Growth Hormone Deficiency With Pituitary AnomaliesPhase 3NCT02558829
Validation of Macimorelin as a Test for Adult Growth Hormone Deficiency
A Phase 3 study testing Macimorelin and Insulin in people with Growth Hormone Deficiency With Pituitary Anomalies, run by AEterna Zentaris at 27 sites in 9 countries.
Trial summary
The Macimorelin Growth Hormone Stimulation Test (GHST) will be compared with the Insulin Tolerance Test (ITT) in an open-label, randomized, 2-way crossover Trial. The trial will include subjects suspected to have adult growth hormone deficiency (AGHD) and a group of healthy control subjects. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Growth Hormone Deficiency With Pituitary Anomalies
- What is being tested?
- Macimorelin and Insulin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 157 participants
- Where
- 27 sitesin 9 countries
- Study dates
- 3 Dec 2015to 29 Nov 2016
- 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 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Suspected growth hormone deficiency (GHD), based on either of the following:
- structural hypothalamic or pituitary disease, or
- surgery or irradiation in these areas, or
- head trauma as an adult, or
- evidence of other pituitary hormone deficiencies, or
- idiopathic childhood onset GHD (without known hypothalamic or pituitary lesion or injury).
- Healthy* control subjects, matching a 'high likelihood GHD' subjects
Who cannot join
- GH therapy within 1 month prior to anticipated first GHST within this trial (within 3 months in case of long-acting GH formulation).
- GHST within 7 days prior to the anticipated first test day within the trial.
- Subjects with a medical history and clinical signs of a not adequately treated thyroid dysfunction or subjects who had a change in thyroid therapy within 30 days prior to anticipated first test day within the trial.
- Untreated hypogonadism or not on a stable substitution treatment within 30 days prior to anticipated first test day within the trial.
- Treatment with drugs directly affecting the pituitary secretion of somatotropin (e.g. somatostatin analogues, clonidine, levodopa, and dopamine agonists) or provoking the release of somatostatin; antimuscarinic agents (atropine).
- Concomitant use of a CYP3A4 inducer (e.g., carbamazepine, phenobarbital, phenytoin, pioglitazone, rifabutin, rifampin, St. John's Wort).
Show all 25Show fewer
- Medical history of ongoing clinically symptomatic severe psychiatric disorders.
- Parkinson's disease.
- Cushing disease or patients on supraphysiologic glucocorticoid therapy within 30 days prior to the anticipated first test day within the trial.
- Type 1 diabetes or untreated or poorly controlled Type 2 diabetes, as defined by HbA1c > 8%.
- Body mass index (BMI) ≥ 40.0 kg/m2.
- Participation in a trial with any investigational drug within 30 days prior to trial entry.
- Vigorous physical exercise within 24 hours prior to each GHST within this trial.
- Known hypersensitivity to macimorelin or insulin, or any of the constituents of either preparation.
- Clinically significant cardiovascular or cerebrovascular disease.
- Prolonged ECG QT interval, defined as corrected QT interval (QTc) > 500 msec.
- Concomitant treatment with any drugs that might prolong QT/QTc.
- Elevation of laboratory parameters indicating hepatic or renal dysfunction or damage (aspartate amino transferase (ASAT), alanine aminotransferase (ALAT), gamma-glutamyl transpeptidase (GGT)> 2.5 x ULN; ), creatinine, or bilirubin > 1.5x ULN).
- Medical history of seizure disorders.
- Known immunosuppression.
- Current active malignancy other than non-melanoma skin cancer.
- Breastfeeding or positive urine pregnancy test (for women of childbearing potential only).
- Women of childbearing age without contraception, such as hormonal contraception or use of condom and spermicides or use of diaphragm and spermicides or Intra Uterine Device (IUD).
- Lack of ability or willingness to give informed consent.
- Anticipated non-availability for trial visits/procedures.
Trial locations and contacts
27 sites in 9 countries.
27 sites in 9 countries
United States5 sites
Texas Diabetes and Endocrinology
Austin, Texas, 78731
Baylor College of Medicine-Endocrinology
Houston, Texas, 77030
VA Puget Sound Health Care System
Seattle, Washington, 98108
Swedish Medical Center - Cherry Hill
Seattle, Washington, 98122
Harbor UCLA Medical Center
Torrance, California, 90509
Germany5 sites
RWTH Aachen University Hospital
Aachen, North Rhine-Westphalia, 52074
Klinik für Endokrinologie, Diabetes und Ernährungsmedizin der Charité
Berlin, 10117
University Hospital Marburg
Marburg, Hesse, 35033
Klinikum der LMU München
Munich, Bavaria, 80336
Max Planck Institut
Munich, Bavaria, 80804
Poland4 sites
Centrum Kliniczno-Badawcze
Elblag, 82-300
Centrum Medyczne Angelius Provita
Katowice, 40-611
Phase I - MTZ Clinical Research Sp. z o.o.
