Trial Outcomes & Findings for Investigation of a New, Oral Growth Hormone Secretagogue, AEZS-130 as a Growth Hormone Stimulation Test. (NCT NCT00448747)

NCT ID: NCT00448747

Last Updated: 2019-07-23

Results Overview

The primary endpoint for each individual is the peak GH concentration following AEZS-130 (macimorelin) administration.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

101 participants

Primary outcome timeframe

GH sampling: pre-dose and 30, 45, 60, 75, 90, 120, 150 min post-dose

Results posted on

2019-07-23

Participant Flow

Overall, 53 AGHD patients and 48 matched control subjects were enrolled at 11 centers across the United States, and all subjects, with the exception of 1 AGHD patient, received macimorelin and completed the study. In Amendment No. 4, the objective of the study was changed to delete the comparison with L-ARG + GHRH.

Participant milestones

Participant milestones
Measure	AGHD Patients (= Cases) All Adult Growth Hormone Deficiency (AGHD) patients enrolled in the study.	Matched Controls (= Controls) All matched control subjects enrolled in the study.
Overall Study STARTED	53	48
Overall Study Received First Drug Administration	53	48
Overall Study Received Second Drug Administration	42	10
Overall Study Received AEZS-130	52	48
Overall Study Received L-ARG-GHRH	43	10
Overall Study Received L-ARG-GHRH and AEZS-130	42	10
Overall Study Per Protocol Population (PPS)	50	48
Overall Study COMPLETED	52	48
Overall Study NOT COMPLETED	1	0

Reasons for withdrawal

Reasons for withdrawal
Measure	AGHD Patients (= Cases) All Adult Growth Hormone Deficiency (AGHD) patients enrolled in the study.	Matched Controls (= Controls) All matched control subjects enrolled in the study.
Overall Study collapsed veins	1	0

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	AGHD Patients (= Cases) n=53 Participants All AGHD patients enrolled in the study.	Matched Controls (= Controls) n=48 Participants All matched control subjects enrolled in the study.	Total n=101 Participants Total of all reporting groups
Age, Customized < 50 years	27 Participants n=99 Participants	19 Participants n=107 Participants	46 Participants n=206 Participants
Age, Customized >= 50 years	26 Participants n=99 Participants	29 Participants n=107 Participants	55 Participants n=206 Participants
Sex: Female, Male Female	31 Participants n=99 Participants	30 Participants n=107 Participants	61 Participants n=206 Participants
Sex: Female, Male Male	22 Participants n=99 Participants	18 Participants n=107 Participants	40 Participants n=206 Participants
Race/Ethnicity, Customized White	49 Participants n=99 Participants	29 Participants n=107 Participants	78 Participants n=206 Participants
Race/Ethnicity, Customized Black or African American	2 Participants n=99 Participants	18 Participants n=107 Participants	20 Participants n=206 Participants
Race/Ethnicity, Customized Asian	2 Participants n=99 Participants	0 Participants n=107 Participants	2 Participants n=206 Participants
Race/Ethnicity, Customized Other	0 Participants n=99 Participants	1 Participants n=107 Participants	1 Participants n=206 Participants
Region of Enrollment United States	53 Participants n=99 Participants	48 Participants n=107 Participants	101 Participants n=206 Participants
Body Mass Index (kg/m^2) Lean (<25)	7 Participants n=99 Participants	7 Participants n=107 Participants	14 Participants n=206 Participants
Body Mass Index (kg/m^2) Overweight (>=25 and <30)	15 Participants n=99 Participants	13 Participants n=107 Participants	28 Participants n=206 Participants
Body Mass Index (kg/m^2) Obese (>=30)	31 Participants n=99 Participants	28 Participants n=107 Participants	59 Participants n=206 Participants
Etiology of AGHD Pituitary Adenoma	34 participants n=99 Participants	0 participants n=107 Participants	34 participants n=206 Participants
Etiology of AGHD CNS tumors	8 participants n=99 Participants	0 participants n=107 Participants	8 participants n=206 Participants
Etiology of AGHD Others	18 participants n=99 Participants	0 participants n=107 Participants	18 participants n=206 Participants

PRIMARY outcome

Timeframe: GH sampling: pre-dose and 30, 45, 60, 75, 90, 120, 150 min post-dose

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

The primary endpoint for each individual is the peak GH concentration following AEZS-130 (macimorelin) administration.

