| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| E.1.1.1 | Medical condition in easily understood language |
| Teenage and adult moderate to severe acne |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Skin and Connective Tissue Diseases [C17] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 14.1 |
| E.1.2 | Level | HLT |
| E.1.2 | Classification code | 10000497 |
| E.1.2 | Term | Acnes |
| E.1.2 | System Organ Class | 100000004858 |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| To evaluate the safety, tolerability, efficacy and pharmacokinetics of three concentrations (0.5 %, 1.5 % and 3 %) of topical anti-Acne product Neramexane mesylate gel, quaque die (qd) when compared to vehicle in subjects with Moderate to Severe Acne. |
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| E.2.2 | Secondary objectives of the trial | |
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
For Stage 1 only:
1. Male or female of any ethnic origin 18 to 65 years of age.
For Stage 2 only:
2. Male or female of any ethnic origin 12 to 65 years of age.
For Stage 1 and 2:
3. Subject must sign the informed consent. For minor (less than 18 years), the legally acceptable representative (i.e. parents or guardian) must complete the informed consent process and sign the informed consent form AND the subject must complete the assent process and sign the appropriate form (if age appropriate).
4. Understanding of study procedures and willingness to abide by all procedures during the course of the study.
5. Moderate to Severe Acne on the face with a combination of inflammatory and non-inflammatory lesions.
6. Has an inflammatory Acne lesion count (papules and pustules) of no less than 20 but no more than 50.
7. Has facial Acne non-inflammatory Acne lesion count (open and closed comedones) of no less than 20 but no more than 100.
8. Has two or fewer nodulocystic lesions (defined as an inflammatory lesion greater than or equal than 5 mm in diameter).
9. Has an Evaluator Global Severity Score EGSS of moderate (=3) or severe (=4) score.
10. Subject is willing to refrain from using antimicrobial topical products (shampoo, soap, Acne preparation) as well as oral and OTC Acne products.
11. Subject must be willing to comply with the study requirements.
12. Stable medical condition.
13. Subject must be in good health and free from any clinically significant disease relevant to the study that as per the physician might interfere with the study evaluation.
14. Woman and all younger female of childbearing potential must be using a highly effective method of birth control.
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| E.4 | Principal exclusion criteria |
For Stage 1 only:
1. Regular use of over-the-counter (OTC) oral drugs in the 4 weeks prior to the (first) administration of the IP.
2. Occasional use of OTC drugs (except paracetamol, maximum 1 g/day) in the 2 weeks prior the (first) administration of the IP.
3. History of blood loss or donation of blood or plasma exceeding 450 ml within the last three months before first administration of IP.
4. Positive results in any of the serology tests (Human Immunodeficiency Virus (HIV1/2) antibodies, hepatitis B surface antigen, antibodies against hepatitis C virus).
5. Use of any prescribed drugs in the 4 weeks prior to the (first) administration of the IP with the exception of hormonal contraceptive.
6. Subject with a positive drug or alcohol breath test.
For Stage 1 and 2:
7. Subject with an Evaluator Global Severity Score EGSS of clear (=0), almost clear (=1), mild (=2) or very severe (=5).
8. Subject with a clinical diagnosis of Acne conglobata, mirror addict Acne, Acne fulminans, secondary Acne (Chloracne, drug induced Acne), facial keloids, and hypertrophic scars, or another dermato-logical condition, or underlying disease that requires the use of interfering topical or systemic therapy.
9. Subject exposed or planning excessive sun exposure within the study timeframe.
10. Subject with any or dermatologic disorder that could be considered a differential diagnosis of Acne e.g. Rosacea, Keratosis Pilaris, etc.
11. Excessive facial hair (e.g., beards, sideburns, moustaches, etc.) that would interfere with diagnosis or assessment of Acne vulgaris.
12. Use on the face within 1 month prior to Baseline of: 1) cryodestruction or chemodestruction, 2) dermabrasion, 3) photodynamic therapy, 4) Acne surgery, 5) intralesional steroids, or 6) x-ray therapy.
13. Use for less than 3 months prior to Baseline of estrogens or oral contraceptives; use of such therapy must remain constant throughout the study.
14. Use within 6 months prior to Baseline of oral retinoids (e.g. Isotretinoin) or therapeutic vitamin A supplements of greater than 10,000 units/day (multivitamins are allowed stage 2 only).
15. Use within 1 month prior to Baseline of: 1) spironolactone, 2) systemic steroids, 3) systemic antibiotics, 4) systemic treatment of Acne vulgaris (other than oral retinoids, which require a 6-month washout), systemic anti-inflammatory agents.
16. Use within 2 weeks prior to Baseline in the face of: 1) topical steroids, 2) topical retinoids, 3) topical Acne treatments including over-the-counter preparations but excluding cosmetic (make-up) products, 4) topical anti-inflammatory agents, 5) medicated cleansers or 6) topical antibiotics.
17. Known hypersensitivity to the IP (s) or vehicle or any of their formulation ingredients.
18. Nursing mother or pregnant woman, as verified by a positive pregnancy test, or plan to become pregnant within the study timeframe.
19. Subject with clinically significant disease relevant to this study as judged by the investigator within 3 months of the study (e.g., significant lab abnormalities, myocardial infarct, stroke, cancer, connective tissue diseases (scleroderma, systemic lupus erythematosus), systemic infection (e.g., significant systemic bacterial, viral or mycotic infection), uncontrolled diabetes, etc.) including subjects with medical conditions that might require the use of immunosuppressive medications during the trial (e.g., severe, uncontrolled asthma, rheumatoid arthritis, autoimmune diseases, etc.).
20. Subject that has used pigmenting agents (self-tanning agents) within the last two weeks prior to Baseline.
21. Subject with abnormal findings, noted on a physical exam or laboratory result, that are considered by the investigator to be clinically important and indicative of conditions that might complicate interpretation of the study results.
22. Subject with severe physical, neurological or mental disease that would interfere with the conduct and/or compliance of this clinical study as judged by the investigator.
23. Systolic blood pressure <95 mmHg or >140 mmHg or diastolic blood pressure <50 mmHg or >95 mmHg in semi-supine position.
24. Pulse rate <45 or >100 beats per minute.
25. Subject with a history of, or known to, abuse alcohol or drugs.
26. Evidence or suspicion that the subject might not comply with the study directives and/ or that he/she is not trustworthy.
27. Subject who is imprisoned or is lawfully kept in an institution.
28. Employee or direct relative of an employee of the CRO, the study site, or Merz.
29. Subject who has participated in a clinical investigational product trial within the last thirty (30) days prior to the first planned study drug administration or during this trial.
30. Previous randomization in this clinical study.
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| E.5 End points |
| E.5.1 | Primary end point(s) |
| • Change from Baseline to Week 12 in inflammatory Acne lesion counts. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
• Change from Baseline to Week 12 in non-inflammatory Acne lesion counts.
• Dichotomized assessment of improvement of two grades (improvement versus no improvement) at Week 12 from Baseline EGSS.
|
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | Yes |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | Yes |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | Yes |
| E.7.1.3.1 | Other trial type description |
| PK evaluation in acne patients |
|
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | Yes |
| E.8.1.7.1 | Other trial design description |
|
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 4 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 14 |
| E.8.5 | The trial involves multiple Member States | No |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 1 |
| E.8.9.1 | In the Member State concerned months | 0 |
| E.8.9.1 | In the Member State concerned days | 0 |
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