This page shows what was measured, who it was measured in, and what that does not settle.
What Adapalene does in the body
Acne
Adapalene is a laboratory-built molecule shaped to fit the same receptors vitamin A acid uses, but with a bulky cage-like group bolted on that makes it greasy, stable in sunlight and unreactive to oxygen. The greasiness concentrates it in the pore rather than spreading it across the whole skin surface. Once inside a pore-lining cell it switches on the genes that make those cells mature and shed, so the plug loosens and fewer new plugs form. The stability is the reason it can be put in the same tube as benzoyl peroxide, which would destroy tretinoin.
What happened in people
Adapalene 0.3% significantly superior to 0.1% and to vehicle on success rate and lesion counts in 653 randomised patients, with a dose-dependent gradient
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
The recorded finding that sits closest to something a person would notice. Written into the record, not signed off, and it carries no population or interval.
The 0.3% strength stayed prescription-only under a separate application while the 0.1% went to the open shelf
Where it acts
The follicular infundibulum — adapalene is strongly lipophilic and concentrates in the sebaceous follicle rather than spreading evenly through the epidermis
Kind of result
The kind of result is not recorded
Supervision
RNAWiki has not recorded a supervision or regulatory status for this substance.
What the registries record it as
The substance registry classes this as chemical.
FDA substance registry · 1L4806J2QF · read 2026-08-29
Its recorded molecular formula is C28H28, weighing 412.53.
US prescribing information · 9a0d9a0d-a9f3-4eb9-be76-166ef182d13a · read 2026-08-30
Where each sentence above came from
No recorded sentence describes the change this makes in a way that stands on its own. The page opens with what it is taken for instead, and the recorded explanation follows below.
Shown as the opening line on this page.
A limit recorded against this substance. Not signed off as a reviewed claim.
The four opening statements run to 124 words.
Words this page uses
Four words worth knowing first
Chosen from what this page shows, with each one explained before the word it depends on.
Placebo
A placebo is a dummy treatment given so the real one can be compared with it.
A picture of it, and where the picture fails
A placebo is like a blank control in an experiment.
Where that stops being true. A blank does nothing. People given a placebo often do get better.
What people get wrong. A placebo effect is read as imaginary. The improvement is measured and real.
An inactive intervention matched in appearance to the test intervention, used to control for non-specific effects.
Comparator
A comparator is whatever the treatment was measured against.
A picture of it, and where the picture fails
It is like the other runner in a race.
Where that stops being true. A race has one winner. A study can show both arms improved.
What people get wrong. Results are read without asking what the other group got. Beating nothing is not beating a treatment.
The control condition against which the experimental intervention is assessed.
Randomisation
Randomisation means chance decides who gets which treatment.
A picture of it, and where the picture fails
It is like a coin toss deciding the groups.
Where that stops being true. A coin toss is fair once. Fairness here comes from doing it for everyone.
What people get wrong. It is thought to make groups identical. It makes them similar on average, including on things nobody measured.
Allocation of participants to arms by a chance process, so that unmeasured factors are balanced in expectation.
What happened in people◇Read from sources, not yet reviewed
What happened in people
Each card is one study: the exact question it asked, who was in it, and whether it showed what it set out to show.
Investigator’s Global Assessment success rate and lesion counts at 12 weeks, adapalene 0.3% against 0.1% and vehicle
✓ The study showed what it set out to show
Who was studied
Adapalene Gel 0.3% phase 3 (PMID 16443054, NDA 021753)
How many people
653
Study design
Phase 3, multicentre, randomised, double-blind, vehicle- and active-controlled
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
Adapalene 0.3% significantly superior to both 0.1% and vehicle on success rate, total lesion count and inflammatory lesion count by generalised estimating equations across weeks 8 and 12. Label Table 3: IGA success 21% against 16% against 9%
Repeated elsewhere
Replicated
What this does not prove. Meeting one endpoint in one population does not carry to other goals or other people.
The limits of this study, and where it came from
Main limit. The absolute success rate is easy to lose behind the word "superior": 79% of patients on the strongest strength were not clear or almost clear at 12 weeks, and the vehicle arm delivered a 33.7% total lesion reduction on its own.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Topical gel, cream and lotion, applied to the skin once daily
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
Multicentre, randomised, double-blind, vehicle- and active-controlled
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
Fixed combination significantly more effective than each corresponding monotherapy, with significant differences in total lesion count from week 1
Repeated elsewhere
Replicated
What this does not prove. Meeting one endpoint in one population does not carry to other goals or other people.
The limits of this study, and where it came from
Main limit. Tolerability was reported as comparable to adapalene monotherapy in this trial, but in the pooled network meta-analysis withdrawal for adverse events was 2.5% for adapalene with benzoyl peroxide against 1.0% for adapalene alone.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Topical gel, cream and lotion, applied to the skin once daily
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
Superior efficacy and better tolerability of adapalene 0.1% gel against tretinoin 0.025% gel
✗ The study did not show it
Who was studied
Cunliffe 1998 adapalene against tretinoin meta-analysis (PMID 9990421)
How many people
900
Study design
Meta-analysis of five multicentre randomised investigator-blind comparative trials
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
Equivalent efficacy on total lesion count reduction; significant advantage for adapalene on inflammatory and total lesions at week 1 only; considerably greater local tolerability at all assessments
Repeated elsewhere
Partially Replicated
What this does not prove. A study that did not show an effect does not show that no effect exists anywhere.
The limits of this study, and where it came from
Main limit. Three of four authors were employees of the manufacturer, published and unpublished company studies were pooled together, and the analysis appeared in a journal supplement. The superiority objective was not met and the conclusion nevertheless describes a pharmacologic advance.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Topical gel, cream and lotion, applied to the skin once daily
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
RNAWiki holds 3 written-up human studies for this substance, each with the question it asked.
How we know it
Each card names the study, the number of people and what the study set out to measure.
What this does not prove
These summaries were written by a person and have not been signed off as reviewed claims.
Why it matters
A study that failed is as informative as one that worked, and both are here.
What we still do not know
No reviewed claim exists, so no exact population, effect size or interval is published yet.
What it changes in the body◇Read from sources, not yet reviewed
The path through the body
From what a person takes to what changes. A solid line is a step measured in people. A dashed line is a step nobody has measured that way.
Start
Adapalene
What a person takes: Topical gel, cream and lotion, applied to the skin once daily.
The measurement behind this step
Applied to affected skin. The molecule is strongly lipophilic and concentrates in sebaceous follicles rather than distributing evenly across the epidermis. It is photostable and resistant to oxidation, which is what allows co-formulation in a single product with benzoyl peroxide — a combination that is chemically impossible with tretinoin. The 0.1% gel is sold over the counter in the United States; the 0.3% gel is prescription-only.
Getting in
It goes where the oil is
Adapalene is unusually greasy for a drug. Applied to skin it does not spread evenly — it collects in the oily pores, which is exactly where acne starts.
╌╌Described, with no measurement named. No measurement is named for this step, so it is drawn as an unconfirmed link.
The measurement behind this step
Calculated logP on the stored structure is 6.84. That lipophilicity, conferred by the adamantane cage, drives partitioning into sebum-filled follicles rather than uniform distribution across the interfollicular stratum corneum, and is the design rationale for a follicular-targeted retinoid.
It survives light and oxygen, which the natural molecule does not
The bulky cage on the molecule makes it chemically tough. Sunlight does not rearrange it and peroxides do not destroy it. That is the only reason it can share a tube with benzoyl peroxide.
╌╌Described, with no measurement named. No measurement is named for this step, so it is drawn as an unconfirmed link.
The measurement behind this step
Adapalene has no polyene chain to isomerise. The rigid adamantyl-naphthoic acid scaffold is photostable under ICH Q1B conditions and resistant to oxidative degradation by benzoyl peroxide at formulation concentration, unlike all-trans retinoic acid, which isomerises to its 13-cis form in light and degrades in the presence of peroxides.
Inside the cell the drug goes straight to receptors sitting on DNA. It skips the shuttle protein that natural vitamin A acid uses, which is part of why it behaves differently.
──Measured in people. Written by a person from the study named beside the step. Not signed off as a reviewed claim.
