Efficacy and Safety of ATX01 in Adult Patients With CIPN (Chemotherapy-induced Peripheral Neuropathy) (ACT)
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|ClinicalTrials.gov Identifier: NCT05593614|
Recruitment Status : Recruiting
First Posted : October 25, 2022
Last Update Posted : April 12, 2023
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|Condition or disease||Intervention/treatment||Phase|
|Chemotherapy-induced Peripheral Neuropathy||Drug: ATX01 10% Drug: ATX01 15% Drug: Placebo||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||240 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||A Multicenter, Randomized, Double-blind, Parallel-group, Placebo-controlled, Phase 2 Study to Assess the Efficacy and Safety of ATX01 (Topical Amitriptyline Hydrochloride 10% and 15% w/w) in Comparison to Placebo, in Cancer Survivor Adult Patients With Chemotherapy-induced Peripheral Neuropathy (CIPN)|
|Actual Study Start Date :||February 28, 2023|
|Estimated Primary Completion Date :||December 2023|
|Estimated Study Completion Date :||December 31, 2023|
Experimental: ATX01 10%
A bottle of hydrogel formulation containing 10% amitriptyline hydrochloride w/w for topical use on the hands and/or feet, morning and night for 3 months.
Drug: ATX01 10%
A 100 mL bottle of hydrogel formulation containing 10% amitriptyline hydrochloride w/w
Experimental: ATX01 15%
A bottle of hydrogel formulation containing 15% amitriptyline hydrochloride w/w for topical use on the hands and/or feet, morning and night for 3 months.
Drug: ATX01 15%
A 100 mL bottle of hydrogel formulation containing 15% amitriptyline hydrochloride w/w
Placebo Comparator: ATX01 Placebo
A bottle of hydrogel formulation containing no active ingredient, for topical use on the hands and/or feet, morning and night for 3 months.
A 100 mL bottle of hydrogel formulation containing no active substance
- Change from baseline to Week 12 in the weekly mean of the daily NPRS score assessing average pain intensity in target study extremities related to CIPN in the past 24 hours. [ Time Frame: 12 weeks ]
- Percentage of patients achieving ≥30% pain reduction from baseline in the weekly mean NPRS average pain intensity related to CIPN at Week 12 [ Time Frame: 12 weeks ]
- Percentage of patients achieving ≥50% pain reduction from baseline in the weekly mean NPRS average pain intensity related to CIPN at Week 12. [ Time Frame: 12 weeks ]
- Mean change from baseline to each visit in tingling/pins and needles intensity and numbness intensity in target study extremities as measured by the numerical rating scale (NRS) assessing each symptom [ Time Frame: 4 weeks, 8 weeks, 12 weeks ]
- Proportion of patients achieving various percentages of reduction in average pain intensity in target study extremities (cumulative responder curve) throughout the study. [ Time Frame: 4 weeks, 8 weeks, 12 weeks ]
- Change from baseline to Week 4 and 8 in the weekly mean of the daily NPRS score assessing average pain intensity in target study extremities related to CIPN in the past 24 hours [ Time Frame: 4 weeks, 8 weeks ]
- Change from baseline to each visit in the weekly mean of the daily NPRS assessing worst pain intensity in target study extremities related to CIPN in the past 24 hours [ Time Frame: 4 weeks, 8 weeks, 12 weeks ]
- Percentage of patients with at least "improved" on the Patient Global Impression of Change (PGI-C) at each visit [ Time Frame: 4 weeks, 8 weeks, 12 weeks ]
- Mean change from baseline to each visit in pain interference with daily life using the Brief Pain Inventory Short Form questionnaire (BPI-SF item 9 only) [ Time Frame: 4 weeks, 8 weeks, 12 weeks ]
- Mean change from baseline to each visit in the calculated mean NPRS average pain intensity in the nontarget study extremities [ Time Frame: 4 weeks, 8 weeks, 12 weeks ]
- Mean change from baseline to Week 12 in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-CIPN 20-item scale (EORTC QLQ CIPN20) [ Time Frame: 12 weeks ]
- Use of rescue medication including the proportion of patients using rescue medication, the frequency, and amount used [ Time Frame: Up to 12 weeks ]
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|Ages Eligible for Study:||18 Years and older (Adult, Older Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
- Male or female patients of 18 years and older.
- Patients having signed a written informed consent prior to any study-related procedure.
- Body mass index of 18 to 32 kg/m2 (inclusive).
- With an estimated life expectancy ≥6 months at study entry.
