A Multiple Dose Study of Debio 1450 [Intravenous (IV) and Oral] in Healthy Volunteers

Bacterial Infections Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02214433
• Other study ID #: Debio 1450-103
• Secondary ID: 217595
• Status: Completed
• Phase: Phase 1
• First received: August 8, 2014
• Last updated: February 24, 2015
• Start date: August 2014
• Est. completion date: February 2015

Study information

• Verified date: February 2015
• Source: Debiopharm International SA
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

Other known NCT identifiers

• NCT02214355

Recruitment information / eligibility

• Status: Completed
• Enrollment: 70
• Est. completion date: February 2015
• Est. primary completion date: February 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 55 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Bacterial Infections

Intervention

Drug:
• Placebo IV Solution
A sterile IV solution of 5% dextrose in water
• Debio 1450 IV Solution
A white to off-white powder (40 mg Debio 1450 per vial) to be reconstituted and formulated in a sterile IV solution of 5% dextrose in water
• Placebo Tablet or Capsule
Placebo tablet or capsule, matching Debio 1450 coated tablet or capsule
• Debio 1450 Tablet
Debio 1450 40 mg coated tablets
• Debio 1450 Capsule
Debio 1450 40 mg capsules
• Debio 1450 Oral Solution
Lyophilized Debio 1450 (40 mg per vial) reconstituted in 5% dextrose in water
• Pantoprazole
Pantoprazole 40 mg orally

Locations

Country	Name	City	State
United States	Early Phase Clinical Unit	Baltimore	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
Debiopharm International SA

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants with clinically significant change from baseline in safety parameters	Categories: vital signs, 12-lead electrocardiogram (ECG), clinical laboratory parameters, adverse events, pulmonary function, physical examination, concomitant medication	within 10 days post-dose	No
Primary	Maximum observed plasma concentration (Cmax) of Debio 1450 (prodrug) and Debio 1452 (active moiety)	Categories: Placebo Tablet or Capsule, Placebo IV Solution, Debio 1450 IV solution, Debio 1450 Tablet, Debio 1450 Capsule, Debio 1450 oral solution	within 60 hours post-dose, depending on the assessment schedule for the cohort	No
Primary	Time of maximum observed plasma concentration (tmax) of Debio 1450 and Debio 1452	Categories: Placebo Tablet or Capsule, Placebo IV Solution, Debio 1450 IV solution, Debio 1450 Tablet, Debio 1450 Capsule, Debio 1450 oral solution	within 60 hours post-dose, depending on the assessment schedule for the cohort	No
Primary	Area under the plasma concentration-time curve (AUC) of Debio 1450 and Debio 1452	Categories: Placebo Tablet or Capsule, Placebo IV Solution, Debio 1450 IV solution, Debio 1450 Tablet, Debio 1450 Capsule, Debio 1450 oral solution	within 60 hours post-dose, depending on the assessment schedule for the cohort	No
Primary	Percentage of AUC(0-o) that is due to extrapolation beyond the last quantifiable concentration measurement (%AUCex) of Debio 1450 and Debio 1452	Categories: Placebo Tablet or Capsule, Placebo IV Solution, Debio 1450 IV solution, Debio 1450 Tablet, Debio 1450 Capsule, Debio 1450 oral solution	within 60 hours post-dose, depending on the assessment schedule for the cohort	No
Primary	Elimination half-life (t1/2) of Debio 1450 and Debio 1452	Categories: Placebo Tablet or Capsule, Placebo IV Solution, Debio 1450 IV solution, Debio 1450 Tablet, Debio 1450 Capsule, Debio 1450 oral solution	within 60 hours post-dose, depending on the assessment schedule for the cohort	No
Primary	Terminal elimination rate constant (Az) of Debio 1450 and Debio 1452	Categories: Placebo Tablet or Capsule, Placebo IV Solution, Debio 1450 IV solution, Debio 1450 Tablet, Debio 1450 Capsule, Debio 1450 oral solution	within 60 hours post-dose, depending on the assessment schedule for the cohort	No
Primary	Mean residence time (MRT) of Debio 1450 and Debio 1452	Categories: Placebo Tablet or Capsule, Placebo IV Solution, Debio 1450 IV solution, Debio 1450 Tablet, Debio 1450 Capsule, Debio 1450 oral solution	within 60 hours post-dose, depending on the assessment schedule for the cohort	No
Primary	Apparent clearance following oral administration (CL/F) of Debio 1450 and Debio 1452	Categories: Placebo Tablet or Capsule, Placebo IV Solution, Debio 1450 IV solution, Debio 1450 Tablet, Debio 1450 Capsule, Debio 1450 oral solution	within 60 hours post-dose, depending on the assessment schedule for the cohort	No
Primary	Apparent volume of distribution of Debio 1450 and Debio 1452 during terminal phase (Vz/F)	Categories: Placebo Tablet or Capsule, Placebo IV Solution, Debio 1450 IV solution, Debio 1450 Tablet, Debio 1450 Capsule, Debio 1450 oral solution	within 60 hours post-dose, depending on the assessment schedule for the cohort	No
Primary	Cumulative amount of unchanged Debio 1450 and Debio 1452 excreted in urine (Ae)	Categories: Placebo Tablet or Capsule, Placebo IV Solution, Debio 1450 IV solution, Debio 1450 Tablet, Debio 1450 Capsule, Debio 1450 oral solution	within 60 hours post-dose, depending on the assessment schedule for the cohort	No
Primary	Percentage of cumulative amount of unchanged Debio 1450 and Debio 1452 excreted in urine (Ae%)	Categories: Placebo Tablet or Capsule, Placebo IV Solution, Debio 1450 IV solution, Debio 1450 Tablet, Debio 1450 Capsule, Debio 1450 oral solution	within 60 hours post-dose, depending on the assessment schedule for the cohort	No
Primary	Renal clearance following oral administration	Categories: Placebo Tablet or Capsule, Debio 1450 Tablet, Debio 1450 Capsule, Debio 1450 oral solution	within 60 hours post-dose, depending on the assessment schedule for the cohort	No