Outcome measures

Outcome measures
Measure	Cases/AEZS-130 Administered n=50 Participants All AGHD patients who were enrolled in the study and following macimorelin administration.	Control/AEZS-130 Administered n=48 Participants All matched control subjects who enrolled in the study and following macimorelin administration.	Peak GH & Age CART analysis of Peak GH following macimorelin \& Age Case Definition: GH ≤ 2.85 or (2.85 \<GH ≤7.15 \& age ≤47.5) Control Definition: GH \> 7.15 or (2.85 \<GH ≤7.15 \& age \>47.5)	Peak GH & BMI & Age CART analysis of Peak GH following macimorelin \& BMI \& Age Case Definition: GH≤0.85 or (0.85\<GH≤2.85 and BMI\>27.94) or (2.85\<GH≤7.15 and age ≤47.5) Control Definition: GH \> 7.15 or (0.85 \<GH ≤2.85 \& BMI ≤27.94) or (2.85\<GH≤7.15 and age \>47.5)
Receiver Operating Characteristic (ROC) Analysis on Peak GH (Growth Hormon) Concentrations	2.36 ng/mL Standard Deviation 5.69	17.71 ng/mL Standard Deviation 19.11	—	—

SECONDARY outcome

Timeframe: 15 min. before macimorelin administration and at 150 min after macimorelin administration

Population: Modified Intent-to-treat analysis set used for analysis of mean IGF-1 values taken pre- and post-macimorelin administration.

Descriptive summaries for IGF-1 and correlation with GH concentrations based on macimorelin treatment. Mean IGF-1 values taken pre- and post- macimorelin administration.

Outcome measures

Outcome measures
Measure	Cases/AEZS-130 Administered n=52 Participants All AGHD patients who were enrolled in the study and following macimorelin administration.	Control/AEZS-130 Administered n=48 Participants All matched control subjects who enrolled in the study and following macimorelin administration.	Peak GH & Age CART analysis of Peak GH following macimorelin \& Age Case Definition: GH ≤ 2.85 or (2.85 \<GH ≤7.15 \& age ≤47.5) Control Definition: GH \> 7.15 or (2.85 \<GH ≤7.15 \& age \>47.5)	Peak GH & BMI & Age CART analysis of Peak GH following macimorelin \& BMI \& Age Case Definition: GH≤0.85 or (0.85\<GH≤2.85 and BMI\>27.94) or (2.85\<GH≤7.15 and age ≤47.5) Control Definition: GH \> 7.15 or (0.85 \<GH ≤2.85 \& BMI ≤27.94) or (2.85\<GH≤7.15 and age \>47.5)
Peak Insulin-Like Growth Factor (IGF)-1 Concentration Following Treatment 15 min before AEZS-130	58.1 ng/mL Standard Deviation 37.29	128.1 ng/mL Standard Deviation 52.47	—	—
Peak Insulin-Like Growth Factor (IGF)-1 Concentration Following Treatment 150 min after AEZS-130	53.0 ng/mL Standard Deviation 34.57	125.9 ng/mL Standard Deviation 54.26	—	—

SECONDARY outcome

Timeframe: GH sampling: pre-dose and 30, 45, 60, 75, 90, 120, 150 min post-dose

Population: PPS = per protocol set. Decision tree for sex abandoned. Following Amendment No. 4, no comparison with L-ARG + GHRH was performed.

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.

