Clinical trial NCT02176005: Safety and Efficacy Study of DAV132 in Healthy Volunteers
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Da Volterra
Sponsor class: INDUSTRY
First posted: 2014-06-26
Enrollment: 44
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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.

Primary outcomes:
measure: 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)
timeFrame: D1 pre-dose, D2, D3, D4, D5, D6, D7, D8, D9, D12, D16
Secondary outcomes:
measure: 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)
timeFrame: D1 pre-dose, D2, D3, D4, D5, D6, D7, D8, D9, D12, D16, D23, D30, D37
measure: Moxifloxacin Plasma Pharmacokinetics: AUC(0-24h) of Moxifloxacin Plasma Concentrations Over Time on D1
timeFrame: D1: at pre-dose; 0h30; 1h; 1h30; 2h; 3h; 4h; 6h; 12h and 24h post-dose
measure: Moxifloxacin Plasma Pharmacokinetics: AUC(0-24h) of Moxifloxacin Plasma Concentrations Over Time on D5
timeFrame: D5: at pre-dose; 0h30; 1h; 1h30; 2h; 3h; 4h; 6h; 12h; 24h; 32h; 48h; 56h and 72h post-dose
measure: Moxifloxacin Plasma Pharmacokinetics: Cmax of Moxifloxacin in Plasma on D1
timeFrame: D1: at pre-dose; 0h30; 1h; 1h30; 2h; 3h; 4h; 6h; 12h and 24h post-dose
measure: Moxifloxacin Plasma Pharmacokinetics: Cmax of Moxifloxacin in Plasma on D5
timeFrame: D5: at pre-dose; 0h30; 1h; 1h30; 2h; 3h; 4h; 6h; 12h; 24h; 32h; 48h; 56h and 72h post-dose
measure: Number of Adverse Events (Including Abnormal Laboratory Findings) Related to Study Product
timeFrame: From randomization to 37 days after the beginning of treatment
measure: Percentage of Subjects With Adverse Events Related to Study Product
timeFrame: From randomization to 37 days after the beginning of treatment
Other outcomes:
Locations:
city: Paris
country: France
facility: CLINICAL INVESTIGATION CENTER (CIC), Groupe Hospitalier Bichat-Claude Bernard
Study officials:
affiliation: CIC Bichat, Paris France
name: Xavier Duval, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Edlund C, Beyer G, Hiemer-Bau M, Ziege S, Lode H, Nord CE. Comparative effects of moxifloxacin and clarithromycin on the normal intestinal microflora. Scand J Infect Dis. 2000;32(1):81-5. doi: 10.1080/00365540050164272.
citation: Burkhardt O, Borner K, Stass H, Beyer G, Allewelt M, Nord CE, Lode H. Single- and multiple-dose pharmacokinetics of oral moxifloxacin and clarithromycin, and concentrations in serum, saliva and faeces. Scand J Infect Dis. 2002;34(12):898-903. doi: 10.1080/0036554021000026963.
citation: de Gunzburg J, Ghozlane A, Ducher A, Le Chatelier E, Duval X, Ruppe E, Armand-Lefevre L, Sablier-Gallis F, Burdet C, Alavoine L, Chachaty E, Augustin V, Varastet M, Levenez F, Kennedy S, Pons N, Mentre F, Andremont A. Protection of the Human Gut Microbiome From Antibiotics. J Infect Dis. 2018 Jan 30;217(4):628-636. doi: 10.1093/infdis/jix604.