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Trial record 2 of 5 for:    "Hypopituitarism" | "Zinc"

Validation of Macimorelin as a Test for Adult Growth Hormone Deficiency

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02558829
Recruitment Status : Completed
First Posted : September 24, 2015
Results First Posted : February 9, 2018
Last Update Posted : April 10, 2018
Sponsor:
Information provided by (Responsible Party):
AEterna Zentaris

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: None (Open Label);   Primary Purpose: Diagnostic
Condition Growth Hormone Deficiency With Pituitary Anomalies
Interventions Drug: Macimorelin
Drug: Insulin
Enrollment 157
Recruitment Details

Study centers: 30 sites in 9 countries had been initiated,i.e. 25 sites in Europe (Austria, Germany, Spain, France, Italy, Poland, Serbia, and UK) with 21 of them becoming active, and 5 sites in the USA.

Study period: first subject screened: 01-Oct-2015, first subject randomized (= enrolled): 03-Dec-2015, Last subject completed: 29-Nov-2016.

Pre-assignment Details A subject registered in the eCRF as ‘eligible’ was assigned to the applicable Group A/B/C (= stratum). The sequence for performance of both growth hormone stimulation tests (GHSTs) in Group A/B/C subjects was assigned by stratified randomization. Healthy control subjects (Group D) were tested in the same sequence as the matched Group A subjects.
Arm/Group Title Group A Test Sequence MAC-ITT Group A Test Sequence ITT-MAC Group B Test Sequence MAC-ITT Group B Test Sequence ITT- MAC Group C Test Sequence MAC-ITT Group C Test Sequence ITT-MAC Group D Test Sequence MAC-ITT Group D Test Sequence ITT-MAC
Hide Arm/Group Description

Group A: High likelihood of GHD:

  • structural hypothalamic or pituitary lesions and low IGF-1, and/or - three or more pituitary hormone deficiencies (PHD) and low IGF-1, or
  • childhood onset GHD with structural lesions and low IGF-1.

Randomization of GHST administration to following test sequence:

1st Macimorelin-GHST (MAC), 2nd Insulin Tolerance Test (ITT).

Macimorelin GHST: administration of macimorelin acetate, 0.5 mg/kg body weight, drinking solution, single dose.

Insulin Tolerance Test: administration of regular human insulin, 0.10 U/kg (0.15 U/kg if BMI > 30 kg/m2), intravenous injection, single dose.

Group A: High likelihood of GHD:

  • structural hypothalamic or pituitary lesions and low IGF-1, and/or - three or more pituitary hormone deficiencies (PHD) and low IGF-1, or
  • childhood onset GHD with structural lesions and low IGF-1

Randomization of GHST administration to following test sequence:

1st Insulin Tolerance Test (ITT), 2nd Macimorelin-GHST (MAC)

Insulin Tolerance Test: administration of regular human insulin, 0.10 U/kg (0.15 U/kg if BMI > 30 kg/m2), intravenous injection, single dose.

Macimorelin GHST: administration of macimorelin acetate, 0.5 mg/kg body weight, drinking solution, single dose.

Group B: intermediate likelihood of GHD:

- eligible subjects not qualifying for either high or low likelihood (Group A/C)

Randomization of GHST administration to following test sequence:

1st Macimorelin-GHST (MAC), 2nd Insulin Tolerance Test (ITT).

Macimorelin GHST: administration of macimorelin acetate, 0.5 mg/kg body weight, drinking solution, single dose.

Insulin Tolerance Test: administration of regular human insulin, 0.10 U/kg (0.15 U/kg if BMI > 30 kg/m2), intravenous injection, single dose.

Group B: intermediate likelihood of GHD:

- eligible subjects not qualifying for either high or low likelihood (Group A/C)

Randomization of GHST administration to following test sequence:

1st Insulin Tolerance Test (ITT), 2nd Macimorelin-GHST (MAC)

Insulin Tolerance Test: administration of regular human insulin, 0.10 U/kg (0.15 U/kg if BMI > 30 kg/m2), intravenous injection, single dose.

