Clinical trial NCT04434300: Subcutaneous Daptomycin in Healthy Volunteers (DAPTOSC)
Official title: Comparison of the Pharmacokinetic and the Safety of Daptomycin Administered Subcutaneously Compared to the Intravenous Route : a Cross-over Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Antibiotics
Subcutaneous Injection
Daptomycin
Lead sponsor: University Hospital, Caen
Sponsor class: OTHER
First posted: 2020-06-16
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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).

Primary outcomes:
measure: daptomycin dosage after intravenous route
timeFrame: before injection
measure: daptomycin dosage after intravenous route
timeFrame: 30 minutes after injection
measure: daptomycin dosage after intravenous route
timeFrame: 1 hours after injection
measure: daptomycin dosage after intravenous route
timeFrame: 1,50 hours after injection
measure: daptomycin dosage after intravenous route
timeFrame: 2 hours after injection
measure: daptomycin dosage after intravenous route
timeFrame: 3 hours after injection
measure: daptomycin dosage after intravenous route
timeFrame: 4 hours after injection
measure: daptomycin dosage after intravenous route
timeFrame: 8 hours after injection
measure: daptomycin dosage after intravenous route
timeFrame: 10 hours after injection
measure: daptomycin dosage after intravenous route
timeFrame: 24 hours after injection
measure: daptomycin dosage after subcutaneous route
timeFrame: before injection
measure: daptomycin dosage after subcutaneous route
timeFrame: 30 minutes after injection
measure: daptomycin dosage after subcutaneous route
timeFrame: 1 hours after injection
measure: daptomycin dosage after subcutaneous route
timeFrame: 1.50 hours after injection
measure: daptomycin dosage after subcutaneous route
timeFrame: 2 hours after injection
measure: daptomycin dosage after subcutaneous route
timeFrame: 3 hours after injection
measure: daptomycin dosage after subcutaneous route
timeFrame: 4 hours after injection
measure: daptomycin dosage after subcutaneous route
timeFrame: 8 hours after injection
measure: daptomycin dosage after subcutaneous route
timeFrame: 10 hours after injection
measure: daptomycin dosage after subcutaneous route
timeFrame: 24 hours after injection
Secondary outcomes:
measure: Local adverse events
timeFrame: within the first 24hours after injection
measure: Local adverse events
timeFrame: 3 days after the infusion
measure: Local adverse events
timeFrame: 7 days after the infusion
measure: Systemic adverse events
timeFrame: within the first 24hours after injection
measure: Systemic adverse events
timeFrame: 3 days after the infusion
measure: Systemic adverse events
timeFrame: 7 days after the infusion
Other outcomes:
Locations:
city: Caen
country: France
facility: CHU Caen
state: Normandie
Study officials:
References: