E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Eradication of Staphylococcus aureus from the nose. |
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E.1.1.1 | Medical condition in easily understood language |
Bacterial eradication from the nose. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Bacterial Infections and Mycoses [C01] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10067910 |
E.1.2 | Term | Staphylococcal colonization |
E.1.2 | System Organ Class | 100000004862 |
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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 efficacy of LTX-109 (3%) gel in an intensive dosing regimen to anterior nares in healthy volunteers who have persistent carriage of S. aureus. |
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E.2.2 | Secondary objectives of the trial |
Secondary objectives - To evaluate the efficacy of LTX-109 (3%) gel at different time points after an intensive dosing regimen to anterior nares in healthy volunteers who have persistent carriage of S. aureus. - To evaluate the safety and tolerability of LTX-109 (3%) gel applied in an intensive dosing regimen to anterior nares in healthy volunteers who have persistent carriage of S. aureus. Exploratory objective - To explore the efficacy of LTX-109 (3%) gel in 2 different dosing regimens applied to anterior nares in healthy volunteers who have persistent carriage of S. aureus.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Willing and able to give written informed consent for participation in the study. 2. Male or female subject aged 18 to 65 years, inclusive. 3. Persistent nasal carrier of S. aureus (MSSA), confirmed by 2 positive bacterial cultures from the nose during the screening period. 4. Medically healthy subjects without abnormal clinically significant medical history, physical findings, vital signs, or laboratory values at the time of screening, as judged by the Investigator. 5. Women of child bearing potential (WOCBP) must practice abstinence (only allowed when this is the preferred and usual lifestyle of the subject) or must agree to use a highly effective method of contraception with a failure rate of < 1% to prevent pregnancy (combined [oestrogen and progestogen containing] hormonal contraception associated with inhibition of ovulation [oral, intravaginal, transdermal], progestogen-only hormonal contraception associated with inhibition of ovulation [oral, injectable, implantable], intrauterine device [IUD]or intrauterine hormone-releasing system [IUS]) from the date of dosing until 2 weeks after last dose. Female subjects must refrain from donating eggs from the date of dosing until 3 months after dosing with the IMP. Their male partner must agree to use a condom from date of first dosing until 2 weeks after last dose if he has not undergone vasectomy. Women of non-childbearing potential are defined as pre-menopausal females who are sterilised (tubal ligation or permanent bilateral occlusion of fallopian tubes); or females who have undergone hysterectomy or bilateral oophorectomy; or post-menopausal defined as 12 months of amenorrhea (in questionable cases a blood sample with detection of follicle stimulating hormone [FSH]≥25 IU/L is confirmatory). Male subjects must be willing to use condom or be vasectomised or practice sexual abstinence to prevent pregnancy and drug exposure of a partner and refrain from donating sperm from the date of dosing until 3 months after dosing with the IMP. Their female partner of child-bearing potential must use contraceptive methods with a failure rate of < 1% to prevent pregnancy (see above). |
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E.4 | Principal exclusion criteria |
1. History of any clinically significant disease or disorder which, in the opinion of the Investigator, may either put the subject at risk because of participation in the study, or influence the results or the subject’s ability to participate in the study. 2. Any clinically significant illness, medical/surgical procedure or trauma within 4 weeks of the administration of IMP. 3. Severe eczema or skin wounds, dry or sensitive skin assessed as clinically significant by the Investigator. 4. Any positive result at screening for serum hepatitis B surface antigen, hepatitis C antibody and Human Immunodeficiency Virus (HIV). 5. History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity, as judged by the Investigator, or history of hypersensitivity to drugs with a similar chemical structure or class to LTX-109 or chlorhexidine. 6. S. aureus (MSSA and/or MRSA) decolonisation attempt in the 6 months prior to screening Visit 2. 7. MRSA positive at screening (Visit 1 and/or Visit 2). 8. Inability to take medications nasally. 9. Nasal polyps or significant anatomical nasal abnormality, as judged by the Investigator. 10. Evidence of open wound, lesion, inflammation, erythema or infection (including active rhinitis, sinusitis or upper respiratory infection or severe acne vulgaris) affecting the nostril area, lip and skin close to the nose. 11. History of multiple episodes (>3) of epistaxis within 12 months prior to screening Visit 2. 12. Disease in the region of the application sites, significant history of trauma or skin disease in the region of the application sites, current nasal skin or nasal septum condition requiring treatment or nasal surgery in the 6 months prior to screening Visit 2. 13. In situ nasal jewellery or open nasal piercings. 14. Previous or concurrent treatment with antimicrobials for an infection within the last 28 days prior to the first administration of IMP. 15. Regular use of cortisone or anticoagulation medication within 14 days prior to the first administration of IMP and regular use of nasal decongestants within 30 days prior to the first IMP administration, at the discretion of the Investigator. 16. Planned treatment or treatment with another investigational drug within 28 days prior to the first administration of IMP. Subjects consented and screened but not dosed in previous Phase I studies are not excluded. 17. Positive screen for drugs of abuse or alcohol at screening Visit 2 or on admission to the unit prior to first administration of the IMP. 18. History of alcohol abuse or excessive intake of alcohol, as judged by the Investigator. 19. Presence or history of drug abuse, as judged by the Investigator. 20. Investigator considers the subject unlikely to comply with study procedures, restrictions and requirements. 21. Female subjects who are pregnant or who are currently breast feeding. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Number of subjects on LTX-109 versus placebo with bacterial eradication period lasting for 6 hours, from 6 to 12 hours after start of treatment (the “Operation Window” [OW]). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
According to study flow chart and schedule of events. |
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E.5.2 | Secondary end point(s) |
Secondary efficacy endpoints - Number of subjects on LTX-109 versus placebo with bacterial eradication at 4 ½, 6 and 12 hours after start of treatment. - Percentage change in colony forming units (CFUs) in subjects from baseline on LTX-109 versus placebo at 4 ½, 6 and 12 hours after start of treatment. - Number of subjects on LTX-109 versus placebo with bacterial eradication period lasting for 48 hours, from 6 to 54 hours after start of treatment (“48 hours Eradication Window”) Secondary safety endpoints - Occurrence and frequency of adverse events (AEs). - Clinically significant changes in laboratory parameters, vital signs and physical examination findings. - Local tolerability assessed by qualified health care professional: Erythema, Swelling, Lesions - Local tolerability assessed by subject: Pruritus, Discomfort Exploratory efficacy endpoints Cohort 1 (4 applications after the OW) and Cohort 2 (2 applications after the OW): - Number of subjects on LTX-109 versus placebo with bacterial eradication at 36 and 54 hours after start of treatment. - Number of subjects on LTX-109 versus placebo with bacterial eradication period lasting for 48 hours, from 6 to 54 hours after start of treatment. - Number of subjects on LTX-109 versus placebo with bacterial eradication period lasting for 7 days (from Day 1 at 6 hours to Day 7). - Percentage change in CFUs in subjects from baseline on LTX-109 versus placebo at 36 and 54 hours and for 7 days (from Day 1 at 6 hours to Day 7) after start of treatment. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
According to study flow chart and schedule of events. |
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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 | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
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) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
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 | No |
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 | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
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 | No |
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
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | |