K4 Elite
K4 Elite
Sermorelin (GHRH 1-29 NH2) is the shortest synthetic fragment of human growth hormone-releasing hormone retaining full biological activity. It was FDA-approved as Geref (EMD Serono): a 0.05 mg diagnostic ampoule (NDA 19-863, approved 1990) for testing pituitary GH secretion and 0.5/1.0 mg vials (NDA 20-443, approved 1997) for idiopathic growth hormone deficiency in children with growth failure. Both were discontinued in 2008 and the NDAs withdrawn in 2009; FDA determined in 2013 that withdrawal was not for safety or effectiveness reasons. The efficacy evidence is a 1-year open-label multicentre paediatric study (Thorner et al., 1996) plus smaller paediatric trials, one of which found sermorelin less effective than somatropin; adult data are limited to small studies in healthy elderly volunteers. No approved sermorelin product exists today and the original prescribing information is not available on FDA or DailyMed sites, so adverse-effect data below come from published trials and a peer-reviewed drug review.
Each row records what a published study did: who it enrolled, the regimen it administered to those subjects, and what it reported. These are historical study descriptions, not protocols to follow.
| Study | Population | Regimen as reported | Primary findings |
|---|---|---|---|
| Thorner et al., J Clin Endocrinol Metab 1996 (Geref International Study Group; open-label, multicentre) | Previously untreated prepubertal GH-deficient children (n=110 treated; 86 eligible for efficacy analysis) | Children received GHRH(1-29) 30 µg/kg subcutaneously once daily at bedtime for up to 1 year. | Mean height velocity increased from 4.1 cm/yr at baseline to 8.0 and 7.2 cm/yr at 6 and 12 months; 74% were considered good responders at 6 months; no adverse changes in biochemical or hormonal analyses, no change in fasting glucose and no excessive IGF-I generation were noted. |
| Chen et al., Acta Paediatr Suppl 1993 (randomised, GHRH(1-29) vs GH, China) | Children with proven GH deficiency of hypothalamic origin (n=60; 20 per group) | Patients were randomised to GHRH(1-29)-NH2 30 or 60 µg/kg/day by continuous infusion, or GH 0.1 IU/kg/day, for 6 months. | Mean 6-month height velocities were 9.2, 9.3 and 14.6 cm/yr respectively, with GH significantly better than either GHRH dose; GHRH antibodies developed in 20/20 high-dose and 19/20 low-dose patients and largely disappeared 9 months after stopping. |
| Kirk et al., Clin Endocrinol 1994 (open, idiopathic short stature) | Short prepubertal children with idiopathic short stature and normal GH responses (n=18; 17 male; aged 4.3-11.0 years) | Children received GHRH(1-29)NH2 20 µg/kg by twice-daily subcutaneous injection for one year. | Mean height velocity increased from 4.8 to 7.2 cm/yr at 12 months; fasting blood glucose, insulin and IGF-I increased during therapy; catch-down growth followed cessation. |
| Vittone et al., Metabolism 1997 (open-label, healthy elderly men) | Healthy, non-obese men aged 64-76 with low baseline IGF-I (n=11) | Participants self-administered GHRH(1-29) 2 mg subcutaneously nightly for 6 weeks. | Nocturnal GH release increased without change in IGF-I, IGFBP-3, body composition, glucose, insulin or lipids; two of six strength measures improved; no significant adverse effects were observed. |
| Khorram et al., J Clin Endocrinol Metab 1997 (single-blind, placebo run-in, healthy elderly) | Healthy elderly subjects (10 women, 9 men) | Subjects self-administered subcutaneous placebo nightly for 4 weeks followed by [Nle27]GHRH(1-29)-NH2 10 µg/kg nightly for 16 weeks. | 12-hour integrated GH secretion rose 107% in men and 70% in women and IGF-I by 28% by 4 weeks; several lymphocyte subsets and immunoglobulins increased transiently; no adverse effects were reported. |
Effects recorded in the cited reports. Frequencies are those the source reported, in the population that source studied.
