Investigation of a New, Oral Growth Hormone Secretagogue, Macimorelin (AEZS-130) as a Growth Hormone Stimulation Test.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00448747
Recruitment Status : Completed
First Posted : March 19, 2007
Last Update Posted : July 2, 2017
Information provided by (Responsible Party):
AEterna Zentaris

Brief Summary:

The diagnosis of GH 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 GHRH combined with arginine. 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 AGHD patients and 40 normal 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 is now being reactivated to complete the remaining 30 matched control subjects.

Additionally upon agreement with the FDA in a SPA, 10 additional adult grown hormone deficient and their matched control will be enrolled into this trial for a total treated population approximatively 100 subjects.

Condition or disease Intervention/treatment Phase
Diagnosis of Adult Growth Hormone Deficiency (AGDH) Drug: AEZS-130 (formerly ARD-07) Drug: L-ARG+GHRH Phase 3

Detailed Description:
Thirty control subjects (i.e., without AGHD) will be matched to the 30 AGHD patients who were not previously matched. Matching will be based upon gender, age, BMI, and estrogen status for females. They will receive one oral dose of AEZS-130 followed by serial blood draws for growth hormone, IGF-1 and PK determinations. There will be no cross over due to the unavailability of GHRH (Geref) in the United States. Under Amendment #4 to this protocol, 10 additional AGHD subjects will be enrolled and matched as described above.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 100 participants
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 was applicable as long as GHRH as substance was available.
Masking: None (Open Label)
Primary Purpose: Diagnostic
Official Title: A Multi-center, Study Investigating a New, Oral Growth Hormone Secretagogue (GHS)(AEZS 130, Formerly ARD-07) as a Growth Hormone (GH) Stimulation Test in Terms of Safety and Efficacy
Study Start Date : June 2007
Actual Primary Completion Date : July 2011
Actual Study Completion Date : July 2011

Arm Intervention/treatment
Experimental: AEZS-130 ( formerly ARD-07)
A single oral administration of AEZS-130 (0.5 mg/kg po) as Growth Hormone Stimulation Test
Drug: AEZS-130 (formerly ARD-07)
A single oral administration of AEZS-130 as Growth Hormone Stimulation Test
Other Name: Test 1
Active Comparator: L-ARG+GHRH
This trial was set up as a multi-center, randomized, cross-over study investigating AEZS-130 as a Growth Hormone Stimultation Tests in terms of safety and efficacy compared to L-ARG+GHRH. When GHRH became unavailable on the US market, this comparator arm was no longer available, which was addressed by Amendment No. 3 (version 27Ma 2010). Control subject enrolled under Amendment No. 3 were not randomized as there was no cross-over due to unavailability of L-ARG+GHRH. These control subjects received only AEZS-130
A single administration of L-ARG+GHRH (iv bolus) followed by a 30min infusion of L-ARG as Growth Hormone Stimulation Test
Other Name: Test Control

Primary Outcome Measures :
  1. Descriptive summaries of the diagnostic performance of AEZS-130 [ Time Frame: March 2011 ]
    Included: ROC AUC, ROC Sensitivity, ROC Specificity, CART misclassification. The primary endpoint for each individual is the peak GH concentration following treatment (AEZS-130 or L-ARG+GHRH).

Secondary Outcome Measures :
  1. Peak IGF-1 concentration following treatment [ Time Frame: March 2011 ]
    ROC and CART analyses on IGF-1

  2. Sensitivy and specificity [ Time Frame: March 2011 ]
    summarized for demographic, BMI and estrogen status subgroups containing n>10

  3. Determinations from CART [ Time Frame: March 2011 ]
    cut-point which minimizes the misclassification of case and control subjects, optimal decision tree which incorporates treatment, age, sex and BMI

  4. Safety [ Time Frame: March 2011 ]
    1. Incidence of treatment-emergent AEs
    2. Laboratory findings
    3. Vital signs
    4. ECGs

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes

Inclusion for Matched Control Subjects:

  • Undergone normal growth and development
  • Normal serum 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 LFEs - ASAT; ALAT; GGT or creatinine > 2x ULN)
  • Pregnancy or lactation
  • Active Cushing's disease
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00448747

United States, Arizona
Tempe, Arizona, United States, 85283
United States, California
Cedars-Sinai Medical Center
Los Angeles, California, United States, 90048
Harbor-UCLA Medical Center
Torrance, California, United States, 90502
United States, Illinois
Northwestern University
Chicago, Illinois, United States, 60611-3008
Radiant Research Inc.
Chicago, Illinois, United States, 60654
United States, Maryland
John Hopkins University
Baltimore, Maryland, United States, 21287
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
United States, Nebraska
Lincoln, Nebraska, United States, 68502
United States, New Jersey
Neptune City, New Jersey, United States, 07753
United States, Oregon
Oregon Health & Science University
Portland, Oregon, United States, 97239
United States, Texas
Baylor College of Medicine
Houston, Texas, United States, 77030
Cetero Research
San Antonio, Texas, United States, 78229-4801
United States, Washington
VA Puget Sound HCS University of Washington
Tacoma, Washington, United States, 98493
Sponsors and Collaborators
AEterna Zentaris
Principal Investigator: Beverly MK Biller, MD Massachusetts General Hospital, Boston

Publications of Results:
Responsible Party: AEterna Zentaris Identifier: NCT00448747     History of Changes
Other Study ID Numbers: AEZS 130 047
First Posted: March 19, 2007    Key Record Dates
Last Update Posted: July 2, 2017
Last Verified: June 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: To share IPD is not planned as subjects were not informed about this possibility and thus, no related patient consent is available (data protection issue).

Keywords provided by AEterna Zentaris:
Ghrelin mimetic, growth hormone secretagogue

Additional relevant MeSH terms:
Dwarfism, Pituitary
Bone Diseases, Developmental
Bone Diseases
Musculoskeletal Diseases
Bone Diseases, Endocrine
Pituitary Diseases
Hypothalamic Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Endocrine System Diseases
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs