Subcutaneous Daptomycin in Healthy Volunteers (DAPTOSC)

NCT04434300 | Completed Phase 1 DMC

• 1 other identifier: 2019-004884-32
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

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.

Conditions

Antibiotics; Subcutaneous Injection; Daptomycin

Outcome Measures

Primary Outcomes (20)

• 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 Outcomes (6)

• Local adverse events

  within the first 24hours after injection

• Local adverse events

  3 days after the infusion

• Local adverse events

  7 days after the infusion

• Systemic adverse events

  within the first 24hours after injection

• Systemic adverse events

  3 days after the infusion

Study Arms (2)

Dapto SC-IV

OTHER

First stage : * Subcutaneous injection of daptomycin 10mg/kg * Subcutaneous injection of placebo (physiological serum) Second stage : \- Intravenous injection of daptomycin 10mg/kg

Drug: Daptomycin

Dapto IV-SC

OTHER

First stage : \- Intravenous injection of daptomycin 10mg/kg Second stage : * Subcutaneous injection of daptomycin 10mg/kg * Subcutaneous injection of placebo (physiological serum)

Drug: Daptomycin

Interventions

Daptomycin DRUG

Compare the pharmacokinetic of subcutaneous (SC) and intravenous (IV) routes in the same patient.

Dapto SC-IV

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University Hospital, Caen: lead

Study Sites (1)

CHU Caen

Caen, Normandy, 14000, France

Location

Related Publications (1)

• Maurille C, Baldolli A, Creveuil C, Parienti JJ, Michon J, Peyro-Saint-Paul L, Brucato S, Dargere S, Comets E, Verdier MC, Verdon R. Pharmacokinetics and safety of daptomycin administered subcutaneously in healthy volunteers: a single-blinded randomized crossover trial. J Antimicrob Chemother. 2024 Nov 4;79(11):3016-3022. doi: 10.1093/jac/dkae324.

  PMID: 39271104 RESULT

MeSH Terms

Interventions

Daptomycin

Intervention Hierarchy (Ancestors)

Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Lipopeptides; Lipids; Peptides; Amino Acids, Peptides, and Proteins

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: Subcutaneous administration of daptomycin and placebo will be done blind to the participant. Given the yellow coloration of daptomycin, a masking of the pockets of daptomycin and NaCl will be carried out with a pocket cover and an opaque tube will be used for the administration
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 29, 2020
• First Posted: June 16, 2020
• Study Start: October 15, 2020
• Primary Completion: January 15, 2021
• Study Completion: November 15, 2021
• Last Updated: April 14, 2026

Record last verified: 2021-07

Locations

FR (1)