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

NCT02214433 | Completed Phase 1 DMC

• 2 other identifiers: Debio 1450-103217595
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 1

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.

Conditions

Bacterial Infections

Keywords

Antibiotic; Antibiotic Resistant Bacterial Infection

Outcome Measures

Primary Outcomes (13)

• 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

Study Arms (11)

Part A Period 1 Debio 1450 IV Solution

EXPERIMENTAL

Part A Debio 1450 IV solution infused over two hours on Day 1 after fasting

Drug: Debio 1450 IV Solution

Part A Period 2 Debio 1450 Tablet

EXPERIMENTAL

Debio 1450 Tablet oral dosing once on Day 5, after fasting

Drug: Debio 1450 Tablet

Part A Period 3 Debio 1450 Tablet

EXPERIMENTAL

Debio 1450 Tablet oral dosing once on Day 9, 30 minutes after a high calorie, high fat breakfast, after fasting

Drug: Debio 1450 Tablet

Part A Period 4 Debio 1450 Tablet

EXPERIMENTAL

After preparation with Pantoprazole, Pantoprazole taken with Debio 1450 Tablet oral dosing once on Day 14, after fasting

Drug: Debio 1450 Tablet; Drug: Pantoprazole

Part B Placebo All Cohorts

PLACEBO COMPARATOR

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; Drug: Placebo Tablet or Capsule

Part B Debio 1450 Cohort 1

EXPERIMENTAL

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; Drug: Debio 1450 Tablet

Part B Debio 1450 Cohort 2a

EXPERIMENTAL

Debio 1450 IV solution, once daily on day 1

Drug: Debio 1450 IV Solution

Part B Debio 1450 Cohort 3

EXPERIMENTAL

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; Drug: Debio 1450 Capsule

Part B Debio 1450 Cohort 4

EXPERIMENTAL

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; Drug: Debio 1450 Capsule

Part B Debio 1450 Cohort 2b

EXPERIMENTAL

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; Drug: Debio 1450 Capsule

Part C Debio 1450

EXPERIMENTAL

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; Drug: Debio 1450 Capsule; Drug: Debio 1450 Oral Solution; Drug: Pantoprazole

Interventions

Placebo IV Solution DRUG

A sterile IV solution of 5% dextrose in water

Part B Placebo All Cohorts

Debio 1450 IV Solution DRUG

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

Part A Period 1 Debio 1450 IV Solution; Part B Debio 1450 Cohort 1; Part B Debio 1450 Cohort 2a; Part B Debio 1450 Cohort 2b; Part B Debio 1450 Cohort 3; Part B Debio 1450 Cohort 4; Part C Debio 1450

Placebo Tablet or Capsule DRUG

Placebo tablet or capsule, matching Debio 1450 coated tablet or capsule

Part B Placebo All Cohorts

Debio 1450 Tablet DRUG

Debio 1450 40 mg coated tablets

Part A Period 2 Debio 1450 Tablet; Part A Period 3 Debio 1450 Tablet; Part A Period 4 Debio 1450 Tablet; Part B Debio 1450 Cohort 1

Debio 1450 Capsule DRUG

Debio 1450 40 mg capsules

Part B Debio 1450 Cohort 2b; Part B Debio 1450 Cohort 3; Part B Debio 1450 Cohort 4; Part C Debio 1450

Debio 1450 Oral Solution DRUG

Lyophilized Debio 1450 (40 mg per vial) reconstituted in 5% dextrose in water

Part C Debio 1450

Pantoprazole DRUG

Pantoprazole 40 mg orally

Part A Period 4 Debio 1450 Tablet; Part C Debio 1450

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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:
• the safety or well-being of the participant or study staff
• the safety or well-being of the participant's offspring (such as through pregnancy or breast-feeding)
• the analysis of results

Sponsors & Collaborators

• Debiopharm International SA: lead

Study Sites (1)

Early Phase Clinical Unit

Baltimore, Maryland, 21225, United States

Location

MeSH Terms

Conditions

Bacterial Infections

Interventions

Capsules; afabicin; Pantoprazole

Condition Hierarchy (Ancestors)

Bacterial Infections and Mycoses; Infections

Intervention Hierarchy (Ancestors)

Dosage Forms; Pharmaceutical Preparations; 2-Pyridinylmethylsulfinylbenzimidazoles; Sulfoxides; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Frederick Wittke, MD

  Debiopharm International SA

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 8, 2014
• First Posted: August 12, 2014
• Study Start: August 1, 2014
• Primary Completion: February 1, 2015
• Study Completion: February 1, 2015
• Last Updated: February 25, 2015

Record last verified: 2015-02

Locations

US (1)