Subcutaneous Daptomycin in Healthy Volunteers (DAPTOSC) (DAPTOSC)

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

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.

Study Overview

• Status: Completed
• Conditions: Antibiotics; Subcutaneous Injection; Daptomycin
• Intervention / Treatment: Drug: Daptomycin

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• France
  • Normandie
    • Caen, Normandie, France, 14000
      • CHU Caen

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University Hospital, Caen

Study record dates

Study Major Dates

• Study Start (Actual): October 15, 2020
• Primary Completion (Actual): January 15, 2021
• Study Completion (Actual): November 15, 2021

Study Registration Dates

• First Submitted: April 29, 2020
• First Submitted That Met QC Criteria: June 15, 2020
• First Posted (Actual): June 16, 2020

Study Record Updates

• Last Update Posted (Actual): February 1, 2022
• Last Update Submitted That Met QC Criteria: January 31, 2022
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Anti-Infective Agents; Anti-Bacterial Agents; Daptomycin
• Other Study ID Numbers: 2019-004884-32

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No