The measurement behind this step
Adapalene does not bind the cytosolic retinoic acid-binding proteins CRABP1 and CRABP2, and binds RAR-beta and RAR-gamma preferentially over RAR-alpha. Human epidermis expresses predominantly RAR-gamma, so the selectivity profile overlaps the receptor that matters in skin while avoiding the alpha-mediated effects associated with systemic retinoid toxicity.
The occupied receptor switches on the maturation genes in the cells lining the pore. They stop clumping, the plug loosens, and fewer new plugs form behind it.
╌╌Described, with no measurement named. No measurement is named for this step, so it is drawn as an unconfirmed link.
The measurement behind this step
Ligand-bound RAR/RXR heterodimers exchange corepressors for coactivators at retinoic acid response elements, normalising the abnormal follicular keratinisation that produces the microcomedone. Adapalene additionally suppresses toll-like receptor 2 expression on monocytes and AP-1 signalling, which is the proposed basis for its effect on inflammatory as well as comedonal lesions.
Over twelve weeks the number of spots drops by about 45 in a hundred. On the plain vehicle with no drug in it, the number drops by about 34 in a hundred. The medicine is the gap between those two, not the whole of the first one.
──Measured in people. Written by a person from the study named beside the step. Not signed off as a reviewed claim.
The measurement behind this step
DIFFERIN 0.3% label Table 3: total lesion reduction 45.3% on 0.3%, 41.8% on 0.1%, 33.7% on vehicle from mean baseline counts near 67; IGA success 21%, 16% and 9% respectively at week 12 in 653 randomised patients.
Every number here is a person looking at a face and grading it, or counting spots on it. Nothing in the trial programme measured scarring, and nothing measured what happens after treatment stops.
──Measured in people. Written by a person from the study named beside the step. Not signed off as a reviewed claim.
The measurement behind this step
The registration endpoints are Investigator’s Global Assessment success and lesion counts at 12 weeks. No pivotal adapalene trial had a scar-formation endpoint, none ran a randomised off-treatment follow-up, and the largest network meta-analysis of the field could extract patient-reported improvement from only 11 of 40 trials.
No suggested links are held for this record, so nothing is hidden from this path.
What we know
The record describes 6 steps from taking it to an effect in a person.
How we know it
Each step names the study behind it in the technical detail beside it.
What this does not prove
A change inside the body is a reason to look. It is not a result in a person.
Why it matters
A reader can see exactly where the chain stops being measured in people.
What we still do not know
No reviewed claim binds any of these steps to a named population.
What is missing or unclear◇Read from sources, not yet reviewed
Were people like you studied?
RNAWiki cannot tell whether a study fits you. It can show who was in it, and where the result stops carrying.
Who was studied
People similar to this profile were included.
People with mild to moderate acne, from age 12 upwards. The 0.1% strength can be bought off a shelf; the 0.3% strength cannot.
Who is missing from the studies
Which groups were under-represented in the studies has not been recorded for this substance. Pregnancy, breastfeeding, children, older adults, and people with liver or kidney conditions are commonly excluded from trials; nothing here says whether they were.
What the label states about particular groups
On pediatric, the label states: “Safety and effectiveness have not been established in pediatric patients below the age of 12.”
US prescribing information · 9a0d9a0d-a9f3-4eb9-be76-166ef182d13a · read 2026-08-30
On older people, the label states: “Clinical studies of Adapalene Gel did not include subjects 65 years of age and older to determine whether they respond differently than younger subjects.”
US prescribing information · 9a0d9a0d-a9f3-4eb9-be76-166ef182d13a · read 2026-08-30
On people who are pregnant, the label states: “Risk Summary Available data from clinical trials with Adapalene Gel use in pregnant women are insufficient to establish a drug-associated risk of major birth defects, miscarriage or other adverse maternal or fetal outcomes.”
US prescribing information · 9a0d9a0d-a9f3-4eb9-be76-166ef182d13a · read 2026-08-30
On people who are breastfeeding, the label states: “Risk Summary There are no data on the presence of topical adapalene gel or its metabolite in human milk, the effects on the breastfed infant, or the effects on milk production.”
US prescribing information · 9a0d9a0d-a9f3-4eb9-be76-166ef182d13a · read 2026-08-30
Where the result stopped carrying
The manufacturer’s meta-analysis set out to demonstrate superiority over tretinoin and demonstrated equivalence
The vehicle arm of the pivotal trial reduced total lesions by a third, absorbing most of the apparent effect
Patient-reported improvement was extractable from only 11 of 40 trials in the largest network meta-analysis of topical acne treatment
No pivotal adapalene trial measured scarring, and none ran a randomised off-treatment follow-up
This is a scope explorer, not a diagnosis engine.
It shows who was studied so you can see whether people similar to you were included.
RNAWiki cannot tell whether a study fits you. It can show who was in it.
What it would be like to take◇Read from sources, not yet reviewed
Why it might seem to do nothing
A real effect and a noticed effect are different things. These are the recorded reasons the two come apart.
It was studied in different people
The people in the studies were not much like the reader.
On this record: Which groups were under-represented in the studies has not been recorded for this substance. Pregnancy, breastfeeding, children, older adults, and people with liver or kidney conditions are commonly excluded from trials; nothing here says whether they were.
The evidence may simply be wrong
Small early studies often do not hold up.
On this record: RNAWiki has not yet published a reviewed conclusion for this use.
Other reasons RNAWiki checked and found nothing for (11)
It was studied for a different goal
The studies measured something else entirely. Nothing in this record points to this reason.
A different form was studied
The studied form is not the form on the shelf. Nothing in this record points to this reason.
There was nothing to correct
Where a level is already normal, topping it up may change nothing. Nothing in this record points to this reason.
Something else had to happen too
In the studies it was paired with training, a diet or another treatment. Nothing in this record points to this reason.
The change is too small to feel
A real change can still sit below what a person notices. Nothing in this record points to this reason.
Day-to-day swing hides it
Sleep, food, stress and time of day move most numbers more than this would. Nothing in this record points to this reason.
Not enough time yet
The studies ran longer than the person has waited. Nothing in this record points to this reason.
It was not taken as studied
Missed days change the result, and studies count them. Nothing in this record points to this reason.
Something else changed at the same time
Two changes at once cannot be told apart afterwards. Nothing in this record points to this reason.
The product may not be what it says
Contents of a sold product are not always what the label states. Nothing in this record points to this reason.
No recorded reason
RNAWiki has nothing stored that would explain it. Nothing in this record points to this reason.
None of these is a reason to take more. Taking more is not a step this page ever suggests.
What it would be like to take◇Read from sources, not yet reviewed
What taking it involves
The recorded facts about getting hold of it and using it. Nothing here is a suggestion about what you should do.
How it is supplied
Prescription only
❝ Quoted from a source
Where this came from
Copied from a source RNAWiki stored, with the source named.
Read from the recorded approval status.
No source is stored against this line.
Form and route
Topical gel, cream and lotion, applied to the skin once daily
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
The form and route recorded on this substance.
No source is stored against this line.
Who oversees it
RNAWiki has not recorded a supervision or regulatory status for this substance.
❝ Quoted from a source
Where this came from
Copied from a source RNAWiki stored, with the source named.
No register row and no identity class settled the question.
No source is stored against this line.
What is in the pack
Applied to affected skin. The molecule is strongly lipophilic and concentrates in sebaceous follicles rather than distributing evenly across the epidermis. It is photostable and resistant to oxidation, which is what allows co-formulation in a single product with benzoyl peroxide — a combination that is chemically impossible with tretinoin. 3% gel is prescription-only.
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
Recorded notes on how this is sold and what that means for what is in the pack.
No source is stored against this line.
Where it is registered
Regulatory records are listed in the technical disclosure at the foot of this page.
# Counted from records
Where this came from
A count of rows RNAWiki holds. It describes our records, not your body.
Register entries are stored per jurisdiction and shown with their dates.
No source is stored against this line.
Why people stop
Not recorded.
∅ Nothing recorded
Where this came from
RNAWiki holds nothing here and says so rather than guessing.
No record of why people stopped taking it is stored for this substance.
No source is stored against this line.
What it would be like to take◇Read from sources, not yet reviewed
What can go wrong
Sorted by where each line came from. A regulator's label and a report somebody sent in are not the same kind of fact.
