PT-141 (Bremelanotide) in Human Clinical Trials: Populations, Endpoints and Findings

Q: What is bremelanotide approved for?

Bremelanotide is approved in the United States for acquired, generalised hypoactive sexual desire disorder in premenopausal women . That is the only approved indication and the only population studied in the phase 3 programme .

Q: How large was the bremelanotide phase 3 programme?

RECONNECT comprised two identical phase 3 randomised, double-blind, placebo-controlled multicentre trials that randomised 1,267 women in total, with 1,247 in the safety population and 1,202 in the efficacy population, over 24 weeks of double-blind treatment . The wider development programme comprised 3,500 participants across 43 completed studies .

Q: What effect size did the phase 3 trials report?

On the Female Sexual Function Index desire domain, the change against placebo was 0.30 in study 301 (P<.001) and 0.42 in study 302 (P<.001), 0.35 integrated. On the distress item, the change was −0.37 (P<.001) and −0.29 (P=.005), −0.33 integrated . These are differences on questionnaire scales, and the trials used prespecified responder definitions developed separately .

Q: What adverse events were reported with bremelanotide?

In the integrated double-blind phase 3 population of 1,247, nausea occurred in 40.0% against 1.3% on placebo, flushing in 20.3% against 1.3%, headache in 11.3% against 1.9% and injection-site reactions in 5.4% against 0.5%. Nausea was the most common reason for discontinuation. Focal hyperpigmentation occurred in more than a third of participants following up to 16 consecutive daily administrations .

Q: Does bremelanotide affect blood pressure?

Yes, transiently. A randomised, double-blind, placebo-controlled ambulatory monitoring trial in 397 premenopausal women reported systolic increases against placebo of 2.4 to 3.0 mmHg at 1.25 mg and 3.1 to 3.2 mmHg at 1.75 mg in the 0-4 hour window, with peaks typically lasting under 15 minutes, accompanied by heart-rate reductions of 4.6 to 4.7 beats per minute at 1.75 mg (P<0.001) . The integrated safety review advises caution in people at cardiovascular risk .

Q: Has bremelanotide been studied in men?

Not in the trials described here. The early development programme addressed sexual dysfunction broadly , but the phase 2b, phase 3 and long-term extension trials all enrolled premenopausal women with hypoactive sexual desire disorder or female sexual arousal disorder .

Q: How long have bremelanotide trials run?

The double-blind core phase ran 24 weeks, followed by a 52-week open-label extension; participants in the phase 3 studies received the compound for up to 18 months . Of 856 eligible patients who completed the core phase, 684 entered the extension and 272 completed it .

Q: What receptor does PT-141 act on?

It is a melanocortin receptor agonist, with the melanocortin-4 receptor as the receptor of interest for the studied indication . Structural work has described ligand recognition and activation at that receptor , and the central mechanism proposed for the indication has been reviewed .

Bremelanotide completed a full development programme of 43 studies and 3,500 participants, including two identical phase 3 trials. This article sets out each trial, the endpoints used, the effect sizes reported, the cardiovascular findings, and what the programme never tested.

By Elegance Peptides Editorial Team Published September 22, 2026 Updated September 22, 2026

PT-141, developed as bremelanotide, is one of very few compounds in this library to have completed a full pharmaceutical development programme and reached approval. Its clinical record comprises 43 completed studies and approximately 3,500 participants, ending in two identical phase 3 trials and an approval in the United States for one narrowly defined indication in one population ^{[12, 9]}.

That record is also a case study in how a development programme changes shape under its own data. The compound was first pursued as a melanocortin agonist for sexual dysfunction generally ^[1]. A cardiovascular finding in early trials redirected the route of administration and the monitoring requirements for everything that followed ^[5]. The programme that reached phase 3 enrolled premenopausal women only, used questionnaire endpoints agreed in advance, and produced effect sizes that are statistically unambiguous and numerically modest.

