The Effects of RPL554 in Addition to Tiotropium in COPD Patients
調査の概要
状態
条件
研究の種類
入学 (実際)
段階
- フェーズ2
参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
説明
Inclusion Criteria:
- Sign an informed consent document indicating they understand the purpose of and procedures required for the study and are willing to participate in the study.
- Male or female aged between 40 and 75 years inclusive, at the time of informed consent.
If male: must agree to meet the following from the first dose up to 1 month after the last dose of study treatment:
- Not donate sperm
- Either: be sexually abstinent in accordance with a patient's usual and preferred lifestyle (but agree to abide by the contraception requirements below should their circumstances change) Or: use a condom with all sexual partners. If the partner is of childbearing potential the condom must be used with spermicide and a second highly effective form of contraception must also be used
If female: either be:
Of non-childbearing potential defined as being:
- Either: post-menopausal (being spontaneously amenorrhoeic for at least 1 year with an appropriate clinical profile [e.g. age appropriate, history of vasomotor symptoms]
- Or: permanently sterilised e.g. tubal occlusion, hysterectomy, bilateral oophorectomy, bilateral salpingectomy
- Of childbearing potential and agreeing to use a highly effective method of contraception until completion of the end of study visit.
Have a 12-lead ECG recording at screening and randomisation (pre-dose in Treatment Period 1) showing the following:
- Heart rate between 45 and 90 beats per minute (bpm)
- QT interval corrected for heart rate using Fridericia's formula (QTcF) ≤450 msec for males and ≤470 ms for females
- QRS interval ≤120 msec
- No clinically significant abnormalities (as judged by the Investigator) including morphology (e.g. left bundle branch block, atrio-ventricular nodal dysfunction, ST segment abnormalities)
Have a screening Holter report with a minimum of 18 hours recording that is able to be evaluated for rhythm analysis which shows no abnormality which indicates a significant impairment of patient safety or which may significantly impairs interpretation in the opinion of the Investigator including:
- Significant arrhythmias including atrial flutter, atrial fibrillation, ventricular tachycardia
- Any symptomatic arrhythmia (except isolated extra systoles)
- Any sustained second or third degree heart block
- Capable of complying with all study restrictions and procedures including ability to use the study nebuliser and HandiHaler® DPI correctly.
- Body mass index (BMI) between 18 and 33 kg/m2 (inclusive) with a minimum weight of 45 kg.
- COPD diagnosis: Patients with a diagnosis of COPD as defined by the American Thoracic Society (ATS)/European Respiratory Society (ERS) guidelines (Celli and MacNee, 2004) with symptoms compatible with COPD for at least 1 year prior to screening.
Post-bronchodilator (four puffs of salbutamol) spirometry at screening:
- Post-bronchodilator forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) ratio of ≤0.70
- Post-bronchodilator FEV1 ≥40 % and ≤80% of predicted normal
- Demonstrates ≥150 mL increase from pre-bronchodilator FEV1
- Clinically stable COPD in the 4 weeks prior to screening and randomisation (pre-dose in Treatment Period 1).
- A chest X-ray (post-anterior) at screening, or in the 12 months prior to screening showing no abnormalities, which are both clinically significant and unrelated to COPD.
- Meet the concomitant medication restrictions and be expected to do so for the rest of the study.
- Smoking history of ≥10 pack years.
- Capable of withdrawing from long acting bronchodilators for the duration of the study, and short acting bronchodilators for 8 hours prior to spirometry.
Exclusion Criteria:
- A history of life-threatening COPD exacerbation including Intensive Care Unit admission and/or requiring intubation.
- COPD exacerbation requiring oral steroids, or lower respiratory tract infection requiring antibiotics, in the 3 months prior to screening or randomisation (pre-dose in Treatment Period 1).
- A history of one or more hospitalisations for COPD in the 12 months prior to screening or randomisation (pre-dose in Treatment Period 1).
- Lactation (female patients only).
- Positive urine or serum pregnancy test at screening, or a positive urine pregnancy test prior to randomisation (female patients of childbearing potential only).
- Prior exposure to RPL554 or known hypersensitivity to RPL554 or its components.
- Intolerance or hypersensitivity to tiotropium.
- Evidence of cor pulmonale.
- Other respiratory disorders: Patients with a current diagnosis of asthma, active tuberculosis, lung cancer, bronchiectasis, sarcoidosis, lung fibrosis, interstitial lung diseases, sleep apnoea, known alpha-1 antitrypsin deficiency or other active pulmonary diseases.
- Previous lung resection or lung reduction surgery.
- Use of oral COPD medications (e.g. oral steroids, theophylline and romifulast) in the 3 months prior to screening or randomisation (pre-dose in Treatment Period 1).
- History of, or reason to believe, a patient has drug or alcohol abuse within the past 3 years.
- Inability to perform technically acceptable spirometry or whole body plethysmography (at screening or randomisation [pre dose in Treatment Period 1])
- Received an experimental drug within 30 days or five half lives, whichever is longer.
- Patients with a history of chronic uncontrolled disease including, but not limited to, endocrine, active hyperthyroidism, neurological, hepatic, gastrointestinal, renal, haematological, urological, immunological, or ophthalmic diseases that the Investigator believes are clinically significant.
- Documented cardiovascular disease: arrhythmias, angina, recent or suspected myocardial infarction, congestive heart failure, a history of unstable, or uncontrolled hypertension, or has been diagnosed with hypertension in the 3 months prior to screening or randomisation.
- Concurrent use of non-cardioselective oral beta-blockers.
- Has had major surgery, (requiring general anaesthesia) in the 6 weeks prior to screening or randomisation (pre-dose in Treatment Period 1), or will not have fully recovered from surgery, or planned surgery through the end of the study.
- A disclosed history or one known to the Investigator, of significant non compliance in previous investigational studies or with prescribed medications.
- Requires oxygen therapy, even on an occasional basis.
- Clinically significant prostatic hyperplasia (judged by the Investigator) or bladder-neck obstruction or with narrow-angle glaucoma.
- Any other reason that the Investigator considers makes the patient unsuitable to participate.
研究計画
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:トリプル
武器と介入
参加者グループ / アーム |
介入・治療 |
---|---|
実験的:Lower Dose Nebulised Treatment
1.5 mg nebulised RPL554 twice daily plus 10 mcg tiotropium DPI once daily for 3 days
|
|
実験的:Higher Dose Nebulised Treatment
6 mg nebulised RPL554 twice daily plus 10 mcg tiotropium DPI once daily for 3 days
|
|
プラセボコンパレーター:Placebo
Nebulised RPL554 matched placebo twice daily plus 10 mcg tiotropium DPI once daily for 3 days
|
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 |
---|---|---|
Peak Forced Expired Volume in 1 Second (FEV1) on the Third Day of Dosing
時間枠:Day 3
|
Peak forced expired volume in 1 second (FEV1) over 4 hours on the third day of dosing
|
Day 3
|
Average FEV1 Over 12 Hours on the Third Day of Dosing
時間枠:Day 3
|
Average FEV1 area under the curve (AUC) over 12 hours on the third day of dosing
|
Day 3
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
---|---|---|
Peak FEV1 on Day 1
時間枠:Day 1
|
Peak FEV1 over 4 hours on Day 1
|
Day 1
|
Average FEV1 Over 12 Hours on Day 1
時間枠:Day 1
|
Average FEV1 AUC over 12 hours on Day 1
|
Day 1
|
協力者と研究者
スポンサー
出版物と役立つリンク
研究記録日
主要日程の研究
研究開始
一次修了 (実際)
研究の完了 (実際)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (見積もり)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
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。
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