Multiple Dose Study in Heart Failure of BAY 1067197 (PARSiFAL)
2019年6月19日 更新者：Bayer
A Double Blinded, Placebo Controlled, Study to Investigate the Safety, Tolerability, Pharmacokinetics and Acute Cardiovascular Responses of a 7 Day Oral Treatment With the Partial Adenosine A1 Receptor Agonist BAY1067197 in Patients With Chronic Systolic Heart Failure: the PARSiFAL-pilot Study.
This is a study to investigate the safety, tolerability and early effects on cardiac function of the partial A1 agonist BAY1067197 in patients with chronic heart failure.
BAY1067197 will be applied once daily over 7 days in addition to standard therapy including a beta-blocker.
The aim of the study is to assess if a 7 day treatment with BAY1067197 is well tolerated when given on top of standard therapy for heart failure.
Furthermore, the study aims to assess if cardiac function improves in the early course of therapy.
調査の概要
研究の種類
介入
入学 (実際)
31
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。
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～75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:
- Clinical diagnosis of chronic systolic heart failure of ischemic or non-ischemic etiology:(New York Heart Association)NYHA class I-III and treatment with standard pharmacological therapy for the treatment of systolic heart failure including β-blocker ≥ 4 weeks prior to randomization
- Left ventricular ejection fraction ≤ 40%: by any imaging technique within the last 3 months will be accepted for screening purposes but will be verified by baseline CMR(Cardiac Magnetic Resonance Tomography)
- Sinus rhythm for at least 4 weeks prior to randomization
- No planned changes to heart failure related drug therapy for the duration of study drug treatment
- Substantial dysfunctional but viable myocardium as demonstrated by the baseline CMR: Based on a standard 17-segment model (AHA - American Heart Association), 3 or more segments require demonstration of dysfunction (defined by visible assessment of the performing investigator) and viability (defined as < 25% of segment area with scar burden - in patients with CAD (Coronary Artery Disease) or no (i.e. zero) scar burden in patients without CAD [idiopathic CM patient])
- Men or confirmed postmenopausal women or women without childbearing potential.
- Age: 18 to 75 years (inclusive) at the first screening visit.
- Body Mass Index (BMI) :above /equal 18.0 and below/equal 34.9kg/m²
- Exclusion Criteria:
- Atrial fibrillation / atrial flutter within the last 4 weeks prior to randomization or currently persistent/permanent atrial fibrillation / atrial flutter
- Primary valvular disease (severe valvular disease) with planned valve repair or replacement
- Non-idiopathic non-ischemic causes for cardiomyopathy (constrictive, restrictive, or hypertrophic cardiomyopathy; acute myocarditis)
- Listing for heart transplantation and/or anticipated/implanted ventricular assist device Clinically relevant ventricular arrhythmias within the last 2 months (sustained ventricular tachycardia, ventricular flutter or fibrillation), based on either medical history or ICD-testing results (if applicable)
- Unstable cardiac condition, indicated by requirement of IV drug (diuretic, inotrope, etc.) or NYHA IV within 4 weeks prior to randomization
- Coronary revascularization within 4 weeks prior to randomization or if revascularization is anticipated or needed
- Current permanent or intermittent AV-Block > I° or history of AV-Block > I° within six months before enrollment
- PR duration ≥ 300 ms
- Acute Coronary Syndrome (defined as unstable angina [UA], non-ST elevation myocardial infarction [NSTEMI], ST elevation myocardial infarction [STEMI]) within 2 months prior to randomization
- Subjects with untreated hyperthyroidism or hypothyroidism and non-stable thyroid function (intake of stable thyroid hormone substitution allowed)
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：並列代入
- マスキング：トリプル
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
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プラセボコンパレーター：プラセボ
|
5 mg / or 10 mg / or 20 mg Placebo for 7 d treatment once daily as oral application
|
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アクティブコンパレータ：BAY1067197 (10 mg)
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10 mg BAY1067197 for 7 d treatment once daily as oral application
|
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アクティブコンパレータ：BAY1067197
|
The dose escalation to the second dose step will proceed only if the previous dose step has shown acceptable safety and tolerability 5 mg / or 10 mg / or 20 mg BAY1067197 for 7 d treatment as oral application.
|
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プラセボコンパレーター：Placebo (10 mg)
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10 mg Placebo for 7 d treatment once daily as oral application
|
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 |
|---|---|---|
|
Number of Subjects With Relevant Changes in Heart Rate
時間枠：From the start of study treatment up to Day 29
|
Heart rate was measured by monitor measurements after 30 minutes resting in a supine position.