- Patients with painful sensory CIPN resulting from prior treatment of cancer with taxanes or platins. A diagnosis of CIPN should be supported by i) onset of pain in hands or feet after exposure to taxanes or platins, ii) presence of painful symptoms in a symmetrical stocking and/or glove distribution, AND iii) painful symptoms may be accompanied by nonpainful symptoms (eg, tingling/pins and needles intensity and numbness intensity).
- Patients who have stopped their chemotherapy treatment with taxanes or platins or any other neurotoxic chemotherapy for ≥24 weeks at the time of the screening visit.
- Patients with CIPN pain for ≥24 weeks at the time of the screening visit.
- Patients with a mean value of pain intensity ≥4 and ≤9 in target study extremities (left and right feet or left and right hands) on the 11 point NPRS at baseline.
- Patients with symmetrical stocking or glove distribution pain, NPRS (≤1 point difference) in the target study extremities at screening.
- Neuropathic Pain (DN4) score ≥4 in the target study extremities (hands or feet) at the screening visit
- Treatment naïve patients or patients in whom any prior CIPN treatment (except oral amitriptyline [AMT]) has not been modified during the 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).
- 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 (EoS) Visit. Male patients should agree not to donate sperm until 30 calendar days after the last dose of study drug.
Females must comply with the following in order to be enrolled:
- WOCBP with negative serum pregnancy test results can be enrolled only if willing to use an acceptable contraceptive method, ie, 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.
- Patients who are not compliant in completion of pain ratings during the screening period. Patients having <5 of 7 records of average pain intensity in the target study extremities from Day -7 to Day -1 will be excluded. If a patient misses records of 2 days out of 7 days, the patient will be included in the study; however, patients missing 3 or more days of records will be excluded from the study.
- Clinical evidence of a preexisting painful peripheral neuropathy resulting from another cause than chemotherapy, eg, diabetic neuropathy, posttraumatic neuropathy, carpal/tarsal tunnel syndrome, radiculopathy, spinal stenosis, brachial plexopathy, or other preexisting symptomatic neuropathy due to alcoholism, vitamin B deficiency, hypothyroidism, human immunodeficiency virus.
- Skin abnormality, irritation, or lesions of any type on the hands or feet (or only on the hands if the study drug is not applied on the feet and vice versa [only on the feet if the study drug is not applied on the hands]).
- 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. Patients with a medical history of bipolar disorder, alcohol abuse, or psychotic disorder are also excluded.
- Patients who are at significant risk of suicide, or are a danger to self or others, in the opinion of the investigator, based upon clinical interview and the Columbia-Suicide Severity Rating Scale (C SSRS) at screening and baseline. Affirmative answer to suicidal ideation questions 4 or 5, or suicidal behavior (actual attempt, interrupted attempt, aborted attempt, and/or preparatory acts/behavior) within the last 6 months is exclusionary.
- 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 msec for males or >450 msec for females.
- A history of additional risk factors for Torsade de Pointe (eg, 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 (eg, quinidine, disopyramide, procainamide) and Class 3 antiarrhythmics (eg, amiodarone, sotalol), antihistamines, antipsychotics known to prolong QT interval, and antimalarials (eg, mefloquine, quinine), tricyclic antidepressants (eg, AMT), tetracyclic antidepressants (eg, 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.
- Patients likely to require neurotoxic chemotherapy treatment or any other treatment during the study, which may interfere with compliance to the protocol, ability to complete the study and study assessments except treatments authorized in inclusion criterion #11.
- Failure to respond to more than 2 analgesics (regardless of the route of administration) from different drug classes (including antidepressants and anticonvulsants) due to lack of efficacy or intolerability to treat CIPN at any time in the past.
- Treatment with oral or topical AMT or nortriptyline in the past 4 weeks.
- Any known hypersensitivity to AMT (regardless of the route of administration) in any salt form or to any constituent of the topical formulation.
- Any contraindication to the use of acetaminophen/paracetamol.
- 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 previous 12 weeks.
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.
- Poor metabolizer for cytochrome P450 CYP2D6.
- Intake in the 4 weeks preceding the screening visit of any strong inhibitor of cytochrome P450 CYP2D6.
- 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 hands or feet.
- The patient is an employee of the investigator, study site, sponsor, or CRO 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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05593614
|Other Study ID Numbers:||
2022-000435-23 ( EudraCT Number )
|First Posted:||October 25, 2022 Key Record Dates|
|Last Update Posted:||April 12, 2023|
|Last Verified:||April 2023|
|Studies a U.S. FDA-regulated Drug Product:||Yes|
|Studies a U.S. FDA-regulated Device Product:||No|
Peripheral Nervous System Diseases
Nervous System Diseases