An interventional study of ultra-micronised PEA and liposomal PEA in PK in Healthy Volunteers, Liposomal Encapsulation and Palmitoylethanolamide, sponsored by S&R Farmaceutici S.p.A.. Completed at 1 site in Italy. Open to participants aged 18 Years to 70 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-09-04.
Sponsored by S&R Farmaceutici S.p.A. · Not applicable, Interventional, and Treatment
This is a crossover pharmacokinetic study comparing two oral formulations of palmitoylethanolamide (PEA) as a dietary supplement: ultra-micronized PEA 600 mg (Normast 600) and liposomal PEA 600 mg (AliaMed), in 6 healthy subjects following a single oral dose.
Eligible subjects presenting at the Crabion S.r.l. research center for routine screening, who meet the inclusion criteria and provide informed consent, will be enrolled and allocated to one of two groups using non-random, systematic alternate allocation.
On Day 1, after a fasting baseline blood draw (T0), Group 1 subjects will receive a single 600 mg dose of ultra-micronized PEA (Normast 600), while Group 2 subjects will receive a single 600 mg dose of liposomal PEA (AliaMed). Subjects may eat breakfast immediately after dosing. Blood samples (\~3 mL each) will be collected at 0.5, 1, 2, 4, and 24 hours post-dose. Subjects will remain at the center for approximately 4 hours (through the penultimate draw) and will return the following morning for the final 24-hour sample. Subjects will be monitored throughout their stay and asked to report any adverse effects.
A 7-day washout period will follow. On Day 2 (post-washout), subjects will cross over to the alternate formulation: Group 1 will receive liposomal PEA and Group 2 will receive ultra-micronized PEA, each as a single 600 mg dose. Blood samples will be collected at the same time points as Day 1 (0.5, 1, 2, 4, and 24 hours) and analyzed per the same parameters.
**Detailed Description**
Palmitoylethanolamide (PEA) is an endogenous lipid mediator belonging to the N-acylethanolamine family, extensively studied for its analgesic, immunomodulatory, antimicrobial, and anti-inflammatory properties. It is currently used as a nutraceutical for its antinociceptive, neuroprotective, and immunomodulatory effects, particularly in supporting brain and joint health and in mitigating inflammatory processes. Despite this significant potential, the clinical utility of PEA is limited by its poor water solubility, extensive gastrointestinal metabolism, and consequently low oral bioavailability. Over the years, several technological strategies have been explored to improve the pharmacokinetic profile of PEA, including particle-size reduction techniques such as micronization and ultra-micronization, as well as the use of lipid-based carriers such as liposomal delivery systems.
This single-center, open-label, randomized (systematic alternate allocation), two-treatment, two-period, single-dose crossover study is designed to compare the oral absorption of a single 600 mg dose of PEA administered in two different technological formulations: an ultra-micronized formulation (Normast 600, tablet) and a liposomal formulation (AliaMed, sachet), in order to evaluate the impact of formulation technology on the nutraceutical utilization of the molecule.
A total of 6 healthy adult subjects will be enrolled at the Crabion S.r.l. research center (Corciano, Perugia, Italy) among individuals presenting for routine laboratory testing who meet the eligibility criteria and provide written informed consent.
Participants will be allocated to one of two sequence groups using non-random, systematic alternate allocation: Group 1 (n=3) will receive Treatment A (ultra-micronized PEA, Normast 600) in Period 1 followed, after washout, by Treatment B (liposomal PEA, AliaMed) in Period 2; Group 2 (n=3) will receive Treatment B in Period 1 followed by Treatment A in Period 2. On Day 1 of each period, after a fasting baseline blood draw (T0), subjects will take a single oral 600 mg dose of PEA according to group assignment; breakfast will be permitted immediately after dosing. Venous blood samples (\~3 mL per draw) will be collected at 0.5, 1, 2, 4, and 24 hours post-dose. Subjects will remain at the research center for approximately 4 hours (through the 4-hour draw) and will return the following morning for the 24-hour sample. A 7-day washout period separates the two treatment periods, after which the crossover occurs and the alternate formulation is administered following the same sampling schedule.
