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

A Phase 1 Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Single and Multiple Ascending Doses of Debio 1450 in Healthy Subjects

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.

Study Overview

• Status: Completed
• Conditions: Bacterial Infections
• Intervention / Treatment: Drug: Debio 1450 IV Solution; Drug: Debio 1450 Tablet; Drug: Pantoprazole; Drug: Placebo IV Solution; Drug: Placebo Tablet or Capsule; Drug: Debio 1450 Capsule; Drug: Debio 1450 Oral Solution

• Study Type: Interventional
• Enrollment (Actual): 70
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21225
      • Early Phase Clinical Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

11

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part A Period 1 Debio 1450 IV Solution; Part A Debio 1450 IV solution infused over two hours on Day 1 after fasting	Drug: 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
Experimental: Part A Period 2 Debio 1450 Tablet; Debio 1450 Tablet oral dosing once on Day 5, after fasting	Drug: Debio 1450 Tablet; Debio 1450 40 mg coated tablets
Experimental: Part A Period 3 Debio 1450 Tablet; Debio 1450 Tablet oral dosing once on Day 9, 30 minutes after a high calorie, high fat breakfast, after fasting	Drug: Debio 1450 Tablet; Debio 1450 40 mg coated tablets
Experimental: Part A Period 4 Debio 1450 Tablet; After preparation with Pantoprazole, Pantoprazole taken with Debio 1450 Tablet oral dosing once on Day 14, after fasting	Drug: Debio 1450 Tablet; Debio 1450 40 mg coated tablets; Drug: Pantoprazole; Pantoprazole 40 mg orally
Placebo Comparator: Part B Placebo All Cohorts; Placebo IV solution on days 1-5 and then Placebo Tablet or Capsule on Days 6-10, according to the cohort dosing schedule	Drug: Placebo IV Solution; A sterile IV solution of 5% dextrose in water; Drug: Placebo Tablet or Capsule; Placebo tablet or capsule, matching Debio 1450 coated tablet or capsule
Experimental: Part B Debio 1450 Cohort 1; Debio 1450 IV solution, once daily on days 1-5, then Debio 1450 Tablet, once daily on days 6-10	Drug: 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; Drug: Debio 1450 Tablet; Debio 1450 40 mg coated tablets
Experimental: Part B Debio 1450 Cohort 2a; Debio 1450 IV solution, once daily on day 1	Drug: 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
Experimental: Part B Debio 1450 Cohort 3; Debio 1450 IV solution, twice daily on days 1-5, then Debio 1450 Capsule, twice daily on days 6-10	Drug: 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; Drug: Debio 1450 Capsule; Debio 1450 40 mg capsules
Experimental: Part B Debio 1450 Cohort 4; Debio 1450 IV solution, twice daily on days 1-5, then Debio 1450 Capsule, twice daily on days 6-10	Drug: 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; Drug: Debio 1450 Capsule; Debio 1450 40 mg capsules
Experimental: Part B Debio 1450 Cohort 2b; Debio 1450 IV solution, once daily on days 1-5, then Debio 1450 Capsule, once daily on days 6-10	Drug: 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; Drug: Debio 1450 Capsule; Debio 1450 40 mg capsules
Experimental: Part C Debio 1450; Debio 1450 (IV formulation in Period 1, capsule formulation in Periods 2, 4 and 5 (with Pantoprazole), and Debio 1450 oral solution in Period 3).	Drug: 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; Drug: Pantoprazole; Pantoprazole 40 mg orally; Drug: Debio 1450 Capsule; Debio 1450 40 mg capsules; Drug: Debio 1450 Oral Solution; Lyophilized Debio 1450 (40 mg per vial) reconstituted in 5% dextrose in water

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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
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
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
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
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
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
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
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
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

Collaborators and Investigators

• Sponsor: Debiopharm International SA
• Investigators: Study Director: Frederick Wittke, MD, Debiopharm International SA

Study record dates

Study Major Dates

• Study Start: August 1, 2014
• Primary Completion (Actual): February 1, 2015
• Study Completion (Actual): February 1, 2015

Study Registration Dates

• First Submitted: August 8, 2014
• First Submitted That Met QC Criteria: August 8, 2014
• First Posted (Estimate): August 12, 2014

Study Record Updates

• Last Update Posted (Estimate): February 25, 2015
• Last Update Submitted That Met QC Criteria: February 24, 2015
• Last Verified: February 1, 2015

More Information

Terms related to this study

• Keywords: Antibiotic; Antibiotic Resistant Bacterial Infection
• Additional Relevant MeSH Terms: Infections; Bacterial Infections and Mycoses; Bacterial Infections; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Gastrointestinal Agents; Anti-Ulcer Agents; Proton Pump Inhibitors; Pharmaceutical Solutions; Pantoprazole
• Other Study ID Numbers: Debio 1450-103; 217595 (Other Identifier: CRO)