·Worth asking a clinician aboutWritten into the record from the studies named on this page
Local irritation is the main effect and is milder than with tretinoin: the pooled comparison found considerably greater local tolerability at every assessment point. In the higher-strength fixed-combination trial, erythema, scaling, dryness and stinging peaked at week 1 and decreased thereafter, with skin irritation reported in 4% of subjects against 0% on vehicle. Systemic absorption is minimal. Sun sensitivity and avoidance of application to abraded or eczematous skin are label cautions.
Nobody counted how many people took this and were fine, so this cannot be turned into a rate.
Over a long time. No completed tested study window is recorded, so long-term effects are not established by the registry record.
Groups the studies covered thinly. Which groups were under-represented in the studies has not been recorded for this substance. Pregnancy, breastfeeding, children, older adults, and people with liver or kidney conditions are commonly excluded from trials; nothing here says whether they were.
What is missing or unclear◇Read from sources, not yet reviewed
Does the exact form matter?
Evidence belongs to the exact thing that was tested. A different salt, a different mixture or a different preparation is a different question.
The form that was studied
Topical gel, cream and lotion, applied to the skin once daily
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
The form used in the studies cited on this page.
No source is stored against this line.
What is sold
The molecule is strongly lipophilic and concentrates in sebaceous follicles rather than distributing evenly across the epidermis. It is photostable and resistant to oxidation, which is what allows co-formulation in a single product with benzoyl peroxide — a combination that is chemically impossible with tretinoin. 3% gel is prescription-only.
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
Recorded notes on which forms are sold and how they compare.
No source is stored against this line.
What is recorded as being sold
86 products list this as an active ingredient in the United States drug directory. 65 of them contain it and nothing else.
FDA National Drug Code directory · 72162-1430 · read 2026-08-29
They are sold as cream, gel, powder and swab, taken cutaneous and topical.
FDA National Drug Code directory · 72162-1430 · read 2026-08-29
The regulator's established pharmacologic class for it is retinoid [epc] and retinoids [cs].
FDA National Drug Code directory · 72162-1430 · read 2026-08-29
75 published labels name it as an active ingredient. 54 of them describe this substance alone, which is where its own label text on this page comes from.
US prescribing information · 0739d631-171b-42a8-bd55-0022b8df2d8a · read 2026-08-29
Those labels are classed as human otc drug and human prescription drug.
US prescribing information · 0739d631-171b-42a8-bd55-0022b8df2d8a · read 2026-08-29
ADAPALENE is topical at 3 DOSAGE FORMS AND STRENGTHS Each gram of Adapalene Gel, 0.3% contains 3 mg adapalene in an off-white aqueous gel., recorded as fda label in effect 2022-11-28 in the United States.
US prescribing information · 9a0d9a0d-a9f3-4eb9-be76-166ef182d13a · read 2026-08-30
Recorded price in US: 0.338–2.49014 USD per one gram, across 15 priced products whose strengths and pack forms differ, as of 2026-08-26, paid by retail pharmacies buying the product, as surveyed by the Centers for Medicare & Medicaid Services. It is not a list price, an insurance price, or what anyone pays at a counter..
Recorded source · 2026-08-26 · read 2026-08-28
Evidence carries across two names for one substance. It does not carry across a salt, a mirror form or a mixture.
What it would be like to take◇Read from sources, not yet reviewed
What you could measure
This one is decided with a clinician, so this section holds questions to ask rather than a plan to run.
RNAWiki could not confidently classify this substance, so no self-experiment plan is offered.
Questions worth asking
Which of the trials of Adapalene studied people like me?
What was measured, and for how long?
Was the result a laboratory value or a health outcome?
What would we watch for, and when would we stop?
Tracking can show whether something changed for you. It cannot show what caused it.
RNAWiki records evidence. It does not say whether this substance is right for you.
What is missing or unclear◇Read from sources, not yet reviewed
Claims that go past the evidence
Things said about this substance that sound reasonable, and the exact step that is missing between the evidence and the claim.
✗Goes past the evidence
That adapalene is a pharmacologic advance over tretinoin — the pooled comparison found equivalence on efficacy and reported a tolerability advantage
Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.
The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.
What would change this
A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.
RNAWiki has not yet published a reviewed conclusion for this use.