Macimorelin GHST: administration of macimorelin acetate, 0.5 mg/kg body weight, drinking solution, single dose.

Group C: Low likelihood of GHD

  • one risk factor for GHD only, such as history of distant traumatic brain injury (TBI) or one PHD only with otherwise normal pituitary function or
  • isolated idiopathic childhood onset GHD without additional pituitary deficits.

Randomization of GHST administration to following test sequence:

1st Macimorelin-GHST (MAC), 2nd Insulin Tolerance Test (ITT).

Macimorelin GHST: administration of macimorelin acetate, 0.5 mg/kg body weight, drinking solution, single dose.

Insulin Tolerance Test: administration of regular human insulin, 0.10 U/kg (0.15 U/kg if BMI > 30 kg/m2), intravenous injection, single dose.

Group C: Low likelihood of GHD

  • one risk factor for GHD only, such as history of distant traumatic brain injury (TBI) or one PHD only with otherwise normal pituitary function or
  • isolated idiopathic childhood onset GHD without additional pituitary deficits.

Randomization of GHST administration to following test sequence:

1st Insulin Tolerance Test (ITT), 2nd Macimorelin-GHST (MAC)

Insulin Tolerance Test: administration of regular human insulin, 0.10 U/kg (0.15 U/kg if BMI > 30 kg/m2), intravenous injection, single dose.

Macimorelin GHST: administration of macimorelin acetate, 0.5 mg/kg body weight, drinking solution, single dose.

Group D: Healthy control. Healthy subjects matching Group A subjects by sex, age, BMI, and estrogen status (females only).

Randomization of GHST administration to following test sequence:

1st Macimorelin-GHST (MAC), 2nd Insulin Tolerance Test (ITT).

Macimorelin GHST: administration of macimorelin acetate, 0.5 mg/kg body weight, drinking solution, single dose.

Insulin Tolerance Test: administration of regular human insulin, 0.10 U/kg (0.15 U/kg if BMI > 30 kg/m2), intravenous injection, single dose.

Group D: Healthy control. Healthy subjects matching Group A subjects by sex, age, BMI, and estrogen status (females only).

Randomization of GHST administration to following test sequence:

1st Insulin Tolerance Test (ITT), 2nd Macimorelin-GHST (MAC)

Insulin Tolerance Test: administration of regular human insulin, 0.10 U/kg (0.15 U/kg if BMI > 30 kg/m2), intravenous injection, single dose.

Macimorelin GHST: administration of macimorelin acetate, 0.5 mg/kg body weight, drinking solution, single dose.

Period Title: Overall Study
Started [1] 21 21 24 18 18 26 18 11
Completed [2] 20 18 21 16 16 24 17 8
Not Completed 1 3 3 2 2 2 1 3
[1]
Safety population (SAF): all randomized subjects who took at least one dose of trial medication.
[2]
Modified Intention-to-Treat (mITT): randomized subjects with both GHSTs of the cross-over evaluable.
Arm/Group Title Group A Group B Group C Group D Total
Hide Arm/Group Description

High likelihood of growth hormone deficiency (GHD):

  • Structural hypothalamic or pituitary lesions and low insulin-like growth factor 1 (IGF-1), and/or
  • Three or more pituitary hormone deficiencies (PHD) and low IGF-1, or
  • Childhood onset GHD with structural lesions and low IGF-1.

