BL, period BL, treatment, and period as fixed effects and participant as a random effect. BL is the FEV1 value recorded pre-dose on Day 1 of each TP, mean BL is the mean of the BLs for each participant, and period BL is the difference between the BL and the mean BL in each TP for each participant. Change from BL for each TP is the weighted mean FEV1 at Day 7 minus the BL value for that TP.
Baseline and Day 7 of each treatment period (TP; up to Study Day 49)

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

2011年7月1日

一次修了 (実際)

2011年10月1日

研究の完了 (実際)

2011年10月27日

試験登録日

最初に提出

2011年6月9日

QC基準を満たした最初の提出物

2011年6月9日

最初の投稿 (見積もり)

2011年6月13日

学習記録の更新

投稿された最後の更新 (実際)

2017年11月8日

QC基準を満たした最後の更新が送信されました

2017年10月9日

最終確認日

2017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?

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

  1. データセット仕様
    情報識別子:115321
    情報コメント:For additional information about this study please refer to the GSK Clinical Study Register
  2. インフォームド コンセント フォーム
    情報識別子:115321
    情報コメント:For additional information about this study please refer to the GSK Clinical Study Register
  3. 統計分析計画
    情報識別子:115321
    情報コメント:For additional information about this study please refer to the GSK Clinical Study Register
  4. 研究プロトコル
    情報識別子:115321
    情報コメント:For additional information about this study please refer to the GSK Clinical Study Register
  5. 個人参加者データセット
    情報識別子:115321
    情報コメント:For additional information about this study please refer to the GSK Clinical Study Register
  6. 臨床研究報告書
    情報識別子:115321
    情報コメント:For additional information about this study please refer to the GSK Clinical Study Register
  7. 注釈付き症例報告書
    情報識別子:115321
    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。

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