Warsaw, 02-106
Wromedica
Wroclaw, 51-685
France3 sites
CHU de Lyon HCL-GH Est
Bron, 69677
GHU Paris-Sud - Hôpital de Bicêtre
Le Kremlin-Bicêtre, 94270
Hôpital Haut-Lévêque
Pessac, 33600
Spain3 sites
Hospital de Sant Pau
Barcelona, 08026
Hospital Universitari Vall d' Hebron
Barcelona, 08035
Hospital de Conxo
Santiago de Compostela, 15706
Austria2 sites
Krankenanstalt Rudolfstiftung
Vienna, 1030
Medical University & General Hospital of Vienna, AKH,
Vienna, 1090
Serbia2 sites
Clinical Centre of Serbia
Belgrade, 11000
Clinical Centre of Vojvodina
Novi Sad, 21000
United Kingdom2 sites
St Bartholomew's Hospital
London, EC1A 7BE
The Christie NHS Foundation Trust
Manchester, M20 4BX
About this study
Official title: Confirmatory Validation of Oral Macimorelin as a Growth Hormone (GH) Stimulation Test (ST) for the Diagnosis of Adult Growth Hormone Deficiency (AGHD) in Comparison With the Insulin Tolerance Test (ITT)
The Macimorelin Growth Hormone Stimulation Test (GHST) will be compared with the Insulin Tolerance Test (ITT) in an open-label, randomized, 2-way crossover Trial. The trial will include subjects suspected to have adult growth hormone deficiency (AGHD) and a group of healthy control subjects.
Read the detailed description
Trial subjects will be assigned to groups of descending likelihood of having AGHD:
Group A, B, C: High, intermediate, and low likelihood of GHD, respectively; Group D: Healthy control subjects matching Group A subjects .
The sequential order of the GHSTs for suspected AGHD subjects (Group A-C) will be determined by stratified randomization; healthy control subjects (Group D) will be tested in the same sequence as the matched Group A subjects.
Serum concentrations of GH will be measured at pre-defined time points before and after GHST with macimorelin or insulin. A peak GH value below the GHST-specific cut-off value will be considered 'test positive'. The ITT will be considered as comparator (non-reference standard) to assess positive and negative agreement of both GHSTs, based on the predefined cut-off values.
The following cut-off values for simulated GH levels were used for both GHST tests to be compared: macimorelin-GHST: GH: 2.8 ng/mL, ITT: GH: 5.1 ng/mL.
Amendment no. 1 (repeatability extension): had been issued for selected sites in Europe to obtain exploratory data on the repeatability of the MAC in a subset of subjects (planned N=30, 10 per Group) that had completed the core study.
- Being tested
- Macimorelin, Insulin
- Keywords
- Adult Growth Hormone Deficiency
- Medical subject headings
- Growth Hormone Deficiency With Pituitary Anomalies, Dwarfism, Pituitary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MacimorelinDrug
Also called Macimorelin-GHST (MAC)
macimorelin acetate, 0.5 mg/kg body weight, drinking solution, single dose
InsulinDrug
Also called Insulin Tolerance Test (ITT)
Insulin, 0.10 U/kg (0.15 U/kg if BMI > 30 kg/m2), intravenous injection, single dose
| Study group | Role | What they receive |
|---|---|---|
| GHST Sequence A | Experimental | 1st Macimorelin-GHST, 2nd Insulin Tolerance Test Receives: Drug: Macimorelin; Drug: Insulin |
| GHST Sequence B | Experimental | 1st Insulin Tolerance Test, 2nd Macimorelin-GHST Receives: Drug: Macimorelin; Drug: Insulin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Co-primary Efficacy Variables: Percent Positive and Percent Negative Agreement of Macimorelin-GHST (MAC) With ITT
In the primary efficacy analysis, the estimated percentages of the agreements and the two-sided 95% confidence interval (or one-sided 97.5% confidence interval) of the percent agreement based on Clopper-Pearson are presented. The probability for a "Negative Agreement" equals the sum of the probability of both tests being correct (negative test results for both tests for subjects with "true non-AGHD") and the probability of both tests being wrong (negative test results for both tests for subjects with "true AGHD").
The performance of the GHST with Macimorelin was considered to be acceptable if the lower bound of the two-sided 95% confidence interval (or lower bound of the one-sided 97.5% confidence interval) for the primary efficacy variables was 75% or higher for 'percent negative agreement', and 70% or higher for the 'percent positive agreement'.
