EUCTR2015-004876-31-GB进行中（未招募）1 期
An open-label, single arm study to investigate the safety, pharmacokinetics and pharmacodynamics of repeat doses of inhaled nemiralisib in patients with APDS/PASLI
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 20
研究概览
简要总结
暂无简介。
研究设计
- 研究类型
- Interventional clinical trial of medicinal product
入排标准
- 性别
- All
入选标准
- •A subject will be eligible for inclusion in this study only if all of the following criteria apply:
- •1. Male and female subjects aged 18 or older at the time of signing the informed consent.
- •TYPE OF SUBJECT AND DIAGNOSIS INCLUDING DISEASE SEVERITY
- •2. Patients with a clinical phenotype consistent with APDS, including a history of recurrent (frequency greater than would be expected in an immunocompetent individual) ear, sinus or pulmonary infections, and who have a known type 1 APDS associated genetic PI3Kdelta mutation (e.g. E1021K, N334K, E525K and C416R) or type 2 APDS-associated mutation
- •3. Body weight =40 kg and body mass index (BMI) =17kg/m2 (inclusive)
- •4. Female subject. A female subject is eligible to participate if she is not pregnant (as confirmed by a negative urine human chorionic gonadotrophin (hCG) test), not lactating, and at least one of the following conditions applies:
- •- Non-reproductive potential defined as:
- •o Pre-menopausal females with one of the following:
- •– Documented tubal ligation
- •– Documented hysteroscopic tubal occlusion procedure with followup confirmation of bilateral tubal occlusion
- •– Hysterectomy
- •– Documented Bilateral Oophorectomy
- •o Postmenopausal defined as 12 months of spontaneous amenorrhea [in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) and estradiol levels consistent with menopause (refer to laboratory reference ranges for confirmatory levels)]. Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the highly effective contraception methods if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrolment.
- •- Reproductive potential and agrees to follow one of the options listed in the Modified List of Highly Effective Methods for Avoiding Pregnancy in Females of Reproductive Potential (FRP) (see Appendix 5 of the study protocol) from 30 days prior to the first dose of study medication and until completion of the follow-up telephone call at 1-2 weeks from last dose.
- •The investigator is responsible for ensuring that subjects understand how to properly use these methods of contraception.
- •INFORMED CONSENT
- •5. Capable of giving signed informed consent as described in Section 10.2 of the study protocol which includes compliance with the requirements and restrictions listed in the consent form and in this protocol’.
- •Are the trial subjects under 18? no
- •Number of subjects for this age range:
- •F.1.2 Adults (18-64 years) yes
- •F.1.2.1 Number of subjects for this age range 19
- •F.1.3 Elderly (>=65 years) yes
- •F.1.3.1 Number of subjects for this age range 1
排除标准
- •A subject will not be eligible for inclusion in this study if any of the following criteria apply:
- •CONCURRENT CONDITIONS/MEDICAL HISTORY (INCLUDES LIVER
- •FUNCTION AND QTc INTERVAL)
- •1. Alanine aminotransferase (ALT) >2xULN and bilirubin >1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
- •2. Current or chronic history of liver disease except where hepatomegaly is identified by their clinician to be secondary to APDS, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
- •3. QTc > 450 millisecond (msec) or QTc > 480 msec in subjects with Bundle Branch Block
- •NOTES: The QTc is the QT interval corrected for heart rate (HR) according to Bazett’s formula (QTcB), Fridericia’s formula (QTcF), and/or another method, machineread or manually over-read.
- •The specific formula that will be used to determine eligibility and discontinuation for an individual subject should be determined prior to initiation of the study. In other words, several different formulae cannot be used to calculate the QTc for an individual subject and then the lowest QTc value used to include or discontinue the subject from the trial.
- •For purposes of data analysis, QTcB, QTcF, another QT correction formula, or a composite of available values of QTc will be used as specified in the Reporting and Analysis Plan (RAP).
- •4. A subject with a clinical abnormality or laboratory parameter(s) which is/are not specifically listed in the inclusion or exclusion criteria, outside the reference range for the population being studied may be included only if the investigator, in consultation with the Medical Monitor if required, agree and document that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
- •CONCOMITANT MEDICATIONS
- •5. CYTOCHROME P450 3A4:
- •Strong CYP3A4 substrates:
- •Strong inhibitors of cytochrome P450 3A4: Currently, only limited in vivo information is available on the in vivo metabolism of nemiralisib; and, the role of
- •cytochrome P450s (CYPs) in the elimination of nemiralisib is based upon in vitro data. In vitro studies indicate that nemiralisib is predominantly metabolised by CYP3A4 enzymes with minor contributions from CYP1A1, CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP2D6 and CYP2J2. Co-administration of nemiralisib with
- •CYP3A4 inhibitors may result in increased systemic exposure to nemiralisib.
- •Regular or chronic treatment with medications that are considered strong inhibitors
- •of CYP3A4 are not permitted:
- •Antiretrovirals including protease inhibitors (e.g., indinavir, nelfinavir,ritonavir, saquinavir, atazanavir)
- •Oral antifungal treatments such as ketoconazole and itraconazole. Short courses of up to 14 days are allowed for fluconazole and voriconazole,but chronic
- •administrations are not permitted. It is recommended that amphotericin or posaconazole are used as oral antifungal treatment of choice.
- •Antibiotics such as telithromycin and troleandomycin (macrolide). Short courses up to 14 days are allowed for mibefradil (calcium channel blocker), erythromycin
- •and clarithromycin (including intravenous clarithromycin) but chronic administrations are not permitted. Azithromycin may be used chronically and is
- •recommended as the macrolide antibiotic of choice.
- •Anti-epileptic treatments; and anti-tuberculous therapy.
- •These medications must all have been stopped at least 14 days prior to fir
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