Intermediate likelihood of GHD:

• Eligible subjects not qualifying for either high or low likelihood (Group A/C)

Low likelihood of GHD:

  • One risk factor for GHD only, such as history of distant traumatic brain injury (TBI) or one PHD only with otherwise normal pituitary function or
  • Isolated idiopathic childhood onset GHD without additional pituitary deficits
Healthy control. Healthy subjects matching Group A subjects by sex, age, body mass index (BMI), and estrogen status (females only). Total of all reporting groups
Overall Number of Baseline Participants 42 42 44 29 157
Hide Baseline Analysis Population Description
Baseline participants = safety analysis set (SAF, N=157). Efficacy analysis is based on the modified Intention-to-Treat (mITT, N=140): all randomized subjects in whom both GHSTs of the cross-over are evaluable. (In the EU only: 34 patients from the mITT underwent a repeated MAC (repeatability extension, Amendment 1).)
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 42 participants 42 participants 44 participants 29 participants 157 participants
42.3  (15.0) 45.8  (11.8) 34.9  (10.5) 40.0  (12.4) 40.7  (13.1)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 42 participants 42 participants 44 participants 29 participants 157 participants
Female
17
  40.5%
24
  57.1%
9
  20.5%
14
  48.3%
64
  40.8%
Male
25
  59.5%
18
  42.9%
35
  79.5%
15
  51.7%
93
  59.2%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 42 participants 42 participants 44 participants 29 participants 157 participants
Hispanic or Latino
4
   9.5%
9
  21.4%
2
   4.5%
0
   0.0%
15
   9.6%
Not Hispanic or Latino
34
  81.0%
29
  69.0%
36
  81.8%
29
 100.0%
128
  81.5%
Unknown or Not Reported
4
   9.5%
4
   9.5%
6
  13.6%
0
   0.0%
14
   8.9%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 42 participants 42 participants 44 participants 29 participants 157 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asian
2
   4.8%
1
   2.4%
2
   4.5%
0
   0.0%
5
   3.2%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
1
   2.3%
0
   0.0%
1
   0.6%
Black or African American
0
   0.0%
1
   2.4%
2
   4.5%
0
   0.0%
3
   1.9%
White
36
  85.7%
36
  85.7%
34
  77.3%
29
 100.0%
135
  86.0%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
4
   9.5%
4
   9.5%
5
  11.4%
0
   0.0%
13
   8.3%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 42 participants 42 participants 44 participants 29 participants 157 participants
Austria
4
   9.5%
3
   7.1%
0
   0.0%
0
   0.0%
7
   4.5%
United States
6
  14.3%
13
  31.0%
18
  40.9%
0
   0.0%
37
  23.6%
Poland
2
   4.8%
4
   9.5%
14
  31.8%
29
 100.0%
49
  31.2%
United Kingdom
0
   0.0%
1
   2.4%
0
   0.0%
0
   0.0%
1
   0.6%
Italy
0
   0.0%
1
   2.4%
0
   0.0%
0
   0.0%
1
   0.6%
France
3
   7.1%
5
  11.9%
4
   9.1%
0
   0.0%
12
   7.6%
Serbia
12
  28.6%
2
   4.8%
7
  15.9%
0
   0.0%
21
  13.4%
Germany
8
  19.0%
12
  28.6%
1
   2.3%
0
   0.0%
21
  13.4%
Spain
7
  16.7%
1
   2.4%
0
   0.0%
0
   0.0%
8
   5.1%
Body Mass Index (kg/m^2)  
Mean (Standard Deviation)
Unit of measure:  Kg/m^2
Number Analyzed 42 participants 42 participants 44 participants 29 participants 157 participants
27.6  (4.6) 29.8  (4.5) 27.9  (5.7) 26.1  (3.2) 28.0  (4.8)
1.Primary Outcome
Title Co-primary Efficacy Variables: Percent Positive and Percent Negative Agreement of Macimorelin-GHST (MAC) With ITT
Hide Description

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.

