Diagnosis of Growth Hormone Deficiency MedDRA version: 20.0 Level: LLT Classification code 10073227 Term: Growth hormone stimulation test System Organ Class: 100000004848
Conditions
Interventions
Trade Name: Macrilen
Product Name: macimorelin
Pharmaceutical Form: Granules for oral suspension
INN or Proposed INN: macimorelin
CAS Number: 381231-18-1
Current Sponsor code: AEZS-130
Other descripti
Sponsors
Aeterna Zentaris GmbH
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female pediatric patients from 2 to less than 18 years of age; 2. Suspected GHD based on auxological and clinical criteria; 3. Indication for the performance of provocative GHST 4. A subject with sex steroid priming prior to GHSTs that are part of the standard diagnostic procedures must also have sex steroid priming for the macimorelin GHST. Are the trial subjects under 18? yes Number of subjects for this age range: 24 F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Lack of suitability for the trial: 1. Established diagnosis of a disease that is sufficient to explain growth deficiency or metabolic disorders that are also associated with GHD (e.g. Turner syndrome, skeletal dysplasias, malnutrition, etc.); 2. Ongoing GH therapy; 3. Subjects with a medical history and clinical signs of a not adequately treated thyroid dysfunction, or subjects who had a change in thyroid therapy within 30 days prior to anticipated macimorelin test day; 4. Untreated hypogonadism or not on a stable substitution treatment within 30 days prior to the anticipated macimorelin test day; 5. 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 (atropine); 6. Concomitant use of a CYP3A4 inducer (e.g. carbamazepine, phenobarbital, phenytoin, pioglitazone, rifabutin, rifampin, St. John's Wort); 7. Concomitant use of a CYP3A4 inhibitor; 8. Medical history of ongoing clinically symptomatic psychiatric disorders; 9. Cushing disease or subjects on supraphysiologic glucocorticoid therapy within 30 days prior to the anticipated macimorelin test day; 10. Participation in a trial with any investigational drug within 30 days prior to trial entry; 11. Vigorous physical exercise within 24 hours prior to the macimorelin test dose. Safety concerns: 12. Known hypersensitivity to any of the constituents of the macimorelin preparation; 13. Prolonged ECG QT interval, defined as QTc > 500 msec; 14. Concomitant treatment with any drugs that might prolong QT/QTc (see list of drugs at http://www.torsades.org/medical-pros/drug-lists/printable-drug-list.cfm 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; 15. Elevation of laboratory parameters indicating hepatic or renal dysfunction or damage (AST, ALT, GGT > 2.5 x ULN; creatinine or bilirubin > 1.5x ULN); 16. Current active malignancy other than non-melanoma skin cancer; 17. Girls of childbearing age without effective contraception, defined as hormonal contraception or use of condom (male or female) and spermicides or use of diaphragm and spermicides or Intra Uterine Device (IUD). Administrative reasons: 18. Lack of ability or willingness to give informed consent by the subject and/or his/her legal representative; 19. Anticipated non-availability for trial visits/procedures.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To investigate the safety and tolerability of macimorelin acetate after ascending single oral doses of macimorelin in pediatric patients with suspected GHD.;Secondary Objective: - To investigate the pharmacokinetics (PK) of macimorelin acetate in pediatric subjects with suspected GHD; -To investigate the pharmacodynamics (PD) of macimorelin acetate as measured by growth hormone (GH) release in pediatric subjects with suspected GHD; - To explore the PK/PD relationship following single oral dose administration of macimorelin acetate in pediatric subjects with suspected GHD;Primary end point(s): SAFETY AND TOLERABILITY - Subjective tolerability (including acceptability of taste and impact on sleep, appetite, and gastrointestinal symptoms), adverse events (AEs); - Determination of changes in laboratory parameters which are relevant to safety; - Influence on vital parameters (pulse rate, blood pressure, electrocardiogram [ECG]). PHARMACOKINETICS - Concentration-time profiles of macimorelin; - Target parameters: AUC, Cmax, Tmax, T1/2. PHARMACODYNAMICS - Concentration-time profiles of GH; - Target parameters: Cmax, Tmax; - Preliminary PK/PD: Tmax for macimorelin vs. Tmax for GH; Cmax for macimorelin vs. Cmax for GH OTHER - Establishment of a recommended dose for diagnostic purposes in pediatric subjects with suspected GHD; - Exploration of a suitable GH cut-off point for a subsequent testing to establish the diagnosis of GHD in pediatric subjects.;Timepoint(s) of evaluation of this end point: SAFETY AND TOLERABILITY - D1, D7+, D14+, D21+ PHARMACOKINETICS - Blood sampling for macimorelin plasma concentrations: pre-dose (sampling time window: +/- 15 minutes, then 15, 30, 45, 60, 90, 120 (sampling time window: +/- 5 minutes) and 360 minutes (sampling time window: +/- 10 minutes) after the oral administration of the macimorelin dose. PHARMACODYNAMICS: - Blood sampling for GH serum concentrations: pre-dose (sampling time window: +/- 15 minutes, then 15, 30, 45, | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Not applicable.;Timepoint(s) of evaluation of this end point: Not applicable. | — |
Countries
Hungary, Poland, Russian Federation, Serbia, Ukraine
Contacts
Public ContactRegulatory Unit
Accelsiors CRO and Consultancy Services Ltd
Outcome results
None listed