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Label indication MACRILEN is indicated for the diagnosis of adult growth hormone deficiency (AGHD). MACRILEN is a growth hormone (GH) secretagogue receptor agonist indicated for the diagnosis of adult growth hormone deficiency ( 1 ). Limitations of Use : The safety and diagnostic performance has not been established for subjects with BMI > 40kg/m 2 ( 1 ). FDA label
Also known as AEZS-130 (formerly ARD-07), Macimorelin, Macrilen, Macimorelin GHST, Macimorelin test, Macrilen GHST, Macrilen test
AEZS-130 · 4 trials · 4 indications
Assuming the outcome of GHD status adjudication final clinical diagnosis as the "true" GHD status, the diagnostic efficacy (estimated sensitivity, specificity, misclassification) of the macimorelin GHST will be based on the area under the receiver operating characteristic curve (ROC AUC).
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.
The primary endpoint for each individual is the peak GH concentration following AEZS-130 (macimorelin) administration.
The change of body weight(kg)will be measured between day 1 and day (Day 7-Day 1).
The change of IGF-1 plasma levels will be measured between day 1 (prior to dosing) and day 7.
The change of quality of life score (Anderson Symptom Assessment Scale \[ASAS; absolute score\], Functional Assessment of Chronic Illness-Fatigue \[FACIT-F; total score\]) will be measured between day 1 and day 7. The ASAS is a validated measure of quality of life (QOL) associated with symptom clusters commonly seen in cancer patient populations. The absolute score ranges from 0-100 with higher scores indicative of worse cancer symptoms. The FACIT-F is a validated measure of QOL associated with fatigue related to chronic illness. To account for missing items, the FACIT-F total score (sum of subscales) was adjusted by calculating the percent total score of items completed with the following: (FACIT-F Total Score)/(N items completed ×4 (maximum possible score for each item ) × 100% Scores range from 0 to 160 with higher scores indicative of greater fatigue. Tests consists of 5 subscales: Physical, Social/Family, Emotional, and Functional Well-Being, and Additional Concerns.
| Arm | Type | Description |
|---|---|---|
| standard GHST order randomized: arginine - clonidine | ACTIVE_COMPARATOR | At visit 2 (V2), all subjects will perform the macimorelin GHST and will be randomized 1:1 to the order of the clonidine and arginine GHSTs at visit 3 (V3) and visit 4 (V4). In this arm, those subjects will be presented which will have been randomized to the arginine GHST at V3 and the clonidine GHST at V4. At visit 5 (V5) all subjects will perform the macimorelin GHST. |
| standard GHST order randomized: clonidine - arginine | ACTIVE_COMPARATOR | At V2, all subjects will perform the macimorelin GHST and will be randomized 1:1 to the order of the clonidine and arginine GHSTs at V3 and V4. In this arm, those subjects will be presented which will have been randomized to the clonidine GHST at V3 and to the arginine GHST at V4. At V5 all subjects will perform the macimorelin GHST. |
| GHST Sequence A | EXPERIMENTAL | 1st Macimorelin-GHST, 2nd Insulin Tolerance Test |
| GHST Sequence B | EXPERIMENTAL | 1st Insulin Tolerance Test, 2nd Macimorelin-GHST |
| AEZS-130 ( formerly ARD-07) | EXPERIMENTAL | A single oral administration of AEZS-130 (0.5 mg/kg po) as Growth Hormone Stimulation Test |
| L-ARG+GHRH | ACTIVE_COMPARATOR | This trial was set up as a multi-center, randomized, cross-over study investigating AEZS-130 as a Growth Hormone Stimulation Tests in terms of safety and efficacy compared to L-ARG+GHRH. When GHRH became unavailable on the US market, this comparator arm was no longer available, which was addressed by Amendment No. 3 (version 27-March-2010). Control subject enrolled under Amendment No. 3 were not randomized as there was no cross-over due to unavailability of L-ARG+GHRH. These control subjects received only AEZS-130 |
| Macimorelin | ACTIVE_COMPARATOR | - |
| Placebo | PLACEBO_COMPARATOR | - |
| Name | Type | Description |
|---|---|---|
| Macimorelin | DRUG | Dosage form: granules for oral solution, Dosage: 1.0 mg/kg body weight, Frequency and duration: single oral dose administration. Macimorelin will be supplied in single-use aluminum pouches (synonymous: sachets) each containing 63.6 mg macimorelin as acetate, which provide 0.5 mg/mL of macimorelin when dissolved in 120 mL of water. The excess amount of 3.6 mg represents an overfill, which is needed to obtain the target concentration. |
| Arginine | DIAGNOSTIC_TEST | For the arginine GHST, R-Gene® 10 from Pfizer will be provided as labelled investigational medicinal product (IMP). After an overnight fast, soluble arginine hydrochloride (0.5 g/kg) will be given i.v. as an infusion with an infusion duration of 30 min. |
| Clonidine | DIAGNOSTIC_TEST | For the clonidine GHST, CATAPRESAN® 75 tablets (Boehringer Ingelheim) will be provided as labelled IMP. Each tablet contains 75 ug clonidine hydrochloride. The tablets will be provided in boxes containing 10 tablets. The target dose is 0.15 mg/m2 body surface with a dose range of 0.08 - 0.15 mg/m2. Maximum dose will be 0.25 mg. After an overnight fast, clonidine (0.15 mg/m2 body surface) will be given orally. |
| Insulin | DRUG | Insulin, 0.10 U/kg (0.15 U/kg if BMI \> 30 kg/m2), intravenous injection, single dose |
| AEZS-130 (formerly ARD-07) | DRUG | A single oral administration of AEZS-130 as Growth Hormone Stimulation Test |
| L-ARG+GHRH | DRUG | A single administration of L-ARG+GHRH (iv bolus) followed by a 30min infusion of L-ARG as Growth Hormone Stimulation Test |
| Placebo | DRUG | placebo (Powerade®) daily for 7 days. |
Inclusion Criteria: 1. Informed consent of subject, parent(s) or legally acceptable representative (LAR) of subject and child assent, if appropriate, must be obtained before any trial-related activities. Trial-related activities are any procedures that are carried out as part of the trial, includin...
AEZS-130 is an oral small molecule developed by COSCIENS Biopharma Inc. (ticker CSCI) as a growth hormone stimulation test for the diagnosis of Adult Growth Hormone Deficiency (AGDH). It is an investigational product in Phase 3 development and has been studied in a single completed Phase 3 trial.
AEZS-130 is being developed for the diagnosis of Adult Growth Hormone Deficiency (AGDH). It is intended for use as a growth hormone stimulation test, evaluating whether adult patients have growth hormone deficiency. The program is in Phase 3 development and is not approved for commercial use.
AEZS-130 is developed by COSCIENS Biopharma Inc., which trades under the ticker CSCI. The company is the sponsor of the clinical program evaluating the drug as a growth hormone stimulation test for diagnosing Adult Growth Hormone Deficiency.
AEZS-130 is in Phase 3 development. It is an investigational drug and has not been approved by the FDA. One Phase 3 trial has been completed, and no trials are currently active. The completed study enrolled 101 participants and was conducted in the United States.
AEZS-130 has been studied in one completed Phase 3 trial, NCT00448747, titled Investigation of a New, Oral Growth Hormone Secretagogue, AEZS-130 as a Growth Hormone Stimulation Test. The trial enrolled 101 participants aged 18 years and older, including healthy volunteers, and was active-controlled and randomized.
Yes, AEZS-130 was formerly known as ARD-07. Both names refer to the same oral small molecule developed by COSCIENS Biopharma Inc. (ticker CSCI) for the diagnosis of Adult Growth Hormone Deficiency. Searches for either name refer to the same Phase 3 investigational asset.