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Investigation of a New, Oral Growth Hormone Secretagogue, 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.
 
ClinicalTrials.gov Identifier: NCT00448747
Recruitment Status : Completed
First Posted : March 19, 2007
Results First Posted : July 23, 2019
Last Update Posted : July 23, 2019
Sponsor:
Information provided by (Responsible Party):
AEterna Zentaris

Brief 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.


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) were matched to the 30 AGHD patients who were not previously matched. Matching was based upon gender, age, BMI, and estrogen status for females. They received one oral dose of AEZS-130 followed by serial blood draws for growth hormone (GH), insulin-like growth factor 1 (IGF-1) and pharmacokinetic (PK) determinations. There was no cross over due to the unavailability of GHRH (Geref) in the United States. Under Amendment #4 to this protocol, 10 additional AGHD subjects were to be enrolled and matched as described above.

Furthermore, the objective of the study was changed to delete comparison with L-ARG + GHRH.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 101 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 were applicable only 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 Ardana (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 Names:
  • Test 1
  • Macimorelin

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 Stimulation 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 27-March-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
Drug: L-ARG+GHRH
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. Receiver Operating Characteristic (ROC) Analysis on Peak GH (Growth Hormon) Concentrations [ Time Frame: GH sampling: pre-dose and 30, 45, 60, 75, 90, 120, 150 min post-dose ]
    The primary endpoint for each individual is the peak GH concentration following AEZS-130 (macimorelin) administration.


Secondary Outcome Measures :
  1. Peak Insulin-Like Growth Factor (IGF)-1 Concentration Following Treatment [ Time Frame: 15 min. before macimorelin administration and at 150 min after macimorelin administration ]
    Descriptive summaries for IGF-1 and correlation with GH concentrations based on macimorelin treatment. Mean IGF-1 values taken pre- and post- macimorelin administration.

  2. Classification and Regression Tree (CART) Analysis of Peak Growth Hormone (GH) Following Macimorelin Administration [ Time Frame: GH sampling: pre-dose and 30, 45, 60, 75, 90, 120, 150 min post-dose ]

    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.


  3. Number of Participants With Drug Related Adverse Events (AEs) [ Time Frame: 14 days ]
    Total number of participants with drug related AEs, following macimorelin administration of L-Arginine (ARG) - Growth Hormone Releasing Hormone (GHRH) administration.



Information from the National Library of Medicine

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

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 ClinicalTrials.gov identifier (NCT number): NCT00448747


Locations
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United States, Arizona
Celerion
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
Celerion
Lincoln, Nebraska, United States, 68502
United States, New Jersey
Celerion
Neptune, 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
Investigators
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Principal Investigator: Beverly MK Biller, MD Massachusetts General Hospital, Boston
Publications of Results:
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Responsible Party: AEterna Zentaris
ClinicalTrials.gov Identifier: NCT00448747    
Other Study ID Numbers: AEZS 130 047
First Posted: March 19, 2007    Key Record Dates
Results First Posted: July 23, 2019
Last Update Posted: July 23, 2019
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