Study of Oral Deucrictibant XR Tablet for Prophylaxis and Deucrictibant Soft Capsule for On-Demand Treatment of Angioedema Attacks in Adults With Acquired Angioedema Due to C1 Inhibitor Deficiency (CREAATE)
A Phase 3, Randomized, Double-blind, Placebo-controlled, 3-Part Study to Evaluate the Efficacy and Safety of Orally Administered Deucrictibant XR Tablet for Prophylaxis and Deucrictibant Soft Capsule for On-demand Treatment of Angioedema Attacks in Adults With Acquired Angioedema Due to C1 Inhibitor Deficiency
This is a Phase 3, multicenter, 3-part study, with 2 randomized, double-blind, placebo-controlled parts and an open-label extension part, to evaluate the efficacy and safety of orally administered deucrictibant XR tablet for prophylaxis, and deucrictibant soft capsule for on-demand treatment of angioedema attacks in adult participants aged ≥ 18 years with AAE-C1INH.
調査の概要
状態
詳細な説明
The study consists of a Screening Period, during which eligibility is confirmed, a Part 1 Prophylaxis Double-blind Treatment Phase, a Part 2 On-demand, Double-blind Treatment Phase, and a Part 3 On-demand Open-label Extension Phase. Approximately 24 participants will be randomized in Part 1 into 2 parallel arms for a treatment period of 12 weeks. During the prophylaxis treatment period participants will receive blinded study drug (deucrictibant 40 mg XR or placebo randomized in a 1:1 ratio). Upon completion of Part 1, participants will roll-over into Part 2. In addition to rollover participants completing Part 1, new deucrictibant treatment-naïve participants will be enrolled directly into Part 2 and this may occur while Part 1 is ongoing. During the on-demand period participants will receive blinded study drug (deucrictibant 20 mg soft capsule or matching placebo randomized in a 1:1 ratio, 2-period, 2-treatment crossover design) for 2 qualifying AAE-C1INH attacks. Participants completing Part 2 may roll over into Part 3 where all AAE-C1INH attacks will be treated with open-label deucrictibant 20 mg soft capsule.
研究の種類
入学 (推定)
段階
- フェーズ 3
連絡先と場所
研究連絡先
- 名前：Pharvaris Clinical Team
- 電話番号：0031-712-036-410
- メール：clinicaltrials@pharvaris.com
研究場所
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California
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San Diego、California、アメリカ、92093
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Walnut Creek、California、アメリカ、94598,
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Missouri
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St Louis、Missouri、アメリカ、63130
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Pennsylvania
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Hershey、Pennsylvania、アメリカ、17033
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Bristol、イギリス
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Cambridge、イギリス
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Leicester、イギリス
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London、イギリス
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Newcastle upon Tyne、イギリス
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Plymouth、イギリス
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Milan、イタリア
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- Study Site 1
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Milan、イタリア
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- Study Site 2
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Milan、イタリア
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- Study Site 3
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Padova、イタリア
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Roma、イタリア
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Amsterdam、オランダ
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Clayton、オーストラリア
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Vienna、オーストリア
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Edmonton、カナダ
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Basel、スイス
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Madrid、スペイン
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Ankara、トルコ（Türkiye）
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Berlin、ドイツ
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Frankfurt am Main、ドイツ
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Munich、ドイツ
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Auckland、ニュージーランド
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Budapest、ハンガリー
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Grenoble、フランス
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Lille、フランス
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Paris、フランス
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Sofia、ブルガリア
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Krakow、ポーランド
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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:
- Provision of written informed consent
- Male or female (sex at birth) aged ≥18 years
- Diagnosis of AAE-C1INH
- History of AAE-C1INH attacks prior to the Screening Visit.
- If underlying disease associated with AAE is present, the underlying disease must be stable throughout the duration of part 1.
- Reliable access and ability to use available therapy to effectively manage AAE- C1INH attacks.
- Female participants of childbearing potential must agree to the protocol-specified pregnancy testing and to be abstinent from heterosexual intercourse or to use an acceptable contraception method.