Time Frame 90 minutes
Hide Outcome Measure Data
Hide Analysis Population Description
All subjects from Groups A, B, C, D included in the modified intention-to-treat (mITT) analysis, N=140
Arm/Group Title Positive MAC, Positive ITT Positive MAC, Negative ITT Negative MAC, Positive ITT Negative MAC, Negative ITT
Hide Arm/Group Description:
Test outcome positive for MAC and for ITT
Test outcome positive for MAC and negative for ITT
Test outcome negative for MAC and positive for ITT
Test outcome negative for MAC and for ITT
Overall Number of Participants Analyzed 140 140 140 140
Measure Type: Count of Participants
Unit of Measure: Participants
55
  39.3%
4
   2.9%
19
  13.6%
62
  44.3%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Positive MAC, Positive ITT, Negative MAC, Positive ITT
Comments 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 performance of the MAC (cut-off point 2.8 ng/mL) was considered to be acceptable if the lower bound of the two-sided 95% CI (or lower bound of the one-sided 97.5% CI) was 75% or higher for ‘percent negative agreement’, and 70% or higher for the ‘percent positive agreement’.
Type of Statistical Test Other
Comments Positive percent agreement [%] = 100% x A/(A+C). A= MAC outcome positive and ITT outcome positive; C = MAC outcome negative and ITT positive
Method of Estimation Estimation Parameter CI (Clopper Pearson): positive agreement
Estimated Value 74.32
Confidence Interval (2-Sided) 95%
62.84 to 83.78
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Positive MAC, Negative ITT, Negative MAC, Negative ITT
Comments Please refer to Statistical Analysis 1.
Type of Statistical Test Other
Comments Negative percent agreement [%] = 100% x D/(B+D). D = MAC outcome negative and ITT outcome negative; B = MAC outcome positive and ITT outcome negative
Method of Estimation Estimation Parameter CI (Clopper Pearson): negative agreement
Estimated Value 93.94
Confidence Interval (2-Sided) 95%
85.20 to 98.32
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Overall Agreements (Positive/ Negative) for MAC and ITT
Hide Description 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.
Time Frame 90 minutes
Hide Outcome Measure Data
Hide Analysis Population Description
All subjects from Groups A, B, C, D included in the modified intention-to-treat (mITT) analysis, N=140
Arm/Group Title Positive MAC, Positive ITT Positive MAC, Negative ITT Negative MAC, Positive ITT Negative MAC, Negative ITT
Hide Arm/Group Description:
Test outcome positive for MAC and for ITT
Test outcome positive for MAC and negative for ITT
Test outcome negative for MAC and positive for ITT
Test outcome negative for MAC and for ITT
Overall Number of Participants Analyzed 140 140 140 140
Measure Type: Count of Participants
Unit of Measure: Participants
55
  39.3%
4
   2.9%
19
  13.6%
62
  44.3%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Positive MAC, Positive ITT, Positive MAC, Negative ITT, Negative MAC, Positive ITT, Negative MAC, Negative ITT
Comments This variable was analyzed using the same methodology described for the analyses for the primary efficacy variables. in the below, the results for Step 1 (peak GH level among all post baseline samples) are presented.
Type of Statistical Test Other
Comments The secondary diagnostic accuracy measure was ‘percent overall agreement’.
Method of Estimation Estimation Parameter overall agreement
Estimated Value 83.57
Confidence Interval (2-Sided) 95%
76.38 to 89.29
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Number of Participants With Any Test Emergent Adverse Event (TEAE), With Any TEAE Likely or Possibly Related, and With Any Test Emergent Severe AE
Hide Description 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.
Time Frame up to 70 days
Hide Outcome Measure Data
Hide Analysis Population Description
All subjects of Group A, B, C, D in the safety population.
Arm/Group Title Insulin Tolerance Test (ITT), All Groups, SAF Population Macimorelin GHST (MAC), All Groups, SAF Population
Hide Arm/Group Description:
All subjects of Group A, B, C, and D with at least one ITT performed: N=157
All subjects of Group A, B, C, and D with at least one macimorelin GHST: N=154 (three subjects were not exposed to MAC but were exposed to ITT only).
Overall Number of Participants Analyzed 157 154
Measure Type: Count of Participants
Unit of Measure: Participants
Any TEAE (any relation)
151
  96.2%
39
  25.3%
Any TEAE (likely or possible related)
149
  94.9%
22
  14.3%
Any test emergent severe AE
11
   7.0%
1
   0.6%
4.Secondary Outcome
Title ECG: Change in Heart Rate From Baseline at 60 Minutes Post-dose
Hide Description 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.
Time Frame 60 minutes
Hide Outcome Measure Data
Hide Analysis Population Description
All subjects of Group A, B, C, D in the safety population. Because of single ECGs missing, the number of participants analyzed here is lower than the number of the subjects in the SAF.
Arm/Group Title MAC, Heart Rate at Pre-dose MAC, HR at Post-dose ITT, HR at Pre-dose ITT, HR at Post-dose
Hide Arm/Group Description:
Macimorelin GHST, heart rate (HR) value at test/time point pre-dose.
Macimorelin GHST, HR value at test/time point 60 minutes post-dose.
Insulin Tolerance Test, HR value at test/time point pre-dose.
Insulin Tolerance Test, HR value at test/time point 60 minutes post-dose.
Overall Number of Participants Analyzed 153 153 156 155
Mean (Standard Deviation)
Unit of Measure: beats per minute
63.4  (10.35) 60.5  (9.47) 63.7  (10.70) 65.6  (10.90)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection MAC, Heart Rate at Pre-dose, MAC, HR at Post-dose
Comments