At each visit, clinical examination and blood collection are performed for: complete blood count (T0 and 24h only), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) (all time points), plasma PEA quantification (all time points), and plasma 2-arachidonoylglycerol (2-AG) quantification (all time points). Blood is collected using a 22G two-way cannula needle into NaEDTA-anticoagulated tubes (hematology, PEA, 2-AG, ESR) and into dry tubes with separator gel (CRP). PEA and 2-AG are quantified by liquid chromatography-tandem mass spectrometry (LC-MS/MS) following protein precipitation, extraction, and purification with appropriate organic solvents; absolute quantification is based on a multi-level calibration curve prepared in matrix, with linearity, accuracy, and precision verified according to international bioanalytical guidelines.
Sample size was calculated using G*Power 3.1.9.7 based on the primary endpoint (AUC₁ ≠ AUC₂), using a paired-samples t-test consistent with the crossover design, an effect size of 1.327 derived from AUC data of a reference pharmacokinetic comparison study of two PEA formulations, a type I error probability (α) of 0.05, and a statistical power (1-β) of 80%, yielding a total sample size of 6 subjects.
The overall study duration is 24 days, comprising: subject enrollment (1 day); the study phase itself, including both treatment periods and washout (9 days); execution of chemical/biochemical analyses at the CRABION S.r.l. laboratory (7 days); and statistical analysis and data processing (7 days). Blood samples will not be retained beyond the end of the study, as they will be fully utilized for study-related analyses.
The study will be conducted in accordance with the ethical principles of the Declaration of Helsinki, Good Clinical Practice (GCP) guidelines, and applicable clinical research regulations. The main procedural risk is associated with venipuncture and may occasionally include mild discomfort or transient pain, minor hematoma at the puncture site, vasovagal reaction (spontaneously and rapidly resolving), or, in very rare cases, local inflammation or infection. These risks are considered minimal and proportionate to the scientific objective of the study; appropriate monitoring is in place to ensure immediate intervention if such events occur.
S&R Farmaceutici S.p.A. is the lead sponsor of 2 studies on the registry; none are open to participants now.
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Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
The other ingredients in a medicine besides the active drug, such as fillers, colours or preservatives.
BMI (body mass index)
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Excipients
The other ingredients in a medicine besides the active drug, such as fillers, colours or preservatives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
In this arm of the study, participants initially take a single dose of 600 mg micronised PEA (u-micron) and, following a washout period, take 600 mg of liposomal PEA
Dietary Supplement: ultra-micronised PEA
In this arm of the study, participants initially take liposomal PEA and, following a washout period, take micronised PEA (u-micron)
Dietary Supplement: liposomal PEA
Participants received ultra-micronised PEA followed by liposomal PEA after the washout period.
Participants received liposomal PEA followed by ultra-micronized PEA after the washout period.
Comparison of the AUC after single dose between Liposomal PEA and ultra-micronised PEA
The primary objective of the study is to compare systemic exposure to palmitoylethanolamide (PEA), expressed as the area under the curve (AUC), following a single dose of the two PEA formulations under evaluation: * Liposomal PEA * Ultra-micronised PEA
Time frame: From the enrollment to the end of the study at 9 days
Evaluation of half-life (t1/2)
Evaluation of half-life of both PEA formulations
Time frame: From enrollment to the end of the study at 9 days
Evaluation of Cmax
Evaluation of the difference in maximum plasma concentration (Cmax) between the two PEA formulations.
Time frame: From enrollment to the end of the study at 9 days
Evaluation of Tmax
Evaluation of the difference in time to reach maximum plasma concentration (Tmax) between the two PEA formulations.
Time frame: From enrollment to the end of the study at 9 days
Evaluation of erythrocyte sedimentation rate (ESR)
Assessment of the safety and tolerability of the two PEA formulations by monitoring changes in erythrocyte sedimentation rate (ESR) levels
Time frame: From enrollment to the end of the study at 9 days
Evaluation of C-reactive protein (CRP)
Assessment of the safety and tolerability of the two PEA formulations by monitoring changes in C-reactive protein (CRP) levels
Time frame: From enrollment to the end of the study at 9 days
Plan to share: No — Individual participant data collected during the study will not be made available to other researchers due to institutional policies and participant privacy considerations.
This study is completed, as verified in Sep 2026. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: Pea