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

Study Overview
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Brief Summary
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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.

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

Conditions
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Bacterial Infections

Intervention / Treatment
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* 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


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Antibiotic, Antibiotic Resistant Bacterial Infection