This article sets out each stage: population, design, duration, primary endpoint, results as reported, adverse events, limitations. It describes published research, contains no guidance of any kind on handling any material, and makes no recommendation.

The molecule and its receptor

In vitro research

Bremelanotide is a cyclic heptapeptide melanocortin receptor agonist, described in 2003 as a melanocortin agonist for the treatment of sexual dysfunction ^[1]. It is a metabolite of an earlier melanocortin analogue in the same chemical family, which is the reason the melanocortin pigmentation effects recur throughout its safety record.

The receptor of interest for the studied indication is the melanocortin-4 receptor, a class A G protein-coupled receptor expressed in the central nervous system. Structural work has described ligand recognition and activation at that receptor ^[11], and the proposed central mechanism for the indication has been reviewed in detail ^[10].

The melanocortin receptor family is the reason the safety profile of this compound looks the way it does. The same family governs pigmentation, cardiovascular tone and nausea pathways, and a systemically administered agonist reaches all of them.

The animal work behind the indication

Animal research

The indication pursued in the clinical programme originated in rodent behavioural work. A 2004 study reported selective facilitation of sexual solicitation behaviour in the female rat by a melanocortin receptor agonist ^[3], and a 2007 review set out the preclinical central-nervous-system effects on female sexual function across the programme's animal models ^[4].

The relevant caution is the ordinary one for behavioural pharmacology: a solicitation behaviour in a rat is an operational proxy chosen by the experimenter, and the construct it is held to represent in a person is defined by a clinical questionnaire rather than by the animal model. The animal work identified a candidate indication; it did not establish one.

Early human trials and the cardiovascular redirection

Human clinical research

Results from pharmaceutical clinical trials describe the investigational material and populations used in those studies and should not be interpreted as establishing the effects of research-grade materials offered for laboratory use.

Intranasal administration in women with arousal disorder. An early trial reported an effect on the subjective sexual response in premenopausal women with sexual arousal disorder following intranasal bremelanotide ^[2]. This trial belongs to the first phase of the programme, before the route of administration and the target population had settled.

The ambulatory blood pressure trial. 397 premenopausal women with female sexual dysfunction, either normotensive or with controlled hypertension, were studied in a randomised, double-blind, placebo-controlled, parallel-arm trial of three amounts — 0.75, 1.25 and 1.75 mg — with ambulatory blood pressure and heart rate monitored alongside pharmacokinetic exposure ^[5].

Ambulatory systolic pressure increased against placebo by 2.4 and 3.0 mmHg at 1.25 mg (P=0.029 and 0.076) and by 3.1 and 3.2 mmHg at 1.75 mg (P=0.006 and 0.027) in the 0-4 hour window following two administrations separated by 24 hours. Peak increases typically lasted less than 15 minutes, and similar increases occurred in diastolic pressure. Heart rate fell by 4.6 to 4.7 beats per minute in the same window at 1.75 mg (P<0.001). Twenty-six participants discontinued after randomisation because of prespecified pressure increases, in similar proportions across the four groups ^[5].

Why this trial matters more than its size suggests. Its stated consequence was procedural: the results led to in-clinic blood pressure monitoring in the larger trials that followed ^[5]. A transient 3 mmHg increase in a screened population of normotensive or controlled-hypertensive premenopausal women is a small finding, and it is small partly because the population was screened for cardiovascular risk. The integrated safety review that closed the programme still advises caution in people at cardiovascular risk and that blood pressure be well controlled ^[12].

Phase 2b and the definition of response

Human clinical research

A phase 2b amount-ranging study in premenopausal women with hypoactive sexual desire disorder, female sexual arousal disorder, or both, was used to establish what a clinically meaningful change on each instrument would be, deriving minimal important differences from changes measured across a single-blind phase in order to account for placebo response. Seven endpoints were examined, including the Female Sexual Function Index desire domain, a sexual distress scale total and item scores, and the number of satisfying sexual events ^[6].

