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

NCT00448747 | Completed Phase 3 Results

• 1 other identifier: AEZS 130 047
• Study Type: interventional
• Target: 101
• Locations: 1 country
• Sites: 13

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.

Conditions

Diagnosis of Adult Growth Hormone Deficiency (AGDH)

Keywords

Ghrelin mimetic, growth hormone secretagogue

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• Peak Insulin-Like Growth Factor (IGF)-1 Concentration Following Treatment

  15 min. before macimorelin administration and at 150 min after macimorelin administration

• Classification and Regression Tree (CART) Analysis of Peak Growth Hormone (GH) Following Macimorelin Administration

  GH sampling: pre-dose and 30, 45, 60, 75, 90, 120, 150 min post-dose

• Number of Participants With Drug Related Adverse Events (AEs)

  14 days

Study Arms (2)

AEZS-130 ( formerly ARD-07)

EXPERIMENTAL

A single oral administration of AEZS-130 (0.5 mg/kg po) as Growth Hormone Stimulation Test

Drug: AEZS-130 (formerly ARD-07)

L-ARG+GHRH

ACTIVE COMPARATOR

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

Interventions

AEZS-130 (formerly ARD-07) DRUG

A single oral administration of AEZS-130 as Growth Hormone Stimulation Test

Also known as: Test 1, Macimorelin

AEZS-130 ( formerly ARD-07)

L-ARG+GHRH DRUG

A single administration of L-ARG+GHRH (iv bolus) followed by a 30min infusion of L-ARG as Growth Hormone Stimulation Test

Also known as: Test Control

L-ARG+GHRH

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may not qualify if:

• 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
• Confirmed GH deficiency with a low IGF-1
• 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
• 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

Sponsors & Collaborators

• AEterna Zentaris: lead

Study Sites (13)

Celerion

Tempe, Arizona, 85283, United States

Location

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

Location

Harbor-UCLA Medical Center

Torrance, California, 90502, United States

Location

Northwestern University

Chicago, Illinois, 60611-3008, United States

Location

Radiant Research Inc.

Chicago, Illinois, 60654, United States

Location

John Hopkins University

Baltimore, Maryland, 21287, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Celerion

Lincoln, Nebraska, 68502, United States

Location

Celerion

Neptune City, New Jersey, 07753, United States

Location

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

Cetero Research

San Antonio, Texas, 78229-4801, United States

Location

VA Puget Sound HCS University of Washington

Tacoma, Washington, 98493, United States

Location

Related Publications (1)

• 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 deficiency. J Clin Endocrinol Metab. 2013 Jun;98(6):2422-9. doi: 10.1210/jc.2013-1157. Epub 2013 Apr 4.

  PMID: 23559086 RESULT

MeSH Terms

Interventions

macimorelin

Results Point of Contact

• Title: Nicola Ammer
• Organization: Aeterna Zentaris

nammer@aezsinc.com

+496942602

Study Officials

• Beverly MK Biller, MD

  Massachusetts General Hospital, Boston

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: March 16, 2007
• First Posted: March 19, 2007
• Study Start: June 1, 2007
• Primary Completion: July 1, 2011
• Study Completion: July 1, 2011
• Last Updated: July 23, 2019
• Results First Posted: July 23, 2019

Record last verified: 2017-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (13)