Safety and Efficacy Study of DAV132 in Healthy Volunteers

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

The purpose of this study is to determine whether DAV132 is safe and effective for capturing fecal residues of moxifloxacin in healthy volunteers.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Moxifloxacin; Device: DAV132; Other: Negative Control

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.

• Study Type: Interventional
• Enrollment (Actual): 44
• Phase: Phase 1

Contacts and Locations

Study Locations

• France
  • Paris, France, 75O18
    • CLINICAL INVESTIGATION CENTER (CIC), Groupe Hospitalier Bichat-Claude Bernard

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Da Volterra
• Investigators: Principal Investigator: Xavier Duval, MD, CIC Bichat, Paris France

Publications and helpful links

General Publications

• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start: March 1, 2014
• Primary Completion (Actual): October 1, 2014
• Study Completion (Actual): December 1, 2014

Study Registration Dates

• First Submitted: June 25, 2014
• First Submitted That Met QC Criteria: June 25, 2014
• First Posted (Estimate): June 26, 2014

Study Record Updates

• Last Update Posted (Actual): February 28, 2020
• Last Update Submitted That Met QC Criteria: February 16, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Anti-Bacterial Agents; Moxifloxacin
• Other Study ID Numbers: DAV132-CL-1002; ID-RCB number 2013-A01504-41 (Other Identifier: ANSM (French Agency))