Diagnosis of Adult Growth Hormone Deficiency (AGDH) Clinical Trial
Official title:
A Multi-center, Study Investigating a New, Oral Growth Hormone Secretagogue (GHS)(AEZS 130, Formerly Ardana (ARD)-07) as a Growth Hormone (GH) Stimulation Test in Terms of Safety and Efficacy
| NCT number | NCT00448747 |
| Other study ID # | AEZS 130 047 |
| Secondary ID | |
| Status | Completed |
| Phase | Phase 3 |
| First received | |
| Last updated | |
| Start date | June 2007 |
| Est. completion date | July 2011 |
| Verified date | June 2017 |
| Source | AEterna Zentaris |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
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.
| Status | Completed |
| Enrollment | 101 |
| Est. completion date | July 2011 |
| Est. primary completion date | July 2011 |
| Accepts healthy volunteers | Accepts Healthy Volunteers |
| Gender | All |
| Age group | 18 Years and older |
| Eligibility |
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 |
| Country | Name | City | State |
|---|---|---|---|
| United States | John Hopkins University | Baltimore | Maryland |
| United States | Massachusetts General Hospital | Boston | Massachusetts |
| United States | Northwestern University | Chicago | Illinois |
| United States | Radiant Research Inc. | Chicago | Illinois |
| United States | Baylor College of Medicine | Houston | Texas |
| United States | Celerion | Lincoln | Nebraska |
| United States | Cedars-Sinai Medical Center | Los Angeles | California |
| United States | Celerion | Neptune | New Jersey |
| United States | Oregon Health & Science University | Portland | Oregon |
| United States | Cetero Research | San Antonio | Texas |
| United States | VA Puget Sound HCS University of Washington | Tacoma | Washington |
| United States | Celerion | Tempe | Arizona |
| United States | Harbor-UCLA Medical Center | Torrance | California |
| Lead Sponsor | Collaborator |
|---|---|
| AEterna Zentaris |
United States,
Garcia JM, Swerdloff R, Wang C, Kyle M, Kipnes M, Biller BM, Cook D, Yuen KC, Bonert V, Dobs A, Molitch ME, Merriam GR. Macimorelin (AEZS-130)-stimulated growth hormone (GH) test: validation of a novel oral stimulation test for the diagnosis of adult GH d — View Citation
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Receiver Operating Characteristic (ROC) Analysis on Peak GH (Growth Hormon) Concentrations | The primary endpoint for each individual is the peak GH concentration following AEZS-130 (macimorelin) administration. | GH sampling: pre-dose and 30, 45, 60, 75, 90, 120, 150 min post-dose | |
| Secondary | Peak Insulin-Like Growth Factor (IGF)-1 Concentration Following Treatment | Descriptive summaries for IGF-1 and correlation with GH concentrations based on macimorelin treatment. Mean IGF-1 values taken pre- and post- macimorelin administration. | 15 min. before macimorelin administration and at 150 min after macimorelin administration | |
| Secondary | Classification and Regression Tree (CART) Analysis of Peak Growth Hormone (GH) Following Macimorelin Administration | The CART Analysis for macimorelin estimated: a) a macimorelin cut-point that minimized the misclassification of AGHD patients and healthy control subjects; b) an optimal decision tree for macimorelin that incorporated age, sex and BMI. Sensitivity (correct identification of AGHD cases) and specificity (correct identification of control subjects) for macimorelin was summarized for age, gender, BMI and estrogen status subgroups containing n > 10. At least 8 of the 10 newly enrolled AGHD patients should have been correctly classified for a protocol pre-specified threshold of Peak GH concentration which was 8.5 (ng/ml). Software CART Version 6.0 was used. |
GH sampling: pre-dose and 30, 45, 60, 75, 90, 120, 150 min post-dose | |
| Secondary | Number of Participants With Drug Related Adverse Events (AEs) | Total number of participants with drug related AEs, following macimorelin administration of L-Arginine (ARG) - Growth Hormone Releasing Hormone (GHRH) administration. | 14 days |