| Effect | Frequency / context | Source |
|---|---|---|
| Transient facial flushing and injection-site pain | Described as the most commonly reported adverse events with intravenous single doses and repeated once-daily subcutaneous doses in a peer-reviewed review of the clinical programme (Prakash & Goa, BioDrugs 1999); percentages are not given in the abstract. | Sermorelin: a review of its use in the diagnosis and treatment of children with idiopathic growth hormone deficiency ↗ |
| Anti-GHRH antibodies | Developed in 39 of 40 children receiving continuous-infusion GHRH(1-29) 30 or 60 µg/kg/day for 6 months, disappearing about 9 months after stopping, with no correlation to growth response (Chen et al., 1993); also positive in 3 of 8 children after 6 weeks of intranasal dosing (Hümmelink et al., 1993). | A comparative study of growth hormone (GH) and GH-releasing hormone(1-29)-NH2 for stimulation of growth in children with GH deficiency ↗ |
| Injection-site irritation | Mild irritation reported by 3 patients receiving GHRH(1-29) infusion; no serious side-effects were seen (Chen et al., 1993). | A comparative study of growth hormone (GH) and GH-releasing hormone(1-29)-NH2 for stimulation of growth in children with GH deficiency ↗ |
| Increased fasting glucose, insulin and IGF-I | Observed during 12 months of 20 µg/kg twice-daily dosing in children with idiopathic short stature (Kirk et al., 1994); by contrast no change in fasting glucose or excessive IGF-I generation occurred with 30 µg/kg once daily in GH-deficient children (Thorner et al., 1996). | Treatment with GHRH(1-29)NH2 in children with idiopathic short stature induces a sustained increase in growth velocity ↗ |
| Attenuation of GH response with continuous exposure | With continuous subcutaneous infusion, the 24-h integrated GH concentration rose initially then fell by 3-6 months, with one child showing complete suppression of GH secretion (Tauber et al., 1993, n=6). | Growth hormone (GH) profiles in response to continuous subcutaneous infusion of GH-releasing hormone(1-29)-NH2 in children with GH deficiency ↗ |
| Nasal irritation (intranasal formulation) | Sneezing, rhinorrhoea and mild mucosal burning in most of 8 children given 50 µg/kg intranasally three times daily; treatment discontinued in 2 (Hümmelink et al., 1993). | Intranasal administration of growth hormone-releasing hormone(1-29)-NH2 in children with growth hormone deficiency: effects on growth hormone secretion and growth ↗ |
| Catch-down growth after cessation | Height velocity fell to 3.89 cm/yr in the first 3 months after stopping therapy in children with idiopathic short stature (Kirk et al., 1994). | Treatment with GHRH(1-29)NH2 in children with idiopathic short stature induces a sustained increase in growth velocity ↗ |
Interactions documented in trial reports, prescribing information or pharmacology references.
| Agent | Type | Note | Source |
|---|---|---|---|
| Atropine (muscarinic cholinergic blockade) | pharmacodynamic | Prior atropine 1.2 mg IV significantly reduced the GH response to an IV bolus of GRF 1-29 in healthy subjects, whereas metoclopramide, thymoxamine and TRH did not (Jordan et al., 1986). | Influence of dopaminergic, adrenergic and cholinergic blockade and TRH administration on GH responses to GRF 1-29 ↗ |
| Somatostatin (1-14) | pharmacodynamic (study design) | Intermittent somatostatin infusion suppressed GH release during continuous GHRH(1-29) infusion in a 'peptide clamp' study, illustrating that somatostatin tone governs the response to sermorelin (Achermann et al., 1999). | The relative roles of continuous growth hormone-releasing hormone (GHRH(1-29)NH2) and intermittent somatostatin(1-14)(SS) in growth hormone (GH) pulse generation: studies in normal and post cranial irradiated individuals ↗ |
Exclusions and label contraindications recorded in the cited sources.