RAD-140 Safety Study: What the 2021 First-in-Human Trial Actually Found

RAD-140 (Testolone) is an investigational selective androgen receptor modulator (SARM). The most frequently cited human paper was published online in 2021 and in print in 2022. It is important to describe that study accurately: it was a phase 1 dose-escalation trial in 22 postmenopausal women with ER-positive/HER2-negative metastatic breast cancer, not a placebo-controlled study in healthy male volunteers.

This evidence review explains the study design, the adverse-event results, what the trial can and cannot tell researchers, and how the human findings differ from earlier cell and animal research. RAD-140 has not been authorized by Health Canada for medical use and this article is not medical advice.

RAD-140 safety study: quick answer

Study: LoRusso et al., first-in-human phase 1 trial (ClinicalTrials.gov NCT03088527; PMID 34565686).
Participants: 22 heavily pretreated postmenopausal patients with metastatic breast cancer; 21 had androgen-receptor-positive tumours.
Design: open-label 3+3 dose escalation with 50 mg, 100 mg, or 150 mg RAD-140 once daily.
Primary purpose: characterize safety, tolerability, dose-limiting toxicity, pharmacokinetics, and preliminary antitumour activity.
Main safety signal: laboratory elevations in AST, ALT, and bilirubin were among the most frequent treatment-emergent adverse events.
Key limitation: a small oncology trial without a healthy-volunteer or placebo group cannot establish safety for unsupervised use or for a different population.

What is RAD-140?

RAD-140 is a nonsteroidal ligand of the androgen receptor. It was designed to produce tissue-selective androgen-receptor activity, with the research goal of separating anabolic effects in muscle and bone from unwanted activity in other androgen-responsive tissues. That selectivity is a development objective, not proof that the compound is free of androgenic, cardiovascular, hepatic, endocrine, or other risks.

Early characterization included receptor assays and animal models. A 2011 discovery paper described oral bioavailability and anabolic-androgenic activity in preclinical models. A separate 2014 study reported neuroprotective signals in cultured rat neurons and a rat kainate-lesion model. Neither study was a human safety trial, and neither supports claims of proven neuroprotection or clinical benefit in people.

The first-in-human trial at a glance

Study feature	What was reported
Trial identifier	NCT03088527
Publication	Published online August 2021; Clinical Breast Cancer, January 2022
Population	22 postmenopausal women with ER-positive/HER2-negative metastatic breast cancer; participants were heavily pretreated
Design	Open-label phase 1, 3+3 dose escalation plus a pharmacokinetic expansion cohort
Dose levels studied	50 mg (n=6), 100 mg (n=13), and 150 mg (n=3) once daily
Endpoints	Safety, tolerability, maximum tolerated dose, pharmacokinetics, androgen-receptor engagement, and preliminary antitumour activity

What the study found about safety

The paper reported that the most frequent treatment-emergent adverse events occurring in more than 10% of participants included:

Elevated AST: 59.1%
Elevated ALT: 45.5%
Elevated total bilirubin: 27.3%
Vomiting, dehydration, decreased appetite, and decreased weight: 27.3% each

Grade 3 or 4 treatment-emergent adverse events occurred in 16 of 22 participants (72.7%). Grade 3 or 4 elevations in AST or ALT and hypophosphatemia were each reported in 22.7% of participants. These results should not be softened into a claim that RAD-140 was simply “well tolerated at all doses.” Liver-related laboratory abnormalities were a prominent signal in this small trial.

The oncology setting matters. Participants had advanced cancer and extensive prior treatment, so some events may have had multiple possible causes. At the same time, that context does not justify dismissing the abnormalities or extrapolating safety to healthy people. The appropriate conclusion is narrower: the trial generated the first published human pharmacokinetic and safety observations under clinical monitoring, while leaving substantial uncertainty about long-term and non-oncology exposure.

Androgen-receptor engagement and pharmacokinetics

The investigators followed sex hormone-binding globulin (SHBG) and prostate-specific antigen (PSA) as surrogate markers of androgen-receptor engagement. Pharmacokinetic sampling was included to characterize systemic exposure across the studied dose levels. These measurements show that the trial was designed to study target engagement and drug disposition; they do not establish a safe consumer dose, a bodybuilding protocol, or a favourable benefit-risk profile outside the trial population.

How the 2021 human evidence differs from preclinical research

Discovery and anabolic models

The 2011 discovery paper described RAD-140 as a potent, orally bioavailable nonsteroidal SARM and reported activity in preclinical anabolic-androgenic models. Animal data can help select compounds for further study, but species differences, experimental endpoints, and controlled laboratory conditions limit translation to humans.

Neuroprotection research

In 2014, RAD-140 reduced cell death in cultured rat hippocampal neurons exposed to selected insults and showed neuroprotective effects in a male-rat kainate lesion model. The mechanism involved MAPK/ERK signalling in that experimental system. This is preliminary animal and cell evidence, not evidence that RAD-140 prevents or treats Alzheimer disease or another neurological condition in humans.

What researchers should not conclude

The study did not enroll healthy men or recreational users.
It did not compare RAD-140 with placebo.
It did not establish long-term cardiovascular, reproductive, endocrine, or hepatic safety.
It did not validate stacking RAD-140 with another investigational compound.
It did not authorize RAD-140 as a medicine, supplement, or performance-enhancing product.

Canadian regulatory and safety context

Health Canada states that SARMs have not been authorized in Canada for any medical use and specifically lists testolone (RAD-140) among SARM ingredients associated with serious safety concerns, including hormonal suppression and heart and liver disease. Authorized prescription drugs carry an eight-digit Drug Identification Number (DIN) and can be checked in Health Canada’s Drug Product Database.

A “research use only” statement does not turn an unauthorized health product into an authorized medicine and must not be interpreted as permission for human use. Health Canada may take action against unauthorized products, including seizure and border measures. For a fuller, current explanation, read Is RAD-140 legal in Canada?

How to read a RAD-140 research claim critically

Identify the evidence level: receptor assay, cell model, animal study, phase 1 trial, or later-stage controlled trial.
Check the population: advanced-cancer patients cannot be treated as interchangeable with healthy participants.
Separate biomarkers from outcomes: target engagement or a laboratory change is not the same as a proven clinical benefit.
Report adverse events numerically: avoid replacing observed frequencies with vague language such as “generally safe.”
Check authorization status: investigational status is different from Health Canada authorization.

Related research resources

References

Last reviewed: July 2026. This article summarizes published research and regulatory information. It does not provide medical or legal advice and does not recommend human use.