ErythromelalgiaPhase 2EASENCT05917912
EASE (Efficacy of ATX01 Study in Erythromelalgia)
A Phase 2 study testing Amitriptyline Hydrochloride in people with Erythromelalgia, run by AlgoTherapeutix at 2 sites in 2 countries.
Trial summary
The goal of this two-center, randomized, double-blinded, parallel-group, placebo-controlled clinical study is designed to compare the efficacy of twice daily applications of ATX01 versus placebo during two consecutive 3-week treatment periods. The primary objective is the comparison between Treatments (ATX01 15% vs. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Erythromelalgia
- What is being tested?
- Amitriptyline Hydrochloride
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 14 participants
- Where
- 2 sitesin 2 countries
- Study dates
- 14 Jun 2023to 29 Feb 2024
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female patients 18 years of age and older.
- Documented diagnosis of erythromelalgia, as characterized by redness, warmth, and burning pain of the extremities (most commonly feet), typically precipitated by heat or exercise and relieved by cooling.
- Mean pain attack intensity, measured on the 11-point NPRS, of ≥4 and ≤9 at baseline and ≥4 pain attacks per week as documented through eDiary use during the 3 weeks prior to randomization (Day -21 to Day -1).
- Use of concomitant medications, with the exception of topical agents applied to the hands or feet, are permitted if the dose has been stable for at least 4 weeks preceding the screening visit and is planned to be maintained at the same regimen during the course of the study (prior treatment includes pharmacological and nonpharmacological treatments).
- Patients having signed a written informed consent prior to any study related procedure.
- Male patients should agree to use a condom along with another medically acceptable contraceptive method, where applicable according to local guidelines, if he is engaged in sexual activity with a woman of childbearing potential (WOCBP) from the day of the signature of the informed consent and up to 90 days after the end-of-study visit. Male patients should agree not to donate sperm until 90 calendar days after the last dose of study drug.
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- Females must comply with the following in order to be enrolled:
- WOCBP with negative pregnancy test results can be enrolled only if willing to use an acceptable contraceptive method, i.e. oral contraceptives, patch contraceptives, injection contraceptives, implantable hormonal contraceptives, male condom with intravaginal spermicide, diaphragm or cervical cap with spermicide, vaginal contraceptive ring, intrauterine device or system, surgical sterilization (hysterectomy, bilateral oophorectomy, and/or bilateral salpingectomy), tubal ligation/occlusion, vasectomized partner, or sexual abstinence, if this is the patient's current practice, from at least 14 days prior to the screening visit and throughout the study and for at least 30 days after the completion of the study.
- Or surgically sterilized for at least 6 months.
- Or menopausal, for at least 1 year.
Who cannot join
- Clinical evidence of a pre-existing pain disorder in the extremities resulting from another cause than erythromelalgia, e.g. complex regional pain syndrome (CRPS), diabetic neuropathy, chemotherapy-induced peripheral neuropathy (CIPN).
- Evidence of skin breakdown, ulcers, papules and > +2 pitting edema of the affected limbs.
- Presence of glaucoma.
- Presence of urinary retention (or significant prostatic hypertrophy at risk of urinary retention).
- History of coronary artery disease.
- History and /or presence of major depressive episode.
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- The patient has suicidal risk in the opinion of the investigator based upon clinical interview and the Columbia Suicide-Severity Rating Scale.
- Pregnant or lactating women.
- Abnormality in the 12-lead electrocardiogram (ECG) at screening that in the opinion of the investigator increases the risk of participating in the study, such as a corrected QT Fridericia (QTcF) interval >430 ms for males or >450 ms for females.
- A history of additional risk factors for Torsade de Pointe (e.g. heart failure, hypokalemia, family history of Long QT Syndrome).
- The use of concomitant medications within 24 weeks prior to Day 1 and/or during the study or the equivalent of 5 half-lives that prolong the QT/QTc interval, eg, Class 1 antiarrhythmics (e.g. quinidine, disopyramide, procainamide) and Class 3 antiarrhythmics (e.g. amiodarone, sotalol), antihistamines, antipsychotics known to prolong QT interval, and antimalarials (e.g. mefloquine, quinine), tricyclic antidepressants (e.g. AMT), tetracyclic antidepressants (e.g. maprotiline), cisapride.
- The use of monoamine oxidase inhibitors within 24 weeks (or the equivalent of 5 half-lives) prior to Day 1 and/or during the study.
