Comparison of the substance macimorelin (drinking solution) with insulin (injection) to confirm that it works as diagnostic test for lacking growth hormone in adults

Phase 1

Conditions: Diagnosis of Adult Growth Hormone Deficiency (AGHD)
Therapeutic area: Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Diagnosis [E01]

Registration Number: EUCTR2015-002337-22-AT

Lead Sponsor: Aeterna Zentaris GmbH

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 110

Inclusion Criteria

1. Male or female, aged between 18 and 65 years.
2. Suspected growth hormone deficiency (GHD), based on either of the following:
- structural hypothalamic or pituitary disease, or
- surgery or irradiation in these areas, or
- head trauma as an adult, or
- evidence of other pituitary hormone deficiencies, or
- idiopathic childhood onset GHD (without known hypothalamic or pituitary lesion or injury).
OR (recruitment at dedicated trial sites only)
3. Group D: Healthy* control
Subject matching a Group A subject by
- sex, age (+/- 5 years), BMI (+/- 2 kg/m2), and estrogen status** (women only);
* ‘healthy’ comprising:
- history of normal growth and development,
- serum prolactin concentration within normal range limits,
- history of regular, age-appropriate menses in females
- serum testosterone concentration within normal range limits for males.
** matching for ‘estrogen status’:
- Group A subjects below 50 years and on oral estrogen therapy will be matched to control subjects who are also taking estrogen (as an oral contraceptive or for replacement); the route of estrogen administration (e.g. oral vs transdermal) must also be matched.
- Group A subjects 50 years or older and with untreated estrogen deficiency will be matched to female control subjects who are not receiving estrogen.
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 110
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. GH therapy within 1 month prior to anticipated first GHST within this trial (within 3 months in case of long-acting GH formulation).
Note: A patient with ongoing GH therapy will not be a candidate for this trial, if a corresponding treatment-free interval is not medically justifiable.
2. GHST within 7 days prior to the anticipated first test day within the trial.
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 first test day within the trial.
4. Untreated hypogonadism or not on a stable substitution treatment within 30 days prior to anticipated first test day within the trial.
Note: Postmenopausal status will not be considered as an exclusion.
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. Medical history of ongoing clinically symptomatic severe psychiatric disorders.
8. Parkinson’s disease.
9. Cushing disease or patients on supraphysiologic glucocorticoid therapy within 30 days prior to the anticipated first test day within the trial.
10. Type 1 diabetes or untreated or poorly controlled Type 2 diabetes, as defined by HbA1c > 8%.
11. Body mass index (BMI) = 40.0 kg/m2.
12. Participation in a trial with any investigational drug within 30 days prior to trial entry.
13. Vigorous physical exercise within 24 hours prior to each GHST within this trial.

Safety concerns:
14. Known hypersensitivity to macimorelin or insulin, or any of the constituents of either preparation.
15. Clinically significant cardiovascular or cerebrovascular disease.
16. Prolonged ECG QT interval, defined as QTc > 500 msec.
17. 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 (registration required), a copy of which is included in the Investigator’s File).
Note: A patient who receives such treatment will not be a candidate for this trial, 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.
18. Elevation of laboratory parameters indicating hepatic or renal dysfunction or damage (ASAT, ALAT , GGT > 2.5 x ULN; creatinine, or bilirubin > 1.5x ULN).
19. Medical history of seizure disorders.
20. Known immunosuppression.
21. Current active malignancy other than non-melanoma skin cancer.
22. Breastfeeding or positive urine pregnancy test (for women of childbearing potential only).
23. Women of childbearing age without contraception, such as hormonal contraception or use of condom and spermicides or use of diaphragm and spermicides or Intra Uterine Device (IUD).