A clinical study with macimorelin acetate comparing three doses in their safety and tolerability in children with suspected growth hormone deficiency (GHD)

• Register: EUCTR
• Last refreshed on: 26 March 2024
• Main ID: EUCTR2018-001988-23-HU
• Date of registration: 05/09/2018
• Prospective Registration: Yes
• Primary sponsor: Aeterna Zentaris GmbH
• Public title: A clinical study with macimorelin acetate comparing three doses in their safety and tolerability in children with suspected growth hormone deficiency (GHD)
• Scientific title: Open label, group comparison, dose escalation trial to investigate safety, tolerability, pharmacokinetics and pharmacodynamics of macimorelin acetate after single oral dosing of 0.25 mg/kg, 0.5 mg/kg, and 1 mg/kg in pediatric patients with suspected growth hormone deficiency (GHD)
• Date of first enrolment: 07/11/2018
• Target sample size: 24
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2018-001988-23
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: yes Other trial design description: open label, group-comparison, single dose, dose-escalation trial If controlled, specify comparator, Other Medicinial Product: Placebo: Other: Number of treatment arms in the trial: 3
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Hungary, Poland, Russian Federation, Serbia, Ukraine

Contacts

• Name: Regulatory Unit
• Affiliation: Accelsiors CRO and Consultancy Services Ltd

• Name: Regulatory Unit
• Affiliation: Accelsiors CRO and Consultancy Services Ltd

Key inclusion & exclusion 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:
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.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Diagnosis [E01]

Diagnosis of Growth Hormone Deficiency
MedDRA version: 20.0 Level: LLT Classification code 10073227 Term: Growth hormone stimulation test System Organ Class: 100000004848

Intervention(s)

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 descriptive name: MACIMORELIN ACETATE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 63.6-

Primary Outcome(s)

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, 60, 90, 120 (sampling time window: +/- 5 minutes) and 360 minutes (sampling time window: +/- 10 minutes) after the oral administration of the macimorelin dose;

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.

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 Outcome(s)

Secondary end point(s): Not applicable.

Timepoint(s) of evaluation of this end point: Not applicable.

Secondary ID(s)

AEZS-130-P01

Source(s) of Monetary Support

Aeterna Zentaris GmbH

Ethics review

Status: Approved
Approval date: 16/10/2018
Contact:

Results

• Results available: Yes
• Date Posted: 09/08/2020
• Date Completed: 24/01/2020
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2018-001988-23/results