K4 Elite
K4 Elite
AOD9604 (Tyr-hGH177-191) is a synthetic 16-amino-acid fragment of the C-terminus of human growth hormone developed by Metabolic Pharmaceuticals (Australia) as an oral or intravenous anti-obesity candidate. Between 2001 and 2006 six randomised, double-blind, placebo-controlled trials (about 893 participants) were run; safety data were summarised in a sponsor-authored 2013 review (Stier et al.), but the efficacy results were never published in a peer-reviewed journal. The largest Phase 2b trial (502 randomised, 24 weeks) did not show a statistically significant difference in weight loss versus placebo and the sponsor terminated obesity development in February 2007; an FDA 2024 compounding advisory review concluded there is a lack of evidence of effectiveness. The published human data concern oral and intravenous routes only; no human data for subcutaneous administration were identified by FDA. A 'GRAS' designation cited by the sponsor was a self-affirmed expert-panel conclusion; no AOD9604 entry was located in the FDA GRAS Notice Inventory.
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 |
|---|---|---|---|
| METAOD001 — Phase 1 dose-escalation (summarised in Stier et al., J Endocrinol Metab 2013) | Healthy adult males with BMI 24-30 kg/m2 (n=15; 14 completed) | Each subject received three single intravenous infusions of AOD9604 (range 25-400 µg/kg over 20 minutes) and placebo, separated by 7-day washouts; a single intravenous dose of recombinant hGH (0.12 IU/kg) was used as a positive control. | 29 adverse events were reported by 12 subjects with no serious adverse events; no significant glycerol, glucose or IGF-1 trends were observed versus placebo. |
| METAOD002 — Phase 2a single-dose Latin-square (Stier et al., 2013) | Healthy clinically obese males aged 19-50, BMI >=35 kg/m2 (n=23) | Each subject received four single intravenous infusions (25, 50 and 100 µg/kg AOD9604, or placebo) over 20 minutes, separated by 7-day washouts. | 118 adverse events and no serious adverse events were reported; mild or moderate headache occurred in 16/23 (69.6%); no significant changes in glucose or IGF-1 versus placebo. |
| METAOD003 / METAOD004 — Phase 2a oral single-dose and 7-day multiple-dose studies (Stier et al., 2013) | Healthy clinically obese males (n=17, BMI >=35; and n=36, BMI >=30 kg/m2) | In METAOD003 subjects received three increasing single oral doses (9, 27 and 54 mg capsules) or placebo separated by 2-week washouts; in METAOD004 subjects received 9, 27 or 54 mg AOD9604 or placebo orally once daily for 7 days (n=9 per group). | In METAOD003 two serious adverse events occurred at 54 mg (diarrhoea, deemed possibly related; bronchial pneumonia, deemed unrelated); in METAOD004 no serious adverse events occurred and the 54 mg group experienced more headache, diarrhoea and flatulence. IGF-1, fasting glucose, insulin and OGTT parameters were unchanged. |
| METAOD005 — Phase 2b, 12-week oral (Stier et al., 2013; FDA PCAC briefing 2024) | Healthy obese adults, BMI >=35 kg/m2, aged 30-65 (n=300; 5 Australian hospitals) | After a 2-week single-blind placebo run-in, participants received AOD9604 1, 5, 10, 20 or 30 mg or placebo orally once daily for 12 weeks (n=50 per group). | Five serious adverse events were reported, all in AOD9604 groups (basal cell carcinoma, lipoma and squamous cell carcinoma at 20 mg; breast cancer at 5 mg; malignant melanoma at 10 mg), judged unrelated by investigators; IGF-1 did not change significantly. The FDA 2024 review describes reported weight changes as small differences of unclear therapeutic meaning and notes that no full publication of methods and results was located. |
| METAOD006 / 'OPTIONS' study — Phase 2b, 24-week oral (Stier et al., 2013; FDA PCAC briefing 2024) | Obese adults aged 18-65, BMI 30-45 kg/m2 (536 enrolled, 502 randomised; 16 Australian centres) | After a 4-week single-blind placebo run-in, participants received AOD9604 0.25, 0.5 or 1 mg tablets or placebo orally once daily for 24 weeks alongside a dietitian-supervised diet and exercise programme, followed by 4 weeks of follow-up. | Per the sponsor's 2007 disclosure quoted by FDA, weight loss versus placebo at 12 and 24 weeks was too low to reach statistical significance and development for obesity was terminated; 18 participants (3.6%) had at least one serious adverse event, distributed similarly across groups. |
Effects recorded in the cited reports. Frequencies are those the source reported, in the population that source studied.
| Effect | Frequency / context | Source |
|---|---|---|
| Headache | Most common adverse event across studies; 69.6% (16/23) after intravenous dosing in METAOD002; 42.6% during the 12-week oral treatment phase of METAOD005 and 25.9% in the 24-week METAOD006, with similar distribution across active and placebo groups (Stier et al., 2013). | Safety and Tolerability of the Hexadecapeptide AOD9604 in Humans ↗ |
| Gastrointestinal events (diarrhoea, flatulence, nausea, increased appetite) | Gastrointestinal disorders in 30.4% (diarrhoea 9.0%) during METAOD005 treatment and 22.9% (diarrhoea 7.8%) in METAOD006, similar to placebo; more headache, diarrhoea and flatulence at the 54 mg oral dose in METAOD004; one serious diarrhoea event at 54 mg deemed possibly related (Stier et al., 2013). | Safety and Tolerability of the Hexadecapeptide AOD9604 in Humans ↗ |
| Euphoria (mild to moderate) | Reported by 5/23 subjects during intravenous AOD9604 periods and none during placebo in METAOD002; deemed possibly related (Stier et al., 2013). | Safety and Tolerability of the Hexadecapeptide AOD9604 in Humans ↗ |
| Chest tightness (severe intensity) | One event at 50 µg/kg intravenous in METAOD002, deemed possibly related to treatment (Stier et al., 2013). | Safety and Tolerability of the Hexadecapeptide AOD9604 in Humans ↗ |
| Hypoglycaemia (unspecified), fatigue, dizziness | Hypoglycaemia unspecified (3), fatigue (4) and dizziness (3) among 29 adverse events in the intravenous Phase 1 study (METAOD001); treatment allocation for each event was not specified (Stier et al., 2013; FDA 2024). | FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, December 4, 2024 — AOD-9604 ↗ |
| Malignancies reported as serious adverse events | Five serious adverse events in METAOD005 (12 weeks oral) were all in AOD9604 groups: basal cell carcinoma, lipoma and squamous cell carcinoma (20 mg), breast cancer (5 mg), malignant melanoma (10 mg); investigators judged them unrelated. FDA's 2024 review stated it had concerns about these reports given the limited study detail. | FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, December 4, 2024 — AOD-9604 ↗ |
| IGF-1 elevation, impaired glucose tolerance, anti-drug antibodies | Not observed: no significant change in serum IGF-1, OGTT parameters or fasting glucose/insulin in any study, and no anti-AOD9604 antibodies detected in tested participants (Stier et al., 2013). | Safety and Tolerability of the Hexadecapeptide AOD9604 in Humans ↗ |
| Post-marketing reports | FDA searches of FAERS (to January 2024) and CAERS (2004-2024) retrieved no adverse-event reports for AOD-9604; FDA noted absence of reports does not imply safety. | FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, December 4, 2024 — AOD-9604 ↗ |
No interactions with a verifiable citation have been indexed for this compound.
Exclusions and label contraindications recorded in the cited sources.