✗Goes past the evidence
That a topical retinoid clears acne, when four in five patients on the strongest strength were not clear or almost clear at 12 weeks
Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.
The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.
What would change this
A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.
RNAWiki has not yet published a reviewed conclusion for this use.
✗Goes past the evidence
That over-the-counter status reflects stronger evidence rather than a regulatory judgment about self-selection and labelling
Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.
The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.
What would change this
A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.
RNAWiki has not yet published a reviewed conclusion for this use.
✗Goes past the evidence
That the top of the Southampton network ranking is settled, when its authors grade their own confidence in it as low
Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.
The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.
What would change this
A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.
RNAWiki has not yet published a reviewed conclusion for this use.
What is missing or unclear◇Read from sources, not yet reviewed
What nobody knows yet
Open questions, each with why it is open and what would close it.
Missing populations
Which groups were under-represented in the studies has not been recorded.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
Missing long-term data
No completed tested study window is recorded.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
No reviewed conclusion
RNAWiki has not yet published a reviewed conclusion for this use.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
Missing interaction studies
No interaction was found in the registers checked. Not finding one is not the same as showing there is none.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
Formulation uncertainty
Several salts, forms or products of Adapalene are recorded. Results from one form may not transfer to another.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
Mechanism not reviewed
No reviewed mechanism story exists for this substance.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
What happened in people◇Read from sources, not yet reviewed
Check any of this yourself
Every line above traced back to the study it came from. This is the technical layer, and the vocabulary changes here.
Every line above can be traced to the study named beside it. Follow the link and read it.
The pivotal trial: 653 patients, and a dose-dependent effect at both strengths
In plain words
Six hundred and fifty-three people were randomised to the strong gel, the weak gel or plain vehicle for twelve weeks. The strong gel beat both. The effect got bigger with the stronger concentration, which is the pattern you expect from a drug that is really doing something.
What was measured
Investigator’s Global Assessment success rate and lesion counts at 12 weeks, three arms
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Thiboutot and colleagues randomised 653 patients aged 12 to 52 with mild to moderate acne 2:2:1 to adapalene gel 0.3%, adapalene gel 0.1% or vehicle once daily for 12 weeks, analysed with generalised estimating equations across weeks 8 and 12. Adapalene 0.3% was significantly superior to both 0.1% and vehicle on success rate, total lesion count and inflammatory lesion count, with a consistent dose-dependent effect across all efficacy measures. Signs and symptoms were mostly mild to moderate and transient. The trial did not study any adjunctive topical or oral agent.
Written into the record, not signed off as a reviewed claim
Read the same table again: 21% clear, and the vehicle got two-thirds of the way
In plain words
The numbers behind that trial are printed in the label. One patient in five on the strongest gel was clear or almost clear at twelve weeks. Nearly one in ten on the plain vehicle was too. And the vehicle alone shifted lesion counts down by a third.
What was measured
IGA success 21% against 16% against 9%; total lesion reduction 45.3% against 41.8% against 33.7%
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Table 3 of the DIFFERIN 0.3% label reports the primary efficacy results at week 12. IGA success — clear or almost clear — was 53 of 258 (21%) on adapalene 0.3%, 41 of 261 (16%) on adapalene 0.1% and 12 of 134 (9%) on vehicle. Total lesions fell by 45.3% on 0.3%, 41.8% on 0.1% and 33.7% on vehicle from mean baseline counts of 67.1, 69.1 and 67.2. Inflammatory lesions fell 51.6%, 49.7% and 40.7%. The drug effect is real and consistent across every measure, and it is the gap between those columns — roughly 12 percentage points on success and 12 points on lesion reduction — not the size of the column itself.
Source
DIFFERIN (adapalene) Gel 0.3% United States prescribing information, section 14, Table 3 (NDA 021753)
Role in the trial
Not matched to a registered study
Identity check
no open identity hold
Audit mark
caution
Review state
Written into the record, not signed off as a reviewed claim
The fixed combination beat both of its own components
In plain words
Putting adapalene and benzoyl peroxide in one tube was tested against each of them alone and against plain vehicle in the same trial. The combination won, and the difference in lesion counts showed up within a week.