At 1.75 mg, responder rates on all seven endpoints reached statistical significance against placebo in the overall modified intention-to-treat population (P ≤ .03). These responder definitions were then carried into the phase 3 registration trials ^[6].

Limitations, and a point in the programme's favour. Defining responder thresholds before the registration trials, from separate data, and pre-registering them, is good practice and comparatively rare. The limitations the authors name are equally real: the thresholds derive from a single trial and a population restricted to premenopausal women with these two diagnoses, so they do not transfer to other populations or instruments.

RECONNECT: the phase 3 trials

Human clinical research

Population, design, duration. Two identical phase 3, randomised, double-blind, placebo-controlled, multicentre trials — studies 301 and 302 — in premenopausal women with hypoactive sexual desire disorder, randomised 1:1 to 24 weeks of bremelanotide 1.75 mg administered subcutaneously as needed, or placebo. Study 301 ran from January 2015 to July 2016 and study 302 from January 2015 to August 2016. Of 1,267 women randomised, 1,247 were in the safety population and 1,202 in the modified intention-to-treat efficacy population. 85.6% were White, 96.6% were at sites in the United States, and mean age was 39 years ^{[7, 14, 15]}.

Coprimary endpoints. Change from baseline to end of study in the Female Sexual Function Index desire domain score, and in item 13 of the Female Sexual Distress Scale-Desire/Arousal/Orgasm.

Results as reported. Increases in the desire domain score against placebo were 0.30 in study 301 (P<.001) and 0.42 in study 302 (P<.001), 0.35 integrated (P<.001). Reductions in the distress item were −0.37 (P<.001) and −0.29 (P=.005), −0.33 integrated (P<.001). Women receiving bremelanotide experienced more nausea, flushing and headache — each in 10% or more of participants in both studies — than those receiving placebo ^[7]. Prespecified and integrated subgroup analyses of the two studies have been published separately ^[13].

The open-label extension. Women who completed the 24-week core phase without serious adverse events could enter a 52-week open-label extension. Of 856 eligible completers, 684 enrolled and 272 completed. The most common drug-related adverse events were nausea (40.4%), flushing (20.6%) and headache (12.0%); nausea was the only severe event experienced by more than one participant in both studies. Change from baseline to end of extension ranged from 1.25 to 1.30 on the desire domain and −1.4 to −1.7 on the distress item for those who had received bremelanotide in the core phase, and 0.70 to 0.77 and −0.9 for those who had received placebo. All analyses were descriptive ^[8].

Limitations. The effect sizes are the central issue and the publications state them plainly: 0.35 of a point on the desire domain and −0.33 on a single distress item, integrated across 1,202 women. Whether a change of that magnitude is meaningful to a person is precisely what the responder analyses were constructed to address ^[6], and it remains a question about instruments rather than a settled fact. The extension is open-label and its analyses descriptive, so its larger numbers are not comparable to the controlled phase. And of 684 women who entered the extension, fewer than half finished it — attrition on that scale is itself a result.

The integrated safety profile

Human clinical research

A review of the programme's safety across phases 1 to 3 covers 3,500 participants in 43 completed studies, with exposure in the phase 3 studies of up to 18 months ^[12].

In the integrated double-blind phase 3 population of 1,247, adverse events on bremelanotide against placebo were: nausea 40.0% against 1.3%, flushing 20.3% against 1.3%, headache 11.3% against 1.9%, injection-site reactions 5.4% against 0.5%. Nausea was the most common reason for discontinuation. There were no deaths and a few participants experienced serious adverse events. Focal hyperpigmentation was rare with administration according to the approved labelling but occurred in more than a third of participants after up to 16 consecutive daily administrations. Small, transient but statistically significant blood pressure increases were observed on ambulatory monitoring. Most drug-drug interactions were not clinically significant, with the exception of interactions lowering plasma concentrations of indomethacin and naltrexone. 70% of the bremelanotide group proceeded from the double-blind to the open-label phase, against 87% of the placebo group ^[12]. The approval and its basis have been summarised in the drug-review literature ^[9].

What the hyperpigmentation finding means in practice. It is a frequency that depends on how often the compound is administered: rare at the studied frequency, common at daily administration for 16 days. That is a frequency-dependent relationship reported in the safety literature, and it is the clearest example in this programme of a finding whose magnitude is inseparable from the regimen that produced it.

What the evidence base does not establish

Anything in men. The entire phase 2b and phase 3 programme enrolled premenopausal women ^{[6, 7, 8]}. The approved indication is defined accordingly, and the trials provide no evidence about any other population.

Anything in postmenopausal women. The same restriction applies. "Premenopausal" is an inclusion criterion in every trial above, not a descriptive detail.

A large effect. The phase 3 coprimary differences are 0.35 points and −0.33 points on their respective scales ^[7]. The trials were adequately powered and the results are statistically robust; the magnitude is what it is, and the responder framework exists because the raw scale differences are hard to interpret ^[6].

Long-term controlled data. The controlled phase is 24 weeks. Everything beyond that is open-label and descriptive, with fewer than half of extension entrants completing ^[8].

Cardiovascular safety in unscreened populations. The blood-pressure trial enrolled normotensive women and women with controlled hypertension ^[5], and the integrated review advises caution in people at cardiovascular risk ^[12]. What happens in populations the trials excluded has not been measured.

Effects of administration frequencies the trials did not study. The hyperpigmentation finding shows that at least one safety outcome scales with how frequently the compound is administered ^[12]. Regimens outside those studied have no safety data behind them.

All of the research described in this article is research into a pharmaceutical product, conducted by its sponsors under registered protocols, using material manufactured to a regulatory standard and administered under clinical supervision in defined populations. None of it is research into, or evidence about, research-grade material supplied for laboratory use.

Frequently Asked Questions

What is bremelanotide approved for?

Bremelanotide is approved in the United States for acquired, generalised hypoactive sexual desire disorder in premenopausal women ^{[9, 12]}. That is the only approved indication and the only population studied in the phase 3 programme ^[7].

How large was the bremelanotide phase 3 programme?

RECONNECT comprised two identical phase 3 randomised, double-blind, placebo-controlled multicentre trials that randomised 1,267 women in total, with 1,247 in the safety population and 1,202 in the efficacy population, over 24 weeks of double-blind treatment ^{[7, 14, 15]}. The wider development programme comprised 3,500 participants across 43 completed studies ^[12].

What effect size did the phase 3 trials report?

On the Female Sexual Function Index desire domain, the change against placebo was 0.30 in study 301 (P<.001) and 0.42 in study 302 (P<.001), 0.35 integrated. On the distress item, the change was −0.37 (P<.001) and −0.29 (P=.005), −0.33 integrated ^[7]. These are differences on questionnaire scales, and the trials used prespecified responder definitions developed separately ^[6].

What adverse events were reported with bremelanotide?

In the integrated double-blind phase 3 population of 1,247, nausea occurred in 40.0% against 1.3% on placebo, flushing in 20.3% against 1.3%, headache in 11.3% against 1.9% and injection-site reactions in 5.4% against 0.5%. Nausea was the most common reason for discontinuation. Focal hyperpigmentation occurred in more than a third of participants following up to 16 consecutive daily administrations ^[12].

Does bremelanotide affect blood pressure?

Yes, transiently. A randomised, double-blind, placebo-controlled ambulatory monitoring trial in 397 premenopausal women reported systolic increases against placebo of 2.4 to 3.0 mmHg at 1.25 mg and 3.1 to 3.2 mmHg at 1.75 mg in the 0-4 hour window, with peaks typically lasting under 15 minutes, accompanied by heart-rate reductions of 4.6 to 4.7 beats per minute at 1.75 mg (P<0.001) ^[5]. The integrated safety review advises caution in people at cardiovascular risk ^[12].