The following cut-off values for stimulated GH levels were used: - MAC: GH: 2.8 ng/mL, - ITT: GH: 5.1 ng/mL.
Measured: 90 minutes
Secondary outcomes (3)
Overall Agreements (Positive/ Negative) for MAC and ITT
As part of the secondary efficacy analysis, the percent of overall agreement was analyzed, using the same methodology described for the analyses for the primary efficacy variables.
Measured: 90 minutes
Number of Participants With Any Test Emergent Adverse Event (TEAE), With Any TEAE Likely or Possibly Related, and With Any Test Emergent Severe AE
GHST ('Test') emergent AEs (TEAEs): AEs occurring or observed from the day of first GHST (administration of an IMP) throughout End-of-Study (EOS) visit or Early Termination, whichever occurred first. TEAEs were analyzed and compared for both GHSTs. Detailed listings are presented in the Adverse Events section. The frequencies presented in this section refer to number of subjects with any TEAE, each subject was counted only once within each category.
Measured: up to 70 days
ECG: Change in Heart Rate From Baseline at 60 Minutes Post-dose
During the GHSTs, ECGs were measured at pre-dose (up to 15 min before) and 60 minutes post-dose. Furthermore, ECGs were measured at screening and at End-of-Study (EOS) Visit.
Measured: 60 minutes
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Sep 2015 (estimated)
- Study start3 Dec 2015
- Primary completion29 Nov 2016
- Study completion29 Nov 2016
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 Growth Hormone Deficiency With Pituitary AnomaliesStudies 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
- Masking
- None (open label)
- Enrolment
- 157 participants (actual)
Sponsor and investigators
- Lead sponsor
- AEterna Zentaris
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Jose M Garcia, MD PhD, Study chair, Baylor College of Medicine, Houston, TX, U.S.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02558829
- Sponsor's protocol ID
- AEZS-130-052
- Other IDs
- 2015-002337-22, 2015
- Status last verified
- Mar 2018
- First submitted
- 21 Sep 2015
- Last updated
- 10 Apr 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- Undecided
Publications
Garcia JM, Biller BMK, Korbonits M, Popovic V, Luger A, Strasburger CJ, Chanson P, Medic-Stojanoska M, Schopohl J, Zakrzewska A, Pekic S, Bolanowski M, Swerdloff R, Wang C, Blevins T, Marcelli M, Ammer N, Sachse R, Yuen KCJ. Macimorelin as a Diagnostic Test for Adult GH Deficiency. J Clin Endocrinol Metab. 2018 Aug 1;103(8):3083-3093. doi: 10.1210/jc.2018-00665.
PubMed 29860473
Study at a glance
From the registry record, last updated by the sponsor on 10 Apr 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Confirmatory Validation of Oral Macimorelin as a Growth Hormone (GH) Stimulation Test (ST) for the Diagnosis of Adult Growth Hormone Deficiency (AGHD) in Comparison With the Insulin Tolerance Test (ITT)
- ClinicalTrials.gov ID
- NCT02558829
- Acronym / sponsor ID
- AEZS-130-052
- Keywords
- Adult Growth Hormone Deficiency
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 157 participants (actual)
- Lead sponsor
- AEterna ZentarisIndustry (pharma, biotech, devices)
- Study start
- 3 Dec 2015 (actual)
- Primary completion
- 29 Nov 2016 (actual)
- Study completion
- 29 Nov 2016 (actual)
- First posted
- 24 Sep 2015 (estimated)
- Results
- Posted 9 Feb 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The Macimorelin Growth Hormone Stimulation Test (GHST) will be compared with the Insulin Tolerance Test (ITT) in an open-label, randomized, 2-way crossover Trial. The trial will include subjects suspected to have adult growth hormone deficiency (AGHD) and a group of healthy control subjects.
Detailed description
Trial subjects will be assigned to groups of descending likelihood of having AGHD:
Group A, B, C: High, intermediate, and low likelihood of GHD, respectively; Group D: Healthy control subjects matching Group A subjects .
The sequential order of the GHSTs for suspected AGHD subjects (Group A-C) will be determined by stratified randomization; healthy control subjects (Group D) will be tested in the same sequence as the matched Group A subjects.
Serum concentrations of GH will be measured at pre-defined time points before and after GHST with macimorelin or insulin. A peak GH value below the GHST-specific cut-off value will be considered 'test positive'. The ITT will be considered as comparator (non-reference standard) to assess positive and negative agreement of both GHSTs, based on the predefined cut-off values.
The following cut-off values for simulated GH levels were used for both GHST tests to be compared: macimorelin-GHST: GH: 2.8 ng/mL, ITT: GH: 5.1 ng/mL.