Females of non-childbearing potential (surgically sterile, or postmenopausal with ≥ 12 months amenorrhea and postmenopausal FSH confirmation) are not required to use contraception during the study.
• Capable of recording, without assistance, eDiary and ePRO data using an electronic device, as evidenced by the eDiary and ePRO training.
Exclusion Criteria:
- Participation in a clinical study with any other investigational drug within the last 30 days or within 5 half-lives of the investigational drug at the Screening Visit (whichever is longer).
- Receiving long-term prophylaxis (LTP) treatment for AAE-C1INH and satisfied with this treatment. Participants who are not satisfied (eg, tolerability issues, lack of efficacy) and have previously stopped LTP treatment for AAE-C1INH, for reasons other than participation in this study, can sign the ICF and begin the Screening Period only if their last dose of the treatment was received prior to the timepoint before the Screening Visit
- Any females who are pregnant, plan to become pregnant, or are currently breast-feeding
- Abnormal hepatic function
- Moderate or severe renal impairment
- Any clinically significant comorbidity or systemic dysfunction that would interfere with the participant's safety or ability to participate in the study.
- History of epilepsy and/or other significant neurological diseases
- Any clinically significant and uncontrolled gastrointestinal dysfunction that may impact study drug absorption
- Evidence of current alcohol or drug abuse
- Use of medications that are moderate and strong inhibitors of cytochrome P450 (CYP) 3A4, or strong inducers of CYP3A4 within the last 30 days or within 5 half-lives (whichever is longer) at the time of the Screening Visit
- Known hypersensitivity to deucrictibant or any of the excipients of the study drug
- Use of angiotensin-converting enzyme (ACE) inhibitors or any estrogen-containing medications with systemic absorption within 5 half-lives before the Screening Visit
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：4倍
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：パート1 - アーム1 - アクティブ
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Part 1: Deucrictibant 40 mg extended-release tablet for once daily oral use Part 2: Deucrictibant 20 mg soft capsule oral use Part 3: Deucrictibant 20 mg soft capsule oral use |
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プラセボコンパレーター：第1部 - アーム2 - プラセボ
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Part 1: Placebo Comparator tablet for once daily oral use Part 2: Placebo Comparator soft capsule oral use |
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実験的：パート2 - アーム1
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Part 1: Deucrictibant 40 mg extended-release tablet for once daily oral use Part 2: Deucrictibant 20 mg soft capsule oral use Part 3: Deucrictibant 20 mg soft capsule oral use Part 1: Placebo Comparator tablet for once daily oral use Part 2: Placebo Comparator soft capsule oral use |
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実験的：パート2 - アーム2
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Part 1: Deucrictibant 40 mg extended-release tablet for once daily oral use Part 2: Deucrictibant 20 mg soft capsule oral use Part 3: Deucrictibant 20 mg soft capsule oral use Part 1: Placebo Comparator tablet for once daily oral use Part 2: Placebo Comparator soft capsule oral use |
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実験的：パート3 - オープンラベル
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Part 1: Deucrictibant 40 mg extended-release tablet for once daily oral use Part 2: Deucrictibant 20 mg soft capsule oral use Part 3: Deucrictibant 20 mg soft capsule oral use |
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 |
時間枠 |
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Part 1: Time-normalized number of Investigator-confirmed AAE-C1INH attacks during Treatment Phase
時間枠：12 weeks
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12 weeks
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Part 2: Time to symptom relief, Patient Global Impression of Change (PGI-C) rating of at least "better"
時間枠：12 hours post-treatment
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12 hours post-treatment
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Part 3: Incidence of treatment-emergent adverse events (TEAEs), treatment-emergent adverse events of special interest (AESIs), and serious adverse events (SAEs)
時間枠：Through study termination, an average of 36 weeks
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Through study termination, an average of 36 weeks
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Part 3: Number of participants with clinically significant changes from baseline in Hematology parameters
時間枠：Through study termination, an average of 36 weeks
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Through study termination, an average of 36 weeks
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Part 3: Number of participants with clinically significant changes from baseline in Urinalysis parameters
時間枠：Through study termination, an average of 36 weeks
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Through study termination, an average of 36 weeks
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Part 3: Number of participants with clinically significant changes from baseline in Biochemistry parameters
時間枠：Through study termination, an average of 36 weeks
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Through study termination, an average of 36 weeks
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Part 3: Number of participants with clinically significant changes from baseline in vital signs