Has bremelanotide been studied in men?

Not in the trials described here. The early development programme addressed sexual dysfunction broadly ^[1], but the phase 2b, phase 3 and long-term extension trials all enrolled premenopausal women with hypoactive sexual desire disorder or female sexual arousal disorder ^{[6, 7, 8]}.

How long have bremelanotide trials run?

The double-blind core phase ran 24 weeks, followed by a 52-week open-label extension; participants in the phase 3 studies received the compound for up to 18 months ^{[7, 8, 12]}. Of 856 eligible patients who completed the core phase, 684 entered the extension and 272 completed it ^[8].

What receptor does PT-141 act on?

It is a melanocortin receptor agonist, with the melanocortin-4 receptor as the receptor of interest for the studied indication ^[1]. Structural work has described ligand recognition and activation at that receptor ^[11], and the central mechanism proposed for the indication has been reviewed ^[10].

References

PT-141: a melanocortin agonist for the treatment of sexual dysfunction Annals of the New York Academy of Sciences; 2003. PMID 12851303 doi:10.1111/j.1749-6632.2003.tb03167.x
An effect on the subjective sexual response in premenopausal women with sexual arousal disorder by bremelanotide (PT-141), a melanocortin receptor agonist The Journal of Sexual Medicine; 2006. PMID 16839319 doi:10.1111/j.1743-6109.2006.00268.x
Selective facilitation of sexual solicitation in the female rat by a melanocortin receptor agonist Proceedings of the National Academy of Sciences of the United States of America; 2004. PMID 15226502 doi:10.1073/pnas.0400491101
Bremelanotide: an overview of preclinical CNS effects on female sexual function The Journal of Sexual Medicine; 2007. PMID 17958619 doi:10.1111/j.1743-6109.2007.00610.x
Usefulness of ambulatory blood pressure monitoring to assess the melanocortin receptor agonist bremelanotide Journal of Hypertension; 2017. PMID 27977473 doi:10.1097/HJH.0000000000001221
Responder Analyses from a Phase 2b Dose-Ranging Study of Bremelanotide The Journal of Sexual Medicine; 2019. PMID 31277966 doi:10.1016/j.jsxm.2019.05.012
Bremelanotide for the Treatment of Hypoactive Sexual Desire Disorder: Two Randomized Phase 3 Trials Obstetrics and Gynecology; 2019. PMID 31599840
Long-Term Safety and Efficacy of Bremelanotide for Hypoactive Sexual Desire Disorder Obstetrics and Gynecology; 2019. PMID 31599847 doi:10.1097/AOG.0000000000003514
Bremelanotide: New Drug Approved for Treating Hypoactive Sexual Desire Disorder The Annals of Pharmacotherapy; 2020. PMID 31893927 doi:10.1177/1060028019899152
The neurobiology of bremelanotide for the treatment of hypoactive sexual desire disorder in premenopausal women CNS Spectrums; 2022. PMID 33455598 doi:10.1017/S109285292100002X
Structural insights into ligand recognition and activation of the melanocortin-4 receptor Cell Research; 2021. PMID 34433901 doi:10.1038/s41422-021-00552-3
Safety Profile of Bremelanotide Across the Clinical Development Program Journal of Women's Health; 2022. PMID 35147466 doi:10.1089/jwh.2021.0191
Prespecified and Integrated Subgroup Analyses from the RECONNECT Phase 3 Studies of Bremelanotide Journal of Women's Health; 2022. PMID 35230162 doi:10.1089/jwh.2021.0225
1. Study to Evaluate the Efficacy/Safety of Bremelanotide in Premenopausal Women With Hypoactive Sexual Desire Disorder. NCT02333071
2. Study to Evaluate the Efficacy/Safety of Bremelanotide in Premenopausal Women With Hypoactive Sexual Desire Disorder. NCT02338960

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