Investigation of a New, Oral Growth Hormone Secretagogue, AEZS-130 as a Growth Hormone Stimulation Test.
Condition: Diagnosis of Adult Growth Hormone Deficiency (AGDH)
Intervention: AEZS-130 (formerly ARD-07); L-ARG+GHRH
Intervention description: A single oral administration of AEZS-130 as Growth Hormone Stimulation Test; A single administration of L-ARG+GHRH (iv bolus) followed by a 30min infusion of L-ARG as Growth Hormone Stimulation Test
Phase: Phase 3
Study type: Interventional
Primary purpose: Diagnostic
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: Multi-center, randomized, open-label, cross-over trial to compare AEZS-130 to an established GH stimulation test, L-ARG+GHRH, in the diagnosis of GH deficiency and in terms of safety. Following Amendment no. 3 (version 27 May 2010) , no cross-over was performed anymore due to unavailability of L-ARG+GHRH with resulting single arm testing of AEZS-130. Thus, two treatment arms were applicable only as long as GHRH as substance was available.
Masking: None (Open Label)
Enrollment: 101.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Ghrelin mimetic, growth hormone secretagogue

Summary:

      The diagnosis of growth hormone deficiency (GHD) in adults is established by laboratory
      testing in patients with an appropriate clinical history of hypothalamic pituitary disease.
      Two tests that are considered to be gold standard tests for the diagnosis of GHD are the
      insulin tolerance test (ITT) and growth hormone releasing hormone (GHRH) combined with
      L-arginine (L-ARG). However, these tests are either bothersome (given intravenously) to the
      patient or are linked with side effects. Therefore, an orally available compound like
      AEZS-130 (formerly ARD-07), if demonstrated to be safe and providing adequate sensitivity and
      specificity could be a welcome alternative and/or complement to the current available tests.

      The intent was to recruit 40 adult GHD (AGHD) patients and 40 healthy control subjects into
      this trial, but the original sponsor (Ardana Biosciences Ltd.) discontinued the study for
      financial reasons before this was completed. At the time of withdrawal of GHRH from the
      market in 2008, 42 AGHD patients and 10 normal controls had completed the study at 9 US
      sites. This study reactivated to complete the remaining 30 matched control subjects.

      Additionally upon agreement with the FDA in a Special Protocol Assessment (SPA), 10
      additional adult growth hormone deficient and their matched control were planned to be
      enrolled into this trial for a total treated population of approximatively 100 subjects.
    

Eligibility criteria:

        Inclusion for Matched Control Subjects:

          -  Undergone normal growth and development

          -  Normal serum prolactin (PRL) concentrations

          -  Females should have a history of regular, age-appropriate menses

          -  Males should have normal serum testosterone concentrations

          -  Matched GHD subject already enrolled in study; matched in terms of sex, age, BMI and
             Estrogen status (women only)

        Exclusion Criteria for Matched Control Subjects:

          -  Inability or unwillingness to comply with study medication

          -  Pregnancy or lactation

          -  Clinically relevant ECG abnormalities (including QT/QTc interval > 450 ms) at any time
             prior to dosing at Visit 2

          -  Treatment with any drugs that might prolong QT/QTc

        Inclusion criteria dor Adult GHD Subjects:

          -  Confirmed GH deficiency with a low IGF-1

          -  3 months of stable treatment for those requiring hormone replacement therapy for
             hormones deficiencies other than GHD

          -  subjects with hypogonadism must be treated with sex steroid therapy, excluding women
             over 50 yr of age

          -  women on estrogen therapy, for whatever reason, must be on stable treatment for ar
             least 3 months prior to study

        Exclusion criteria for Adult GHD Subjects:

          -  Untreated hypothyroidism

          -  Known hypersensitivity to any excipient in study medication

          -  Inability or unwillingness to comply with study procedures

          -  Intracranial lesions stable for less than 12 months

          -  GH therapy within one month of study entry

          -  Clinically significant cardiovascular, or cerebrovascular disease

          -  Current active malignancy other than non-melanoma skin cancer

          -  Renal or hepatic dysfunction (> 3 x ULN liver function enzymes (LFEs) - aspartate
             amino transferase (ASAT); alanine amino transferase (ALAT); gamma-glutamyltransferase
             (GGT) or creatinine > 2x ULN)

          -  Pregnancy or lactation

          -  Active Cushing's disease

          -  Clinically relevant ECG abnormalities (including QT/heart rate corrected QT interval
             (QTc) interval > 450 ms) at any time prior to dosing at Visit 2

          -  Treatment with any drugs that might prolong QT/QTc