A 12-Week Pharmacokinetic and Pharmacodynamic Study of Two Selective Androgen Receptor Modulators (SARMs) in Postmenopausal Subjects.

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... The remaining 17 were clinical trials. Nine of the trials were early phase tolerability, pharmacokinetic, or dose finding studies [32,33,[35][36][37]39,40,42,47], two trials were bioavailability or drug-interaction studies [38,43], one was a small pilot efficacy study [41], and the remainder were larger efficacy trials [21,34,44,45,48]. The 17 clinical trials tested 13 unique SARM compounds and included a total of 2136 patients with 1447 patients exposed to a SARM. ...
... kg (7 trials reported weight). Nine studies included only men (N = 948, exposed N = 648) [33,[35][36][37][38]43,44,47,48], four studies included only females (N = 768, exposed N = 492) [21,32,41,45], and the remaining four studies included both males and females. Of these studies, Clark et al. included 24.2% females (N = 24, exposed N = 18) [39], Dalton et al. included 50% females (N = 60, exposed N = 48) [34], Neil et al. included 50% females (N = 46, exposed N = 31) [40], and Ristic et al. included 76.9% females (N = 83, exposed N = 62) [42]. ...
... Most patients only had mild ALT elevations and were able to continue the SARM with ALT returning to baseline by day 28 of therapy. [21,[32][33][34][35][36][37][38][39][40][41][42][43]45,47,48]. For each respective SARM, doses were considered low if they were in the 1st quartile, medium if in the 2-3rd quartile, and high if in the 4th quartile of doses across all included trials of the respective SARM. ...
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Selective Androgen Receptor Modulators (SARMs) are not FDA approved, and obtaining SARMs for personal use is illegal. Nevertheless, SARM use is increasingly popular amongst recreational athletes. Recent case reports of drug-induced liver injury (DILI) and tendon rupture raise serious concerns for the safety of recreational SARM users. On 10 November 2022 PubMed, Scopus, Web of Science, and were searched for studies that reported safety data of SARMs. A multi-tiered screening approach was utilized, and any study or case report of generally healthy individuals exposed to any SARM was included. Thirty-three studies were included in the review with 15 case reports or case series and 18 clinical trials (total patients N = 2136 patients, exposed to SARM N = 1447). There were case reports of drug-induced liver injury (DILI) (N = 15), Achilles tendon rupture (N = 1), rhabdomyolysis (N = 1), and mild reversible liver enzyme elevation (N = 1). Elevated alanine aminotransferase (ALT) was commonly reported in clinical trials in patients exposed to SARM (mean 7.1% across trials). Two individuals exposed to GSK2881078 in a clinical trial were reported to have rhabdomyolysis. Recreational SARM use should be strongly discouraged, and the risks of DILI, rhabdomyolysis, and tendon rupture should be emphasized. However, despite warnings, if a patient refuses to discontinue SARM use, ALT monitoring or dose reduction may improve early detection and prevention of DILI.
This review highlights selective androgen receptor modulators (SARMs) as emerging agents in late-stage clinical development for the prevention and treatment of muscle wasting associated with cancer. Muscle wasting, including a loss of skeletal muscle, is a cancer-related symptom that begins early in the progression of cancer and affects a patient's quality of life, ability to tolerate chemotherapy, and survival. SARMs increase muscle mass and improve physical function in healthy and diseased individuals, and potentially may provide a new therapy for muscle wasting and cancer cachexia. SARMs modulate the same anabolic pathways targeted with classical steroidal androgens, but within the dose range in which expected effects on muscle mass and function are seen androgenic side-effects on prostate, skin, and hair have not been observed. Unlike testosterone, SARMs are orally active, nonaromatizable, nonvirilizing, and tissue-selective anabolic agents. Recent clinical efficacy data for LGD-4033, MK-0773, MK-3984, and enobosarm (GTx-024, ostarine, and S-22) are reviewed. Enobosarm, a nonsteroidal SARM, is the most well characterized clinically, and has consistently demonstrated increases in lean body mass and better physical function across several populations along with a lower hazard ratio for survival in cancer patients. Completed in May 2013, results for the Phase III clinical trials entitled Prevention and treatment Of muscle Wasting in patiEnts with Cancer1 (POWER1) and POWER2 evaluating enobosarm for the prevention and treatment of muscle wasting in patients with nonsmall cell lung cancer will be available soon, and will potentially establish a SARM, enobosarm, as the first drug for the prevention and treatment of muscle wasting in cancer patients.
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