Effect of Minocycline & Amoxicillin on Antibiotic Resistant Bacteria and Indigenous Microbiotas (ANTIRESDEV)

Helperby Therapeutics

Status and phase: Completed; Phase 4

Conditions: Antibiotic Resistant Bacteria

Treatments: Drug: 2 doses of minocycline daily for five days; Other: 2 doses of placebo daily for five days; Drug: 3 doses of amoxicillin daily for 7 days

Study type: Interventional

Funder types: Industry

Identifiers

NCT02030912

C09040

Details and patient eligibility

About

A randomised, open labelled study design is selected in order to determine the emergence and persistence of antibiotic resistant bacteria in humans and on the composition of the indigenous microbiotas at various body sites. These will involve the administration to volunteers of minocycline and amoxicillin- a control group will receive a placebo. Microbiology of the skin, saliva, faecal, skin and nasal micro flora, safety and adverse events, vital signs, will be evaluated. The objectives of metagenomic analysis are:

• To identify the in vivo molecular mechanisms responsible for antibiotic resistance and its transfer in the indigenous oral and faecal microbiotas using metagenomics resistome analysis.
• To determine the impact of the use of antimicrobial agents on the oral resistome
• To determine the impact of the use of antimicrobial agents on the faecal resistome
• To determine the ecological impact of the use of antimicrobial agents on the relative abundance of phylotypes of the indigenous oral microbiota
• To determine the ecological impact of the use of antimicrobial agents on the relative abundance of phylotypes of the indigenous faecal microbiotas

Enrollment: 42 patients

Sex: All

Ages: 18 to 40 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

1. Men and women aged between 18 and 40 years.
2. Following verbal & written information about the trial, the subject has signed & dated informed consent before any study related activity was carried out.
3. Subject legally competent and able to communicate effectively with the study personnel
4. Normal finding in the medical history and physical examination, unless the investigator considers an abnormality to be clinically irrelevant.
5. Male or female subjects who are using a medically acceptable method of contraception or of non-childbearing potential (i.e., surgically sterile-bilateral tubal ligation or removal of both ovaries and/or uterus at least 6 months prior to dosing or naturally postmenopausal for at least one year with a Screening FSH leve≥l 40 mIU/L). - - A negative serum pregnancy test is required at Screening for females.

Exclusion criteria

1. Regular use of medication, except contraceptive, vitamin tablets, treatment with antimicrobial agents within the 3 months preceding the study, Use of antibiotics for 4 weeks prior to the study drug application or use of concomitant systemic or topical antibiotics, Systemic treatment with immunosuppressive drugs e.g. cyclosporine, azathioprine or oral corticosteroids within 4 weeks prior to baseline visit (Visit 2) .

2. Participation in a trial with another investigational drug within the 3 months preceding the study

3. Present or residual gastrointestinal, renal insufficiency or hepatic disorder

4. Abnormal pathology of nasal passages

5. Any clinically significant allergy or drug intolerance

6. Active hay fever, on-going cold/flu symptoms, including rhinitis at baseline (visit 2)

7. Any medical history of renal insufficiency or hepatic disorder or other conditions known to interfere with the absorption, distribution, metabolism or excretion of drugs

8. history of hypersensitivity to beta-lactams or tetracycline

9. pregnant or breast-feeding women

10. Subjects known or suspected of not being able to comply with trial protocol (e.g. alcoholism, drug dependency, or psychological state). History of regular alcohol consumption exceeding an average weekly intake of alcohol greater than 21 units for female and 28 units for male.

    One unit is equivalent to a half-pint of beer or one measure of spirits or one glass of wine.

11. Subjects with known or suspected immunodeficiency.

Trial design

Primary purpose: Health Services Research

Allocation: Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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42 participants in 3 patient groups, including a placebo group

3 doses of amoxicillin daily for 7 days

Active Comparator group

Description:

Cohort A: 3 doses of amoxicillin daily for 7 days (n=14). Follow up 12 months.

Treatment:

Drug: 3 doses of amoxicillin daily for 7 days

2 doses of minocycline daily for 5 days

Active Comparator group

Description:

Cohort B: 2 doses of minocycline daily for five days (n=14). Follow up 12 months.

Treatment:

Drug: 2 doses of minocycline daily for five days

2 doses of placebo daily for 5 days

Placebo Comparator group

Description:

Cohort C: 2 doses of placebo daily for five days (n=14). Follow up 12 months.

Treatment:

Other: 2 doses of placebo daily for five days