Multicenter, Open Label Trial to Investigate the Efficacy and Safety of a Single Oral Dose of 1.0 mg/kg Macimorelin Acetate as Growth Hormone Stimulation Test (GHST) in Pediatric Patients With Suspected Growth Hormone Deficiency (GHD)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 101
- 试验地点
- 45
- 主要终点
- Area under the Receiver Operator Characteristic curve (ROC AUC) based on GH concentration during GHST following macimorelin administration
研究概览
简要总结
This research study will find out if a new growth hormone stimulation test is safe and works as well as other tests to diagnose growth hormone deficiency (GHD) in children. The stimulation test will use a new growth hormone stimulating substance called macimorelin. By now, only adults in the USA can get this new stimulation test. The results of this study are expected to help children and teenagers with suspected GHD to get the macimorelin stimulation test.
The macimorelin test will be compared to a clonidine and an arginine test. Both are known standard stimulation tests. Altogether two macimorelin tests are planned to be performed in the study, to show how repeatable macimorelin tests results are (under a set of similar conditions).
详细描述
Each study participant (patient) will have 5 to 6 visits in total with the study doctor.
The study will last for about 1 to 4 months, dependent on how close the visits are done. At the visits 2, 3, 4 and 5, the patient will get a stimulation test done and blood samples will be taken. At those 4 visits, the patient will have either to drink a macimorelin drink, take some clonidine tablets or get an arginine infusion. In total, the patient will get 2 macimorelin, 1 clonidine and 1 arginine test done. The level of growth hormone (GH) will be measured 4 times during the clonidine and during the arginine test and 5 times during the macimorelin test. After the test, questions on the test tolerability will be captured from patients and parents. After the arginine test, a urine dipstick test is to be done by the patient at home.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Diagnostic
- 盲法
- Single (Outcomes Assessor)
盲法说明
This study is open label. Masking is performed with regard to the GHST results (i.e. growth hormone (GH) values).
GH values from all GHSTs will be assessed centrally by a central lab: GH values following the two standard GHSTs at V3 and V4 will not be disclosed to the trial site prior to the end of V5 (i.e., the second macimorelin GHST). To avoid bias in the final diagnostic assessments by the investigators, macimorelin pharmacodynamic (PD) data will remain blinded to the trial sites, clinical research associates (CRAs), and trial management at contract research organization (CRO) and Sponsor until trial closure.
An Independent Adjudication Committee (IAC) is established to perform ongoing blinded adjudication of subjects' growth hormone deficiency status. The IAC will adjudicate in a consistent manner by use of pre-defined definitions and guidelines.
入排标准
- 年龄范围
- 2 Years 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Informed consent of subject, parent(s) or legally acceptable representative (LAR) of subject and child assent, if appropriate, must be obtained before any trial-related activities. Trial-related activities are any procedures that are carried out as part of the trial, including activities to determine suitability for the trial.
- •Male and female pediatric subjects from 2 to less than 18 years of age at the time of signing informed consent.
- •Indication for the performance of growth hormone stimulation test.
- •Presence of a height measurement minimum 6 and maximum 18 months prior to screening.
排除标准
- •Established diagnosis of a disease that is sufficient to explain growth deficiency or metabolic disorders that are also associated with short stature (e.g., Turner syndrome, skeletal dysplasia's, celiac disease, etc.).
- •Ongoing growth hormone therapy.
- •Presence of hypothyroidism and/or adrenal insufficiency without adequate and stable replacement therapy treatment for at least 30 days prior to first GHST.
- •Treatment with drugs directly affecting the pituitary secretion of somatotropin (e.g., somatostatin analogues, clonidine, levodopa and dopamine agonists) or provoking the release of somatostatin (antimuscarinic agents e.g., atropine).
- •Medical history of ongoing clinically symptomatic psychiatric disorders.
- •2nd or 3rd degree atrioventricular-block, prolongation of the QRS complex over 120 milliseconds, prolongation of the QTc interval over 450 milliseconds, or any other clinically significant abnormal electrocardiogram results at the V2 pre-dose electrocardiogram (ECG) as judged by the investigator.
- •Previous participation in this trial. Participation is defined as signed informed consent.
- •Participation in any clinical trial of an approved or non-approved investigational medicinal product within 30 days before screening.
- •Known or suspected hypersensitivity to trial product(s) or related products;
- •Any disorder, which in the investigator's opinion might jeopardize subject's safety or compliance with the protocol.