Pre/post dose comparison of ECGs was done for both GHSTs. 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.

Calculations were done from two time points: baseline and 60 min post-dose. Baseline is either the screening or pre-dose value.

Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.9
Parameter Dispersion
Type: Standard Deviation
Value: 6.38
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection ITT, HR at Pre-dose, ITT, HR at Post-dose
Comments [Not Specified]
Type of Statistical Test Other
Comments Please refer to Statistical Analysis 1 for this secondary outcome measure.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 1.8
Parameter Dispersion
Type: Standard Deviation
Value: 8.15
Estimation Comments [Not Specified]
5.Other Pre-specified Outcome
Title Sensitivity and Specificity of the MAC, GH: 2.8 ng/mL
Hide Description Exploratory evaluation of sensitivity and specificity of the MAC as performance characteristic, based on test outcome in Group A and Group D subjects.
Time Frame 90 minutes
Hide Outcome Measure Data
Hide Analysis Population Description
All high likelihood AGHD subjects of Group A (N=38) of the mITT population as ‘true’ AGHD subjects and all healthy matching subjects of Group D (N=25) of the mITT population as ‘true’ AGHD negative subjects
Arm/Group Title Positive MAC, Group A Positive MAC, Group D Negative MAC, Group A Negative MAC, Group D
Hide Arm/Group Description:
Positive test outcome of the MAC in subjects of AGHD likelihood group A (high likelihood)
positive test outcome of the MAC in subjects of Group D (healthy matched controls)
Negative test outcome of the MAC in subjects of AGHD likelihood group A (high likelihood)
Negative test outcome of the MAC in subjects of Group D (healthy matched controls)
Overall Number of Participants Analyzed 38 25 38 25
Measure Type: Count of Participants
Unit of Measure: Participants
33
  86.8%
1
   4.0%
5
  13.2%
24
  96.0%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Positive MAC, Group A, Negative MAC, Group A
Comments Sensitivity was estimated for the MAC at the pre-defined cut-off point GH: 2.8 ng/mL.
Type of Statistical Test Other
Comments Sensitivity is the probability that the test result is positive given the subject has the disease (for the purpose of this analysis, all group A subjects were assumed to have AGHD, but none of the group D subjects). Sensitivity (SS) was estimated by: SS = TP/(TP+FN). TP=True AGHD positive subject; FN=False AGHD negative subject.
Method of Estimation Estimation Parameter CI (Clopper Pearson)
Estimated Value 0.87
Confidence Interval (2-Sided) 95%
0.72 to 0.96
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Positive MAC, Group D, Negative MAC, Group D
Comments Specificity was estimated for the MAC at the pre-defined cut-off point GH: 2.8 ng/mL.
Type of Statistical Test Other
Comments

Specificity is the probability that the test result is negative given the subject does not have the disease.

Specificity (SP) was estimated by: SP = TN/(TN+FP). TN = True AGHD negative Subjects; FP = False AGHD positive subjects.