- The use of opioids within 4 weeks (or the equivalent of 5 half-lives) prior to Day 1 and/or during the study.
- History of illicit drug use or confirmed drugs of abuse at screening. Positive urine drug screen for prescribed medication is allowed at the discretion of the investigator.
- Use of more than 2 analgesics (regardless of the route of administration) from different drug classes (including antidepressants and antiepileptics) on top of study drug.
- Treatment with oral or topical amitriptyline or nortriptyline in the past 4 weeks or current treatment with any other tricyclic antidepressant.
- Any known hypersensitivity to amitriptyline (regardless of the route of administration) in any salt form or to any constituent of the topical formulation.
- Use of glutathione, vitamin E, minocycline, or calcium magnesium supplements within 12 weeks of screening.
- Any topical treatment on treated extremities for any indication, other than cosmetic use of creams and lotions, within the 12 weeks prior to screening.
- Any topical treatment for pain including use of:
- over-the-counter capsaicin on extremities within 12 weeks of screening,
- and/or Qutenza within 24 weeks of screening,
- and/or nonsteroidal anti-inflammatory drugs, menthol, methyl salicylate, local anesthetics within 1 week of screening.
- Implanted active medical device (eg, spinal cord stimulator, intrathecal pump, or peripheral nerve stimulator) for the treatment of pain or any etiology.
- Regional anesthetic block for pain of any etiology within 3 months prior to screening.
- Intake in the 4 weeks preceding screening visit of any medication susceptible to inhibit or induce cytochrome P450 CYP2D6.
- Poor metabolizers of CYP2D6 substrates.
- Treatment with an investigational drug in the previous 4 weeks or greater, according to local requirements
- Any condition that the investigator feels would place the patient at increased risk if the investigational therapy is initiated, such as, but not limited to, hyperthyroidism, convulsive disorder, advanced hepatic disease, pylorus, stenosis, or paralytic ileus.
- The investigator considers the patient unfit for the study as a result of the medical interview, physical examination, or screening investigations, in particular any status or disease making the patient unable to follow instructions.
- The patient is unable to apply the study drug on feet and/or hands.
- The patient is an employee of the investigator, study site, sponsor, or contract research organization with direct involvement in the proposed study or other studies under the direction of the investigator, study site, or sponsor, or a family member of the site employee or the Investigator.
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
About this study
Official title: A Randomized, Double-blind, Placebo-controlled, 2-period, Crossover Study to Evaluate the Efficacy and Safety of ATX01 (Topical Amitriptyline Hydrochloride 15% w/w) in Adult Patients With Pain Due to Erythromelalgia (EM)
The goal of this two-center, randomized, double-blinded, parallel-group, placebo-controlled clinical study is designed to compare the efficacy of twice daily applications of ATX01 versus placebo during two consecutive 3-week treatment periods. The primary objective is the comparison between Treatments (ATX01 15% vs. Placebo) of mean pain attack intensity score assessed for the final week of each treatment period using an 11-point Numerical Pain Rating Scale (NPRS). Mean pain attack intensity is defined as the sum of the pain intensity score of each pain attack during the last 7 full days (Day 14 to Day 20) of each Treatment Period divided by the total number of erythromelalgia pain attacks during that 7-day period.
Participants will apply on feet and/or hands twice a day in the morning and in the evening, approximately 12 hours apart from the morning administration for 3 consecutive weeks each and record the pain intensity of each attack that occurs.
- Conditions
- Erythromelalgia
- Being tested
- Amitriptyline Hydrochloride, Placebo
- Medical subject headings
- Erythromelalgia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Amitriptyline HydrochlorideDrug
hydrogel bottle of ATX01 15% , 0,5ml (1pump) per hand, 1ml (2 pumps) per feet during 3 weeks
PlaceboDrug
hydrogel bottle of placebo , 0,5ml (1pump) per hand, 1ml (2 pumps) per feet during 3 weeks
| Study group | Role | What they receive |
|---|---|---|
| Sequence A | Active comparator | i)screening and randomization; ii) baseline period (3 weeks); iii) treatment period 1 with placebo(3 weeks); iv) wash-out period (3 weeks); v), treatment period 2 with ATX-01(3 weeks); vi) follow-up visit Receives: Drug: Amitriptyline Hydrochloride; Drug: Placebo |
| Sequence B | Active comparator | i)screening and randomization; ii) baseline period (3 weeks); iii) treatment period 1 with ATX-01(3 weeks); iv) wash-out period (3 weeks); v), treatment period 2 with placebo (3 weeks); vi) follow-up visit Receives: Drug: Amitriptyline Hydrochloride; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Comparison between Treatments (ATX01 15% vs. Placebo) of mean pain attack intensity score
Comparison between Treatments (ATX01 15% vs. Placebo) of mean pain attack intensity score assessed for the final week of each treatment period using an 11-point Numerical Pain Rating Scale (NPRS). Mean pain attack intensity is defined as the sum of the pain intensity score of each pain attack during the last 7 full days (Day 14 to Day 20) of each Treatment Period divided by the total number of erythromelalgia pain attacks during that 7-day period
Measured: during the last 7 full days (Day 14 to Day 20) of each Treatment Period
Secondary outcomes (11)
Mean pain attack intensity score for complete treatment period
11 point Numeric Pain Rating Scale Scale: 0-10 10 means worst possible pain
Measured: through study completion, an average of 15 weeks
Patient Global Impression of Change (PGI-C) score
Patient Global Impression: Global Change (PGI-C) Scale: 1-7 7 means very much worse
Measured: through study completion, an average of 15 weeks
Change in pain interference with daily life using the Brief Pain Inventory - Short Form questionnaire (BPI-SF)
Brief Pain Inventory Pain Interference Questionnaire Scale: 0-10 10 means completely interferes
Measured: through study completion, an average of 15 weeks
Change in quality of life, measured using the EuroQol-5-Dimension (EQ-5D) instrument
EuroQol-5-Dimension scale
Measured: through study completion, an average of 15 weeks
Change in Beck Depression Inventory (BDI) score.
BDI Scale:0-3 3 means worse
Measured: through study completion, an average of 15 weeks
Maximum pain intensity score, assessed by 11-point NPRS.
11 point Numeric Pain Rating Scale Scale: 0-10 10 means worst possible pain
Measured: through study completion, an average of 15 weeks
Mean number of pain attacks per day
Measured: through study completion, an average of 15 weeks
Mean and maximum duration of pain attacks
Measured: through study completion, an average of 15 weeks
Mean frequency of use of rescue measures (e.g., cooling).
Measured: through study completion, an average of 15 weeks
Mean duration of use of rescue measures (e.g., cooling).
Measured: through study completion, an average of 15 weeks
Change in pain score before and after rescue measures (e.g., cooling).
11 point Numeric Pain Rating Scale Scale: 0-10 10 means worst possible pain
Measured: through study completion, an average of 15 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jun 2023
- Study start14 Jun 2023
- Primary completion29 Feb 2024
- Study completion29 Feb 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for ErythromelalgiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- AlgoTherapeutix
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05917912
- Sponsor's protocol ID
- ATX01-23-01-EM
- Other IDs
- 2022-003804-34, 161942
- Acronym
- EASE
- Status last verified
- May 2023
- First submitted
- 5 Jun 2023
- Last updated
- 18 Apr 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-blind, Placebo-controlled, 2-period, Crossover Study to Evaluate the Efficacy and Safety of ATX01 (Topical Amitriptyline Hydrochloride 15% w/w) in Adult Patients With Pain Due to Erythromelalgia (EM)
- ClinicalTrials.gov ID
- NCT05917912
- Acronym / sponsor ID
- EASE / ATX01-23-01-EM
- Conditions
- Erythromelalgia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 14 participants (actual)
- Lead sponsor
- AlgoTherapeutixIndustry (pharma, biotech, devices)
- Study start
- 14 Jun 2023 (actual)
- Primary completion
- 29 Feb 2024 (actual)
- Study completion
- 29 Feb 2024 (actual)
- First posted
- 26 Jun 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this two-center, randomized, double-blinded, parallel-group, placebo-controlled clinical study is designed to compare the efficacy of twice daily applications of ATX01 versus placebo during two consecutive 3-week treatment periods. The primary objective is the comparison between Treatments (ATX01 15% vs. Placebo) of mean pain attack intensity score assessed for the final week of each treatment period using an 11-point Numerical Pain Rating Scale (NPRS). Mean pain attack intensity is defined as the sum of the pain intensity score of each pain attack during the last 7 full days (Day 14 to Day 20) of each Treatment Period divided by the total number of erythromelalgia pain attacks during that 7-day period.
