Healthy
Conditions
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.
Interventions
DEVICEDAV132
DAV132 is associated to moxifloxacin or it is evaluated alone
DRUGMoxifloxacin
Moxifloxacin is used alone or associated to DAV132
OTHERNegative Control
Moxifloxacin is used alone
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
* 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.
Design outcomes
Primary
| 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
| Measure | Time frame |
|---|---|
| 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 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 |
| 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 |
| 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 |
Countries
France
Participant flow
Recruitment details
Healthy volunteers were recruited from March 20th, 2014 (date of first enrolment) and October 17th, 2014 (date of last completed)
Participants by arm
| Arm | Count |
|---|---|
| Moxifloxacin Moxifloxacin (400mg x1/day taken orally for 5 days) used alone | 14 |
| DAV132 + Moxifloxacin DAV132 (7.5g x3/day taken orally for 7 days) associated to Moxifloxacin (400mg x1/day taken orally for 5 days) | 14 |
| DAV132 DAV132 (7.5g x3/day taken orally for 7 days) used alone | 8 |
| Negative Control Negative control: microcrystalline cellulose (7.5g x3/day taken orally for 7 days) | 8 |
| Total | 44 |
Baseline characteristics
| Characteristic | Moxifloxacin | DAV132 + Moxifloxacin | DAV132 | Negative Control | Total |
|---|---|---|---|---|---|
| Age, Continuous | 35.4 years STANDARD_DEVIATION 10.4 | 38.6 years STANDARD_DEVIATION 12.1 | 27.9 years STANDARD_DEVIATION 9.1 | 36.7 years STANDARD_DEVIATION 11.8 | 35.3 years STANDARD_DEVIATION 11.3 |
| Body Mass Index (BMI) at screening visit | 24.1 kg/m^2 STANDARD_DEVIATION 3.3 | 24.9 kg/m^2 STANDARD_DEVIATION 3.2 | 23.6 kg/m^2 STANDARD_DEVIATION 3.2 | 23.3 kg/m^2 STANDARD_DEVIATION 2 | 24.1 kg/m^2 STANDARD_DEVIATION 3 |
| Region of Enrollment France | 14 Participants | 14 Participants | 8 Participants | 8 Participants | 44 Participants |
| Sex: Female, Male Female | 9 Participants | 10 Participants | 4 Participants | 5 Participants | 28 Participants |
| Sex: Female, Male Male | 5 Participants | 4 Participants | 4 Participants | 3 Participants | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 14 | 0 / 14 | 0 / 8 | 0 / 8 |
| other Total, other adverse events | 6 / 14 | 10 / 14 | 2 / 8 | 1 / 8 |
| serious Total, serious adverse events | 0 / 14 | 0 / 14 | 0 / 8 | 0 / 8 |
Outcome results
Primary
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)
Time frame: D1 pre-dose, D2, D3, D4, D5, D6, D7, D8, D9, D12, D16
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Moxifloxacin | 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) | 758.4 μg/g.day | Standard Deviation 359.3 |
| Moxifloxacin + DAV132 | 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) | 8.28 μg/g.day | Standard Deviation 7.21 |
p-value: <0.00000195% CI: [0.006, 0.0144]General linear model
Secondary
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)
Time frame: D1 pre-dose, D2, D3, D4, D5, D6, D7, D8, D9, D12, D16, D23, D30, D37
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Moxifloxacin | 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) | 758.7 μg/g.day | Standard Deviation 359.5 |
| Moxifloxacin + DAV132 | 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) | 8.74 μg/g.day | Standard Deviation 7.73 |
p-value: <0.00000195% CI: [0.0061, 0.0151]General linear model
Secondary
Moxifloxacin Plasma Pharmacokinetics: AUC(0-24h) of Moxifloxacin Plasma Concentrations Over Time on D1
Time frame: D1: at pre-dose; 0h30; 1h; 1h30; 2h; 3h; 4h; 6h; 12h and 24h post-dose
