Healthy Subjects
Conditions
Brief summary
The purpose of this study is to evaluate whether different DAV132 dose regimens are safe and effective for capturing fecal residues of moxifloxacin in healthy volunteers.
Detailed description
The aim of the study is to evaluate the performances of different DAV132 dose regimens in healthy volunteers: * To capture antibiotic residues in the colon without interfering with its systemic pharmacokinetics. * To prevent antibiotic-induced changes of the intestinal microbiota. In addition, the security of DAV132 given at different dose regimens during 7 days will be evaluated. This is a prospective, randomized, controlled, repeated doses, 12 parallel groups, open-label study, blinded to analytical and microbiological evaluations.
Interventions
Sponsors
Da Volterra
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
Yes
Inclusion criteria
1. Healthy adults (males and females), able to read and write, aged from 18 to 60 years old inclusive. 2. Body mass index (BMI) 18.5 - 30 kg/m² inclusive. 3. Considered as healthy individuals according to a comprehensive clinical assessment (detailed medical history and full physical examination). 4. Normal vital signs after 10-min rest in supine position: systolic blood pressure 95 - 140 mmHg inclusive, diastolic blood pressure 45 - 90 mmHg inclusive and heart rate (pulse rate) 50 - 100 bpm inclusive. Out of range values can be accepted if judged clinically non relevant by the Investigator. 5. Normal 12-lead ECG after 10-min rest in supine position: PR interval 120 - 220 msec exclusive, QRS complex \<120 msec, and QT interval \<430 msec if male or \<450 msec if female. 6. Normal hematology and blood biochemistry test results. Out of range values can be accepted if judged clinically non relevant by the Investigator excepted for potassium and magnesium for which normal values are required. 7. Normal digestive transit, with at least one daily stool. 8. Females participating in the study: * either must be of non-child bearing potential (surgically sterilized at least 3 months prior to inclusion, or postmenopausal). Menopause is defined as being over 60 years of age, or between 45 and 60 years of age and being amenorrheic for at least 2 years with plasma FSH levels \>30 IU/L; * or must have a negative pregnancy test and be not breastfeeding at screening, and must use abstinence or a double contraception method during the treatment period and for an additional period of 2 weeks after the end of investigational treatment. The accepted double contraception methods include the use of a highly effective method of birth control (intrauterine device or hormonal contraception) in addition to one of the following contraceptive options: (1) condom, (2) diaphragm or cervical/vault cap, (3) spermicide. 9. Having given and signed the written study informed consent prior to undertake any study-related procedure. 10. Covered by the French health insurance system.
Exclusion criteria
Criteria related to the healthy status 1. Any history or presence of clinically relevant cardiovascular, pulmonary, gastrointestinal, hepatic, renal, metabolic, hematological, neurological, bone and joint, muscular, psychiatric, systemic, ocular, gynecologic (if female), or infectious disease; or signs of acute illness. 2. Any history of relevant gastrointestinal disorders within three months prior to inclusion. 3. Frequent headaches and/or migraine, recurrent nausea and/or vomiting (for each event, more than twice a month). Subject suffering from migraine on D1 will be excluded. 4. Presence or history of drug hypersensitivity, or allergic disease diagnosed and treated by a physician. Criteria specific to the study 5. Contraindications to fluoroquinolones, or risk factors for adverse effects associated to fluoroquinolones as defined in the moxifloxacin Summary of Product Characteristics, and other than those already included into the inclusion/
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Area under the curve of free moxifloxacin fecal concentrations from D1 to D16 (AUC D1-D16) | over 16 days after treatment start |
Secondary
| Measure | Time frame |
|---|---|
| Area under the curve of moxifloxacin plasma concentrations from 0 to 24 hours (AUC0-24h) on D1 and D5 | over 5 days after treatment start |
| Maximum moxifloxacin plasma concentrations (Cmax) on D1 and D5 | over 5 days after treatment start |
| Bacterial diversity of the intestinal microbiota (16S rDNA profiling) | over 37 days after treatment start |
| Number of subjects with samples positive for treatment-emergent quinolone / fluoroquinolone-resistant Enterobacteriaceae | over 37 days after treatment start |
| Occurrence of Clostridium difficile infection, evaluated by identification of C. difficile in diarrheic stools | over 37 days after treatment start |
| Number of adverse events and percentage of subjects with at least one adverse event | over 37 days after treatment start |
Countries
France
Outcome results
None listed