Participants will apply on feet and/or hands twice a day in the morning and in the evening, approximately 12 hours apart from the morning administration for 3 consecutive weeks each and record the pain intensity of each attack that occurs.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Sequence A | Active comparator | Drug: Amitriptyline Hydrochloride, Drug: Placeboi)screening and randomization; ii) baseline period (3 weeks); iii) treatment period 1 with placebo(3 weeks); iv) wash-out period (3 weeks); v), treatment period 2 with ATX-01(3 weeks); vi) follow-up visit |
| Sequence B | Active comparator | Drug: Amitriptyline Hydrochloride, Drug: Placeboi)screening and randomization; ii) baseline period (3 weeks); iii) treatment period 1 with ATX-01(3 weeks); iv) wash-out period (3 weeks); v), treatment period 2 with placebo (3 weeks); vi) follow-up visit |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Male or female patients 18 years of age and older.
- Documented diagnosis of erythromelalgia, as characterized by redness, warmth, and burning pain of the extremities (most commonly feet), typically precipitated by heat or exercise and relieved by cooling.
- Mean pain attack intensity, measured on the 11-point NPRS, of ≥4 and ≤9 at baseline and ≥4 pain attacks per week as documented through eDiary use during the 3 weeks prior to randomization (Day -21 to Day -1).
- Use of concomitant medications, with the exception of topical agents applied to the hands or feet, are permitted if the dose has been stable for at least 4 weeks preceding the screening visit and is planned to be maintained at the same regimen during the course of the study (prior treatment includes pharmacological and nonpharmacological treatments).
- Patients having signed a written informed consent prior to any study related procedure.
Key exclusion criteria (32 listed)
- Clinical evidence of a pre-existing pain disorder in the extremities resulting from another cause than erythromelalgia, e.g. complex regional pain syndrome (CRPS), diabetic neuropathy, chemotherapy-induced peripheral neuropathy (CIPN).
- Evidence of skin breakdown, ulcers, papules and > +2 pitting edema of the affected limbs.
- Presence of glaucoma.
- Presence of urinary retention (or significant prostatic hypertrophy at risk of urinary retention).
- History of coronary artery disease.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Amitriptyline Hydrochloridehydrogel bottle of ATX01 15% , 0,5ml (1pump) per hand, 1ml (2 pumps) per feet during 3 weeks | Drug | Sequence A, Sequence B |
| Placebohydrogel bottle of placebo , 0,5ml (1pump) per hand, 1ml (2 pumps) per feet during 3 weeks | Drug | Sequence A, Sequence B |
Primary outcome
Comparison between Treatments (ATX01 15% vs. Placebo) of mean pain attack intensity score
Time frame: during the last 7 full days (Day 14 to Day 20) of each Treatment Period
Comparison between Treatments (ATX01 15% vs. Placebo) of mean pain attack intensity score assessed for the final week of each treatment period using an 11-point Numerical Pain Rating Scale (NPRS). Mean pain attack intensity is defined as the sum of the pain intensity score of each pain attack during the last 7 full days (Day 14 to Day 20) of each Treatment Period divided by the total number of erythromelalgia pain attacks during that 7-day period
11 secondary outcomes
Mean pain attack intensity score for complete treatment period
Time frame: through study completion, an average of 15 weeks
Patient Global Impression of Change (PGI-C) score
Time frame: through study completion, an average of 15 weeks
Change in pain interference with daily life using the Brief Pain Inventory - Short Form questionnaire (BPI-SF)
Time frame: through study completion, an average of 15 weeks
Change in quality of life, measured using the EuroQol-5-Dimension (EQ-5D) instrument
Time frame: through study completion, an average of 15 weeks
Change in Beck Depression Inventory (BDI) score.
Time frame: through study completion, an average of 15 weeks
Maximum pain intensity score, assessed by 11-point NPRS.
Time frame: through study completion, an average of 15 weeks
Mean number of pain attacks per day
Time frame: through study completion, an average of 15 weeks
Mean and maximum duration of pain attacks
Time frame: through study completion, an average of 15 weeks
Mean frequency of use of rescue measures (e.g., cooling).
Time frame: through study completion, an average of 15 weeks
Mean duration of use of rescue measures (e.g., cooling).
Time frame: through study completion, an average of 15 weeks
Change in pain score before and after rescue measures (e.g., cooling).
Time frame: through study completion, an average of 15 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Apr 2024.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Amitriptyline Hydrochloride in people with Erythromelalgia, run by AlgoTherapeutix at 2 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 32 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States, Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Comparison between Treatments (ATX01 15% vs. Placebo) of mean pain attack intensity score (time frame: during the last 7 full days (Day 14 to Day 20) of each Treatment Period). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Apr 2024.