時間枠：Through study termination, an average of 36 weeks
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Through study termination, an average of 36 weeks
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Part 3: Number of participants with clinically significant changes from baseline in physical examinations
時間枠：Through study termination, an average of 36 weeks
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Through study termination, an average of 36 weeks
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Part 3: Number of participants with clinically significant changes in electrocardiogram (ECG)
時間枠：Through study termination, an average of 36 weeks
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Through study termination, an average of 36 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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Part 1: Proportion of participants who are AAE-C1INH attack-free during Treatment Phase
時間枠：12 weeks
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12 weeks
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Part 1: Time-normalized number of Investigator-confirmed AAE-C1INH attacks treated with on-demand medication during Treatment Phase
時間枠：12 weeks
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12 weeks
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Part 1: Time-normalized number of Investigator-confirmed moderate or severe AAE-C1INH attacks during Treatment Phase
時間枠：12 weeks
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12 weeks
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Part 1: Time-normalized number of Investigator-confirmed severe AAE-C1INH attacks during Treatment Phase
時間枠：12 weeks
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12 weeks
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Part 1: Proportion of participants achieving ≥50%, ≥70% and ≥90% reduction in AAE-C1NH attack rate relative to baseline during Treatment Phase
時間枠：12 weeks
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12 weeks
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Part 1: Incidence of TEAEs, treatment-emergent AESIs, and SAEs
時間枠：12 weeks
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12 weeks
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Part 1: Number of participants with clinically significant changes from baseline in Hematology parameters
時間枠：12 weeks
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12 weeks
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Part 1: Number of participants with clinically significant changes from baseline in Urinalysis parameters
時間枠：12 weeks
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12 weeks
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Part 1: Number of participants with clinically significant changes from baseline in Biochemistry parameters
時間枠：12 weeks
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12 weeks
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Part 1: Number of participants with clinically significant changes from baseline in Vital signs
時間枠：12 weeks
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12 weeks
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Part 1: Number of participants with clinically significant changes from baseline in physical examination
時間枠：12 weeks
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12 weeks
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Part 1: Number of participants with clinically significant changes from baseline in ECG parameters
時間枠：12 weeks
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12 weeks
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Part 1: Pre-dose plasma concentrations of Deucrictibant
時間枠：At Weeks 6 and 12
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Deucrictibant plasma concentrations will be analyzed using liquid chromatography-mass spectrometry/mass spectrometry methods |
At Weeks 6 and 12
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Part 1: Pre-dose plasma concentrations of deucrictibant metabolites
時間枠：At Weeks 6 and 12
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Deucrictibant metabolites plasma concentrations will be analyzed using liquid chromatography-mass spectrometry/mass spectrometry methods |
At Weeks 6 and 12
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Part 1: Pharmacokinetics [PK]: Urine concentrations of Deucrictibant and deucrictibant metabolites
時間枠：At Week 12
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At Week 12
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Part 1: Change from baseline in Angioedema Quality of Life (AE-QoL) questionnaire total score, functioning domain score, and fears/shame domain score
時間枠：Baseline (Day 1) and at Weeks 4, 8 and 12
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The AE-QoL is a short 17-item questionnaire designed to retrospectively assess HRQoL, with a recall period of 4 weeks. Its results can be displayed as a total score or as 4 domain scores. The scores range from 0 to 100, after linear transformation of raw values, with higher scores indicating higher HRQoL impairment. |
Baseline (Day 1) and at Weeks 4, 8 and 12
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Part 1: Change from baseline in Angioedema Control Test 4-week version (AECT-4wk)
時間枠：Baseline (Day 1) and at Week 12
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AECT-4wk measures disease control retrospectively, it comprises 4 questions over a 4-week recall period. Scores for the responses in the AECT range from 0 to 16, with higher scores indicating better disease control (≤ 9 poorly controlled; ≥ 10 well controlled) |