Outcome measures

Outcome measures
Measure	Cases/AEZS-130 Administered n=98 Participants All AGHD patients who were enrolled in the study and following macimorelin administration.	Control/AEZS-130 Administered n=98 Participants All matched control subjects who enrolled in the study and following macimorelin administration.	Peak GH & Age n=98 Participants CART analysis of Peak GH following macimorelin \& Age Case Definition: GH ≤ 2.85 or (2.85 \<GH ≤7.15 \& age ≤47.5) Control Definition: GH \> 7.15 or (2.85 \<GH ≤7.15 \& age \>47.5)	Peak GH & BMI & Age n=98 Participants CART analysis of Peak GH following macimorelin \& BMI \& Age Case Definition: GH≤0.85 or (0.85\<GH≤2.85 and BMI\>27.94) or (2.85\<GH≤7.15 and age ≤47.5) Control Definition: GH \> 7.15 or (0.85 \<GH ≤2.85 \& BMI ≤27.94) or (2.85\<GH≤7.15 and age \>47.5)
Classification and Regression Tree (CART) Analysis of Peak Growth Hormone (GH) Following Macimorelin Administration Specificity	91.7 percentage of participants	85.4 percentage of participants	89.6 percentage of participants	95.8 percentage of participants
Classification and Regression Tree (CART) Analysis of Peak Growth Hormone (GH) Following Macimorelin Administration Misclassification	13.3 percentage of participants	11.2 percentage of participants	10.2 percentage of participants	9.2 percentage of participants
Classification and Regression Tree (CART) Analysis of Peak Growth Hormone (GH) Following Macimorelin Administration Sensitivity	82.0 percentage of participants	92.0 percentage of participants	90.0 percentage of participants	86.0 percentage of participants

SECONDARY outcome

Timeframe: 14 days

Population: Safety Population

Total number of participants with drug related AEs, following macimorelin administration of L-Arginine (ARG) - Growth Hormone Releasing Hormone (GHRH) administration.

Outcome measures

Outcome measures
Measure	Cases/AEZS-130 Administered n=53 Participants All AGHD patients who were enrolled in the study and following macimorelin administration.	Control/AEZS-130 Administered n=48 Participants All matched control subjects who enrolled in the study and following macimorelin administration.	Peak GH & Age CART analysis of Peak GH following macimorelin \& Age Case Definition: GH ≤ 2.85 or (2.85 \<GH ≤7.15 \& age ≤47.5) Control Definition: GH \> 7.15 or (2.85 \<GH ≤7.15 \& age \>47.5)	Peak GH & BMI & Age CART analysis of Peak GH following macimorelin \& BMI \& Age Case Definition: GH≤0.85 or (0.85\<GH≤2.85 and BMI\>27.94) or (2.85\<GH≤7.15 and age ≤47.5) Control Definition: GH \> 7.15 or (0.85 \<GH ≤2.85 \& BMI ≤27.94) or (2.85\<GH≤7.15 and age \>47.5)
Number of Participants With Drug Related Adverse Events (AEs) following AEZS-130 administration	10 Participants	6 Participants	—	—
Number of Participants With Drug Related Adverse Events (AEs) following L-ARG+GHRH administration	19 Participants	3 Participants	—	—

