Safety and Efficacy Study of DAV132 in Healthy Volunteers

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to determine whether DAV132 is safe and effective for capturing fecal residues of moxifloxacin in healthy volunteers.

Detailed Description
-----------------
The proposed study, DAV132-CL-1002, is to evaluate performances of DAV132 in healthy volunteers: To capture residual concentration of antibiotics in colon without interfering with their systemic pharmacokinetics parameters. To explore the influence of DAV132 to prevent the modification of gut flora due to antibiotic. In addition, the security and acceptability of DAV132 used during 7 days will be evaluated. The proposed study is prospective, randomized, controlled, four parallel groups, repeated doses, open-label study blinded to analytical and microbiological evaluations.

Official Title
-----------------
Influence of the Administration of DAV132 7.5g Tid for 7 Days on the Fecal Levels of Moxifloxacin During and After a 5-day Oral Treatment With Moxifloxacin 400mg Oad in Healthy Volunteers

Conditions
-----------------
Healthy

Intervention / Treatment
-----------------
* Device: DAV132
* Drug: Moxifloxacin
* Other: Negative Control


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Healthy volunteers Normal digestive transit, with usually one daily stool. Females participating in the study : must be either of non-child bearing potential (surgically sterilized at least 3 months prior to inclusion, or postmenopausal or having a negative pregnancy test and be not breastfeeding at screening, and using abstinence or a double contraception method during the treatment period and for additional period of 2 weeks after the end of investigational treatment. Having given and signed the written study informed consent prior to undertaking any study-related procedure. Covered by the French Health Insurance system. Exclusion Criteria: Any history or presence of clinically relevant cardiovascular, pulmonary, gastrointestinal, hepatic, renal, metabolic, haematological, neurological, bone and joint, muscular, psychiatric, systemic, ocular, gynaecologic (if female), or infectious disease, or signs of acute illness. Contra-indications to fluoroquinolones, or risk factors for adverse events associated to fluoroquinolones. Subjects with a family history of, or actual glucose-6-phosphate dehydrogenase deficiency should be excluded. Subjects with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should be excluded. Contra-indications to DAV132, risk of gastrointestinal obstruction, perforation or haemorrhage, recent digestive tract surgery. Fecal colonisation by Clostridium difficile. Recent history of hospitalisation (within 3 months prior to inclusion). Any antibiotic administration within 3 months before inclusion. Any vaccination within the last 28 days.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Moxifloxacin<br>Moxifloxacin, oral tablets, 400mg/day, once daily 5 days | Drug: Moxifloxacin<br>* Moxifloxacin is used alone or associated to DAV132<br>* Other names: Avelox;|
| Experimental: moxifloxacin + DAV132<br>Moxifloxacin : 400mg/day for 5 days DAV132: 7.5g x3/day for 7 days | Device: DAV132<br>* DAV132 is associated to moxifloxacin or it is evaluated alone<br>Drug: Moxifloxacin<br>* Moxifloxacin is used alone or associated to DAV132<br>* Other names: Avelox;|
| Experimental: DAV132<br>DAV132 oral, 7.5g x3/day for 7 days | Device: DAV132<br>* DAV132 is associated to moxifloxacin or it is evaluated alone<br>|
| Placebo Comparator: Negative control<br>Negative control: 7.5g x3/day for 7 days | Other: Negative Control<br>* Moxifloxacin is used alone<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Moxifloxacin Fecal Pharmacokinetics: Area Under the Free Moxifloxacin Fecal Concentration-time Curve Over the Period Time From Beginning of Treatment to 16 Days After the Beginning of Treatment (AUC D1-D16) |  | D1 pre-dose, D2, D3, D4, D5, D6, D7, D8, D9, D12, D16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Moxifloxacin Fecal Pharmacokinetics: Area Under the Free Moxifloxacin Fecal Concentration-time Curve Over the Period Time From Beginning of Treatment to 37 Days After the Beginning of Treatment (AUC D1-D37) |  | D1 pre-dose, D2, D3, D4, D5, D6, D7, D8, D9, D12, D16, D23, D30, D37 | 
| Moxifloxacin Plasma Pharmacokinetics: AUC(0-24h) of Moxifloxacin Plasma Concentrations Over Time on D1 |  | D1: at pre-dose; 0h30; 1h; 1h30; 2h; 3h; 4h; 6h; 12h and 24h post-dose | 
| Moxifloxacin Plasma Pharmacokinetics: AUC(0-24h) of Moxifloxacin Plasma Concentrations Over Time on D5 |  | D5: at pre-dose; 0h30; 1h; 1h30; 2h; 3h; 4h; 6h; 12h; 24h; 32h; 48h; 56h and 72h post-dose | 
| Moxifloxacin Plasma Pharmacokinetics: Cmax of Moxifloxacin in Plasma on D1 |  | D1: at pre-dose; 0h30; 1h; 1h30; 2h; 3h; 4h; 6h; 12h and 24h post-dose | 
| Moxifloxacin Plasma Pharmacokinetics: Cmax of Moxifloxacin in Plasma on D5 |  | D5: at pre-dose; 0h30; 1h; 1h30; 2h; 3h; 4h; 6h; 12h; 24h; 32h; 48h; 56h and 72h post-dose | 
| Number of Adverse Events (Including Abnormal Laboratory Findings) Related to Study Product |  | From randomization to 37 days after the beginning of treatment | 
| Percentage of Subjects With Adverse Events Related to Study Product |  | From randomization to 37 days after the beginning of treatment |