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

Sponsor

Debiopharm International SA (Industry)

Overall Status

Completed

CT.gov ID

NCT02214433

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

11.6

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Bacterial Infections	Drug: Placebo IV Solution Drug: Debio 1450 IV Solution Drug: Placebo Tablet or Capsule Drug: Debio 1450 Tablet Drug: Debio 1450 Capsule Drug: Debio 1450 Oral Solution Drug: Pantoprazole	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

70 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Basic Science

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 Start Date :

Aug 1, 2014

Actual Primary Completion Date :

Feb 1, 2015

Actual Study Completion Date :

Feb 1, 2015

Arms and Interventions

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: 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 Drug: Pantoprazole Pantoprazole 40 mg orally

Outcome Measures

Primary Outcome Measures

Number of participants with clinically significant change from baseline in safety parameters [within 10 days post-dose]
Categories: vital signs, 12-lead electrocardiogram (ECG), clinical laboratory parameters, adverse events, pulmonary function, physical examination, concomitant medication
Maximum observed plasma concentration (Cmax) of Debio 1450 (prodrug) and Debio 1452 (active moiety) [within 60 hours post-dose, depending on the assessment schedule for the cohort]
Categories: Placebo Tablet or Capsule, Placebo IV Solution, Debio 1450 IV solution, Debio 1450 Tablet, Debio 1450 Capsule, Debio 1450 oral solution
Time of maximum observed plasma concentration (tmax) of Debio 1450 and Debio 1452 [within 60 hours post-dose, depending on the assessment schedule for the cohort]
Categories: Placebo Tablet or Capsule, Placebo IV Solution, Debio 1450 IV solution, Debio 1450 Tablet, Debio 1450 Capsule, Debio 1450 oral solution
Area under the plasma concentration-time curve (AUC) of Debio 1450 and Debio 1452 [within 60 hours post-dose, depending on the assessment schedule for the cohort]
Categories: Placebo Tablet or Capsule, Placebo IV Solution, Debio 1450 IV solution, Debio 1450 Tablet, Debio 1450 Capsule, Debio 1450 oral solution
Percentage of AUC(0-o) that is due to extrapolation beyond the last quantifiable concentration measurement (%AUCex) of Debio 1450 and Debio 1452 [within 60 hours post-dose, depending on the assessment schedule for the cohort]
Categories: Placebo Tablet or Capsule, Placebo IV Solution, Debio 1450 IV solution, Debio 1450 Tablet, Debio 1450 Capsule, Debio 1450 oral solution
Elimination half-life (t1/2) of Debio 1450 and Debio 1452 [within 60 hours post-dose, depending on the assessment schedule for the cohort]
Categories: Placebo Tablet or Capsule, Placebo IV Solution, Debio 1450 IV solution, Debio 1450 Tablet, Debio 1450 Capsule, Debio 1450 oral solution
Terminal elimination rate constant (Az) of Debio 1450 and Debio 1452 [within 60 hours post-dose, depending on the assessment schedule for the cohort]
Categories: Placebo Tablet or Capsule, Placebo IV Solution, Debio 1450 IV solution, Debio 1450 Tablet, Debio 1450 Capsule, Debio 1450 oral solution
Mean residence time (MRT) of Debio 1450 and Debio 1452 [within 60 hours post-dose, depending on the assessment schedule for the cohort]
Categories: Placebo Tablet or Capsule, Placebo IV Solution, Debio 1450 IV solution, Debio 1450 Tablet, Debio 1450 Capsule, Debio 1450 oral solution
Apparent clearance following oral administration (CL/F) of Debio 1450 and Debio 1452 [within 60 hours post-dose, depending on the assessment schedule for the cohort]
Categories: Placebo Tablet or Capsule, Placebo IV Solution, Debio 1450 IV solution, Debio 1450 Tablet, Debio 1450 Capsule, Debio 1450 oral solution
Apparent volume of distribution of Debio 1450 and Debio 1452 during terminal phase (Vz/F) [within 60 hours post-dose, depending on the assessment schedule for the cohort]
Categories: Placebo Tablet or Capsule, Placebo IV Solution, Debio 1450 IV solution, Debio 1450 Tablet, Debio 1450 Capsule, Debio 1450 oral solution
Cumulative amount of unchanged Debio 1450 and Debio 1452 excreted in urine (Ae) [within 60 hours post-dose, depending on the assessment schedule for the cohort]
Categories: Placebo Tablet or Capsule, Placebo IV Solution, Debio 1450 IV solution, Debio 1450 Tablet, Debio 1450 Capsule, Debio 1450 oral solution
Percentage of cumulative amount of unchanged Debio 1450 and Debio 1452 excreted in urine (Ae%) [within 60 hours post-dose, depending on the assessment schedule for the cohort]
Categories: Placebo Tablet or Capsule, Placebo IV Solution, Debio 1450 IV solution, Debio 1450 Tablet, Debio 1450 Capsule, Debio 1450 oral solution
Renal clearance following oral administration [within 60 hours post-dose, depending on the assessment schedule for the cohort]
Categories: Placebo Tablet or Capsule, Debio 1450 Tablet, Debio 1450 Capsule, Debio 1450 oral solution

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 55 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Early Phase Clinical Unit	Baltimore	Maryland	United States	21225

Sponsors and Collaborators

Debiopharm International SA

Investigators

Study Director: Frederick Wittke, MD, Debiopharm International SA

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Debiopharm International SA

ClinicalTrials.gov Identifier:

NCT02214433

Other Study ID Numbers:

Debio 1450-103
217595
NCT02214355

First Posted:

Aug 12, 2014

Last Update Posted:

Feb 25, 2015

Last Verified:

Feb 1, 2015

Keywords provided by Debiopharm International SA

Antibiotic

Antibiotic Resistant Bacterial Infection

Additional relevant MeSH terms:

Bacterial Infections

Pantoprazole

Pharmaceutical Solutions

Study Results

No Results Posted as of Feb 25, 2015