Subcutaneous Daptomycin in Healthy Volunteers (DAPTOSC)

Study Overview
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Brief Summary
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Background: Multidrug-resistant bacteria are a major public health problem worldwide, notably due to excess mortality and an increase in the length of hospital stay. Antibiotics that can be used to treat these infections are limited. Daptomycin is one of the most widely used antibiotics for the treatment of infections with gram-positive bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA). However, it is only administered intravenously (IV). It is therefore interesting to find new routes of administration in order to widen the possibilities of using daptomycin, especially in people who have difficulties with the venous approach. Methods/design: In a randomized, single blinded, crossover, noninferiority study in the CHU of Caen, the investigators aim to demonstrate the pharmacokinetic bioequivalence between the subcutaneous and the intravenous route of daptomycin in healthy volunteers. They will conclude the bioequivalence if the confidence interval of the area under the curve obtained is entirely within the interval [80% - 125%]. Discussion: This clinical trial could, if bioequivalence is demonstrated, lead to the completion of a clinical trial in infected patients in order to assess the efficacy and safety of daptomycin by the subcutaneous route.

Official Title
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Comparison of the Pharmacokinetic and the Safety of Daptomycin Administered Subcutaneously Compared to the Intravenous Route : a Cross-over Study

Conditions
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Antibiotics, Subcutaneous Injection, Daptomycin

Intervention / Treatment
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* Drug: Daptomycin
* Drug: Daptomycin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy volunteer from 18 to 65 years old Subject determined in good health by a doctor Signature of free and informed consent Affiliated to the French healthcare insurance Fluent in French Exclusion Criteria: Active bacterial or viral infection Immunocompromised Body mass index <20 or> 30 kg / m2 Kidney failure with glomerular filtration rate <90ml / min / m2 calculated according to the CKD-EPI method Known or suspected liver disease Pregnant or lactating woman Guardianship or curators Any situation that could interfere with the self / hetero assessment of pain (dementia, psychiatric disorders, for example) Concomitant intake of myotoxic drugs (statins, fibrates, ciclosporin, for example) Allergy or known side effects to daptomycin Dermatological pathologies which may interfere with the subcutaneous injection (eczema, psoriasis, etc.) Localized tattoo or piercing on the abdomen which may interfere with the subcutaneous injection or the evaluation of possible local effects of the injection Parenteral exposure to daptomycin in the previous 30 days The inclusion of the subject in another interventional research protocol (during the present study and in the 3 months before inclusion).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Dapto SC-IV<br>First stage : Subcutaneous injection of daptomycin 10mg/kg Subcutaneous injection of placebo (physiological serum) Second stage : - Intravenous injection of daptomycin 10mg/kg | Drug: Daptomycin<br>* Compare the pharmacokinetic of subcutaneous (SC) and intravenous (IV) routes in the same patient.<br>|
| Other: Dapto IV-SC<br>First stage : - Intravenous injection of daptomycin 10mg/kg Second stage : Subcutaneous injection of daptomycin 10mg/kg Subcutaneous injection of placebo (physiological serum) | Drug: Daptomycin<br>* Compare the pharmacokinetic of subcutaneous (SC) and intravenous (IV) routes in the same patient.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| daptomycin dosage after intravenous route | measurement of daptomycin blood concentration after intravenous route | before injection | 
| daptomycin dosage after intravenous route | measurement of daptomycin blood concentration after intravenous route | 30 minutes after injection | 
| daptomycin dosage after intravenous route | measurement of daptomycin blood concentration after intravenous route | 1 hours after injection | 
| daptomycin dosage after intravenous route | measurement of daptomycin blood concentration after intravenous route | 1,50 hours after injection | 
| daptomycin dosage after intravenous route | measurement of daptomycin blood concentration after intravenous route | 2 hours after injection | 
| daptomycin dosage after intravenous route | measurement of daptomycin blood concentration after intravenous route | 3 hours after injection | 
| daptomycin dosage after intravenous route | measurement of daptomycin blood concentration after intravenous route | 4 hours after injection | 
| daptomycin dosage after intravenous route | measurement of daptomycin blood concentration after intravenous route | 8 hours after injection | 
| daptomycin dosage after intravenous route | measurement of daptomycin blood concentration after intravenous route | 10 hours after injection | 
| daptomycin dosage after intravenous route | measurement of daptomycin blood concentration after intravenous route | 24 hours after injection | 
| daptomycin dosage after subcutaneous route | measurement of daptomycin blood concentration after subcutaneous route | before injection | 
| daptomycin dosage after subcutaneous route | measurement of daptomycin blood concentration after subcutaneous route | 30 minutes after injection | 
| daptomycin dosage after subcutaneous route | measurement of daptomycin blood concentration after subcutaneous route | 1 hours after injection | 
| daptomycin dosage after subcutaneous route | measurement of daptomycin blood concentration after subcutaneous route | 1.50 hours after injection | 
| daptomycin dosage after subcutaneous route | measurement of daptomycin blood concentration after subcutaneous route | 2 hours after injection | 
| daptomycin dosage after subcutaneous route | measurement of daptomycin blood concentration after subcutaneous route | 3 hours after injection | 
| daptomycin dosage after subcutaneous route | measurement of daptomycin blood concentration after subcutaneous route | 4 hours after injection | 
| daptomycin dosage after subcutaneous route | measurement of daptomycin blood concentration after subcutaneous route | 8 hours after injection | 
| daptomycin dosage after subcutaneous route | measurement of daptomycin blood concentration after subcutaneous route | 10 hours after injection | 
| daptomycin dosage after subcutaneous route | measurement of daptomycin blood concentration after subcutaneous route | 24 hours after injection | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Local adverse events | Occurrence of local adverse events (pain, erythema, edema, necrosis) | within the first 24hours after injection | 
| Local adverse events | Occurrence of local adverse events (pain, erythema, edema, necrosis) | 3 days after the infusion | 
| Local adverse events | Occurrence of local adverse events (pain, erythema, edema, necrosis) | 7 days after the infusion | 
| Systemic adverse events | Occurrence of systemic adverse events | within the first 24hours after injection | 
| Systemic adverse events | Occurrence of systemic adverse events | 3 days after the infusion | 
| Systemic adverse events | Occurrence of systemic adverse events | 7 days after the infusion |