Validation of Macimorelin as a Test for Adult Growth Hormone Deficiency

NCT ID: NCT02558829

Last Updated: 2018-04-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 157 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-12-03
• Study Completion Date: 2016-11-29

Brief 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.

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.

Conditions

Growth Hormone Deficiency With Pituitary Anomalies

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

GHST Sequence A

1st Macimorelin-GHST, 2nd Insulin Tolerance Test

Group Type: EXPERIMENTAL

Macimorelin

Intervention Type: DRUG

macimorelin acetate, 0.5 mg/kg body weight, drinking solution, single dose

Insulin

Intervention Type: DRUG

Insulin, 0.10 U/kg (0.15 U/kg if BMI \> 30 kg/m2), intravenous injection, single dose

GHST Sequence B

1st Insulin Tolerance Test, 2nd Macimorelin-GHST

Group Type: EXPERIMENTAL

Macimorelin

Intervention Type: DRUG

macimorelin acetate, 0.5 mg/kg body weight, drinking solution, single dose

Insulin

Intervention Type: DRUG

Insulin, 0.10 U/kg (0.15 U/kg if BMI \> 30 kg/m2), intravenous injection, single dose

Interventions

Macimorelin

macimorelin acetate, 0.5 mg/kg body weight, drinking solution, single dose

Intervention Type: DRUG

Insulin

Insulin, 0.10 U/kg (0.15 U/kg if BMI \> 30 kg/m2), intravenous injection, single dose

Intervention Type: DRUG

Other Intervention Names

Macimorelin-GHST (MAC); Insulin Tolerance Test (ITT)

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

• 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).
• 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

AEterna Zentaris

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jose M Garcia, MD PhD

Role: STUDY_CHAIR

Baylor College of Medicine, Houston, TX, U.S.

Locations

Harbor UCLA Medical Center

Torrance, California, United States

Texas Diabetes and Endocrinology

Austin, Texas, United States

Baylor College of Medicine-Endocrinology

Houston, Texas, United States

VA Puget Sound Health Care System

Seattle, Washington, United States

Swedish Medical Center - Cherry Hill

Seattle, Washington, United States

Krankenanstalt Rudolfstiftung

Vienna, , Austria

Medical University & General Hospital of Vienna, AKH,

Vienna, , Austria

CHU de Lyon HCL-GH Est

Bron, , France

GHU Paris-Sud - Hôpital de Bicêtre

Le Kremlin-Bicêtre, , France

Hôpital Haut-Lévêque

Pessac, , France

Klinikum der LMU München

Munich, Bavaria, Germany

Max Planck Institut

Munich, Bavaria, Germany

University Hospital Marburg

Marburg, Hesse, Germany

RWTH Aachen University Hospital

Aachen, North Rhine-Westphalia, Germany

Klinik für Endokrinologie, Diabetes und Ernährungsmedizin der Charité

Berlin, , Germany

San Luca Hospital

Milan, , Italy

Centrum Kliniczno-Badawcze

Elblag, , Poland

Centrum Medyczne Angelius Provita

Katowice, , Poland

Phase I - MTZ Clinical Research Sp. z o.o.

Warsaw, , Poland

Wromedica

Wroclaw, , Poland

Clinical Centre of Serbia

Belgrade, , Serbia

Clinical Centre of Vojvodina

Novi Sad, , Serbia

Hospital de Sant Pau

Barcelona, , Spain

Hospital Universitari Vall d' Hebron

Barcelona, , Spain

Hospital de Conxo

Santiago de Compostela, , Spain

St Bartholomew's Hospital

London, , United Kingdom

The Christie NHS Foundation Trust

Manchester, , United Kingdom

Countries

United States; Austria; France; Germany; Italy; Poland; Serbia; Spain; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 29860473 (View on PubMed)

Other Identifiers

2015-002337-22

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

AEZS-130-052

Identifier Type: -

Identifier Source: org_study_id