Clinical trial NCT02214433: A Multiple Dose Study of Debio 1450 [Intravenous (IV) and Oral] in Healthy Volunteers
Official title: A Phase 1 Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Single and Multiple Ascending Doses of Debio 1450 in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Bacterial Infections
Keywords: Antibiotic
Antibiotic Resistant Bacterial Infection
Lead sponsor: Debiopharm International SA
Sponsor class: INDUSTRY
First posted: 2014-08-12
Enrollment: 70
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: Debio 1450-103 is a trial to study the pharmacokinetics (PK) of an experimental drug called Debio 1450 in healthy adult volunteers. Originally, Part A was registered separately (in NCT02214355). The registrations have been revised so all parts of this single trial (Parts A-C) are now included in this single registration (NCT02214433).

The primary purpose of each part is provided below:

* 10 volunteers participate in PART A to assess the PK of a single oral dose of Debio 1450 (tablet formulation) under varying gastric conditions
* 40 volunteers participate in PART B to assess the safety, tolerability and PK of multiple ascending doses of Debio 1450, administered sequentially IV and orally, once or twice daily.
* An additional 10 volunteers participate in PART C which is designed to assess the absolute bioavailability of various formulations of Debio 1450 under varying gastric conditions

The dose administered during Part A is based on the safety, tolerability and PK data from study Debio 1450-102 \[NCT02162199\], a single ascending dose (SAD) study, in which single oral doses up to 800 mg/day are being investigated. Doses are adjusted during Parts B and C based on the available safety and PK data from preceding cohorts.


Eligibility criteria: Inclusion Criteria:

* Meets protocol-specified criteria for qualification and/or contraception
* Is willing and able to remain confined in the study unit for the entire duration of each treatment period and comply with restrictions related to food, drink and medications
* Voluntarily consents to participate and provides written informed consent prior to any protocol-specific procedures

Exclusion Criteria:

* Has a history or current use of over-the-counter medications, dietary supplements, or drugs (including nicotine and alcohol) outside protocol-specified parameters
* Has signs, symptoms or history of any condition that, per protocol or in the opinion of the investigator, might compromise:

  1. the safety or well-being of the participant or study staff
  2. the safety or well-being of the participant's offspring (such as through pregnancy or breast-feeding)
  3. the analysis of results

Primary outcomes:
measure: Number of participants with clinically significant change from baseline in safety parameters
timeFrame: within 10 days post-dose
measure: Maximum observed plasma concentration (Cmax) of Debio 1450 (prodrug) and Debio 1452 (active moiety)
timeFrame: within 60 hours post-dose, depending on the assessment schedule for the cohort
measure: Time of maximum observed plasma concentration (tmax) of Debio 1450 and Debio 1452
timeFrame: within 60 hours post-dose, depending on the assessment schedule for the cohort
measure: Area under the plasma concentration-time curve (AUC) of Debio 1450 and Debio 1452
timeFrame: within 60 hours post-dose, depending on the assessment schedule for the cohort
measure: Percentage of AUC(0-o) that is due to extrapolation beyond the last quantifiable concentration measurement (%AUCex) of Debio 1450 and Debio 1452
timeFrame: within 60 hours post-dose, depending on the assessment schedule for the cohort
measure: Elimination half-life (t1/2) of Debio 1450 and Debio 1452
timeFrame: within 60 hours post-dose, depending on the assessment schedule for the cohort
measure: Terminal elimination rate constant (Az) of Debio 1450 and Debio 1452
timeFrame: within 60 hours post-dose, depending on the assessment schedule for the cohort
measure: Mean residence time (MRT) of Debio 1450 and Debio 1452
timeFrame: within 60 hours post-dose, depending on the assessment schedule for the cohort
measure: Apparent clearance following oral administration (CL/F) of Debio 1450 and Debio 1452
timeFrame: within 60 hours post-dose, depending on the assessment schedule for the cohort
measure: Apparent volume of distribution of Debio 1450 and Debio 1452 during terminal phase (Vz/F)
timeFrame: within 60 hours post-dose, depending on the assessment schedule for the cohort
measure: Cumulative amount of unchanged Debio 1450 and Debio 1452 excreted in urine (Ae)
timeFrame: within 60 hours post-dose, depending on the assessment schedule for the cohort
measure: Percentage of cumulative amount of unchanged Debio 1450 and Debio 1452 excreted in urine (Ae%)
timeFrame: within 60 hours post-dose, depending on the assessment schedule for the cohort
measure: Renal clearance following oral administration
timeFrame: within 60 hours post-dose, depending on the assessment schedule for the cohort
Secondary outcomes:
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Early Phase Clinical Unit
state: Maryland
Study officials:
affiliation: Debiopharm International SA
name: Frederick Wittke, MD
role: STUDY_DIRECTOR
References: