Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Macimorelin · 3 trials · 3 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 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 |
| 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 |
| 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...
Macimorelin is an investigational small molecule being studied for growth hormone deficiency, growth hormone deficiency with pituitary anomalies, and cancer cachexia. It is in Phase 2 and Phase 3 clinical trials for these conditions. Macimorelin is not approved and remains in clinical development.
Macimorelin is a small molecule that stimulates the release of growth hormone. It is being studied as a diagnostic test for growth hormone deficiency and as a potential treatment for cancer cachexia. The exact mechanism involves activating the ghrelin receptor to promote growth hormone secretion.
Macimorelin is being developed by COSCIENS Biopharma Inc., a biopharmaceutical company. The company is conducting clinical trials to evaluate the drug for growth hormone deficiency and cancer cachexia. COSCIENS Biopharma Inc. is the sponsor of the ongoing research.
Macimorelin is in Phase 2 and Phase 3 clinical trials. It has completed a Phase 2 trial for cancer cachexia and Phase 3 trials for growth hormone deficiency. The drug is investigational and has not been approved by regulatory authorities.
Macimorelin has been studied in three completed trials: NCT01614990 for cancer cachexia, NCT02558829 for growth hormone deficiency with pituitary anomalies, and NCT04786873 for growth hormone deficiency in children. These trials were conducted in multiple countries including the United States and European nations.
Macimorelin is a distinct investigational drug being developed as a diagnostic test for growth hormone deficiency. It is not the same as other growth hormone stimulation tests currently available. Its unique mechanism and oral administration differentiate it from existing diagnostic options.