Amendment no. 1 (repeatability extension): had been issued for selected sites in Europe to obtain exploratory data on the repeatability of the MAC in a subset of subjects (planned N=30, 10 per Group) that had completed the core study.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| GHST Sequence A | Experimental | Drug: Macimorelin, Drug: Insulin1st Macimorelin-GHST, 2nd Insulin Tolerance Test |
| GHST Sequence B | Experimental | Drug: Macimorelin, Drug: Insulin1st Insulin Tolerance Test, 2nd Macimorelin-GHST |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Suspected growth hormone deficiency (GHD), based on either of the following:
- Healthy* control subjects, matching a 'high likelihood GHD' subjects
Key exclusion criteria (25 listed)
- GH therapy within 1 month prior to anticipated first GHST within this trial (within 3 months in case of long-acting GH formulation).
- GHST within 7 days prior to the anticipated first test day within the trial.
- Subjects with a medical history and clinical signs of a not adequately treated thyroid dysfunction or subjects who had a change in thyroid therapy within 30 days prior to anticipated first test day within the trial.
- Untreated hypogonadism or not on a stable substitution treatment within 30 days prior to anticipated first test day within the trial.
- Treatment with drugs directly affecting the pituitary secretion of somatotropin (e.g. somatostatin analogues, clonidine, levodopa, and dopamine agonists) or provoking the release of somatostatin; antimuscarinic agents (atropine).
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 |
|---|---|---|
| MacimorelinAlso: Macimorelin-GHST (MAC)macimorelin acetate, 0.5 mg/kg body weight, drinking solution, single dose | Drug | GHST Sequence A, GHST Sequence B |
| InsulinAlso: Insulin Tolerance Test (ITT)Insulin, 0.10 U/kg (0.15 U/kg if BMI > 30 kg/m2), intravenous injection, single dose | Drug | GHST Sequence A, GHST Sequence B |
Primary outcome
Co-primary Efficacy Variables: Percent Positive and Percent Negative Agreement of Macimorelin-GHST (MAC) With ITT
Time frame: 90 minutes
In the primary efficacy analysis, the estimated percentages of the agreements and the two-sided 95% confidence interval (or one-sided 97.5% confidence interval) of the percent agreement based on Clopper-Pearson are presented. The probability for a "Negative Agreement" equals the sum of the probability of both tests being correct (negative test results for both tests for subjects with "true non-AGHD") and the probability of both tests being wrong (negative test results for both tests for subjects with "true AGHD"). The performance of the GHST with Macimorelin was considered to be acceptable if the lower bound of the two-sided 95% confidence interval (or lower bound of the one-sided 97.5% confidence interval) for the primary efficacy variables was 75% or higher for 'percent negative agreement', and 70% or higher for the 'percent positive agreement'. The following cut-off values for stimulated GH levels were used: - MAC: GH: 2.8 ng/mL, - ITT: GH: 5.1 ng/mL.
3 secondary outcomes
Overall Agreements (Positive/ Negative) for MAC and ITT
Time frame: 90 minutes
Number of Participants With Any Test Emergent Adverse Event (TEAE), With Any TEAE Likely or Possibly Related, and With Any Test Emergent Severe AE
Time frame: up to 70 days
ECG: Change in Heart Rate From Baseline at 60 Minutes Post-dose
Time frame: 60 minutes
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Apr 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 29860473Garcia JM, Biller BMK, Korbonits M, Popovic V, Luger A, Strasburger CJ, Chanson P, Medic-Stojanoska M, Schopohl J, Zakrzewska A, Pekic S, Bolanowski M, Swerdloff R, Wang C, Blevins T, Marcelli M, Ammer N, Sachse R, Yuen KCJ. Macimorelin as a Diagnostic Test for Adult GH Deficiency. J Clin Endocrinol Metab. 2018 Aug 1;103(8):3083-3093. doi: 10.1210/jc.2018-00665.
- Individual participant dataSharing planned: Undecided
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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.
Jose M Garcia, MD PhD study chair
Baylor College of Medicine, Houston, TX, U.S.
27 sites in 9 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Macimorelin and Insulin in people with Growth Hormone Deficiency With Pituitary Anomalies, run by AEterna Zentaris at 27 sites in 9 countries.
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 7 inclusion and 25 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 10 Apr 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 27 sites in United States, Germany, Poland, France, Spain and 4 more countries. 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 9 Feb 2018). 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?
Co-primary Efficacy Variables: Percent Positive and Percent Negative Agreement of Macimorelin-GHST (MAC) With ITT (time frame: 90 minutes). 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 NCT02558829, 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 10 Apr 2018.