Study of Treprostinil Administered Via Soft Mist Inhaler (SMI) in Participants With Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease (PH-COPD) (SUMMIT 201)
A Multicenter, Randomized, Double-blind, Placebo-controlled, Phase 2 Study to Evaluate the Safety and Tolerability of Treprostinil Administered Via a Soft Mist Inhaler (SMI) in Participants With Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease (PH-COPD)
The primary purpose of this study is to evaluate the safety and tolerability of treprostinil administered with a soft mist inhaler (SMI) over 16 weeks in approximately 40 participants with PH-COPD.
調査の概要
状態
詳細な説明
SMI-PH-201 is a Phase 2, randomized, double-blind, placebo-controlled, parallel-group, multicenter, safety and tolerability study with secondary endpoints evaluating the efficacy of the study drug on exercise capacity and NT-proBNP.
Eligible participants will be randomly assigned 1:1 to treprostinil SMI or placebo at the Baseline Visit and receive study drug over a 16-week period. Participants will return to the clinic for follow-up visits at Weeks 4, 8, 12, 15, and 16.
Study drug will be administered via a combination drug-device product that consists of the SMI with an associated cartridge containing a propellant-free, liquid-based formulation of treprostinil inhalation spray. Participants will receive study drug in multi-use cartridges containing either treprostinil (in concentrations of 1.34, 2.68, 4.02, and 5.36 mg/mL) or placebo.
研究の種類
入学 (推定)
段階
- フェーズ2
連絡先と場所
研究連絡先
- 名前：United Therapeutics Global Medical Information
- 電話番号：919-485-8350
- メール：clinicaltrials@unither.com
研究場所
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Alabama
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Birmingham、Alabama、アメリカ、35233
- University of Alabama at Birmingham, Lung Health Center
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Arizona
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Phoenix、Arizona、アメリカ、85006
- Banner University Medical Center Phoenix
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Tucson、Arizona、アメリカ、85719
- University of Arizona/Banner Health
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California
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Palo Alto、California、アメリカ、94305
- Stanford Health Care
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San Francisco、California、アメリカ、94143
- University of California San Francisco Medical Center
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Illinois
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Chicago、Illinois、アメリカ、60637
- University of Chicago Medical Center
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Kentucky
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Lexington、Kentucky、アメリカ、40536
- University of Kentucky
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Massachusetts
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Boston、Massachusetts、アメリカ、02115
- Brigham and Women's Hospital
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Boston、Massachusetts、アメリカ、02114
- Massachusetts General Hospital
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Michigan
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Detroit、Michigan、アメリカ、48202
- Henry Ford Health System
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North Carolina
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Chapel Hill、North Carolina、アメリカ、27514
- University of North Carolina at Chapel HIll
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Pennsylvania
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Philadelphia、Pennsylvania、アメリカ、19140
- Temple University Hospital
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Pittsburgh、Pennsylvania、アメリカ、15213
- University of Pittsburgh Medical Center
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South Carolina
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Charleston、South Carolina、アメリカ、29425
- Medical University of South Carolina
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Texas
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Dallas、Texas、アメリカ、75246
- Baylor University Medical Center
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Virginia
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Falls Church、Virginia、アメリカ、22042
- Inova Fairfax Hospital
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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:
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Give voluntary informed consent to participate in the study
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Are ≥18 years of age, inclusive, at the time of signing informed consent
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Willing to undergo right heart catheterization (RHC) during Screening. A RHC performed within 12 months prior to the Baseline Visit is acceptable for determining eligibility, even if done without oxygen or vasodilator challenge, and repeat RHC is not required. The following parameters must be documented for eligibility:
- Pulmonary vascular resistance ≥4 Wood units
- Pulmonary capillary wedge pressure or left ventricular end diastolic pressure ≤15 mmHg
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Diagnosis of PH-COPD (WHO Group 3) with the following documented parameters at Screening:
- FEV1 ≥35%
- FEV1/FVC <70%
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Resting SpO2 ≥90%, with or without supplemental oxygen by any mode of delivery and supplemental O2 ≤8 L/min at rest at Screening
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If on chronic COPD medication, must be on a stable and optimized dose for ≥45 days prior to the Baseline Visit
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Women of childbearing potential (WOCBP) must be nonpregnant (as confirmed by a pregnancy test at Screening and Baseline) and nonlactating and agree to use 1 of the following:
- Abstain from penile-vaginal intercourse (when it is in line with their preferred and usual lifestyle) OR
- Use medically acceptable, highly effective contraception for the duration of the study and at least 30 days after discontinuing study drug. Medically acceptable, highly effective forms of contraception include approved hormonal contraceptives (oral, injectable, transdermal, intravaginal, and implantable), hormonal or non-hormonal intrauterine devices or systems, or monogamous intercourse with a partner who has undergone vasectomy. Barrier methods alone or with spermicide may be considered with Sponsor approval if they have a proven track record of excellent compliance. Note: Women who are successfully sterilized (including hysterectomy, bilateral salpingectomy, bilateral tubal occlusion, or bilateral oophorectomy) or postmenopausal (defined as amenorrhea for at least 12 consecutive months and >50 years of age or in the documented clinical opinion of a Women's Health Specialist) are not considered to be WOCBP for study purposes.