Baseline (Day 1) and at Week 12
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Part 1: Patient Global Assessment-Status (PGA-S) at baseline
時間枠：At Baseline (Day 1)
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PGA-Status assesses on a 5-point scale how the participant's QoL has been impacted by AAE-C1INH since start taking the study drug |
At Baseline (Day 1)
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Part 1: Patient Global Assessment of Change (PGA-Change) at Week 12
時間枠：At Week 12
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PGA-Change assesses on a 5-point scale how the participant's QoL has been impacted by AAE-C1INH since start taking the study drug |
At Week 12
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Part 1: Change from baseline in EuroQol 5 Dimension 5 level (EQ 5D 5L)
時間枠：Baseline (Day 1) and at Week 12
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EQ 5D 5L is a brief, multiattribute, generic, health status measure composed of 5 questions with Likert response options (descriptive system) and a visual analog scale (EQ-VAS). The latter asks patients to rate their own health from 0 to 100 (the worst and best imaginable health, respectively) |
Baseline (Day 1) and at Week 12
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Part 2: Time to complete symptom resolution, Patient Global Impression of Severity (PGI-S) rating of "no symptoms
時間枠：sustained within 24 hours post-treatment
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sustained within 24 hours post-treatment
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Part 2: Time to symptom relief defined as PGI-S rating of at least 1 point reduction
時間枠：12 hours post-treatment
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12 hours post-treatment
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Part 2: Proportion of study drug-treated attacks achieving complete symptom resolution defined as achieving PGI- S rating of "no symptoms"
時間枠：At 24 hours post-treatment
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At 24 hours post-treatment
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Part 2: Time to onset of symptom relief, defined as PGI-C rating of at least "a little better"
時間枠：Within 12 hours post-treatment
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Within 12 hours post-treatment
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Part 2: Time to End of Progression (EoP) in attack symptoms
時間枠：Within 12 hours post-treatment
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EOP is defined as the earliest post-treatment timepoint after which all subsequent PGI-C ratings are stable or improved |
Within 12 hours post-treatment
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Part 2: Incidence of TEAEs, treatment-emergent AESIs, and SAEs
時間枠：Up to 24 weeks
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Up to 24 weeks
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Part 2: Number of participants with clinically significant changes from baseline in Hematology parameters
時間枠：24 weeks
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24 weeks
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Part 2: Number of participants with clinically significant changes from baseline in Urinalysis parameters
時間枠：24 weeks
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24 weeks
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Part 2: Number of participants with clinically significant changes from baseline in Biochemistry parameters
時間枠：24 weeks
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24 weeks
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Part 2: Number of participants with clinically significant changes from baseline in Vital signs
時間枠：24 weeks
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24 weeks
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Part 2: Number of participants with clinically significant changes from baseline in physical examination
時間枠：24 weeks
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24 weeks
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Part 2: Number of participants with clinically significant changes from baseline in ECG parameters
時間枠：24 weeks
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24 weeks
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Part 2: Pharmacokinetics [PK]: Deucrictibant and deucrictibant metabolites plasma concentration-time profiles
時間枠：Day 1
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Day 1
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Part 3: Time to symptom relief, as PGI-C rating of at least "better"
時間枠：12 hours post-treatment
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12 hours post-treatment
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Part 3: Time to symptom relief, as PGI-S rating of at least 1 point reduction
時間枠：12 hours post-treatment
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12 hours post-treatment
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Part 3: Proportion of study drug-treated attacks achieving complete symptom resolution, defined as achieving PGI-S rating of "no symptoms"
時間枠：24 hours post-treatment
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24 hours post-treatment
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協力者と研究者
捜査官
- スタディディレクター：Study Director, Pharvaris、Pharvaris Netherlands B.V.
研究記録日
主要日程の研究
研究開始 (実際)
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
追加の関連 MeSH 用語
その他の研究ID番号
- PHA022121-C308
医薬品およびデバイス情報、研究文書
米国FDA規制医薬品の研究
米国FDA規制機器製品の研究
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