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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
AEterna Zentaris
ClinicalTrials.gov Identifier:
NCT00448747
First received: March 16, 2007
Last updated: February 19, 2014
Last verified: July 2011
  Purpose

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 Intervention Phase
Diagnosis of Adult Growth Hormone Deficiency (AGDH)
Drug: diagnostic
Phase 3

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by AEterna Zentaris:

Primary Outcome Measures:
  • Diagnostic efficacy [ Time Frame: March 2011 ] [ Designated as safety issue: No ]
    Diagnostic efficacy will be based on the area under the ROC curve (> 0.85) using peak GH levels.


Secondary Outcome Measures:
  • Sensitivity(ROC) [ Time Frame: March 2011 ] [ Designated as safety issue: No ]
  • Specificity (ROC) [ Time Frame: March 2011 ] [ Designated as safety issue: No ]
  • Misclassification (CART) analyses [ Time Frame: March 2011 ] [ Designated as safety issue: No ]
  • Safety [ Time Frame: March 2011 ] [ Designated as safety issue: No ]
    1. Incidence of treatment-emergent AEs
    2. Laboratory findings
    3. Vital signs
    4. ECGs


Enrollment: 98
Study Start Date: June 2007
Study Completion Date: July 2011
Primary Completion Date: July 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: AEZS 130 ( formerly ARD-07) Drug: diagnostic
A single administration of AEZS-130
Other Name: AEZS-130 (formerly ARD-07)

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00448747

Locations
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
Principal Investigator: Beverly MK Biller, MD Massachusetts General Hospital, Boston
  More Information

No publications provided by AEterna Zentaris

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: AEterna Zentaris
ClinicalTrials.gov Identifier: NCT00448747     History of Changes
Other Study ID Numbers: AEZS 130 047
Study First Received: March 16, 2007
Last Updated: February 19, 2014
Health Authority: United States: Food and Drug Administration

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

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

ClinicalTrials.gov processed this record on July 28, 2014