Method of Estimation Estimation Parameter CI (Clopper Pearson)
Estimated Value 0.96
Confidence Interval (2-Sided) 95%
0.80 to 1.00
Estimation Comments [Not Specified]
6.Other Pre-specified Outcome
Title Agreement (Positive/Negative) for MAC Core Study Part and MAC Repeatability Extension (Amendment 1)
Hide Description 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 that had completed the core study. Pre-defined MAC cut-off point GH: 2.8 ng/mL. Agreements were calculated with two-sided 95% confidence intervals.
Time Frame 90 minutes
Hide Outcome Measure Data
Hide Analysis Population Description
All subjects included in the modified intention-to-treat (mITT) analysis who also participated in the repeatability extension, i.e. N=34 (comprising 13 Group A, 12 Group B, and 9 Group C subjects).
Arm/Group Title Positive MAC Core, Positive MAC Repeatability Positive MAC Core, Negative MAC Repeatability Negative MAC Core, Negative MAC Repeatability Negative MAC Core, Positive MAC Repeatability
Hide Arm/Group Description:
Test outcome positive for MAC in core study part and positive for MAC in the repeatability extension.
Test outcome positive for MAC in core study part and negative for MAC in the repeatability extension.
Test outcome negative for MAC in core study part and negative for MAC in the repeatability extension.
Test outcome negative for MAC in core study part and positive for MAC in the repeatability extension.
Overall Number of Participants Analyzed 34 34 34 34
Measure Type: Count of Participants
Unit of Measure: Participants
16
  47.1%
2
   5.9%
16
  47.1%
0
   0.0%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Positive MAC Core, Positive MAC Repeatability, Positive MAC Core, Negative MAC Repeatability
Comments Please refer to Statistical Analysis 1 for this outcome.
Type of Statistical Test Other
Comments Positive percent agreement [%] = 100% x A/(A+C). A= test outcome positive for MAC core study part and positive for MAC repeatability extension; C = test outcome positive for MAC core study part and negative for MAC repeatability extension.
Method of Estimation Estimation Parameter CI (Clopper Pearson): positive agreement
Estimated Value 88.89
Confidence Interval (2-Sided) 95%
65.29 to 98.62
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Negative MAC Core, Negative MAC Repeatability, Negative MAC Core, Positive MAC Repeatability
Comments Amendment no 1 had been issued for selected sites in Europe to obtain exploratory data on the repeatability of the MAC in a subset of subjects that had completed the core study.
Type of Statistical Test Other
Comments Negative percent agreement [%] = 100% x D/(B+D). D = test outcome negative for MAC core study part and negative for MAC repeatability extension; B = test outcome negative for MAC core study part and positive for MAC repeatability extension
Method of Estimation Estimation Parameter CI (Clopper Pearson): negative agreement
Estimated Value 100.00
Confidence Interval (2-Sided) 95%
79.41 to 100.00
Estimation Comments [Not Specified]
Time Frame Throughout the trial, i.e. over a period of ca. 15 months, the subjects were questioned and/or examined by the Investigators or his/her designee for evidence of adverse events (AEs). Per subject, the time frame for collection of such data was up to 70 days.
Adverse Event Reporting Description GHST emergent adverse events (TEAEs): all untoward effects during or after a GHST were documented in the electronic Case Report Form (eCRF), to ensure balanced representation of both GHSTs. Safety analyses were conducted using data from the Safety Population (SAF). The number and percentage of subjects with TEAEs was displayed for each GHST test drug by SOC and preferred term. Additionally, TEAEs were tabulated for each GHST by severity and by relationship to the GHST test drug.
 
Arm/Group Title Macimorelin GHST (MAC), SAF Population Insulin Tolerance Test (ITT), SAF Population
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Macimorelin GHST (MAC): combined safety data from core study and repeatability extension (Amendment 1, European sites only)).

All subjects of Group A, B, C, D with at least one macimorelin GHST performed: N=154.