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Males with a partner of childbearing potential must agree to use a condom for the duration of treatment and for at least 48 hours after discontinuing study drug
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In the opinion of the Investigator, able to communicate effectively with study site staff, and considered reliable, willing, and likely to be cooperative with protocol requirements, including attending all study visits
Exclusion Criteria:
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6MWD <150 meters during Screening
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DLCO ≤25% during Screening
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Pregnant or lactating
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Known intolerance or significant lack of efficacy to a prostacyclin or prostacyclin analogue that resulted in discontinuation or inability to effectively titrate that therapy
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Confirmed diagnosis of PAH or PH for any reason other than associated with COPD
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Received any PAH-approved therapy within 60 days prior to Baseline. As needed (PRN) use of a PDE5-I (eg, sildenafil, tadalafil, vardenafil) for erectile dysfunction is permitted. Daily use of a PDE5-I, even if for an indication other than PH, is not allowed.
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Unable or unwilling to use Sponsor-provided devices (eg, SMI)
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Confirmed diagnosis of idiopathic pulmonary fibrosis, combined pulmonary fibrosis and emphysema, diffuse parenchymal lung disease, or interstitial lung disease. Redacted computed tomography scan results conducted within 6 months prior to Baseline must be provided to the Sponsor's Medical Monitor with the Pre Baseline Form to confirm eligibility.
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Previous diagnosis of homozygous alpha-1 antitrypsin deficiency
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Myocardial infarction within 6 months prior to Baseline or unstable angina within 30 days prior to Baseline
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Evidence of clinically significant left-sided heart disease (including, but not limited to, left ventricular ejection fraction <40% and/or left ventricular hypertrophy) or clinically significant cardiologic conditions, such as congestive heart failure, coronary artery disease, or valvular heart disease. Note: Participants with abnormal left ventricular function attributable to the effects of right ventricular overload will not be excluded, but a discussion with and approval by the Sponsor's Medical Monitor is required.
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Any form of congenital heart disease (repaired or unrepaired) other than a patent foramen ovale
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Recent exacerbation of COPD and/or active pulmonary or upper respiratory infection that required hospitalization, symptomatic treatment, or treatment with antibiotics and/or corticosteroids:
- If hospitalized, within 180 days prior to Baseline
- If not hospitalized, within 90 days prior to Baseline
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Initiation of pulmonary rehabilitation within 12 weeks prior to Baseline or, in the opinion of the Investigator, pulmonary rehabilitation is likely to be needed during the Treatment Period
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Use of any other investigational drug/device or participation in any investigational study in which the participant received a medical intervention (ie, procedure, device, medication/supplement) within 30 days prior to Baseline. Participation in non-interventional, observational, or registry studies is permitted.
