Validation of Macimorelin as a Test for Adult Growth Hormone Deficiency
Condition: Growth Hormone Deficiency With Pituitary Anomalies
MeSH terms: Dwarfism, Pituitary; Endocrine System Diseases
Intervention: Macimorelin; Insulin
Intervention description: macimorelin acetate, 0.5 mg/kg body weight, drinking solution, single dose; Insulin, 0.10 U/kg (0.15 U/kg if BMI > 30 kg/m2), intravenous injection, single dose
Intervention MeSH terms: Insulin; Insulin, Globin Zinc
Phase: Phase 3
Study type: Interventional
Primary purpose: Diagnostic
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Masking description: This was an open label trial. No masking with regard to the Growth Hormone Stimulation Tests (GHSTs) performed was done. However, Data Review Committee/Sponsor/Project Management was masked towards the Growth Hormone (GH) values as results fo both tests. GH values were provided to the investigator only after both GHSTs had been performed, to avoid bias.
Enrollment: 157.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Adult Growth Hormone Deficiency

Summary:

      The Macimorelin Growth Hormone Stimulation Test (GHST) will be compared with the Insulin
      Tolerance Test (ITT) in an open-label, randomized, 2-way crossover Trial. The trial will
      include subjects suspected to have adult growth hormone deficiency (AGHD) and a group of
      healthy control subjects.
    

Eligibility criteria:

        Inclusion Criteria:

          -  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).

          -  Healthy* control subjects, matching a 'high likelihood GHD' subjects

        Exclusion Criteria:

          -  GH therapy within 1 month prior to anticipated first GHST within this trial (within 3
             months in case of long-acting GH formulation).

          -  GHST within 7 days prior to the anticipated first test day within the trial.

          -  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.

          -  Untreated hypogonadism or not on a stable substitution treatment within 30 days prior
             to anticipated first test day within the trial.

          -  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).

          -  Concomitant use of a CYP3A4 inducer (e.g., carbamazepine, phenobarbital, phenytoin,
             pioglitazone, rifabutin, rifampin, St. John's Wort).

          -  Medical history of ongoing clinically symptomatic severe psychiatric disorders.

          -  Parkinson's disease.

          -  Cushing disease or patients on supraphysiologic glucocorticoid therapy within 30 days
             prior to the anticipated first test day within the trial.

          -  Type 1 diabetes or untreated or poorly controlled Type 2 diabetes, as defined by HbA1c
             > 8%.

          -  Body mass index (BMI) ≥ 40.0 kg/m2.

          -  Participation in a trial with any investigational drug within 30 days prior to trial
             entry.

          -  Vigorous physical exercise within 24 hours prior to each GHST within this trial.

          -  Known hypersensitivity to macimorelin or insulin, or any of the constituents of either
             preparation.

          -  Clinically significant cardiovascular or cerebrovascular disease.

          -  Prolonged ECG QT interval, defined as corrected QT interval (QTc) > 500 msec.

          -  Concomitant treatment with any drugs that might prolong QT/QTc.

          -  Elevation of laboratory parameters indicating hepatic or renal dysfunction or damage
             (aspartate amino transferase (ASAT), alanine aminotransferase (ALAT), gamma-glutamyl
             transpeptidase (GGT)> 2.5 x ULN; ), creatinine, or bilirubin > 1.5x ULN).

          -  Medical history of seizure disorders.

          -  Known immunosuppression.

          -  Current active malignancy other than non-melanoma skin cancer.

          -  Breastfeeding or positive urine pregnancy test (for women of childbearing potential
             only).

          -  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).

          -  Lack of ability or willingness to give informed consent.

          -  Anticipated non-availability for trial visits/procedures.