What was measured
Success rate and total lesion count at 12 weeks, combination against each monotherapy and vehicle in one trial
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Thiboutot and colleagues randomised 517 subjects 2:2:2:1 in a double-blind controlled trial to adapalene 0.1% plus benzoyl peroxide 2.5% fixed combination, adapalene alone, benzoyl peroxide alone or vehicle for 12 weeks. The fixed combination was significantly more effective than either monotherapy, with significant differences in total lesion count observed as early as week 1. Adverse event frequency and cutaneous tolerability for the combination were similar to adapalene monotherapy. The authors note the result was generated in a controlled trial and that practice may differ. This is the trial behind the network meta-analysis ranking that put adapalene with benzoyl peroxide at the top of the topical field.
Written into the record, not signed off as a reviewed claim
It set out to beat tretinoin and demonstrated equivalence instead
In plain words
A meta-analysis pooled every comparison of adapalene against tretinoin the manufacturer could find, published and unpublished, in nine hundred patients. The stated goal was to show adapalene worked better. It worked the same. It was gentler, which is a genuine finding, and the paper concluded it was a pharmacologic advance.
What was measured
Total lesion count reduction, adapalene 0.1% against tretinoin 0.025% in 900 patients: equivalent
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
Cunliffe and colleagues pooled five multicentre randomised investigator-blind trials, published and unpublished, from the United States and Europe: 450 patients on adapalene 0.1% gel against 450 on tretinoin 0.025% gel, analysed by intention to treat. The stated purpose was "to determine if adapalene 0.1% gel provided superior efficacy and better tolerability than tretinoin 0.025% gel". Adapalene demonstrated equivalent efficacy on total lesion count reduction, a significant advantage at week 1 on inflammatory and total lesions, and considerably greater local tolerability at every assessment. The authors concluded the findings "suggest that adapalene 0.1% gel constitutes a pharmacologic advance over such classic retinoids as tretinoin". Three of the four authors were employees of the manufacturer, the analysis included unpublished company studies, and it was published in a journal supplement rather than a regular issue.
Written into the record, not signed off as a reviewed claim
The first topical retinoid to be sold without a prescription
In plain words
For twenty years a retinoid was something a doctor prescribed, partly because of the birth-defect history of the oral ones. Adapalene 0.1% was moved onto the open shelf. Nothing new was discovered about how well it works — what changed was the judgment about whether people could choose it safely on their own.
What was measured
That over-the-counter status reflects stronger evidence — it reflects a regulatory judgment about self-selection and labelling comprehension, made on the efficacy dataset that already existed
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
The 0.1% gel is now listed in Drugs@FDA under NDA 020380 with an over-the-counter marketing status, while the 0.3% gel remains prescription-only under a separate application, NDA 021753. The fixed combination with benzoyl peroxide has since followed, listed over the counter under NDA 220736. An Rx-to-OTC switch is a determination that a condition is self-recognisable, that a product can be used safely without supervision and that the labelling can be understood — it is not a new efficacy finding, and the efficacy evidence behind the OTC product is the same 1990s dataset that supported the prescription version.
Source
openFDA Drugs@FDA records for NDA 020380 (DIFFERIN 0.1%, over-the-counter), NDA 021753 (DIFFERIN 0.3%, prescription) and NDA 220736 (DIFFERIN EPIDUO, over-the-counter)
Role in the trial
Not matched to a registered study
Identity check
no open identity hold
Audit mark
verified
Review state
Written into the record, not signed off as a reviewed claim
Ranked first in a network the authors themselves rate low-confidence
In plain words
The largest pooled comparison of acne creams put adapalene with benzoyl peroxide at the top. The same paper says the trials underneath report their results so inconsistently that the confidence in the whole ranking is low.
What was measured
That the top of a network meta-analysis ranking is a settled finding, when the paper producing it grades its own confidence as low and had patient-reported data from a quarter of its trials
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Stuart and colleagues pooled 40 randomised trials with 18,089 participants. Patient Global Assessment of Improvement — their primary outcome — was reported in only 11 of the 40. Adapalene with benzoyl peroxide ranked highest for self-reported improvement (54% against 35% for benzoyl peroxide alone) and clindamycin with benzoyl peroxide second (49% against 35%). Withdrawals were low everywhere but higher for the combinations (2.5% and 2.7%) than for benzoyl peroxide (1.6%) or adapalene alone (1.0%). Confidence in the evidence, assessed with CINeMA, was low overall, and the authors state that inconsistent reporting precluded firmer conclusions.