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In the opinion of the Investigator, the participant has any condition that would interfere with the interpretation of study assessments, study participation or cooperation, or has any disease or condition (ie, peripheral vascular disease, musculoskeletal disorder, morbid obesity) that would likely be the primary limit to ambulation (as opposed to PH)
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：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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実験的：treprostinil SMI
Inhaled treprostinil administered via a SMI at concentrations of 1.34, 2.68, 4.02, and 5.36 mg/mL |
Inhaled treprostinil administered via a SMI four times daily in concentrations of 1.34, 2.68, 4.02, and 5.36 mg/mL |
|
プラセボコンパレーター：placebo
Inhaled placebo administered via a SMI |
Placebo administered via a SMI |
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 |
|---|---|---|
|
Incidence of serious adverse events, severe adverse events, cardiopulmonary hospitalizations, and deaths
時間枠：16 weeks
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Number and type of serious adverse events, severe adverse events, cardiopulmonary hospitalizations, and deaths observed in participants during and after use of inhaled treprostinil and placebo. |
16 weeks
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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Change in peak 6-Minute Walk Distance (6MWD) from baseline to Week 16
時間枠：16 weeks
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The intent of the 6MWD test is to evaluate exercise capacity associated with carrying out activities of daily living. Change in 6MWD from baseline to Week 16 correlates with the current clinical standard for assessing patient functional status in the treatment of PH and is considered an objective measure of patient functional status. Participants will be instructed to walk down a corridor at a comfortable speed as far as they can manage for six minutes. Peak exposure 6MWD will occur by conducting the 6-minute walk test within 10 to 60 minutes after the most recent dose of study drug. |
16 weeks
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Change in trough 6MWD from baseline to Week 15
時間枠：15 weeks
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The intent of the 6MWD test is to evaluate exercise capacity associated with carrying out activities of daily living. Change in 6MWD from baseline to Week 15 correlates with the current clinical standard for assessing patient functional status in the treatment of PH and is considered an objective measure of patient functional status. Participants will be instructed to walk down a corridor at a comfortable speed as far as they can manage for six minutes. Trough exposure 6MWD will occur by conducting 6-minute walk test at least four hours after the most recent study drug dose. |
15 weeks
|
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Change in N-terminal pro-brain natriuretic peptide (NT-proBNP) from baseline to Week 16
時間枠：16 weeks
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The NT-proBNP serum concentration is a useful biomarker associated with changes in right heart morphology and function. NT-proBNP serum concentration will be assessed to compare the severity of heart failure at baseline and Week 16. |
16 weeks
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Change in overall adverse events
時間枠：16 weeks
|
The incidence of adverse events among participants throughout the 16-week study will be measured by the number of participants analyzed and the percentage of those participants who experienced an adverse event. |
16 weeks
|
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Change in Forced Expiratory Volume in One Second (FEV1) as % predicted
時間枠：16 weeks
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FEV1 is a standard indicator of lung function and measures the maximal amount of air forcefully exhaled in 1 second. |
16 weeks
|
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Change in Forced Vital Capacity (FVC) in mL
時間枠：16 weeks
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FVC is a standard indicator of lung function and measures the amount of air a person can forcefully and quickly exhale after taking a deep breath. |
16 weeks
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Change in FEV1/FVC ratio
時間枠：16 weeks
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The FEV1/FVC ratio measures how much air is exhaled in one second compared to a full breath. This helps determine if the lung condition is restrictive or obstructive and its severity. |
16 weeks
|
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Change in Total Lung Capacity (TLC) in mL
時間枠：16 weeks
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TLC is a standard indicator of lung function and measures the maximum volume of lung capacity after very deep inhalation. |
16 weeks
|
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Change in Lung Diffusion Capacity (DLCO) as % predicted
時間枠：16 weeks
|
DLCO is a standard indicator of lung function and measures how well oxygen moves from the lungs to the blood. |
16 weeks
|
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Change in the saturation of peripheral capillary oxygenation (SpO2)
時間枠：16 weeks
|
Pulse oximetry will measure SpO2 as a percentage, indicating hypoxemia and respiratory distress. |
16 weeks
|
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Change in supplemental oxygen use
時間枠：16 weeks
|
Supplemental oxygen use, as measured in L, indicates chronic hypoxemia. |
16 weeks
|
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Change in 12-lead electrocardiogram (ECG)
時間枠：16 weeks
|
The 12-lead ECG measures electrical cardiac activity, including heart rate and rhythm (PR interval, QT interval, QT interval corrected for heart rate by Fridericia's formula, and QRS duration). |
16 weeks
|
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Incidence of acute exacerbations of COPD
時間枠：16 weeks
|
An acute exacerbation of COPD is defined as an event characterized by increased dyspnea and/or cough and sputum that worsens in <14 days, which may be accompanied by tachypnea and/or tachycardia, and is often associated with increased local and systemic inflammation caused by infection, pollution, or other insult to the airways. For this study, the following diagnostic criteria will be used to support a diagnosis of acute COPD exacerbation:
|
16 weeks
|
協力者と研究者
スポンサー
研究記録日
主要日程の研究
研究開始 (推定)
一次修了 (推定)
研究の完了 (推定)
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 (実際)
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
本研究に関する用語
キーワード
その他の研究ID番号
- SMI-PH-201
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