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Moxifloxacin | Moxifloxacin Plasma Pharmacokinetics: AUC(0-24h) of Moxifloxacin Plasma Concentrations Over Time on D1 | 42.1 µg/mL.h | Standard Deviation 7.01 |
| Moxifloxacin + DAV132 | Moxifloxacin Plasma Pharmacokinetics: AUC(0-24h) of Moxifloxacin Plasma Concentrations Over Time on D1 | 41.9 µg/mL.h | Standard Deviation 9.57 |
p-value: 0.80695% CI: [0.8608, 1.1182]General linear model
Secondary
Moxifloxacin Plasma Pharmacokinetics: AUC(0-24h) of Moxifloxacin Plasma Concentrations Over Time on D5
Time frame: D5: at pre-dose; 0h30; 1h; 1h30; 2h; 3h; 4h; 6h; 12h; 24h; 32h; 48h; 56h and 72h post-dose
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Moxifloxacin | Moxifloxacin Plasma Pharmacokinetics: AUC(0-24h) of Moxifloxacin Plasma Concentrations Over Time on D5 | 57.6 µg/mL.h | Standard Deviation 13.83 |
| Moxifloxacin + DAV132 | Moxifloxacin Plasma Pharmacokinetics: AUC(0-24h) of Moxifloxacin Plasma Concentrations Over Time on D5 | 50.5 µg/mL.h | Standard Deviation 10.91 |
p-value: 0.13995% CI: [0.76, 1.0155]General linear model
Secondary
Moxifloxacin Plasma Pharmacokinetics: Cmax of Moxifloxacin in Plasma on D1
Time frame: D1: at pre-dose; 0h30; 1h; 1h30; 2h; 3h; 4h; 6h; 12h and 24h post-dose
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Moxifloxacin | Moxifloxacin Plasma Pharmacokinetics: Cmax of Moxifloxacin in Plasma on D1 | 4.02 µg/mL | Standard Deviation 1.33 |
| Moxifloxacin + DAV132 | Moxifloxacin Plasma Pharmacokinetics: Cmax of Moxifloxacin in Plasma on D1 | 4.63 µg/mL | Standard Deviation 0.97 |
p-value: 0.10495% CI: [0.9982, 1.3861]General linear model
Secondary
Moxifloxacin Plasma Pharmacokinetics: Cmax of Moxifloxacin in Plasma on D5
Time frame: D5: at pre-dose; 0h30; 1h; 1h30; 2h; 3h; 4h; 6h; 12h; 24h; 32h; 48h; 56h and 72h post-dose
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Moxifloxacin | Moxifloxacin Plasma Pharmacokinetics: Cmax of Moxifloxacin in Plasma on D5 | 4.89 µg/mL | Standard Deviation 1.21 |
| Moxifloxacin + DAV132 | Moxifloxacin Plasma Pharmacokinetics: Cmax of Moxifloxacin in Plasma on D5 | 4.60 µg/mL | Standard Deviation 1.24 |
p-value: 0.51995% CI: [0.7969, 1.1066]General linear model
Secondary
Number of Adverse Events (Including Abnormal Laboratory Findings) Related to Study Product
Time frame: From randomization to 37 days after the beginning of treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Moxifloxacin | Number of Adverse Events (Including Abnormal Laboratory Findings) Related to Study Product | 1 events related to study product |
| Moxifloxacin + DAV132 | Number of Adverse Events (Including Abnormal Laboratory Findings) Related to Study Product | 0 events related to study product |
| DAV132 | Number of Adverse Events (Including Abnormal Laboratory Findings) Related to Study Product | 0 events related to study product |
| Negative Control | Number of Adverse Events (Including Abnormal Laboratory Findings) Related to Study Product | 0 events related to study product |
Secondary
Percentage of Subjects With Adverse Events Related to Study Product
Time frame: From randomization to 37 days after the beginning of treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Moxifloxacin | Percentage of Subjects With Adverse Events Related to Study Product | 7.14 % of subjects with at last 1 related AE |
| Moxifloxacin + DAV132 | Percentage of Subjects With Adverse Events Related to Study Product | 0 % of subjects with at last 1 related AE |
| DAV132 | Percentage of Subjects With Adverse Events Related to Study Product | 0 % of subjects with at last 1 related AE |
| Negative Control | Percentage of Subjects With Adverse Events Related to Study Product | 0 % of subjects with at last 1 related AE |