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What is not here
7 questions this page could not answer
These sections were prepared and left out because there was nothing to put in them. They are listed rather than hidden, so the gaps in this record are visible.
What was measured, goal by goal — found nothing in the sources checked.
How close this is to real life — found nothing in the sources checked.
Felt, measured, or meaningful — found nothing in the sources checked.
How long anything takes — found nothing in the sources checked.
What it may clash with — found nothing in the sources checked.
Other ways to the same goal — found nothing in the sources checked.
What changed on this page — found nothing in the sources checked.
The record as stored
The full record, for auditing
Everything above is built from what is below. This layer keeps the technical vocabulary, record identifiers and every stored row, so a reader who wants to check the page can.
The older medicine-wide conclusion held in this record
Written for a clinical reader, and about the medicine as a whole rather than about one indication, population and set of trials. RNAWiki does not treat it as a programme conclusion and no reviewer has signed it off in that form. It is here word for word because it is what the record holds.
A synthetic naphthoic acid retinoid whose adamantyl group makes it photostable and oxidation-resistant where tretinoin is neither — in its 653-patient pivotal trial the 0.3% gel put 21% of patients clear or almost clear against 16% on 0.1% and 9% on plain vehicle, a real and statistically significant difference that leaves four in five patients not clear at twelve weeks.
7 to 51 hours hours; The terminal apparent half-life, determined in 15 of 16 subjects, ranged from 7 to 51 hours, with a mean of 17.2 ± 10.2 hours.
recorded 2026-08-30 · last checked 2026-09-04
Q6
Which 17 trials of Adapalene posted no result?
Posted no result
17 of 17 completed trials
Registrations
NCT00719121, NCT01182636, NCT00757523, NCT01220102, NCT01501799 and NCT01387048, and 11 more
Completion dates
oldest 2007-03; newest 2023-09-20
Show the evidence
Trial
NCT00719121
2007-03
NCT01182636
2008-04
NCT00757523
2009-06-24
NCT01220102
2010-11
NCT01501799
2011-12
NCT01387048
2012-10
11 further recorded trials
NCT01618773
2013-09
NCT01742637
2014-03
NCT02411942
2015-02
NCT01406080
2015-11
NCT03585140
2016-11-30
NCT03626298
2018-04-30
NCT03650361
2019-02-16
NCT03832647
2020-02-17
NCT03615768
2020-04-07
NCT04797793
2021-01-08
NCT06451237
2023-09-20
Q7
At the median, Adapalene's trials enrolled 66 people — anything larger?
Median enrolment
66
Largest enrolment
6036
Registered trials counted
45
Q8
What do 1618 spontaneous reports say about Adapalene — and not say?
These are reports people sent to a regulator. They do not show the medicine caused the reaction. Nobody counted how many people took the medicine and reported nothing. The same event can be reported more than once, and many reports are incomplete. News coverage, lawsuits and new warnings change how often people report. A count is not a rate and not a risk.
Adapalene appears in spontaneous reports to regulators. Across the 10 most-reported reaction terms, 1618 reaction mentions were counted: erythema 318; skin burning sensation 249; dry skin 220; acne 164. FAERS via Open Targets · CHEMBL1265 · 2026-06-24
Show the evidence
erythema
318
skin burning sensation
249
dry skin
220
acne
164
skin exfoliation
154
skin irritation
114
4 more recorded rows
pruritus
111
rash
106
pain of skin
100
hypersensitivity
82
recorded 2026-06-24 · last checked 2026-09-04
Q9
Which 10 reactions does Adapalene's label not list?
ChEMBL 37 — CC BY-SA 3.0 Unported · ChEMBL ATC CC BY-SA · ClinicalTrials.gov — US Government work · Open Targets 26.06 — CC0 · mixed register set; per-register licences in docs/specs/corpus-20k-sources.md · openFDA / DailyMed — US Government work
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✓ source coverage passed: 7 source rows
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