The relevant changes in heart rate were recorded and analysed.
|
From the start of study treatment up to Day 29
|
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Number of Subjects With Relevant Changes in Blood Pressure
時間枠：From the start of study treatment up to Day 29
|
Blood pressure was measured by monitor measurements after 30 minutes resting in a supine position.
The relevant changes in blood pressure were recorded and analysed.
|
From the start of study treatment up to Day 29
|
|
Number of Subjects With More than First Degree Atrio-Ventricular (AV) Block
時間枠：After 7 day tratment and day 28
|
A complete standard 12-lead ECG was recorded and evaluated parameters such as heart rate, PR/PQinterval, QRSD interval, QT interval (uncorrected).
Clinically relevant findings in ECG such as a second degree AV-block Mobitz type I (Wenkebach), Mobitz type II - or any third-degree AV block were recorded and reported.
A 24-hour Holter ECG was recorded with a standard Holter ECG recorder for the purpose of detecting AV blocks, no higher degree AV blocks > 1 or clinically relevant effect on HR were observed during Holter monitoring periods.
|
After 7 day tratment and day 28
|
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Change From Baseline in Left Ventricular Ejection Fraction (LVEF)
時間枠：Baseline to day 7
|
The change in LVEF between the post and the pre-treatment measurements were analyzed using Bayesian statistics to quantify the difference between BAY1067197 treatment and placebo measured by CMR.
LVEF is the fraction of blood (in percent) pumped out of the heart's left ventricular chamber with each heart beat, and is a measure of cardiac output for the heart.
|
Baseline to day 7
|
|
Maximum Observed Concentration of BAY84-3174 in Plasma (Cmax) After First Dose of BAY1067197
時間枠：Day 1: pre-dose and 0.5, 1, 2, 3, 4, 6, 12 and 24 hours post-dose
|
Maximum observed BAY84-3174 concentration in plasma, directly taken from analytical data.
Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
|
Day 1: pre-dose and 0.5, 1, 2, 3, 4, 6, 12 and 24 hours post-dose
|
|
Maximum Observed Concentration of BAY84-3174 in Plasma Divided by Dose (Cmax/D) After First Dose of BAY1067197
時間枠：Day 1: pre-dose and 0.5, 1, 2, 3, 4, 6, 12 and 24 hours post-dose
|
Maximum observed drug concentration, directly taken from analytical data, divided by dose.
Geometric mean and %CV were reported.
|
Day 1: pre-dose and 0.5, 1, 2, 3, 4, 6, 12 and 24 hours post-dose
|
|
Area Under the Concentration Versus Time Curve of BAY84-3174 for the Dosing Interval (AUCtau) After First Dose of BAY1067197
時間枠：Day 1: pre-dose and 0.5, 1, 2, 3, 4, 6, 12 and 24 hours post-dose
|
AUCtau is defined as area under the plasma concentration time profile from time zero to the end of the dosing interval after the first dose and dosing interval was 24 h for both arms.
Geometric mean and %CV were reported.
|
Day 1: pre-dose and 0.5, 1, 2, 3, 4, 6, 12 and 24 hours post-dose
|
|
Area Under the Concentration Versus Time Curve of BAY84-3174 for the Dosing Interval Divided by Dose (AUCtau/D) After First Dose of BAY1067197
時間枠：Day 1: pre-dose and 0.5, 1, 2, 3, 4, 6, 12 and 24 hours post-dose
|
AUCtau/D is defined as area under the plasma concentration time profile from time zero to the end of the dosing interval divided by dose after the first dose and dosing interval was 24 h for both arms.