All subjects of Group A, B, C, D valid for safety (SAF) analysis: N=157. (three subjects were exposed to the ITT only).

Repeatability extension (planned repetition of the MAC): subjects of Group A, B, C valid for safety (SAF)analysis: N=34.

Insulin Tolerance Test (ITT) All subjects of Group A, B, C, D with at least one ITT performed: N=157. All subjects of Group A, B, C, D valid for safety (SAF) analysis: N=157.
All-Cause Mortality
Macimorelin GHST (MAC), SAF Population Insulin Tolerance Test (ITT), SAF Population
Affected / at Risk (%) Affected / at Risk (%)
Total   0/154 (0.00%)      0/157 (0.00%)    
Show Serious Adverse Events Hide Serious Adverse Events
Macimorelin GHST (MAC), SAF Population Insulin Tolerance Test (ITT), SAF Population
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1/154 (0.65%)      1/157 (0.64%)    
Injury, poisoning and procedural complications     
Upper limp fracture  1 [1]  1/154 (0.65%)  1 1/157 (0.64%)  1
1
Term from vocabulary, MedDRA 18.0
Indicates events were collected by systematic assessment
[1]
The patient had underwent an ITT on July 5 and the macimorelin GHST on July 12, 2016. On July 13, the patient fell of a ladder accidentally and broke his left arm. Causality reported by investigator: unrelated to study treatment.
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 2%
Macimorelin GHST (MAC), SAF Population Insulin Tolerance Test (ITT), SAF Population
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   39/154 (25.32%)      151/157 (96.18%)    
Cardiac disorders     
Palpitations  1  1/154 (0.65%)  1 17/157 (10.83%)  18
Gastrointestinal disorders     
Nausea  1  5/154 (3.25%)  5 21/157 (13.38%)  22
General disorders     
Fatigue  1  6/154 (3.90%)  6 43/157 (27.39%)  49
Hunger  1  5/154 (3.25%)  5 46/157 (29.30%)  51
Asthenia  1  1/154 (0.65%)  1 30/157 (19.11%)  32
Chills  1  1/154 (0.65%)  1 9/157 (5.73%)  12
Feeling cold  1  1/154 (0.65%)  1 6/157 (3.82%)  6
Feeling hot  1  2/154 (1.30%)  2 44/157 (28.03%)  50
Thirst  1  1/154 (0.65%)  1 12/157 (7.64%)  13
Nervous system disorders     
Dizziness  1  6/154 (3.90%)  7 43/157 (27.39%)  48
Dysgeusia  1  7/154 (4.55%)  7 5/157 (3.18%)  7
Headache  1  6/154 (3.90%)  6 15/157 (9.55%)  16
Somnolence  1  1/154 (0.65%)  1 57/157 (36.31%)  62
Tremor  1  1/154 (0.65%)  1 25/157 (15.92%)  28
Skin and subcutaneous tissue disorders     
Hyperhidrosis  1  2/154 (1.30%)  2 105/157 (66.88%)  120
1
Term from vocabulary, MedDRA (18.0)
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
INSTITUTIONS / INVESTIGATORS are allowed to publish data pursuant to the Sponsor’s publication policies per individual agreements. Any material prepared for publication shall be submitted to the Sponsor for review and comment within an individually agreed period (30 up to 180 days). INSTITUTION / INVESTIGATOR shall modify the publication / presentation according to the comments by the Sponsor, provided that the scientific neutrality of the publication is not impaired hereby.
Results Point of Contact
Name/Title: Dr. Nicola Ammer
Organization: Aeterna Zentaris
Phone: +496942602 ext 3472
Responsible Party: AEterna Zentaris
ClinicalTrials.gov Identifier: NCT02558829     History of Changes
Other Study ID Numbers: AEZS-130-052
2015-002337-22 ( EudraCT Number )
First Submitted: September 21, 2015
First Posted: September 24, 2015
Results First Submitted: November 27, 2017
Results First Posted: February 9, 2018
Last Update Posted: April 10, 2018