- •Concomitant treatment with any drugs that might prolong QT/QTc Note: A subject who receives such treatment will not be a candidate for this study, if his/her condition does not allow for a treatment-free period of at least 5 elimination half-lives of the drug that might prolong QT/QTc before the GHST;
- •Elevation of laboratory parameters indicating hepatic or renal dysfunction or damage (aspartate amino transferase (AST), alkaline phosphatase (ALT), gamma-glutamyl transferase (GGT) > 2.5 x upper limit of normal (ULN); creatinine or bilirubin > 1.5x ULN);
- •Current active malignancy other than non-melanoma skin cancer;
- •Female of child-bearing potential and not using an adequate contraceptive method (adequate contraceptive measures as required by local regulation or practice).
- •Male of reproductive age who or whose partner(s) is not using an adequate contraceptive method (adequate contraceptive measures as required by local regulation or practice).
- •Lack of ability or willingness to give informed consent by the subject and/or his/her legal representative;
- •Anticipated non-availability for trial visits/procedures.
研究组 & 干预措施
standard GHST order randomized: arginine - clonidine
At visit 2 (V2), all subjects will perform the macimorelin GHST and will be randomized 1:1 to the order of the clonidine and arginine GHSTs at visit 3 (V3) and visit 4 (V4).
In this arm, those subjects will be presented which will have been randomized to the arginine GHST at V3 and the clonidine GHST at V4.
At visit 5 (V5) all subjects will perform the macimorelin GHST.
干预措施: Macimorelin (Drug)
standard GHST order randomized: arginine - clonidine
At visit 2 (V2), all subjects will perform the macimorelin GHST and will be randomized 1:1 to the order of the clonidine and arginine GHSTs at visit 3 (V3) and visit 4 (V4).
In this arm, those subjects will be presented which will have been randomized to the arginine GHST at V3 and the clonidine GHST at V4.
At visit 5 (V5) all subjects will perform the macimorelin GHST.
干预措施: Arginine (Diagnostic Test)
standard GHST order randomized: arginine - clonidine
At visit 2 (V2), all subjects will perform the macimorelin GHST and will be randomized 1:1 to the order of the clonidine and arginine GHSTs at visit 3 (V3) and visit 4 (V4).
In this arm, those subjects will be presented which will have been randomized to the arginine GHST at V3 and the clonidine GHST at V4.
At visit 5 (V5) all subjects will perform the macimorelin GHST.
干预措施: Clonidine (Diagnostic Test)
standard GHST order randomized: clonidine - arginine
At V2, all subjects will perform the macimorelin GHST and will be randomized 1:1 to the order of the clonidine and arginine GHSTs at V3 and V4.
In this arm, those subjects will be presented which will have been randomized to the clonidine GHST at V3 and to the arginine GHST at V4.
At V5 all subjects will perform the macimorelin GHST.
干预措施: Macimorelin (Drug)
standard GHST order randomized: clonidine - arginine
At V2, all subjects will perform the macimorelin GHST and will be randomized 1:1 to the order of the clonidine and arginine GHSTs at V3 and V4.
In this arm, those subjects will be presented which will have been randomized to the clonidine GHST at V3 and to the arginine GHST at V4.
At V5 all subjects will perform the macimorelin GHST.
干预措施: Arginine (Diagnostic Test)
standard GHST order randomized: clonidine - arginine
At V2, all subjects will perform the macimorelin GHST and will be randomized 1:1 to the order of the clonidine and arginine GHSTs at V3 and V4.
In this arm, those subjects will be presented which will have been randomized to the clonidine GHST at V3 and to the arginine GHST at V4.
At V5 all subjects will perform the macimorelin GHST.
干预措施: Clonidine (Diagnostic Test)
结局指标
主要结局
Area under the Receiver Operator Characteristic curve (ROC AUC) based on GH concentration during GHST following macimorelin administration
时间窗: Derived from Cmax GH measurements collected in the time frame from 0 to 90 minutes after initial macimorelin GHST (visit 2 (day 0)) and GH adjudication status performed by the adjudication committee after visit 4 (between day 11 and day 58)).
Assuming the outcome of GHD status adjudication final clinical diagnosis as the "true" GHD status, the diagnostic efficacy (estimated sensitivity, specificity, misclassification) of the macimorelin GHST will be based on the area under the receiver operating characteristic curve (ROC AUC).
次要结局
- Sensitivity for the macimorelin GHST(Derived from Cmax GH measurements collected in the time frame from 0 to 90 minutes after initial macimorelin GHST (visit 2 (day 0)) and GH adjudication status performed by the adjudication committee after visit 4 (between day 11 and day 58)).)
- Specificity for the macimorelin GHST(Derived from Cmax GH measurements collected in the time frame from 0 to 90 minutes after initial macimorelin GHST (visit 2 (day 0)) and GH adjudication status performed by the adjudication committee after visit 4 (between day 11 and day 58)).)
- Overall agreement between the outcome of the macimorelin GHST and the combined outcome from the 2 standard GHSTs(Visit 4 (between day 11 and day 58))