Geometric mean and %CV were reported.
|
Day 1: pre-dose and 0.5, 1, 2, 3, 4, 6, 12 and 24 hours post-dose
|
|
Maximum Observed Concentration of BAY84-3174 in Plasma (Cmax,md) After Multiple Dose Administration During a Dosing Interval
時間枠：Day 7: pre dose and 0.5, 1, 2, 3, 4, 6 and 12 hours post dose; Day 8, Day 14, Day 22 and Day 29
|
Cmax,md is defined as maximum observed drug concentration in plasma after multiple-dose administrations during a dosing interval directly taken from analytical data.Geometric mean and %CV were reported.
|
Day 7: pre dose and 0.5, 1, 2, 3, 4, 6 and 12 hours post dose; Day 8, Day 14, Day 22 and Day 29
|
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Maximum Observed Concentration of BAY84-3174 in Plasma Divided by Dose (Cmax,md/D) After Multiple Dose Administration During a Dosing Interval
時間枠：Day 7: pre dose and 0.5, 1, 2, 3, 4, 6 and 12 hours post dose; Day 8, Day 14, Day 22 and Day 29
|
Maximum observed drug concentration, directly taken from analytical data divided by dose after multiple doses.
Geometric mean and %CV were reported.
|
Day 7: pre dose and 0.5, 1, 2, 3, 4, 6 and 12 hours post dose; Day 8, Day 14, Day 22 and Day 29
|
|
Area Under the Concentration Versus Time Curve of BAY84-3174 During any Dosing Interval (AUCtau,md) After Multiple Dose Administration
時間枠：Day 7: pre-dose and 0.5, 1, 2, 3, 4, 6, 12 and 24 hours post-dose
|
AUCtau,md is defined as area under the plasma concentration time profile from time zero during the dosing interval after multiple-dose administrations and dosing interval was 24 h for both arms. Geometric mean and %CV were reported. |
Day 7: pre-dose and 0.5, 1, 2, 3, 4, 6, 12 and 24 hours post-dose
|
|
Area Under the Concentration Versus Time Curve of BAY84-3174 During any Dosing Interval Divided by Dose (AUCtau,md/D) After Multiple Dose Administration
時間枠：Day 7: pre-dose and 0.5, 1, 2, 3, 4, 6, 12 and 24 hours post-dose
|
AUCtau,md/D is defined as area under the plasma concentration time profile from time zero to the end of the dosing interval after multiple dose of administrations divided by dose and dosing interval was 24 h for both arms.
Geometric mean and %CV were reported.
|
Day 7: pre-dose and 0.5, 1, 2, 3, 4, 6, 12 and 24 hours post-dose
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Changes From Baseline for Wall Motion Score Index at Day (WMSI) as Measured by Cardiac Magnetic Resonance at Day 7
時間枠：Baseline to day 7
|
Wall motion score index will cover the changes in wall motion score from baseline also.
|
Baseline to day 7
|
|
Number of Subjects With Clinically Relevant Changes Observed in Echocardiography Parameters
時間枠：Baseline, Day 6 and 15
|
Septal mitral annulus (e' septal), Lateral mitral annulus (e' lateral), E/e' average (average of e' lateral and e' septal), E/e' Lateral ratio, E/e' Septal ratio, Peak early doppler transmitral flow velocity (E), Peak atrial doppler transmitral flow velocity (A), E/A Ratio, Deceleration time (DT), Global longitudinal strain, Cardiac output, Stroke volume, Stroke volume index, Peak systolic tissue Doppler Velocity (Smax), Left ventricular end-systolic volume (LVESV), Left ventricular enddiastolic volume (LVEDV), Left atrial volume index (LAVI), Peak pulmonary systolic pressure (PAPsys).
|
Baseline, Day 6 and 15
|
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Number of Subjects With Clinically Relevant Changes Observed in Biomarkers
時間枠：Baseline up to Day 15
|
N-terminal prohormone of brain natriuretic peptide (NT-proBNP), renin, mid-region pro-atrial natriuretic peptide (MR-proANP) are biomarkers which show effect on neurohormones.
|
Baseline up to Day 15
|
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Time to Reach Maximum Observed Concentration of BAY84-3174 in Plasma (tmax) After First Dose of BAY1067197
時間枠：Day 1: pre-dose and 0.5, 1, 2, 3, 4, 6, 12 and 24 hours post-dose
|
Time to reach maximum drug concentration in the measured matrix, directly taken from analytical data
|
Day 1: pre-dose and 0.5, 1, 2, 3, 4, 6, 12 and 24 hours post-dose
|
|
Area Under the Concentration Versus Time Curve of BAY84-3174 for the Dosing Interval Divided by Dose per Body Weight (AUCtau,md,norm) After Multiple Dose Administration
時間枠：Day 7: pre-dose and 0.5, 1, 2, 3, 4, 6, 12 and 24 hours post-dose
|
AUCtau,md,norm is defined as area under the plasma concentration time profile from time zero to the end of the dosing interval after multiple dosing divided by dose per body weight.
