Recalcitrant acne vulgaris MedDRA version: 20.0 Level: LLT Classification code 10000519 Term: Acne vulgaris System Organ Class: 100000004858
Conditions
Interventions
Product Name: Nacystelyn
Product Code: NAL
Pharmaceutical Form: Powder for oral solution in sachet
INN or Proposed INN: L-Lysine-N-acetylcysteinate
CAS Number: 89344-48-9
Current Sponsor code: NAL
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Sponsors
LABORATOIRES SMB S.A
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patients must satisfy the following criteria before entering the study: 1.Males or females, aged between 12 and 50 years, inclusively. 2.Patients presenting a severe recalcitrant acne vulgaris with 10 or more inflammatory nodules with a diameter of 5 mm or greater (facial and/or truncal). 3.Weight between 40 – 110 kg. 4.Able to comply with all study procedures. 5.Patients who are willing and able to provide written informed consent, after being informed of all the pertinent aspects of the study. If the patient is female and of childbearing potential, she must be using two separate and efficient means of birth control. (See “contraception and pregnancy tests section for more details). Contraception should be used for at least 1 month prior to starting treatments, throughout treatments and continue for at least 1 month after stopping treatments. A negative pregnancy test must be provided at screening and within 11 days prior to initiating therapy or the day of the randomisation at the latest. Even female patients who normally do not employ contraception due to a history of infertility, amenorrhea or claim absence of sexual activity will have to use contraception while taking the study treatments Note: A woman is considered of childbearing potential, i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilization methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. Are the trial subjects under 18? yes Number of subjects for this age range: 20 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 70 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range 0
Exclusion criteria
Exclusion criteria: Patients who meet any of the following criteria will be excluded from participating in the study: 1.Evidence of any clinically significant immunological, neoplastic, endocrine, hematological, gastrointestinal, neurological, cardiovascular, or psychiatric abnormalities. 2.Abnormal liver function (hepatocellular insufficiency, chronic or active liver disease, biliary tract disease, sustained elevation of serum liver enzymes (simultaneously ASAT and ALAT > 2x UNL)). 3.Abnormal renal function (clearance of creatinine 20 mg/L) or any renal disease likely to lead to renal dysfunctions. 4.No clinically significant abnormal laboratory value and/or vital signs measurement as per the judgement of the study investigator. 5.Patients with any sensitivity or allergy to any of the products used within this clinical trial: known hypersensitivity to isotretinoin, retinoic acid and derivatives of vitamin A. 6.Any skin disease that might interfere with the evaluation of severe recalcitrant nodular acne. 7.Patients with a history or current psychiatric illness (e.g. depression, psychotic symptoms, suicidal behavior). 8.Patients who, during the past month, have received systemic corticosteroids and during the past 7 days have received topical corticosteroids. For isotretinoin 6 months wash out period should be fulfilled. 9.Recent history of alcoholism (above 21 beverages per week. One alcoholic beverage is defined as 30 mL distilled spirits, 120 mL wine, or 330 mL beer) or drug abuse. 10.Use of any prohibited medication as detailed in the concomitant medication section of the protocol. 11.Use of any investigational drug or participation in any clinical trial within 3 months of their first dosing. 12.Donation of blood during the study and for one month after discontinuation of study treatment. 13.Pregnant and breastfeeding women 14.Subjects who were unlikely to co-operate with the requirements of the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare the efficacy of the nacystelyn in combination with isotretinoin of different concentrations in patients with recalcitrant acne vulgaris;Secondary Objective: To assess the efficacy, the safety and the tolerability of the study treatments;Primary end point(s): The main study hypothesis is that Test 2 is non-inferior to Reference on the relative change in the number of facial and truncal nodules between W0 and W20 A mixed model for repeated measures with baseline value, group, time and interaction group*time as fixed factors will be built. The natural logarithm of the relative change from baseline will be regressed over time (W4, W8, W12, W16, W20). All timepoints will be included into the model for taking into account the variability of all timepoint measures. Several covariance structure of the matrix will be tested (UN, AR(1), TOEPH, VC). The matrix will be selected according to the Akaike information criterion (AIC). The preferred model is the one with the minimum AIC value. Interaction group*time will be kept in the model even if not significant. A simple effect of groups on the change from W0 to W20 will be assessed at W20 using a test of slice effect using this mixed model. Contrast between Test 2 and Reference will be calculated at W20 and will be expressed along with a 95% two-sided confidence interval after exponentiation. If the ratio Test 2 / Reference is > 0.85, test 2 will be considered non-inferior to Reference. No adjustment of Type 1 error risk will be made. ;Timepoint(s) of evaluation of this end point: W4, W8, W12, W16, W20 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): All endpoints involving relative changes from baseline over time will be analyzed as the primary endpoint unless the comparison to a non-inferiority threshold. A slice effect will be tested at each time point. For the comparison of Test 1 and Reference on the relative change in the number of nodules between W0 and W8, no adjustment of Type 1 error rate will be made. For other comparisons involving Test 1 vs Reference and Test 2 vs Reference a Dunnett’s adjustment will be made. End points involving absolute changes from baseline over time will be analyzed as follows. A mixed model for repeated measures with baseline value, group, time and interaction group*time as fixed factors will be built. The absolute change from baseline will be regressed over time (W4, W8, W12, W16, W20). All timepoints will be included into the model for taking into account the variability of all timepoint measures. Several covariance structure of the matrix will be tested (UN, AR(1), TOEPH, VC). The matrix will be selected according to the Akaike information criterion (AIC). The preferred model is the one with the minimum AIC value. Interaction group*time will be kept in the model even if not significant. A test of slice effect will be performed at each time point using this mixed model. Contrasts between Test 1 and reference and between Test 2 and Reference will be calculated at each time point and will be expressed along with a 95% two-sided confidence interval with a Dunnett’s adjustment. The percentage of patients with a 90% clearance of the nodules will be estimated at each time point (W2, W4, W8, W12, W16, W20) using the Kaplan-Meier method. Estimates will be calculated at each time point along with a 95% two-sided confidence interval. The same method will apply for the percentage of patients with PGSA 0 or 1, and for the percentage of patients with PAE 0 or 1. Groups will be compared by the log rank test. ;Timepoint(s) of evaluation of this end point: W4 | — |
Countries
Bulgaria
Contacts
Public ContactCLINICAL DEPARTMENT
LABORATOIRES SMB S.A
Outcome results
None listed