Adverse Events

AEZS-130: Cases

Serious events: 0 serious events

Other events: 19 other events

Deaths: 0 deaths

AEZS-130: Controls

Serious events: 1 serious events

Other events: 10 other events

Deaths: 0 deaths

L-ARG+GHRH: Cases

Serious events: 0 serious events

Other events: 26 other events

Deaths: 0 deaths

L-ARG+GHRH: Controls

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	AEZS-130: Cases n=52 participants at risk All AGHD patients (cases) who received AEZS-130 (macimorelin).	AEZS-130: Controls n=48 participants at risk All matched control subjects who received AEZS-130 (macimorelin).	L-ARG+GHRH: Cases n=43 participants at risk All AGHD patients (cases) who received L-ARG+GHRH.	L-ARG+GHRH: Controls n=10 participants at risk All matched control subjects who received L-ARG+GHRH.
Investigations ECG QT prolonged	0.00% 0/52 • 14 days (time window between test visit (V2) and end-of-trial visit (V3) Only adverse events that occurred after the first dose of study drug (referred to as treatment-emergent adverse events (TEAEs)) were considered in the safety analysis. All treatment-emergent adverse events were summarized in terms of number and percentage of subjects and number and percentage of events within each treatment period by MedDRA system organ class and preferred term. A TEAE was attributed to the treatment that the subject received prior to the adverse event.	2.1% 1/48 • Number of events 1 • 14 days (time window between test visit (V2) and end-of-trial visit (V3) Only adverse events that occurred after the first dose of study drug (referred to as treatment-emergent adverse events (TEAEs)) were considered in the safety analysis. All treatment-emergent adverse events were summarized in terms of number and percentage of subjects and number and percentage of events within each treatment period by MedDRA system organ class and preferred term. A TEAE was attributed to the treatment that the subject received prior to the adverse event.	0.00% 0/43 • 14 days (time window between test visit (V2) and end-of-trial visit (V3) Only adverse events that occurred after the first dose of study drug (referred to as treatment-emergent adverse events (TEAEs)) were considered in the safety analysis. All treatment-emergent adverse events were summarized in terms of number and percentage of subjects and number and percentage of events within each treatment period by MedDRA system organ class and preferred term. A TEAE was attributed to the treatment that the subject received prior to the adverse event.	0.00% 0/10 • 14 days (time window between test visit (V2) and end-of-trial visit (V3) Only adverse events that occurred after the first dose of study drug (referred to as treatment-emergent adverse events (TEAEs)) were considered in the safety analysis. All treatment-emergent adverse events were summarized in terms of number and percentage of subjects and number and percentage of events within each treatment period by MedDRA system organ class and preferred term. A TEAE was attributed to the treatment that the subject received prior to the adverse event.
Investigations ECG T wave abnormal	0.00% 0/52 • 14 days (time window between test visit (V2) and end-of-trial visit (V3) Only adverse events that occurred after the first dose of study drug (referred to as treatment-emergent adverse events (TEAEs)) were considered in the safety analysis. All treatment-emergent adverse events were summarized in terms of number and percentage of subjects and number and percentage of events within each treatment period by MedDRA system organ class and preferred term. A TEAE was attributed to the treatment that the subject received prior to the adverse event.	2.1% 1/48 • Number of events 1 • 14 days (time window between test visit (V2) and end-of-trial visit (V3) Only adverse events that occurred after the first dose of study drug (referred to as treatment-emergent adverse events (TEAEs)) were considered in the safety analysis. All treatment-emergent adverse events were summarized in terms of number and percentage of subjects and number and percentage of events within each treatment period by MedDRA system organ class and preferred term. A TEAE was attributed to the treatment that the subject received prior to the adverse event.	0.00% 0/43 • 14 days (time window between test visit (V2) and end-of-trial visit (V3) Only adverse events that occurred after the first dose of study drug (referred to as treatment-emergent adverse events (TEAEs)) were considered in the safety analysis. All treatment-emergent adverse events were summarized in terms of number and percentage of subjects and number and percentage of events within each treatment period by MedDRA system organ class and preferred term. A TEAE was attributed to the treatment that the subject received prior to the adverse event.	0.00% 0/10 • 14 days (time window between test visit (V2) and end-of-trial visit (V3) Only adverse events that occurred after the first dose of study drug (referred to as treatment-emergent adverse events (TEAEs)) were considered in the safety analysis. All treatment-emergent adverse events were summarized in terms of number and percentage of subjects and number and percentage of events within each treatment period by MedDRA system organ class and preferred term. A TEAE was attributed to the treatment that the subject received prior to the adverse event.

Other adverse events

Additional Information

Nicola Ammer

Aeterna Zentaris

Phone: +496942602

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Study Protocol Section 10.7 Draft versions of abstracts or manuscripts must be made available to the co-authors and to the sponsor before any presentation of results or submission for publication. At least 2 weeks should be allowed for review and comment of an abstract and 4 weeks in the case of a full paper, respectively. Multiple review cycles are usual for full papers and respective planning must account for this.
Publication restrictions are in place

Restriction type: OTHER