The dosing interval was 24 h for both arms.
Geometric mean and %CV were reported.
|
Day 7: pre-dose and 0.5, 1, 2, 3, 4, 6, 12 and 24 hours post-dose
|
|
Maximum Observed Concentration of BAY84-3174 in Plasma Divided by Dose per Body Weight (Cmax,md,norm) After Multiple Dose Administration
時間枠：Day 7: pre dose and 0.5, 1, 2, 3, 4, 6 and 12 hours post dose; Day 8, Day 14, Day 22 and Day 29
|
Cmax,md,norm defined as maximum observed drug concentration in plasma after the first dose followed by multiple-dose administrations during a dosing interval divided by dose per body weight.
Geometric mean and %CV were reported.
|
Day 7: pre dose and 0.5, 1, 2, 3, 4, 6 and 12 hours post dose; Day 8, Day 14, Day 22 and Day 29
|
|
Time to Reach Maximum Observed Concentration of BAY84-3174 in Plasma (tmax,md) After Multiple Dose Administration
時間枠：Day 7: pre dose and 0.5, 1, 2, 3, 4, 6 and 12 hours post dose; Day 8, Day 14, Day 22 and Day 29
|
tmax,md defines as time to reach maximum drug concentration in the measured matrix after multiple dose administrations directly taken from analytical data.
|
Day 7: pre dose and 0.5, 1, 2, 3, 4, 6 and 12 hours post dose; Day 8, Day 14, Day 22 and Day 29
|
|
Half-Life Associated With the Terminal Slope (t1/2,md) After Multiple-Dose Administration
時間枠：Day 7: pre dose and 0.5, 1, 2, 3, 4, 6 and 12 hours post dose; Day 8, Day 14, Day 22 and Day 29
|
t1/2,md is defiend as time to reach maximum observed drug concentration in plasma after the first dose followed by multiple-dose administrations.
Geometric mean and %CV were reported.
|
Day 7: pre dose and 0.5, 1, 2, 3, 4, 6 and 12 hours post dose; Day 8, Day 14, Day 22 and Day 29
|
|
Maximum Observed Concentration of BAY84-3174 in Plasma After First Dose Divided by Dose per Body Weight (Cmax,norm)
時間枠：Day 1: pre-dose and 0.5, 1, 2, 3, 4, 6, 12 and 24 hours post-dose
|
Cmax,norm is defined as maximum observed drug concentration in plasma after the first dose divided by dose per body weight.
Geometric mean and %CV were reported.
|
Day 1: pre-dose and 0.5, 1, 2, 3, 4, 6, 12 and 24 hours post-dose
|
|
Area Under the Concentration Versus Time Curve of BAY84-3174 for the Dosing Interval Divided by Dose per Body Weight (AUCtau,norm) After First Dose of BAY1067197
時間枠：Day 1: pre-dose and 0.5, 1, 2, 3, 4, 6, 12 and 24 hours post-dose
|
AUCtau,norm is defined as area under the plasma concentration time profile from time zero to the end of the dosing interval divided by dose per body weight after the first dose.
Dosing interval was 24 h for both arms.
Geometric mean and %CV were reported.
|
Day 1: pre-dose and 0.5, 1, 2, 3, 4, 6, 12 and 24 hours post-dose
|
協力者と研究者
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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1月28日
一次修了 (実際)
2015年1月29日
研究の完了 (実際)
2015年4月2日
試験登録日
最初に提出
2014年1月17日
QC基準を満たした最初の提出物
2014年1月17日
最初の投稿 (見積もり)
2014年1月20日
学習記録の更新
投稿された最後の更新 (実際)
2019年6月21日
QC基準を満たした最後の更新が送信されました
2019年6月19日
最終確認日
2019年6月1日
詳しくは
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。