Diagnosis of Adult Growth Hormone Deficiency (AGDH)Phase 3NCT00448747

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

A Phase 3 study testing AEZS-130 (formerly ARD-07) and L-ARG+GHRH in people with Diagnosis of Adult Growth Hormone Deficiency (AGDH), run by AEterna Zentaris at 13 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 years and olderHealthy volunteers can take part
Conditions the study is for: Diagnosis of Adult Growth Hormone Deficiency (AGDH)
What is being tested?: AEZS-130 (formerly ARD-07) and L-ARG+GHRH
Type of treatment: Pill or oral medicine, Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 101 participants
Where: 13 sitesUnited States
Study dates: Jun 2007to Jul 2011
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
Healthy volunteers accepted
Adult, Older adult

Who may be able to join

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)
Confirmed GH deficiency with a low IGF-1

Show all 9Show fewer

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

Who cannot join

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
Untreated hypothyroidism
Known hypersensitivity to any excipient in study medication

Show all 16Show fewer

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

Trial locations and contacts

13 sites in 1 country.

City, postcode or hospital

13 sites in 1 country

United States13 sites

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

Other trials in United States

About this study

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

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.

Read the 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.

Conditions: Diagnosis of Adult Growth Hormone Deficiency (AGDH)
Being tested: AEZS-130 (formerly ARD-07), L-ARG+GHRH
Keywords: Ghrelin mimetic, growth hormone secretagogue

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

AEZS-130 (formerly ARD-07)Drug
Also called Test 1, Macimorelin
A single oral administration of AEZS-130 as Growth Hormone Stimulation Test
L-ARG+GHRHDrug
Also called Test Control
A single administration of L-ARG+GHRH (iv bolus) followed by a 30min infusion of L-ARG as Growth Hormone Stimulation Test

Study groups in NCT00448747
Study group	Role	What they receive
AEZS-130 ( formerly ARD-07)	Experimental	A single oral administration of AEZS-130 (0.5 mg/kg po) as Growth Hormone Stimulation Test Receives: 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 Receives: Drug: L-ARG+GHRH

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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
Descriptive summaries for IGF-1 and correlation with GH concentrations based on macimorelin treatment. Mean IGF-1 values taken pre- and post- macimorelin administration.
Measured: 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
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.
Measured: GH sampling: pre-dose and 30, 45, 60, 75, 90, 120, 150 min post-dose
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.
Measured: 14 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jun 2007Jul 2011

First posted19 Mar 2007 (estimated)
Study startJun 2007
Primary completionJul 2011
Study completionJul 2011

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Diagnosis of Adult Growth Hormone Deficiency (AGDH)Studies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Diagnosis
Allocation: Randomised
Intervention model: Crossover
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)
Enrolment: 101 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00448747
Sponsor's protocol ID: AEZS 130 047
Status last verified: Jun 2017
First submitted: 16 Mar 2007
Last updated: 23 Jul 2019
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
Individual data sharing: No: 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).

Publications

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.
PubMed 23559086

Study at a glance

From the registry record, last updated by the sponsor on 23 Jul 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT00448747
Acronym / sponsor ID: AEZS 130 047
Conditions: Diagnosis of Adult Growth Hormone Deficiency (AGDH)
Keywords: Ghrelin mimetic, growth hormone secretagogue
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 101 participants (actual)
Lead sponsor: AEterna ZentarisIndustry (pharma, biotech, devices)
Study start: Jun 2007
Primary completion: Jul 2011 (actual)
Study completion: Jul 2011 (actual)
First posted: 19 Mar 2007 (estimated)
Results: Posted 23 Jul 2019

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

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

Study design

Primary purpose: Diagnosis
Allocation: Randomised
Intervention model: Crossover
Masking: None (open label)
Number of arms: 2
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.

Arm	Type	Receives
AEZS-130 ( formerly ARD-07)	Experimental	Drug: AEZS-130 (formerly ARD-07)A single oral administration of AEZS-130 (0.5 mg/kg po) as Growth Hormone Stimulation Test
L-ARG+GHRH	Active comparator	Drug: L-ARG+GHRHThis 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

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Accepted
Age groups: Adult, Older adult

Key inclusion criteria (9 listed)

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)

Key exclusion criteria (16 listed)

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
Untreated hypothyroidism

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
AEZS-130 (formerly ARD-07)Also: Test 1, MacimorelinA single oral administration of AEZS-130 as Growth Hormone Stimulation Test	Drug	AEZS-130 ( formerly ARD-07)
L-ARG+GHRHAlso: Test ControlA single administration of L-ARG+GHRH (iv bolus) followed by a 30min infusion of L-ARG as Growth Hormone Stimulation Test	Drug	L-ARG+GHRH

Primary outcome

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.

3 secondary outcomes

Peak Insulin-Like Growth Factor (IGF)-1 Concentration Following Treatment
Time frame: 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
Time frame: GH sampling: pre-dose and 30, 45, 60, 75, 90, 120, 150 min post-dose
Number of Participants With Drug Related Adverse Events (AEs)
Time frame: 14 days

Results and safety

Results posted to the registry on 23 Jul 2019, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
AGHD Patients (= Cases)	53	52
Matched Controls (= Controls)	48	48

Primary outcome: 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. Mean (Standard Deviation). Unit: ng/mL

Measure	Cases/AEZS-130 Administered n = 50	Control/AEZS-130 Administered n = 48
Value	2.36 (5.69)	17.71 (19.11)

Cases/AEZS-130 Administered vs Control/AEZS-130 Administered: ROC AUC: 0.923
Cases/AEZS-130 Administered vs Control/AEZS-130 Administered: sensitivity (percent): 82
Cases/AEZS-130 Administered vs Control/AEZS-130 Administered: Specificity (percent): 92

Population analysed: PPS = per protocol set: this was considered to be the most appropriate for determination of the diagnostic utility of macimorelin

3 secondary outcomes are reported in the full results.

Adverse events

Time frame: 14 days (time window between test visit (V2) and end-of-trial visit (V3). Other adverse events reported at 2% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
AEZS-130: Cases	0 of 52 (0%)	19 of 52 (36.5%)	0 of 52
AEZS-130: Controls	1 of 48 (2.1%)	10 of 48 (20.8%)	0 of 48
L-ARG+GHRH: Cases	0 of 43 (0%)	26 of 43 (60.5%)	0 of 43
L-ARG+GHRH: Controls	0 of 10 (0%)	3 of 10 (30%)	0 of 10

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 23 Jul 2019.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 23559086Garcia 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.
Individual participant dataSharing planned: No. 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).

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Beverly MK Biller, MD principal investigator

Massachusetts General Hospital, Boston

13 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing AEZS-130 (formerly ARD-07) and L-ARG+GHRH in people with Diagnosis of Adult Growth Hormone Deficiency (AGDH), run by AEterna Zentaris at 13 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 23 Jul 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 13 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 23 Jul 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00448747, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Jul 2019.