Validation of Macimorelin as a Test for Adult Growth Hormone Deficiency

NCT02558829 | Completed Phase 3 Results

• 2 other identifiers: AEZS-130-0522015-002337-22
• Study Type: interventional
• Target: 157
• Locations: 9 countries
• Sites: 27

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.

Conditions

Growth Hormone Deficiency With Pituitary Anomalies

Keywords

Adult Growth Hormone Deficiency

Outcome Measures

Primary Outcomes (1)

• 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.

  90 minutes

Secondary Outcomes (3)

• Overall Agreements (Positive/ Negative) for MAC and ITT

  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

  up to 70 days

• ECG: Change in Heart Rate From Baseline at 60 Minutes Post-dose

  60 minutes

Other Outcomes (2)

• Sensitivity and Specificity of the MAC, GH: 2.8 ng/mL

  90 minutes

• Agreement (Positive/Negative) for MAC Core Study Part and MAC Repeatability Extension (Amendment 1)

  90 minutes

Study Arms (2)

GHST Sequence A

EXPERIMENTAL

1st Macimorelin-GHST, 2nd Insulin Tolerance Test

Drug: Macimorelin; Drug: Insulin

GHST Sequence B

EXPERIMENTAL

1st Insulin Tolerance Test, 2nd Macimorelin-GHST

Drug: Macimorelin; Drug: Insulin

Interventions

Macimorelin DRUG

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

Also known as: Macimorelin-GHST (MAC)

GHST Sequence A; GHST Sequence B

Insulin DRUG

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

Also known as: Insulin Tolerance Test (ITT)

GHST Sequence A; GHST Sequence B

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• AEterna Zentaris: lead

Study Sites (27)

Harbor UCLA Medical Center

Torrance, California, 90509, United States

Location

Texas Diabetes and Endocrinology

Austin, Texas, 78731, United States

Location

Baylor College of Medicine-Endocrinology

Houston, Texas, 77030, United States

Location

VA Puget Sound Health Care System

Seattle, Washington, 98108, United States

Location

Swedish Medical Center - Cherry Hill

Seattle, Washington, 98122, United States

Location

Krankenanstalt Rudolfstiftung

Vienna, 1030, Austria

Location

Medical University & General Hospital of Vienna, AKH,

Vienna, 1090, Austria

Location

CHU de Lyon HCL-GH Est

Bron, 69677, France

Location

GHU Paris-Sud - Hôpital de Bicêtre

Le Kremlin-Bicêtre, 94270, France

Location

Hôpital Haut-Lévêque

Pessac, 33600, France

Location

Klinikum der LMU München

Munich, Bavaria, 80336, Germany

Location

Max Planck Institut

Munich, Bavaria, 80804, Germany

Location

University Hospital Marburg

Marburg, Hesse, 35033, Germany

Location

RWTH Aachen University Hospital

Aachen, North Rhine-Westphalia, 52074, Germany

Location

Klinik für Endokrinologie, Diabetes und Ernährungsmedizin der Charité

Berlin, 10117, Germany

Location

San Luca Hospital

Milan, 20149, Italy

Location

Centrum Kliniczno-Badawcze

Elblag, 82-300, Poland

Location

Centrum Medyczne Angelius Provita

Katowice, 40-611, Poland

Location

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

Warsaw, 02-106, Poland

Location

Wromedica

Wroclaw, 51-685, Poland

Location

Clinical Centre of Serbia

Belgrade, 11000, Serbia

Location

Clinical Centre of Vojvodina

Novi Sad, 21000, Serbia

Location

Hospital de Sant Pau

Barcelona, 08026, Spain

Location

Hospital Universitari Vall d' Hebron

Barcelona, 08035, Spain

Location

Hospital de Conxo

Santiago de Compostela, 15706, Spain

Location

St Bartholomew's Hospital

London, EC1A 7BE, United Kingdom

Location

The Christie NHS Foundation Trust

Manchester, M20 4BX, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 29860473 DERIVED

MeSH Terms

Conditions

Growth Hormone Deficiency With Pituitary Anomalies; Dwarfism, Pituitary

Interventions

macimorelin; Insulin

Condition Hierarchy (Ancestors)

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; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Proinsulin; Insulins; Pancreatic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: Dr. Nicola Ammer
• Organization: Aeterna Zentaris

nammer@aezsinc.com

+496942602

Study Officials

• Jose M Garcia, MD PhD

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

  STUDY CHAIR

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
• Masking Details: This was an open label trial. No masking with regard to the Growth Hormone Stimulation Tests (GHSTs) performed was done. However, Data Review Committee/Sponsor/Project Management was masked towards the Growth Hormone (GH) values as results fo both tests. GH values were provided to the investigator only after both GHSTs had been performed, to avoid bias.
• Purpose: DIAGNOSTIC
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 21, 2015
• First Posted: September 24, 2015
• Study Start: December 3, 2015
• Primary Completion: November 29, 2016
• Study Completion: November 29, 2016
• Last Updated: April 10, 2018
• Results First Posted: February 9, 2018

Record last verified: 2018-03

Locations

US (5); FR (3); PL (4); AU (2); ES (3); IT (1); GB (2); DE (5); SE (2)